Circulating Cell-Free Mitochondrial DNA and Depressive Symptoms Among Low-Active Adults Who Smoke.

OBJECTIVES: Mitochondrial dysfunction is implicated in the pathophysiology of psychiatric disorders. Levels of circulating cell-free mitochondrial DNA (cf-mtDNA) are observed to be altered in depression. However, the few studies that have measured cf-mtDNA in depression have reported conflicting findings. This study examined cf-mtDNA and depressive symptoms in low-active adults who smoke. METHODS: Participants were adults 18 to 65 years old ( N = 109; 76% female) with low baseline physical activity and depressive symptoms recruited for a smoking cessation study. Self-report measures assessed depression severity, positive and negative affect, and behavioral activation. Blood was collected and analyzed for cf-mtDNA. Relationships between depressive symptoms and cf-mtDNA were examined with correlations and linear regression. RESULTS: Levels of cf-mtDNA were associated with categorically defined depression (Center for Epidemiologic Studies Depression Scale score >15), lower positive affect, and decreased behavioral activation ( p < .05). Relationships remained significant after adjustment for age, sex, and nicotine dependence. In a linear regression model including all depressive symptom measures as predictors, Center for Epidemiologic Studies Depression Scale group and lower positive affect remained significant. CONCLUSIONS: This work suggests that mitochondrial changes are associated with depressive symptoms in low-active adults who smoke. Higher levels of cf-mtDNA in association with depression and with lower positive affect and decreased behavioral activation are consistent with a possible role for mitochondrial function in depressive symptoms.

Early childhood trauma exposure and neurocognitive and emotional processes: Associations in young children in a partial hospital program.

Early childhood trauma has been linked to neurocognitive and emotional processing deficits in older children, yet much less is known about these associations in young children. Early childhood is an important developmental period in which to examine relations between trauma and executive functioning/emotion reactivity, given that these capacities are rapidly developing and are potential transdiagnostic factors implicated in the development of psychopathology. This cross-sectional study examined associations between cumulative trauma, interpersonal trauma, and components of executive functioning, episodic memory, and emotion reactivity, conceptualized using the RDoC framework and assessed with observational and performance-based measures, in a sample of 90 children (ages 4-7) admitted to a partial hospital program. Children who had experienced two or more categories of trauma had lower scores in episodic memory, global cognition, and inhibitory control as measured in a relational (but not computerized) task, when compared to children with less or no trauma. Interpersonal trauma was similarly associated with global cognition and relational inhibitory control. Family contextual factors did not moderate associations. Findings support examining inhibitory control in both relationally significant and decontextualized paradigms in early childhood, and underscore the importance of investigating multiple neurocognitive and emotional processes simultaneously to identify potential targets for early intervention.

Maternal Childhood Adversity and Infant Epigenetic Aging: Moderation by Restless Sleep During Pregnancy.

Maternal exposure to childhood adversity is associated with detrimental health outcomes throughout the lifespan and may have implications for offspring. Evidence links maternal adverse childhood experiences (ACEs) to detrimental birth outcomes, yet the impact on the infant's epigenome is unclear. Moreover, maternal sleep habits during pregnancy may influence this association. Here, we explore whether restless sleep during pregnancy moderates the association between exposure to maternal childhood adversity and infant epigenetic age acceleration in 332 mother-infant dyads (56% female; 39% Black; 25% Hispanic). During the 2nd trimester, mothers self-reported childhood adversity and past-week restless sleep; DNA methylation from umbilical vein endothelial cells was used to estimate five epigenetic clocks. Multivariable linear regression was used to test study hypotheses. Despite no evidence of main effects, there was evidence of an interaction between maternal ACEs and restless sleep in predicting infant epigenetic age acceleration using the EPIC Gestational Age clock. Only infants whose mothers reported exposure to both ACEs and restless sleep demonstrated accelerated epigenetic aging. Results provide preliminary evidence that maternal childhood adversity and sleep may influence the infant epigenome.

Examining the Biological Impacts of Parent-Child Relationship Dynamics on Preschool-Aged Children who have Experienced Adversity.

Parent-child relationship dynamics have been shown to predict socioemotional and behavioral outcomes for children, but little is known about how they may affect biological development. The aim of this study was to test if observational assessments of parent-child relationship dynamics (cohesion, enmeshment, and disengagement) were associated with three biological indices of early life adversity and downstream health risk: (1) methylation of the glucocorticoid receptor gene (NR3C1), (2) telomere attrition, and (3) mitochondrial biogenesis, indexed by mitochondrial DNA copy number (mtDNAcn), all of which were measured in children's saliva. We tested hypotheses using a sample of 254 preschool-aged children (M age = 51.04 months) with and without child welfare-substantiated maltreatment (52% with documented case of moderate-severe maltreatment) who were racially and ethnically diverse (17% Black, 40% White, 23% biracial, and 20% other races; 45% Hispanic) and from primarily low-income backgrounds (91% qualified for public assistance). Results of path analyses revealed that: (1) higher parent-child cohesion was associated with lower levels of methylation of NR3C1 exon 1D and longer telomeres, and (2) higher parent-child disengagement was associated with higher levels of methylation of NR3C1 exon 1D and shorter telomeres. Results suggest that parent-child relationship dynamics may have distinct biological effects on children.

