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Sexually divergent development of depression-related brain networks during healthy human adolescence.

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Sexual differences in human brain development could be relevant to sex differences in the incidence of depression during adolescence. We tested for sex differences in parameters of normative brain network development using fMRI data on N = 298 healthy adolescents, aged 14 to 26 years, each scanned one to three times. Sexually divergent development of functional connectivity was located in the default mode network, limbic cortex, and subcortical nuclei. Females had a more "disruptive" pattern of development, where weak functional connectivity at age 14 became stronger during adolescence. This fMRI-derived map of sexually divergent brain network development was robustly colocated with i prior loci of reward-related brain activation ii a map of functional dysconnectivity in major depressive disorder (MDD), and iii an adult brain gene transcriptional pattern enriched for genes on the X chromosome, neurodevelopmental genes, and risk genes for MDD. We found normative sexual divergence in adolescent development of a cortico-subcortical brain functional network that is relevant to depression.



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American Association for the Advancement of Science (AAAS)
Wellcome Trust (104025/Z/14/Z)
MQ: Transforming Mental Health (MQF17-24 Vertes)
National Institute for Health Research (NIHRDH-IS-BRC-1215-20014)
British Academy (PFO\170517)
Medical Research Council (MR/M009041/1)
Department of Health (via National Institute for Health Research (NIHR)) (156239)
Cambridgeshire and Peterborough NHS Foundation Trust (CPFT) (unknown)
MQ: Transforming Mental Health (MQ17-24 Vertes)
Wellcome Trust collaborative award for the Neuroscience in Psychiatry Network at University College London and the University of Cambridge Wellcome Trust collaborative award for the Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA) (grant number: 104025/Z/14/Z), which was also funded by Janssen, GlaxoSmithKline, Lundbeck and Pfizer. National Institute of Health Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014) Mental Health Theme (ETB). National Institute of Health Research Senior Investigator award (ETB). Gates Cambridge Trust (LD) MQ: Transforming Mental Health grant MQF17_24 (PEV) Alan Turing Institute (SEM) and EPSRC grant EP/N510129/1 (PEV) British Academy Post-Doctoral fellowship (RAIB) Autism Research Trust (RAIB) Cambridge Philosophical Society Henslow Fellowship Lucy Cavendish College, University of Cambridge (SEM) UK Research and Innovation (UKRI) Data to Early Diagnosis and Precision Medicine Industrial Strategy Challenge Fund (FV) MRC Clinical Research Infra-structure award MR/M009041/1