Resting-state functional connectivity changes in older adults with sleep disturbance and the role of amyloid burden.

Sleep and related disorders could lead to changes in various brain networks, but little is known about the role of amyloid ß (Aß) burden-a key Alzheimer's disease (AD) biomarker-in the relationship between sleep disturbance and altered resting state functional connectivity (rsFC) in older adults. This cross-sectional study examined the association between sleep disturbance, Aß burden, and rsFC using a large-scale dataset from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Sample included 489 individuals (53.6% cognitively normal, 32.5% mild cognitive impairment, and 13.9% AD) who had completed sleep measures (Neuropsychiatric Inventory), PET Aß data, and resting-state fMRI scans at baseline. Within and between rsFC of the Salience (SN), the Default Mode (DMN) and the Frontal Parietal network (FPN) were compared between participants with sleep disturbance versus without sleep disturbance. The interaction between Aß positivity and sleep disturbance was evaluated using the linear regressions, controlling for age, diagnosis status, gender, sedatives and hypnotics use, and hypertension. Although no significant main effect of sleep disturbance was found on rsFC, a significant interaction term emerged between sleep disturbance and Aß burden on rsFC of SN (ß = 0.11, P = 0.006). Specifically, sleep disturbance was associated with SN hyperconnectivity, only with the presence of Aß burden. Sleep disturbance may lead to altered connectivity in the SN when Aß is accumulated in the brain. Individuals with AD pathology may be at increased risk for sleep-related aberrant rsFC; therefore, identifying and treating sleep problems in these individuals may help prevent further disease progression.

Potential genetic and epigenetic mechanisms in insomnia: A systematic review.

Insomnia is a stress-related sleep disorder conceptualised within a diathesis-stress framework, which it is thought to result from predisposing factors interacting with precipitating stressful events that trigger the development of insomnia. Among predisposing factors genetics and epigenetics may play a role. A systematic review of the current evidence for the genetic and epigenetic basis of insomnia was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) system. A total of 24 studies were collected for twins and family heritability, 55 for genome-wide association studies, 26 about candidate genes for insomnia, and eight for epigenetics. Data showed that insomnia is a complex polygenic stress-related disorder, and it is likely to be caused by a synergy of genetic and environmental factors, with stress-related sleep reactivity being the important trait. Even if few studies have been conducted to date on insomnia, epigenetics may be the framework to understand long-lasting consequences of the interaction between genetic and environmental factors and effects of stress on the brain in insomnia. Interestingly, polygenic risk for insomnia has been causally linked to different mental and medical disorders. Probably, by treating insomnia it would be possible to intervene on the effect of stress on the brain and prevent some medical and mental conditions.

Sleep Disturbances Associated With Posttraumatic Stress Disorder.

Sleep disturbances, namely insomnia and recurrent nightmares, are ubiquitous following trauma exposure and are considered hallmarks of posttraumatic stress disorder (PTSD). Other sleep disorders frequently co-occur with PTSD. This article describes research examining sleep problems most common in PTSD, including prevalence and clinical characteristics. Sleep disturbances are often robust to trauma-focused treatment; thus, evidence for psychological and pharmacological interventions for insomnia and nightmares in PTSD are discussed. Given the high prevalence of sleep problems in PTSD, more work is needed to empirically study putative mechanisms linking trauma exposure and sleep, as well as how to best target these symptoms in patients with PTSD.

Hyperarousal and Insomnia in Survivors of Cancer.

