Adverse birth outcomes related to concentrations of per- and polyfluoroalkyl substances (PFAS) in maternal blood collected from pregnant women in 1960-1966.

BACKGROUND: Prior animal and epidemiological studies suggest that per- and polyfluoroalkyl substances (PFAS) exposure may be associated with reduced birth weight. However, results from prior studies evaluated a relatively small set of PFAS. OBJECTIVES: Determine associations of gestational PFAS concentrations in maternal serum samples banked for 60 years with birth outcomes. METHODS: We used data from 97 pregnant women from Boston and Providence that enrolled in the Collaborative Perinatal Project (CPP) study (1960-1966). We quantified concentrations of 27 PFAS in maternal serum in pregnancy and measured infant weight, height and ponderal index at birth. Covariate-adjusted associations between 11 PFAS concentrations (>75% detection limits) and birth outcomes were estimated using linear regression methods. RESULTS: Median concentrations of PFOA, PFNA, PFHxS, and PFOS were 6.189, 0.330, 14.432, and 38.170 ng/mL, respectively. We found that elevated PFAS concentrations during pregnancy were significantly associated with lower birth weight and ponderal index at birth, but no significant associations were found with birth length. Specifically, infants born to women with PFAS concentrations ≥ median levels had significantly lower birth weight (PFOS: ß = -0.323, P = 0.006; PFHxS: ß = -0.292, P = 0.015; PFOA: ß = -0.233, P = 0.03; PFHpS: ß = -0.239, P = 0.023; PFNA: ß = -0.239, P = 0.017). Similarly, women with PFAS concentrations ≥ median levels had significantly lower ponderal index (PFHxS: ß = -0.168, P = 0.020; PFHxA: ß = -0.148, P = 0.018). CONCLUSIONS: Using data from this US-based cohort study, we found that 1) maternal PFAS levels from the 1960s exceeded values in contemporaneous populations and 2) that gestational concentrations of certain PFAS were associated with lower birth weight and infant ponderal index. Additional studies with larger sample size are needed to further examine the associations of gestational exposure to individual PFAS and their mixtures with adverse birth outcomes.

Sex-dependent associations of maternal androgen levels with offspring BMI and weight trajectory from birth to early childhood.

CONTEXT: In preclinical studies, high androgen levels during pregnancy are associated with low birth weight and rapid postnatal weight gain in the offspring. However, human data linking prenatal androgens with birth weight and early life weight gain in the offspring are scarce. DESIGN: We evaluated 516 mother-child pairs enrolled in the New England birth cohorts of the Collaborative Perinatal Project (1959-1966). We assayed androgen bioactivity in maternal sera during third-trimester using a receptor-mediated luciferase expression bioassay. Age and sex-specific BMI Z-scores (BMIz), defined using established standards, were assessed at birth, 4 months, 1 year, 4 years, and 7 years. We used linear mixed models to evaluate the relation of maternal androgens with childhood BMIz overall and by sex. We examined the association of maternal androgens with fetal growth restriction. The association of weight trajectories with maternal androgens was examined using multinomial logistic regression. RESULTS: Higher maternal androgen levels associated with lower BMIz at birth (ß = - 0.39, 95% CI: - 0.73, - 0.06); this relation was sex-dependent, such that maternal androgens significantly associated with BMIz at birth in girls alone (ß = - 0.72, 95% CI: - 1.40, - 0.04). The relation of maternal androgens with fetal growth restriction revealed dose threshold effects that differed by sex. There was no significant association between maternal androgens and weight trajectory overall. However, we found a significant sex interaction (p = 0.01); higher maternal androgen levels associated with accelerated catch-up growth in boys (aOR = 2.14, 95% CI: 1.14, 4.03). CONCLUSION: Our findings provide evidence that maternal androgens may have differential effects on the programming of intrauterine growth and postnatal weight gain depending on fetal sex.

Prenatal maternal immune disruption and sex-dependent risk for psychoses.

