https://orcid.org/0009-0009-0260-4004
Figures
Abstract
Sleep is critical for emotional regulation, memory, and cognitive performance. Sleep disturbances, including insomnia, hypersomnia, and circadian misalignment, are highly prevalent and clinically significant across various psychiatric disorders. Once considered secondary, sleep problems are now recognized as active contributors to the onset, course, and relapse of mental illness. This narrative review synthesizes current evidence on the bidirectional interactions between sleep and major psychiatric conditions such as major depressive disorder, bipolar disorder, anxiety disorders, posttraumatic stress disorder, schizophrenia, attention deficit and hyperactivity disorder, and substance use disorders. We highlight convergent neurobiological mechanisms, including dysregulation of circadian systems, neurotransmitter networks (GABA, serotonin, dopamine, orexin), affective circuitry (prefrontal-amygdala interactions), and stress-immune pathways. Findings consistently show that sleep problems are transdiagnostic features, impacting diagnostic presentation, prognostic trajectories, and underlying pathology. For instance, chronic insomnia increases depression risk, sleep loss can precipitate manic episodes, and distinct sleep architecture anomalies are linked to schizophrenia. Sleep disturbances also predict worse outcomes in substance use disorders, including increased craving and relapse risk. Sleep is a tractable factor in mental health, offering a potent intervention leverage point. Routine, structured sleep assessment should be integrated into psychiatric care, emphasizing first-line behavioral and chronobiological strategies like Cognitive Behavioral Therapy for Insomnia (CBT-I) and light/rhythm therapies. Directly addressing sleep significantly improves psychiatric outcomes, reducing symptoms of depression and anxiety, decreasing suicidal ideation, and lowering relapse risk in bipolar disorder and psychoses. Future research should prioritize causal designs, mechanistic neuroimaging, biomarker identification, and responsible integration of objective measurement technologies and artificial intelligence for early warning systems and personalized treatment protocols.
Citation: Hyndych A, Koval K, Dzeruzhynska N, Mader EC (2025) Sleep and psychiatric disorders: Bidirectional interactions and shared neurobiological mechanisms. PLOS Ment Health 2(12): e0000531. https://doi.org/10.1371/journal.pmen.0000531
Editor: Karli Montague-Cardoso, PLOS: Public Library of Science, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND
Published: December 31, 2025
Copyright: © 2025 Hyndych et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
1. Introduction
Sleep is a fundamental biological process that supports emotional regulation, memory, and cognitive performance [1,2]. Across psychiatry, convergent evidence shows that sleep disturbances: insomnia, hypersomnia, and circadian misalignment, are highly prevalent and clinically consequential, cutting across diagnostic boundaries and associating with worse symptoms and functioning [3–5]. Historically framed as secondary to mental illness, sleep problems are now recognized as active contributors to the onset, course, and relapse of a psychiatric disorder [3]. Longitudinal and cohort data indicate that insomnia prospectively increases risk for depression and broader psychopathology [6–9], predicts psychotic-like experiences in youth [10], and forecasts internalizing symptoms in population cohorts [11]. Genetic causal inference further supports bidirectionality between sleep traits and psychiatric risk [12,13]. Concurrently, clinical reports and reviews highlight how psychiatric symptoms, such as rumination, hyperarousal, and anhedonia, hinder sleep regulation, forming self-perpetuating cycles that sustain the illness [3,14] (Fig 1).
Conceptual diagram illustrating how sleep disturbance triggers increases in emotional reactivity, stress and HPA-axis activation, reward-system dysregulation, and reductions in cognitive control. These changes contribute to worsening psychiatric symptoms, which in turn maintain hyperarousal, rumination, and regulatory disruption, perpetuating the cycle. HPA = hypothalamic–pituitary–adrenal.
From a mechanistic perspective, common biological pathways likely link sleep dysregulation and psychopathology. Circadian rhythm disruption is a recurring theme, with animal and human studies pointing to dysfunction of the suprachiasmatic nucleus, variations in clock genes, and network-level failure in anxiety, mood, and psychotic disorders [15–19]. Neurochemical systems central to sleep: serotonin, dopamine, gamma-aminobutyric acid (GABA), and related modulators, also play transdiagnostic roles in affect, salience, and cognitive control, providing substrates for reciprocal sleep-symptom effects [20,21]. Affective neuroscience adds a complementary line: rapid eye movement (REM) and sleep loss alter amygdala-prefrontal dynamics and emotional memory processes needed for fear resolution and mood regulation [22,23], and inflammatory axes connect chronic sleep disturbance with elevated cortisol responses and low-grade inflammation seen in multiple disorders [24–28] and psychopathology share interconnected circuitry rather than intersecting only incidentally [3,19,29].
This narrative review synthesizes current evidence on these reciprocal relationships across major depressive disorder, bipolar disorder, anxiety disorders, posttraumatic stress disorder (PTSD), schizophrenia, attention deficit and hyperactivity disorder (ADHD), and substance use disorders. We emphasize convergent neurobiology: circadian systems, neurotransmitter networks, affective circuitry, and stress-immune pathways, and derive clinical implications for integrated assessment and sleep-focused interventions in routine psychiatric care.
We consulted peer-reviewed literature indexed in PubMed/MEDLINE, PsycINFO, Scopus, and Google Scholar, along with practice guidelines from specialist organizations (e.g., AASM, FDA). Searches covered January 1990 through March 2025 and used combinations of sleep-related terms (e.g., insomnia, sleep disturbance, REM sleep, circadian rhythm), psychiatric disorder terms (depression, bipolar disorder, anxiety, PTSD, schizophrenia, ADHD, autism spectrum disorder, substance use), mechanistic terms (HPA axis, inflammation, orexin, neurocircuitry), and treatment-related terms (CBT-I, chronotherapy, IPSRT, melatonin, orexin antagonists). Boolean operators (AND/OR) were used to refine queries, and reference lists of key articles were reviewed to identify additional sources.
Although this is a narrative review, we aimed to differentiate areas where the evidence base is relatively strong from domains supported by more preliminary findings. Where available, we give greater weight to randomized controlled trials, meta-analyses, and large prospective cohort studies, which provide more robust support for causal or temporal associations. In contrast, findings generated from small laboratory experiments, cross-sectional clinical samples, or uncontrolled designs are described as tentative or hypothesis-generating. Many studies in the sleep–psychiatry literature rely heavily on self-report measures, short follow-up periods, or heterogeneous samples; therefore, some associations should be interpreted cautiously. When relevant, we explicitly note when conclusions rest on stronger versus weaker methodological foundations.
2. Sleep disturbances as a transdiagnostic feature of psychiatric illness
Sleep symptoms cut across diagnostic boundaries and carry diagnostic, prognostic, and mechanistic significance. In DSM-5, they are both primary (within the Sleep-Wake Disorders) and criterion-level features in major psychiatric categories: insomnia or hypersomnia in depressive episodes, decreased need for sleep in mania/hypomania, sleep disturbance in generalized anxiety, and insomnia/nightmares within trauma- and stressor-related disorders; in neurodevelopmental, neurocognitive, obsessive-compulsive, and eating disorders, they are commonly reported as associated features rather than defining criteria [30]. Framing sleep as a transdiagnostic construct clarifies shared pathways (arousal, circadian, immune) and highlights targets that generalize across conditions.
Prospective data show that sleep problems are not merely epiphenomenal. Chronic insomnia confers ~2–3 × risk for incident depression and predicts a more relapsing course; broader longitudinal syntheses link persistent insomnia to later anxiety and other disorders [7–9]. Beyond mood disorders, actigraphic disturbance in youth at clinical high risk for psychosis forecasts subsequent positive-symptom escalation [31], and in opioid use disorder, higher insomnia severity at intake and post-treatment predicts return to use and non-fatal overdose [32].
The reverse direction is likewise evident. Disorder-specific processes disrupt sleep initiation, depth, and continuity: rumination and worry drive nocturnal cognitive arousal in mood-anxiety disorders [33]; sleep loss amplifies affective reactivity and erodes cognitive control [34]; in PTSD, sleep is characterized by reduced efficiency and slow-wave sleep with increased wake after sleep onset, while REM alterations are variable, and trauma-related nightmares are common [35]; substance use maps onto the binge-withdrawal-preoccupation cycle with characteristic sleep deterioration [36]. In neurodevelopmental conditions ASD/ADHD), alterations in melatonin and neuromodulatory systems (GABA, norepinephrine (NE)/5-hydroxytryptamine (5-HT)/ dopamine/histamine) provide shared circuit substrates linking sleep and core symptomatology [37,38]. Together, these reciprocal pathways position sleep disturbance as both an upstream risk factor and a downstream amplifier of psychopathology.
3. Shared neurobiological and physiological substrates
The high comorbidity between sleep disturbance and psychiatric illness reflects overlapping disruptions in brain circuitry, neuromodulators, circadian timing, and immune-endocrine function. Here, we highlight brain structures most consistently implicated in both sleep regulation and psychopathology (Fig 2).
Conceptual diagram illustrating shared pathways linking sleep disturbance to psychiatric disorders. Arrows indicate core mechanistic domains implicated across diagnoses, including PFC–amygdala circuitry, circadian timing regulated by the suprachiasmatic nucleus (SCN), arousal and HPA-axis activation, reward/motivation pathways, and immune–inflammatory signaling.
3.1. Brain structures involved in sleep and psychopathology
Prefrontal cortex (PFC).
Acute sleep loss compromises prefrontal function. Neuroimaging meta-analysis and multimodal studies show reduced frontal recruitment and weakened fronto-cortical connectivity after a night of total sleep deprivation—patterns consistent with impaired top-down control [39,40]. Analogous prefrontal circuit abnormalities are prominent in clinical populations: in major depressive disorder, standardized fMRI protocols identify convergent dysregulation across cognitive and emotional tasks within prefrontal networks [41]. Across anxiety disorders, meta-analytic work indicates altered medial PFC/rostral anterior cingulate cortex (ACC) engagement during emotional processing [42], and in generalized anxiety disorder specifically, resting-state analyses demonstrate reduced ventromedial prefrontal cortex (vmPFC)-insula functional connectivity, pointing to disrupted appraisal/interoceptive control loops [43].
Amygdala.
The amygdala, central to threat detection and emotional memory, shows heightened responsivity after sleep loss. A single night without sleep produces amplified amygdala responses to negative stimuli alongside reduced functional coupling with medial prefrontal regulatory regions—a prefrontal-amygdala “disconnect” [44]. Subsequent experimental work converges on this circuitry: partial sleep restriction (“sleep debt”) diminishes amygdala-anterior cingulate/medial PFC connectivity while increasing negative emotional reactivity [23].
Hippocampus.
The hippocampus underpins episodic and contextual memory and is a key node for sleep-dependent consolidation. Convergent evidence shows that slow-wave sleep (SWS) coordinates hippocampal sharp-wave ripples, thalamo-cortical spindles, and cortical slow oscillations to enable systems consolidation, i.e., gradual redistribution of memories from hippocampus to neocortex [45–47]. When sleep is curtailed or fragmented, hippocampal encoding and next-day recall degrade, and the hippocampus shows reduced support for new learning [46,48]. In clinical populations, structural hippocampal vulnerability intersects with sleep disruption: large-scale meta/mega-analyses report smaller hippocampal volumes in major depression [49] and PTSD [50]. Given that SWS is often reduced or fragmented across these disorders, impaired ripple-spindle-slow-oscillation coupling provides a plausible pathway from disturbed sleep to intrusive memories, impaired contextualization, and cognitive symptoms.
Hypothalamus (SCN, orexin/hypocretin).
The anterior hypothalamus houses the suprachiasmatic nucleus (SCN), the master circadian pacemaker that synchronizes sleep-wake timing via neural and endocrine outputs, including regulation of nocturnal melatonin release by the pineal gland. Circadian disruption—through SCN network alterations, clock-gene dysregulation, or misaligned zeitgebers—has been linked to mood and anxiety pathology [15,17,19]. Human imaging work further suggests altered SCN-centered connectivity in youth with depression and insomnia symptoms [18].
Adjacent hypothalamic orexin (hypocretin) neurons stabilize wakefulness and integrate arousal, stress, and reward signals; loss of orexin causes narcolepsy, highlighting its wake-promoting role. Pharmacologic blockade of orexin signaling (dual orexin receptor antagonists, DORAs) improves sleep onset and maintenance in insomnia, underscoring clinical leverage at this node [51,52]. Because orexin also interfaces with stress and reward circuits, dysregulation may contribute to hyperarousal in mood/anxiety disorders and to transdiagnostic sleep-psychopathology coupling [17,53].
3.2. Neurotransmitter systems
GABA.
GABA is the principal inhibitory transmitter governing sleep initiation and maintenance [54]. Convergent neurochemistry and pharmacology point to reduced GABAergic tone in insomnia and hyperarousal states, while many hypnotics (benzodiazepines, “Z-drugs”: Zolpidem, Zaleplon, and Eszopiclone) exert their effects as positive allosteric modulators at GABA_A receptors [55,56]. Magnetic resonance spectroscopy studies have reported lower cortical GABA in chronic insomnia, consistent with difficulty down-regulating arousal at night [55]. Clinically, augmentation of GABA_A signaling consolidates sleep but can shift non-rapid eye movement sleep (NREM) microarchitecture toward lighter stage N2, underscoring a trade-off between sedation and physiological sleep depth [55,56].
Serotonin (5-HT).
Serotonin modulates both mood and sleep architecture, especially the REM phase. Depressive states are linked to reduced serotonergic tone and characteristic REM changes (shortened REM latency, increased REM pressure), while selective serotonin reuptake inhibitor (SSRIs)/ serotonin-norepinephrine reuptake inhibitors (SNRIs) typically suppress REM and may fragment sleep early in treatment even as mood improves [57,58]. Beyond REM control, serotonergic pathways interface with circadian timing, helping entrain sleep-wake rhythms via raphe-SCN signaling [58].
Dopamine.
Dopamine promotes wakefulness, motivation, and salience. Mesocorticolimbic and nigrostriatal dopamine pathways increase arousal and shorten sleep, and dopaminergic activation by stimulants enhances alertness at the cost of longer sleep-onset latency and shorter total sleep time when taken later in the day [59]. In psychotic disorders, hyperdopaminergia contributes to positive symptoms and may destabilize sleep-wake regulation; antipsychotic D2-receptor blockade can secondarily improve sleep continuity while introducing dose-dependent sedation [59–62].
Orexin (Hypocretin).
Orexin neurons in the lateral hypothalamus stabilize wakefulness by tonically exciting arousal systems (monoaminergic and cholinergic). Loss of orexin signaling causes narcolepsy, illustrating its leading role in state stability; more subtle dysregulation has been implicated in hyperarousal phenotypes across mood/anxiety conditions [53]. Clinically, dual orexin receptor antagonists (DORAs) improve sleep onset and maintenance without GABAergic sedation, offering a mechanistically distinct option for insomnia and a window into the arousal-stress-reward nexus [52].
3.3. Circadian rhythms and sleep homeostasis
Suprachiasmatic nucleus and CLOCK genes.
The suprachiasmatic nucleus (SCN) serves as the brain’s master circadian pacemaker, regulating 24-hour rhythms via core clock genes such as CLOCK, ARNTL (BMAL1), PER1–3, CRY1–2, and NPAS2, which coordinate sleep-wake timing, hormonal secretion, and emotional regulation. Disruptions of these rhythms are consistently observed in mood and anxiety disorders, prompting early candidate-gene studies to examine associations between circadian genes (e.g., CLOCK, NPAS2, PER2/3, CRY2, RORA, NR1D1) and psychiatric illness [15–17,19,63]. However, the most recent and very large, hypothesis-free genome-wide association studies of major depressive disorder (MD)—a 2025 trans-ancestry meta-analysis of 688,808 cases and 4,364,225 controls—have identified 697 independent SNP associations at 635 loci but did not prioritize canonical clock genes among the 308 high-confidence genes associated with MD; instead, the hits were enriched for synaptic and neuronal signaling genes [64]. Similarly, a large GWAS of 41,917 individuals with bipolar disorder (BD) and 371,549 controls identified 64 risk loci enriched for synaptic and brain-expressed genes rather than circadian-clock genes [65]. These findings suggest that, at the level of common genetic variation detectable by current GWAS, core clock genes do not represent major direct risk loci for MD or BD. Rather, circadian disruption in psychiatric disorders may more often reflect systems-level dysregulation of SCN-mediated pathways, environmental and behavioral influences, epigenetic mechanisms, or rare variants not captured by GWAS—while circadian signaling may still meaningfully impact emotion-regulation circuits and remain a valid target for chronobiological interventions.
Genetic overlap and shared heritability.
Large-scale genome-wide association studies (GWAS) have revealed significant overlapping heritability between sleep traits and major mental illnesses [66,67]. For example, a recent meta-GWAS of insomnia (n > 1.3 million) identified hundreds of risk loci and found that polygenic risk for insomnia is strongly genetically correlated with major depressive disorder and related conditions [66]. Twin and family studies likewise show that much of the co-occurrence of disordered sleep and mood disorders is due to common genetic influences: the genetic correlation between insomnia (or poor sleep quality) and depression is often very high (r ≈ 0.6–0.8) in twin analyses [68], supporting the hypothesis that shared hereditary factors underlie both sleep disturbance and depression [69]. Notably, even normal variation in circadian rhythm and sleep duration shows genetic overlap with psychiatric risk: e.g., a predisposition toward “eveningness” (late chronotype) and longer habitual sleep are associated with higher genetic risk for schizophrenia and bipolar disorder, whereas depression, anxiety and post-traumatic stress disorder are linked to insomnia and shorter sleep [67]. Mendelian randomization analyses further bolster evidence of a causal interplay: genetic liability to insomnia increases the risk of developing depression (and vice versa) in bidirectional MR experiments [66,70]. Collectively, these findings indicate that overlapping biological pathways (such as those regulating sleep–wake cycles and affective brain circuits) may contribute to both sleep abnormalities and psychiatric disorders, explaining their frequent co-morbidity.
Circadian misalignment and psychiatric symptoms.
When internal rhythms drift from environmental or social time (shift work, irregular schedules, social jetlag, evening chronotype), risk for mood and anxiety symptoms may rise [19,71]. Meta-analytic and epidemiologic work links eveningness and social jetlag with higher depressive symptom burden and poorer mental health [19,71] while shift work is associated with greater odds of depression/anxiety [72]. Mechanistically, misalignment has been linked to altered endocrine profiles (e.g., cortisol awakening response), emotion-regulation difficulties, and reduced cognitive control [17,19].
On the other hand, sleep deprivation can produce rapid, short-lived antidepressant effects by acutely altering neural circuits and neurochemical systems implicated in depression. One night of wakefulness increases synaptic potentiation and glutamatergic signaling in prefrontal and limbic regions, enhancing plasticity in mood-regulatory networks [73,74]. It also boosts dopaminergic transmission in the mesocorticolimbic system, which can transiently improve reward processing and motivation [75,76]. Sleep loss increases adenosine activity and A1 receptor signaling, modulating monoamine pathways implicated in antidepressant response [77,78]. At the systems level, sleep deprivation rapidly adjusts circadian and clock-gene rhythms, helping realign mis-timed oscillators commonly observed in depression (Benedetti & Colombo, 2011; Wirz-Justice et al., 2013). Functional imaging studies also show reduced default mode network hyperconnectivity and improved prefrontal–amygdala regulation, mechanisms linked to lower negative affect [79,80]. These neurobiological shifts likely converge to produce the characteristic, but temporary, antidepressant response.
Social zeitgebers and behavioral rhythms.
