David A. Kalmbach

Shift work disorder, depression, and anxiety in the transition to rotating shifts: the role of sleep reactivity.

AIM The aim of this study is to investigate premorbid sleep reactivity as a vulnerability to incident shift work disorder (SWD), and related changes in depression as well as anxiety following a transition to a rotating shifts work schedule. METHODS This is a longitudinal study with two waves of data collection. The community-based sample included normal sleeping non-shift workers (N = 96; 62.5% female; 47.9 ± 13.3 years) without a lifetime history of insomnia or baseline excessive daytime sleepiness who transitioned to rotating shift work one year later. Participants reported demographic characteristics, trait sleep reactivity on the Ford Insomnia Response to Stress Test, depression symptoms on the Quick Inventory of Depression Symptomatology, and anxiety symptoms on the Beck Anxiety Inventory. SWD was determined based on significant sleep disturbance and/or excessive sleepiness in the context of working in a rotating-shift schedule. RESULTS Analyses revealed that the odds were over five times greater for highly sleep-reactive individuals to develop SWD after transitioning to rotating shifts (OR = 5.59, p = 0.04). Nearly 90% of participants who suffered from SWD were accurately identified as high risk at one year before disease onset. Furthermore, individuals who developed SWD reported greater increases in symptoms of depression and anxiety. Finally, analyses revealed significant indirect effects wherein high sleep reactivity increased risk for SWD, which led to greater severity of anxiety and depression symptoms. CONCLUSIONS The Ford Insomnia Response to Stress Test (FIRST) accurately identifies a focused target population in which the premorbid psychobiological processes complicit in SWD onset and progression, as well as shift work-related depression and anxiety changes, can be better investigated, thus improving future preventative efforts.

How Changes in Depression and Anxiety Symptoms Correspond to Variations in Female Sexual Response in a Nonclinical Sample of Young Women: A Daily Diary Study

INTRODUCTION A large body of literature supports the co-occurrence of depression, anxiety, and sexual dysfunction. However, the manner in which affective symptoms map onto specific female sexual response indices is not well understood. AIMS The present study aimed to examine changes in depression and anxiety symptoms and their correspondence to fluctuations in desire, subjective arousal, genital response, orgasmic function, and vaginal pain. METHODS The study used a 2-week daily diary approach to examine same-day and temporal relations between affective symptoms and sexual function. MAIN OUTCOME MEASURES The unique relations between shared and disorder-specific symptoms of depression and anxiety (i.e., general distress, anhedonia, and anxious arousal) and female sexual response (i.e., desire, subjective arousal, vaginal lubrication, orgasmic function, and sexual pain) were examined, controlling for baseline levels of sexual distress, depression, and anxiety, as well as age effects and menstruation. RESULTS Analyses revealed that changes in depression and anxiety severity corresponded to same-day variations in sexual response. Specifically, anhedonia (depression-specific symptom) was related to poorer same-day sexual desire, whereas greater anxious arousal (anxiety-specific symptom) was independently related to simultaneous increases in subjective sexual arousal, vaginal lubrication, and sexual pain. Increases in general distress (i.e., shared symptoms) were associated with greater same-day difficulties achieving orgasm. Notably, only one temporal relation was found; it indicated that higher levels of anhedonia predicted a next-day decrease in sexual desire. CONCLUSIONS It is proposed that the simultaneous changes in affective symptoms and sexual function may indicate that they are products of shared underlying mechanisms. That is, in response to stress, the processes manifesting as feelings of weak positive affect and amotivation are the very same processes responsible for diminished capacity for sexual desire. In contrast, the physiological hyperarousal associated with anxiety also gives rise to sexual arousal difficulties and vaginal pain.

