Prenatal Immune Challenge – ‘Disease Primer’ Increasing the Offspring’s Vulnerability to Stress

Prenatal Immune Challenge

A recent study published in Science is probably the first to provide evidence suggesting that prenatal immune challenge can function as a “disease primer” that amplifies the offspring’s susceptibility to stress and its detrimental neuro-pathological effects in peri-pubertal life.

Epidemiologic studies indicate that prenatal infection may play an important role in the etiopathogenesis of schizophrenia, which is primarily a neurodevelopmental disorder.

One possible reason proposed to explain the association between infection in utero and schizophrenia in the offspring, and particularly why several different infections could give rise to schizophrenia, is that they act through stimulation of the cytokine response.

In fact, an excess of proinflammatory maternal cytokines has been associated with several neurodevelopmental disorders.  To add further complexity, maternal stress during pregnancy and childhood trauma has also been implicated in the pathogenesis of schizophrenia.

The possibility of whether the actual combination of prenatal infection and postnatal stress contributes to schizophrenia is poorly understood, and this hypothesis may need direct verification.

However, the recent study published in the March issue of Science magazine suggests that stress in puberty has the potential to unmask latent psychopathology in neurodevelopmentally vulnerable subjects with prenatal infectious histories.

In this study, Sandra Giovanoli and colleagues from the Swiss Federal Institute of Technology, Zurich, Switzerland, and the University of Duisburg-Essen, Essen, Germany, used a model of prenatal immune activation in mice. A cytokine associated viral-like acute-phase response was induced by the viral mimetic [poly(I:C)], a synthetic analog of double-stranded RNA.

The authors found that only the combined immune activation and stress led to a 2.5- to 3-fold increase in hippocampal and prefrontal brain regions’ expression of markers characteristic of activated microglia. Moreover, the hippocampal microglia response was accompanied by the presence of elevated levels of the proinflammatory cytokines interleukin (IL)-1-beta and tumor necrosis factor (TNF)-alpha.

According to the authors, prenatal infection and stress in puberty may thus be important etiological risk factors for long-term mental illness especially upon combined exposure. More comments for this study are available on

Source: Science, 2013 Mar 1;339(6123):1095-9. doi: 10.1126/science.1228261
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