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Patients with depression and bipolar disorder have previously been shown to have impaired white matter (WM) integrity compared with healthy controls. This study aimed to investigate potential sex differences that may provide further insight into the pathophysiology of these highly debilitating mood disorders.Participants aged 17 to 30 years (168 with depression [60% females], 107 with bipolar disorder [74% females], and 61 controls [64% females]) completed clinical assessment, self-report measures, and a neuropsychological assessment battery. Participants also underwent magnetic resonance imaging from which diffusion tensor imaging data were collected among five fronto-limbic WM tracts: cingulum bundle (cingulate gyrus and hippocampus subsections), fornix, stria terminalis, and the uncinate fasciculus. Mean fractional anisotropy (FA) scores were compared between groups using analyses of variance with sex and diagnosis as fixed factors.Among the nine WM tracts analyzed, one revealed a significant interaction between sex and diagnosis, controlling for age. Male patients with bipolar disorder had significantly lower FA scores in the fornix compared with the other groups. Furthermore, partial correlations revealed a significant positive association between FA scores for the fornix and psychomotor speed.Our findings suggest that males with bipolar disorder may be at increased risk of disruptions in WM integrity, especially in the fornix, which is thought to be responsible for a range of cognitive functions. More broadly, our findings suggest that sex differences may exist in WM integrity and thereby alter our understanding of the pathophysiology of mood disorders.

Each human brain has a unique functional synchronisation pattern (functional connectome) analogous to a fingerprint that underpins brain functions and related behaviours. Here we examine functional connectome (whole-brain and 13 networks) maturation by measuring its uniqueness in adolescents who underwent brain scans longitudinally from 12 years of age every four months. The uniqueness of a functional connectome is defined as its ratio of self-similarity (from the same subject at a different time point) to the maximal similarity-to-others (from a given subject and any others at a different time point). We found that the unique whole brain connectome exists in 12 years old adolescents, with 92% individuals having a whole brain uniqueness value greater than one. The cingulo-opercular network (CON; a long-acting 'brain control network' configuring information processing) demonstrated marginal uniqueness in early adolescence with 56% of individuals showing uniqueness greater than one (i.e., more similar to her/his own CON four months later than those from any other subjects) and this increased longitudinally. Notably, the low uniqueness of the CON correlates (β = -18.6, FDR-Q 0.001) with K10 levels at the subsequent time point. This association suggests that the individualisation of CON network is related to psychological distress levels. Our findings highlight the potential of longitudinal neuroimaging to capture mental health problems in young people who are undergoing profound neuroplasticity and environment sensitivity period.

The present study investigated differences in white matter (WM) integrity between 96 young people with affective and/or psychotic symptoms classified at an early stage of mental disorder (i.e. 'attenuated syndrome'; stage 1b), 85 young people classified at a more advanced stage of mental disorder (i.e. 'discrete disorder'; stage 2), and 81 demographically matched healthy controls using diffusion tensor imaging. The relationship between WM integrity (indexed by fractional anisotropy; FA) across the tracts and neuropsychological functioning was also investigated. A significant reduction in FA was identified in those with more advanced disorder in the body of the corpus callosum. Clinical stage groups were associated with significant neuropsychological impairment, which was significantly greater in those with discrete disorders. Compared to those in the earlier stage of disorder, participants at the later clinical stage showed decreased FA in the body of the corpus callosum that was associated with worse performance in attentional set formation maintenance, shifting and flexibility. These results provide further support for clinical staging of mental disorder and highlight the potential for utilising neuroanatomical biomarkers to support the classification of stages of mental disorder in the future.