June Machover Reinisch

Association Between Prenatal Exposure to Bacterial Infection and Risk of Schizophrenia

Recent research suggests that prenatal exposure to nonviral infection may be associated with increased risk of schizophrenia, and we hypothesized an association between maternal bacterial infection during pregnancy and elevated offspring risk of schizophrenia. Data on maternal infections from the Copenhagen Perinatal Cohort were linked with the Danish National Psychiatric Register. Offspring cases of narrowly defined schizophrenia (International Classification of Diseases, Eighth Revision [ICD-8]) and more broadly defined schizophrenia (ICD-8 and ICD-10) were identified before the ages of 32-34 and 45-47 years, respectively. The effect of prenatal exposure to bacterial infections was adjusted for prenatal exposure to analgesics and parental social status. In a risk set of 7941 individuals, 85 cases (1.1%) of ICD-8 schizophrenia were identified by the age of 32-34 years and 153 cases (1.9%) of more broadly defined schizophrenia by the age of 45-47 years. First-trimester exposure conferred an elevated risk of ICD-8 schizophrenia (odds ratio 2.53; 95% confidence interval [CI] 1.07-5.96) and also of broadly defined schizophrenia (odds ratio 2.14; 95% CI 1.06-4.31). Second-trimester exposure also conferred a significantly elevated risk of schizophrenia but only in unadjusted analyses. These findings suggest a relationship between maternal bacterial infection in pregnancy and offspring risk of schizophrenia, and this effect was somewhat stronger for ICD-8 schizophrenia with earlier onset. Post hoc analyses showed that upper respiratory tract and gonococcal infections were associated with elevated risk of the disease. An association between risk of schizophrenia and prenatal exposure to bacterial infections might be mediated through transplacental passage of maternally produced cytokines in response to bacterial infections.

HORMONAL CONTRIBUTIONS TO SEXUALLY DIMORPHIC BEHAVIORAL DEVELOPMENT IN HUMANS

Nineteen studies on the behavioral effects of prenatal exposure to hormones administered for the treatment of at-risk human pregnancy are reviewed. Because the role of prenatal exposure to hormones in the development of human behavioral sex differences is potentially confounded by societys differential treatment of the sexes, comparisons between exposed and unexposed subjects were evaluated and summarized separately for male and female subjects. Therefore, this review focuses on data for individuals whose prenatal hormone environments were atypical relative to what is normal for their own sex. Overall, it appears that prenatal exposure to androgen-based synthetic progestin exerted a masculinizing and/or defeminizing influence on human behavioral development, whereas prenatal exposure to natural progesterone and progesterone-based synthetic progestin had a feminizing and/or demasculinizing influence, particularly among female subjects. The data on prenatal exposure to synthetic estrogen derive primarily from subjects exposed to diethylstibestrol (DES). DES-exposed male subjects appeared to be feminized and/or demasculinized, and there is some evidence that exposed female subjects were masculinized. These findings are discussed in the context of prenatal hormonal contributions to sexually dimorphic behavioral development both within and between the sexes. Recommendations for the conduct of future research in developmental behavioral endocrinology are presented.

Prenatal Gonadal Steroidal Influences on Gender-Related Behavior

Publisher Summary A primary role of steroid hormones during early development is the establishment of morphological sex differences, which provide the foundation for sex differences of behavior. This chapter discusses the influence of prenatal exposure to steroid hormones on the behavioral development of humans, the process of sexual differentiation, and laboratory animal experiments that provide support for the conclusions of the human studies. Available evidence suggests that exposure to steroid hormones during gestation does affect human behavioral development in a manner generally consistent with that demonstrated experimentally in laboratory animals. It follows, based upon the concordance of evidence between the laboratory animal and human studies of behavioral alteration in response to critical period exposure to steroids, that the human brain is likely to undergo a process of sexual differentiation similar to that of other mammals. Sex differences in human brain morphology have been identified, await only is definitive empirical evidence of the role hormones play in brain differentiation.

High-Risk Sexual Behavior at a Midwestern University: A Confirmatory Survey

According to a 1991 study of sexual behavior based on a random sample of heterosexual undergraduates at a Midwestern university, 80% of the males and 73% of the females had experienced vaginal or anal intercourse. The average age at first vaginal intercourse was 17.2 years for both sexes. Seventeen percent of the sexually experienced males and 18% of the sexually experienced females had engaged in heterosexual anal intercourse; among these respondents, the average age at first anal intercourse was 20.3 for males and 19.1 for females. Although less than four years, on average, had elapsed since the respondents had first had vaginal intercourse, males reported an average of 8.0 lifetime vaginal-sex partners and females reported an average of 6.1. Overall, the findings from this random sample of students are similar to those from a 1988 convenience sample of the same college population.

