Context-dependent approach and avoidance behavioral profiles as predictors of psychopathology.

Inhibition (a temperamental profile characterized by elevated levels of avoidance behaviors) is associated with increased likelihood for developing anxiety and depression, whereas exuberance (a temperamental profile characterized by elevated levels of approach behaviors) is associated with increased likelihood for developing externalizing conditions (e.g., attention deficit/hyperactivity disorder and conduct disorder). However, not all children who exhibit high levels of approach or avoidance behaviors develop emotional or behavioral problems. In this preregistered study, we assessed context-dependent profiles of approach and avoidance behaviors in 3-year-old children (N = 366). Using latent profile analysis, four groups were identified: nonsocial approachers, social approachers, social avoiders, and nonsocial avoiders. Analyses revealed that there were minimal differences in internalizing and externalizing symptoms across the four context-dependent groups. However, exploratory analyses assessed whether high levels of approach or avoidance combined across contexts, similar to findings reported in prior work, were related to psychopathology. Children identified as high in avoidance behavior at 3 years of age were more likely to show internalizing symptoms at 3 years of age but not at 5 years of age. Children high in approach were more likely to meet criteria for anxiety and externalizing disorders by age 5 years. These findings further our understanding of individual differences in how young children adjust their behavior based on contextual cues and may inform methods for identifying children at increased likelihood for the development of emotional and behavioral problems. RESEARCH HIGHLIGHTS: Context-dependent approach and avoidance profiles were identified in 3-year-old children using a person-centered approach. Children who were high in approach behavior, regardless of context, at age three had a higher likelihood for developing an anxiety or externalizing disorder by age five. These findings may help identify children at increased risk of developing emotional and behavioral problems.

Prenatal exposure to air pollution and BWGA Z-score: Modifying effects of placenta leukocyte telomere length and infant sex.

BACKGROUND: Air pollutants, such as fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3), have been associated with adverse birth outcomes, including low birth weight, often exhibiting sex-specific effects. However, the modifying effect of placental telomere length (TL), reflecting cumulative lifetime oxidative stress in mothers, remains unexplored. METHOD: Using data from a Northeastern U.S. birth cohort (n = 306), we employed linear regression and weighted quantile sum models to assess trimester-average air pollution exposures and birth weight for gestational age (BWGA) z-scores. Placental TL, categorized by median split, was considered as an effect modifier. Interactions among air pollutants, placental TL, infant sex, and BWGA z-score were evaluated. RESULTS: Without placental TL as a modifier, only 1st trimester O3 was significantly associated with BWGA z-scores (coefficient: 0.33, 95% CI: 0.03, 0.63). In models considering TL interactions, a significant modifying effect was observed between 3rd trimester NO2 and BWGA z-scores (interaction p-value = 0.02). Specifically, a one interquartile range (1-IQR) increase in 3rd trimester NO2 was linked to a 0.28 (95% CI: 0.06, 0.52) change in BWGA z-score among shorter placental TL group, with no significant association among longer TL group. Among male infants, there were significant associations between 3rd trimester PM2.5 exposure and BWGA z-scores in the longer TL group (coefficient: -0.34, 95% CI: -0.61, -0.02), and between 1st trimester O3 exposure and BWGA z-scores among males in the shorter TL group (coefficient: 0.59, 95% CI: 0.06, 1.08). For females, only a negative association in 2nd trimester mixture model was observed within the longer TL group (coefficient: -0.10, 95% CI: -0.21, -0.01). CONCLUSION: These findings highlight the need to consider the complex interactions among prenatal air pollutant exposures, placental TL, and fetal sex to better elucidate those at greatest risk for adverse birth outcomes.

Prenatal exposure to a mixture of organochlorines and metals and internalizing symptoms in childhood and adolescence.

BACKGROUND: Although prenatal chemical exposures influence neurobehavior, joint exposures are not well explored as risk factors for internalizing disorders through adolescence. OBJECTIVE: To evaluate associations of prenatal organochlorine and metal exposures, considered individually and as a mixture, with mid-childhood and adolescent internalizing symptoms. METHODS: Participants were 468 children from a prospective cohort recruited at birth (1993-1998) in New Bedford, Massachusetts. Organochlorines (hexachlorobenzene, p,p'-dichlorodiphenyl dichloroethylene, polychlorinated biphenyls) and metals (lead, manganese) were analyzed in cord blood. Internalizing symptoms (anxiety, depressive, somatic) were assessed via multiple informants on the Conners' Rating Scale (CRS) at 8-years and Behavior Assessment System for Children, Second Edition (BASC-2) at 15-years; higher T-scores indicate greater symptoms. Overall and sex-specific covariate-adjusted associations were evaluated using Bayesian Kernel Machine Regression (BKMR) and five-chemical linear regression models. RESULTS: The cohort was socioeconomically diverse (35% household income <$20,000; 55% maternal ≤ high school education at birth). Most chemical concentrations were consistent with background levels [e.g., median (range) cord blood lead: 1.1 (0-9.4) µg/dL]. BKMR suggested linear associations and no interactions between chemicals. The overall mixture was positively associated with Conners' Parent Rating Scale (CPRS) and BASC-2 Self Report of Personality (SRP) anxiety and depressive symptoms, and negatively with somatic symptoms. Prenatal lead was positively associated with adolescent anxiety symptoms [1.56 (95% CI: 0.50, 2.61) BASC-2 SRP Anxiety score increase per doubling lead]. For CRPS and BASC-2 SRP, a doubling of cord blood manganese was positively associated with internalizing symptoms for girls [e.g., 3.26 (95% CI: 0.27, 6.25) BASC-2 SRP Depression score increase], but not boys. Organochlorine exposures were not adversely associated with internalizing symptoms. DISCUSSION: Low-level prenatal lead exposure was positively associated with adolescent anxiety symptoms, and prenatal manganese exposure was positively associated with internalizing symptoms for girls from mid-childhood through adolescence. In utero neurotoxicant metal exposures may contribute to the emergence of anxiety and depression.

Metal mixtures are associated with increased anxiety during pregnancy.

BACKGROUND: Exposure to low-dose toxic metals in the environment is ubiquitous. Several murine studies have shown metals induce anxiety-like behaviors, and mechanistic research supports that metals disrupt neurotransmitter signaling systems implicated in the pathophysiology of anxiety. In this study, we extend prior research by examining joint exposure to six metals in relation to maternal anxiety symptoms during pregnancy. METHODS: The sample includes 380 participants enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort. Spot urine was collected during pregnancy (mean ± standard deviation: 31.1 ± 6.1 weeks), and concentrations of six metals (barium [Ba], cadmium [Cd], chromium [Cr], cesium [Cs], lead [Pb], antimony [Sb]) were measured by Inductively Coupled Plasma - Mass Spectrometry. Trait anxiety symptoms were measured during pregnancy using a short version of the Spielberger State Trait Anxiety Inventory (STAI-T) and information on covariates was collected by questionnaire. We used weighted quantile sum (WQS) regression as the primary modeling approach to examine metals, treated as a mixture, in relation to higher (≥20) vs. lower anxiety symptoms while adjusting for urinary creatinine and key sociodemographic variables. RESULTS: The sample is socioeconomically and racially/ethnically diverse. Urinary metal concentrations were log-normally distributed and 25% of the sample had an STAI-T score ≥20. Joint exposure to metals was associated with elevated anxiety symptoms (ORWQS = 1.56, 95% CI: 1.24, 1.96); Cd (61.8%), Cr (14.7%), and Cs (12.7%) contributed the greatest weight to the mixture effect. CONCLUSION: Exposure to metals in the environment may be associated with anxiety symptoms during pregnancy. This is a public health concern, as anxiety disorders are highly prevalent and associated with significant co-morbidities, especially during pregnancy when both the mother and developing fetus are susceptible to adverse health outcomes.

