Introduction: Organophosphates are widely used pesticides that have been shown to affect child neurodevelopment. Previous studies that explored their potential effects on Autism Spectrum Disorder (ASD) relied either on proxies of external exposure or on questionnaires completed by the parents to identify autism-like behaviors but did not provide a clinical diagnosis of ASD. Aims: We studied the associations between prenatal biologic markers for exposure to organophosphate pesticides and the risk of having a child with ASD or other developmental concerns (ODC). Method: We analyzed 203 mother-child pairs of the ongoing MARBLES (Markers of Autism Risk in Babies − Learning Early Signs) mother-child cohort, which enrolls mothers who are either pregnant or planning a pregnancy and whose expected child has an elevated risk to develop ASD. Seven metabolites of organophosphate pesticides were assessed in repeated urine samples collected during pregnancy. At 36 months, children were assessed with intruments measuring cognitive function and adaptive behaviors, and with two gold-standard diagnostic instruments for ASD: the Autism Diagnostic Observation Schedule and the Autism Diagnostic Interview-Revised. Children were classified in one of the following groups: ASD (n = 46), ODC (n = 55) and typically developing (TD, n = 102). Results: After adjustment for potential confounders, organophosphate metabolite concentrations were not associated with an increased risk of ASD or ODC when boys and girls were studied together. After stratification by sex, dimethylthiophosphate (DMTP) pregnancy concentration tended to be associated with an increased ASD risk among girls (OR for a doubling in the DMTP concentration: 1.64 (95%CI, 0.95; 2.82)) but not among boys (OR: 0.84, 95%CI: 0.63; 1.11). Discussion: This is the first study of clinically confirmed diagnoses of ASD that utilized repeated measurements of organophosphate metabolites during pregnancy to explore the associations between these pesticides and ASD risk in children. The association we observed among girls, as well as the lack of association in boys, need to be replicated in further studies with similar design and larger sample size. In light of the higher baseline risk for ASD in this cohort, generalizability to children lacking a first degree relative affected by ASD is unknown.
IMPORTANCE The association between lead exposure and children's IQ has been well studied, but few studies have examined the effects of blood lead concentrations on children's behavior. OBJECTIVE To evaluate the association between blood lead concentrations and behavioral problems in a community sample of Chinese preschool children with a mean blood lead concentration of less than 10 μg/dL. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort studywas conducted at 4 preschools in Jintan, Jiangsu province of China. Participants included 1341 children aged 3 to 5 years. EXPOSURES Lead. MAIN OUTCOMES AND MEASURES Blood lead concentrationswere measured in children aged 3 to 5 years. Behavioral problems were assessed using Chinese versions of the Child Behavior Checklist and Caregiver-Teacher Report Form when children were aged 6 years. RESULTS The mean (SD) blood lead concentration was 6.4 (2.6) μg/dL, with the 75th and 90th percentiles being 7.5 and 9.4 μg/dL, respectively. General linear modeling showed significant associations between blood lead concentrations and increased scores for teacher-reported behavioral problems. A 1-μg/dL increase in the blood lead concentration resulted in a 0.322 (95%CI, 0.058 to 0.587), 0.253 (95%CI, 0.016 to 0.500), and 0.303 (95%CI, 0.046 to 0.560) increase of teacher-reported behavior scores on emotional reactivity, anxiety problems, and pervasive developmental problems, respectively (P < .05), with adjustment for parental and child variables. Spline modeling showed that mean teacher-reported behavior scores increased with blood lead concentrations, particularly for older girls. CONCLUSIONS AND RELEVANCE Blood lead concentrations, even at a mean concentration of 6.4 μg/dL, were associated with increased risk of behavioral problems in Chinese preschool children, including internalizing and pervasive developmental problems. This association showed different patterns depending on age and sex. As such, continued monitoring of blood lead concentrations, as well as clinical assessments of mental behavior during regular pediatric visits, may be warranted.
Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD.
Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either D-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients' level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS).