Dimensional Affective Sensitivity to Hormones across the Menstrual Cycle (DASH-MC): A transdiagnostic framework for ovarian steroid influences on psychopathology.

Fluctuations in progesterone (P4) and estradiol (E2) across the menstrual cycle can exert direct effects on biological systems implicated in neuropsychiatric disorders and represent a key biological source of variability in affective, cognitive, and behavioral disorders. Although these cyclical symptoms may be most readily identified when they occur exclusively in relation to the menstrual cycle, as in DSM-5 premenstrual dysphoric disorder, symptom changes of similar magnitude occur in a larger proportion of people with ongoing psychiatric disorders. Studies investigating cyclical regulation of brain and behavior often produce inconsistent results, which may be attributed to a lack of focus on specific hormonal events and individual differences in related sensitivities. We propose a transdiagnostic Dimensional Affective Sensitivity to Hormones across the Menstrual Cycle (DASH-MC) framework, postulating that atypical neural responses to several key hormonal events provoke specific temporal patterns of affective and behavioral change across the menstrual cycle. We review prospective and experimental evidence providing initial support for these dimensions, which include (1) luteal-onset negative affect caused by a sensitivity to E2 or P4 surges (mediated by neuroactive metabolites such as allopregnanolone), typified by irritability and hyperarousal; (2) perimenstrual-onset negative affect caused by a sensitivity to low or falling E2, typified by low mood and cognitive dysfunction; and (3) preovulatory-onset positive affect dysregulation caused by a sensitivity to E2 surges, typified by harmful substance use and other risky reward-seeking. This multidimensional, transdiagnostic framework for hormone sensitivity can inform more precise research on ovarian steroid regulation of psychopathology, including further mechanistic research, diagnostic refinement, and precision psychiatry treatment development. Additionally, given the high rates of hormone sensitivity across affective disorders, the DASH-MC may guide broader insights into the complex neurobiological vulnerabilities driving female-biased affective risk, as well as potential triggers and mechanisms of affective state change in psychiatric disorders.

Correlates of Menarcheal Age in a Psychiatric Sample of Adolescents.

ABSTRACT: Early pubertal timing is associated with more adverse childhood experiences (ACEs) and increased risk for psychopathology during adolescence. However, most work to date has used community or epidemiological samples, and it remains unclear whether these associations persist in acute clinical samples. The present study examined associations between age at menarche and ACEs, psychiatric symptoms, and emotion regulation difficulties in a sample of N = 140 adolescents on a psychiatric inpatient unit. Youth with early menarche reported higher levels of depressive symptoms, more severe suicidal ideation, and greater difficulty with emotion regulation than youth with normative age at menarche. There was a marginal effect of youth with early menarche reporting more ACEs and more anxiety symptoms. These results suggest menarcheal age, and ACEs may be useful risk factors to assess in inpatient settings to predict risk for more severe outcomes, and future research on pubertal timing in high acuity settings is warranted.

Improving rigor through gender inclusivity in reproductive psychiatric science.

Accurately defining the individuals that research involves and generalizes to is critical for rigorous and reproducible science. In reproductive psychiatry, which historically focuses on the impact of the menstrual cycle, pregnancy, and menopause on mental health, this means moving beyond characterizing samples and relevant populations as "women" in favor of language that precisely identifies the physiological characteristics pertinent to the research being conducted and accurately reflects the varied genders represented in those populations. Concrete recommendations are provided for precise use of sex and gender terminology and gender inclusivity throughout the scientific process, including study conceptualization, etiquette in research environments, recruitment, methods, and dissemination. Recommendations are discussed in depth and presented in a checklist format for ease of use by research teams. Suggested items for assessing gender and relevant sex-related physiology in the context of reproductive psychiatry are also provided.

Associations Between Pubertal Stage and Depression: A Systematic Review of the Literature.

The current article systematically reviews the literature and provides results from 36 studies testing the relation between pubertal stage and depression, as well as moderators and mediators of this relation. Results indicate that there is a significant relation between advancing pubertal stage and depression among girls, and this effect is strongest among White girls. Among boys, risk for depression does not increase with pubertal stage. Importantly, gonadal development appears to be driving the pubertal stage effect. Increasing hormone concentrations, shared environmental stressors, and body esteem appear to be mechanisms of this relation; increases in nonshared environmental stressors (negative life events, peer victimization) moderate the relation between pubertal stage and depression. Inconsistencies in findings across studies can be explained by methodological differences. Future work on this topic should control for age, examine differences by sex, and utilize within-person analyses to evaluate the effect of pubertal stage on depression over time.

Negative Inferential Style Mediates the Association between Racial Identity and Depressive Symptoms among African American Adolescents.