Genetic Basis of Chronotype in Humans: Insights From Three Landmark GWAS

Study Objectives: Chronotype, or diurnal preference, refers to behavioral manifestations of the endogenous circadian system that governs preferred timing of sleep and wake. As variations in circadian timing and system perturbations are linked to disease development, the fundamental biology of chronotype has received attention for its role in the regulation and dysregulation of sleep and related illnesses. Family studies indicate that chronotype is a heritable trait, thus directing attention toward its genetic basis. Although discoveries from molecular studies of candidate genes have shed light onto its genetic architecture, the contribution of genetic variation to chronotype has remained unclear with few related variants identified. In the advent of large‐scale genome‐wide association studies (GWAS), scientists now have the ability to discover novel common genetic variants associated with complex phenotypes. Three recent large‐scale GWASs of chronotype were conducted on subjects of European ancestry from the 23andMe cohort and the UK Biobank. This review discusses the findings of these landmark GWASs in the context of prior research. Methods: We systematically reviewed and compared methodological and analytical approaches and results across the three GWASs of chronotype. Results: A good deal of consistency was observed across studies with 9 genes identified in 2 of the 3 GWASs. Several genes previously unknown to influence chronotype were identified. Conclusions: GWAS is an important tool in identifying common variants associated with the complex chronotype phenotype, the findings of which can supplement and guide molecular science. Future directions in model systems and discovery of rare variants are discussed.

DSM-5 insomnia and short sleep: Comorbidity landscape and racial disparities

STUDY OBJECTIVES We estimated rates of cardiometabolic disease, pain conditions, and psychiatric illness associated with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) insomnia disorder (current and in remission) and habitual short sleep (fewer than 6 h), and examined the roles of insomnia and short sleep in racial disparities in disease burden between black and non-Hispanic white Americans. METHODS This epidemiological survey study was cross-sectional. The community-based sample consisted of 3,911 subjects (46.0 y ± 13.3; 65.4% female; 25.0% black) across six sleep groups based on DSM-5 insomnia classification (never vs. remitted vs. current) and self-reported habitual sleep duration (normal vs. short). Vascular events, cardiometabolic disease, pain conditions, and psychiatric symptoms were self-reported. RESULTS Short sleeping insomniacs were at elevated risk for myocardial infarction, stroke, treated hypertension, diabetes, chronic pain, back pain, depression, and anxiety, independent of sex, age, and obesity. Morbidity profiles for insomniacs with normal sleep duration and former insomniacs, irrespective of sleep duration, were similar with elevations in treated hypertension, chronic pain, depression, and anxiety. Regarding racial disparities, cardiometabolic and psychiatric illness burden was greater for blacks, who were more likely to have short sleep and the short sleep insomnia phenotype. Evidence suggested that health disparities may be attributable in part to race-related differences in sleep. CONCLUSIONS Insomnia disorder with short sleep is the most severe phenotype of insomnia and comorbid with many cardiometabolic and psychiatric illnesses, whereas morbidity profiles are highly similar between insomniacs with normal sleep duration and former insomniacs. Short sleep endemic to black Americans increases risk for the short sleep insomnia phenotype and likely contributes to racial disparities in cardiometabolic disease and psychiatric illness.

The Transaction Between Depression and Anxiety Symptoms and Sexual Functioning: A Prospective Study of Premenopausal, Healthy Women.

A number of studies have called attention to the problematic interplay between depression and anxiety symptoms and sexual difficulties. However, despite the bidirectional conceptualization of the association between affective and sexual problems, few studies have adequately examined temporal precedence or state-level fluctuations between these two constructs. Using Clark and Watson’s (1991) tripartite model of anxiety and depression, the current study employed a repeated measures design to examine how weekly changes in affective symptoms were related to weekly changes in sexual functioning in a non-clinical sample of premenopausal women. First, we examined how general distress, anxious arousal, and anhedonia were concurrently related to various indices of sexual functioning. Next, we examined lagged effects of mood and anxiety symptoms predicting later levels of sexual functioning. Finally, we tested sexual functioning’s influence on later reports of affective symptoms. Hierarchical linear modeling analyses revealed that, of the three symptom types tested, anhedonic depression was the most consistently related to sexual problems, and that these relations were more proximal than distal. The preponderance of data suggested temporal precedence of mood on sexual symptoms. These findings emphasize the importance of prospective studies in the investigation of mental and sexual health.

