Prenatal exposure to influenza and increased cerebrospinal fluid spaces in schizophrenia.

Several epidemiological studies have suggested that maternal exposure to influenza during midgestation is a risk factor for schizophrenia. In exploring the possible pathogenic mechanism, we examined the relationship between computed tomography structural brain measures in 83 schizophrenia patients and 113 controls and also their risk of maternal exposure to influenza. Four brain measures of the cerebrospinal fluid (CSF) spaces (lateral ventricle, maximum third ventricle, sulcal fluid, and sylvian fissure) were investigated in relation to the risk exposure level. In schizophrenia patients, these measures, in particular sylvian fissures, were found to increase with higher levels of risk exposure to influenza during the susceptible period (i.e., midgestation); no such effect was found in controls. These results indicate that risk for midgestational influenza exposure is associated with generalized enlargement of the CSF spaces, especially in the region of the temporal lobe. The findings suggest that certain morphological abnormalities of the brain frequently reported in schizophrenia patients may be partly attributable to antenatal exposure to influenza.