Effects of prenatal exposure to diethylstilbestrol (DES) on hemispheric laterality and spatial ability in human males

Ten males exposed to diethylstilbestrol (DES), a nonsteroidal synthetic estrogen, during gestation were compared to their matched, unexposed brothers on measures of brain hemispheric specialization for processing nonlinguistic spatial information and cognitive abilities. DES exposure was associated with reduced hemispheric laterality and lowered spatial ability. These data provide direct evidence of a relationship between brain laterality, spatial cognitive ability, and prenatal exposure to hormones in human males. Further, the implications of these findings for understanding sexual differentiation of the human brain are discussed.

Early developmental milestones and risk of schizophrenia: A 45-year follow-up of the Copenhagen Perinatal Cohort

The aim of the present study was to investigate the relationship between age of neuromotor milestone attainment and risk of adult schizophrenia. 5765 mothers of the Copenhagen Perinatal Cohort recorded 12 developmental milestones during the childs first year of life. Cohort members were followed until they were 46-48 years old through record linkage with the Danish Psychiatric Central Research Register. The age at which milestones were met in the 92 individuals who later developed schizophrenia was compared with milestone attainment in the 691 individuals who developed other psychiatric disorders and in the 4982 cohort controls who were never admitted to a psychiatric department. Group comparisons were adjusted for gender, mothers age, fathers age, parental social status, breadwinners education, single mother status and parity. Individuals who developed schizophrenia reached all developmental milestones later than controls and differed significantly from the controls with respect to the mean age of reaching the 12 milestones. Five developmental milestones in particular (smiling, lifting head, sitting, crawling, and walking) differed significantly. Individuals who later developed psychiatric disorders other than schizophrenia reached most developmental milestones earlier than those who developed schizophrenia, but later than the controls. The two psychiatric groups only differed significantly with respect to age of walking without support. The findings corroborate and methodologically extend previous research from prospective longitudinal cohort studies suggesting developmental delays observable as early as within the first year of life. These early developmental delays may not only characterize schizophrenia, but may be associated with a range of psychiatric disorders.

A test of sex differences in aggressive response to hypothetical conflict situations.

Male (n = 289) and female (n = 268) college students were administered the Leifer-Roberts Response Hierarchy (Reinisch Revision) to evaluate the utility of this measure in reflecting sex differences in self-described potential for aggressive response. The Response Hierarchy provides a retrospective estimate of where physical and verbal aggression reside in an individuals hierarchy of possible behavioral responses to hypothetical conflict situations in adolescence. A score is obtained for: (a) physical aggression, (b) verbal aggression, (c) nonaggressive coping, and (d) withdrawal. When asked to respond as they would have or did at age 13 years, verbal aggression was the most frequent response with no significant sex difference in mean scores. Men selected physical aggression significantly more often than women (p less than .001). Using the binomial effect size display (BESD) to illustrate the magnitude of the sex difference, 69% of the men would be classified as physically aggressive (above the median), whereas only 31% of the women would be so classified. It was concluded that the Response Hierarchy consistently demonstrates sex differences among college students in retrospectively reported preference for choosing physical aggression versus other coping strategies as a response to hypothetical interpersonal conflict situations of adolescence.

Early barbiturate exposure: The brain, sexually dimorphic behavior and learning

Barbiturates, one of the most widely prescribed and abused classes of drugs, reportedly have been prescribed in as many as 25% of pregnancies in the U.S. and Europe over the last 30 years. Nevertheless, there exists little if any data on long-term consequences of prenatal exposure to barbiturates in humans. Evidence from laboratory animals indicates that exposure to barbiturates during early developmental periods results in abnormal neural and biochemical differentiation of the central nervous system, deficits in learning, retarded attainment of developmental milestones, alteration of behavioral and physiological sex differences, increased activity, and decreased responsiveness to aversive and appetitive stimuli. Barbiturates appear to influence the brain via two routes: (1) by direct action on neural tissue; and (2) indirectly by altering hepatic metabolism of steroid hormones. It is concluded that prenatal exposure to barbiturates in human subjects may lead to learning disabilities, decreased IQ, performance deficits, increased incidence of psychosocial maladjustment, and demasculinization of gender identity and sex role behavior in males.

The prenatal development project

The primary aim of the Prenatal Development Project (PDP) is to evaluate the developmental effects of prenatal exposure to steroid hormones and psychoactive drugs, particularly synthetic progestin, corticosteroids and barbiturates. Data collection has taken place at the Psykologisk Institut, now the Institute of Preventive Medicine, since 1981. The PDP database is unique for its breadth and depth as well as its combination of prospective longitudinal and cross‐sectional perspectives. This article describes the database, including subject selection, perinatal information, the comprehensive contemporary evaluation and archival information from Danish registers. The unique matching procedures designed specifically for these projects and data analytic strategies are explained. The value of the PDP database is discussed both in relation to specific project aims (evaluating effects of prenatal drug exposure) and in relation to developmental and psychological research in general.

Height, weight and body mass index in early adulthood and risk of schizophrenia

Objective:  To illuminate the possible associations between height, weight, and body mass index (BMI) during early adulthood and the development of schizophrenia.