Daily Affect and Female Sexual Function

INTRODUCTION The specific affective experiences related to changes in various aspects of female sexual function have received little attention as most prior studies have focused instead on the role of clinical mood and anxiety disorders and their influence on sexual dysfunction. AIM We sought to understand the transaction between daily affect and female sexual function in effort to provide a more nuanced understanding of the interplay between affective and sexual experiences. METHODS The present study used a 2-week daily diary approach to examine same-day and temporal relations between positive and negative affect states and sexual function in young women. MAIN OUTCOME MEASURES We examined the unique relations between positive (i.e., joviality, serenity, self-assurance) and negative (i.e., fear, sadness, hostility) affects and female sexual response (i.e., desire, subjective arousal, vaginal lubrication, orgasmic function, and sexual pain) while controlling for higher order sexual distress, depression, and anxiety, as well as age effects and daily menstruation. RESULTS Analyses revealed different aspects of both positive and negative affects to be independently related to sexual response indices. Specifically, results indicated that joviality was related to same-day sexual desire and predicted increased desire the following day. This latter relation was partially mediated by sexual activity. Further, greater sexual desire predicted next-day calmness, which was partially mediated by sexual activity. Notably, fear was related to same-day subjective arousal, lubrication, orgasmic function, and vaginal pain, whereas poorer orgasmic function predicted greater next-day sadness. CONCLUSIONS These findings describe the manner in which changes in affect correspond to variations in female sexual function, thus highlighting the inextricability of mental and sexual health. Further, these findings may offer insight into the progression of normative levels of affect and sexual function as they develop into comorbid depression, anxiety, and sexual dysfunction.

Sleep Disturbance and Short Sleep as Risk Factors for Depression and Perceived Medical Errors in First-Year Residents

Study Objectives While short and poor quality sleep among training physicians has long been recognized as problematic, the longitudinal relationships among sleep, work hours, mood, and work performance are not well understood. Here, we prospectively characterize the risk of depression and medical errors based on preinternship sleep disturbance, internship-related sleep duration, and duty hours. Methods Survey data from 1215 nondepressed interns were collected at preinternship baseline, then 3 and 6 months into internship. We examined how preinternship sleep quality and internship sleep and work hours affected risk of depression at 3 months, per the Patient Health Questionnaire 9. We then examined the impact of sleep loss and work hours on depression persistence from 3 to 6 months. Finally, we compared self-reported errors among interns based on nightly sleep duration (≤6 hr vs. >6 hr), weekly work hours (<70 hr vs. ≥70 hr), and depression (non- vs. acutely vs. chronically depressed). Results Poorly sleeping trainees obtained less sleep and were at elevated risk of depression in the first months of internship. Short sleep (≤6 hr nightly) during internship mediated the relationship between sleep disturbance and depression risk, and sleep loss led to a chronic course for depression. Depression rates were highest among interns with both sleep disturbance and short sleep. Elevated medical error rates were reported by physicians sleeping ≤6 hr per night, working ≥ 70 weekly hours, and who were acutely or chronically depressed. Conclusions Sleep disturbance and internship-enforced short sleep increase risk of depression development and chronicity and medical errors. Interventions targeting sleep problems prior to and during residency hold promise for curbing depression rates and improving patient care.

Reciprocal dynamics between self-rated sleep and symptoms of depression and anxiety in young adult women: a 14-day diary study

OBJECTIVES The objective of this study was to characterize the day-to-day associations among sleep disturbance, depression, and anxiety in a sample of young adult women. METHODS One hundred and seventy-one women (20.1 ± 3.3 years) completed in-laboratory baseline assessment followed by daily online surveys across a two-week period. Daily measures included the Mood and Anxiety Symptom Questionnaire-Short Form to assess shared and disorder-specific symptoms of depression and anxiety (general distress, anhedonic depression, and anxious arousal), as well as self-reported total sleep time (TST), sleep-onset latency (SOL), and sleep quality (SQ). RESULTS Findings supported bidirectional day-to-day relationships between sleep and affective symptoms. When women felt greater general distress (shared features of anxiety and depression), they experienced longer SOL and worse SQ at night. Specificity among depression, anxiety, and sleep disturbance was observed such that higher levels of depression-specific anhedonia presaged longer SOL, shorter TST, and poorer SQ. In the other direction, when women had poor-quality sleep, they later experienced greater anhedonic depression and anxious arousal. The influence of TST on anhedonia was complex such that a single night of short sleep led to less anhedonic depression the next day, whereas women who obtained shorter sleep across the two-week period reported greater anhedonia. CONCLUSIONS Reciprocal dynamics between nightly sleep disturbance and daily experiences of depression and anxiety may serve as a process by which insomnia, depression, and anxiety develop into comorbid clinical states over time in women. The associations of anhedonic depression with nightly sleep disturbance and chronic short sleep were especially toxic, offering insight into daily mechanisms driving the most prevalent phenotype of comorbid insomnia.