External cues (zeitgebers) such as light, particularly morning daylight – the dominant entraining signal, along with meal timing, physical activity, and social contact, synchronize internal clocks; disruption of these routines may precipitate mood episodes [81]. Although CBT-I is the first-line treatment for sleep disorders, therapies that stabilize daily rhythms—most notably light therapy and Interpersonal and Social Rhythm Therapy (IPSRT)—improve outcomes in bipolar disorder [82] by regularizing sleep-wake timing and social schedules [83], with supportive data for delayed relapse and better mood stability in subsequent trials [84–86]. Together, these findings position rhythm assessment and zeitgeber hygiene as integral elements of routine psychiatric care.
3.4. Inflammatory and endocrine pathways
HPA axis hyperactivity and cortisol dysregulation.
Sleep, particularly deep slow-wave sleep (SWS), exerts an inhibitory influence on the hypothalamic-pituitary-adrenal (HPA) axis and cortisol secretion [87]. Conversely, acute and chronic sleep deprivation activate the HPA axis, increasing cortisol levels and promoting a state of central nervous system hyperarousal that undermines sleep continuity and promotes a vicious cycle [88–91]. This hyperactivity can be a contributing factor to clinical insomnia, while in other sleep disorders like obstructive sleep apnea (OSA), HPA axis hyperactivity may be a consequence of the disorder that then contributes to other pathologies [92].
The relationship between the HPA axis and psychiatric illness is more complex than simple hyperactivity. Research shows that while some individuals with PTSD exhibit elevated cortisol levels, others have abnormally low levels [93,94], pointing to broader HPA-axis dysregulation rather than a uniform up- or down-regulation [95,96]. This pathological imbalance may be influenced by genetic predispositions and early-life trauma [97,98]. Furthermore, research indicates that epigenetic modifications, such as DNA methylation, on HPA axis and inflammatory genes are consistently implicated in the pathophysiology of PTSD, providing a molecular basis for the lasting biological imprint of trauma [99,100].
Pro-inflammatory cytokines and sleep fragmentation.
Elevated C-reactive protein (CRP) and Interleukin-6 (IL-6) are consistently observed with sleep disturbance and with extreme sleep durations, and meta-analytic data in depression show increases in IL-6/ Tumor Necrosis Factor-Alpha (TNF-α) and CRP [101–104]. Inflammatory activation alters sleep architecture, often reducing slow-wave sleep and fragmenting continuity, as shown in human experimental endotoxin studies, clinical samples in which TNF-α blockade improves continuity, and population data linking higher IL-6 to shorter SWS [105–109]. Notably, a large meta-analysis found no consistent rise in CRP/IL-6 after acute sleep deprivation, implicating chronic disturbance as the driver of low-grade inflammation [104]. Conceptually, these links fit within the social signal transduction/sickness-behavior framework whereby inflammatory signaling shapes mood and behavior [110].
Bidirectional feedback between stress, inflammation, and sleep.
The HPA axis and pro-inflammatory signaling are not isolated systems but components of a shared, self-reinforcing feedback loop [90,111]. Sleep loss acutely activates inflammatory pathways and heightens stress reactivity, while persistent disturbance is associated with elevated CRP/IL-6. Even though acute deprivation alone does not reliably raise these markers, together they sustain a vicious cycle of hyperarousal and low-grade inflammation [104,109,112]. This perpetual feedback transforms an adaptive, short-term response into a chronic, pathological process that may contribute to disease progression and psychiatric relapse [90].
The mechanisms of this cycle are both systemic and cellular, involving key non-neuronal cells within the central nervous system. Chronic stress and sleep disruption bias microglia toward a pro-inflammatory state and alter astrocytic functions that gate sleep and metabolic clearance, contributing to fragmentation [113–115]. Chronic sleep fragmentation also impairs glymphatic transport, which is enhanced during deep sleep, thus promoting the accumulation of neurotoxic metabolites and further neuroinflammation [116–119].
3.5. Metabolic dysregulation
Insulin sensitivity and glucose regulation.
Metabolic disturbances emerge rapidly when sleep is curtailed or fragmented. A recent meta-analysis of controlled sleep-manipulation studies demonstrates that even short-term restriction significantly reduces whole-body insulin sensitivity and impairs glucose tolerance in healthy adults [120]. A large prospective cohort from the Multi-Ethnic Study of Atherosclerosis found that higher N3 proportion and longer N3 duration were associated with lower incident type 2 diabetes risk in older adults [121]. These alterations are relevant to psychiatric disorders: individuals with major depressive disorder show higher insulin resistance compared with healthy controls [122], and longitudinal data indicate a bidirectional relationship between depression and metabolic syndrome [123].
Appetite signaling and energy homeostasis.
Sleep loss alters endocrine mechanisms governing energy balance. Acute sleep restriction lowers leptin and increases ghrelin, shifting appetite toward greater caloric intake and preference for energy-dense foods [124]. Restricted sleep also elevates circulating endocannabinoids, enhancing reward-driven eating behaviors [125]. Appetite-related hormone dysregulation is clinically relevant: leptin and ghrelin abnormalities are documented in atypical depression and in antipsychotic-treated schizophrenia, where weight gain and altered appetite regulation are common [126,127]. Sleep loss may exacerbate these vulnerabilities by further altering leptin–ghrelin signaling.
Circadian control of metabolic processes.
Metabolic efficiency is strongly shaped by circadian phase. Forced-desynchrony and simulated shift-work experiments show that identical meals consumed during circadian misalignment result in higher postprandial glucose excursions and reduced insulin sensitivity compared with aligned conditions, even when sleep opportunity is held constant [128]. Core metabolic processes—including glucose tolerance, lipid oxidation, and resting energy expenditure—follow intrinsic circadian rhythms regulated by central and peripheral clocks; disruption of these rhythms impairs substrate utilization and reduces metabolic flexibility [129]. Circadian and metabolic disturbances co-occur in bipolar disorder: actigraphy data link sleep/circadian irregularities to metabolic syndrome components [130], and reviews highlight high rates of obesity, insulin resistance, and type 2 diabetes, conceptualized as “chrono-metabolic” or “metabolic jet lag” phenomena in bipolar illness [131,132].
Metabolic conditions that alter sleep physiology.
Metabolic dysfunction is highly prevalent in severe mental illness and is often amplified by second-generation antipsychotics, which substantially increase the risk of obesity and metabolic syndrome [133]; in schizophrenia, the presence of metabolic disorders is independently associated with poorer sleep quality and more severe sleep disturbance [134].
Metabolic dysfunction can, in turn, degrade sleep. Obesity increases upper-airway collapsibility and the likelihood of obstructive sleep apnea, producing recurrent arousals and intermittent hypoxia that further impair insulin sensitivity [135]. Diabetes-related hyperglycemia and nocturnal glucose variability correlate with reduced slow-wave sleep and increased nocturnal awakenings [136]. Interventions that improve metabolic health—including weight loss or treatment of sleep apnea—produce parallel improvements in sleep continuity and neurocognitive/mood outcomes [137].
4. Disorder-specific sections: Bidirectional sleep-psychopathology interactions
4.1. Major Depressive Disorder (MDD)
Prevalence and types of sleep disturbances.
Sleep disturbances are among the most prevalent and diagnostically significant features of major depressive disorder (MDD) [138]. According to DSM-5 criteria, individuals may present with either insomnia or hypersomnia as one of the A-criteria for a major depressive episode, underscoring the heterogeneity of sleep-related manifestations [30]. Epidemiological evidence indicates that sleep complaints occur in up to 90% of depressive episodes, with insomnia symptoms reported by about 85% in a large population-based sample and commonly manifesting as difficulty initiating or maintaining sleep or early-morning awakening [139]. Hypersomnia, while less common overall, appears more frequent in younger patients with depression [140] and is a hallmark of episodes with atypical features [141] and is also enriched in bipolar-spectrum depressions [142], suggesting distinct mechanisms and clinical trajectories.
Bidirectional effects of sleep and depression.
Prospective and meta-analytic studies indicate a robust, bidirectional relationship between insomnia and depression. Persistent insomnia is associated with approximately a 2- to 3-fold increased risk for incident depression and predicts a poorer course, with elevated relapse and recurrence risk when insomnia persists after mood remission [7–9,143]. Cognitive mechanisms help explain this coupling: rumination mediates the link between low mood and poor sleep quality [144], and nighttime cognitive intrusions (worry/intrusive thoughts) prospectively elevate depression risk via worsening insomnia [145,146]. A recent framework proposes a self-reinforcing triad: mind-wandering, sleep disruption, and negative affect, that maintains both insomnia and depressive symptoms [147].
Neurobiological mechanisms.
Foundational accounts emphasized monoaminergic dysregulation, particularly reduced serotonergic tone, as a shared substrate for depression and associated sleep abnormalities [20,148]. Characteristic rapid eye movement (REM) changes are among the most robust neurophysiological markers of depression: higher REM density consistently differentiates unmedicated patients with major depressive disorder (MDD) from healthy controls [149] and has been linked to greater depressive symptom severity in population-based samples [150]. Beyond monoamines, dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis provides another mechanistic link between sleep and mood pathology. Large cohort studies show that individuals with MDD exhibit elevated cortisol awakening responses and altered diurnal secretion patterns [151], while experimental and clinical data suggest that corticotropin-releasing hormone and glucocorticoid excess contribute to disrupted sleep architecture [152,153].
Contemporary circuit-level work integrates these pathways with affect regulation. Functional MRI indicates that sleep disturbance and deprivation alter connectivity among prefrontal-limbic networks central to emotional control (including amygdala and insula) [44,154]. In first-episode, drug-naïve MDD with comorbid insomnia, resting-state analyses show broader prefrontal-limbic abnormalities with reduced left insula activity versus MDD without insomnia [155]. Poorer sleep quality is also linked to increased amygdala-subgenual anterior cingulate cortex (sgACC) connectivity in clinical samples, consistent with a hyperreactive affective circuit [156]. Emerging evidence also suggests slow-wave activity (SWA) may operate atypically in MDD: experimental disruption of slow-wave sleep selectively altered waking theta in depressed participants, consistent with an altered homeostatic process that could undermine mood regulation [157].
Interventions targeting sleep.
Targeting insomnia meaningfully improves both sleep and mood outcomes in MDD. CBT-I consistently enhances sleep and reduces depressive symptoms, and as an adjunct to usual care, it increases depression response (with remission gains varying by trial) [158–160]. Despite this, implementation remains limited; major guidelines recommend integrating sleep and chronobiology interventions, especially CBT-I, into routine care rather than assuming sleep will normalize with antidepressants alone [161,162]. Pharmacologically, SSRIs typically increase REM latency, suppress REM, and can initially worsen sleep continuity, warranting proactive management [57,163]. Low-dose trazodone is often used to mitigate SSRI-related insomnia, with benefits balanced against tolerability [164,165]. Emerging options include dual orexin receptor antagonism (e.g., seltorexant) for residual insomnia in antidepressant-treated MDD; phase 2 randomized, placebo-controlled multicenter trials report improvements in sleep and suggest possible adjunctive antidepressant effects, but sample sizes are modest and long-term data are lacking, so the evidence is promising but still preliminary [166,167].
4.2. Bipolar Disorder (BD)
Prevalence and types of sleep disturbances.
Sleep–circadian disturbance is a core feature of bipolar disorder, manifesting as reduced sleep need and insomnia during manic episodes and hypersomnia during bipolar depression [168,169]. Importantly, abnormalities such as delayed sleep phase, irregular sleep timing, and residual insomnia frequently persist into euthymia, reflecting a trait-like rhythm instability that contributes to relapse risk and functional burden [168,170,171].
Bidirectional effects of sleep and bipolar disorder.
Sleep and circadian disturbances in bipolar disorder are both markers and drivers of mood instability. Insomnia is a common prodromal feature and frequently precedes manic episodes, whereas hypersomnolence more often heralds depressive episodes [172]. Prospective syntheses and actigraphy studies show that instability in sleep—particularly night-to-night variability in timing and duration and irregular rest-activity rhythms—predicts relapse even during euthymia, while average sleep duration is less informative [173–176].
Sleep loss is a well-recognized trigger of mania [177], and therapeutic sleep deprivation for bipolar depression can rapidly improve mood but carries a risk of switching to mania or hypomania, with rates of 5–10%—comparable to those observed with antidepressant treatments [178].
Neurobiological mechanisms.
Circadian clock pathways show vulnerability in BD: polymorphisms in CLOCK and related genes (BMAL1/ARNTL, PER, CRY) align with altered sleep-wake timing [15,63], and epigenetic Brain and muscle Arnt-like protein-1 gene (ARNTL) methylation differences suggest rhythm misalignment at the molecular level [179]. Lithium engages these clocks, lengthening circadian period and increasing amplitude in cellular/animal models, which provides a mechanistic basis for rhythm stabilization [180,181]. These data align the pharmacology of a first-line mood stabilizer with core-clock modulation and help explain why interventions that target circadian organization can complement medication in BD.
Interventions targeting sleep.
Rhythm-focused care is central. IPSRT regularizes sleep/wake and other zeitgebers, delaying relapse and improving mood stability, although samples are modest and largely from specialized centers [83,86]. Chronotherapies, including bright light exposure (morning or midday), phase-advance protocols, and controlled sleep deprivation, can produce rapid antidepressant effects, particularly when paired with mood stabilizers and close monitoring for mood switches [82,182,183]. Adjunctive melatonin or ramelteon has shown modest and mixed benefits, with small trials suggesting possible improvements in sleep and circadian alignment and potential relapse prevention, though evidence remains limited [184,185]. In acute manic or depressive episodes, sedating second-generation antipsychotics such as olanzapine, asenapine, and risperidone tend to increase total sleep time and improve sleep continuity in addition to stabilizing mood, based primarily on secondary sleep outcomes from controlled trials and small polysomnographic studies rather than dedicated sleep RCTs [186,187].
4.3. Anxiety disorders
Prevalence and types of sleep disturbances.
Clinically significant sleep disturbance is the norm across anxiety disorders. In generalized anxiety disorder (GAD), insomnia is reported by up to ~90% of patients, driven by persistent worry and cognitive hyperarousal [188]. Panic disorder is marked by insomnia, nocturnal panic attacks, and fragmented sleep; meta-analysis shows longer sleep latency, poorer efficiency, and shorter total sleep time, with over half of patients reporting at least one nocturnal panic episode [189], findings echoed by early polysomnography documenting reduced efficiency and frequent awakenings [190].
Bidirectional effects of sleep and anxiety disorders.
Sleep and anxiety amplify each other. Prospective data suggest sleep problems more strongly predict later anxiety than vice versa [191], and chronic insomnia forecasts elevated anxiety, potentially via inflammatory pathways [192]. Polysomnography in large samples links higher state/trait anxiety with lighter sleep and reduced SWS [193]. Longitudinal work also shows insomnia and anxiety co-predict over time [194].
Neurobiological mechanisms.
REM-related mechanisms (extinction and safety learning): REM sleep supports emotional-memory updating, particularly fear extinction and safety learning. Causal rodent evidence shows that infralimbic medial prefrontal cortex (mPFC) activity during REM is required to consolidate extinction [195]. In humans, greater REM duration relates to better safety-signal learning in trauma-exposed veterans, while reduced REM predicts stronger fear-potentiated startle in PTSD [196,197]. Consequently, REM fragmentation, frequent in GAD/PTSD, likely weakens extinction consolidation and may blunt gains from exposure-based therapies [198].
Endocrine and noradrenergic mechanisms: HPA-axis dysregulation and heightened locus coeruleus–norepinephrine (LC–NE) output contribute to sleep disruption across anxiety presentations, with elevated nighttime sympathetic activity impairing both REM continuity and restorative NREM sleep [199–204].
Interventions targeting sleep.
CBT-I improves insomnia and anxiety outcomes in comorbid GAD, with sleep gains often preceding or predicting reductions in worry, panic, and avoidance [205,206]. For panic disorder, CBT tailored to nocturnal panic reduces night awakenings and panic severity [207]. Hypnotic augmentation strategies, such as eszopiclone combined with SSRIs [208], also demonstrate potential benefits when used selectively. Together, these findings underscore that treating sleep disturbance is a clinically meaningful pathway for improving anxiety symptoms.
4.4. Post-Traumatic Stress Disorder (PTSD)
Prevalence and types of sleep disturbances.
In post-traumatic stress disorder, disturbed sleep is diagnostically central—nightmares, insomnia, and hyperarousal are core DSM-5 criteria [30]. Objective monitoring consistently demonstrates abnormalities. Actigraphy indicates lower sleep efficiency, more fragmentation, and longer time in bed compared with controls [209]. Polysomnography reveals reduced total sleep time, diminished slow-wave sleep, and elevated REM density and fragmentation [35]. Nightmares and REM-related dysregulation are especially prominent and are among the most persistent symptoms across the illness course.
Bidirectional relationship between PTSD and sleep.
A robust longitudinal literature supports a bidirectional relationship between sleep and PTSD. In military and Veteran cohorts, pre-deployment sleep disturbance—particularly insomnia and nightmares—predicts post-deployment PTSD symptoms, indicating that disturbed sleep functions as a vulnerability factor rather than a mere consequence [210,211]. Large prospective military and Veteran cohorts, in which pre-deployment insomnia and nightmares predict post-deployment PTSD and PTSD predicts later onset of insomnia and obstructive sleep apnea [212,213], provide the most robust temporal evidence because they use repeated measures and adjust for baseline symptoms and deployment exposures. Among treatment-seeking veterans, insomnia and nightmares are longitudinally associated with higher PTSD severity and tend to persist even when daytime PTSD symptoms partially improve, suggesting that sleep disturbance is both a maintaining factor and a marker of incomplete recovery [214,215]. Beyond deployment samples, adverse childhood experiences and documented maltreatment show dose–response, long-term associations with insomnia and other sleep disturbances from adolescence into adulthood, supporting enduring effects of early trauma on sleep-regulatory systems [216,217].
Neurobiological mechanisms.
PTSD is characterized by intertwined alterations in fear circuitry, REM regulation, the HPA axis, and noradrenergic signaling. Nightlong recordings show more awakenings and higher heart rate, with awakenings positively related to adrenocorticotropic hormone (ACTH) and both ACTH/cortisol inversely related to slow-wave sleep [199]; this pattern aligns with corticotropin-releasing factor (CRF) hypersecretion and relatively low cortisol due to enhanced negative feedback sensitivity [200,201]. Evidence of elevated nocturnal central noradrenergic activity has been demonstrated in combat-related PTSD, where nocturnal 3-methoxy-4-hydroxyphenylglycol (MHPG) levels fail to show the normal nighttime decline and correlate with reduced sleep time [202]. Locus coeruleus (LC) output further suppresses REM-generating circuits in animal models: down-regulating NE synthesis increases REM, while local NE infusion into the pedunculopontine tegmentum prevents it [203]. Consistent with these mechanistic findings, neuromelanin-sensitive MRI reveals elevated LC signal in military PTSD, most pronounced in the caudal LC and correlating with hyperarousal severity [204].
Interventions targeting sleep.
CBT-I effectively improves insomnia and sleep efficiency in PTSD, often with parallel reductions in PTSD symptom severity [218]. For nightmares and REM-related hyperarousal, prazosin shows mixed efficacy—positive RCTs demonstrating sleep and nightmare improvements [219,220] versus a large negative trial [221]—but remains a targeted option for select patients. Complementary approaches such as brief behavioral treatment for insomnia (BBTI) in trauma-exposed populations [222], Continuous Positive Airway Pressure (CPAP) for comorbid sleep apnea [223], and hypnotic augmentation strategies like eszopiclone plus SSRI [208] further underscore the clinical value of addressing sleep directly as part of PTSD management.
