The Dynamic Interplay Between Puberty and Structural Brain Development as a Predictor of Mental Health Difficulties in Adolescence: A Systematic Review.

Puberty is a time of intense reorganization of brain structure and a high-risk period for the onset of mental health problems, with variations in pubertal timing and tempo intensifying this risk. We conducted 2 systematic reviews of articles published up to February 1, 2024, focusing on 1) the role of brain structure in the relationship between puberty and mental health, and 2) precision psychiatry research evaluating the utility of puberty in making individualized predictions of mental health outcomes in young people. The first review provides inconsistent evidence about whether and how pubertal and psychopathological processes may interact in relation to brain development. While most studies found an association between early puberty and mental health difficulties in adolescents, evidence on whether brain structure mediates this relationship is mixed. The pituitary gland was found to be associated with mental health status during this time, possibly through its central role in regulating puberty and its function in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes. In the second review, the design of studies that have explored puberty in predictive models did not allow for a quantification of its predictive power. However, when puberty was evaluated through physically observable characteristics rather than hormonal measures, it was more commonly identified as a predictor of depression, anxiety, and suicidality in adolescence. Social processes may be more relevant than biological ones to the link between puberty and mental health problems and represent an important target for educational strategies.

The eBRAIN study: The impact of early adversity on trajectories of brain maturation and mental health in young adolescents - A prospective cohort study.

Introduction: More than 1 in 10 people are thought to experience a mental health problem during adolescence, with most adult psychopathology beginning during this time. Experiences of stress or adversity during childhood are important risk factors for poorer mental health outcomes and are also associated with alterations in neurodevelopment. There is evidence to suggest that this relationship is mediated by inflammation and the immune system. The eBRAIN study (The Impact of Early Adversity on Trajectories of Brain Maturation and Mental Health in Young Adolescents) will assess how early life adversity might affect trajectories of brain development throughout adolescence, whether these neurobiological changes are associated with psychopathology, and if they can potentially be explained by an activation of the immune system. Methods: A cohort of 220 adolescents between the ages of 11-14 will be recruited into this study. Each participant will complete three study visits, each one year apart, at the Institute of Psychiatry, Psychology and Neuroscience, King's College London, London (UK). At each study visit, they will be assessed with structural and functional MRI scans, biological sample collection as well as questionnaires and interviews to collect demographic information, assess experiences of adversity, and details of psychopathology. The study will also collect information about factors such as diet and nutrition, physical exercise, and cognition. Ethics and dissemination: Ethical approval for this study has been received by King's College London Research Ethics Committee (REC reference: HR-18/19-9033). Findings from the study will be published in peer-reviewed journals and disseminated at national and international conferences. Patient and public involvement (PPI) is an important component of the study, 'Study Champions' recruited from participants, their parents and teachers at collaborating schools have been invited to take an active role in study governance and dissemination.