Prenatal exposure to PM2.5 and childhood cognition: Accounting for between-site heterogeneity in a pooled analysis of ECHO cohorts in the Northeastern United States.

BACKGROUND: Emerging studies have investigated the adverse health effects of PM2.5 using data from multiple cohorts, and results often are not generalizable across cohorts. We aimed to assess associations between prenatal PM2.5 and childhood cognition in two U.S. cohorts while accounting for between-site heterogeneity. METHODS: Analyses included 348 mother-child dyads enrolled in the dual site (New York City and Boston) PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort and in the First Thousand Days of Life (FTDL) study (Northern Virginia) participating in the Environmental influences on Child Health Outcomes (ECHO) national consortium. Residential prenatal PM2.5 exposure was estimated using a validated satellite-based model and childhood cognition was measured using the NIH Toolbox Cognition Battery at three to eight years of age. We used a log-linear model applied to contingency tables formed by cross-classifying covariates by site to examine between-site heterogeneity using 3rd trimester PM2.5 exposure, age-corrected cognition scores, and covariates potentially causing heterogeneities. Multivariable linear regression models informed by the combinability analysis were used to estimate the coefficients and 95% confidence intervals (CIs) for the association between 3rd trimester PM2.5 exposure and age-corrected cognition scores (mean = 100, SD = 15). RESULTS: The log-linear model indicated that inter-study associations were similar between PRISM-NYC and FTDL, which were different from those in PRISM-Boston. Accordingly, we combined the data of PRISM-NYC and FTDL cohorts. We observed associations between 3rd trimester PM2.5 and cognition scores, findings were varying by site, childsex, and test. For example, a 1 µg/m3 increase of 3rd trimester PM2.5 was associated with -4.35 (95% CI = -8.73, -0.25) mean early childhood cognition scores in females in PRISM-Boston. In the pooled NYC + FTDL site, the association between PM2.5 and childhood cognition may be modified by maternal education and urbanicity. CONCLUSIONS: We found associations between prenatal PM2.5 and impaired childhood cognition. Since multi-site analyses are increasingly conducted, our findings suggest the needed awareness of between-site heterogeneity.

Integrated and diurnal indices of maternal pregnancy cortisol in relation to sex-specific parasympathetic responsivity to stress in infants.

Maternal hypothalamic-pituitary-adrenal axis activity may prenatally program sex-specific stress-response pathways. We investigated associations between maternal cortisol during pregnancy and infant parasympathetic responsivity to stress among 204 mother-infant pairs. Cortisol indices included 3rd trimester hair cortisol, as well as diurnal slope and area under the curve, derived from saliva samples collected during pregnancy. Mother-infant dyads participated in the Repeated Still-Face Paradigm (SFP-R) at age 6 months. We calculated respiration-adjusted respiratory sinus arrhythmia (RSAc ), an indicator of parasympathetic activation, from infant respiration and cardiac activity measured during the SFP-R. We used multivariable linear mixed models to examine each cortisol index in relation to infant RSAc and investigated sex differences using cross-product terms. Diurnal cortisol indices were not associated with RSAc . There was no association between hair cortisol and baseline RSAc . However, hair cortisol was associated with sex-specific changes in RSAc over the SFP-R such that, among girls, parasympathetic withdrawal was reduced with increasing prenatal exposure to cortisol. Consistently higher levels of prenatal cortisol exposure may lead to dampened parasympathetic responsivity to stress during infancy, particularly among girls. Maternal hair cortisol may be particularly valuable for studying the effects of prenatal cortisol exposure on infant autonomic reactivity.

Maternal Lifetime Trauma and Birthweight: Effect Modification by In Utero Cortisol and Child Sex.

