School-age social behavior and pragmatic language ability in children with prenatal serotonin reuptake inhibitor exposure.

Studies examining associations between fetal serotonin reuptake inhibitor (SRI) exposure and child autism spectrum disorder (ASD) diagnoses or delayed language remain mixed and rarely prospectively follow children or employ gold-standard assessments. We prospectively followed a cohort of mother-child dyads from pregnancy through early elementary school (N = 178), and obtained maternal and alternate-caregiver ratings of behaviors related to ASD (N = 137), as well as direct, gold-standard assessments of child ASD symptoms and pragmatic language among dyads who experienced prenatal depression and either took SRIs or were medication free during pregnancy (N = 44). Prenatal SRI exposure was related to maternal ratings of ASD-related behaviors (ß = 0.24 95% confidence interval; CI [0.07, 0.48]), and, among boys, alternative caregiver ratings (males-only ß = 0.28 95% CI [0.02, 0.55], females-only ß = -0.21 95% CI [-0.63, 0.08]). However, results of our direct assessments suggest an association between SRI exposure and reduced pragmatic language scores (ß = -0.27, 95% CI [-0.53, -0.01], but not ASD (Autism Diagnostic Observation Schedule ß = 0.14 95% CI [-0.15, 0.41]; Social Responsiveness Scale ß = 0.08 95% CI [-0.25, 0.40]). These discrepancies point to issues regarding how ASD is assessed, and the possibility that SRIs may be more strongly associated with language or other broader behaviors that coincide with ASD. Larger prospective studies that incorporate thorough, gold-standard assessments of ASD, language, and other ASD-related behaviors are needed.

Maternal early-life trauma and affective parenting style: the mediating role of HPA-axis function.

A history of childhood trauma is associated with increased risk for psychopathology and interpersonal difficulties in adulthood and, for those who have children, impairments in parenting and increased risk of negative outcomes in offspring. Physiological and behavioral mechanisms are poorly understood. In the current study, maternal history of childhood trauma was hypothesized to predict differences in maternal affect and HPA axis functioning. Mother-infant dyads (N = 255) were assessed at 6 months postpartum. Mothers were videotaped during a 3-min naturalistic interaction, and their behavior was coded for positive, neutral, and negative affect. Maternal salivary cortisol was measured six times across the study visit, which also included an infant stressor paradigm. Results showed that childhood trauma history predicted increased neutral affect and decreased mean cortisol in the mothers and that cortisol mediated the association between trauma history and maternal affect. Maternal depression was not associated with affective measures or cortisol. Results suggest that early childhood trauma may disrupt the development of the HPA axis, which in turn impairs affective expression during mother-infant interactions in postpartum women. Interventions aimed at treating psychiatric illness in postpartum women may benefit from specific components to assess and treat trauma-related symptoms and prevent secondary effects on parenting.

Social stress and the oxytocin receptor gene interact to predict antisocial behavior in an at-risk cohort.

Polymorphisms in the oxytocin receptor gene are commonly associated with prosocial behaviors in the extant literature, yet their role in antisocial behaviors has rarely been explored, particularly during the transition from adolescence to early adulthood. We examined a prospective cohort (N = 404), collecting youth, mother, and clinician reports of conduct-disordered and antisocial behavior at ages 15 and 20. The oxytocin receptor gene rs53576 polymorphism was hypothesized to interact with social stress to predict antisocial outcomes. Structural equation modeling results revealed a significant main effect at age 15 (p = .025); those with the G allele exhibited higher levels of conduct problems. Structural equation modeling revealed a significant Gene × Environment interaction at age 20 (p = .029); those with the G allele who experienced high social stress exhibited higher levels of antisocial behavior. Heterozygous (AG) grouping models were compared, and parameter estimations supported G dominant groupings. These novel findings suggest that rs53576 polymorphisms may influence social salience and contribute to risk for antisocial outcomes, particularly under conditions of high social stress.

