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

Abstract

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.