OBJECTIVES: To evaluate associations between maternal lifetime traumatic stress and offspring birthweight and examine modifying effects of third trimester cortisol and fetal sex. STUDY DESIGN: Analyses included 314 mother-infant dyads from an ethnically mixed pregnancy cohort. Maternal lifetime trauma was reported via the Life Stressor Checklist-Revised. Fenton birthweight for gestational age z-scores (BWGA-z) were calculated. A 3-cm scalp-nearest maternal hair segment collected at birth was assayed to reflect cumulative third trimester cortisol secretion. Multivariable regression was used to investigate associations between maternal lifetime trauma and BWGA-z and examine 2- and 3-way interactions with cortisol and fetal sex. Because subjects with low or high cortisol levels could represent susceptible populations, varying coefficient models that relax the linearity assumption on cortisol level were used to assess the modification of maternal lifetime trauma associations with BWGA-z as a function of cortisol. RESULTS: Women were primarily minorities (41% Hispanic, 26% black) with ≤12 years education (63%); 63% reported ≥1 traumatic event. Prenatal cortisol modified the association between maternal lifetime trauma and birthweight. Women with higher lifetime trauma and increased cortisol had significantly lower birthweight infants in males; among males exposed to the 90th percentile of cortisol, a 1-unit increase in trauma score was associated with a 0.19-unit decrease in BWGA-z (95% CI, -0.34 to -0.04). Associations among females were nonsignificant, regardless of cortisol level. CONCLUSIONS: These findings underscore the need to consider complex interactions among maternal trauma, disrupted in utero cortisol production, and fetal sex to fully elucidate intergenerational effects of maternal lifetime trauma.

Lifetime exposure to traumatic and other stressful life events and hair cortisol in a multi-racial/ethnic sample of pregnant women.

We examined whether lifetime exposure to stressful and traumatic events alters hypothalamic-pituitary-adrenal (HPA) axis functioning, as indexed by hair cortisol, regardless of associated psychopathology, among pregnant women of different racial/ethnic backgrounds. 180 women provided hair samples for measurement of integrated cortisol levels throughout pregnancy and information regarding their lifetime exposure to stressful and traumatic life events. Results indicate that increased lifetime exposure to traumatic events was associated with significantly greater hair cortisol over the course of pregnancy. Similarly, greater lifetime exposure to stressful and traumatic events weighted by reported negative impact (over the previous 12 months) was associated with significantly greater hair cortisol during pregnancy. All analyses controlled for maternal age, education, body mass index (BMI), use of inhaled corticosteroids, race/ethnicity, and post-traumatic stress disorder (PTSD) and depressive symptoms. Following stratification by race/ethnicity, associations between stressful and traumatic life events and hair cortisol were found among Black women only. This is the first study to consider associations between lifetime stress exposures and hair cortisol in a sociodemographically diverse sample of pregnant women. Increased exposure to stressful and traumatic events, independent of PTSD and depressive symptoms, was associated with higher cortisol production, particularly in Black women. Future research should investigate the influence of such increased cortisol exposure on developmental outcomes among offspring.

N100 Repetition Suppression Indexes Neuroplastic Defects in Clinical High Risk and Psychotic Youth.

Highly penetrant mutations leading to schizophrenia are enriched for genes coding for N-methyl-D-aspartate receptor signaling complex (NMDAR-SC), implicating plasticity defects in the disease's pathogenesis. The importance of plasticity in neurodevelopment implies a role for therapies that target these mechanisms in early life to prevent schizophrenia. Testing such therapies requires noninvasive methods that can assess engagement of target mechanisms. The auditory N100 is an obligatory cortical response whose amplitude decreases with tone repetition. This adaptation may index the health of plasticity mechanisms required for normal development. We exposed participants aged 5 to 17 years with psychosis (n = 22), at clinical high risk (CHR) for psychosis (n = 29), and healthy controls (n = 17) to an auditory tone repeated 450 times and measured N100 adaptation (mean amplitude during first 150 tones - mean amplitude during last 150 tones). N100 adaptation was reduced in CHR and psychosis, particularly among participants <13 years old. Initial N100 blunting partially accounted for differences. Decreased change in the N100 amplitude with tone repetition may be a useful marker of defects in neuroplastic mechanisms measurable early in life.