Reflective supervision and consultation and its impact within early childhood-serving programs: A systematic review.

Reflective supervision and consultation (RS/C) is regarded as best practice within the infant/early childhood mental health field. Benefits of RS/C on the early childhood workforce and children and families have been demonstrated through case studies, conceptual pieces, and individual research studies. However, findings across studies have not been summarized using gold-standard methodology, thus the state of existing empirical support for RS/C is unclear. This systematic review examined the collective evidence for RS/C across diverse early childhood-serving programs. Electronic databases were searched to identify studies investigating associations between RS/C and professionals' reflective capacity and well-being, child/family outcomes, and implementation factors. Twenty-eight papers were identified. Studies showed positive associations between RS/C and early childhood-serving professionals' reflective capacity and well-being, with qualitative studies reporting more consistent results than studies using quantitative methods. Many methodological limitations were identified, including incomplete reporting of study designs and participant characteristics, variability in outcome measures, and lack of randomization and comparison groups. Furthermore, few studies examined child and family outcomes. Therefore, while RS/C shows great promise, it was difficult to ascertain its overall effectiveness from an empirical standpoint. Establishing RS/C as an empirically supported approach will be possible with more rigorous research.

A la consulta y supervisión con reflexión (RS/C) se le considera como práctica óptima dentro del campo de la salud mental infantil y la temprana niñez. Los beneficios de RS/C en la fuerza laboral de la temprana niñez, así como en niños y familias, han quedado demostrados a través de estudios de casos, componentes conceptuales y estudios individuales de investigación. Sin embargo, los resultados en la gama de estudios no han sido resumidos usando una metodología arquetípica; por tanto, el estado del apoyo empírico existente para RS/C no está claro. Esta sistemática revisión examinó la evidencia colectiva de RS/C a lo largo de los diversos programas que se dedican a la temprana niñez. Se investigaron bancos electrónicos de datos para identificar estudios que investigaron las asociaciones entre RS/C y la capacidad de reflexión y bienestar de profesionales, los resultados en niño y familia, así como los factores de implementación. Se identificaron veintiocho artículos. Los estudios mostraron asociaciones positivas entre RS/C y la capacidad de reflexión y bienestar de profesionales que prestan servicios en al campo de la temprana niñez, con estudios cualitativos que reportaron resultados más consistentes que los estudios que usaron métodos cuantitativos. Se identificaron muchas limitaciones metodológicas, incluyendo un incompleto reporte de los diseños del estudio y las características de los participantes, la variabilidad en las medidas para los resultados, así como una falta de aleatorización y grupos de comparación. Es más, pocos estudios examinaron los resultados en el niño y la familia. Por tanto, mientras que RS/C muestra gran promesa, fue difícil cerciorarse de su efectividad en términos generales desde un punto de vista empírico. Establecer RS/C como un acercamiento empíricamente apoyado será posible con una investigación más rigurosa.

La supervision et la conversation par réflexion (RS/C) est considérée comme étant la meilleure pratique dans le domaine de la santé mentale du nourrisson et de la petite enfance. Les bénéfices de la RS/C sur les effectifs de la petite enfance et les enfants et leurs familles ont été prouvés au travers d'études de cas, de travaux conceptuels et d'études individuelles de recherche. Cependant les résultats au travers des études n'ont pas été résumés au moyen d'une méthodologie de référence et par conséquent l'état du soutien empirique existent pour le RS/C n'est pas clair. Cette revue systématique a examiné les preuves collectives de la RS/C au travers de divers programmes servant la petite enfance. Les bases de données électroniques ont été utilisées afin d'identifier des études se penchant sur les liens entre la RS/C et la capacité de réflexion des professionnels ainsi que leur bien-être, les résultats pour l'enfant/la famille et les facteurs de mise en place. Vingt-huit études ont été identifiées. Les études ont démontré des liens positifs entre la RS/C et la capacité de réflexion et le bien-être de professionnels de la petite enfance, avec des études qualitatives faisant état de résultats plus constants que les études utilisant des méthodes quantitatives. Plusieurs limitations méthodologiques ont été identifiées, y compris le fait de rapporter de manière incomplète les méthodologies des études et les caractéristiques des participants, la variabilité des mesures des résultats, et le manque de de groupes de randomisation et de contrôle. De plus, peu d'études ont examiné les résultats de l'enfant et de la famille. En conclusion, bien que la RS/C soit promettante, il était difficile de vérifier son efficacité générale d'un point de vue empirique. L'établissement de la RS/C en tant qu'approche soutenue empiriquement sera possible avec des recherches plus rigoureuses.