BACKGROUND: Previous studies suggest that abnormalities in maternal immune activity during pregnancy alter the offspring's brain development and are associated with increased risk for schizophrenia (SCZ) dependent on sex. METHOD: Using a nested case-control design and prospectively collected prenatal maternal sera from which interleukin (IL)-1ß, IL-8, IL-6, tumor necrosis factor (TNF)-α and IL-10 were assayed, we investigated sex-dependent associations between these cytokines and 88 psychotic cases [SCZ = 44; affective psychoses (AP) = 44] and 100 healthy controls from a pregnancy cohort followed for > 40 years. Analyses included sex-stratified non-parametric tests adjusted for multiple comparisons to screen cytokines associated with SCZ risk, followed by deviant subgroup analyses using generalized estimating equation (GEE) models. RESULTS: There were higher prenatal IL-6 levels among male SCZ than male controls, and lower TNF-α levels among female SCZ than female controls. The results were supported by deviant subgroup analyses with significantly more SCZ males with high IL-6 levels (>highest quartile) compared with controls [odd ratio (OR)75 = 3.33, 95% confidence interval (CI) 1.13-9.82], and greater prevalence of low TNF-α levels (

MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume.

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.

Neuropsychological performance and family history in children at age 7 who develop adult schizophrenia or bipolar psychosis in the New England Family Studies.

BACKGROUND: Persons developing schizophrenia (SCZ) manifest various pre-morbid neuropsychological deficits, studied most often by measures of IQ. Far less is known about pre-morbid neuropsychological functioning in individuals who later develop bipolar psychoses (BP). We evaluated the specificity and impact of family history (FH) of psychosis on pre-morbid neuropsychological functioning. METHOD: We conducted a nested case-control study investigating the associations of neuropsychological data collected systematically at age 7 years for 99 adults with psychotic diagnoses (including 45 SCZ and 35 BP) and 101 controls, drawn from the New England cohort of the Collaborative Perinatal Project (CPP). A mixed-model approach evaluated full-scale IQ, four neuropsychological factors derived from principal components analysis (PCA), and the profile of 10 intelligence and achievement tests, controlling for maternal education, race and intra-familial correlation. We used a deviant responder approach (<10th percentile) to calculate rates of impairment. RESULTS: There was a significant linear trend, with the SCZ group performing worst. The profile of childhood deficits for persons with SCZ did not differ significantly from BP. Neuropsychological impairment was identified in 42.2% of SCZ, 22.9% of BP and 7% of controls. The presence of psychosis in first-degree relatives (FH+) significantly increased the severity of childhood impairment for SCZ but not for BP. CONCLUSIONS: Pre-morbid neuropsychological deficits are found in a substantial proportion of children who later develop SCZ, especially in the SCZ FH+ subgroup, but less so in BP, suggesting especially impaired neurodevelopment underlying cognition in pre-SCZ children. Future work should assess genetic and environmental factors that explain this FH effect.

Lifetime characteristics of participants and non-participants in a smoking cessation trial: implications for external validity and public health impact.

BACKGROUND: Detailed information about the characteristics of smokers who do and do not participate in smoking cessation treatment is needed to improve efforts to reach, motivate, and treat smokers. PURPOSE: The aim of this study is to explore a broad range of characteristics related to participation in a smoking cessation trial. METHODS: Eligible smokers were recruited from a longitudinal birth cohort. Participants and non-participants were compared on a broad range of sociodemographics, smoking, psychiatric and substance abuse disorders, personality, and prospective measures from early childhood. Eligible smokers were compared to a matched regional subsample of the Behavioral Risk Factor Surveillance System (BRFSS). RESULTS: Few differences were observed, most of which were statistically significant but not clinically meaningful. Compared to non-participants, participants were more likely to be single, have lower income, be more nicotine-dependent, be more motivated to quit, and have higher levels of depressed mood and stress even after covariance of gender, income, and marital status. Sociodemographic differences between participants and the BRFSS sample reflect the skew toward lower socioeconomic status in the original birth cohort. CONCLUSIONS: The encouraging conclusion is that smokers who enroll in cessation trials may not differ much from non-participants. Information about treatment participants can inform the development of recruitment strategies, improve the tailoring of treatment to individual smoker profiles, help to estimate potential selection bias, and improve estimates of population impact.

Fetal growth restriction and the development of major depression.

OBJECTIVE: To test the association between fetal growth restriction and the lifetime risk of major depression and the number of recurrent episodes. METHOD: Study subjects (n = 1101) were offspring of participants in the Providence, RI, site of the National Collaborative Perinatal Project. Cox regression was used to investigate the relation between measures of birth size and the lifetime risk of depression and the mean number of depressive episodes was compared across categories of birth size. RESULTS: There was no association between low birth weight, gestational age, ponderal index and small for gestational age and the lifetime risk of major depression, or the number of recurrent episodes. CONCLUSION: Fetal growth restriction, as reflected by multiple measures of birth size, is not associated with the risk of a major depression or the subsequent recurrence of depressive episodes. Results of this study do not support a 'fetal programming' effect in depression.

