Background Prenatal exposure to phthalates, a group of synthetic chemicals widely used in consumer products, has previously been associated with adverse infant and child development. Studies also suggest that maternal depression and anxiety, may amplify the harmful effects of phthalates on infant and child neurodevelopment. Study design Our analysis included a subset of dyads enrolled in the Atlanta African American Maternal-Child Cohort (N = 81). We measured eight phthalate metabolites in first and second trimester (8–14 weeks and 24–32 weeks gestation) maternal urine samples to estimate prenatal exposures. Phthalate metabolite concentrations were averaged across visits and natural log-transformed for analysis. Maternal symptoms of depression and anxiety were assessed using validated questionnaires (Edinberg Postnatal Depression Scale and State Trait Anxiety Inventory, respectively) and the total score on each scale was averaged across study visits. The NICU Network Neurobehavioral Scale (NNNS) was administered at two weeks of age. Our primary outcomes included two composite NNNS scores reflecting newborn attention and arousal. Linear regression was used to estimate associations between individual phthalate exposures and newborn attention and arousal. We assessed effect modification by maternal depression and anxiety. Results Higher levels of urinary phthalate metabolites were not associated with higher levels of infant attention and arousal, but true associations may still exist given the limited power of this analysis. In models examining effect modification by maternal depression, we observed that an interquartile range increase in mono (2-ethlyhexyl) phthalate (MEHP), mono (2-ethyl-5-oxohexyl) phthalate (MEOHP), and mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) was associated with a significant increase in newborn arousal only among those with high depressive symptoms (MEHP: β = 0.71, 95% confidence interval [CI] = 0.10, 1.32 for high, β = −0.30, 95% CI = −0.73, 0.12 for low; MEOHP: β = 0.60, 95% CI = −0.03, 1.23 for high, β = −0.12, 95% CI = −0.58, 0.33 for low; MEHHP: β = 0.54, 95% CI = −0.04, 1.11 for high, β = −0.11, 95% CI = −0.54, 0.32 for low). Similar patterns were observed in models stratified by maternal anxiety, although CIs were wide. Conclusion Our results suggest maternal anxiety and depression symptoms may exacerbate the effect of phthalates on infant neurodevelopment. Future studies are needed to determine the optimal levels of attention and arousal in early infancy.

Although offspring of women exposed to childhood trauma exhibit elevated rates of psychopathology, many children demonstrate resilience to these intergenerational impacts. Among the variety of factors that likely contribute to resilience, epigenetic processes have been suggested to play an important role. The current study used a prospective design to test the novel hypothesis that offspring epigenetic aging – a measure of methylation differences that are associated with infant health outcomes – moderates the relationship between maternal exposure to childhood adversity and offspring symptomatology. Maternal childhood adversity was self-reported during pregnancy via the ACEs survey and the CTQ, which assessed total childhood trauma as well as maltreatment subtypes (i.e., emotional, physical, and sexual abuse). Offspring blood samples were collected at or shortly after birth and assayed on a DNA methylation microarray, and offspring symptomatology was assessed with the CBCL/1.5–5 when offspring were 2–4 years old. Results indicated that maternal childhood trauma, particularly sexual abuse, was predictive of offspring symptoms (ps = 0.003–0.03). However, the associations between maternal sexual abuse and offspring symptomatology were significantly attenuated in offspring with accelerated epigenetic aging. These findings further our understanding of how epigenetic processes may contribute to and attenuate the intergenerational link between stress and psychopathology.

BACKGROUND: Anxiety disorders tend to precede onset of comorbid depression. Several researchers have suggested a causal role for anxiety in promoting depressive episodes, but few studies have identified specific mechanisms. The current study proposes an interpersonal model of comorbidity, where anxiety disorders disrupt interpersonal functioning, which in turn elevates risk for depression. METHODS: At age 15 (T1), 815 adolescents oversampled for maternal depression completed diagnostic interviews, social chronic stress interviews, and self-report measures. At age 20 (T2), participants repeated all measures and reported on self-perceived interpersonal problems. At approximately age 23 (T3), a subset of participants (n= 475) completed a self-report depressive symptoms measure. RESULTS: Consistent with other samples, anxiety disorders largely preceded depressive disorders. Low sociability and interpersonal oversensitivity mediated the association between T1 social anxiety disorder and later depression (including T2 depressive diagnosis and T3 depressive symptoms), controlling for baseline. Interpersonal oversensitivity and social chronic stress similarly mediated the association between generalized anxiety disorder before age 15 and later depression. CONCLUSIONS: Interpersonal dysfunction may be one mechanism through which anxiety disorders promote later depression, contributing to high comorbidity rates.