BACKGROUND: Cancer survivors are prone to insomnia due to the physical and psychological sequelae of cancer and treatment. Individuals with insomnia may present symptoms of hyperarousal. Cancer survivors with insomnia and trait hyperarousal may require different clinical treatments than patients with insomnia without trait hyperarousal. To our knowledge, no study has examined these factors previously. This study examined the relation between insomnia and trait hyperarousal in cancer survivors. METHODS: The sample included 160 individuals with previous cancer diagnoses who met DSM-5 criteria for insomnia disorder. Measures were collected with cross-sectional batteries of questionnaires, including the Insomnia Severity Index (ISI) and Hyperarousal Scale (HAS). This study is based on baseline data collected in a randomized clinical trial comparing CBT-I to acupuncture for cancer survivors with insomnia (Garland, Gehrman, Barg, Xie, & Mao, 2016). RESULTS: Hyperarousal was positively associated with insomnia (ISI total score) in bivariate correlations (r = .350, p < .01) and linear regressions (F = 22.06, p < .001). In bivariate correlations, hyperarousal was related to perceptions about the consequences of disturbed sleep rather than reported sleep patterns. For example, hyperarousal was positively related to reported satisfaction (r = .159, p < .05) and worry about sleep (r = .415, p < .01), but not to falling asleep, staying asleep, or awakening too early. In regressions, younger age, insomnia duration, and worry about sleep were uniquely associated with hyperarousal when adjusting for insomnia (B = 0.200, B = 0.177, B = -0.182, p < .05). CONCLUSIONS: Hyperarousal is associated with psychological appraisal of insomnia rather than reported sleep pattern. Younger age and longer duration of insomnia are associated with trait hyperarousal. These findings suggest targeting trait hyperarousal with amplified psychological treatment may lead to more personalized, effective treatment for insomnia.

Insomnia Symptoms and Suicide-Related Ideation in U.S. Army Service Members.

Background: Insomnia has been identified as a key risk factor for suicide, though most studies have been limited to global measures of these constructs. The aim of the present study was to evaluate the link between insomnia symptoms and five different aspects of suicide-related ideation. Participants: 1,160 active U.S. Army service members (719 male; Mage = 31.2; SDage = 8.62). Methods: As part of an archival analysis, retrospectively assessed insomnia, depression, anxiety symptoms, as well as suicide-related ideation, were evaluated. Suicide-related ideation was assessed in terms of: thoughts of death, thoughts of suicide, suicidal plan, suicidal intent, and suicidal communication. Results: Subjects with clinically significant insomnia symptoms were 3.5 times more likely to report any suicide-related ideation, and approximately 3 times more likely to report thoughts of death and thoughts of suicide. More frequent nocturnal awakenings (i.e., waking up three or more times during a single night) were associated with a greater likelihood of reporting thoughts of death or suicide, whereas greater middle insomnia (i.e., waking up and having difficulty getting back to sleep) was associated with lower odds of experiencing thoughts of suicide, suicidal plan, and suicidal intent. Conclusions: A more refined delineation of insomnia and suicide-related ideation may serve to clarify the nature of the association, and potentially offer some clues as to the underlying mechanisms. With regard to potential clinical implications, the results support that careful assessment of insomnia symptoms, suicide-related ideation, and their respective subtypes, is important and may influence how we estimate risk for suicide.

Genome-Wide Association Analyses in 128,266 Individuals Identifies New Morningness and Sleep Duration Loci.

Disrupted circadian rhythms and reduced sleep duration are associated with several human diseases, particularly obesity and type 2 diabetes, but until recently, little was known about the genetic factors influencing these heritable traits. We performed genome-wide association studies of self-reported chronotype (morning/evening person) and self-reported sleep duration in 128,266 white British individuals from the UK Biobank study. Sixteen variants were associated with chronotype (P<5x10-8), including variants near the known circadian rhythm genes RGS16 (1.21 odds of morningness, 95% CI [1.15, 1.27], P = 3x10-12) and PER2 (1.09 odds of morningness, 95% CI [1.06, 1.12], P = 4x10-10). The PER2 signal has previously been associated with iris function. We sought replication using self-reported data from 89,283 23andMe participants; thirteen of the chronotype signals remained associated at P<5x10-8 on meta-analysis and eleven of these reached P<0.05 in the same direction in the 23andMe study. We also replicated 9 additional variants identified when the 23andMe study was used as a discovery GWAS of chronotype (all P<0.05 and meta-analysis P<5x10-8). For sleep duration, we replicated one known signal in PAX8 (2.6 minutes per allele, 95% CI [1.9, 3.2], P = 5.7x10-16) and identified and replicated two novel associations at VRK2 (2.0 minutes per allele, 95% CI [1.3, 2.7], P = 1.2x10-9; and 1.6 minutes per allele, 95% CI [1.1, 2.2], P = 7.6x10-9). Although we found genetic correlation between chronotype and BMI (rG = 0.056, P = 0.05); undersleeping and BMI (rG = 0.147, P = 1x10-5) and oversleeping and BMI (rG = 0.097, P = 0.04), Mendelian Randomisation analyses, with limited power, provided no consistent evidence of causal associations between BMI or type 2 diabetes and chronotype or sleep duration. Our study brings the total number of loci associated with chronotype to 22 and with sleep duration to three, and provides new insights into the biology of sleep and circadian rhythms in humans.

