This paper reviews several converging lines of research that suggest that prenatal exposure to environmental stress may increase risk for Autistic Disorder (AD). We first discuss studies finding that prenatal exposure to stressful life events is associated with significantly increased risk of AD, as well as other disorders, such as schizophrenia and depression. We then review evidence from animal and human studies that prenatal stress can produce both (a) abnormal postnatal behaviors that resemble the defining symptoms of AD, and (b) other abnormalities that have elevated rates in AD, such as learning deficits, seizure disorders, perinatal complications, immunologic and neuroinflammatory anomalies, and low postnatal tolerance for stress. We explain why an etiologic role for prenatal stress is compatible with genetic factors in AD, and describe how stress can disrupt fetal brain development. Finally, we discuss implications for understanding underlying processes in AD, including potential gene-environment interactions, and developing new therapies and early prevention programs.

Hurricanes and tropical storms served as natural experiments for investigating whether autism is associated with exposure to stressful events during sensitive periods of gestation. Weather service data identified severe storms in Louisiana from 1980 to 1995 and parishes hit by storm centers during this period. Autism prevalences in different cohorts were calculated using anonymous data on birth dates and parishes of children diagnosed with autism in the state mental health system, together with corresponding census data on all live births in Louisiana. Prevalence increased in dose-response fashion with severity of prenatal storm exposure, especially for cohorts exposed near the middle or end of gestation (p < 0.001). Results complement other evidence that factors disrupting development during sensitive gestational periods may contribute to autism.

Background The brain undergoes major remodeling during adolescence, resulting in improved cognitive control and decision-making, and reduced impulsivity, components of behavior mediated in part by the maturing frontal lobe. Gamma-amino butyric acid (GABA), the main inhibitory neurotransmitter system, also matures during adolescence, with frontal lobe GABA receptors reaching adult levels late in adolescence. Thus, the objective of this study was to characterize in vivo developmental differences in brain GABA levels. Methods Proton magnetic resonance spectroscopy (MRS) was employed at 4 Tesla to acquire metabolite data from the anterior cingulate cortex (ACC) and the parieto-occipital (POC) cortex in adolescents (n=30) and emerging adults (n=20). Results ACC GABA/Cr levels were significantly lower in adolescents relative to emerging adults, whereas no age differences were observed in the POC. Lower ACC GABA/Cr levels were significantly associated with greater impulsivity and worse response inhibition, with relationships being most pronounced for ACC GABA/Cr and No-Go response inhibition in adolescent males. Conclusions These data provide the first human developmental in vivo evidence confirming frontal lobe GABA maturation, which was linked to impulsiveness and cognitive control. These findings suggest that reduced GABA may be an important neurobiological mechanism in the immature adolescent brain, contributing to the reduced, yet rapidly developing, ability to inhibit risky behaviors and to make decisions, which could compromise adolescent health and safety.

Previous surveys found a large (>10-fold) variation in schizophrenia prevalence at different geographic sites and a tendency for prevalence to increase with latitude. We conducted meta-analyses of prevalence studies to investigate whether these findings pointed to underlying etiologic factors in schizophrenia or were the result of methodological artifacts or the confounding of sites' latitude with level of healthcare at those sites. We found that these patterns were still present after controlling for an index of healthcare--infant mortality--and focusing on 49 studies that used similar diagnostic and ascertainment methods. The tendencies for schizophrenia prevalence to increase with both latitude and colder climate were still large and significant and present on several continents. The increase in prevalence with latitude was greater for groups with low fish consumption, darker skin, and higher infant mortality--consistent with a role of prenatal vitamin D deficiency in schizophrenia. Previous research indicates that poor prenatal healthcare and nutrition increase risk for schizophrenia within the same region. These adverse conditions are more prevalent in developing countries concentrated near the equator, but schizophrenia prevalence is lowest at sites near the equator. This suggests that schizophrenia-producing environmental factors associated with higher latitude may be so powerful they overwhelm protective effects of better healthcare in industrialized countries. The observed patterns of correlations of risk factors with prevalence are consistent with an etiologic role for prenatal vitamin D deficiency and exposure to certain infectious diseases. Research to elucidate environmental factors that underlie variations in schizophrenia prevalence deserves high priority.

Background The brain undergoes dynamic and requisite changes into the early twenties that are associated with improved cognitive efficiency, particularly in prefrontal regions that are still undergoing neuromaturation. As alcohol consumption is typically initiated and progresses to binge drinking during this time, the objective of the present study was to investigate the impact of binge alcohol consumption on frontal lobe cortical thickness in emerging adults. Methods Twenty-three binge drinking (BD; 11 females, mean age 21.5 ± 1.4) and thirty-one light drinking (LD; 15 females, mean age 21.9 ± 1.6) emerging adults underwent high-resolution magnetic resonance imaging at 3 Tesla. Cortical surface reconstruction and thickness estimation were performed using Freesurfer for three a priori brain regions of interest: bilateral anterior cingulate cortex (ACC), posterior cingulate cortex (PCC) and parieto-occipital sulcus (POS). Cortical thickness measurements were then compared between BD and LD groups. Results Cortical thickness was significantly lower in BD than LD in the right middle ACC (mid-ACC; p≤0.05) and in the left dorsal PCC (dPCC; p≤0.01). No significant differences in cortical thickness were observed in the POS. Cortical thickness in the mid-ACC correlated negatively with higher quantity and frequency of drinks consumed (p<0.01), and positively with the number of days elapsed since most recent use (p<0.05). Furthermore, less cortical thickness in the mid-ACC in the BD group alone correlated with reported patterns of high quantity and frequency of alcohol consumption (p≤0.05). Conclusions Findings suggest that past and recent patterns of intermittent heavy alcohol consumption are associated with less frontal cortical thickness (i.e. ‘thinness’) of the right mid-ACC and left dPCC in emerging adults, but not the POS. While cortical thinness could have predated binge drinking, this pattern of maladaptive consumption may have acute neurotoxic effects that interfere with the finalization of neuromaturational processes in the vulnerable frontal cortex, resulting in increased microarchitectural pruning.