Does Infection Increase Risk of Psychosis and Schizophrenia?

New research is examining the link between schizophrenia/psychosis and select infections affecting the CNS. Two reports investigated this link in children and military personnel in the January 2008 issue of the American Journal of Psychiatry.

A study conducted by Dr Christina Dalman and associates found that serious infections in the CNS during childhood may play a role in the later development of schizophrenia and nonaffective psychoses, although only to a small degree. The study used the Swedish National Inpatient Register to track the development of 1.2 million children born between 1973 and 1985.

Dalman and coworkers found that 2435 children had been hospitalized for bacterial infections and 6550 for viral CNS infections when followed up using data from the register. Of the sample, 2269 had received a diagnosis of nonaffective psychosis; 23 patients from this group had a CNS infection before 12 years. The risk of children having nonaffective psychosis, including schizophrenia, increased slightly later in life if the child had a viral CNS infection (risk ratio, 1.5; 95% confidence interval [CI], 1.0-2.4), with a higher risk noted in females (risk ratio, 2.3; 95% CI, 1.3-7.3). The risk was greater in those who had mumps and cytomegalovirus infection, which suggests that this could be because these illnesses invade the brain parenchyma. No evidence of increased risk of psychosis or schizophrenia was found in children who had a bacterial infection (risk ratio, 0.9; 95% CI, 0.3-2.3). The authors also restricted the analyses to schizophrenia and found similar results (viral CNS infection: risk ratio, 1.6; 95% CI, 1.0-2.5; bacterial infection: risk ratio, 0.9; 95% CI, 0.4-2.1).

While performing their analysis, the authors took into account confounders such as parental psychotic illness, urban living areas, and winter birth. They found that male sex and urban living were associated with increased risk of psychosis and viral/bacterial CNS infections; winter birth was not associated with the development of psychosis. In addition, parental psychotic illness was weakly related to bacterial infection in the CNS.

In another report, researchers found a significant positive association between infections such as Toxoplasma gondii and herpesvirus infections and schizophrenia in discharged military personnel with schizophrenia. Dr David Niebuhr and colleagues included 180 patients from the army, navy, and air force who were discharged for a disability associated with schizophrenia and who had banked se- rum available and 532 military comparison subjects who were not discharged. Of the total sample, 83% were male and 57% were 25 years old or younger. Twenty-eight (7%) T gondii-positive serum specimens were identified in patients with schizophrenia and 63 (5.3%) T gondii-positive serum specimens were found in the comparison group (some subjects had more than 1 specimen available).

When T gondii was examined alone as a continuous variable, the antibody-level effect on the risk of schizophrenia was significant (hazard ratio, 1.24); however, when it was analyzed categorically, T gondii was a positive, although nonsignificant, predictor of schizophrenia risk (hazard ratio, 1.31). Of the other infectious agents analyzed, human herpesvirus 6 was the only one with a significant positive correlation (hazard ratio, 1.2).