Cognitive functioning prior to the onset of psychosis: the role of fetal exposure to serologically determined influenza infection

Abstract

Background: Previous studies have linked prenatal influenza exposure to increased risk of schizophrenia; however, no study has examined the neurodevelopmental sequelae of this prenatal insult before the onset of psychotic symptoms using serological evidence of infection. This study sought to examine the contribution of prenatal influenza A and B exposure to cognitive performance among children who developed psychoses in adulthood versus nonpsychiatric control children.

Methods: Subjects were 111 cases (70 with schizophrenia and 41 with affective psychoses) and 333 matched control subjects followed from gestation until age 7 through the Collaborative Perinatal Project. The Wechsler Intelligence Scale for Children (age 7) was administered and adult psychiatric morbidity was assessed by medical records review and confirmed by a validation study. Assays were conducted from archived prenatal maternal sera collected at birth, and influenza infection was determined by immunoglobulin G (IgG) antibody titers >75th percentile.

Results: Significant decreases in verbal IQ and the information subtest, as well as similar nonsignificant reductions in full scale IQ scores and vocabulary, comprehension, digit span, and picture arrangement subtests were found among cases who were prenatally exposed to influenza B versus cases who were not exposed. Fetal exposure to influenza B did not lead to any significant differences in cognitive performance among control children.

Conclusions: Cumulatively, these findings suggest that a genetic and/or an environmental factor associated with psychosis rendered the fetal brain particularly vulnerable to the effects of influenza B, leading to poorer cognitive performance even before symptom onset.

Figure 1

ANCOVA age 7 WISC performance and verbal IQ scores by influenza B and group status. Figure displays least square mean values for WISC VIQ and PIQ scores by influenza B and case status. p values and Cohen's d effect sizes are presented for significant post hoc comparisons, as well as post hoc comparisons that approached significance. All analyses controlled for child's handedness, maternal social class, child's race, and child's sex. ANCOVA, analysis of covariance; VIQ, verbal IQ; PIQ, performance IQ; WISC, Wechsler Intelligence Scale for Children.

Figure 2

ANCOVA analyses for age 7 full scale WISCIQ scores by influenza B and case status. Figure displays least square mean values for WISC FIQ scores by influenza B and case status. p values and Cohen's d effect sizes are presented for significant post hoc comparisons, as well as post hoc comparisons that approached significance. All analyses controlled for child's handedness, maternal social class, child's race, and child's sex. ANCOVA, analysis of covariance; FIQ, full scale IQ; WISC, Wechsler Intelligence Scale for Children.

Figure 3

ANCOVA analyses for age 7WISC verbal subscales by influenza B and case status. Figure displays least square mean values for verbal subscales of the WISC by influenza B and case status. p values and Cohen's d effect sizes are presented for significant post hoc comparisons, as well as post hoc comparisons that approached significance. All analyses controlled for child's handedness, maternal social class, child's race, and child's sex. ANCOVA, analysis of covariance; WISC, Wechsler Intelligence Scale for Children.

Figure 4

ANCOVA analyses for age 7 WISC performance subscales by influenza B and case status. Figure displays least square mean values for performance subscales of the WISC by influenza B and case status. p values and Cohen's d effect sizes are presented for significant post hoc comparisons, as well as post hoc comparisons that approached significance. All analyses controlled for child's handedness, maternal social class, child's race, and child's sex. ANCOVA, analysis of covariance; WISC, Wechsler Intelligence Scale for Children.