Physiological regulation in infants of women with a mood disorder: examining associations with maternal symptoms and stress.

BACKGROUND: The offspring of mothers with mood disorders may evidence increased behavioral problems as early as preschool; however, no study to date has examined psychophysiological characteristics during infancy, particularly among offspring of mothers diagnosed with bipolar disorder. Elucidating psychobiological mechanisms of risk early in development is critical to inform prevention and early intervention efforts. METHOD: This study compared physiological and behavioral responsivity in 6-month-old infants (N = 329) of mothers with lifetime histories of bipolar disorder (BD, n = 44), major depressive disorder (MDD, n = 244), or no history of Axis I disorders (CTL, n = 41). Infant respiratory sinus arrhythmia (RSA) was measured in a laboratory stressor paradigm. Measures of infant affect and behavior during mother-infant interaction, current maternal depressive symptoms, and exposure to stressful life events were examined with respect to diagnostic group and RSA. RESULTS: Groups did not differ in baseline RSA or infant affect measures. However, during the stressor task, infants of mothers with BD evidenced increases in RSA, while infants of MDD and CTL mothers evidenced decreases in RSA. Though levels of postnatal stress and current levels of maternal depressive symptoms differed among groups, neither of these factors predicted infant psychophysiological responses. CONCLUSIONS: At 6 months of age, infants of mothers with BD show differences in psychophysiological regulation. These differences cannot be accounted for by perinatal outcome, current maternal depressive symptoms, or exposure to stressful life events, and thus may reflect endophenotypic markers of psychopathological risk.

Smoking in pregnancy and parenting stress: maternal psychological symptoms and socioeconomic status as potential mediating variables.

INTRODUCTION: The purpose of this study was to examine the impact of smoking in pregnancy on parenting stress. Maternal psychological symptoms and socioeconomic status (SES) were evaluated as potential mediating factors between prenatal cigarette use and later parenting stress. METHOD: The sample included 218 mothers who were recruited at the hospital after birth and completed a 6-month visit with their infants at a university laboratory. Based on the mothers' responses to interviews at the hospital on tobacco use during pregnancy, the sample included 77 nonsmokers and 141 smokers. Information on sociodemographic variables, prenatal care, and other substance use during pregnancy was collected at the hospital interview. At the 6-month visit, the mothers completed measures of parenting stress and psychological symptoms. Cotinine levels were assessed at both timepoints. RESULTS: Regression analysis showed that maternal smoking during pregnancy predicted parenting stress in infancy. Maternal symptoms of psychological distress and SES were evaluated simultaneously to determine whether they functioned as mediating variables between smoking in pregnancy and parenting stress. A multiple mediation analysis (Preacher & Hayes, 2008a) showed that maternal psychological symptoms functioned as a mediating variable but that SES did not. CONCLUSIONS: Results suggest that mothers who smoke in pregnancy are likely to experience higher levels of psychological symptoms, which, in turn, predict higher levels of parenting stress. Smoking in pregnancy may be a marker for symptoms of psychological distress in mothers.

Memory and brain volume in adults prenatally exposed to alcohol.

The impact of prenatal alcohol exposure on memory and brain development was investigated in 92 African-American, young adults who were first identified in the prenatal period. Three groups (Control, n=26; Alcohol-related Neurodevelopmental Disorder, n=36; and Dysmorphic, n=30) were imaged using structural MRI with brain volume calculated for multiple regions of interest. Memory was measured using the Verbal Selective Reminding Memory Test and its nonverbal counterpart, the Nonverbal Selective Reminding Memory Test, which each yielding measures of learning and recall. For both Verbal and Nonverbal Recall and Slope, linear trends were observed demonstrating a spectrum of deficits associated with prenatal alcohol exposure. Dysmorphic individuals performed significantly poorer than unexposed controls on 5 of 6 memory outcomes. Alcohol-exposed individuals demonstrated significantly lower total brain volume than controls, as well as lower volume in a number of specific regions including hippocampus. Mediation analyses indicated that memory performance associated with effects of prenatal alcohol exposure was mediated from dysmorphic severity through hippocampal volume, particularly right hippocampus. These results indicate that the association between the physical effects of prenatal alcohol exposure and deficits in memory are mediated by volumetric reduction in specific brain regions.