Prevalence, predictors and correlates of insomnia in US army soldiers.

The objective of this study was to investigate the rates, predictors and correlates of insomnia in a national sample of US Army soldiers. Data were gathered from the cross-sectional survey responses of the All-Army Study, of the Army Study to Assess Risk and Resilience in Service members. Participants were a representative sample of 21 499 US Army soldiers who responded to the All-Army Study self-administered questionnaire between 2011 and 2013. Insomnia was defined by selected DSM-5 criteria using the Brief Insomnia Questionnaire. The results highlight significant functional difficulties associated with insomnia among US soldiers, as well as insights into predictors of insomnia specific to this population. Insomnia was present in 22.76% of the sample. Predictors of insomnia status in logistic regression included greater number of current mental health disorders, less perceived open lines of communication with leadership, less unit member support and less education. Insomnia had global, negative associations with health, social functioning, support, morale, work performance and Army career intentions. The results provide the strongest evidence to-date that insomnia is common in a military population, and is associated with a wide array of negative factors in the domains of health, military readiness and intentions to remain in military careers.

Sleep and Dreaming in Posttraumatic Stress Disorder.

PURPOSE OF REVIEW: Sleep disturbances are core features of posttraumatic stress disorder (PTSD). This review aims to characterize sleep disturbances, summarize the knowledge regarding the relationships between trauma exposure and sleep difficulties, and highlight empirically supported and/or utilized treatments for trauma-related nightmares and insomnia. RECENT FINDINGS: Trauma-related nightmares and insomnia, and other sleep disorders, are frequently reported among trauma survivors. The roles of fear of sleep, REM density, and decreased parasympathetic activity are beginning to inform the relationship between trauma exposure and sleep difficulties. Additionally, the potential adaptive role of sleep loss immediately following a traumatic experience is being recognized. Interventions targeting these sleep disturbances show promise in reducing symptoms. Research in understanding the role of sleep on the development, course, and treatment of PTSD is expanding. Longitudinal investigations are needed to further elucidate these relationships and identify treatments most effective in ameliorating symptoms.

Insomnia in breast cancer: Independent symptom or symptom cluster?

OBJECTIVE: This study examined insomnia in the context of breast cancer, both as an independent symptom and as a component of a symptom cluster that includes depression, anxiety, fatigue, and pain. METHOD: Women with a history of breast cancer currently taking an aromatase inhibitor and who had completed cancer treatment at least one month prior to enrollment were included (n = 413). Participants completed validated measures of insomnia, fatigue, pain, depression, and anxiety. Factor analysis was utilized to examine the extent to which these symptoms could be represented by common latent factors. Insomnia severity was then separated into a symptom cluster component (I-SC) and an insomnia-unique (I-U) component. The associations between each insomnia component and demographic and clinical factors were examined in multivariate models. RESULTS: A single-factor solution provided the best fit to the symptom measures. Some 53.3% of the variance in insomnia severity was captured by this symptom cluster (I-SC), with the remaining 43.7% being unique to insomnia (I-U). Unique patterns of demographic factors (e.g., age and body-mass index), but not clinical factors, were associated with each insomnia measure. SIGNIFICANCE OF RESULTS: Approximately 50% of insomnia severity was related to the symptom cluster, with the rest being unique to insomnia. Different sociodemographic risk factors were related to the different insomnia measures. Stronger underlying foundations for the mechanisms of each component could lead to refined diagnoses and targeted interventions for addressing the overall insomnia burden in cancer patients.

Influence of Sleep Disturbance on Global Functioning After Posttraumatic Stress Disorder Treatment.