Negative inferential style is a cognitive vulnerability for depression. Yet, few studies have explored how this risk factor intersects with culturally-specific protective factors, such as racial identity, in a unified cognitive risk-cultural asset model in youth of color. The current study addressed this gap by exploring the interplay between negative inferential style, racial identity, and depressive symptoms in an urban African-American adolescent community sample (N = 233; 51.9% female). Cross-lagged panel analyses estimated concurrent and prospective relationships between study variables. Racial identity dimensions of regard, but not centrality, were significant predictors of inferential style, and buffered against the development of depressive symptoms via the development of a less negative inferential style. Implications for the study of racial identity and cognition, and treatment of African-American adolescents are discussed.

Concurrent and Longitudinal Associations of Sex and Race with Inflammatory Biomarkers during Adolescence.

Chronic, systemic inflammation is implicated in physical and mental health; little is known about whether sex and racial differences detected in adulthood are observed during adolescence or about normative changes occurring during adolescence. This longitudinal, United States-based study examined four biomarkers of systemic inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and IL-8) in 315 adolescents (51% female; 58% black; baseline age = 16.49 years (SD = 1.56; range: 12.14-21.28)] at three timepoints. Notable results included: general decline in inflammatory biomarkers in older adolescents, lower levels of TNF-α/IL-8 in black adolescents, elevated CRP/IL-6 in females, and especially higher levels of IL-6 in black, female adolescents. Implications are discussed, particularly the potential health implications of elevated IL-6 in black females.

Mood symptoms and impairment due to substance use: A network perspective on comorbidity.

BACKGROUND: Mood disorders and problematic substance use co-occur and confer reciprocal risk for each other. Few studies use analytic approaches appropriate for testing whether specific features of one disorder confer risk for the other. METHODS: 445 participants (59.8% female, Mean age = 20.3 years) completed measures of depression and hypo/mania symptoms and substance use-related impairment; 330 had complete data at follow-up. Of these, 28% reported a history of depression, 4% of bipolar spectrum disorder, 11% of substance use disorder, and 55% reported substance-related impairment. Symptoms and domains of substance-related impairment were modeled in cross-sectional and cross-lagged panel network models. RESULTS: Impulsive and interpersonal impairment were most highly comorbid with mood symptoms. Suicidal ideation, sadness, decreased need for sleep, and guilt were the symptoms most highly comorbid with impairment. Interpersonal impairment due to substance use was the strongest cross-construct predictor of mood symptoms and suicidal ideation was most predictive of impairment. Social, intrapersonal, and physical impairment due to substance use were most predicted by previous mood symptoms and decreased need for sleep, guilt, and euphoria were most strongly predicted by past impairment. LIMITATIONS: Measures do not assess all mood symptoms, participants with low reward sensitivity were excluded, only self-report measures were used, and some variables were single-items. CONCLUSIONS: Components of these syndromes that confer cross-construct risk might not be the same components that are predicted by the other construct. The bidirectional relationship between mood symptoms and problematic substance use might be better conceptualized at the element, rather than diagnostic, level.

Pubertal Synchrony and Depressive Symptoms: Differences by Race and Sex.

Individual differences in the timing and tempo of pubertal development have been shown to be related to depressive symptoms during adolescence, particularly among girls. Another measure of variability in pubertal development is pubertal synchrony, the degree to which the development of pubertal indicators (e.g., breast growth and ancillary hair growth) are synchronized within the individual. Pubertal synchrony also has been hypothesized to be related to depressive symptoms, but, to date, only one study has tested this hypothesis. However, it remains unclear whether pubertal synchrony confers risk for depressive symptoms more proximally in time or differentially among boys or non-White youth. The current study examined the relation between pubertal synchrony and depressive symptoms concurrently and six months later as a function of race and sex in a community sample of 215 youth (53% female, 44.7% African American; mean age = 12.90 years (SD = 0.86)). Girls with asynchronous development at Time 1 reported significantly higher depressive symptoms at Time 2 than girls with synchronous development and boys with asynchronous development. In addition, boys with asynchronous development at Time 1 had lower depressive symptoms at Time 2 than boys with synchronous development. Race did not moderate pubertal synchrony-depression relations. These results suggest that pubertal asynchrony is a risk factor for girls, but a protective factor for boys, and lend support for pubertal synchrony as a potential contributor to the gender gap in depression that emerges during adolescence.

Early Pubertal Timing Mediates the Association between Low Socioeconomic Status and Poor Attention and Executive Functioning in a Diverse Community Sample of Adolescents.

Low socioeconomic status (SES) may be associated with earlier pubertal timing and impaired attention and executive function (EF) in youth; however, whether pubertal timing mediates the relation between SES and attention or executive functioning remains unclear. Structural equation models tested concurrent and prospective relations between SES, pubertal timing, and attention and executive functioning measures in a gender and racially diverse sample of adolescents (N = 281, 45.6% male, 50.5% White/Caucasian, 46.3% Black/African American, 3.2% Biracial/other, and 44.5% low SES; complete data were not available on some measures). Youth from low SES families experienced earlier pubertal timing, and this accelerated development was associated with worse performance on attention and executive functioning tasks, both concurrently and longitudinally. These findings highlight a pathway by which youth from low socioeconomic backgrounds may develop worse attention and executive functioning abilities during adolescence.

