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BACKGROUND: Identifying neural predictors of worsening subthreshold hypomania severity can help identify risk of progression to BD . While diffusion Magnetic Resonance Imaging (dMRI) studies reported white matter microstructural abnormalities in tracts supporting emotional regulation in individuals with BD, it remains unknown whether similar patterns of white matter microstructure predict worsening of subthreshold hypomania severity in non-BD individuals. METHODS: dMRI data were collected in: 81 non-BD individuals recruited across a range of subthreshold depression and hypomania, and followed for six months; and independent samples of 75 BD and 58 healthy individuals. All individuals were assessed using standardized diagnostic assessments, mood and anxiety symptom rating scales. Global probabilistic tractography and a tract-profile approach examined fractional anisotropy(FA), a measure of fiber collinearity, in tracts supporting emotional regulation shown to have abnormalities in BD: forceps minor (FMIN), anterior thalamic radiation (ATR), cingulum bundle (CB), and uncinate fasciculus (UF). RESULTS: Lower FA in left CB (middle,β=−0.22,P=0.022; posterior,β=−0.32,P

Adolescence represents a window of vulnerability for developing psychological symptoms following concussion, especially in girls. Concussion-related lesions in emotion regulation circuits may help explain these symptoms. However, the contribution of sex and pubertal maturation remains unclear. Using the neurite density index (NDI) in emotion regulation tracts (left/right cingulum bundle [CB], forceps minor [FMIN], and left/right uncinate fasciculus), we sought to elucidate these relationships.No adolescent had a history of anxiety and/or depression. The Screen for Child Anxiety Related Emotional Disorders and Children's Depression Rating Scale were used at scan to assess anxiety and depressive symptoms in 55 concussed adolescents (41.8% girls) and 50 control adolescents with no current/history of concussion (44% girls). We evaluated if a mediation-moderation model including the NDI (mediation) and sex or pubertal status (moderation) could help explain this relationship.Relative to control adolescents, concussed adolescents showed higher anxiety (p = .003) and lower NDI, with those at more advanced pubertal maturation showing greater abnormalities in 4 clusters: the left CB frontal (p = .002), right CB frontal (p = .011), FMIN left-sided (p = .003), and FMIN right-sided (p = .003). Across all concussed adolescents, lower NDI in the left CB frontal and FMIN left-sided clusters partially mediated the association between concussion and anxiety, with the CB being specific to female adolescents. These effects did not explain depressive symptoms.Our findings indicate that lower NDI in the CB and FMIN may help explain anxiety following concussion and that adolescents at more advanced (vs less advanced) status of pubertal maturation may be more vulnerable to concussion-related injuries, especially in girls.

Background Prevention of suicide in individuals with early-onset bipolar disorder (BD) remains a challenge. Diffusion magnetic resonance imaging studies in BD have identified neural correlates of emotional dysregulation implicated in BD and suicide. Using diffusion magnetic resonance imaging, we sought to identify neural signatures of suicide attempts in adults with childhood-onset BD who have been clinically followed for up to 19 years as part of the COBY (Course and Outcome of Bipolar Youth) study. Methods Diffusion magnetic resonance imaging data were collected in 68 adults with BD: 20 in the suicide attempter (SA+) group and 48 in the non–suicide attempter (SA−) group. Multivariate analysis of covariance was used to identify the effect of group (SA+, SA−) on mean fractional anisotropy (indirect index of fiber collinearity) in key white matter tracts of emotional regulation. The effect of suicidal ideation and other clinical factors was further explored. False discovery rate was used to account for multiple comparison. Forty healthy control subjects were included. Results Analyses revealed a main effect of group on fractional anisotropy (F5,59 = 3.0, p = .017). Specifically, the SA+ group showed lower fractional anisotropy than the SA− and healthy control groups in the middle portion of the forceps minor (FMIN) (F1,63 = 8.5, p = .010) and in the anterior (F1,63 = 7.8, p = .010) and posterior (F1,63 = 8.7, p = .006) portion of the right cingulum bundle (CB). Abnormalities in the FMIN, but not CB, were also associated with suicidal ideation (F1,64 = 10.6, p = .002) and levels of emotional distress at scan. Conclusions FMIN and CB abnormalities have been associated with emotional dysregulation in BD. Our findings suggest that the FMIN may represent a generic marker of suicidal ideation and, more broadly, emotional distress, while CB may represent a specific marker of attempted suicide.