Differences in maternal smoking across successive pregnancies - dose-dependent relation to BMI z-score in the offspring: an individual patient data (IPD) meta-analysis.

INTRODUCTION: Uncontrolled family factors may bias the estimation of the association between maternal smoking during pregnancy and offspring body mass index (BMI). The objective was to assess if there is an association between maternal smoking during pregnancy and offspring BMI z-score independent of factors in the siblings' shared environment and if such association is linear. METHODS: We performed an individual patient data meta-analysis using five studies providing sibling data (45,299 children from 14,231 families). In a multi-level model, separating within-family and between-family effects and with random intercept for families, we analysed the dose-response association between maternal number of cigarettes per day during pregnancy and offspring's BMI z-score using B-splines to allow for non-linear associations. RESULTS: A linear within-family effect for number of cigarettes smoked in the range from 1 to 30 cigarettes per day on the offspring's BMI z-score was observed. Each additional cigarette per day between sibling pregnancies resulted in an increase in BMI z-score of 0.007 (95% CI [0.006, 0.009]). A between family-effect emerged only with doses ≥25 cigarettes per day. CONCLUSIONS: The number of cigarettes mothers smoke per day during pregnancy is positively associated with offspring BMI z-score even among siblings, suggesting that the association is not entirely explained by confounding by family factors.

Neural - hormonal responses to negative affective stimuli: Impact of dysphoric mood and sex.

BACKGROUND: Maladaptive responses to negative affective stimuli are pervasive, including clinically ill and healthy people, and men and women respond differently at neural and hormonal levels. Inspired by the Research Domain Criteria initiative, we used a transdiagnostic approach to investigate the impact of sex and dysphoric mood on neural-hormonal responses to negative affective stimuli. METHODS: Participants included 99 individuals with major depressive disorder, psychosis and healthy controls. Functional magnetic resonance imaging (fMRI) was complemented with real-time acquisition of hypothalamo-pituitary-adrenal (HPA) and -gonadal (HPG) hormones. fMRI data were analyzed in SPM8 and task-related connectivity was assessed using generalized psychophysiological interaction. RESULTS: Across all participants, elevated cortisol response predicted lower brain activity in orbitofrontal cortex and hypothalamus-amygdala connectivity. In those with worse dysphoric mood, elevated cortisol response predicted lower activity in hypothalamus and hippocampus. In women, elevated cortisol response was associated with lower activity in medial prefrontal cortex and low hypothalamo-hippocampal connectivity. In women with high dysphoric mood, elevated cortisol response was associated with low hypothalamo-hippocampal connectivity. There were no interactions with diagnosis or medication. LIMITATIONS: There was limited power to correct for multiple comparisons across total number of ROIs and connectivity targets; cortisol responses were relatively low. CONCLUSIONS: We conclude that the pathophysiology in neural-hormonal responses to negative affective stimuli is shared across healthy and clinical populations and varies as a function of sex and dysphoric mood. Our findings may contribute to the development of hormonal adjunctive therapeutics that are sex-dependent, underscoring the importance of one's sex to precision medicine.

Prenatal immune programming of the sex-dependent risk for major depression.

Maternal immune functioning during pregnancy contributes to sex-dependent deficits in neurodevelopment and to behaviors associated with affective traits in preclinical studies, and has been indirectly associated with offspring depression in epidemiologic studies. We therefore investigated the association between immune activity during pregnancy and the risk of depression among male and female offspring. We conducted a case-control study of depression (n=484 cases and n=774 controls) using data from the New England Family Study, a pregnancy cohort enrolled between 1959 and 1966 that assessed psychiatric outcomes in adult offspring (mean age=39.7 years). We assayed concentrations of three pro-inflammatory cytokines, interleukin (IL)-1ß, IL-6 and tumor necrosis factor (TNF)-α, and the anti-inflammatory cytokine, IL-10, in maternal serum collected at the end of the second and beginning of the third trimesters. High maternal TNF-α was associated with reduced odds of depression among both male and female offspring (odds ratio (OR)=0.68; confidence interval (CI)=0.48, 0.98). However, when considering the TNF-α to IL-10 ratio, a measure of the ratio of pro- to anti-inflammatory loading, maternal immune effects on offspring depression differed significantly by sex (χ(2)=13.9, degrees of freedom=4, P=0.008). Among females, higher maternal TNF-α:IL-10 was associated with reduced odds of depression (OR=0.51; CI=0.32, 0.81), whereas, among males, high maternal TNF-α:IL-10 was associated with elevated odds of depression (OR=1.86; CI=1.02, 3.39). Thus, the balance between TNF-α and IL-10 in maternal prenatal serum was associated with depression in a sex-dependent manner. These findings are consistent with the role of TNF-α in the maturation of the sexually dimorphic fetal brain circuitry that regulates stress and affective responses, and support a prenatal stress-immune model of depression pathogenesis.

