Associations of hippocampal subfield volumes with psychiatric symptoms, childhood adversity and cardiorespiratory fitness in adolescents and young adults

• Decreased CA1 volume associated with psychiatric symptoms and childhood adversity • Cardiorespiratory fitness associated with larger CA1 volume • Cardiorespiratory fitness moderated depression-hippocampal volume association • No hippocampal volume difference between psychiatric symptom group and controls Reduced hippocampal volumes are frequently observed in psychiatric disorders and have been linked to childhood adversity. Conversely, physical activity is associated with increased hippocampal volumes. This study aimed to integrate these risk and protective factors in young people by examining both group-level differences and dimensional associations. We investigated the associations between hippocampal subfield volumes, early-stage psychiatric symptoms, childhood adversity and cardiorespiratory fitness as a proxy measure for long-term physical activity (VO 2 max/kg), using multi-level models. The sample included 122 participants aged 16-24 years, categorized into a symptom and healthy control group. A transdiagnostic approach was employed to capture the heterogeneous and pluripotent nature of early-stage symptomatology. No significant group differences in overall or subfield hippocampal volumes were observed between participants with early-stage psychiatric symptoms and healthy controls. However, within the symptom group, reduced CA1 subfield volumes showed clear associations with more childhood adversity, depressive and PTSD symptoms. In contrast, cardiorespiratory fitness was associated with greater right CA1 volume. Moreover, the negative association between depressive symptoms and overall hippocampal volume was moderated by cardiorespiratory fitness, being significant only in individuals with low fitness levels. These findings indicate that the CA1 volumetric variation may be influenced by environmental risk and protective factors. Future research should explore these dynamics longitudinally, accounting for the type, severity and duration of both psychiatric symptoms and childhood adversity.