Chronic insomnia and recurrent nightmares are prominent features of posttraumatic stress disorder (PTSD). Evidence from adult research indicates that these sleep disturbances do not respond as well to cognitive-behavioral therapies for PTSD and are associated with poorer functional outcomes. This study examined the effect of prolonged exposure therapy for adolescents versus client-centered therapy on posttraumatic sleep disturbance, and the extent to which sleep symptoms impacted global functioning among adolescents with sexual abuse-related PTSD. Participants included 61 adolescent girls seeking treatment at a rape crisis center. The Child PTSD Symptom Scale-Interview (Foa, Johnson, Feeny, & Treadwell, 2001) was used to assess PTSD diagnosis and severity of symptoms, including insomnia and nightmares. The Children's Global Assessment Scale (Shaffer et al., 1983) was used to assess global functioning. There were significant main effects of time and treatment on insomnia symptoms. Additionally, there was a main effect of time on nightmares. Results also showed that insomnia and nightmares significantly predicted poorer global functioning posttreatment (R2 = .21). Despite significant improvements in posttraumatic sleep disturbance, there were still clinically significant insomnia symptoms after treatment, suggesting that additional interventions may be warranted to address residual sleep disturbance in PTSD.

Stress Reactivity in Insomnia.

This study examined whether individuals with primary insomnia (PI) are more reactive to stress than good sleepers (GS). PI and GS (n = 20 per group), matched on gender and age, completed three nights of polysomnography. On the stress night, participants received a mild electric shock and were told they could receive additional shocks during the night. Saliva samples were obtained for analysis of cortisol and alpha amylase along with self-report and visual analog scales (VAS). There was very little evidence of increased stress on the stress night, compared to the baseline night. There was also no evidence of greater stress reactivity in the PI group for any sleep or for salivary measures. In the GS group, stress reactivity measured by VAS scales was positively associated with an increase in sleep latency in the experimental night on exploratory analyses. Individuals with PI did not show greater stress reactivity compared to GS.

Sleep diaries of Vietnam War veterans with chronic PTSD: the relationships among insomnia symptoms, psychosocial stress, and nightmares.

Impaired sleep and nightmares are known symptoms of posttraumatic stress disorder (PTSD) in the veteran population. In order to assess prospectively the sleep disturbances in this population, sleep diaries are an effective way to obtain information over an extended period of time. In this investigation, a sample of veterans (N = 105) completed daily sleep diaries for a 6-week period. Greater PTSD severity and nightmare-related distress were correlated with more awakenings, shorter duration of sleep, longer sleep latency, and greater frequency of nightmares. Perceived frequency of daytime stressors was associated with an increased number of nightmares, nightmare-related distress, and longer sleep latency. The use of sleep diaries in future investigations may allow targeted treatments for veteran populations with PTSD and sleep disturbances.

A Fully Remote Randomized Trial of Transcranial Alternating Current Stimulation for the Acute Treatment of Major Depressive Disorder.

Objective: Major depressive disorder (MDD) is common, but current treatment options have significant limitations in terms of access and efficacy. This study examined the effectiveness of transcranial alternating current stimulation (tACS) for the acute treatment of MDD.Methods: We performed a triple-blind, fully remote, randomized controlled trial comparing tACS with sham treatment. Adults aged 21-65 years meeting DSM 5 criteria for MDD and having a score on the Beck Depression Inventory, Second Edition (BDI-II), between 20 and 63 were eligible to participate. Participants utilized tACS or sham treatment for two 20-minute treatment sessions daily for 4 weeks. The primary outcome was change in BDI-II score from baseline to the week 2 time point in an intent-to treat analysis, followed by analyses of treatment-adherent participants. Secondary analyses examined change at the week 1 and 4 time points, responder rates, subgroup analyses, other self-report mood measures, and safety. The study was conducted from April to October 2022.Results: A total of 255 participants were randomized to active or sham treatment. Improvement in intent-to-treat analysis was not statistically significant at week 2 (P= .056), but there were significant effects in participants with high adherence (P= .005). Significantly greater improvement at week 1 (P= .020) and greater response at week 4 (P= .028) occurred following tACS. Improvements were significantly larger for female participants. There were no significant effects on secondary mood measures. Side effects were minimal and mild.Conclusions: Rapid, clinically significant improvement in depression in adults with MDD was associated with tACS, particularly for women. Compared to other depression therapies, tACS has 3 key advantages: rapid, clinically significant treatment effect, the ability of patients to use the treatment on their own at home, and the rarity and low impact of adverse events.Trial Registration: ClinicalTrials.gov identifier: NCT05384041.

Bipolar disorder is characterized by chronotype instability: A longitudinal investigation of circadian typology and mood.

