Sleep Health at the Genomic Level: Six Distinct Factors and Their Relationships With Psychopathology.

Background: Poor sleep is associated with many negative health outcomes, including multiple dimensions of psychopathology. In the past decade, sleep researchers have advocated for focusing on the concept of sleep health as a modifiable health behavior to mitigate or prevent these outcomes. Sleep health dimensions often include sleep efficiency, duration, satisfaction, regularity, timing, and daytime alertness. However, there is no consensus on how to best operationalize sleep health at the phenotypic and genetic levels. In some studies, specific sleep health domains were examined individually, while in others, sleep health domains were examined together (e.g., with an aggregate sleep health score). Methods: Here, we compared alternative sleep health factor models using genomic structural equation modeling on summary statistics from previously published genome-wide association studies of self-reported and actigraphic sleep measures with effective sample sizes up to 452,633. Results: Our best-fitting sleep health model had 6 correlated genetic factors pertaining to 6 sleep health domains: circadian preference, efficiency, alertness, duration, noninsomnia, and regularity. All sleep health factors were significantly correlated (|rgs| = 0.11-0.51), except for the circadian preference factor with duration and noninsomnia. Better sleep health was generally significantly associated with lower genetic liability for psychopathology (|rgs| = 0.05-0.48), yet the 6 sleep health factors showed divergent patterns of associations with different psychopathology factors, especially when controlling for covariance among the sleep health factors. Conclusions: These results provide evidence for genetic separability of sleep health constructs and their differentiation with respect to associations with mental health.

Anxiety-specific associations with substance use: Evidence of a protective factor in adolescence and a risk factor in adulthood.

Externalizing psychopathology is a strong risk factor for substance use, whereas the role of internalizing manifestations of distress, and anxiety in particular, in predicting substance use remains unclear. Studies have suggested that anxiety may be either a protective or risk factor for substance use. The present study aimed to clarify evidence for anxiety-specific associations with substance use, examining sex and developmental period (adolescence vs. adulthood) as potential moderators that may help explain conflicting results in the literature. In a longitudinal twin sample, cross-sectional associations of anxiety with substance use differed in adolescents and adults and in girls/women and boys/men. Controlling for externalizing psychopathology and depression, anxiety was associated with reduced substance use in adolescent girls and increased substance use in adult women. In contrast, anxiety-specific associations with substance use were not significant in boys and men. Possible explanations for these contrasting results across development and sex are discussed.

Large-scale brain network activation during emotional inhibitory control: Associations with alcohol misuse in college freshmen.

BACKGROUND: The transition to college is associated with increased risk of alcohol misuse and a consequent increase in negative, alcohol-related social and health impacts. Traits associated with ongoing brain maturation during this period, including impulsivity in emotional contexts, could contribute to risky alcohol use. METHODS: This functional magnetic resonance imaging (fMRI) study examined brain network activation strength during an emotional inhibitory control task (Go-NoGo), which required participants to ignore background images with negative or neutral emotional valence during performance. Participants were 60 college freshmen (aged 18-20 years, 33 women). Survey measures, completed at baseline and one-year follow-up (follow-up n = 52, 29 women), assessed alcohol misuse alcohol use disorders identification test (AUDIT), alcohol/substance use counseling center assessment of psychological symptoms (C-CAPS), and negative consequences of alcohol use young adult alcohol consequences questionnaire (YAACQ). Measures were examined relative to network activation strength, on the Negative NoGo > Neutral NoGo contrast, of four large-scale brain networks implicated in top-down regulation of cognition and attention: right and left lateral frontoparietal networks (rL-FPN; lL-FPN), dorsal attention network (DAN), and salience network (SN). RESULTS: Activation strength of DAN was negatively associated with scores on the AUDIT (p = 0.013) and YAACQ (p = 0.004) at baseline, and with C-CAPS score at baseline and follow-up (p = 0.002; p = 0.005), and positively associated with accuracy on NoGo trials with negative backgrounds (p = 0.014). Activation strength of rL-FPN was positively associated with C-CAPS score at follow-up (p = 0.003). SN activation strength was negatively associated with accuracy on NoGo trials with negative (p < 0.001) and neutral (p = 0.002) backgrounds and with the accuracy difference between negative versus neutral NoGo trials (p = 0.003). CONCLUSION: These findings suggest that less engagement of large-scale brain circuitry that supports top-down attentional control, specifically during negative emotions, is associated with more problematic drinking in emerging adults who attend college. This pattern of network activation may serve as a risk marker for ongoing self-regulation deficits during negative emotion that could increase risk of problematic alcohol use and negative impacts of drinking.

Children's Knowledge of Cannabis and Other Substances in States with Different Cannabis Use Regulations.

Background: Public acceptance of cannabis continues to increase across the US, yet there has been little research on how cannabis legalization affects young children. The present study compared knowledge of cannabis and other substances among children living in states with different cannabis laws and examined whether the association between such substance knowledge and externalizing behavior varies by state cannabis regulations. Methods: Participants were from the Adolescent Brain Cognitive DevelopmentSM Study (ABCD Study®) at the baseline assessment (N = 11,875, ages 9-11, collected from 2016 to 2018). Chi-square difference tests were used to compare nested models testing group differences in knowledge of substances and the association between externalizing disorder/behavior and substance knowledge as a function of state legality of cannabis use (recreational, medical, low THC/CBD, none). Results: Children living in states with more permissive cannabis laws had a greater knowledge of cannabis and reported more alcohol experimentation. In contrast, knowledge regarding alcohol, tobacco, and other illicit drugs was not greater in children from states with more permissive cannabis laws. Externalizing disorder/behavior was not significantly associated with cannabis knowledge in any group and not significantly different across groups. The association between externalizing disorder/behavior and illicit drug knowledge was significant only in states with the recreational and medical use laws but did not differ significantly across groups. Conclusion: Children living in environments with more permissive cannabis regulations have greater knowledge of cannabis, but not other substances, and report more experimentation with alcohol.