Pregnancy/delivery complications and psychiatric diagnosis. A prospective study.

We examined the hypothesis that pregnancy and delivery complications result in increased risk for the development of psychiatric disorders. The study sample included 1068 pregnancies classified as chronic fetal hypoxia, other complications, preterm birth, or normal pregnancy/delivery that had initially been studied prospectively from the prenatal period through age 7 years. Subjects were recontacted (ages 18 to 27 years) and lifetime psychiatric diagnoses made with the Diagnostic Interview Schedule. Preterm subjects had significantly higher rates of cognitive impairment. Subjects with chronic fetal hypoxia had higher rates of both cognitive impairment and psychotic disorders, although these differences failed to reach statistical significance due to the small number of cases. With these exceptions, the data did not support the hypothesis that rates of psychiatric disorders are higher among subjects born with complications of pregnancy and delivery than among normal controls born without complications.

Maternal infections and subsequent psychosis among offspring.

BACKGROUND: We tested the hypothesis that maternal infections during pregnancy are associated with the subsequent development of schizophrenia and other psychoses in adulthood. METHODS: We conducted a nested case-control study of 27 adults with schizophrenia and other psychotic illnesses and 54 matched unaffected control subjects (matched for sex, ethnicity, and date of birth) from the Providence, RI, cohort of the Collaborative Perinatal Project. We retrieved stored blood samples that had been obtained from these mothers at the end of pregnancy. These samples were analyzed for total class-specific immunoglobulins and for specific antibodies directed at recognized perinatal pathogens capable of affecting brain development. RESULTS: Maternal levels of IgG and IgM class immunoglobulins before the mothers were delivered of their neonates were significantly elevated among the case series (t = 3.06, P =.003; t = 2.93, P =.004, respectively, for IgG and IgM immunoglobulin-albumin ratios). Secondary analyses indicated a significant association between maternal antibodies to herpes simplex virus type 2 glycoprotein gG2 and subsequent psychotic illness (matched t test = 2.43, P =.02). We did not find significant differences between case and control mothers in the serum levels of IgA class immunoglobulins, or in specific IgG antibodies to herpes simplex virus type 1, cytomegalovirus, Toxoplasma gondii, rubella virus, human parvovirus B19, Chlamydia trachomatis, or human papillomavirus type 16. CONCLUSIONS: The offspring of mothers with elevated levels of total IgG and IgM immunoglobulins and antibodies to herpes simplex virus type 2 are at increased risk for the development of schizophrenia and other psychotic illnesses in adulthood.

Prevalence and risk factors for posttraumatic stress disorder among chemically dependent adolescents.

OBJECTIVE: This study ascertained the prevalence of posttraumatic stress disorder (PTSD) among chemically dependent adolescents and identified factors that influence the risk of PTSD after a qualifying trauma. METHOD: The study group consisted of 297 adolescents aged 15-19 years who met the DSM-III-R criteria for dependence on alcohol or other drugs and who were receiving treatment in seven publicly funded Massachusetts facilities. PTSD and other axis I diagnoses were assessed by the Diagnostic Interview Schedule. Data on risk factors were collected by a specially constructed interview schedule. RESULTS: The lifetime prevalence of PTSD was 29.6% (24.3% for males and 45.3% for females), and the current prevalence was 19.2% (12.2% for males and 40.0% for females). These prevalences reflect a high occurrence of traumatic exposures and a high case rate among those who experienced trauma. The risk of PTSD varied with the nature of the trauma, the number of traumas experienced, psychiatric comorbidity, and familial characteristics. The higher rate of PTSD among females was due to a greater frequency of rape, which carries a high risk of PTSD development, and to a high rate of comorbid conditions. CONCLUSIONS: The lifetime prevalence of PTSD among these chemically dependent adolescents is five times that reported for a community sample of adolescents. This extremely high rate provides new understanding of the etiologic connection between PTSD and chemical dependence and has implications for their treatment.

Depressive illness among chemically dependent adolescents.

