Maternal Infections and Risk of Schizophrenia

Evidence accumulated over several decades indicates that infections during pregnancy can elevate the risk of schizophrenia in the offspring. Maternal immune activation, triggered by viral or bacterial pathogens, leads to the release of pro-inflammatory cytokines that cross the placental barrier and may perturb neurodevelopmental processes. Key windows of vulnerability appear in early gestation, when neuronal proliferation and migration are at their peak, and again in late gestation, when synaptic refinement intensifies. Disruption of these stages can alter microglial function, synaptic organisation and epigenetic landscapes, setting the scene for neural circuit abnormalities that manifest as cognitive, social and behavioural deficits in adolescence or early adulthood. Globally, this body of work underscores the importance of infection prevention, antenatal surveillance and potential immunomodulatory strategies to reduce long-term psychiatric morbidity.

Research from Nature Portfolio

Recent experimental studies have delineated molecular pathways by which maternal infection shapes foetal brain development. One investigation used a rodent model of prenatal viral challenge to demonstrate that elevated maternal interleukin-6 induces persistent epigenetic modifications in neuronal progenitor cells, leading to microglial priming and adult behaviours reminiscent of psychotic phenotypes. A complementary study identified dysregulation of the complement cascade within the placenta following maternal bacterial exposure; alterations in complement components were shown to accelerate synaptic pruning in offspring, producing circuit deficits analogous to those observed in patients with schizophrenia. Together, these findings illuminate how distinct immune mediators and placental mechanisms converge to influence neurodevelopmental trajectories and psychiatric risk.

Maternal Infections and Risk of Schizophrenia publication trend

The graph below shows the total number of articles in maternal infections and risk of schizophrenia across all publications each year (not limited to Nature Index journals).

Technical terms

Maternal immune activation: The mother’s systemic inflammatory response to infection, characterised by elevated cytokines.

Cytokines (e.g. interleukin-6): Small proteins released by immune cells that modulate inflammation and can cross the placenta.

Microglial priming: A state in which brain immune cells become hypersensitive, leading to exaggerated responses to later challenges.

Epigenetic modifications: Chemical changes to DNA or chromatin that alter gene expression without changing the genetic code.

Complement system: A cascade of plasma proteins involved in immune defence and synaptic pruning during development.

Synaptic pruning: The elimination of excess neuronal connections, a process essential for mature neural circuit formation.

C-reactive protein (CRP): An acute-phase protein produced by the liver in response to maternal inflammation, used as a marker of prenatal immune activation.

References

1. Schizophrenia: a tale of two critical periods for prefrontal cortical development. Translational Psychiatry (2015).
2. Associations Between Maternal Prenatal C-Reactive Protein and Risk Factors for Psychosis in Adolescent Offspring: Findings From the Northern Finland Birth Cohort 1986. Schizophrenia Bulletin (2020).