Objective: Women with anorexia nervosa (AN) have been shown to demonstrate differences in functional connectivity in brain regions associated with cognitive control, somatosensory processing, and emotion regulation. However, previous studies have been conducted on small samples and have inconsistent findings. Therefore, this study aimed to identify aberrant brain networks related to the core clinical symptoms of AN and to explore the longitudinal association with clinical outcome in a large population of adolescents experiencing their first episode of AN. Methods: Functional MRI (fMRI) of brain resting-state functional connectivity (RS-FC) of female adolescents with first-onset AN (n = 56) were compared to age- and education-matched typically developing (TD) adolescents (n = 64). To account for the severity of underweight, separate analyses were performed to investigate differences in RS-FC between underweight AN participants and TD adolescents, as well as between underweight (n = 30) and weight-restored AN (n = 26) participants. Clinical outcomes, i.e. body mass index and eating disorder (ED) symptoms, were assessed at baseline and one-year follow-up. Independent component analyses (ICA) were used to extract the brain networks of interest: the default mode (DMN), left and right frontoparietal (FPN), and the insular (IN) networks. Linear regression analyses were conducted to assess differences in RS-FC between AN and TD participants, as well as to assess whether RS-FC was associated with clinical symptoms at baseline and at one-year of follow-up. Two statistical models were used: model 1 adjusted for age and socioeconomic status (SES), and model 2 additionally adjusted for baseline anxiety and depressive symptoms. Results: Underweight AN participants had lower RS-FC between the DMN-IN, as well as between the FPN-IN compared to the TD adolescents. After correction for multiple testing, no significant differences in RS-FC were found between underweight AN participants and weight-restored AN participants, as well as between the whole AN group and the TD group. RS-FC was not associated with the severity of clinical symptoms at baseline nor at one-year of follow-up. Conclusion: AN is associated with changes in RS-FC between the FPN-IN and DMN-IN during the underweight state. These changes in RS-FC were no longer observed in weight-restored AN participants, emphasizing the impact of underweight on RS-FC in AN. Changes in these brain networks may partly explain the impaired cognitive control and difficulties with emotion and behavioral regulation in individuals with AN during the underweight state.

Objective To identify common genetic variants associated with the presence of brain microbleeds (BMBs).MethodsWe performed genome-wide association studies in 11 population-based cohort studies and 3 case-control or case-only stroke cohorts. Genotypes were imputed to the Haplotype Reference Consortium or 1000 Genomes reference panel. BMBs were rated on susceptibility-weighted or T2*-weighted gradient echo MRI sequences, and further classified as lobar or mixed (including strictly deep and infratentorial, possibly with lobar BMB). In a subset, we assessed the effects of APOE ϵ2 and ϵ4 alleles on BMB counts. We also related previously identified cerebral small vessel disease variants to BMBs.ResultsBMBs were detected in 3,556 of the 25,862 participants, of which 2,179 were strictly lobar and 1,293 mixed. One locus in the APOE region reached genome-wide significance for its association with BMB (lead single nucleotide polymorphism rs769449; odds ratio [OR]any BMB [95% confidence interval (CI)] 1.33 [1.21-1.45]; p = 2.5 × 10-10). APOE ϵ4 alleles were associated with strictly lobar (OR [95% CI] 1.34 [1.19-1.50]; p = 1.0 × 10-6) but not with mixed BMB counts (OR [95% CI] 1.04 [0.86-1.25]; p = 0.68). APOE ϵ2 alleles did not show associations with BMB counts. Variants previously related to deep intracerebral hemorrhage and lacunar stroke, and a risk score of cerebral white matter hyperintensity variants, were associated with BMB.ConclusionsGenetic variants in the APOE region are associated with the presence of BMB, most likely due to the APOE ϵ4 allele count related to a higher number of strictly lobar BMBs. Genetic predisposition to small vessel disease confers risk of BMB, indicating genetic overlap with other cerebral small vessel disease markers.