Pubertal Status and Age are Differentially Associated with Inflammatory Biomarkers in Female and Male Adolescents.

A better understanding of the maturational correlates of inflammatory activity during adolescence is needed to more appropriately study both normal and abnormal development. Inflammation is the immune system's first response to infection, injury, or psychological stress, and it has been shown to be elevated in individuals with both physical and psychological conditions. This study examined unique associations between (1) pubertal status and inflammatory biomarkers, and (2) age and inflammatory biomarkers, and whether these relationships differed by sex in a diverse sample of 155 adolescents (54.2% female, 45.8% male; Mage = 16.22) from a northeastern city in the US. A more advanced pubertal status was uniquely associated with lower levels of tumor necrosis factor alpha (TNF-α) and interleukin-8 (IL-8). Chronological age was uniquely associated with lower IL-8 levels. The association between pubertal status and C-reactive protein (CRP) levels differed by sex: more mature females had higher CRP, whereas pubertal status and CRP were not significantly associated in males. These findings highlight an important relation between pubertal development and inflammatory activity during adolescence.

Pubertal Timing and Substance use in Adolescence: an Investigation of Two Cognitive Moderators.

Off-time pubertal development is a predictor of substance use among adolescents. Early-maturing girls and early- and late-maturing boys appear to be at greater risk for substance use, although findings are more consistent for girls. Although cognitive factors are also important in the etiology of adolescent substance use, few studies have investigated potential cognitive risk and protective factors in these associations. The current study tested whether future orientation or cognitive style (e.g., attributions youth make about the causes and consequences of negative life events) moderated the association between pubertal timing and substance use two years later and whether this effect was stronger for females. Multiple linear regressions revealed cognitive style and future orientation significantly moderated the association between pubertal timing and substance use, and these effects did not differ by sex. Importantly, the pattern of these interactions differed, such that early pubertal timing predicted more substance use in the context of more negative and moderate cognitive styles and greater and moderate future orientation. Follow-up analyses revealed that an adolescent's attributions about the consequences, globality, and self-worth implications of negative life events significantly moderated the pubertal timing - future substance use association. Furthermore, the pattern of these interactions predicted each of the four types of substances assessed in the context of cognitive style, but only predicted nicotine and marijuana use in the context of future orientation. These results highlight which cognitive factors may influence risk for substance use for early-maturing youth.

A Factor Analysis and Test of Longitudinal Measurement Invariance of the Children's Depression Inventory (CDI) Across Adolescence.

Depression increases dramatically during adolescence. This finding has been demonstrated using multiple measures, including the Children's Depression Inventory (CDI). The CDI is one of the most commonly used measures to assess depression in youth. However, there is little agreement on its factor structure, and it is possible that its factor structure changes over time. Yet, no study to date has investigated whether this structure is longitudinally invariant from early- to mid-adolescence. The present study examined the factor structure of the CDI in a sample of 227 adolescents aged approximately 13 at baseline and 16 at follow-up. The analyses revealed that a one-factor structure was a good fit to the data at each assessment. Moreover, tests of measurement invariance supported configural, metric, and scalar invariance across time. These findings suggest that changes in depressive symptoms during adolescence are due to true developmental changes, rather than changes in measurement properties.

Parents' behavioral inhibition moderates association of preschoolers' BI with risk for age 9 anxiety disorders.

BACKGROUND: Temperamental behavioral inhibition (BI) in children predicts later anxiety disorders. However, many children with BI do not develop anxiety disorders, suggesting the importance of identifying moderating factors. The current study examined whether parents' history of BI moderates the associations between preschoolers' BI and anxiety disorders at age 9. METHODS: The sample was 392 children and their parents from the community. Child BI was measured at age 3 using observational (Laboratory Temperament Assessment Battery; Lab-TAB) and parent report (Behavior Inhibition Questionnaire; BIQ) measures. In addition, both parents reported on their own history of childhood BI using the Retrospective Measure of Behavioral Inhibition (RMBI). When the children were 9 years old, a parent and the child were interviewed using the Kiddie Schedule for the Affective Disorders and Schizophrenia - Present and Lifetime version (K-SADS-PL). RESULTS: Parents' reports of their own BI moderated the associations of both observed and parent-reported child BI at age 3 with children's anxiety disorders at age 9. Among children whose parents reported having had higher childhood BI, those who exhibited high BI at age 3 were more likely to meet criteria for anxiety disorders at age 9. LIMITATIONS: The major limitation is the use of a retrospective measure of parental BI. CONCLUSIONS: These findings demonstrate that parents' histories of childhood BI moderate the association between their young children's BI and subsequent anxiety disorders. Thus, parental BI appears to identify a subgroup of BI children at particularly high risk for developing anxiety disorders by late childhood.