BACKGROUND: Chronotype is associated with circadian rhythmicity, a core etiological factor underlying bipolar disorder (BD). Given converging evidence linking late chronotype with poor mental health, the goal of the present study was to examine chronotype (in)stability and its relation to mood symptoms over time. METHODS: Participants with BD I (n = 271), BD II (n = 88), and healthy controls (n = 217) were included (follow-upM=10 years, Range=5-15) from the Prechter Longitudinal Study. Chronotype category and midpoint of sleep, corrected for weekend sleep-debt (MSFsc), were measured with the Munich Chronotype Questionnaire administered every 12 months alongside clinician-rated mood and medication usage. Self-reported mood was measured bi-monthly. Mixed effects models tested whether mood was associated with (in)stability of chronotype category and MSFsc covarying for age, sex, age, and medication. RESULTS: Compared to HC, individuals with BD self-reported having a later chronotype that significantly fluctuated over time. Individuals with BDI showed significantly less stability in MSFsc than HC. Anticonvulsant use was associated with more stability in MSFsc whereas antidepressant use was associated with less stability in MSFsc. CONCLUSIONS: In a large longitudinal cohort, individuals with BD displayed significant instability in circadian typology. Psychopharmacology in BD may have differential impacts on circadian timing that is important to monitor.

Prevalence and risk factors for insomnia among breast cancer patients on aromatase inhibitors.

PURPOSE: Insomnia is increasingly recognized as a major symptom outcome in breast cancer; however, little is known about its prevalence and risk factors among women receiving aromatase inhibitors (AIs), a standard treatment to increase disease-free survival among breast cancer patients. METHODS: A cross-sectional survey study was conducted among postmenopausal women with stage 0-III breast cancer receiving adjuvant AI therapy at an outpatient breast oncology clinic of a large university hospital. The insomnia severity index (ISI) was used as the primary outcome. Multivariate logistic regression analyses were performed to evaluate risk factors. RESULTS: Among 413 participants, 130 (31.5 %) had subthreshold insomnia on the ISI, and 77 (18.64 %) exceeded the threshold for clinically significant insomnia. In a multivariate logistic regression model, clinically significant insomnia was independently associated with severe joint pain (adjusted odds ratio (AOR) 4.84, 95 % confidence interval (CI) 1.71-13.69, P = 0.003), mild/moderate hot flashes (AOR 2.28, 95 % CI 1.13-4.60, P = 0.02), severe hot flashes (AOR 2.29, 95 % CI 1.23-6.81, P = 0.015), anxiety (AOR 1.99, 95 % CI 1.08-3.65, P = 0.027), and depression (AOR 3.57, 95 % CI 1.48-8.52, P = 0.004). Age (>65 vs. <55 years; AOR 2.31; 95 % CI 1.11-4.81; P = 0.026) and time since breast cancer diagnosis (<2 vs. 2-5 years; AOR 1.94; 95 % CI 1.02-3.69; P = 0.045) were also found to be significant risk factors. Clinical insomnia was more common among those who used medication for treating insomnia and pain. CONCLUSIONS: Insomnia complaints exceed 50 % among AI users. Clinically significant insomnia is highly associated with joint pain, hot flashes, anxiety and depression, age, and time since diagnosis.

Do pregnant women accurately report sleep time? A comparison between self-reported and objective measures of sleep duration in pregnancy among a sample of urban mothers.

PURPOSE: Survey questions are commonly used to assess sleep duration because of their low cost and convenience. Responses to these questions correlate moderately with objectively measured sleep duration in nonpregnant individuals, but little is known about the validity of self-reported sleep measures in pregnancy. The aim of the present study was to determine the extent to which self-reported gestational sleep duration assessed by questionnaire predicted objectively measured gestational sleep duration via actigraphy. METHODS: We analyzed data from 80 mothers enrolled in an ancillary study of Project BABIES, a prospective cohort study of urban, pregnant women. Sleep measurements were collected in midpregnancy and included 7 days of wrist actigraphy, a sleep log, and survey questions about sleep time adapted from the Pittsburgh Sleep Quality Index. RESULTS: Mean measured gestational sleep duration derived from actigraphy was 6.87 h [standard deviation (SD) 0.87], and questionnaire-assessed nocturnal sleep time averaged 7.29 h (SD 1.84). While the difference between measures did not reach statistical significance (p = 0.07 for paired samples t test), over half (62 %) of participants reported a habitual average nightly sleep time that differed more than 1 h from their average actigraphically measured sleep duration (39 % overestimated by more than an hour; 23 % underestimated by more than an hour). There was no correlation between measures (r = 0.007; 95 % confidence interval -0.21, 0.23). CONCLUSION: Questionnaire-derived reports of usual sleep hours do not reflect objectively measured sleep time in urban, pregnant women. Actigraphy is preferable to accurately assess gestational sleep duration.