Racial/ethnic and sociodemographic factors associated with micronutrient intakes and inadequacies among pregnant women in an urban US population.

OBJECTIVE: To assess sociodemographic correlates of micronutrient intakes from food and dietary supplements in an urban, ethnically diverse sample of pregnant women in the USA. DESIGN: Cross-sectional analyses of data collected using a validated semi-quantitative FFQ. Associations between racial, ethnic and sociodemographic factors and micronutrient intakes were examined using logistic regression controlling for pre-pregnancy BMI, maternal age and smoking status. SETTING: Prenatal clinics, Boston, MA, USA. SUBJECTS: Analyses included pregnant women (n 274) in the PRogramming of Intergenerational Stress Mechanisms (PRISM) study, an urban longitudinal cohort designed to examine how stress influences respiratory health in children when controlling for other environmental exposures (chemical stressors, nutrition). RESULTS: High frequencies of vitamin E (52 %), Mg (38 %), Fe (57 %) and vitamin D (77 %) inadequacies as well as suboptimal intakes of choline (95 %) and K (99 %) were observed. Factors associated with multiple antioxidant inadequacies included being Hispanic or African American, lower education and self-reported economic-related food insecurity. Hispanics had a higher prevalence of multiple methyl-nutrient inadequacies compared with African Americans; both had suboptimal betaine intakes and higher odds for vitamin B6 and Fe inadequacies compared with Caucasians. Nearly all women (98 %) reported Na intakes above the tolerable upper limit; excessive intakes of Mg (35 %), folate (37 %) and niacin (38 %) were also observed. Women reporting excessive intakes of these nutrients were more likely Caucasian or Hispanic, more highly educated, US-born and did not report food insecurity. CONCLUSIONS: Racial/ethnic and other sociodemographic factors should be considered when tailoring periconceptional dietary interventions for urban ethnic women in the USA.

Sociodemographic risk, developmental competence, and PTSD symptoms in young children exposed to interpersonal trauma in early life.

Young children are disproportionately exposed to interpersonal trauma (maltreatment, witnessing intimate partner violence [IPV]) and appear particularly susceptible to negative sequelae. Little is known about the factors influencing vulnerability to traumatic stress responses and other negative outcomes in early life. This study examined associations among interpersonal trauma exposure, sociodemographic risk, developmental competence, and posttraumatic stress disorder (PTSD) symptoms in 200 children assessed from birth to first grade via standardized observations, record reviews, and maternal and teacher interviews. More severe PTSD symptoms were predicted by greater trauma exposure (r = .43), greater sociodemographic risk (r = .22), and lower developmental competence (rs=−.31 and −.54 for preschool and school-age developmental competence, respectively). Developmental competence partially mediated the association between trauma exposure and symptoms. Trauma exposure fully mediated the association between sociodemographic risk and symptoms. Neither sociodemographic risk nor developmental competence moderated trauma exposure effects on symptoms. The findings suggest that (a)exposure to maltreatment and IPV has additive effects on posttraumatic stress risk in early life, (b) associations between sociodemographic adversity and poor mental health may be attributable to increased trauma exposure in disadvantaged populations, and (c) early exposures have a negative cascade effect on developmental competence and mental health.

Latent profiles of maternal disrupted communication: Relations to affect and behaviour in early infancy.