4.5. Schizophrenia and psychotic disorders
Prevalence and types of sleep disturbances.
Sleep disturbance is the rule rather than the exception across the psychosis spectrum: ~ 63% of people with schizophrenia report poor sleep quality, conferring a ~ 4 × higher risk versus controls [224]. Across clinical high risk, early psychosis, and chronic stages, pooled prevalence is ~ 50%, with consistently poorer subjective sleep than in non-psychiatric samples [225]. Typical complaints include prolonged sleep latency, frequent awakenings, shortened total sleep time, and non-restorative sleep; polysomnography (PSG) corroborates longer sleep latency, more wake after sleep onset, and reduced efficiency, with greater fragmentation (and more severe spindle deficits) in chronic illness [225,226].
Bidirectional effects of sleep and psychotic symptoms.
Poor sleep quality degrades cognition, emotion regulation, and reality monitoring, amplifying persecutory ideation and other positive symptoms [227]. Within-person data show that worse efficiency/longer latency predicts next-day increases in hallucinations and disorganization, although these findings come from small, intensively monitored samples [228,229]. Conversely, active psychotic symptoms and hyperarousal disrupt initiation and continuity of sleep and may perturb melatonin rhythms, creating a self-reinforcing loop [228]. In high-risk youth, actigraphic sleep disturbances—decreased efficiency, increased wake after sleep onset (WASO) and awakenings, and nocturnal movements—predicted escalation of positive symptoms over 12 months [31]; in schizophrenia-spectrum disorders, a large eight-year cohort showed that baseline insomnia (especially when combined with nightmares) independently predicted suicide risk over eight years [230].
Neurobiological mechanisms: spindles and circuits.
Reductions in stage-2 sleep spindles are a robust electrophysiological signature, with large effects and associations with longer illness duration and cognitive deficits [226]. High-density electroencephalography (EEG) demonstrates marked decreases in spindle number, amplitude, and duration [231], and lower spindle density/coherence predicts impaired overnight memory and greater positive-symptom burden [232]. Converging neuroimaging shows thalamocortical dysconnectivity—reduced thalamo-prefrontal coupling alongside relative hyperconnectivity with sensorimotor/auditory networks—implying relay dysfunction that may disrupt both cognitive processing and sleep rhythms [233–235]. Dysconnectivity extends to basal ganglia circuits [236], and animal work indicates selective loss of thalamic glutamatergic input to auditory cortex driven by elevated D2 signaling, offering a circuit-level mechanism relevant to sensory gating and arousal regulation [237]. In sum, converging evidence links disrupted sleep spindles to broader thalamocortical and basal ganglia dysconnectivity, offering a unifying explanation for how a single circuit-level disturbance can underlie both impaired sleep physiology and the cognitive and clinical symptoms of psychotic illness.
Interventions targeting sleep.
Second-generation antipsychotics (SGAs) exert variable effects on sleep. SGAs such as olanzapine and quetiapine can improve total sleep time and continuity—effects plausibly linked to histamine-1 (H₁) and 5-HT₂ receptor antagonism—while clozapine appears to stabilize non-REM sleep without altering REM [238] Clinically, olanzapine and risperidone are associated with fewer sleep complaints than quetiapine or aripiprazole, yet residual insomnia, short sleep, and daytime sedation remain common, underscoring the limits of medication alone [239].
Adjunctive CBT-I in psychosis reliably reduces insomnia severity and improves sleep quality, with modest but meaningful reductions in psychotic symptoms across short- and long-term follow-up [240]. Treatment response is heterogeneous—higher baseline symptom burden and mood disturbance predict weaker functional gains—underscoring the value of personalized CBT-I delivery [241].
4.6. ADHD and neurodevelopmental disorders
Prevalence and types of sleep disturbances.
Sleep problems are highly prevalent in ADHD and other neurodevelopmental conditions, including ASD and intellectual disabilities. In ADHD, approximately 25–55% report clinically significant sleep disturbance even without other psychiatric comorbidity, most often delayed sleep onset, short sleep duration, bedtime resistance, and increased nocturnal motor activity [242]. Polysomnography in untreated adults with ADHD also shows alterations in sleep architecture—e.g., longer slow-wave sleep—though objective findings vary across age groups and studies [243,244].
In ASD, sleep difficulties are reported in up to ~80% of individuals, with frequent problems initiating and maintaining sleep, sleep-disordered breathing, and restless leg syndrome [245,246]. Pediatric sleep-lab cohorts confirm elevated rates of insomnia, circadian rhythm disorders, and nonspecific restlessness relative to non-ASD peers, and point to increased sleep-disordered breathing and restless legs in autistic populations, possibly related to sensory sensitivities and melatonin dysregulation [245,247].
Bidirectional effects of sleep and neurodevelopmental symptoms.
Delayed sleep-wake timing is common and clinically relevant. In adults with ADHD, indications of delayed sleep phase syndrome (DSPS) are markedly overrepresented (26% vs 2% in controls), alongside shorter and later sleep that correlate with hyperactivity and mood seasonality [248]. In adolescents, however, moderate/high DSPS risk is equally frequent in ADHD and controls—about one-third of both groups—suggesting that while DSPS may serve as a diagnostic marker in adults, in younger populations it reflects a broader transdiagnostic vulnerability [249]. Longitudinal data show reciprocal associations: insufficient or delayed sleep forecasts next-day hyperactivity/impulsivity and broader behavioral difficulties, and daytime symptoms predict that night’s sleep disruption [250,251]. Conceptually, a delayed circadian phase may even masquerade as “late-onset ADHD” in teens, underscoring shared mechanisms between circadian misalignment and attentional dysregulation [252].
In ASD, trajectories are nuanced. In high-functioning children, reductions in sleep problems over one year accompany improved social functioning, whereas baseline sleep disturbance predicts later anxiety [253]. In a larger ASD cohort, persistent sleep problems were linked to later ADHD symptoms (in younger children) and somatic complaints (in older children), with sensory over-responsivity prospectively predicting future sleep difficulties [254]. Population-based data further suggest that early sleep problems do not independently drive increases in autistic traits once baseline symptoms are considered; instead, higher autistic traits and ASD diagnoses predict more persistent or worsening sleep problems, implying that sleep disturbance may be integral to the ASD phenotype rather than a primary upstream cause [255].
Neurobiological mechanisms.
Multiple systems implicated in ADHD and ASD overlap with sleep regulation. In ASD, clinical and animal studies point to dysregulation of key neuromodulatory circuits that govern arousal and sleep, including the noradrenergic locus coeruleus, serotonergic dorsal raphe, dopaminergic ventral tegmental area, and histaminergic tuberomammillary nucleus [37,38]. These disruptions have downstream effects on NREM continuity, spindle dynamics, REM expression, and daytime behavior. Importantly, experimental studies show that improving sleep can reduce stereotypies and enhance social functioning, highlighting mechanistic links between sleep circuits and core symptoms [256].
Gene-to-circuit evidence implicates GABAergic, histaminergic, dopaminergic, serotonergic, and orexinergic pathways—via mutations in MECP2, VGAT, SLC6A1, HRH1–3, SLC6A3 genes, and others—in hyperarousal, prolonged awakenings, REM disruption, and circadian instability [38]. Melatonin pathway disruption is especially salient: acetylserotonin O-methyltransferase (ASMT) promoter/splicing variants are associated with markedly reduced ASMT expression/activity and low melatonin levels in ASD, supporting melatonin deficiency as a risk factor with implications for sleep timing and behavior [257]. Broader circadian/autonomic alterations (e.g., CLOCK-related changes, sympathetic hyperarousal, HPA-axis dysregulation) further connect sleep pathology with autism-specific symptom clusters [258].
Interventions targeting sleep.
Behavioral approaches—sleep hygiene, structured routines, and parent-mediated programs—show benefit and should be first line, particularly in younger children [259]. In ADHD, stimulants can either improve or impair sleep: by reducing evening restlessness, they may facilitate bedtime, but dosing close to bedtime delays sleep onset and shortens total sleep; adjusting timing/formulation or considering non-stimulants (e.g., guanfacine, atomoxetine) can mitigate sleep costs [242,260].
Melatonin is an evidence-supported option for delayed sleep phase and insomnia in both ADHD and ASD, with favorable long-term safety. Trials document improvements in sleep onset latency, total sleep time, and parent-rated outcomes; in ADHD, benefits were observed when melatonin was combined with structured sleep hygiene [261], and long-term follow-up confirms sustained efficacy and safety [262]. In ASD, meta-analytic and trial data demonstrate that both immediate- and prolonged-release melatonin formulations shorten sleep latency, reduce night awakenings, extend total sleep time, and improve associated daytime behaviors [263–265].
4.7. Substance Use Disorders (SUDs)
Prevalence and types of sleep disorders.
Clinically significant sleep problems are the rule rather than the exception across substance use disorders (SUDs). In alcohol use disorder (AUD), PSG and meta-analytic evidence show longer sleep onset latency, lower sleep efficiency, reduced slow-wave sleep (SWS), and heightened REM pressure/REM density—abnormalities that can persist into abstinence [266,267]. Cocaine- and alcohol-dependent cohorts similarly exhibit marked SWS loss and increased REM, with these age-related changes occurring earlier than in controls [268]. Among stimulant users, poor sleep quality and curtailed sleep duration are common, and in cocaine dependence, these disturbances have been linked to stronger craving and earlier relapse [269,270].
Population data from Chinese illicit drug users underscore the breadth of the problem: 68.5% screened positive for sleep disturbance (Pittsburgh Sleep Quality Index (PSQI)>5), and 43.9% reported poor sleep quality (PSQI>8), with higher PSQI scores in heroin users and a dose–response association with longer use duration [271]. In methamphetamine withdrawal, sleep is especially impaired early (97.8% poor sleepers in week 1) but improves substantially by week 4 of abstinence (52.2%), largely independent of changes in mood symptoms [272]. In opioid use disorder (OUD), > 75% report multidimensional sleep deficiency (satisfaction, timing, efficiency, duration), reflecting a problem that is both prevalent and clinically consequential [273].
Substance-specific effects on sleep.
Many of the substances involved in substance use disorders have characteristic and often bidirectional effects on sleep. Alcohol is acutely sedating at sleep onset but RCTs, systematic reviews, and prospective AUD cohorts consistently show that it disrupts sleep architecture—suppressing REM and deep sleep early in the night, increasing light sleep and fragmentation, and producing REM rebound and persistent insomnia with long-term use, with chronic alcohol use disorder showing enduring macro- and microarchitectural abnormalities linked to mood and cortical atrophy [274–276]. Cannabinoids modulate sleep in a dose- and formulation-dependent manner: Δ9-THC can shorten sleep latency and acutely increase slow-wave sleep but, with chronic or heavy use and during withdrawal, is linked to poorer subjective sleep quality, reduced total sleep time, and insomnia complaints, with polysomnographic data showing heterogeneous effects on staging [277–279]. Opioids, including in the context of opioid use disorder and chronic opioid therapy, fragment sleep, reduce slow-wave and REM sleep, and increase the risk of sleep-disordered breathing and daytime sleepiness; sleep deficiency in OUD is now recognized as both a consequence of opioid exposure and a predictor of craving and relapse [280,281]. Stimulants such as cocaine and amphetamines shorten sleep time, prolong sleep onset latency, and suppress REM, whereas early abstinence is characterized by hypersomnia, REM rebound, and persistent insomnia, with chronic use producing long-lasting disruption of sleep architecture and circadian timing [282–284]. Finally, nicotine from combustible and electronic cigarettes is associated with longer sleep latency, shorter sleep duration, and poorer subjective sleep quality, with systematic reviews and observational data indicating higher rates of insomnia and sleep disturbance in both traditional smokers and e-cigarette users [285–287]. Together, these substance-specific alterations in sleep architecture and continuity both contribute to and are maintained by the underlying addiction, reinforcing the bidirectional relationship between sleep disruption and substance use disorders.
Bidirectional effects of sleep and substance use disorders.
Sleep disturbance is not just epiphenomenal—it predicts worse substance outcomes. Poor baseline sleep in stimulant users tracks with heavier recent use [288] and, across substance use disorders more broadly, poorer nightly sleep quality predicts stronger next-day craving [289]. In AUD, persistent insomnia after detoxification doubles relapse risk over subsequent months [290]. In OUD, higher insomnia severity at treatment intake predicts return to use and non-fatal overdose; symptom improvement during treatment tracks with better outcomes, and persistent insomnia over the first six months portends relapse risk [32]. More broadly, lifetime insomnia and hypersomnia map onto distinct, higher-risk substance patterns and predict increased cocaine use/relapse [291]. These data support a reciprocal cycle in which sleep disruption sustains drug seeking/use, and ongoing use further degrades sleep [267].
Neurobiological mechanisms.
Converging human and preclinical work points to overlapping circuitry for sleep, reward, stress, and pain. In AUD, sleep pathology aligns with the addiction cycle: during intoxication, faster sleep onset but poorer sleep; during withdrawal, SWS loss and only partial REM recovery; during protracted abstinence, persistent insomnia, reduced delta power, and heightened REM—changes linked to adaptations in GABA/glutamate, dopamine, stress systems (corticotropin-releasing factor, norepinephrine, orexin), and circadian regulation [36,267]. In opioid states, sleep deficiency amplifies stress signaling and hyperalgesia, while opioids directly disrupt ventilatory control during sleep, increasing central and obstructive apnea, and thereby fragmenting sleep [273]. The orexin (hypocretin) system—integrating arousal, stress, and reward—is increasingly implicated across SUDs; its dysregulation contributes to sleep fragmentation and craving, and dual orexin receptor antagonists (DORAs) are under active investigation [273,292].
Interventions targeting sleep.
Routine assessment of sleep (including insomnia, circadian timing, and sleep-disordered breathing) should be part of SUD care, with early intervention to reduce relapse risk [32,290]. Cognitive Behavioral Therapy for Insomnia (CBT-I) is effective in SUD samples and feasible to implement in outpatient addiction programs, though access and adherence can be barriers [293,294].
Pharmacologic options may be considered case-by-case: gabapentin can improve sleep and drinking outcomes in subsets of AUD [295,296], and acamprosate may confer modest sleep benefits alongside anti-relapse efficacy [297]. Sedative-hypnotics warrant caution in AUD/SUD given misuse risk and potential for poor-quality sleep [267]. Novel targets include orexin antagonists for sleep/craving modulation and cannabidiol (CBD) as a non-intoxicating candidate for AUD-related sleep disturbance with an encouraging safety profile, though controlled trials remain limited [292,298].
Finally, timing matters: acute stimulant withdrawal may show meaningful sleep recovery within weeks, while alcohol- and opioid-related sleep pathology can endure for months, reinforcing the need for staged, disorder-specific sleep strategies [36,272,273].
4.8. Other psychiatric disorders
Prevalence and types of sleep disorders.
This section outlines sleep disturbances in less commonly studied psychiatric disorders. In obsessive-compulsive disorder (OCD), sleep complaints are common, but evidence suggests they are largely driven by comorbid depression and trait anxiety [299]. Patients with OCD without depression show sleep patterns similar to controls, whereas higher levels of depression and anxiety independently predict poor sleep quality [299,300].
In eating disorders (EDs), anorexia nervosa (AN) shows shortened total sleep time and greater wake after sleep onset, increased stage 1 sleep, and reduced REM; notably, weight restoration alone may not normalize these abnormalities [301]. Bulimia nervosa (BN) commonly features irregular sleep-wake schedules and circadian instability [302,303].
In borderline personality disorder (BPD), meta-analytic evidence indicates longer sleep-onset latency, lower sleep efficiency, and altered REM parameters, alongside elevated self-reported sleep problems [304]. In younger populations, subjective complaints of poor sleep and insomnia symptoms are pronounced, though actigraphy suggests relatively longer and more efficient sleep compared to clinical controls, highlighting a subjective-objective sleep discrepancy [305]. Somatic symptom disorder is characterized by frequent insomnia—reported in approximately 20–48% of patients—alongside other sleep complaints such as non-restorative sleep and difficulty maintaining sleep [306].
Bidirectional effects of sleep and psychopathology.
Across these disorders, sleep disruption and core symptoms reinforce one another. In OCD, poorer or delayed sleep prospectively relates to more intrusive thoughts and worse emotional regulation, while evening rituals and rumination further postpone sleep [299,307]. In EDs, insufficient or irregular sleep contributes to appetite dysregulation and impulsive eating, and disordered eating patterns destabilize circadian timing [303,308]. In BPD, sleep disturbances are consistently associated with symptoms and functional impairment [309], and early childhood sleep problems have been linked to later BPD [310]. In somatic symptom disorders, sleep disturbance is closely linked with greater symptom severity and functional impairment, and heightened bodily attention and somatic complaints such as pain or gastrointestinal discomfort further interfere with sleep, reinforcing a bidirectional cycle [306].
Neurobiological mechanisms.
Shared neurobiological mechanisms span hyperarousal, circadian misalignment, and interoceptive amplification: in OCD, convergent imaging/review data implicate cortico-striato-thalamo-cortical (CSTC) circuit abnormalities consistent with arousal dysregulation [311–313]. In eating disorders, hypothalamic/orexin pathways link arousal with energy balance; higher plasma orexin-A associates with poorer sleep quality in anorexia nervosa and in obesity, with broader sleep/circadian disruption summarized by recent reviews [303,314]. In borderline personality disorder, mechanistic work indicates a circadian phenotype alongside fronto-limbic (amygdala-prefrontal) alterations compatible with unstable sleep-wake regulation [315,316]. In somatic symptom-spectrum presentations, meta-analytic neuroimaging highlights heightened engagement of interoceptive/salience networks (insula/anterior cingulate), offering a neural basis for non-restorative, fragmented sleep [317].
Interventions targeting sleep.
In OCD, screen for delayed sleep timing because it is associated with poorer exposure and response prevention therapy (ERP) response [318]. If insomnia emerges, manage per insomnia guidance: consider CBT-I and optimize antidepressant choice/timing—avoid activating agents near bedtime; use sedating augmentation at low dose timed before bed when appropriate [57]. In eating disorders, assess sleep and circadian timing; patients show eveningness and impaired sleep, and ED treatment can improve sleep quality. Circadian-supportive measures (regular routines, light and meal timing) are theoretically justified, but direct ED trials of CBT-I or specific circadian protocols are limited [319]. In BPD, morning bright-light therapy shows preliminary circadian and mood benefits in small crossover/open-label studies, and no randomized controlled trials (RCT) of bright light therapy (BLT) or other sleep/chronotherapy exist to date [315]; guided digital CBT-I as an adjunct to dialectical behavior therapy (DBT) is under evaluation [320]. In somatic symptom disorders, prioritize CBT-I alongside graded activity and interoceptive psychoeducation, minimizing polypharmacy [306,321].
5. Clinical implications
5.1. Routine assessment and under-treatment
Sleep disturbance is an active driver of psychopathology, not merely epiphenomenal. Routine screening for insomnia, hypersomnia, circadian misalignment, sleep apnea risk, nightmares, and poor sleep quality should be embedded in every psychiatric assessment. Yet surveys and guideline reviews indicate under-recognition and under-treatment across services, with insomnia rarely treated with first-line behavioral care and often defaulting to sedatives [322]. Brief validated tools (e.g., (ISI), PSQI, STOP-BANG) and a 2–3-minute sleep history (sleep timing/regularity, latency, awakenings, daytime impairment, caffeine/alcohol, shift work, screens) can normalize detection and triage.