Verbal and nonverbal memory in adults prenatally exposed to alcohol.

BACKGROUND: Neurocognitive effects of prenatal alcohol exposure in adulthood are not well documented. Questions persist regarding the extent to which there are specific, measurable effects beyond those associated with global ability deficits, whether individuals without the full fetal alcohol syndrome (FAS) demonstrate alcohol-related cognitive impairments, and whether observed memory effects are specific to a particular modality, i.e., verbal vs. visual/spatial domains. METHODS: In this study, verbal and nonverbal selective reminding paradigms were used to assess memory function in 234 young adults (M age: 22.78, SD: 1.79). Alcohol exposure was quantified prenatally. Alcohol groups included: Individuals with physical effects of alcohol exposure (Dysmorphic group, n = 47); Exposed individuals without such effects (n = 74). Contrast groups included: Controls (n = 59) matched for ethnicity, socioeconomic status, and hospital of birth; Special Education contrast group (n = 54) included to control for disability status. Memory outcomes entailed total recall, delayed recall, and measures of encoding and retrieval, and learning over trials as indexed by slope. RESULTS: Results indicated that Dysmorphic individuals were significantly less efficient in memory performance than Controls on all of the outcomes measured, but they did not differ from those in the Special Education contrast group. The nondysmorphic, alcohol-exposed group was intermediate in their performance, suggesting a continuum of effects of prenatal exposure. Evaluation of the encoding and retrieval aspects of memory performance indicated that learning rather than forgetting accounted for the deficits associated with prenatal alcohol exposure. Finally, no interaction was found between modality of presentation (verbal and nonverbal) and effects of alcohol exposure on memory performance. CONCLUSION: These findings indicate that prenatal alcohol exposure is associated with persistent and specific effects on memory performance, and these problems result from less efficient encoding of information across both verbal and nonverbal modalities. Education and training efforts with this clinical group should take these characteristics into account.

Maternal depression and anxiety effects on the human fetus: Preliminary findings and clinical implications.

Newborns of depressed and anxious mothers show biobehavioral abnormalities suggesting that maternal psychological distress has negative effects on the fetus. Two studies examined the fetuses of depressed and nondepressed mothers: (a) a cross-sectional investigation of fetal activity during the second and third trimesters and (b) an examination of behavioral and heart rate response to vibratory stimulation in late-gestation fetuses. Fetuses of depressed mothers were more active during the fifth, sixth, and seventh gestational months. Assessment of late-term fetuses consisted of a baseline, trials of vibratory stimulation directed towards measuring habituation, and a poststimulation period. During baseline, the fetuses of depressed mothers exhibited a lower heart rate. During stimulation trials, they showed less total movement and appeared to habituate more often. Approximately 35% of the variance in fetal behavior was accounted for by the mothers' depression and anxiety symptoms. Maternal depression may be linked to greater fetal activity during the second and third trimesters and decreased behavioral responsivity during late gestation. The response of late-term fetuses of depressed mothers to vibratory stimulation may reflect "receptor adaptation/effector fatigue" and not true habitation. Future studies should examine the value of clinical interventions provided to the pregnant mother.

Maternal Prenatal Psychological Distress and Preschool Cognitive Functioning: the Protective Role of Positive Parental Engagement.