A critical review of the evidence base of imagery rehearsal for posttraumatic nightmares: pointing the way for future research.

In this article, the authors provide information on key characteristics of imagery rehearsal treatment protocols and examine the quality of reporting of randomized controlled and uncontrolled trials of imagery rehearsal for treating posttraumatic nightmares. Using a reliable and valid scale, two independent psychologists rated 16 trials. Most reports provided insufficient information on a range of variables including the definition of treatment delivery (e.g., therapist supervision, treatment fidelity), description of the participant sample, data analysis (e.g., determination of sample size), and treatment assignment (e.g., randomization procedures). Low methodological quality and poor reporting can lead to inflation of estimates of treatment effects and inadequately substantiated conclusions, such as inflated effect sizes in meta-analytic studies. Numerous imagery rehearsal protocols exist, but in some cases are given different names and tested in pilot studies, slowing progression in the field. Randomized controlled trials of imagery rehearsal with credible comparison conditions, examination of predictors of dropout and outcome, as well as dismantling studies of imagery rehearsal treatment components are needed.

Sleep-related behaviors and beliefs associated with race/ethnicity in women.

Explore how social factors influence sleep, especially sleep-related beliefs and behaviors. Sleep complaints, sleep hygiene behaviors, and beliefs about sleep were studied in 65 black/African American and white/European American women. Differences were found for snoring and discrepancy between sleep duration and need. Sleep behaviors differed across groups for napping, methods for coping with sleep difficulties, and nonsleep behaviors in bed. Beliefs also distinguished groups, with differences in motivation for sleep and beliefs about sleep being important for health and functioning. These findings have important public health implications in terms of developing effective sleep education interventions that include consideration of cultural aspects.

A genome-wide association study of sleep habits and insomnia.

Several aspects of sleep behavior such as timing, duration and quality have been demonstrated to be heritable. To identify common variants that influence sleep traits in the population, we conducted a genome-wide association study of six sleep phenotypes assessed by questionnaire in a sample of 2,323 individuals from the Australian Twin Registry. Genotyping was performed on the Illumina 317, 370, and 610K arrays and the SNPs in common between platforms were used to impute non-genotyped SNPs. We tested for association with more than 2,000,000 common polymorphisms across the genome. While no SNPs reached the genome-wide significance threshold, we identified a number of associations in plausible candidate genes. Most notably, a group of SNPs in the third intron of the CACNA1C gene ranked as most significant in the analysis of sleep latency (P = 1.3 × 10⁻6). We attempted to replicate this association in an independent sample from the Chronogen Consortium (n = 2,034), but found no evidence of association (P = 0.73). We have identified several other suggestive associations that await replication in an independent sample. We did not replicate the results from previous genome-wide analyses of self-reported sleep phenotypes after correction for multiple testing.

Does insomnia treatment prevent depression?

Rates of major depressive disorder (MDD) are increasing globally, in part due to the coronavirus disease 2019 pandemic, contributing to disease burden. It has long been known that insomnia is intricately connected with depression as indicated by greater depression severity and lower treatment response. Furthermore, insomnia is a significant risk factor for new-onset depression. Treatment of insomnia is thus a logical target for prevention of incidents and recurrent MDD. This systematic review sought to evaluate the current evidence for the preventive effects of insomnia treatment on depression onset. A database search yielded 186 studies, six of which met criteria for inclusion in this review. All of the studies utilized cognitive behavioral treatment for insomnia (CBT-I) as the target intervention and most delivered treatment via a digital platform. Four of the studies found significantly lower rates of MDD onset in those who received CBT-I compared to a control condition. The two remaining studies failed to confirm these effects in primary analyses but secondary analyses suggested evidence of a preventive effect. There was significant methodologic heterogeneity across studies in terms of sample selection, outcomes, and follow-up periods, limiting the ability to draw firm conclusions. The evidence overall is in the direction of insomnia treatment reducing the risk for onset of MDD, but further research is warranted.