OBJECTIVE: The purpose of this study was to investigate the prevalence and correlates of depression among adolescents being treated for chemical dependence. METHOD: Using the National Institute of Mental Health Diagnostic Interview Schedule, the authors interviewed 223 adolescents, aged 15-19 years, who were in residential treatment for alcohol or drug dependence diagnosed according to DSM-III-R criteria. Data on sociodemographic characteristics, school and social performance, past history, family composition, familial alcohol and drug abuse, and previous victimization of the subjects were also gathered. RESULTS: Fifty-four (24.7%) of the subjects met the DSM-III-R criteria for depression. Very few of the traditional correlates of depression discriminated depressed from nondepressed subjects, suggesting that the presence of chemical dependence overrides other predictors of depression. Only female gender, paternal psychopathology, and victimization (physical abuse, sexual abuse) emerged as important variables associated with depression. However, subjects whose onset of depression preceded their chemical dependence had different characteristics from those whose depression began after their chemical dependence. CONCLUSIONS: The prevalence of depressive illness in these chemically dependent adolescents was approximately three times that reported for nonreferred groups of similar age. This high rate of depression reflects the contributions of two distinct groups--those with primary depression and those with depression subsequent to chemical dependence--whose characteristics differed, suggesting the possibility of two pathologic processes, similar in manifestation but with different associated features and possibly with distinct etiologies. Confirmation of these findings in further research could indicate that the two forms of depression may require different treatment approaches.

Hypoxic-ischemia-related fetal/neonatal complications and risk of schizophrenia and other nonaffective psychoses: a 19-year longitudinal study.

OBJECTIVE: Epidemiologic evidence linking obstetric complications to schizophrenia has been positive but inconclusive. One reason for the lack of conclusive evidence may be the inconsistency in measuring disturbances of fetal/neonatal brain development based on general obstetric markers of maternal health. The authors used data from the National Collaborative Perinatal Project to examine the relationship between schizophrenia and other nonaffective psychoses and a theoretically derived measure of hypoxic-ischemia-related fetal/neonatal complications. METHOD: Six hundred ninety-three men and women (average age 23) born to a community sample of women between 1959 and 1966 were followed up an average of 19 years after early childhood assessments. Subjects with DSM-IV schizophrenia and other nonaffective psychoses were identified using the Diagnostic Interview Schedule and best-estimate consensus diagnoses. RESULTS: Hypoxic-ischemia-related fetal/neonatal complications were associated with a doubling of the risk of developing a psychotic disorder, compared with no relevant complications (6.9% versus 1.4%). When mood disorders were excluded from the group of psychotic diagnoses, the risk of schizophrenia and other nonaffective psychoses associated with hypoxic-ischemia-related fetal/neonatal complications was strikingly elevated, compared with no relevant complications (5.75% versus 0.39%). Nonpsychotic mood disorders were unrelated to these fetal/neonatal complications. Schizophrenia and other nonaffective psychoses were most strongly associated with hypoxic-ischemia-related fetal/neonatal complications of disordered growth and development. CONCLUSIONS: The data show a strikingly elevated, graded, independent risk of schizophrenia and other nonaffective psychoses associated with this classification of antecedent hypoxic-ischemia-related fetal/neonatal complications.

IQ decline during childhood and adult psychotic symptoms in a community sample: a 19-year longitudinal study.

OBJECTIVE: The goal of this study was to examine cognitive antecedents of psychosis by determining whether variability in IQ during childhood was predictive of psychotic symptoms in adulthood. METHOD: Deviant responder analyses were used to examine prospectively the relationship of IQ at ages 4 and 7 to psychotic symptoms at age 23 in 547 offspring from a community sample (National Collaborative Perinatal Project) that was unselected for psychiatric illness. The authors compared three hypotheses: that 1) low IQ, 2) large IQ fluctuations regardless of direction, or 3) large IQ declines would predict the presence of adult psychotic symptoms. RESULTS: The 10% of individuals with substantially larger than expected IQ declines from age 4 to 7 had a rate of psychotic, but not other psychiatric, symptoms at age 23 that was nearly seven times as high as the rate for other persons. Parental socioeconomic status and IQ at age 7 also predicted adult psychotic symptoms. However, when IQ at age 7, IQ decline between ages 4 and 7, and socioeconomic status were all included in a logistic regression analysis, only IQ decline remained significant. CONCLUSIONS: There is an increased likelihood of developing psychotic symptoms in adulthood for a subgroup of individuals with substantially greater than expected IQ declines during childhood. IQ decline is specific for psychotic symptoms, but follow-up assessment when the study participants are further into the age of risk will be necessary to determine specificity for schizophrenia. The authors discuss the implications of this early cognitive downturn for a neurodevelopmental view of schizophrenia.

