A nonsystematic review found that early-life infection, inflammation, and metabolic alterations could play a role in depression and psychosis in adulthood. These findings were published in the Harvard Review of Psychiatry.

Three-quarters of all psychiatric disorders occur by early adulthood (mid-20s). This fact suggests that bio-psychosocial factors occurring from the fetal period through early adulthood could play a crucial role in risk. This nonsystematic review sought to synthesize key epidemiological evidence of relevant risk factors.

Data from longitudinal cohort and genetic studies collectively indicated that the development of depression and psychosis in adulthood are affected by immuno-metabolic risk factors. It is possible that these factors facilitate some of the risk from genetics or early life adversity.

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Both maternal infections during pregnancy and childhood infections have been associated with the risk for later psychosis in adulthood. Ecological studies have found that risk for schizophrenia was increased among individuals whose mothers were infected with influenza, herpes simplex virus type 2, or the intracellular parasitic protozoan, toxoplasma gondii during pregnancy. In addition, schizophrenia was found to have a dose-response relationship with the number of infections in childhood. Altogether, available data suggests there could be a sensitive period during early life in which exposure to infection could be harmful for future mental health.

Inflammatory markers in childhood and adolescence likely increases the risk for both depression and psychosis in adulthood. Compared with healthy controls, individuals with depression and psychosis have been found to have elevated inflammatory markers such as cytokines and acute-phase proteins circulating in blood and cerebrospinal fluid. This association, however, could be a cause or a consequence, and requires additional study.

Metabolic perturbations of increased BMI or adiposity was associated with increased risk for later depression and lower BMI for later psychosis. It is well established that cardio-metabolic disorders are more prevalent among the population of patients with schizophrenia and depression. This association is thought to be a consequence of the disorder, as schizophrenia itself is associated with a poor diet, physical inactivity, and a high prevalence of smoking. Recent studies have linked disrupted glucose-insulin homeostasis and dyslipidemia among individuals with first-episode psychosis and their unaffected first-degree relatives.

Evidence suggests that risk loci for psychiatric disorders and immuno-metabolic phenotypes are co-heritable, indicating that there may be genetic correlations between psychiatric and metabolic conditions.

The review authors noted that most existing evidence was sourced from Nordic countries, making the study populations relatively homogeneous and with a high socioeconomic background. Future study should recruit more diverse individuals in order to make findings more generalizable.

The review authors concluded, “the emerging understanding of immuno-metabolic risk factors could help improve treatment of adult psychosis and depression — for instance, by using anti-inflammatory drugs for a subgroup of patients. It could also inform preventive lifestyle interventions targeting immuno-metabolic risk factors in childhood and adolescence. Such interventions could ultimately help improve the debilitating rates of morbidity and mortality associated with these disorders in adulthood.”


Kappelmann N, Perry BI, Khandaker GM. Prenatal and childhood immuno-metabolic risk factors for adult depression and psychosis. Harv Rev Psychiatry. 2022;30(1):8-23. doi:10.1097/HRP.0000000000000322

This article originally appeared on Psychiatry Advisor