Few studies have examined how mothering is organized in the first months of infancy, especially regarding risk-related interactions. Person-centred approaches, including latent profile analysis (LPA), add valuable insights about early parenting by identifying distinct profiles of interaction. First, this study aimed to identify profiles of disrupted maternal interaction during the Still-Face Paradigm among 181 mothers and their 3- to 8-month-old infants. Second, the study assessed how each maternal profile was related to infant affect and interactive behaviour. The LPA identified four profiles of maternal interaction: optimal, negative/intrusive, withdrawing and pervasively disrupted. The pervasively disrupted profile, in particular, has not been identified in past research. Each profile was associated with specific aspects of infant affect and behaviour. Recognition of disrupted behavioural profiles among at-risk mothers and infants in the early months could facilitate more precise tailoring of early interventions to the needs of mothers and infants with differing profiles of interactive risk.

Linking maternal disrupted interaction and infant limbic volumes: The role of infant cortisol output.

Despite a large animal literature documenting the role of low maternal nurturance and elevated glucocorticoid production on offspring limbic development, these pathways have not yet been assessed during human infancy. Informed by animal models, the present study examined whether 1) maternal disrupted interaction is related to infant cortisol levels, 2) infant cortisol levels are associated with infant limbic volumes, and 3) infant cortisol levels mediate associations between maternal disrupted interaction and infant limbic volumes. Participants included 57 mother-infant dyads. Infant saliva was measured at one time point before and two time points after the Still-Face Paradigm (SFP) at age 4 months. Five aspects of maternal disrupted interaction were coded during the SFP reunion episode. Between 4 and 25 months (M age = 11.74 months, SD = 6.12), under natural sleep, infants completed an MRI. Amygdala and hippocampal volumes were calculated via automated segmentation. Results indicated that 1) maternal disrupted interaction, and specifically disoriented interaction, with the infant was associated with higher infant salivary cortisol (AUCg) levels during the SFP, 2) higher infant AUCg was related to enlarged bilateral amygdala and hippocampal volumes, and 3) infant AUCg mediated the relation between maternal disrupted interaction and infant amygdala and hippocampal volumes. Findings are consistent with controlled animal studies and provide evidence of a link between increased cortisol levels and enlarged limbic volumes in human infants. Results further suggest that established interventions to decrease maternal disrupted interaction could impact both infant cortisol levels and infant limbic volumes.

Maternal Childhood Abuse Versus Neglect Associated with Differential Patterns of Infant Brain Development.

Severity of maternal childhood maltreatment has been associated with lower infant grey matter volume and amygdala volume during the first two years of life. A developing literature argues that effects of threat (abuse) and of deprivation (neglect) should be assessed separately because these distinct aspects of adversity may have different impacts on developmental outcomes. However, distinct effects of threat versus deprivation have not been assessed in relation to intergenerational effects of child maltreatment. The objective of this study was to separately assess the links of maternal childhood abuse and neglect with infant grey matter volume (GMV), white matter volume (WMV), amygdala and hippocampal volume. Participants included 57 mother-infant dyads. Mothers were assessed for childhood abuse and neglect using the Adverse Childhood Experiences (ACE) questionnaire in a sample enriched for childhood maltreatment. Between 4 and 24 months (M age = 12.28 months, SD = 5.99), under natural sleep, infants completed an MRI using a 3.0 T Siemens scanner. GMV, WMV, amygdala and hippocampal volumes were extracted via automated segmentation. Maternal history of neglect, but not abuse, was associated with lower infant GMV. Maternal history of abuse, but not neglect, interacted with age such that abuse was associated with smaller infant amygdala volume at older ages. Results are consistent with a threat versus deprivation framework, in which threat impacts limbic regions central to the stress response, whereas deprivation impacts areas more central to cognitive function. Further studies are needed to identify mechanisms contributing to these differential intergenerational associations of threat versus deprivation.

Associations of cord blood leukocyte telomere length with adiposity growth from infancy to adolescence.