Background: Single-cohort studies have identified distinct neurobehavioral profiles that are associated with prenatal and neonatal factors based on the NICU Network Neurobehavioral Scale (NNNS). We examined socioeconomic, medical, and substance use variables as predictors of NNNS profiles in a multi-cohort study of preterm and term-born infants with different perinatal exposures. Methods: We studied 1,112 infants with a neonatal NNNS exam from the Environmental influences on Child Health Outcomes (ECHO) consortium. We used latent profile analysis to characterize infant neurobehavioral profiles and generalized estimating equations to determine predictors of NNNS profiles. Results: Six distinct neonatal neurobehavioral profiles were identified, including two dysregulated profiles: a hypo-aroused profile (16%) characterized by lethargy, hypotonicity, and nonoptimal reflexes; and a hyper-aroused profile (6%) characterized by high arousal, excitability, and stress, with low regulation and poor movement quality. Infants in the hypo-aroused profile were more likely to be male, have younger mothers, and have mothers who were depressed prenatally. Infants in the hyper-aroused profile were more likely to be Hispanic/Latino and have mothers who were depressed or used tobacco prenatally. Conclusions: We identified two dysregulated neurobehavioral profiles with distinct perinatal antecedents. Further understanding of their etiology could inform targeted interventions to promote positive developmental outcomes.

Objective: Outcome investigations of prenatal maternal depression and psychotropic exposure rely extensively on maternal retrospective recall. This study compared postnatal recall to prospective documentation of illness and medication exposures. Design: Prospective cohort and retrospective case-control studies. Setting: Emory Women's Mental Health Program (prospective study) and Emory University Department of Psychology (retrospective study). Sample: A total of 164 women who participated in both the prospective and retrospective studies. Methods: Women with a history of mental illness were followed during pregnancy for prospective prenatal assessments of depression and medication exposures. At 6 months postpartum, some of these women also participated in a retrospective study during which they were asked to recall prenatal depression and medication use. Agreement between prospective and retrospective documentation of exposures was analysed. Main outcome measures: Occurrence of maternal depression during pregnancy and maternal use of pharmacological agents during pregnancy. Results: There was only moderate agreement (k = 0.42) in prospective versus retrospective reporting of prenatal depression. Positive predictive value for recalling depression was 90.4%; however, negative predictive value for denying depression was only 53.8%. Participants accurately recalled psychotropic use but significantly underreported use of nonpsychotropic medications. Conclusions: Studies using retrospective data collection may be susceptible to systematic recall bias with underreporting of maternal depression and use of nonpsychotropic agents during pregnancy.

Originally formulated to understand the recurrence of depressive disorders, the stress generation hypothesis has recently been applied in research on anxiety and externalizing disorders. Results from these investigations, in combination with findings of extensive comorbidity between depression and other mental disorders, suggest the need for an expansion of stress generation models to include the stress generating effects of transdiagnostic pathology as well as those of specific syndromes. Employing latent variable modeling techniques to parse the general and specific elements of commonly co-occurring Axis I syndromes, the current study examined the associations of transdiagnostic internalizing and externalizing dimensions with stressful life events over time. Analyses revealed that, after adjusting for the covariation between the dimensions, internalizing was a significant predictor of interpersonal dependent stress, whereas externalizing was a significant predictor of noninterpersonal dependent stress. Neither latent dimension was associated with the occurrence of independent, or fateful, stressful life events. At the syndrome level, once variance due to the internalizing factor was partialled out, unipolar depression contributed incrementally to the generation of interpersonal dependent stress. In contrast, the presence of panic disorder produced a “stress inhibition” effect, predicting reduced exposure to interpersonal dependent stress. Additionally, dysthymia was associated with an excess of noninterpersonal dependent stress. The latent variable modeling framework used here is discussed in terms of its potential as an integrative model for stress generation research.