When a sleep disorder is suspected, add targeted steps: use STOP-BANG if there is snoring, obesity, or sedative use; collect a one-week sleep diary (or actigraphy if a circadian phase disorder is likely or diaries are unreliable); screen trauma-exposed patients for nightmares; and consider sleep-medicine referral or polysomnography when signs suggest OSA, parasomnia, or central hypersomnolence.
5.2. Treating sleep improves psychiatric outcomes
A growing body of evidence demonstrates that targeting insomnia produces benefits that extend beyond sleep itself. Adjunctive CBT-I [159,240,323–325,326], IPSRT [83,84,86,327], bright-light therapy [328], and chronotherapeutic interventions, including carefully timed light exposure, phase-advance protocols, and controlled sleep deprivation with recovery sleep [328–330,331], improve both sleep and broader psychiatric outcomes when added to standard treatment. Mindfulness-based interventions also show supportive evidence for enhancing sleep and contributing to symptom reduction in several psychiatric disorders [332–334].
5.3. Digital sleep tracking and objective measures
Out-of-lab objective monitoring supports personalized care and longitudinal tracking. Actigraphy is validated for estimating sleep duration, fragmentation, and circadian phase in clinical research and is practical in psychiatric populations [335,336]. Consumer wearables show improving agreement for total sleep time and timing but are less reliable for staging; clinicians should interpret device outputs cautiously and prioritize trends over absolutes [337]. Digital CBT-I (dCBT-I) scales access and improves sleep and mental health outcomes at the population level, facilitating stepped-care models [338].
5.4. Challenges with pharmacologic sleep aids in psychiatric populations
Medication for insomnia in psychiatric care is fraught with trade-offs: diagnostic heterogeneity, polypharmacy, substance-use risk, and vulnerability to next-day cognitive and motor impairment narrow therapeutic window. When a drug is indicated, it should be adjunctive to CBT-I, targeted to the primary complaint (sleep-onset versus maintenance; circadian delay/misalignment), time-limited, and paired with a deprescribing plan [161,339].
Agent selection.
For sleep-onset or circadian problems, prefer ramelteon or melatonin [340,341]. For sleep-maintenance or early-morning awakenings, low-dose doxepin (3–6 mg) is appropriate [342]. For mixed onset-and-maintenance presentations, consider a dual orexin receptor antagonist (DORA) [343,344]. These options still carry residual risks—chiefly next-day somnolence—and require monitoring for interactions with psychotropics [161,339].
Notably, the American Academy of Sleep Medicine (AASM) guidelines emphasize the limited strength of evidence supporting pharmacologic treatments for chronic insomnia. Although agents such as low-dose doxepin and the orexin receptor antagonist suvorexant are commonly used, the guidelines indicate that none of the currently available medications carry high-quality evidence or strong recommendations for routine management [340]. This further underscores the importance of prioritizing behavioral, circadian, and systems-based interventions that more directly address underlying mechanisms.
Older adults.
Avoid benzodiazepines and Z-drugs for insomnia; if medication is needed after CBT-I, consider low-dose doxepin (≤6 mg), ramelteon, or a DORA, and keep use short-term [161,339,345].
Higher-risk and off-label options.
Reserve benzodiazepines and Z-hypnotics for brief, time-limited use due to dependence, falls, and cognitive/motor impairment risks—especially in late life [161,345,346]. Do not use antipsychotics (e.g., quetiapine) solely for insomnia because of metabolic and neurologic harms [347]. Condition-specific choices demand nuance: prazosin reduces PTSD-related nightmares in some trials but not others [221,348]. Gabapentin may help when insomnia co-occurs with pain or alcohol use disorder but is not first-line and requires misuse-risk assessment [295].
Safety checks.
Evaluate and treat obstructive sleep apnea before initiating any sedative, and minimize sedatives in untreated apnea or respiratory compromise [349]. Review drug-drug interactions systematically: avoid ramelteon with strong (CYP1A2) inhibitors such as fluvoxamine [350]; use dose limits or avoid DORAs with CYP3A inhibitors/inducers [351]; and note that doxepin exposure increases with CYP2D6/2C19 inhibitors [352].
5.5. Equity, lifespan, and sex differences
Sleep care should account for structural barriers—shift work, housing instability, and limited access to CBT-I/dCBT-I—by offering low-burden digital options, flexible scheduling, brief navigator support, and integration within primary care, addiction care, and community mental health [338,354]. Adolescents commonly show circadian delay [355]. The peripartum period is vulnerable to insomnia symptoms and circadian disruption [356,357]. Older adults face greater fall and cognitive risk with sedatives, so non-pharmacologic strategies and the lowest effective doses are preferred [345]. These differences should inform screening, timing of interventions, and medication choice.
6. Discussion
To integrate the evidence reviewed above, we provide two summary tables that consolidate the main transdiagnostic and disorder-specific sleep disturbance patterns. Table 1 summarizes common transdiagnostic sleep phenotypes, including their operational definitions, typical diagnostic contexts, and brief mechanistic and functional notes. Table 2 outlines disorder-linked patterns across MDD, BD, anxiety disorders, psychosis, SUD, ADHD/ASD, OCD, and eating disorders, including PSG/actigraphy signatures and circadian profiles.
6.1. Future directions
Sleep is both a modifiable risk factor and a mechanistic probe across diagnoses. Priorities include causal designs, explicit engagement, validated sensing and analytics, and translation into early-warning and treatment workflows.
6.2. Close the causality gap
Research should move beyond association to experimental manipulation of sleep with prespecified mediators and target-engagement readouts, so that changes in sleep can be linked causally to changes in psychiatric outcomes. High-frequency within-person longitudinal cohorts, interventional trials with formal mediation, adaptive and factorial designs, and well-designed single-case studies can all contribute. Quasi-experimental opportunities and genetic causal inference can complement trials. Preregistration, directed acyclic graphs, and routine reporting of effect sizes and target-engagement metrics should be standard.
6.3. Mechanistic neuroimaging and biomarkers
Trials should link sleep change to brain and cellular targets using multimodal assessment. Useful approaches include neuroimaging paired with electrophysiology, endocrine and circadian measures, and selected inflammatory and omics panels. Where appropriate, closed-loop perturbations of slow-wave or rapid eye movement sleep can serve as causal probes. Target engagement (for example, increased spindle density or alignment of circadian phase) should be specified a priori as the pathway to clinical change.
6.4. Artificial intelligence (AI) and sensors for objective sleep-psychiatry
Wearables and smartphones can provide continuous, low-burden data, but validation and clinical utility must precede deployment. Device algorithms should be evaluated against polysomnography across diagnostic groups, audited for bias, and documented transparently. Open data standards and preregistered analysis plans are recommended. Prospective studies should test whether risk signals change clinical decisions and improve outcomes. Integration with electronic health records should follow privacy-by-design principles and include human oversight.
6.5. Sleep as early-warning signal and treatment target
Clinical pathways should convert sleep metrics into action, with disorder-specific thresholds that trigger stepped care and timely behavioral or chronobiological supports, alongside universal screening, clear referral routes, deprescribing plans, clinician education, and equity considerations across settings and the lifespan. To improve comparability across studies, the field could converge on a concise core outcome set centered on high-yield, interpretable metrics such as sleep efficiency, a rapid eye movement fragmentation index, change in Insomnia Severity Index, circadian phase by dim-light melatonin onset, and a brief inflammatory panel (interleukin-6 and C-reactive protein).
7. Conclusion
Across diagnoses, sleep disturbance is neither incidental nor epiphenomenal: it interacts bidirectionally with core psychopathology and shares convergent substrates in prefrontal-amygdala circuits, thalamocortical oscillations, neuromodulatory systems (GABA, serotonin, dopamine, orexin), circadian timing, and stress-immune pathways. This common architecture helps explain why insomnia, hypersomnia, and circadian misalignment predict onsets, exacerbate symptom severity, and foreshadow relapse across mood, anxiety/trauma, psychotic, neurodevelopmental, and substance use disorders.
Clinically, sleep is a tractable lever. Routine, structured assessment (e.g., insomnia, circadian timing, apnea risk, nightmares) should be embedded in psychiatric care, with first-line behavioral/circadian strategies (CBT-I, light/chronotherapy, social-rhythm regularization) prioritized and pharmacologic options used judiciously, time-limited, and condition-matched. Although CBT-I is consistently identified as the gold standard for chronic insomnia, its reach remains far below clinical need: the high population prevalence of insomnia contrasts sharply with the limited availability of trained CBT-I clinicians and practical barriers related to cost, time, and access. As highlighted repeatedly in the insomnia literature, scaling CBT-I will require broader dissemination pathways, including brief formats, group-based approaches, digital programs, and stepped-care models, to ensure that evidence-based insomnia treatment is accessible at the population level. Objective monitoring (actigraphy, validated wearables) can augment history, individualize targets (efficiency, timing variability, REM fragmentation), and support stepped-care and relapse-prevention pathways. In parallel, research should move beyond association to mechanism-anchored intervention trials that demonstrate target engagement (e.g., spindles, DLMO, cortisol slope, inflammatory markers) and test whether changing sleep causally improves psychiatric outcomes.
Positioning sleep as both barometer and lever—measured continuously, interpreted mechanistically, and targeted proactively—offers a pragmatic route to earlier intervention, fewer relapses, and better functioning. Closing the causality gap, standardizing sensing/AI, and integrating sleep workflows into routine psychiatry are immediate priorities for the next decade.
References
- 1. Walker MP. The role of sleep in cognition and emotion. Ann N Y Acad Sci. 2009;1156:168–97. pmid:19338508
- 2. Krueger JM, Frank MG, Wisor JP, Roy S. Sleep function: Toward elucidating an enigma. Sleep Med Rev. 2016;28:46–54. pmid:26447948
- 3. Freeman D, Sheaves B, Waite F, Harvey AG, Harrison PJ. Sleep disturbance and psychiatric disorders. Lancet Psychiatry. 2020;7(7):628–37. pmid:32563308
- 4. Lijun C, Ke-qing L, Xiuli S, Ze C, Qinpu J, Yanchao H, et al. A Survey of Sleep Quality in Patients With 13 Types of Mental Disorders. Prim Care Companion CNS Disord. 2012;14(6):PCC.11m01173.
- 5. Sivertsen B, Hysing M, Harvey AG, Petrie KJ. The Epidemiology of Insomnia and Sleep Duration Across Mental and Physical Health: The SHoT Study. Front Psychol. 2021;12:662572. pmid:34194368
- 6. Buysse DJ, Angst J, Gamma A, Ajdacic V, Eich D, Rössler W. Prevalence, course, and comorbidity of insomnia and depression in young adults. Sleep. 2008;31(4):473–80. pmid:18457234
- 7. Baglioni C, Battagliese G, Feige B, Spiegelhalder K, Nissen C, Voderholzer U, et al. Insomnia as a predictor of depression: a meta-analytic evaluation of longitudinal epidemiological studies. J Affect Disord. 2011;135(1–3):10–9. pmid:21300408
- 8. Li L, Wu C, Gan Y, Qu X, Lu Z. Insomnia and the risk of depression: a meta-analysis of prospective cohort studies. BMC Psychiatry. 2016;16(1):375. pmid:27816065
- 9. Hertenstein E, Feige B, Gmeiner T, Kienzler C, Spiegelhalder K, Johann A, et al. Insomnia as a predictor of mental disorders: A systematic review and meta-analysis. Sleep Med Rev. 2019;43:96–105. pmid:30537570
- 10. Wang D, Ma Z, Scherffius A, Liu W, Bu L, Sun M, et al. Sleep disturbance is predictive of psychotic-like experiences among adolescents: A two-wave longitudinal survey. Sleep Med. 2023;101:296–304. pmid:36470165
- 11. Goldstone A, Javitz HS, Claudatos SA, Buysse DJ, Hasler BP, de Zambotti M, et al. Sleep Disturbance Predicts Depression Symptoms in Early Adolescence: Initial Findings From the Adolescent Brain Cognitive Development Study. J Adolesc Health. 2020;66(5):567–74. pmid:32046896
- 12. Sun X, Liu B, Liu S, Wu DJH, Wang J, Qian Y, et al. Sleep disturbance and psychiatric disorders: a bidirectional Mendelian randomisation study. Epidemiol Psychiatr Sci. 2022;31:e26. pmid:35465862
- 13. Wang Z, Chen M, Wei Y-Z, Zhuo C-G, Xu H-F, Li W-D, et al. The causal relationship between sleep traits and the risk of schizophrenia: a two-sample bidirectional Mendelian randomization study. BMC Psychiatry. 2022;22(1):399. pmid:35705942
- 14. Khurshid KA. Bi-Directional Relationship Between Sleep Problems and Psychiatric Disorders. Psychiatr Ann. 2016;46(7):385–7.
- 15. Waddington Lamont E, Legault-Coutu D, Cermakian N, Boivin DB. The role of circadian clock genes in mental disorders. Dialogues Clin Neurosci. 2007;9(3):333–42.
- 16. Landgraf D, Long JE, Proulx CD, Barandas R, Malinow R, Welsh DK. Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice. Biol Psychiatry. 2016;80(11):827–35. pmid:27113500
- 17. Walker WH 2nd, Walton JC, Nelson RJ. Disrupted circadian rhythms and mental health. Handb Clin Neurol. 2021;179:259–70. pmid:34225967
- 18. Cao L, Feng R, Gao Y, Bao W, Zhou Z, Liang K, et al. Suprachiasmatic nucleus functional connectivity related to insomnia symptoms in adolescents with major depressive disorder. Front Psychiatry. 2023;14:1154095. pmid:37260759
- 19. Meyer N, Lok R, Schmidt C, Kyle SD, McClung CA, Cajochen C, et al. The sleep-circadian interface: A window into mental disorders. Proc Natl Acad Sci U S A. 2024;121(9):e2214756121. pmid:38394243
- 20. Harvey AG, Murray G, Chandler RA, Soehner A. Sleep disturbance as transdiagnostic: consideration of neurobiological mechanisms. Clin Psychol Rev. 2011;31(2):225–35. pmid:20471738
- 21. Embang JEG, Tan YHV, Ng YX, Loyola GJP, Wong LW, Guo Y, et al. Role of sleep and neurochemical biomarkers in synaptic plasticity related to neurological and psychiatric disorders: A scoping review. J Neurochem. 2025;169:e16270.
- 22. Baran B, Pace-Schott EF, Ericson C, Spencer RMC. Processing of emotional reactivity and emotional memory over sleep. J Neurosci. 2012;32(3):1035–42. pmid:22262901
- 23. Motomura Y, Kitamura S, Oba K, Terasawa Y, Enomoto M, Katayose Y, et al. Sleep debt elicits negative emotional reaction through diminished amygdala-anterior cingulate functional connectivity. PLoS One. 2013;8(2):e56578. pmid:23418586
- 24. Prather AA, Vogelzangs N, Penninx BWJH. Sleep duration, insomnia, and markers of systemic inflammation: results from the Netherlands Study of Depression and Anxiety (NESDA). J Psychiatr Res. 2015;60:95–102. pmid:25307717
- 25. Voderholzer U, Fiebich BL, Dersch R, Feige B, Piosczyk H, Kopasz M, et al. Effects of sleep deprivation on nocturnal cytokine concentrations in depressed patients and healthy control subjects. J Neuropsychiatry Clin Neurosci. 2012;24(3):354–66. pmid:23037650
- 26. Lee EE, Ancoli-Israel S, Eyler LT, Tu XM, Palmer BW, Irwin MR, et al. Sleep Disturbances and Inflammatory Biomarkers in Schizophrenia: Focus on Sex Differences. Am J Geriatr Psychiatry. 2019;27(1):21–31. pmid:30442531
- 27. Kuhlman KR, Chiang JJ, Bower JE, Irwin MR, Seeman TE, McCreath HE, et al. Sleep problems in adolescence are prospectively linked to later depressive symptoms via the cortisol awakening response. Dev Psychopathol. 2020;32(3):997–1006. pmid:31387652
- 28. Krysta K, Krzystanek M, Bratek A, Krupka-Matuszczyk I. Sleep and inflammatory markers in different psychiatric disorders. J Neural Transm (Vienna). 2017;124(Suppl 1):179–86. pmid:26649857
- 29. Jagannath A, Peirson SN, Foster RG. Sleep and circadian rhythm disruption in neuropsychiatric illness. Curr Opin Neurobiol. 2013;23(5):888–94. pmid:23618559
- 30. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 5th ed. Washington, DC: American Psychiatric Association; 2013.
