Pathways linking physical and mental health: The role of brain structure and environment

Depression and anxiety are prevalent in people with a chronic physical illness. Increasing evidence suggests that co-occurring physical and mental illness is associated with shared biological pathways. However, little is known about the brain’s role in mediating links between physical and mental health. Using multimodal brain imaging and organ-specific physiological markers from the UK Biobank, we establish prospective associations between the baseline health of seven body organs and mental health outcomes at 4-14 years follow-up, focussing on depression and anxiety. We reveal multiple pathways, mediated by the brain, through which poor organ health may lead to poor mental health. We identify several lifestyle factors that influence mental health through their selective impact on the physiology of specific organ systems and brain structure. Our work reveals the interplay between brain, body and lifestyle and their collective influence on mental health. Pathways elucidated here may inform behavioral interventions to mitigate or prevent the synergistic co-occurrence of physical and mental disorders. ### Competing Interest Statement ETB has consulted for GlaxoSmithKline, SR One, Sosei Heptares, and Boehringer Ingelheim. All other authors declare that they have no competing interests. ### Funding Statement YET was supported by a Mary Lugton Postdoctoral Fellowship. AZ was supported by a Senior Rebecca L. Cooper Fellowship. ETB was supported by a Senior Investigator award from the National Institute of Health Research (UK). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The UK Biobank has approval from the North West Multi‐centre Research Ethics Committee (MREC) to obtain and disseminate data and samples from the participants (http://www.ukbiobank.ac.uk/ethics/). Written informed consent was obtained from all participants. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data were obtained from the UK Biobank. Researchers can register to access all data used in this study via the UK Biobank Access Management System ().