Objective: The current study examined the prospective effects of exposure to stressful conditions in early childhood on physical health in young adulthood, and explored continuing exposure to stressors, as well as depression, in adolescence as possible mechanisms of this relationship. Design: A prospective longitudinal design was used to examine 705 mother-child pairs from a community-based sample, followed from offspring birth through age 20. Main Outcome Measures: Mothers provided contemporaneous assessments of early adverse conditions from offspring birth through age 5. Offspring responses to the UCLA Life Stress Interview, Structured Clinical Interview for DSM Disorders (SCID), Physical Functioning subscale of the SF-36 Health Survey, and questions about the presence of chronic disease were used to assess youth stress at age 15, depression from ages 15 to 20, and physical health at age 20. Results: Early adversity conferred risk for elevated levels of social and non-social stress at youth age 15, as well as depression between ages 15 and 20. Social and non-social stress in turn had effects on physical health at age 20, directly and indirectly via depression. Conclusions: Findings suggest that early adverse conditions have lasting implications for physical health, and that continued exposure to increased levels of both social and non-social stress in adolescence, as well as the presence of depression, might be important mechanisms by which early adversity impacts later physical health.

BACKGROUND: This study tests the bisocial interaction hypothesis that birth complications when combined with early maternal rejection of the infant predispose to adult violent crime. METHODS: This hypothesis was tested using a cohort of 4269 consecutive live male births on whom measures of birth complications (age 0), early maternal rejection (age 1 year), and violent crime (age 18 years) were collected. RESULTS: A significant interaction (P < .0001) between birth complications and early maternal rejection indicated that those who suffered both birth complications and early child rejection were most likely to become violent offenders in adulthood. While only 4.5% of the subjects had both risk factors, this small group accounted for 18% of all violent crimes. The effect was specific to violence and was not observed for nonviolent criminal offending. CONCLUSIONS: To our knowledge, this is the first study to show that birth complications in combination with early child rejection predispose to violent crime. The findings illustrate the critical importance of integrating biological with social measures to fully understand how violence develops and also suggest that prenatal, perinatal, and early postnatal health care interventions could significantly reduce violence.

BACKGROUND: Schizophrenia has been associated with habituation of skin conductance activity. Skin conductance data from the Copenhagen High Risk Project were analyzed. We hypothesized that genetic risk for schizophrenia and development of schizophrenia later in life are related to impaired habituation of autonomic nervous system activity. METHODS: Data were collected in 1962, when subjects averaged 15 years of age and had not yet qualified for a psychiatric diagnosis. Nonspecific fluctuations in electrodermal activity were monitored during a rest period free of sensory stimulation. RESULTS: We found that an increasing level of genetic risk for schizophrenia was related to impaired habituation of autonomic nervous system activity over time. Individuals with two schizophrenia-spectrum parent evidenced no habituation, those with one spectrum parent evidence some habituation, and those with normal parents evidenced rapid habituation. Subjects who developed schizophrenia in adulthood evidenced significant deficits in habitation in adolescence. CONCLUSIONS: These results suggest that impaired habituation of spontaneous autonomic nervous system activity may represent a behavioral marker of the genetic predisposition to schizophrenia.

Background: It is commonly assumed that individuals with both biological and psychosocial deficits are more likely to become criminal, but there is surprisingly little empirical support for this assumption. We test the hypothesis that a group with biosocial risk factors are more likely to develop behavioral and academic problems in adolescence and violent criminal offending in adulthood compared with groups with only biological or only social risk factors. Methods: Hypotheses were tested on a sample of 397 male subjects, using obstetric and early neuromotor measures collected in the first year of life; family, social, demographic, and behavioral measures at age 17 to 19 years; and criminal data at 20 to 22 years of age. Results: Cluster analysis of the risk factors indicated a group with obstetric risk factors only, a group with poverty risk factors only, and a biosocial group with both early neuromotor deficits and unstable family environments. The biosocial group had more than double the adult violence, theft, and total crime rates of the other 2 groups and bad significantly more behavioral and academic problems in adolescence. Conclusions: When early neuromotor deficits and negative family factors cluster together, individuals are particularly likely to become criminal and violent compared with those with only poverty or only obstetric risk factors. Because this biosocial group accounted for 70.2% of all crimes committed in the entire sample, early interventions that tackle these deficits might significantly reduce violence.