Pubertal hormone levels differentially modulate the neural circuits implicated in emotion dysregulation in youth with psychopathology

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Project Summary/Abstract: Research Project (4) Pubertal hormone levels differentially modulate the neural circuits implicated in emotion dysregulation in youth with psychopathology Estimates indicate that over 20% of American adolescents suffer from serious psychopathology, including stress, mood, anxiety, and behavioral disorders. Patients with these disorders show emotional dysregulation, which is part of the cognitive control construct within the NIMH’s Research Domain Criteria framework. The critical brain circuitry underlying emotional regulation is known to include the amygdala, frontal, and parietal cortices, with heightened emotional responses in children most commonly linked to aberrations in frontal and parietal activity. Testosterone (T) and cortisol (C) are known to indirectly affect neural processing in these regions in adults, but their particular role in aberrant emotional responses is unknown and studies in children have yet to be conducted. Thus, our goal in this study is to identify the role of T and C reactivity in modulating neural responses associated with emotion regulation in adolescents with and without psychopathology (i.e., emotion regulation issues). Consistent with the NIH’s mission to reduce the burden of mental disorders, the proposed work will yield a better understanding of the biological mechanisms underlying emotion regulation, and thereby support the development of new and improved interventions for adolescents with psychopathology. Specifically, the current proposal aims to: (i) determine the extent to which T reactivity modulates emotion regulation and neural function in youth with emotion regulation issues relative to typically-developing (TD) youth, and the degree to which pubertal status mediates this relationship in each group; (ii) determine the role of C reactivity in emotion regulation and neural function in youth with emotional dysregulation and TD youth, and the degree to which pubertal status mediates these relationships; and (iii) identify the role of biological sex in modulating T and C reactivity in the context of emotion regulation in youth with emotional dysregulation relative to TD youth. We believe identifying sex differences in this context is critical, as there are known sex differences in both hormonal functioning and the prevalence of these disorders during adolescence. These aims will be accomplished by recruiting 210 participants (aged 9-15 years; half male; half community controls), including 105 with psychopathology (i.e., emotion regulation issues) from outpatient mental health clinics. Participants will complete an fMRI protocol assessing emotion regulation following a social challenge paradigm designed to elicit a T response. Our pilot data indicates that increased T reactivity improves emotion regulation in healthy youth, but impairs it in youth with psychopathology. Further, C reactivity also appears to improve emotion regulation in healthy youth, but has not been examined in youth with psychopathology. It is anticipated that the proposed study will show the extent to which T and C reactivity each impact behavior and the neural activity underlying emotion regulation in youth with psychopathology, particularly during the pubertal transition, and the role of biological sex. As current intervention strategies for psychopathology do not consider hormonal mechanisms, these data will be critical in the development of novel treatment approaches.