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Academic performance plays a crucial role in long-term educational attainment and occupational function. Chronotype refers to an individual's daily tendencies for times for waking, activity, and sleep. Social jetlag reflects the mismatch between an individual's chronotype and their social schedule. Because school typically starts early in the morning, later chronotype is often associated with daytime sleepiness, insufficient sleep, and poor academic performance. However, the relationship between academic performance, chronotype, and social jetlag has not been extensively examined in large samples like the Adolescent Brain Cognitive Development (ABCD) study. We hypothesized that greater social jetlag would predict poorer cognitive and academic performance. Year 2 (ages 11–14) cross-sectional data from the ABCD cohort (n = 6,890 adolescents) were used to evaluate academic performance (i.e. self-reported past year grades), NIH Toolbox cognitive performance measures, chronotype, and social jetlag from the Munich Chronotype Questionnaire. We found that later chronotype and greater social jetlag predicted poorer cognitive and academic performance with small effect sizes. Our findings emphasize the importance of individual differences in chronotype and social jetlag when designing class schedules, as aligning school activities with student optimal sleep-wake times may contribute to improved academic performance. [ABSTRACT FROM AUTHOR]

Circadian rhythm disturbances, especially circadian phase delays are associated with impulsive behaviors and have been implicated in psychiatric disorders. Chronotype is a developmentally regulated proxy measure of circadian phase. Past studies have investigated the relationship between chronotype and trauma and found that trauma is associated with evening chronotypes, suggesting the course of chronotype development may be affected by adverse childhood experiences (ACEs). However, the relationships among chronotype, impulsivity and ACEs have largely been studied in a pairwise manner using small, cross-sectional cohorts. We hypothesized that in a cohort of high-risk youth, childhood trauma would be associated with later chronotype, and later chronotype would be associated with higher rates of impulsivity. We analyzed a cross-sectional sample (n = 966) from Year 2 of adolescents at high risk for psychiatric disorders from the ABCD study who were characterized for chronotype, stressful life events, and impulsivity. We used a hierarchical regression model to examine the relationship between chronotype, stressful life events, and impulsivity using the Munich Chronotype Questionnaire (MCTQ), the Life Events Scale, Urgency, Premeditation, Perseverance and Sensation Seeking (UPPS) Impulsive Behavior scale. We found associations between eveningness, stressful life events, and all dimensions of impulsivity. Increased eveningness was associated with a higher number of stressful life events and increased impulsivity. Understanding the role of stressful life events and impulsivity in those predisposed towards eveningness is useful because it may improve our understanding of the biological mechanisms that contribute to psychiatric disorders, and lead to better prevention and treatment efforts using interventions such as increased lifestyle regularity and daytime light exposure. • Impulsivity, later chronotype, stressful life events.→poor mental/physical health • Evening chronotype, stressful life events, and impulsivity are interrelated. • Investigation may help identify interventions to promote mental health & wellbeing. • Future work in prospective studies to clarify these factors will be essential. [ABSTRACT FROM AUTHOR]

Background: Bipolar disorder (BD) is characterized by episodes of depression and mania and disrupted circadian rhythms. Lithium is an effective therapy for BD, but only 30%–40% of patients are fully responsive. Preclinical models show that lithium alters circadian rhythms. However, it is unknown if the circadian rhythm effects of lithium are essential to its therapeutic properties. Methods: In secondary analyses of a multi‐center, prospective, trial of lithium for BD, we examined the relationship between circadian rhythms and therapeutic response to lithium. Using standardized instruments, we measured morningness, diurnal changes in mood, sleep, and energy (circadian rhythm disturbances) in a cross‐sectional study of 386 BD subjects with varying lithium exposure histories. Next, we tracked symptoms of depression and mania prospectively over 12 weeks in a subset of 88 BD patients initiating treatment with lithium. Total, circadian, and affective mood symptoms were scored separately and analyzed. Results: Subjects with no prior lithium exposure had the most circadian disruption, while patients stable on lithium monotherapy had the least. Patients who were stable on lithium with another drug or unstable on lithium showed intermediate levels of disruption. Treatment with lithium for 12 weeks yielded significant reductions in total and affective depression symptoms. Lithium responders (Li‐Rs) showed improvement in circadian symptoms of depression, but non‐responders did not. There was no difference between Li‐Rs and nonresponders in affective, circadian, or total symptoms of mania. Conclusions: Exposure to lithium is associated with reduced circadian disruption. Lithium response at 12 weeks was selectively associated with the reduction of circadian depressive symptoms. We conclude that stabilization of circadian rhythms may be an important feature of lithium's therapeutic effects. Clinical Trials Registry: NCT0127253. [ABSTRACT FROM AUTHOR]

