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Intergenerational transmission of depression: clinical observations and molecular mechanisms

Abstract

Maternal mental illness can have a devastating effect during the perinatal period, and has a profound impact on the care that the baby receives and on the relationships that the baby forms. This review summarises clinical evidence showing the effects of perinatal depression on offspring physical and behavioural development, and on the transmission of psychopathology between generations. We then evaluate a number of factors which influence this relationship, such as genetic factors, the use of psychotropic medications during pregnancy, the timing within the perinatal period, the sex of the foetus, and exposure to maltreatment in childhood. Finally, we examine recent findings regarding the molecular mechanisms underpinning these clinical observations, and identify relevant epigenetic and biomarker changes in the glucocorticoid, oxytocin, oestrogen and immune systems, as key biological mediators of these clinical findings. By understanding these molecular mechanisms in more detail, we will be able to improve outcomes for both mothers and their offspring for generations.

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Acknowledgements

KMS is supported by a Studentship from the Doctoral Training Programme, funded by the Medical Research Council. CMP’s research in perinatal psychiatry has been supported by the Psychiatry Research Trust, and PD’s research in perinatal psychiatry is supported by the Medical Research Foundation, the UK Medical Research Council’s independent charity. Professor Pariante is also supported by ‘Persistent Fatigue Induced by Interferon-alpha: A New Immunological Model for Chronic Fatigue Syndrome’ (MR/J002739/1) and by the grant ‘Immuno-psychiatry: A Consortium to test the Opportunity for Immunotherapeutics in Psychiatry’ (MR/L014815/1), from the Medical Research Council (UK). Additional support has been offered by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’ s College London.

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Correspondence to Carmine M. Pariante.

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CMP and PAZ have received research funding from Johnson & Johnson as part of a program of research on depression and inflammation, and research funding from the Medical Research Council (UK) and the Wellcome Trust for research on depression and inflammation as part of two large consortia that also include Johnson& Johnson, GSK, and Lundbeck. The work presented in this paper is unrelated to this funding. KMS and PD declare that they have no conflict of interest.

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Sawyer, K.M., Zunszain, P.A., Dazzan, P. et al. Intergenerational transmission of depression: clinical observations and molecular mechanisms. Mol Psychiatry 24, 1157–1177 (2019). https://doi.org/10.1038/s41380-018-0265-4

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