Work-Family Conflict and the Sex Difference in Depression Among Training Physicians

Importance Depression is common among training physicians and may disproportionately affect women. The identification of modifiable risk factors is key to reducing this disease burden and its negative impact on patient care and physician career attrition. Objective To determine the presence and magnitude of a sex difference in depressive symptoms and work-family conflict among training physicians; and if work-family conflict impacts the sex difference in depressive symptoms among training physicians. Design, Setting, and Participants A prospective longitudinal cohort study of medical internship in the United States during the 2015 to 2016 academic year in which 3121 interns were recruited across all specialties from 44 medical institutions. Main Outcomes and Measures Prior to and during their internship year, participants reported the degree to which work responsibilities interfered with family life using the Work Family Conflict Scale and depressive symptoms using the Patient Health Questionnaire-9 (PHQ-9). Results Mean (SD) participant age was 27.5 (2.7) years, and 1571 participants (49.7%) were women. Both men and women experienced a marked increase in depressive symptoms during their internship year, with the increase being statistically significantly greater for women (men: mean increase in PHQ-9, 2.50; 95% CI, 2.26-2.73 vs women: mean increase, 3.20; 95% CI, 2.97-3.43). When work-family conflict was accounted for, the sex disparity in the increase in depressive symptoms decreased by 36%. Conclusions and Relevance Our study demonstrates that depressive symptoms increase substantially during the internship year for men and women, but that this increase is greater for women. The study also identifies work-family conflict as an important potentially modifiable factor that is associated with elevated depressive symptoms in training physicians. Systemic modifications to alleviate conflict between work and family life may improve physician mental health and reduce the disproportionate depression disease burden for female physicians. Given that depression among physicians is associated with poor patient care and career attrition, efforts to alleviate depression among physicians has the potential to reduce the negative consequences associated with this disease.

Sleep system sensitization: evidence for changing roles of etiological factors in insomnia

OBJECTIVES To test for sensitization of the sleep system in response to insomnia development and major life stress. In addition, to evaluate the impact on depression and anxiety associated with sleep system sensitization. METHODS A longitudinal study with three annual assessments. The community-based sample included 262 adults with no history of insomnia or depression who developed insomnia one year after baseline (67.6% female; 44.0 ± 13.4 yr). Measures included the Ford Insomnia Response to Stress Test to assess sleep reactivity, Quick Inventory of Depressive Symptomatology, and Beck Anxiety Inventory. Insomnia classification was based on DSM-IV criteria. Sleep system sensitization was operationally defined as significant increases in sleep reactivity. RESULTS Sensitization of the sleep system was observed from baseline to insomnia onset at 1-yr follow-up among insomniacs with low premorbid vulnerability (p < 0.001), resulting in 68.3% of these individuals re-classified as highly sleep reactive. Major life stress was associated with greater sleep system sensitization (p = 0.02). Results showed that sleep reactivity at 2-yr follow-up remained elevated among those with low premorbid vulnerability, even after insomnia remission (p < 0.01). Finally, analyses revealed that increases in sleep reactivity predicted greater depression (p < 0.001) and anxiety (p < 0.001) at insomnia onset. The impact of sensitization on depression was stable at 2-yr follow-up (p = 0.01). CONCLUSIONS Evidence supports sensitization of the sleep system as a consequence of insomnia development and major life stress among individuals with low premorbid sleep reactivity. Sleep system sensitization may serve as a mechanism by which insomnia is perpetuated. Harmful effects of the sensitization process may increase risk for insomnia-related depression and anxiety.