An epidemiological study of season of birth, mental health, and neuroimaging in the UK Biobank

Environmental exposures during the perinatal period are known to have a long-term effect on adult physical and mental health. One such influential environmental exposure is the time of year of birth which affects the amount of daylight, nutrients, and viral load that an individual is exposed to in the key developmental period. Here we investigate associations between season of birth (seasonality), four mental health traits ( n =135,541) and multi-modal neuroimaging measures ( n =33,815) within the UK Biobank. Summer births were associated with probable recurrent Major Depressive Disorder (β=0.024, pcorr= 0.048), greater mean cortical thickness in temporal and occipital lobes and in the middle temporal, fusiform, superior temporal, and lingual gyri regions (β range=0.013 - 0.020, pcorr< 0.05). Winter births were associated with greater white matter integrity globally, in the association fibers, thalamic radiations, and six individual tracts (β range=-0.010 to -0.021, pcorr< 0.05). Results of sensitivity analyses that adjusted for birth weight were similar, with additional associations found between winter birth and frontal, occipital and cingulate lobe surface areas, as well as fractional anisotropy in the forceps minor. Sensitivity analyses also revealed an additional association between summer birth and greater cingulate thickness. Overall, results suggest that seasonality affects brain structure in later life and may have a role in lifetime recurrent Major Depressive Disorder. The small effect sizes observed here warrant further research to validate the results in the context of different latitudes and co-examine genetic and epigenetic measures to potentially reveal informative biological pathways. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement M.V.R is supported under a 2018 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Ref: 27404). D.M.H. is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Reference 213674/Z/18/Z) and a 2018 NARSAD Young Investigator Grant from the Brain & Behavior Research Foundation (Ref: 27404). STRADL UKB Application (#4844) was funded by the Wellcome Trust (Ref: 104036/Z/14/Z). This research was funded in whole, or in part, by the Wellcome Trust [Reference 213674/Z/18/Z]. For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. ### 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: This research was conducted using the UK Biobank resource, application number 4844. The UK Biobank study was conducted under generic approval from the NHS National Research Ethics Service (approval letter dated June 17, 2011, Ref 11/NW/0382). All participants gave full informed written consent. 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 All data produced in the present work are contained in the manuscript. The raw phenotypic data from UK Biobank used in this study are available from: .