Sex differences in brain volumes and psychological distress: The first hundred brains cohort of the longitudinal adolescent brain study

Abstract

Neurodevelopment during early childhood and adolescence are recognised as critical periods, with potential life-long lasting impacts on mental health and wellbeing. The time-frame of these neurodevelopmental changes also correspond to one in five individuals aged 9–17 years old being diagnosed with a mental health condition. Furthermore, sex-based differences in the diagnosed prevalence of mental health conditions are also well characterised and can be leveraged to differentiate development of brain structures between sexes throughout childhood and adolescence. During adolescence, early observed mental health symptoms, alongside measures of brain development, may provide utility toward understanding both the onset timing of various mental conditions, and a neurobiological explanation for disproportionate prevalence's among sexes. This study aims to determine sex differences in psychological distress levels and structural brain volume relationships in early adolescents. To address this question, we first present and then utilise the ‘first hundred brains’ (FHB) cohort, a multimodal dataset of 12-to-13 year-olds individuals enrolled in the Longitudinal Adolescent Brain Study (LABS). The FHB dataset consists of 101 unique individuals (47 female), aged 13.01 ± 0.55 years. Psychological distress was measured using the Kessler-10, a self-report questionnaire probing recent experiences of anxiety and depression symptoms. All participants underwent 3T MRI brain scans. T1-weighted structural scans were processed using FreeSurfer's Sequence Adaptive Multimodal segmentation pipeline, with volume measurements from 39 regions of interest included in the analyses. Findings revealed that compared to age matched males, early adolescent females have significantly higher psychological distress as well as significantly larger hippocampi and ventral diencephalon, bilaterally. Correlational analyses revealed a significant positive association between psychological distress scores and right amygdala volumes for males, but not in females, or the combined cohort. In this initial analysis of the FHB dataset, we have identified significant sex differences in psychological distress, brain volumes, and the relationships between these two metrics. With the peak age-of-onset for many psychiatric disorders occurring during adolescence, research focused on youth mental health vulnerability and opportunity for early detection, prevention and improvement is vitally important.