Considerable animal research and available human studies suggest that psychological distress experienced by mothers during gestation is associated with later neurodevelopmental deficits in offspring; however, little research has examined potential protective factors that might mitigate this risk. The current study examined the impact of maternal prenatal psychological distress during pregnancy on cognitive outcomes in preschoolers (ages 2.5-5 years) and positive parenting as a potential protective factor. Mother-child dyads (N = 162, mean child age = 44 months, 49 % female) were recruited from a longitudinal cohort of women who had previously participated in a study of maternal mood disorders during pregnancy. Maternal prenatal distress was assessed with multiple measures collected throughout pregnancy. During a follow-up visit, mothers were interviewed about their psychological symptoms since the birth of the child, parenting behaviors were recorded during a parent-child interaction, and children's cognitive abilities were measured using the Differential Ability Scales, 2nd Edition. Maternal prenatal distress significantly predicted lower general cognitive abilities; however, this relationship was strongest for children whose mothers exhibited low levels of positive engagement and not significant when mothers exhibited high levels of positive engagement. Results suggest that positive parental engagement can protect against the detrimental effects of maternal prenatal distress on preschoolers' cognitive abilities.

Preschool outcomes following prenatal serotonin reuptake inhibitor exposure: differences in language and behavior, but not cognitive function.

OBJECTIVE: To test the hypothesis that prenatal exposure to serotonin reuptake inhibitors (SRIs) is associated with language and behavioral outcomes in preschool-aged children, while accounting for confounds such as concomitant exposures and maternal mental illness. METHOD: An observational, prospective, longitudinal study of mental illness in pregnancy was conducted at a university-based women's mental health clinic (April 2010-November 2012). A sample of 178 mother-child dyads participated in a laboratory visit at preschool age (2.5-5.5 years). The majority of women (87%) received psychotropic medication during pregnancy. Psychiatric status (based on DSM-IV), other medication use, and substance use were serially assessed and tested as confounds. Primary outcome measures included standardized measures of expressive language and cognitive function and mother and alternate caregiver ratings of child behavior problems, including the Pervasive Developmental Disorders (PDD) subscale of the Child Behavior Checklist. RESULTS: Linear regression analyses revealed that, after controlling for relevant covariates, expressive language scores from the Test of Early Language Development, 3rd edition, were negatively associated with prenatal SRI exposure (ß = -0.15, t = -2.41), while the PDD behavioral problems subscales completed by alternate caregivers and mothers were positively associated with prenatal SRI exposure (ß = 0.17, t = 2.01; ß = 0.16, t = 2.00, respectively). Cognitive function, measured using the Differential Ability Scales, 2nd edition, was not associated with any medication exposures. CONCLUSIONS: The current data suggest a small but significant association between prenatal SRI exposure and preschool outcomes, including expressive language and behavior problems. These data corroborate data from recent, population-based studies, although overall, published findings are mixed. Replication and identification of moderating risk factors are needed to understand potential clinical implications.

Decreased sleep duration is associated with increased fMRI responses to emotional faces in children.

In adults and children, sleep loss is associated with affective dysregulation and increased responsivity to negative stimuli. Adult functional neuroimaging (fMRI) studies have demonstrated associations between restricted sleep and neural alterations in the amygdala and reward circuitry when viewing emotional picture and face stimuli. Despite this, few studies have examined the associations between short sleep duration and emotional responsivity in typically developing children, and no studies have investigated this relationship using fMRI. The current study examined the relationship between sleep duration and fMRI activation to emotional facial expressions in 15 male children (ages 7-11 years). During fMRI scanning, subjects viewed and made perceptual judgments regarding negative, neutral, and positive emotional faces. Maternal reported child sleep duration was negatively associated with (a) activation in the bilateral amygdala, left insula, and left temporal pole activation when viewing negative (i.e., fearful, disgust) vs. neutral faces, (b) right orbitofrontal and bilateral prefrontal activation when viewing disgust vs. neutral faces, and (c) bilateral orbitofrontal, right anterior cingulate, and left amygdala activation when viewing happy vs. neutral faces. Consistent with our prediction, we also noted that emotion-dependent functional connectivity between the bilateral amygdala and prefrontal cortex, cingulate, fusiform, and occipital cortex was positively associated with sleep duration. Paralleling similar studies in adults, these findings collectively suggest that decreased sleep duration in school-aged children may contribute to enhanced reactivity of brain regions involved in emotion and reward processing, as well as decreased emotion-dependent functional connectivity between the amygdala and brain regions associated with emotion regulation.