- 31. Lunsford-Avery JR, LeBourgeois MK, Gupta T, Mittal VA. Actigraphic-measured sleep disturbance predicts increased positive symptoms in adolescents at ultra high-risk for psychosis: A longitudinal study. Schizophr Res. 2015;164(1–3):15–20. pmid:25818627
- 32. Hochheimer M, Ellis JD, Strickland JC, Rabinowitz JA, Hobelmann JG, Huhn AS. Insomnia symptoms are associated with return to use and non-fatal overdose following opioid use disorder treatment. Sleep. 2025;48(4):zsae284. pmid:39657100
- 33. Kalmbach DA, Cuamatzi-Castelan AS, Tonnu CV, Tran KM, Anderson JR, Roth T, et al. Hyperarousal and sleep reactivity in insomnia: current insights. Nat Sci Sleep. 2018;10:193–201. pmid:30046255
- 34. Lim J, Dinges DF. A meta-analysis of the impact of short-term sleep deprivation on cognitive variables. Psychol Bull. 2010;136(3):375–89. pmid:20438143
- 35. Zhang Y, Ren R, Sanford LD, Yang L, Zhou J, Zhang J, et al. Sleep in posttraumatic stress disorder: A systematic review and meta-analysis of polysomnographic findings. Sleep Med Rev. 2019;48:101210. pmid:31518950
- 36. Koob GF, Colrain IM. Alcohol use disorder and sleep disturbances: a feed-forward allostatic framework. Neuropsychopharmacology. 2020;45(1):141–65. pmid:31234199
- 37. Maurer JJ, Choi A, An I, Sathi N, Chung S. Sleep disturbances in autism spectrum disorder: Animal models, neural mechanisms, and therapeutics. Neurobiol Sleep Circadian Rhythms. 2023;14:100095. pmid:37188242
- 38. Ji Q, Li S-J, Zhao J-B, Xiong Y, Du X-H, Wang C-X, et al. Genetic and neural mechanisms of sleep disorders in children with autism spectrum disorder: a review. Front Psychiatry. 2023;14:1079683. pmid:37200906
- 39. Ma N, Dinges DF, Basner M, Rao H. How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies. Sleep. 2015;38(2):233–40. pmid:25409102
- 40. Verweij IM, Romeijn N, Smit DJ, Piantoni G, Van Someren EJ, van der Werf YD. Sleep deprivation leads to a loss of functional connectivity in frontal brain regions. BMC Neurosci. 2014;15:88. pmid:25038817
- 41. Korgaonkar MS, Grieve SM, Etkin A, Koslow SH, Williams LM. Using standardized fMRI protocols to identify patterns of prefrontal circuit dysregulation that are common and specific to cognitive and emotional tasks in major depressive disorder: first wave results from the iSPOT-D study. Neuropsychopharmacology. 2013;38(5):863–71. pmid:23303059
- 42. Etkin A, Wager TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry. 2007;164(10):1476–88. pmid:17898336
- 43. Steinhäuser JL, Teed AR, Al-Zoubi O, Hurlemann R, Chen G, Khalsa SS. Reduced vmPFC-insula functional connectivity in generalized anxiety disorder: a Bayesian confirmation study. Sci Rep. 2023;13(1):9626. pmid:37316518
- 44. Yoo S-S, Gujar N, Hu P, Jolesz FA, Walker MP. The human emotional brain without sleep--a prefrontal amygdala disconnect. Curr Biol. 2007;17(20):R877-8. pmid:17956744
- 45. Diekelmann S, Born J. The memory function of sleep. Nat Rev Neurosci. 2010;11(2):114–26. pmid:20046194
- 46. Rasch B, Born J. About sleep’s role in memory. Physiol Rev. 2013;93(2):681–766. pmid:23589831
- 47. Klinzing JG, Niethard N, Born J. Mechanisms of systems memory consolidation during sleep. Nat Neurosci. 2019;22(10):1598–610. pmid:31451802
- 48. Yoo S-S, Hu PT, Gujar N, Jolesz FA, Walker MP. A deficit in the ability to form new human memories without sleep. Nat Neurosci. 2007;10(3):385–92. pmid:17293859
- 49. Schmaal L, Veltman DJ, van Erp TGM, Sämann PG, Frodl T, Jahanshad N, et al. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group. Mol Psychiatry. 2016;21(6):806–12. pmid:26122586
- 50. Logue MW, van Rooij SJH, Dennis EL, Davis SL, Hayes JP, Stevens JS, et al. Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia. Biol Psychiatry. 2018;83(3):244–53. pmid:29217296
- 51. Herring WJ, Snyder E, Budd K, Hutzelmann J, Snavely D, Liu K, et al. Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant. Neurology. 2012;79(23):2265–74. pmid:23197752
- 52. Dauvilliers Y, Zammit G, Fietze I, Mayleben D, Seboek Kinter D, Pain S, et al. Daridorexant, a New Dual Orexin Receptor Antagonist to Treat Insomnia Disorder. Ann Neurol. 2020;87(3):347–56. pmid:31953863
- 53. Scammell TE, Arrigoni E, Lipton JO. Neural Circuitry of Wakefulness and Sleep. Neuron. 2017;93(4):747–65. pmid:28231463
- 54. Winkelman JW, Buxton OM, Jensen JE, Benson KL, O’Connor SP, Wang W, et al. Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy (1H-MRS). Sleep. 2008;31(11):1499–506. pmid:19014069
- 55. Riemann D, Nissen C, Palagini L, Otte A, Perlis ML, Spiegelhalder K. The neurobiology, investigation, and treatment of chronic insomnia. Lancet Neurol. 2015;14(5):547–58. pmid:25895933
- 56. Rudolph U, Möhler H. GABA-based therapeutic approaches: GABAA receptor subtype functions. Curr Opin Pharmacol. 2006;6(1):18–23. pmid:16376150
- 57. Wichniak A, Wierzbicka A, Walęcka M, Jernajczyk W. Effects of Antidepressants on Sleep. Curr Psychiatry Rep. 2017;19(9):63. pmid:28791566
- 58. Harvey AG. Sleep and circadian functioning: critical mechanisms in the mood disorders? Annu Rev Clin Psychol. 2011;7:297–319. pmid:21166537
- 59. Eban-Rothschild A, Giardino WJ, de Lecea L. To sleep or not to sleep: neuronal and ecological insights. Curr Opin Neurobiol. 2017;44:132–8. pmid:28500869
- 60. Howes OD, McCutcheon R, Owen MJ, Murray RM. The Role of Genes, Stress, and Dopamine in the Development of Schizophrenia. Biol Psychiatry. 2017;81(1):9–20. pmid:27720198
- 61. Monti JM, Monti D. Sleep in schizophrenia patients and the effects of antipsychotic drugs. Sleep Med Rev. 2004;8(2):133–48. pmid:15033152
- 62. Miller DD. Atypical antipsychotics: sleep, sedation, and efficacy. Prim Care Companion J Clin Psychiatry. 2004;6(Suppl 2):3–7. pmid:16001094
- 63. Shi J, Wittke-Thompson JK, Badner JA, Hattori E, Potash JB, Willour VL, et al. Clock genes may influence bipolar disorder susceptibility and dysfunctional circadian rhythm. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(7):1047–55. pmid:18228528
- 64. Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Electronic address: andrew.mcintosh@ed.ac.uk, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium. Trans-ancestry genome-wide study of depression identifies 697 associations implicating cell types and pharmacotherapies. Cell. 2025;188(3):640-652.e9. pmid:39814019
- 65. Mullins N, Forstner AJ, O’Connell KS, Coombes B, Coleman JRI, Qiao Z, et al. Genome-wide association study of more than 40,000 bipolar disorder cases provides new insights into the underlying biology. Nat Genet. 2021;53(6):817–29. pmid:34002096
- 66. Jansen PR, Watanabe K, Stringer S, Skene N, Bryois J, Hammerschlag AR, et al. Genome-wide analysis of insomnia in 1,331,010 individuals identifies new risk loci and functional pathways. Nat Genet. 2019;51(3):394–403. pmid:30804565
- 67. Zammarchi G, Conversano C, Pisanu C. Investigating Shared Genetic Bases between Psychiatric Disorders, Cardiometabolic and Sleep Traits Using K-Means Clustering and Local Genetic Correlation Analysis. Algorithms. 2022;15(11):409.
- 68. Madrid-Valero JJ, Ordoñana JR, Gregory AM. A Narrative Review of Twin Study Contributions to the Understanding of Sleep and Sleep Disorders. Curr Sleep Medicine Rep. 2025;11(1).
- 69. Gasperi M, Herbert M, Schur E, Buchwald D, Afari N. Genetic and Environmental Influences on Sleep, Pain, and Depression Symptoms in a Community Sample of Twins. Psychosom Med. 2017;79(6):646–54. pmid:28658193
- 70. Zhou F, Guo Y, Wang Z, Liu S, Xu H. Assessing the causal associations of insomnia with depressive symptoms and subjective well-being: a bidirectional Mendelian randomization study. Sleep Med. 2021;87:85–91. pmid:34544013
- 71. Kivelä L, Papadopoulos MR, Antypa N. Chronotype and Psychiatric Disorders. Curr Sleep Med Rep. 2018;4(2):94–103. pmid:29888167
- 72. Torquati L, Mielke GI, Brown WJ, Burton NW, Kolbe-Alexander TL. Shift Work and Poor Mental Health: A Meta-Analysis of Longitudinal Studies. Am J Public Health. 2019;109(11):e13–20. pmid:31536404
- 73. Gorgoni M, Ferlazzo F, Moroni F, D’Atri A, Donarelli S, Fanelli S, et al. Sleep deprivation affects somatosensory cortex excitability as tested through median nerve stimulation. Brain Stimul. 2014;7(5):732–9. pmid:24953258
- 74. Wolf E, Kuhn M, Normann C, Mainberger F, Maier JG, Maywald S, et al. Synaptic plasticity model of therapeutic sleep deprivation in major depression. Sleep Med Rev. 2016;30:53–62. pmid:26803484
- 75. Volkow ND, Tomasi D, Wang G-J, Telang F, Fowler JS, Logan J, et al. Evidence that sleep deprivation downregulates dopamine D2R in ventral striatum in the human brain. J Neurosci. 2012;32(19):6711–7. pmid:22573693
- 76. Eban-Rothschild A, Appelbaum L, de Lecea L. Neuronal Mechanisms for Sleep/Wake Regulation and Modulatory Drive. Neuropsychopharmacology. 2018;43(5):937–52. pmid:29206811
- 77. Greene RW, Bjorness TE, Suzuki A. The adenosine-mediated, neuronal-glial, homeostatic sleep response. Curr Opin Neurobiol. 2017;44:236–42. pmid:28633050
- 78. Lazarus M, Chen J-F, Huang Z-L, Urade Y, Fredholm BB. Adenosine and Sleep. Handb Exp Pharmacol. 2019;253:359–81. pmid:28646346
- 79. Gujar N, Yoo S-S, Hu P, Walker MP. Sleep deprivation amplifies reactivity of brain reward networks, biasing the appraisal of positive emotional experiences. J Neurosci. 2011;31(12):4466–74. pmid:21430147
- 80. Pesoli M, Rucco R, Liparoti M, Lardone A, D’Aurizio G, Minino R, et al. A night of sleep deprivation alters brain connectivity and affects specific executive functions. Neurol Sci. 2022;43(2):1025–34. pmid:34244891
- 81. Ehlers CL, Frank E, Kupfer DJ. Social zeitgebers and biological rhythms. A unified approach to understanding the etiology of depression. Arch Gen Psychiatry. 1988;45(10):948–52. pmid:3048226
- 82. Tseng P-T, Chen Y-W, Tu K-Y, Chung W, Wang H-Y, Wu C-K, et al. Light therapy in the treatment of patients with bipolar depression: A meta-analytic study. Eur Neuropsychopharmacol. 2016;26(6):1037–47. pmid:26993616
- 83. Frank E, Kupfer DJ, Thase ME, Mallinger AG, Swartz HA, Fagiolini AM, et al. Two-year outcomes for interpersonal and social rhythm therapy in individuals with bipolar I disorder. Arch Gen Psychiatry. 2005;62(9):996–1004. pmid:16143731
- 84. Inder ML, Crowe MT, Luty SE, Carter JD, Moor S, Frampton CM, et al. Randomized, controlled trial of Interpersonal and Social Rhythm Therapy for young people with bipolar disorder. Bipolar Disord. 2015;17(2):128–38. pmid:25346391
- 85. Crowe M, Inder M, Douglas K, Carlyle D, Wells H, Jordan J, et al. Interpersonal and Social Rhythm Therapy for Patients With Major Depressive Disorder. Am J Psychother. 2020;73(1):29–34. pmid:31752508
- 86. Steardo L Jr, Luciano M, Sampogna G, Zinno F, Saviano P, Staltari F, et al. Efficacy of the interpersonal and social rhythm therapy (IPSRT) in patients with bipolar disorder: results from a real-world, controlled trial. Ann Gen Psychiatry. 2020;19:15. pmid:32165907
- 87. Weitzman ED, Zimmerman JC, Czeisler CA, Ronda J. Cortisol secretion is inhibited during sleep in normal man. J Clin Endocrinol Metab. 1983;56(2):352–8. pmid:6822642
- 88. Meerlo P, Sgoifo A, Suchecki D. Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity. Sleep Med Rev. 2008;12(3):197–210. pmid:18222099
- 89. Minkel J, Moreta M, Muto J, Htaik O, Jones C, Basner M, et al. Sleep deprivation potentiates HPA axis stress reactivity in healthy adults. Health Psychol. 2014;33(11):1430–4. pmid:24818608
- 90. van Dalfsen JH, Markus CR. The influence of sleep on human hypothalamic-pituitary-adrenal (HPA) axis reactivity: A systematic review. Sleep Med Rev. 2018;39:187–94. pmid:29126903
- 91. Vgontzas AN, Bixler EO, Lin HM, Prolo P, Mastorakos G, Vela-Bueno A, et al. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J Clin Endocrinol Metab. 2001;86(8):3787–94. pmid:11502812
- 92. Vgontzas AN, Bixler EO, Chrousos GP. Sleep apnea is a manifestation of the metabolic syndrome. Sleep Med Rev. 2005;9(3):211–24. pmid:15893251
- 93. Baker DG, Ekhator NN, Kasckow JW, Dashevsky B, Horn PS, Bednarik L, et al. Higher levels of basal serial CSF cortisol in combat veterans with posttraumatic stress disorder. Am J Psychiatry. 2005;162(5):992–4. pmid:15863803
- 94. Yehuda R, Southwick SM, Nussbaum G, Wahby V, Giller EL Jr, Mason JW. Low urinary cortisol excretion in patients with posttraumatic stress disorder. J Nerv Ment Dis. 1990;178(6):366–9. pmid:2348190
- 95. Meewisse M-L, Reitsma JB, de Vries G-J, Gersons BPR, Olff M. Cortisol and post-traumatic stress disorder in adults: systematic review and meta-analysis. Br J Psychiatry. 2007;191:387–92. pmid:17978317
- 96. Pan X, Wang Z, Wu X, Wen SW, Liu A. Salivary cortisol in post-traumatic stress disorder: a systematic review and meta-analysis. BMC Psychiatry. 2018;18(1):324. pmid:30290789
- 97. Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB, et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA. 2008;299(11):1291–305. pmid:18349090
- 98. Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, Pariante CM, et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci. 2013;16(1):33–41. pmid:23201972
- 99. Yehuda R, Flory JD, Bierer LM, Henn-Haase C, Lehrner A, Desarnaud F, et al. Lower methylation of glucocorticoid receptor gene promoter 1F in peripheral blood of veterans with posttraumatic stress disorder. Biol Psychiatry. 2015;77(4):356–64. pmid:24661442
- 100. Logue MW, Miller MW, Wolf EJ, Huber BR, Morrison FG, Zhou Z, et al. An epigenome-wide association study of posttraumatic stress disorder in US veterans implicates several new DNA methylation loci. Clin Epigenetics. 2020;12(1):46. pmid:32171335
- 101. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, et al. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010;67(5):446–57. pmid:20015486
- 102. Howren MB, Lamkin DM, Suls J. Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med. 2009;71(2):171–86. pmid:19188531
- 103. Köhler CA, Freitas TH, Maes M, de Andrade NQ, Liu CS, Fernandes BS, et al. Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies. Acta Psychiatr Scand. 2017;135(5):373–87. pmid:28122130
- 104. Irwin MR, Olmstead R, Carroll JE. Sleep Disturbance, Sleep Duration, and Inflammation: A Systematic Review and Meta-Analysis of Cohort Studies and Experimental Sleep Deprivation. Biol Psychiatry. 2016;80(1):40–52. pmid:26140821
- 105. Mullington J, Korth C, Hermann DM, Orth A, Galanos C, Holsboer F, et al. Dose-dependent effects of endotoxin on human sleep. Am J Physiol Regul Integr Comp Physiol. 2000;278(4):R947-55. pmid:10749783
- 106. Hermann DM, Mullington J, Hinze-Selch D, Schreiber W, Galanos C, Pollmächer T. Endotoxin-induced changes in sleep and sleepiness during the day. Psychoneuroendocrinology. 1998;23(5):427–37. pmid:9802118
- 107. Weinberger JF, Raison CL, Rye DB, Montague AR, Woolwine BJ, Felger JC, et al. Inhibition of tumor necrosis factor improves sleep continuity in patients with treatment resistant depression and high inflammation. Brain Behav Immun. 2015;47:193–200. pmid:25529904
- 108. Koreki A, Sado M, Mitsukura Y, Tachimori H, Kubota A, Kanamori Y, et al. The association between salivary IL-6 and poor sleep quality assessed using Apple watches in stressed workers in Japan. Sci Rep. 2024;14(1):22620. pmid:39349506
- 109. Irwin MR. Sleep disruption induces activation of inflammation and heightens risk for infectious disease: Role of impairments in thermoregulation and elevated ambient temperature. Temperature (Austin). 2022;10(2):198–234. pmid:37332305
- 110. Slavich GM, Irwin MR. From stress to inflammation and major depressive disorder: a social signal transduction theory of depression. Psychol Bull. 2014;140(3):774–815. pmid:24417575
- 111. Besedovsky L, Lange T, Haack M. The Sleep-Immune Crosstalk in Health and Disease. Physiol Rev. 2019;99(3):1325–80. pmid:30920354
- 112. Irwin MR, Wang M, Campomayor CO, Collado-Hidalgo A, Cole S. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med. 2006;166(16):1756–62. pmid:16983055
- 113. Herrero Babiloni A, Baril A-A, Charlebois-Plante C, Jodoin M, Sanchez E, De Baets L, et al. The Putative Role of Neuroinflammation in the Interaction between Traumatic Brain Injuries, Sleep, Pain and Other Neuropsychiatric Outcomes: A State-of-the-Art Review. J Clin Med. 2023;12(5):1793. pmid:36902580
- 114. Liu J, Xu Y, Ji Y, Li K, Wang S, Zhao B, et al. Sustained microglial activation and accelerated elimination of dendritic spines during acute sleep deprivation and restoration. Innov Life. 2023;1(3):100037.
- 115. Sriram S, Carstens K, Dewing W, Fiacco TA. Astrocyte regulation of extracellular space parameters across the sleep-wake cycle. Front Cell Neurosci. 2024;18:1401698. pmid:38988660
- 116. Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science. 2013;342(6156):373–7. pmid:24136970
- 117. Deng S, Hu Y, Chen S, Xue Y, Yao D, Sun Q, et al. Chronic sleep fragmentation impairs brain interstitial clearance in young wildtype mice. J Cereb Blood Flow Metab. 2024;44(9):1515–31. pmid:38639025
- 118. Vasciaveo V, Iadarola A, Casile A, Dante D, Morello G, Minotta L, et al. Sleep fragmentation affects glymphatic system through the different expression of AQP4 in wild type and 5xFAD mouse models. Acta Neuropathol Commun. 2023;11(1):16. pmid:36653878
- 119. Ma J, Chen M, Liu G-H, Gao M, Chen N-H, Toh CH, et al. Effects of sleep on the glymphatic functioning and multimodal human brain network affecting memory in older adults. Mol Psychiatry. 2025;30(5):1717–29. pmid:39397082
- 120. Sondrup N, Termannsen A-D, Eriksen JN, Hjorth MF, Færch K, Klingenberg L, et al. Effects of sleep manipulation on markers of insulin sensitivity: A systematic review and meta-analysis of randomized controlled trials. Sleep Med Rev. 2022;62:101594. pmid:35189549
- 121. Kianersi S, Redline S, Mongraw-Chaffin M, Huang T. Associations of Slow-Wave Sleep With Prevalent and Incident Type 2 Diabetes in the Multi-Ethnic Study of Atherosclerosis. J Clin Endocrinol Metab. 2023;108(10):e1044–55. pmid:37084404
- 122. Fernandes BS, Salagre E, Enduru N, Grande I, Vieta E, Zhao Z. Insulin resistance in depression: A large meta-analysis of metabolic parameters and variation. Neurosci Biobehav Rev. 2022;139:104758. pmid:35777578
- 123. Pan A, Keum N, Okereke OI, Sun Q, Kivimaki M, Rubin RR, et al. Bidirectional association between depression and metabolic syndrome: a systematic review and meta-analysis of epidemiological studies. Diabetes Care. 2012;35(5):1171–80. pmid:22517938
- 124. van Egmond LT, Meth EMS, Engström J, Ilemosoglou M, Keller JA, Vogel H, et al. Effects of acute sleep loss on leptin, ghrelin, and adiponectin in adults with healthy weight and obesity: A laboratory study. Obesity (Silver Spring). 2023;31(3):635–41. pmid:36404495
- 125. Gresser D, McLimans K, Lee S, Morgan-Bathke M. The Impact of Sleep Deprivation on Hunger-Related Hormones: A Meta-Analysis and Systematic Review. Obesities. 2025;5(2):48.