Clinical Outcomes Following Acute Residential Psychiatric Treatment in Transgender and Gender Diverse Adolescents.

Importance: Transgender and gender diverse (TGD) individuals, who have a gender identity that differs from their sex assigned at birth, are at increased risk of mental health problems, including depression, anxiety, self-injurious behavior, and suicidality, relative to cisgender peers. Objective: To examine mental health outcomes among TGD vs cisgender adolescents in residential treatment. Design, Setting, and Participants: This cohort study's longitudinal design was used to compare groups at treatment entry and discharge, and 1-month postdischarge follow-up. The setting was an adolescent acute residential treatment program for psychiatric disorders. Participants were TGD or cisgender adolescents enrolled in the treatment program. Statistical analysis was performed October 2019 to March 2021. Exposure: Adolescents participated in a 2-week acute residential treatment program for psychiatric disorders. Main Outcomes and Measures: Primary outcomes were depressive (the Center for Epidemiologic Studies Depression Scale [CES-D]) and anxiety (the Multidimensional Anxiety Scale for Children [MASC]) symptoms, and emotional dysregulation (the Difficulties in Emotion Regulation Scale [DERS]), measured at treatment entry and discharge, and postdischarge follow-up. Age of depression onset, suicidality, self-injury, and childhood trauma also were assessed at treatment entry. Results: Of 200 adolescent participants who completed treatment entry and discharge assessments, the mean (SD) age was 16.2 (1.5) years; 109 reported being assigned female at birth (54.5%), 35 were TGD (17.5%), and 66 (49.3%) completed 1-month follow-up. TGD participants had an earlier mean (SD) age of depression onset (TGD: 10.8 [2.4] years vs cisgender: 11.9 [2.3] years; difference: 1.07 years; 95% CI, 0.14-2.01 years; P = .02), higher mean (SD) suicidality scores (TGD: 44.4 [23.1] vs cisgender: 28.5 [25.4]; difference: 16.0; 95% CI, 6.4-25.5; P = .001), more self-injurious behavior (mean [SD] RBQ-A score for TGD: 3.1 [2.5] vs cisgender: 1.7 [1.9]; difference: 1.42; 95% CI, 0.69-2.21; P = .001) and more childhood trauma (eg, mean [SD] CTQ-SF score for emotional abuse in TGD: 12.7 [5.4] vs cisgender: 9.8 [4.7]; difference: 2.85; 95% CI, 1.06-4.64; P = .002). The TGD group also had higher symptom scores (CES-D mean difference: 7.69; 95% CI, 3.30 to 12.08; P < .001; MASC mean difference: 7.56; 95% CI, 0.46 to 14.66; P = .04; and DERS mean difference: 18.43; 95% CI, 8.39 to 28.47; P < .001). Symptom scores were significantly higher at entry vs discharge (CES-D mean difference, -12.16; 95% CI, -14.50 to -9.80; P < .001; MASC mean difference: -3.79; 95% CI, -6.16 to -1.42; P = .02; and DERS mean difference: -6.37; 95% CI, -10.80 to -1.94; P = .05) and follow-up (CES-D mean difference: -9.69; 95% CI, -13.0 to -6.42; P < .001; MASC mean difference: -6.92; 95% CI, -10.25 to -3.59; P < .001; and DERS mean difference: -12.47; 95% CI, -18.68 to -6.26; P < .001). Conclusions and Relevance: This cohort study found mental health disparities in TGD youth relative to cisgender youth, with worse scores observed across assessment time points. For all participants, primary clinical outcome measures were significantly lower at treatment discharge than at entry, with no significant differences between discharge and 1-month follow-up. Given the substantial degree of mental health disparities reported in TGD individuals, these findings warrant focused clinical attention to optimize treatment outcomes in gender minority populations.

The epidemiology of benzodiazepine misuse: A systematic review.

BACKGROUND: Benzodiazepine misuse is a growing public health problem, with increases in benzodiazepine-related overdose deaths and emergency room visits in recent years. However, relatively little attention has been paid to this emergent problem. We systematically reviewed epidemiological studies on benzodiazepine misuse to identify key findings, limitations, and future directions for research. METHODS: PubMed and PsychINFO databases were searched through February 2019 for peer-reviewed publications on benzodiazepine misuse (e.g., use without a prescription; at a higher frequency or dose than prescribed). Eligibility criteria included human studies that focused on the prevalence, trends, correlates, motives, patterns, sources, and consequences of benzodiazepine misuse. RESULTS: The search identified 1970 publications, and 351 articles were eligible for data extraction and inclusion. In 2017, benzodiazepines and other tranquilizers were the third most commonly misused illicit or prescription drug in the U.S. (approximately 2.2% of the population). Worldwide rates of misuse appear to be similar to those reported in the U.S. Factors associated with misuse include other substance use, receipt of a benzodiazepine prescription, and psychiatric symptoms and disorders. Benzodiazepine misuse encompasses heterogeneous presentations of motives, patterns, and sources. Moreover, misuse is associated with myriad poor outcomes, including mortality, HIV/HCV risk behaviors, poor self-reported quality of life, criminality, and continued substance use during treatment. CONCLUSIONS: Benzodiazepine misuse is a worldwide public health concern that is associated with a number of concerning consequences. Findings from the present review have implications for identifying subgroups who could benefit from prevention and treatment efforts, critical points for intervention, and treatment targets.