Prospective associations between chronic youth sleep problems and young adult health.

OBJECTIVES: The current study investigated prospective associations between youth sleep problems across childhood and adolescence, as well as the relationship between chronic youth sleep problems and young adult health. Exploratory analyses investigated this sleep-health relationship in the context of several established risk factors, including youth depression and environmental stress. DESIGN: This project is an extension of the Mater-University Study of Pregnancy, a longitudinal study that followed more than 7000 children across early development. SETTING: Brisbane, Australia. PARTICIPANTS: Seven hundred ten mother-child dyads assessed from birth to age 20. MEASUREMENTS: We used maternal report measures to assess the persistence of youth sleep problems. We used structural equation modeling to explore the relationship between chronic maternal-reported youth sleep problems and subjective reports of young adult health quality and to assess whether associations remained when other potential health risks were included in the model. RESULTS: Path analyses revealed that sleep problems in early childhood predicted sleep problems in middle adolescence, which predicted sleep problems at age 20. Structural equation models showed that chronic youth sleep problems predicted youth health quality at age 20 (ß = .263, P < .001) over and above the effects of early adversity, chronic childhood illness, maternal depression, lifetime youth depression, and chronic youth stress. CONCLUSIONS: Chronic sleep problems can emerge in childhood and may contribute to negative health outcomes in young adulthood. Chronic youth sleep problems remain a significant predictor of poor health when tested against other known health risk factors, suggesting that sleep may be an important health intervention target.

Prenatal antipsychotic exposure and neuromotor performance during infancy.

CONTEXT: Despite the expanding clinical utility of antipsychotics beyond psychotic disorders to include depressive, bipolar, and anxiety disorders, reproductive safety data regarding the neurodevelopmental sequelae of fetal antipsychotic exposure are scarce. OBJECTIVE: To examine whether intrauterine antipsychotic exposure is associated with deficits in neuromotor performance and habituation in 6-month-old infants. DESIGN, SETTING, AND PARTICIPANTS: A prospective controlled study was conducted from December 1999 through June 2008 at the Infant Development Laboratory of the Emory Psychological Center examining maternal-infant dyads (N=309) at 6 months postpartum with pregnancy exposure to antipsychotics (n=22), antidepressants (n=202), or no psychotropic agents (n=85). Examiners masked to maternal-infant exposure status administered a standardized neuromotor examination (Infant Neurological International Battery [INFANIB]) that tests posture, tone, reflexes, and motor skills and a visual habituation paradigm using a neutral female face. MAIN OUTCOME MEASURES: The INFANIB composite score; number of trials required to achieve a 50% decrease in infant fixation during a visual habituation task; and mean time looking at the stimulus across 10 trials. RESULTS: Infants prenatally exposed to antipsychotics (mean=64.71) showed significantly lower INFANIB scores than those with antidepressant (mean=68.57) or no psychotropic (mean=71.19) exposure, after controlling for significant covariates (F(2,281)=4.51; P=.01; partial η(2)=0.033). The INFANIB scores were also significantly associated with maternal psychiatric history, including depression, psychosis, and overall severity/chronicity (P's.05) and maternal depression during pregnancy was associated with less efficient habituation (r(245)=0.16; P.02). There were no significant differences regarding habituation between medication exposure groups. CONCLUSIONS: Among 6-month-old infants, a history of intrauterine antipsychotic exposure, compared with antidepressant or no psychotropic exposure, was associated with significantly lower scores on a standard test of neuromotor performance, highlighting the need for further scrutiny of the reproductive safety and neurodevelopmental sequelae of fetal antipsychotic exposure. Disentangling medication effects from maternal illness effects, which also contributed, remains a critical challenge.