OBJECTIVE: Leukocyte telomere length (LTL) may be a biomarker for chronic disease susceptibility, but no work has tested this hypothesis directly. Our study investigated associations of LTL at birth with markers of adiposity growth that are linked with cardiometabolic health later in life. METHODS: Participants were 375 children in Project Viva (48% female, 71% White). Body mass index (BMI) trajectories from birth to 18 years were tracked using repeated measures of BMI collected in physical examinations and via medical records, then used to predict age (months) and magnitude (kg/m2 ) of BMI peak and rebound. LTL was measured from cord blood via duplex quantitative PCR. A binary variable indicating LTL shorter than the reference population average was the primary exposure. RESULTS: LTL was unrelated to BMI at peak or rebound, but associations were apparent with the timing of BMI growth milestones. Short LTL was related to a later age of peak for females (ß = 0.99, 95% CI = 0.16, 1.82; psex interaction  = 0.015) and an earlier age of rebound for both males and females (ßcombined  = -5.26, 95% CI = -9.44, -1.08). CONCLUSION: LTL at birth may be an early biomarker of altered adiposity growth. Newborn telomere biology may shed new insight into the developmental origins of health and disease.

Patterns of Maternal Childhood Maltreatment and Disrupted Interaction Between Mothers and Their 4-Month-Old Infants.

Maternal childhood maltreatment (MCM) is associated with parenting disruptions which may contribute to the intergenerational transmission of negative health and social outcomes. Most prior work has used variable-centered approaches to assess MCM. Complementary person-centered approaches can identify groups of participants characterized by similar patterns of maltreatment. The current study assessed both types and patterns of MCM in relation to disrupted parenting among 179 mothers and their 4-month-olds. In variable-centered analyses, physical abuse was related to negative-intrusive maternal behavior and physical neglect to role-confused behavior. Person-centered analyses derived three classes of MCM, which differed in disrupted parenting. For example, mothers who experienced multiple types of maltreatment displayed more withdrawal than mothers in both other classes. Results document the differential effects of particular types and patterns of MCM on aspects of parenting and reveal that mother's history of maltreatment can affect the quality of mother-child interaction as early as 4 months of age.

Maternal Childhood Maltreatment Is Associated With Lower Infant Gray Matter Volume and Amygdala Volume During the First Two Years of Life.

Background: Childhood maltreatment affects approximately 25% of the world's population. Importantly, the children of mothers who have been maltreated are at increased risk of behavioral problems. Thus, one important priority is to identify child neurobiological processes associated with maternal childhood maltreatment (MCM) that might contribute to such intergenerational transmission. This study assessed the impact of MCM on infant gray and white matter volumes and infant amygdala and hippocampal volumes during the first 2 years of life. Methods: Fifty-seven mothers with 4-month-old infants were assessed for MCM, using both the brief Adverse Childhood Experiences screening questionnaire and the more detailed Maltreatment and Abuse Chronology of Exposure scale. A total of 58% had experienced childhood maltreatment. Between 4 and 24 months (age in months: mean = 12.28, SD = 5.99), under natural sleep, infants completed a magnetic resonance imaging scan using a 3T Siemens scanner. Total brain volume, gray matter volume, white matter volume, and amygdala and hippocampal volumes were extracted via automated segmentation. Results: MCM on the Adverse Childhood Experiences and Maltreatment and Abuse Chronology of Exposure scales were associated with lower infant total brain volume and gray matter volume, with no moderation by infant age. However, infant age moderated the association between MCM and right amygdala volume, such that MCM was associated with lower volume at older ages. Conclusions: MCM is associated with alterations in infant brain volumes, calling for further identification of the prenatal and postnatal mechanisms contributing to such intergenerational transmission. Furthermore, the brief Adverse Childhood Experiences questionnaire predicted these alterations, suggesting the potential utility of early screening for infant risk.

Children's exposure to violence and distress symptoms: influence of caretakers' psychological functioning.