- 126. Milaneschi Y, Lamers F, Bot M, Drent ML, Penninx BWJH. Leptin Dysregulation Is Specifically Associated With Major Depression With Atypical Features: Evidence for a Mechanism Connecting Obesity and Depression. Biol Psychiatry. 2017;81(9):807–14. pmid:26742925
- 127. Sentissi O, Epelbaum J, Olié J-P, Poirier M-F. Leptin and ghrelin levels in patients with schizophrenia during different antipsychotics treatment: a review. Schizophr Bull. 2008;34(6):1189–99. pmid:18165262
- 128. Broussard JL, Knud-Hansen BC, Grady S, Knauer OA, Ronda JM, Aeschbach D, et al. Influence of circadian phase and extended wakefulness on glucose levels during forced desynchrony. Sleep Health. 2024;10(1S):S96–102. pmid:37996284
- 129. Mason IC, Qian J, Adler GK, Scheer FAJL. Impact of circadian disruption on glucose metabolism: implications for type 2 diabetes. Diabetologia. 2020;63(3):462–72. pmid:31915891
- 130. Brochard H, Godin O, Geoffroy PA, Yeim S, Boudebesse C, Benizri C, et al. Metabolic syndrome and actigraphy measures of sleep and circadian rhythms in bipolar disorders during remission. Acta Psychiatr Scand. 2018;138(2):155–62. pmid:29845615
- 131. Campbell IH, Frye MA, Campbell H. Metabolic plasticity: an evolutionary perspective on metabolic and circadian dysregulation in bipolar disorder. Mol Psychiatry. 2025;30(11):5600–12. pmid:40681844
- 132. Koning E, McDonald A, Bambokian A, Gomes FA, Vorstman J, Berk M, et al. The concept of “metabolic jet lag” in the pathophysiology of bipolar disorder: implications for research and clinical care. CNS Spectr. 2023;28(5):571–80. pmid:36503605
- 133. Mortimer KRH, Katshu MZUH, Chakrabarti L. Second-generation antipsychotics and metabolic syndrome: a role for mitochondria. Front Psychiatry. 2023;14:1257460. pmid:38076704
- 134. Yan H, Huang Z, Lu Y, Qiu Y, Li M, Li J. Associations between metabolic disorders and sleep disturbance in patients with schizophrenia. Compr Psychiatry. 2023;122:152369. pmid:36702060
- 135. Reutrakul S, Van Cauter E. Sleep influences on obesity, insulin resistance, and risk of type 2 diabetes. Metabolism. 2018;84:56–66. pmid:29510179
- 136. Mao Y. Sleep Architecture Changes in Diabetes. J Clin Med. 2024;13(22):6851. pmid:39597994
- 137. St-Onge M-P, Tasali E. Weight Loss Is Integral to Obstructive Sleep Apnea Management. Ten-Year Follow-up in Sleep AHEAD. Am J Respir Crit Care Med. 2021;203(2):161–2. pmid:32795248
- 138. Tolentino JC, Schmidt SL. DSM-5 Criteria and Depression Severity: Implications for Clinical Practice. Front Psychiatry. 2018;9:450. pmid:30333763
- 139. Geoffroy PA, Hoertel N, Etain B, Bellivier F, Delorme R, Limosin F, et al. Insomnia and hypersomnia in major depressive episode: Prevalence, sociodemographic characteristics and psychiatric comorbidity in a population-based study. J Affect Disord. 2018;226:132–41. pmid:28972930
- 140. Chen Y, Zhang L, Hu S, Zhang H, Sun Q, Hong M, et al. Status and Correlates of Hypersomnia in Hospitalized Patients with Unipolar Depression - Beijing, Henan, and Shandong, China, August 2019-March 2021. China CDC Wkly. 2021;3(42):879–82. pmid:34733575
- 141. Łojko D, Rybakowski JK. Atypical depression: current perspectives. Neuropsychiatr Dis Treat. 2017;13:2447–56. pmid:29033570
- 142. Soehner AM, Kaplan KA, Harvey AG. Prevalence and clinical correlates of co-occurring insomnia and hypersomnia symptoms in depression. J Affect Disord. 2014;167:93–7. pmid:24953480
- 143. Inada K, Enomoto M, Yamato K, Marumoto T, Takeshima M, Mishima K. Effect of residual insomnia and use of hypnotics on relapse of depression: a retrospective cohort study using a health insurance claims database. J Affect Disord. 2021;281:539–46.
- 144. Slavish DC, Graham-Engeland JE. Rumination mediates the relationships between depressed mood and both sleep quality and self-reported health in young adults. J Behav Med. 2015;38(2):204–13. pmid:25195078
- 145. Kalmbach DA, Pillai V, Drake CL. Nocturnal insomnia symptoms and stress-induced cognitive intrusions in risk for depression: A 2-year prospective study. PLoS One. 2018;13(2):e0192088. pmid:29438400
- 146. Kalmbach DA, Cheng P, Drake CL. A pathogenic cycle between insomnia and cognitive arousal fuels perinatal depression: exploring the roles of nocturnal cognitive arousal and perinatal-focused rumination. Sleep. 2021;44(6):zsab028. pmid:33830248
- 147. Fell J. Mind wandering, poor sleep, and negative affect: a threefold vicious cycle?. Front Hum Neurosci. 2024;18:1441565. pmid:39310791
- 148. Adrien J. Neurobiological bases for the relation between sleep and depression. Sleep Med Rev. 2002;6(5):341–51.
- 149. Wichniak A, Antczak J, Wierzbicka A, Jernajczyk W. Alterations in pattern of rapid eye movement activity during REM sleep in depression. Acta Neurobiol Exp (Wars). 2002;62(4):243–50. pmid:12659290
- 150. Luik AI, Zuurbier LA, Whitmore H, Hofman A, Tiemeier H. REM sleep and depressive symptoms in a population-based study of middle-aged and elderly persons. J Sleep Res. 2015;24(3):305–8.
- 151. Vreeburg SA, Hoogendijk WJG, van Pelt J, Derijk RH, Verhagen JCM, van Dyck R, et al. Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study. Arch Gen Psychiatry. 2009;66(6):617–26. pmid:19487626
- 152. Antonijevic I. HPA axis and sleep: identifying subtypes of major depression. Stress. 2008;11(1):15–27. pmid:17853067
- 153. Schmid DA, Wichniak A, Uhr M, Ising M, Brunner H, Held K, et al. Changes of sleep architecture, spectral composition of sleep EEG, the nocturnal secretion of cortisol, ACTH, GH, prolactin, melatonin, ghrelin, and leptin, and the DEX-CRH test in depressed patients during treatment with mirtazapine. Neuropsychopharmacology. 2006;31(4):832–44. pmid:16237393
- 154. Fu W, Dai C, Chen J, Wang L, Song T, Peng Z, et al. Altered insular functional connectivity correlates to impaired vigilant attention after sleep deprivation: A resting-state functional magnetic resonance imaging study. Front Neurosci. 2022;16:889009. pmid:35958999
- 155. Dai K, Liu X, Hu J, Ren F, Jin Z, Xu S, et al. Insomnia-related brain functional correlates in first-episode drug-naïve major depressive disorder revealed by resting-state fMRI. Front Neurosci. 2024;18:1290345. pmid:39268040
- 156. Klumpp H, Hosseini B, Phan KL. Self-Reported Sleep Quality Modulates Amygdala Resting-State Functional Connectivity in Anxiety and Depression. Front Psychiatry. 2018;9:220. pmid:29896128
- 157. Goldschmied JR, Cheng P, Armitage R, Deldin PJ. A preliminary investigation of the role of slow-wave activity in modulating waking EEG theta as a marker of sleep propensity in major depressive disorder. J Affect Disord. 2019;257:504–9. pmid:31319342
- 158. Manber R, Buysse DJ, Edinger J, Krystal A, Luther JF, Wisniewski SR, et al. Efficacy of Cognitive-Behavioral Therapy for Insomnia Combined With Antidepressant Pharmacotherapy in Patients With Comorbid Depression and Insomnia: A Randomized Controlled Trial. J Clin Psychiatry. 2016;77(10):e1316–23. pmid:27788313
- 159. Cunningham JEA, Shapiro CM. Cognitive Behavioural Therapy for Insomnia (CBT-I) to treat depression: A systematic review. J Psychosom Res. 2018;106:1–12. pmid:29455893
- 160. Furukawa Y, Nagaoka D, Sato S, Toyomoto R, Takashina HN, Kobayashi K, et al. Cognitive behavioral therapy for insomnia to treat major depressive disorder with comorbid insomnia: A systematic review and meta-analysis. J Affect Disord. 2024;367:359–66. pmid:39242039
- 161. Sateia MJ, Buysse DJ, Krystal AD, Neubauer DN, Heald JL. Clinical Practice Guideline for the Pharmacologic Treatment of Chronic Insomnia in Adults: An American Academy of Sleep Medicine Clinical Practice Guideline. J Clin Sleep Med. 2017;13(2):307–49. pmid:27998379
- 162. Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675–700. pmid:28875581
- 163. Hutka P, Krivosova M, Muchova Z, Tonhajzerova I, Hamrakova A, Mlyncekova Z, et al. Association of Sleep Architecture and Physiology with Depressive Disorder and Antidepressants Treatment. Int J Mol Sci. 2021;22(3):1333. pmid:33572767
- 164. Kaynak H, Kaynak D, Gözükirmizi E, Guilleminault C. The effects of trazodone on sleep in patients treated with stimulant antidepressants. Sleep Med. 2004;5(1):15–20. pmid:14725822
- 165. Jaffer KY, Chang T, Vanle B, Dang J, Steiner AJ, Loera N, et al. Trazodone for Insomnia: A Systematic Review. Innov Clin Neurosci. 2017;14(7–8):24–34. pmid:29552421
- 166. Brooks S, Jacobs GE, de Boer P, Kent JM, Van Nueten L, van Amerongen G, et al. The selective orexin-2 receptor antagonist seltorexant improves sleep: An exploratory double-blind, placebo controlled, crossover study in antidepressant-treated major depressive disorder patients with persistent insomnia. J Psychopharmacol. 2019;33(2):202–9. pmid:30644312
- 167. Savitz A, Wajs E, Zhang Y, Xu H, Etropolski M, Thase ME, et al. Efficacy and Safety of Seltorexant as Adjunctive Therapy in Major Depressive Disorder: A Phase 2b, Randomized, Placebo-Controlled, Adaptive Dose-Finding Study. Int J Neuropsychopharmacol. 2021;24(12):965–76. pmid:34324636
- 168. Harvey AG, Talbot LS, Gershon A. Sleep Disturbance in Bipolar Disorder Across the Lifespan. Clin Psychol (New York). 2009;16(2):256–77. pmid:22493520
- 169. Steardo L Jr, de Filippis R, Carbone EA, Segura-Garcia C, Verkhratsky A, De Fazio P. Sleep Disturbance in Bipolar Disorder: Neuroglia and Circadian Rhythms. Front Psychiatry. 2019;10:501. pmid:31379620
- 170. Steinan MK, Morken G, Lagerberg TV, Melle I, Andreassen OA, Vaaler AE, et al. Delayed sleep phase: An important circadian subtype of sleep disturbance in bipolar disorders. J Affect Disord. 2016;191:156–63. pmid:26655861
- 171. Ng TH, Chung K-F, Ho FY-Y, Yeung W-F, Yung K-P, Lam T-H. Sleep-wake disturbance in interepisode bipolar disorder and high-risk individuals: a systematic review and meta-analysis. Sleep Med Rev. 2015;20:46–58. pmid:25060968
- 172. Basquin L, Maruani J, Leseur J, Mauries S, Bazin B, Pineau G, et al. Study of the different sleep disturbances during the prodromal phase of depression and mania in bipolar disorders. Bipolar Disord. 2024;26(5):454–67. pmid:38653574
- 173. Ulrichsen A, Tröger A, Jauhar S, Severus E, Bauer M, Cleare A. Do sleep variables predict mood in bipolar disorder: A systematic review. J Affect Disord. 2025;373:364–73. pmid:39740744
- 174. Takaesu Y, Inoue Y, Ono K, Murakoshi A, Futenma K, Komada Y, et al. Circadian Rhythm Sleep-Wake Disorders Predict Shorter Time to Relapse of Mood Episodes in Euthymic Patients With Bipolar Disorder: A Prospective 48-Week Study. J Clin Psychiatry. 2018;79(1):17m11565. pmid:29286593
- 175. Esaki Y, Obayashi K, Saeki K, Fujita K, Iwata N, Kitajima T. Circadian variability of objective sleep measures predicts the relapse of a mood episode in bipolar disorder: Findings from the APPLE cohort. Psychiatry Clin Neurosci. 2023 Aug;77(8):442-8. Erratum in: Psychiatry Clin Neurosci. 2024;78(2):148. https://doi.org/10.1111/pcn.13646
- 176. Ferrand L, Hennion V, Godin O, Bellivier F, Scott J, Etain B. Which Actigraphy Dimensions Predict Longitudinal Outcomes in Bipolar Disorders? J Clin Med. 2022;11(8):2204. pmid:35456294
- 177. Lewis KS, Gordon-Smith K, Forty L, Di Florio A, Craddock N, Jones L, et al. Sleep loss as a trigger of mood episodes in bipolar disorder: individual differences based on diagnostic subtype and gender. Br J Psychiatry. 2017;211(3):169–74. pmid:28684405
- 178. Colombo C, Benedetti F, Barbini B, Campori E, Smeraldi E. Rate of switch from depression into mania after therapeutic sleep deprivation in bipolar depression. Psychiatry Res. 1999;86(3):267–70. pmid:10482346
- 179. Bengesser SA, Reininghaus EZ, Lackner N, Birner A, Fellendorf FT, Platzer M, et al. Is the molecular clock ticking differently in bipolar disorder? Methylation analysis of the clock gene ARNTL. World J Biol Psychiatry. 2018;19(sup2):S21–9. pmid:27739341
- 180. Li J, Lu W-Q, Beesley S, Loudon ASI, Meng Q-J. Lithium impacts on the amplitude and period of the molecular circadian clockwork. PLoS One. 2012;7(3):e33292. pmid:22428012
- 181. Osland TM, Fernø J, Håvik B, Heuch I, Ruoff P, Lærum OD, et al. Lithium differentially affects clock gene expression in serum-shocked NIH-3T3 cells. J Psychopharmacol. 2011;25(7):924–33. pmid:20837565
- 182. Sit DK, Terman M, Wisner KL. Light Therapy and Risk of Hypomania, Mania, or Mixed State Emergence: Response to Benedetti et al. Am J Psychiatry. 2018;175(9):906. pmid:30173552
- 183. Gottlieb JF, Benedetti F, Geoffroy PA, Henriksen TEG, Lam RW, Murray G, et al. The chronotherapeutic treatment of bipolar disorders: A systematic review and practice recommendations from the ISBD task force on chronotherapy and chronobiology. Bipolar Disord. 2019;21(8):741–73. pmid:31609530
- 184. Kishi T, Nomura I, Sakuma K, Kitajima T, Mishima K, Iwata N. Melatonin receptor agonists-ramelteon and melatonin-for bipolar disorder: a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials. Neuropsychiatr Dis Treat. 2019;15:1479–86. pmid:31239683
- 185. McGowan NM, Kim DS, de Andres Crespo M, Bisdounis L, Kyle SD, Saunders KEA. Hypnotic and Melatonin/Melatonin-Receptor Agonist Treatment in Bipolar Disorder: A Systematic Review and Meta-Analysis. CNS Drugs. 2022;36(4):345–63. pmid:35305257
- 186. Gao K, Mackle M, Cazorla P, Zhao J, Szegedi A. Comparison of somnolence associated with asenapine, olanzapine, risperidone, and haloperidol relative to placebo in patients with schizophrenia or bipolar disorder. Neuropsychiatr Dis Treat. 2013;9:1145–57. pmid:24003306
- 187. Monti JM. The effect of second-generation antipsychotic drugs on sleep parameters in patients with unipolar or bipolar disorder. Sleep Med. 2016;23:89–96. pmid:27692282
- 188. Xue Y, Wang W-D, Liu Y-J, Wang J, Walters AS. Sleep disturbances in generalized anxiety Disorder: The central role of insomnia. Sleep Med. 2025;132:106545. pmid:40318600
- 189. Belleville G, Potočnik A. A meta-analysis of sleep disturbances in panic disorder [Internet]. In: Psychopathology – An International and Interdisciplinary Perspective. London: IntechOpen; 2020.
- 190. Pecknold JC, Luthe L. Sleep studies and neurochemical correlates in panic disorder and agoraphobia. Prog Neuropsychopharmacol Biol Psychiatry. 1990;14(5):753–8. pmid:2293254
- 191. Peng A, Ji S, Lai W, Hu D, Wang M, Zhao X, et al. The bidirectional relationship between sleep disturbance and anxiety: Sleep disturbance is a stronger predictor of anxiety. Sleep Med. 2024;121:63–8. pmid:38924831
- 192. Zagaria A, Ballesio A. Insomnia symptoms as long-term predictors of anxiety symptoms in middle-aged and older adults from the English Longitudinal Study of Ageing (ELSA), and the role of systemic inflammation. Sleep Med. 2024;124:120–6. pmid:39293197
- 193. Horváth A, Montana X, Lanquart J-P, Hubain P, Szűcs A, Linkowski P, et al. Effects of state and trait anxiety on sleep structure: A polysomnographic study in 1083 subjects. Psychiatry Res. 2016;244:279–83. pmid:27512915
- 194. Jansson-Fröjmark M, Lindblom K. A bidirectional relationship between anxiety and depression, and insomnia? A prospective study in the general population. J Psychosom Res. 2008;64(4):443–9. pmid:18374745
- 195. Hong J, Choi K, Fuccillo MV, Chung S, Weber F. Infralimbic activity during REM sleep facilitates fear extinction memory. Curr Biol. 2024;34(10):2247-2255.e5. pmid:38714199
- 196. Straus LD, Norman SB, Risbrough VB, Acheson DT, Drummond SPA. REM sleep and safety signal learning in posttraumatic stress disorder: A preliminary study in military veterans. Neurobiol Stress. 2018;9:22–8. pmid:30116769
- 197. Richards A, Inslicht SS, Yack LM, Metzler TJ, Russell Huie J, Straus LD, et al. The relationship of fear-potentiated startle and polysomnography-measured sleep in trauma-exposed men and women with and without PTSD: testing REM sleep effects and exploring the roles of an integrative measure of sleep, PTSD symptoms, and biological sex. Sleep. 2022;45(1):zsab271. pmid:34792165
- 198. Walker MP, van der Helm E. Overnight therapy? The role of sleep in emotional brain processing. Psychol Bull. 2009;135(5):731–48. pmid:19702380
- 199. van Liempt S, Arends J, Cluitmans PJM, Westenberg HGM, Kahn RS, Vermetten E. Sympathetic activity and hypothalamo-pituitary-adrenal axis activity during sleep in post-traumatic stress disorder: a study assessing polysomnography with simultaneous blood sampling. Psychoneuroendocrinology. 2013;38(1):155–65. pmid:22776420
- 200. Newport DJ, Nemeroff CB. Neurobiology of Posttraumatic Stress Disorder. FOC. 2003;1(3):313–21.
- 201. Yehuda R, Halligan SL, Golier JA, Grossman R, Bierer LM. Effects of trauma exposure on the cortisol response to dexamethasone administration in PTSD and major depressive disorder. Psychoneuroendocrinology. 2004;29(3):389–404. pmid:14644068
- 202. Mellman TA, Kumar A, Kulick-Bell R, Kumar M, Nolan B. Nocturnal/daytime urine noradrenergic measures and sleep in combat-related PTSD. Biol Psychiatry. 1995;38(3):174–9. pmid:7578660
- 203. Khanday MA, Somarajan BI, Mehta R, Mallick BN. Noradrenaline from Locus Coeruleus Neurons Acts on Pedunculo-Pontine Neurons to Prevent REM Sleep and Induces Its Loss-Associated Effects in Rats. eNeuro. 2016;3(6):ENEURO.0108-16.2016. pmid:27957531
- 204. McCall A, Forouhandehpour R, Celebi S, Richard-Malenfant C, Hamati R, Guimond S, et al. Evidence for Locus Coeruleus–Norepinephrine System Abnormality in Military Posttraumatic Stress Disorder Revealed by Neuromelanin-Sensitive Magnetic Resonance Imaging. Biol Psychiatry. 2024;96(4):268–77.