Association of prenatal and perinatal complications with subsequent bipolar disorder and schizophrenia.

This paper presents an overview of the recent literature on the association between prenatal and perinatal complications (PPCs) and schizophrenia, then systematically reviews papers published later than 1965 examining the association of PPCs and bipolar disorder. Three of the four studies comparing bipolar cases with normal controls indicated a positive association of PPCs with the development of bipolar disorder in adult life; the four odds ratios ranged from 1.0 to 12.0. The proportion of PPCs among the bipolar samples without comparison subjects ranged from 3.8% to 50.0%. Issues of study design, measurement and severity of exposure, and outcome are addressed. This review suggests that further investigation of genetic interactions, gender differences, and the specificity of effects in the association between PPCs and mental disorders other than schizophrenia is warranted.

The problem of obstetrical complications and schizophrenia.

The use of the term "obstetrical complications" (OCs) and its variations to encompass diverse physiological mechanisms (e.g., genetic, ischemic, hemorrhagic, infectious) of disruption to fetal/neonatal brain development has engendered inconsistency, confusion, and controversy. The principal reason is that the term OCs belies the absence of a fully adequate conceptual framework for characterizing neurodevelopmental risk. We propose that neurodevelopmental risk factors for schizophrenia can be assessed more clearly if broad OC scales are replaced by measures representing more homogeneous pathways of disturbed brain development. Using a new OC classification, we found that disordered growth related to hypoxic-ischemic compromise to early brain development may confer an elevated risk of schizophrenia and other adult-onset psychoses, particularly in the presence of familial risk. Abnormal fetal and neonatal brain growth and development in schizophrenia and OCs may also, at least in part, result from genetic factors and could help explain the relation between seemingly inconsistent OCs identified in prior research.

Maternal recall of pregnancy history: accuracy and bias in schizophrenia research.

Most investigations that report a positive association between obstetric complications and schizophrenia have been case-control studies that are often based on long-term maternal recall of events during pregnancy. We tested the hypothesis that mothers of adult offspring with schizophrenia or other psychoses systematically overreport obstetric complications compared with mothers of unaffected offspring. Subjects were selected from the New England cohorts of the National Collaborative Perinatal Project, a large prospective cohort with well-documented records of pregnancy and delivery. Mothers of 39 offspring with psychosis and 39 control offspring were recontacted and completed a structured interview regarding their pregnancy history. Accuracy of maternal recall varied greatly in relation to the type of pregnancy event, and recall was inaccurate for many specific events. For the control sample only, maternal recall of the total number of complications corresponded closely to chart information. Contrary to the study hypothesis, mothers of offspring with psychosis report fewer complications than indicated in their obstetric records, with no evidence of positive recall bias. These results suggest that previous reports of a positive association between obstetric complications and schizophrenia are not likely to have resulted from biased maternal recall.

The relationship of prenatal and perinatal complications to cognitive functioning at age 7 in the New England Cohorts of the National Collaborative Perinatal Project.

Previous literature shows that children who later develop schizophrenia have elevated rates of prenatal and perinatal complications (PPCs) and neuropsychological deficits in childhood. However, little is known about the relationship of these risk factors to each other. We evaluated the relationship between PPCs and neuropsychological functioning at age 7 in a large epidemiological study of pregnancy, birth, and development: the National Collaborative Perinatal Project (NCPP). Thirteen standardized measures of cognitive abilities were acquired on 11,889 children at approximately age 7. Principal components analysis was used to create three neuropsychological measures: academic achievement skills, verbal-conceptual abilities, and perceptual-motor abilities. We measured the relationship between these factors and three measures of PPCs: low birth weight (LBW), probable hypoxicischemic complications, and chronic hypoxia. All three measures of PPCs were significantly associated with lower neuropsychological performance, after controlling for various confounders. LBW had the strongest association with neuropsychological performance, followed by an index of presumed hypoxic insults. The effect sizes between PPCs and cognitive factors at age 7 were consistently largest with perceptual-motor abilities, followed by academic achievement skills and verbal-conceptual abilities. Future studies will evaluate the effects of specific PPCs and genetic risk factors for psychosis on cognitive functioning in childhood.