The anatomical distance of functional connections predicts brain network topology in health and schizophrenia.

The human brain is a topologically complex network embedded in anatomical space. Here, we systematically explored relationships between functional connectivity, complex network topology, and anatomical (Euclidean) distance between connected brain regions, in the resting-state functional magnetic resonance imaging brain networks of 20 healthy volunteers and 19 patients with childhood-onset schizophrenia (COS). Normal between-subject differences in average distance of connected edges in brain graphs were strongly associated with variation in topological properties of functional networks. In addition, a club or subset of connector hubs was identified, in lateral temporal, parietal, dorsal prefrontal, and medial prefrontal/cingulate cortical regions. In COS, there was reduced strength of functional connectivity over short distances especially, and therefore, global mean connection distance of thresholded graphs was significantly greater than normal. As predicted from relationships between spatial and topological properties of normal networks, this disorder-related proportional increase in connection distance was associated with reduced clustering and modularity and increased global efficiency of COS networks. Between-group differences in connection distance were localized specifically to connector hubs of multimodal association cortex. In relation to the neurodevelopmental pathogenesis of schizophrenia, we argue that the data are consistent with the interpretation that spatial and topological disturbances of functional network organization could arise from excessive "pruning" of short-distance functional connections in schizophrenia.PEV is supported by the Medical Research Council (grant number MR/K020706/1). This work was supported by the Neuroscience in Psychiatry Network (NSPN) which is funded by a Wellcome Trust strategy award to the University of Cambridge and University College London. ETB is employed half-time by the University of Cambridge and half-time by GlaxoSmithKline; he holds stock in GSK.This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1111/jcpp.12365/full

Longitudinally mapping the influence of sex and androgen signaling on the dynamics of human cortical maturation in adolescence

Humans have systematic sex differences in brain-related behavior, cognition, and pattern of mental illness risk. Many of these differences emerge during adolescence, a developmental period of intense neurostructural and endocrine change. Here, by creating “movies” of sexually dimorphic brain development using longitudinal in vivo structural neuroimaging, we show regionally specific sex differences in development of the cerebral cortex during adolescence. Within cortical subsystems known to underpin domains of cognitive behavioral sex difference, structural change is faster in the sex that tends to perform less well within the domain in question. By stratifying participants through molecular analysis of the androgen receptor gene, we show that possession of an allele conferring more efficient functioning of this sex steroid receptor is associated with “masculinization” of adolescent cortical maturation. Our findings extend models first established in rodents, and suggest that in humans too, sex and sex steroids shape brain development in a spatiotemporally specific manner, within neural systems known to underpin sexually dimorphic behaviors

Side Effects and Health Benefits of Depot Medroxyprogesterone Acetate: A systematic review

Objective: Counseling about potential side effects and health benefits of contraceptive methods could facilitate continued method use and method satisfaction, yet no evidence-based compilation of side effects and benefits exists to aid such counseling. Among contraceptive methods in the United States, depot medroxyprogesterone acetate (DMPA) injectables have the highest discontinuation rates, and most discontinuation is attributable to side effects. This review examines the side effects and health benefits of DMPA to inform counseling.Data sources: We searched PubMed, POPLINE, EMBASE, Web of Science, Campbell Collaboration Library of Systematic Reviews, the Cochrane Database of Systematic Reviews, the Cochrane Center Register of Controlled Trials, and ClinicalTrials.gov.Methods of study selection: We included English-language studies published from 1985 to 2016 that enrolled healthy, nonbreastfeeding females aged 13-49 years at risk of unintended pregnancy, compared intramuscular or subcutaneous progestin-only injectables to a contemporaneous comparison group, and addressed at least one key question: 1) What side effects are associated with progestin-only injectable contraceptive use? 2) What health benefits are associated with progestin-only injectable contraceptive use? Study quality was assessed using criteria from the U.S. Preventive Services Task Force.Tabulation, integration, and results: Twenty-four studies met inclusion criteria. None were randomized controlled trials. There were 13 prospective cohort, five retrospective cohort, four case-control, and two cross-sectional studies. Studies of moderate or high risk of bias suggest an association between DMPA use and weight gain, increased body fat mass, irregular bleeding, and amenorrhea. Inconsistent evidence exists for an association between DMPA use and mood or libido changes. Limited evidence exists for an association between DMPA use and decreased risk of cancers and tubal infertility.Conclusion: Higher-quality research is needed to clarify DMPA\u27s side effects and benefits. In absence of such evidence, patient-centered counseling should incorporate the available evidence while acknowledging its limitations and recognizing the value of women\u27s lived experiences