- 205. Jansson-Fröjmark M, Jacobson K. Cognitive behavioural therapy for insomnia for patients with co-morbid generalized anxiety disorder: an open trial on clinical outcomes and putative mechanisms. Behav Cogn Psychother. 2021;49(5):540–55. pmid:33504410
- 206. Lau P, Starick E, Carney CE. Anxiolytic impact of cognitive behavioural therapy for insomnia in patients with co-morbid insomnia and generalized anxiety disorder. Behav Cogn Psychother. 2024;52(4):456–60. pmid:38282533
- 207. Craske MG, Lang AJ, Aikins D, Mystkowski JL. Cognitive behavioral therapy for nocturnal panic. Behav Ther. 2005;36(1):43–54.
- 208. Pollack MH, Hoge EA, Worthington JJ, Moshier SJ, Wechsler RS, Brandes M, et al. Eszopiclone for the treatment of posttraumatic stress disorder and associated insomnia: a randomized, double-blind, placebo-controlled trial. J Clin Psychiatry. 2011;72(7):892–7. pmid:21367352
- 209. Lam L, Ho FY-Y, Wong VW-H, Chan K-W, Poon C-Y, Yeung W-F, et al. Actigraphic sleep monitoring in patients with post-traumatic stress disorder (PTSD): A meta-analysis. J Affect Disord. 2023;320:450–60. pmid:36174789
- 210. van Liempt S, van Zuiden M, Westenberg H, Super A, Vermetten E. Impact of impaired sleep on the development of PTSD symptoms in combat veterans: a prospective longitudinal cohort study. Depress Anxiety. 2013;30(5):469–74. pmid:23389990
- 211. Acheson DT, Kwan B, Maihofer AX, Risbrough VB, Nievergelt CM, Clark JW, et al. Sleep disturbance at pre-deployment is a significant predictor of post-deployment re-experiencing symptoms. Eur J Psychotraumatol. 2019;10(1):1679964. pmid:31723377
- 212. Chinoy ED, Carey FR, Kolaja CA, Jacobson IG, Cooper AD, Markwald RR. The bi-directional relationship between post-traumatic stress disorder and obstructive sleep apnea and/or insomnia in a large U.S. military cohort. Sleep Health. 2022;8(6):606–14. pmid:36163136
- 213. Saguin E, Gomez-Merino D, Sauvet F, Leger D, Chennaoui M. Sleep and PTSD in the Military Forces: A Reciprocal Relationship and a Psychiatric Approach. Brain Sci. 2021;11(10):1310. pmid:34679375
- 214. Pigeon WR, Campbell CE, Possemato K, Ouimette P. Longitudinal relationships of insomnia, nightmares, and PTSD severity in recent combat veterans. J Psychosom Res. 2013;75(6):546–50. pmid:24290044
- 215. Kartal D, Arjmand H-A, Varker T, Cowlishaw S, O’Donnell M, Phelps A, et al. Cross-Lagged Relationships Between Insomnia and Posttraumatic Stress Disorder in Treatment-Receiving Veterans. Behav Ther. 2021;52(4):982–94. pmid:34134836
- 216. Kajeepeta S, Gelaye B, Jackson CL, Williams MA. Adverse childhood experiences are associated with adult sleep disorders: a systematic review. Sleep Med. 2015;16(3):320–30. pmid:25777485
- 217. Desch J, Bakour C, Mansuri F, Tran D, Schwartz S. The association between adverse childhood experiences and insomnia symptoms from adolescence to adulthood: Evidence from the Add Health study. Sleep Health. 2023;9(5):646–53. pmid:37419708
- 218. Talbot LS, Maguen S, Metzler TJ, Schmitz M, McCaslin SE, Richards A, et al. Cognitive behavioral therapy for insomnia in posttraumatic stress disorder: a randomized controlled trial. Sleep. 2014;37(2):327–41. pmid:24497661
- 219. Raskind MA, Peterson K, Williams T, Hoff DJ, Hart K, Holmes H, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry. 2013;170(9):1003–10. pmid:23846759
- 220. Taylor FB, Martin P, Thompson C, Williams J, Mellman TA, Gross C, et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008;63(6):629–32. pmid:17868655
- 221. Raskind MA, Peskind ER, Chow B, Harris C, Davis-Karim A, Holmes HA, et al. Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans. N Engl J Med. 2018;378(6):507–17. pmid:29414272
- 222. Germain A, Richardson R, Moul DE, Mammen O, Haas G, Forman SD, et al. Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US Military Veterans. J Psychosom Res. 2012;72(2):89–96. pmid:22281448
- 223. Colvonen PJ, Masino T, Drummond SPA, Myers US, Angkaw AC, Norman SB. Obstructive Sleep Apnea and Posttraumatic Stress Disorder among OEF/OIF/OND Veterans. J Clin Sleep Med. 2015;11(5):513–8. pmid:25665698
- 224. Chen M-Y, Wang Y-Y, Si TL, Liu Y-F, Su Z, Cheung T, et al. Poor sleep quality in schizophrenia patients: A systematic review and meta-analyses of epidemiological and case-control studies. Schizophr Res. 2024;264:407–15. pmid:38241784
- 225. Bagautdinova J, Mayeli A, Wilson JD, Donati FL, Colacot RM, Meyer N, et al. Sleep Abnormalities in Different Clinical Stages of Psychosis: A Systematic Review and Meta-analysis. JAMA Psychiatry. 2023;80(3):202–10. pmid:36652243
- 226. Lai M, Hegde R, Kelly S, Bannai D, Lizano P, Stickgold R, et al. Investigating sleep spindle density and schizophrenia: A meta-analysis. Psychiatry Res. 2022;307:114265. pmid:34922240
- 227. Reeve S, Sheaves B, Freeman D. The role of sleep dysfunction in the occurrence of delusions and hallucinations: A systematic review. Clin Psychol Rev. 2015;42:96–115. pmid:26407540
- 228. Mulligan LD, Haddock G, Emsley R, Neil ST, Kyle SD. High resolution examination of the role of sleep disturbance in predicting functioning and psychotic symptoms in schizophrenia: A novel experience sampling study. J Abnorm Psychol. 2016;125(6):788–97. pmid:27362488
- 229. Wulff K, Dijk D-J, Middleton B, Foster RG, Joyce EM. Sleep and circadian rhythm disruption in schizophrenia. Br J Psychiatry. 2012;200(4):308–16. pmid:22194182
- 230. Li SX, Lam SP, Zhang J, Yu MWM, Chan JWY, Chan CSY, et al. Sleep Disturbances and Suicide Risk in an 8-Year Longitudinal Study of Schizophrenia-Spectrum Disorders. Sleep. 2016;39(6):1275–82. pmid:27091530
- 231. Ferrarelli F, Huber R, Peterson MJ, Massimini M, Murphy M, Riedner BA, et al. Reduced sleep spindle activity in schizophrenia patients. Am J Psychiatry. 2007;164(3):483–92. pmid:17329474
- 232. Wamsley EJ, Tucker MA, Shinn AK, Ono KE, McKinley SK, Ely AV, et al. Reduced sleep spindles and spindle coherence in schizophrenia: mechanisms of impaired memory consolidation? Biol Psychiatry. 2012;71(2):154–61. pmid:21967958
- 233. Woodward ND, Karbasforoushan H, Heckers S. Thalamocortical dysconnectivity in schizophrenia. Am J Psychiatry. 2012;169(10):1092–9. pmid:23032387
- 234. Baran B, Karahanoğlu FI, Mylonas D, Demanuele C, Vangel M, Stickgold R, et al. Increased Thalamocortical Connectivity in Schizophrenia Correlates With Sleep Spindle Deficits: Evidence for a Common Pathophysiology. Biol Psychiatry Cogn Neurosci Neuroimaging. 2019;4(8):706–14. pmid:31262708
- 235. Ramsay IS, Mueller B, Ma Y, Shen C, Sponheim SR. Thalamocortical connectivity and its relationship with symptoms and cognition across the psychosis continuum. Psychol Med. 2023;53(12):5582–91. pmid:36047043
- 236. Avram M, Brandl F, Bäuml J, Sorg C. Cortico-thalamic hypo- and hyperconnectivity extend consistently to basal ganglia in schizophrenia. Neuropsychopharmacology. 2018;43(11):2239–48. pmid:29899404
- 237. Chun S, Westmoreland JJ, Bayazitov IT, Eddins D, Pani AK, Smeyne RJ, et al. Specific disruption of thalamic inputs to the auditory cortex in schizophrenia models. Science. 2014;344(6188):1178–82. pmid:24904170
- 238. Monti JM, Torterolo P, Pandi Perumal SR. The effects of second generation antipsychotic drugs on sleep variables in healthy subjects and patients with schizophrenia. Sleep Med Rev. 2017;33:51–7. pmid:27321864
- 239. Cederlöf E, Holm M, Taipale H, Tiihonen J, Tanskanen A, Lähteenvuo M, et al. Antipsychotic medications and sleep problems in patients with schizophrenia. Schizophr Res. 2024;267:230–8. pmid:38579432
- 240. Ugurlu M, Karakas Ugurlu G, Kabadayi Sahin E, Kamis GZ, Caykoylu A. Short and long-term effects of cognitive behavioral therapy on sleep problems and psychotic symptoms in patients with psychotic disorders: a meta-analysis. Braz J Psychiatry. 2025;47:e20243623. pmid:39102660
- 241. Waters F, Chiu VW, Dragovic M, Ree M. Different patterns of treatment response to Cognitive-Behavioural Therapy for Insomnia (CBT-I) in psychosis. Schizophr Res. 2020;221:57–62. pmid:32317223
- 242. Hvolby A. Associations of sleep disturbance with ADHD: implications for treatment. Atten Defic Hyperact Disord. 2015;7(1):1–18. pmid:25127644
- 243. Kato T, Ozone M, Kotorii N, Ohshima H, Hyoudou Y, Mori H, et al. Sleep Structure in Untreated Adults With ADHD: A Retrospective Study. J Atten Disord. 2023;27(5):488–98. pmid:36851892
- 244. Marten F, Keuppens L, Baeyens D, Boyer BE, Danckaerts M, Cortese S, et al. Sleep parameters and problems in adolescents with and without ADHD: A systematic review and meta-analysis. JCPP Adv. 2023;3(3):e12151. pmid:37720581
- 245. Estes A, Hillman A, Chen ML. Sleep and Autism: Current Research, Clinical Assessment, and Treatment Strategies. Focus (Am Psychiatr Publ). 2024;22(2):162–9. pmid:38680972
- 246. Smith AM, Johnson AH, Bashore L. Exploration of sleep disturbances in children and adolescents with and without autism in a paediatric sample referred for polysomnography. J Paediatr Child Health. 2023;59(8):948–54. pmid:37162017
- 247. Johnson KP, Zarrinnegar P. Autism Spectrum Disorder and Sleep. Child Adolesc Psychiatr Clin N Am. 2021;30(1):195–208. pmid:33223062
- 248. Bijlenga D, van der Heijden KB, Breuk M, van Someren EJW, Lie MEH, Boonstra AM, et al. Associations between sleep characteristics, seasonal depressive symptoms, lifestyle, and ADHD symptoms in adults. J Atten Disord. 2013;17(3):261–75. pmid:22210799
- 249. Gruber R, Salamon L, Tauman R, Al-Yagon M. Sleep Disturbances in Adolescents with Attention-Deficit/Hyperactivity Disorder. Nat Sci Sleep. 2023;15:275–86. pmid:37113558
- 250. Sidol CA, Becker SP, Peugh JL, Lynch JD, Ciesielski HA, Zoromski AK, et al. Examining bidirectional associations between sleep and behavior among children with attention-deficit/hyperactivity disorder. JCPP Adv. 2023;3(2):e12157. pmid:37753159
- 251. Shen C, Luo Q, Chamberlain SR, Morgan S, Romero-Garcia R, Du J, et al. What Is the Link Between Attention-Deficit/Hyperactivity Disorder and Sleep Disturbance? A Multimodal Examination of Longitudinal Relationships and Brain Structure Using Large-Scale Population-Based Cohorts. Biol Psychiatry. 2020;88(6):459–69.
- 252. Lunsford-Avery JR, Kollins SH. Editorial Perspective: Delayed circadian rhythm phase: a cause of late-onset attention-deficit/hyperactivity disorder among adolescents? J Child Psychol Psychiatry. 2018;59(12):1248–51. pmid:30176050
- 253. May T, Cornish K, Conduit R, Rajaratnam SMW, Rinehart NJ. Sleep in high-functioning children with autism: longitudinal developmental change and associations with behavior problems. Behav Sleep Med. 2015;13(1):2–18. pmid:24283751
- 254. Mazurek MO, Dovgan K, Neumeyer AM, Malow BA. Course and Predictors of Sleep and Co-occurring Problems in Children with Autism Spectrum Disorder. J Autism Dev Disord. 2019;49(5):2101–15. pmid:30684086
- 255. Verhoeff ME, Blanken LME, Kocevska D, Mileva-Seitz VR, Jaddoe VWV, White T, et al. The bidirectional association between sleep problems and autism spectrum disorder: a population-based cohort study. Mol Autism. 2018;9:8. pmid:29423134
- 256. Papadopoulos N, Sciberras E, Hiscock H, Mulraney M, McGillivray J, Rinehart N. The Efficacy of a Brief Behavioral Sleep Intervention in School-Aged Children With ADHD and Comorbid Autism Spectrum Disorder. J Atten Disord. 2019;23(4):341–50. pmid:25646022
- 257. Melke J, Goubran Botros H, Chaste P, Betancur C, Nygren G, Anckarsäter H, et al. Abnormal melatonin synthesis in autism spectrum disorders. Mol Psychiatry. 2008;13(1):90–8. pmid:17505466
- 258. Dell’Osso L, Massoni L, Battaglini S, Cremone IM, Carmassi C, Carpita B. Biological correlates of altered circadian rhythms, autonomic functions and sleep problems in autism spectrum disorder. Ann Gen Psychiatry. 2022;21(1):13. pmid:35534878
- 259. Malkani MK, Pestell CF, Sheridan AMC, Crichton AJ, Horsburgh GC, Bucks RS. Behavioral Sleep Interventions for Children With ADHD: A Systematic Review and Meta-Analysis. J Atten Disord. 2022;26(14):1805–21. pmid:35758199
- 260. Stein MA, Weiss M, Hlavaty L. ADHD treatments, sleep, and sleep problems: complex associations. Neurotherapeutics. 2012;9(3):509–17. pmid:22718078
- 261. Weiss MD, Wasdell MB, Bomben MM, Rea KJ, Freeman RD. Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia. J Am Acad Child Adolesc Psychiatry. 2006;45(5):512–9. pmid:16670647
- 262. Hoebert M, van der Heijden KB, van Geijlswijk IM, Smits MG. Long-term follow-up of melatonin treatment in children with ADHD and chronic sleep onset insomnia. J Pineal Res. 2009;47(1):1–7. pmid:19486273
- 263. Xiong M, Li F, Liu Z, Xie X, Shen H, Li W, et al. Efficacy of Melatonin for Insomnia in Children with Autism Spectrum Disorder: A Meta-analysis. Neuropediatrics. 2023;54(3):167–73. pmid:36827993
- 264. Hayashi M, Mishima K, Fukumizu M, Takahashi H, Ishikawa Y, Hamada I, et al. Melatonin Treatment and Adequate Sleep Hygiene Interventions in Children with Autism Spectrum Disorder: A Randomized Controlled Trial. J Autism Dev Disord. 2022;52(6):2784–93. pmid:34181143
- 265. Yan T, Goldman RD. Melatonin for children with autism spectrum disorder. Can Fam Physician. 2020;66(3):183–5. pmid:32165465
- 266. Yang P, Weng J, Huang X. Sleep features in alcohol use disorder: A systematic review and meta-analysis of polysomnographic findings in case-control studies. Eur J Psychiatry. 2024;38(2):100231.
- 267. Angarita GA, Emadi N, Hodges S, Morgan PT. Sleep abnormalities associated with alcohol, cannabis, cocaine, and opiate use: a comprehensive review. Addict Sci Clin Pract. 2016;11(1):9. pmid:27117064
- 268. Irwin MR, Bjurstrom MF, Olmstead R. Polysomnographic measures of sleep in cocaine dependence and alcohol dependence: Implications for age-related loss of slow wave, stage 3 sleep. Addiction. 2016;111(6):1084–92. pmid:26749502
- 269. Angarita GA, Canavan SV, Forselius E, Bessette A, Pittman B, Morgan PT. Abstinence-related changes in sleep during treatment for cocaine dependence. Drug Alcohol Depend. 2014;134:343–7. pmid:24315572
- 270. Morgan PT, Pace-Schott EF, Sahul ZH, Coric V, Stickgold R, Malison RT. Sleep, sleep-dependent procedural learning and vigilance in chronic cocaine users: Evidence for occult insomnia. Drug Alcohol Depend. 2006;82(3):238–49. pmid:16260094
- 271. Tang J, Liao Y, He H, Deng Q, Zhang G, Qi C, et al. Sleeping problems in Chinese illicit drug dependent subjects. BMC Psychiatry. 2015;15:28. pmid:25884573
- 272. Ardani AR, Saghebi SA, Nahidi M, Zeynalian F. Does abstinence resolve poor sleep quality in former methamphetamine dependents? Sleep Sci. 2016;9(3):255–60. pmid:28123671
- 273. Langstengel J, Yaggi HK. Sleep Deficiency and Opioid Use Disorder: Trajectory, Mechanisms, and Interventions. Sleep Med Clin. 2024;19(4):625–38. pmid:39455182
- 274. Feige B, Gann H, Brueck R, Hornyak M, Litsch S, Hohagen F, et al. Effects of alcohol on polysomnographically recorded sleep in healthy subjects. Alcohol Clin Exp Res. 2006;30(9):1527–37. pmid:16930215
- 275. Gardiner C, Weakley J, Burke LM, Roach GD, Sargent C, Maniar N, et al. The effect of alcohol on subsequent sleep in healthy adults: A systematic review and meta-analysis. Sleep Med Rev. 2025;80:102030. pmid:39631226
- 276. Zhang R, Tomasi D, Manza P, Shokri-Kojori E, Demiral SB, Feldman DE, et al. Sleep disturbances are associated with cortical and subcortical atrophy in alcohol use disorder. Transl Psychiatry. 2021;11(1):428. pmid:34400604
- 277. Althoff MD, Kinney GL, Aloia MS, Sempio C, Klawitter J, Bowler RP. The impact of cannabis use proximal to sleep and cannabinoid metabolites on sleep architecture. J Clin Sleep Med. 2024;20(10):1615–25. pmid:38804689
- 278. Kaul M, Zee PC, Sahni AS. Effects of Cannabinoids on Sleep and their Therapeutic Potential for Sleep Disorders. Neurotherapeutics. 2021;18(1):217–27. pmid:33580483
- 279. Velzeboer R, Malas A, Wei S, Berger R, Parmar V, Lai WWK. Cannabis and sleep architecture: A systematic review and meta-analysis. Sleep Med Rev. 2025;84:102164. pmid:40967124
- 280. Rosen IM, Aurora RN, Kirsch DB, Carden KA, Malhotra RK, Ramar K, et al. Chronic Opioid Therapy and Sleep: An American Academy of Sleep Medicine Position Statement. J Clin Sleep Med. 2019;15(11):1671–3. pmid:31739858
- 281. Tripathi R, Rao R, Dhawan A, Jain R, Sinha S. Opioids and sleep - a review of literature. Sleep Med. 2020;67:269–75. pmid:32081638
- 282. Valentino RJ, Volkow ND. Drugs, sleep, and the addicted brain. Neuropsychopharmacology. 2020;45(1):3–5. pmid:31311031
- 283. Gordon HW. Differential Effects of Addictive Drugs on Sleep and Sleep Stages. J Addict Res (OPAST Group). 2019;3(2):10.33140/JAR.03.02.01. pmid:31403110
- 284. Medigue I, Catoire S, Peyron C, Geoffroy P-A, Bernabeu T, Peter-Derex L, et al. Longitudinal disturbances of objective sleep architecture in cocaine use disorder: A translational systematic review. Neurosci Biobehav Rev. 2025;176:106278. pmid:40619048
- 285. Zhang L, Samet J, Caffo B, Punjabi NM. Cigarette smoking and nocturnal sleep architecture. Am J Epidemiol. 2006;164(6):529–37. pmid:16829553
- 286. da Silva e Silva WC, Costa NL, Rodrigues DdS, da Silva ML, Cunha KdC. Sleep quality of adult tobacco users: A systematic review of literature and meta-analysis. Sleep Epidemiology. 2022;2:100028.
