Abstract
Background Metabolic and inflammatory disorders commonly co-occur with depression and psychosis, with emerging evidence implicating immuno-metabolic dysfunction in their aetiology. Previous studies have reported metabolic dysfunction and inflammation in adults with depression and psychosis. However, longitudinal studies testing the direction of association, and the effects of different dimensions of early-life immuno-metabolic dysfunction on adult psychopathology, are limited.
Methods Using data from 3875 birth cohort participants we examined longitudinal associations of three metabolic hormones (leptin, adiponectin, insulin) at age 9 with risks for depression- and psychosis-spectrum outcomes at age 24. In addition, using nine immuno-metabolic biomarkers, we constructed an exploratory bifactor model showing a general immuno-metabolic factor and three specific factors (adiposity, inflammation, and insulin resistance), which were also used as exposures.
Results Childhood leptin was associated with adult depressive episode (adjusted odds ratio (aOR)=1.28; 95% CI, 1.00-1.64) and negative symptoms (aOR=1.12; 95% CI, 1.05-1.20). The general immuno-metabolic factor was associated with depressive symptoms (aOR=1.05; 95% CI, 1.01-1.08) and psychotic experiences (aOR=1.20; 95% CI, 1.01-1.42). The adiposity factor was associated with negative symptoms (aOR=1.07; 95% CI 1.02-1.12). All associations tended to be stronger in women, though 95% credible intervals overlapped with that for men. In women, the inflammatory factor was associated with depressive episode (aOR=1.23; 95% CI, 1.01-1.47) and atypical depressive symptoms (aOR=1.10; 95% CI, 1.02-1.19).
Conclusions While general immuno-metabolic dysfunction in childhood may contribute to risks for both psychotic and depressive symptoms in adulthood, childhood adiposity and inflammation are linked to affective (depressive, atypical, and negative) symptoms.
Competing Interest Statement
The authors have declared no competing interest.
Funding Statement
The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. A comprehensive list of grant funding is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf ). The outcome data from age 24 was specifically funded by MRC grants MR/L022206/1 and MR/M006727/1. NAD acknowledges funding support from a National Institute for Health Research Academic Clinical Fellowship in Mental Health. BIP acknowledges funding support from the National Institute for Health Research (NIHR) (Doctoral Research Fellowship Grant No. DRF-2018-11-ST2-018). HJJ acknowledges support from the NIHR Bristol Biomedical Research Centre. GMK acknowledges funding support from the Wellcome Trust (Grant No. 201486/Z/16/Z), the Medical Research Council (Grant No. MC_PC_17213, Grant No. MR/S037675/1, and Grant No. MR/W014416/1), The MQ: Transforming Mental Health (Grant No. MQDS17/40), and the BMA Foundation (J. Moulton Grant 2019).
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Ethical approval for the study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees (http://www.bristol.ac.uk/alspac/researchers/research-ethics/). Consent for biological samples was collected in accordance with the UK Human Tissue Act (2004). Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time.
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