Circadian rhythm disturbances are frequently described in psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia. Growing evidence suggests a biological connection between mental health and circadian rhythmicity, including the circadian influence on brain function and mood and the requirement for circadian entrainment by external factors, which is often impaired in mental illness. Mental (as well as physical) health is also adversely affected by circadian misalignment. The marked interindividual differences in this combined susceptibility, in addition to the phenotypic spectrum in traits related both to circadian rhythms and mental health, suggested the possibility of a shared genetic background and that circadian clock genes may also be candidate genes for psychiatric disorders. This hypothesis was further strengthened by observations in animal models where clock genes had been knocked out or mutated. The introduction of genome-wide association studies (GWAS) enabled hypothesis-free testing. GWAS analysis of chronotype confirmed the prominent role of circadian genes in these phenotypes and their extensive polygenicity. However, in GWAS on psychiatric traits, only one clock gene, ARNTL (BMAL1) was identified as one of the few loci differentiating bipolar disorder from schizophrenia, and macaque monkeys where the ARNTL gene has been knocked out display symptoms similar to schizophrenia. Another lesson from genomic analyses is that chronotype has an important genetic correlation with several psychiatric disorders and that this effect is unidirectional. We conclude that the effect of circadian disturbances on psychiatric disorders probably relates to modulation of rhythm parameters and extend beyond the core clock genes themselves. [ABSTRACT FROM AUTHOR]

Circadian rhythm abnormalities have been recognized as a central feature of bipolar disorder (BD) but a coherent biological explanation for them remains lacking. Using genetic mutation of 'clock genes', robust animal models of mania and depression have been developed that elucidate key aspects of circadian rhythms and the circadian clock-mood connection. However, translation of this knowledge into humans remains incomplete. In recent years, very large genome-wide association studies (GWAS) have been conducted and the genetic underpinnings of BD are beginning to emerge. However, these genetic studies in BD do not match well with the evidence from animal studies that implicate the circadian clock in mood regulation. Even larger GWAS have been conducted for circadian phenotypes including chronotype, rhythm amplitude, sleep duration, and insomnia. These studies have identified a diverse set of associated genes, including a minority with previously well-characterized functions in the circadian clock. Taken together, the data from recent GWAS of BD and circadian phenotypes indicate that the genetic organization of the circadian clock, both in health and in BD is complex. The findings from GWAS elucidate potentially novel circadian mechanism that may be partly distinct from those identified in animal models. Pleiotropy, epistasis and nongenetic factors may play important roles in regulating circadian rhythms, some of which may underlie circadian rhythm disturbances in BD. [ABSTRACT FROM AUTHOR]

• Bipolar disorder is characterized by pervasive disruptions in circadian rhythms. • Lithium has effects on cellular and behavioral rhythms. • The effects of lithium on circadian rhythms are context- and dose-dependent. • Lithium responsive bipolar disorder patients show distinct circadian rhythm characteristics: morning chronotype, less variable behavioral rhythms, and shorter period in cultured cells. Bipolar disorder (BD) is characterized by disrupted circadian rhythms affecting sleep, arousal, and mood. Lithium is among the most effective mood stabilizer treatments for BD, and in addition to improving mood symptoms, stabilizes sleep and activity rhythms in treatment responsive patients. Across a variety of experimental models, lithium has effects on circadian rhythms. However, uncertainty exists as to whether these actions directly pertain to lithium's therapeutic effects. Here, we consider evidence from mechanistic studies in animals and cells and clinical trials in BD patients that identify associations between circadian rhythms and the therapeutic effects of lithium. Most evidence indicates that lithium has effects on cellular circadian rhythms and increases morningness behaviors in BD patients, changes that may contribute to the therapeutic effects of lithium. However, much of this evidence is limited by cross-sectional analyses and/or imprecise proxy markers of clinical outcomes and circadian rhythms in BD patients, while mechanistic studies rely on inference from animals or small numbers of patients. Further study may clarify the essential mechanisms underlying lithium responsive BD, better characterize the longitudinal changes in circadian rhythms in BD patients, and inform the development of therapeutic interventions targeting circadian rhythms. [ABSTRACT FROM AUTHOR]

• Chronotype was assessed in a longitudinal cohort followed for a median of 9 years. • Individuals with bipolar I and II disorder have a later chronotype than controls. • Individuals with bipolar I showed greater chronotype instability than controls. • Mood stabilizer use was associated with greater chronotype stability. • Antidepressant use was associated with greater chronotype instability. 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. Participants with BD I (n = 271), BD II (n = 88), and healthy controls (n = 217) were included (follow-up M =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. 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. 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. [ABSTRACT FROM AUTHOR]