- 287. Sulthana H, Jan A, Verma A, Sah R, Mehta R, Ullah A, et al. Impact of electronic cigarette use and sleep duration, sleep issues and insomnia: a systematic review and meta-analysis. Front Public Health. 2025;13:1662234. pmid:40951402
- 288. Mahoney JJ 3rd, De La Garza R 2nd, Jackson BJ, Verrico CD, Ho A, Iqbal T, et al. The relationship between sleep and drug use characteristics in participants with cocaine or methamphetamine use disorders. Psychiatry Res. 2014;219(2):367–71. pmid:24951161
- 289. Freeman LK, Gottfredson NC. Using ecological momentary assessment to assess the temporal relationship between sleep quality and cravings in individuals recovering from substance use disorders. Addict Behav. 2018;83:95–101. pmid:29137841
- 290. Brower KJ, Aldrich MS, Robinson EA, Zucker RA, Greden JF. Insomnia, self-medication, and relapse to alcoholism. Am J Psychiatry. 2001;158(3):399–404. pmid:11229980
- 291. Dolsen MR, Harvey AG. Life-time history of insomnia and hypersomnia symptoms as correlates of alcohol, cocaine and heroin use and relapse among adults seeking substance use treatment in the United States from 1991 to 1994. Addiction. 2017;112(6):1104–11. pmid:28127809
- 292. Gyawali U, James MH. Sleep disturbance in substance use disorders: the orexin (hypocretin) system as an emerging pharmacological target. Neuropsychopharmacology. 2023;48(1):228–9. pmid:35931814
- 293. Currie SR, Clark S, Hodgins DC, El-Guebaly N. Randomized controlled trial of brief cognitive-behavioural interventions for insomnia in recovering alcoholics. Addiction. 2004;99(9):1121–32. pmid:15317632
- 294. Chakravorty S, Morales KH, Arnedt JT, Perlis ML, Oslin DW, Findley JC, et al. Cognitive Behavioral Therapy for Insomnia in Alcohol-Dependent Veterans: A Randomized, Controlled Pilot Study. Alcohol Clin Exp Res. 2019;43(6):1244–53. pmid:30912860
- 295. Mason BJ, Quello S, Goodell V, Shadan F, Kyle M, Begovic A. Gabapentin treatment for alcohol dependence: a randomized clinical trial. JAMA Intern Med. 2014;174(1):70–7. pmid:24190578
- 296. Brower KJ, Myra Kim H, Strobbe S, Karam-Hage MA, Consens F, Zucker RA. A randomized double-blind pilot trial of gabapentin versus placebo to treat alcohol dependence and comorbid insomnia. Alcohol Clin Exp Res. 2008;32(8):1429–38. pmid:18540923
- 297. Staner L, Boeijinga P, Danel T, Gendre I, Muzet M, Landron F, et al. Effects of acamprosate on sleep during alcohol withdrawal: A double-blind placebo-controlled polysomnographic study in alcohol-dependent subjects. Alcohol Clin Exp Res. 2006;30(9):1492–9. pmid:16930211
- 298. Gendy MNS, Frey BN, Van Ameringen M, Kuhathasan N, MacKillop J. Cannabidiol as a candidate pharmacotherapy for sleep disturbance in alcohol use disorder. Alcohol Alcohol. 2023;58(4):337–45. pmid:37139966
- 299. Segalàs C, Labad J, Salvat-Pujol N, Real E, Alonso P, Bertolín S, et al. Sleep disturbances in obsessive-compulsive disorder: influence of depression symptoms and trait anxiety. BMC Psychiatry. 2021;21(1):42. pmid:33446149
- 300. Díaz-Román A, Perestelo-Pérez L, Buela-Casal G. Sleep in obsessive-compulsive disorder: a systematic review and meta-analysis. Sleep Med. 2015;16(9):1049–55. pmid:26298778
- 301. Burger P, Bos RW, Maas J, Simeunovic-Ostojic M, Gemke RJBJ. Sleep disturbances in anorexia nervosa. Eur Eat Disord Rev. 2025;33(2):318–42. pmid:39444255
- 302. Kim S, Lee H-J. Sleep and Circadian Rhythm Disturbances in Eating Disorders. Chronobiol Med. 2020;2(4):141–7.
- 303. Mutti C, Malagutti G, Maraglino V, Misirocchi F, Zilioli A, Rausa F, et al. Sleep Pathologies and Eating Disorders: A Crossroad for Neurology, Psychiatry and Nutrition. Nutrients. 2023;15(20):4488. pmid:37892563
- 304. Winsper C, Tang NKY, Marwaha S, Lereya ST, Gibbs M, Thompson A, et al. The sleep phenotype of Borderline Personality Disorder: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2017;73:48–67. pmid:27988314
- 305. Jenkins CA, Thompson KN, Chanen AM, Hartmann JA, Nicol K, Nicholas CL. Subjective and objective sleep in young people with borderline personality disorder features. J Sleep Res. 2022;31(2):e13463. pmid:34409668
- 306. Ionescu CG, Popa-Velea O, Mihăilescu AI, Talaşman AA, Bădărău IA. Somatic Symptoms and Sleep Disorders: A Literature Review of Their Relationship, Comorbidities and Treatment. Healthcare (Basel). 2021;9(9):1128. pmid:34574901
- 307. Zhao X, Shen L, Pei Y, Wu X, Zhou N. The relationship between sleep disturbance and obsessive- compulsive symptoms: the mediation of repetitive negative thinking and the moderation of experiential avoidance. Front Psychol. 2023;14:1151399. pmid:37476089
- 308. Romo-Nava F, Guerdjikova AI, Mori NN, Scheer FAJL, Burgess HJ, McNamara RK, et al. A matter of time: A systematic scoping review on a potential role of the circadian system in binge eating behavior. Front Nutr. 2022;9:978412. pmid:36159463
- 309. Selby EA. Chronic sleep disturbances and borderline personality disorder symptoms. J Consult Clin Psychol. 2013;81(5):941–7. pmid:23731205
- 310. Morales-Muñoz I, Broome MR, Marwaha S. Association of Parent-Reported Sleep Problems in Early Childhood With Psychotic and Borderline Personality Disorder Symptoms in Adolescence. JAMA Psychiatry. 2020;77(12):1256–65. pmid:32609357
- 311. Li B, Mody M. Cortico-Striato-Thalamo-Cortical Circuitry, Working Memory, and Obsessive-Compulsive Disorder. Front Psychiatry. 2016;7:78. pmid:27199785
- 312. Calzà J, Gürsel DA, Schmitz-Koep B, Bremer B, Reinholz L, Berberich G, et al. Altered Cortico-Striatal Functional Connectivity During Resting State in Obsessive-Compulsive Disorder. Front Psychiatry. 2019;10:319. pmid:31133898
- 313. Goodman WK, Storch EA, Sheth SA. Harmonizing the Neurobiology and Treatment of Obsessive-Compulsive Disorder. Am J Psychiatry. 2021;178(1):17–29. pmid:33384007
- 314. Sauchelli S, Jiménez-Murcia S, Sánchez I, Riesco N, Custal N, Fernández-García JC, et al. Orexin and sleep quality in anorexia nervosa: Clinical relevance and influence on treatment outcome. Psychoneuroendocrinology. 2016;65:102–8. pmid:26741881
- 315. McGowan NM, Saunders KEA. The Emerging Circadian Phenotype of Borderline Personality Disorder: Mechanisms, Opportunities and Future Directions. Curr Psychiatry Rep. 2021;23(5):30. pmid:33835306
- 316. Schulze L, Schmahl C, Niedtfeld I. Neural Correlates of Disturbed Emotion Processing in Borderline Personality Disorder: A Multimodal Meta-Analysis. Biol Psychiatry. 2016;79(2):97–106. pmid:25935068
- 317. Boeckle M, Schrimpf M, Liegl G, Pieh C. Neural correlates of somatoform disorders from a meta-analytic perspective on neuroimaging studies. Neuroimage Clin. 2016;11:606–13. pmid:27182487
- 318. Coles ME, Schubert J, Nota JA. Delayed Sleep Timing in Obsessive-Compulsive Disorder Is Associated With Diminished Response to Exposure and Ritual Prevention. Behav Ther. 2021;52(5):1277–85. pmid:34452679
- 319. Degasperi G, Meneo D, Curati S, Cardi V, Baglioni C, Cellini N. Sleep quality in eating disorders: A systematic review and meta-analysis. Sleep Med Rev. 2024;77:101969. pmid:38959584
- 320. van Trigt S, van der Zweerde T, van Someren EJW, van Straten A, van Marle HJF. Guided internet-based cognitive behavioral therapy for insomnia in patients with borderline personality disorder: Study protocol for a randomized controlled trial. Internet Interv. 2022;29:100563. pmid:35899204
- 321. Orzechowska A, Maruszewska P, Gałecki P. Cognitive Behavioral Therapy of Patients with Somatic Symptoms-Diagnostic and Therapeutic Difficulties. J Clin Med. 2021;10(14):3159. pmid:34300324
- 322. Rosenberg R, Citrome L, Drake CL. Advances in the Treatment of Chronic Insomnia: A Narrative Review of New Nonpharmacologic and Pharmacologic Therapies. Neuropsychiatr Dis Treat. 2021;17:2549–66. pmid:34393484
- 323. Wu JQ, Appleman ER, Salazar RD, Ong JC. Cognitive Behavioral Therapy for Insomnia Comorbid With Psychiatric and Medical Conditions: A Meta-analysis. JAMA Intern Med. 2015;175(9):1461–72. pmid:26147487
- 324. Trockel M, Karlin BE, Taylor CB, Brown GK, Manber R. Effects of cognitive behavioral therapy for insomnia on suicidal ideation in veterans. Sleep. 2015;38(2):259–65. pmid:25515115
- 325. Freeman D, Waite F, Startup H, Myers E, Lister R, McInerney J, et al. Efficacy of cognitive behavioural therapy for sleep improvement in patients with persistent delusions and hallucinations (BEST): a prospective, assessor-blind, randomised controlled pilot trial. Lancet Psychiatry. 2015;2(11):975–83. pmid:26363701
- 326. Riemann D, Baglioni C, Bassetti C, Bjorvatn B, Dolenc Groselj L, Ellis JG, et al. European guideline for the diagnosis and treatment of insomnia. J Sleep Res. 2017;26(6):675–700. pmid:28875581
- 327. Harvey AG, Soehner AM, Kaplan KA, Hein K, Lee J, Kanady J, et al. Treating insomnia improves mood state, sleep, and functioning in bipolar disorder: a pilot randomized controlled trial. J Consult Clin Psychol. 2015;83(3):564–77. pmid:25622197
- 328. Sit DK, McGowan J, Wiltrout C, Diler RS, Dills JJ, Luther J, et al. Adjunctive Bright Light Therapy for Bipolar Depression: A Randomized Double-Blind Placebo-Controlled Trial. Am J Psychiatry. 2018;175(2):131–9. pmid:28969438
- 329. Wirz-Justice A, Benedetti F, Berger M, Lam RW, Martiny K, Terman M, et al. Chronotherapeutics (light and wake therapy) in affective disorders. Psychol Med. 2005;35(7):939–44. pmid:16045060
- 330. Martiny K, Refsgaard E, Lund V, Lunde M, Sørensen L, Thougaard B, et al. The day-to-day acute effect of wake therapy in patients with major depression using the HAM-D6 as primary outcome measure: results from a randomised controlled trial. PLoS One. 2013;8(6):e67264. pmid:23840645
- 331. Sahlem GL, Kalivas B, Fox JB, Lamb K, Roper A, Williams EN, et al. Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: An open label pilot study. J Psychiatr Res. 2014;59:101–7.
- 332. Ong JC, Manber R, Segal Z, Xia Y, Shapiro S, Wyatt JK. A Randomized Controlled Trial of Mindfulness Meditation for Chronic Insomnia. Sleep. 2014;37(9):1553–63.
- 333. Polusny MA, Erbes CR, Thuras P, Moran A, Lamberty GJ, Collins RC, et al. Mindfulness-Based Stress Reduction for Posttraumatic Stress Disorder Among Veterans: A Randomized Clinical Trial. JAMA. 2015;314(5):456–65. pmid:26241597
- 334. Hoge EA, Bui E, Marques L, Metcalf CA, Morris LK, Robinaugh DJ, et al. Randomized controlled trial of mindfulness meditation for generalized anxiety disorder: effects on anxiety and stress reactivity. J Clin Psychiatry. 2013;74(8):786–92.
- 335. Ancoli-Israel S, Cole R, Alessi C, Chambers M, Moorcroft W, Pollak CP. The role of actigraphy in the study of sleep and circadian rhythms. Sleep. 2003;26(3):342–92. pmid:12749557
- 336. Kaplan KA, Talbot LS, Gruber J, Harvey AG. Evaluating sleep in bipolar disorder: comparison between actigraphy, polysomnography, and sleep diary. Bipolar Disord. 2012;14(8):870–9. pmid:23167935
- 337. de Zambotti M, Cellini N, Goldstone A, Colrain IM, Baker FC. Wearable Sleep Technology in Clinical and Research Settings. Med Sci Sports Exerc. 2019;51(7):1538–57. pmid:30789439
- 338. Espie CA, Emsley R, Kyle SD, Gordon C, Drake CL, Siriwardena AN, et al. Effect of Digital Cognitive Behavioral Therapy for Insomnia on Health, Psychological Well-being, and Sleep-Related Quality of Life: A Randomized Clinical Trial. JAMA Psychiatry. 2019;76(1):21–30. pmid:30264137
- 339. Qaseem A, Kansagara D, Forciea MA, Cooke M, Denberg TD; Clinical Guidelines Committee of the American College of Physicians. Management of chronic insomnia disorder in adults: a clinical practice guideline from the American College of Physicians. Ann Intern Med. 2016;165(2):125–33.
- 340. Auger RR, Burgess HJ, Emens JS, Deriy LV, Thomas SM, Sharkey KM, et al. Clinical practice guideline for the treatment of intrinsic circadian rhythm sleep-wake disorders: advanced sleep-wake phase disorder, delayed sleep-wake phase disorder, non-24-hour sleep-wake rhythm disorder, and irregular sleep-wake rhythm disorder. J Clin Sleep Med. 2015;11(10):1199–236.
- 341. Roth T, Seiden D, Sainati S, Wang-Weigand S, Zhang J, Zee P. Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia. Sleep Med. 2006;7(4):312–8.
- 342. Krystal AD, Lankford A, Durrence HH, Ludington E, Jochelson P, Rogowski R, et al. Efficacy and safety of doxepin 3 and 6 mg in a 35-day sleep laboratory trial in adults with chronic primary insomnia. Sleep. 2011 Oct 1;34(10):1433–42.
- 343. Rosenberg R, Murphy P, Zammit G, Mayleben D, Kumar D, Dhadda S, et al. Comparison of Lemborexant With Placebo and Zolpidem Tartrate Extended Release for the Treatment of Older Adults With Insomnia Disorder: A Phase 3 Randomized Clinical Trial. JAMA Netw Open. 2019;2(12):e1918254. pmid:31880796
- 344. Mignot E, Mayleben D, Fietze I, Leger D, Zammit G, Bassetti CLA, et al. Safety and efficacy of daridorexant in patients with insomnia disorder: results from two multicentre, randomised, double-blind, placebo-controlled, phase 3 trials. Lancet Neurol. 2022;21(2):125–39. pmid:35065036
- 345. By the 2023 American Geriatrics Society Beers Criteria® Update Expert Panel. American Geriatrics Society 2023 updated AGS Beers Criteria® for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2023;71(7):2052–81. pmid:37139824
- 346. Glass J, Lanctôt KL, Herrmann N, Sproule BA, Busto UE. Sedative hypnotics in older people with insomnia: meta-analysis of risks and benefits. BMJ. 2005;331(7526):1169.
- 347. Anderson SL, Vande Griend JP. Quetiapine for insomnia: A review of the literature. Am J Health Syst Pharm. 2014;71(5):394–402. pmid:24534594
- 348. Raskind MA, Peskind ER, Hoff DJ, Hart KL, Holmes HA, Warren D, et al. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry. 2007;61(8):928–34. pmid:17069768
- 349. Epstein LJ, Kristo D, Strollo PJ Jr, Friedman N, Malhotra A, Patil SP, et al. Clinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adults. J Clin Sleep Med. 2009;5(3):263–76. pmid:19960649
- 350.
U.S. Food and Drug Administration. Rozerem (ramelteon) prescribing information. Silver Spring (MD): FDA; 2018.
- 351.
U.S. Food and Drug Administration. Quviviq (daridorexant) prescribing information. Silver Spring (MD): FDA; 2022.
- 352.
U.S. Food and Drug Administration. Silenor (doxepin) prescribing information. Silver Spring (MD): FDA; 2020.
- 353. Pottie K, Thompson W, Davies S, Grenier J, Sadowski CA, Welch V, et al. Deprescribing benzodiazepine receptor agonists: Evidence-based clinical practice guideline. Can Fam Physician. 2018;64(5):339–51. pmid:29760253
- 354. Vargas I, Egeler M, Walker J, Benitez DD. Examining the barriers and recommendations for integrating more equitable insomnia treatment options in primary care. Front Sleep. 2023;2:1279903. pmid:39210962
- 355. Adolescent Sleep Working Group, Committee on Adolescence, Council on School Health. School start times for adolescents. Pediatrics. 2014;134(3):642–9. pmid:25156998
- 356. Witkowska-Zimny M, Zhyvotovska A, Isakov R, Boiko DI, Nieradko-Iwanicka B. Maternal Sleeping Problems Before and After Childbirth - A Systematic Review. Int J Womens Health. 2024;16:345–71. pmid:38455339
- 357. Fu T, Wang C, Yan J, Zeng Q, Ma C. Relationship between antenatal sleep quality and depression in perinatal women: A comprehensive meta-analysis of observational studies. J Affect Disord. 2023;327:38–45. pmid:36739002
- 358. Milanak ME, Zuromski KL, Cero I, Wilkerson AK, Resnick HS, Kilpatrick DG. Traumatic Event Exposure, Posttraumatic Stress Disorder, and Sleep Disturbances in a National Sample of U.S. Adults. J Trauma Stress. 2019;32(1):14–22. pmid:30702778
- 359. Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213. pmid:2748771