BACKGROUND: Previous studies linking violence exposure to adverse child behavior have typically relied on parental report of child symptoms without accounting for the informant's mental well-being, despite evidence that parental mental health can influence children's mental health and the parent's report of distress symptoms. PURPOSE: We assess the influence of maternal depression on the violence exposure and child distress association in a subset of the Maternal Infant Smoking Study of East Boston, a prospective birth cohort. METHODS: Mothers reported on their children's violence exposure using the Survey of Children's Exposure to Community Violence (ETV) and completed the Checklist of Child Distress Symptoms (CCDS). The children also completed the ETV survey and the self-report version of the CCDS. Linear regression was used to assess the influence of violence exposure on distress symptoms adjusting for potential confounders, first using parent's report of exposure and outcome and a second time using the child's self-report. The mediating effect of maternal depression on the violence and distress association was also tested. RESULTS: Among the 162 children ages 7 to 11, 51% were boys and 43% self-identified as Hispanic. When using child self-report, increased violence exposure was significantly associated with a broader range of distress symptoms (numbness, arousal, intrusion, avoidance subscales) compared to parent reported findings, which were only significantly related to the intrusion and avoidance subscales. Moreover, a significant mediation effect of maternal depression on the violence and distress association was noted only when mother's report of exposure and outcome was used. CONCLUSION: Considering both parent and child self-report of violence is necessary to obtain a complete picture of violence exposure because parents and children may be offering different, although equally valid information. The influence of maternal depressive symptoms on preadolescent's distress symptoms may be attributed to reporting bias as opposed to more direct effects; thus, the parent's psychological functioning should be taken into consideration when relying on parental report of the child's psychological functioning.

Biomarkers of Allostatic Load as Correlates of Impairment in Youth with Chronic Pain: An Initial Investigation.

Pediatric chronic pain is common and responsible for significant healthcare burden. However, the mechanisms underlying the development and/or maintenance of pediatric chronic pain remain poorly understood. Allostatic load (AL), or wear and tear on the nervous system following significant or prolonged stress, has been proposed to play a role in the maintenance of chronic pain, but minimal research has examined this possibility. This gap in research is particularly notable given the high exposure to adverse childhood experiences (ACEs; abuse/neglect, etc.) and psychological stress in this population. Accordingly, the current study aimed to preliminarily examine the measurement of AL in a treatment-seeking pediatric pain population. Biomarkers were collected during an already scheduled new patient pain evaluation and included salivary cortisol, dehydroepiandrosterone (DHEA), and C-reactive protein, in addition to waist-hip ratio, body-mass index, and blood pressure. A total of 61 children and adolescents with chronic pain (Mage = 14.47 years; 88.5% female and white/Caucasian) completed study procedures and were included in analyses. Preliminary results indicated that a multifactorial AL composite is feasible to assess for in a tertiary pain treatment setting and that over 50% of youth with chronic pain were classified as high risk for AL (two or more risk factors). Further, it was found that individual AL risk factors were significantly associated with functional disability and that AL may moderate the association between psychosocial and functional outcomes. Given the pilot nature of this study, results should be used to inform future investigations with larger and more diverse pediatric pain samples.

Telomere length shortening in hospitalized preterm infants: A pilot study.

Leukocyte telomere length is a biomarker of aging-related health risks. Hospitalized preterm infants frequently experience elevated oxidative stress and inflammation, both of which contribute to telomere shortening. Our aim was to examine changes in telomere length during neonatal intensive care unit (NICU) hospitalization in a cohort of preterm infants <32 weeks' gestation. We conducted a longitudinal study of 10 infants (mean gestational age 27 weeks, range 23.5 to 29, at birth). We isolated DNA from dried blood spots and used Real Time Quantitative PCR to measure relative leukocyte telomere length in triplicate at three time points for each participant. From birth to discharge, infants experienced an average decline in relative telomere length of 0.021 units per week (95% CI -0.040, -0.0020; p = 0.03), after adjustment for gestational age at birth. Our results suggest a measurable decline in telomere length during NICU hospitalization. We speculate that telomere length change may convey information about NICU exposures that carry short- and long-term health risks.