Understanding links between maternal perinatal posttraumatic stress symptoms and infant socioemotional and physical health.

Maternal posttraumatic stress symptoms (PTSS) are associated with adverse consequences for older children, but very few studies have examined links between perinatal maternal PTSS and infant outcomes. Trauma exposure and psychopathology, including PTSS, is often heightened for women during pregnancy through 1 year postpartum. Therefore, the perinatal period may be a critical time for understanding the risk maternal PTSS and other mental health factors pose to the socioemotional and physical health of infants. The present study explored the relation between maternal PTSS and infant socioemotional and physical health problems in a sample of racially and ethnically diverse mother-infant dyads (N = 295) assessed prenatally and at 12 months postpartum. This study also examined whether there are: (1) moderating effects of maternal depressive symptoms and parenting stress on these associations and (2) indirect effects of PTSS on infant outcomes through observed maternal sensitivity. Results indicated that postpartum depressive symptoms and parenting stress, rather than PTSS, were associated with greater infant socioemotional health problems. However, prenatal PTSS were associated with greater infant physical health problems when mothers also reported clinically significant levels of postpartum depressive symptoms. Maternal sensitivity was not associated with maternal PTSS, depressive symptoms, or parenting stress, nor was it related to infant socioemotional and physical health; thus, maternal sensitivity was not tested as an intermediary mechanism linking maternal mental health with infant outcomes. Implications for promoting maternal mental health in the perinatal period to bolster socioemotional and physical health of infants are discussed.

Los síntomas de estrés materno postraumático (PTSS) se asocian con consecuencias adversas para niños de mayor edad, pero pocos estudios han examinado las conexiones entre PTSS materno perinatal y los resultados en el infante. El estar expuesta al trauma y la sicopatología de este, incluyendo PTSS, a menudo se intensifican más en el caso de mujeres durante el embarazo y hasta un año después del parto. Por tanto, el período perinatal pudiera ser un omento crítico para comprender el riesgo que el PTSS materno y otros factores de salud mental presentan para la salud socioemocional y física de los infantes. Este estudio exploró la relación entre el PTSS materno y los problemas de salud socioemocional y física del infante en un grupo muestra de díadas madre-infante racial y étnicamente diversas (N = 295), evaluadas prenatalmente y a los 12 meses después del parto. Este estudio también examinó si hay: (1) efectos moderadores de los síntomas depresivos maternos y el estrés de crianza sobre estas asociaciones y (2) efectos indirectos de PTSS sobre los resultados en el infante a través de la observada sensibilidad materna. Los resultados indican que los síntomas depresivos y el estrés de crianza, en vez de PTSS, estaban asociados con mayores problemas de salud socioemocional del infante. Sin embargo, el PTSS se asoció con mayores problemas de salud física en el infante cuando las madres también reportaron niveles clínicamente significativos de síntomas depresivos. No se corroboró el que la sensibilidad materna fuera un mecanismo intermediario de conexión entre PTSS y otros factores de salud mental materna y resultados en el infante.

Les symptômes des stress posttraumatique (SPT) maternel sont liés à des conséquences adverses pour les enfants plus âgés mais peu d'études ont examiné les liens entre le SPT périnatal maternel et les résultats sur les nourrissons. L'exposition au trauma et la psychopathologie, y compris le SPT, est souvent accrues pour les femmes durant la grossesse jusqu'à un an après la naissance. Par conséquent la période périnatale peut être un moment critique pour la compréhension du risque que posent le SPT maternel et d'autres facteurs de santé mentale à la santé socio-émotionnelle et physique des nourrissons. Cette étude a exploré la relation entre le SPT maternel et les problèmes socio-émotionnels et physiques des nourrissons chez un échantillon de dyades mère-nourrisson racialement et ethniquement diverses (N = 295) évaluées au stade prénatal et à 12 mois après la naissance. Cette étude a aussi examiné s'il existait : (1) des effets modérateurs de symptômes dépressifs maternels et du stress de parentage sur ces associations et (2) des effets indirects de SPT sur les résultats du nourrisson à travers une sensibilité maternelle observée. Les résultats ont indiqué que les symptômes dépressifs postpartum et le stress de parentage, plus que le SPT, étaient liés à des problèmes plus élevés de santé socio-émotionnels du nourrisson. Cependant le SPT prénatal était lié à de plus grands problèmes de santé physique du nourrisson quand les mères faisaient aussi état de niveaux cliniquement élevés de symptômes dépressifs postpartum. La sensibilité maternelle n'était pas liée au SPT maternel, aux symptômes dépressifs ou au stress de parentage, et n'était pas non plus liée à la santé socio-émotionnelle et physique du nourrisson. Donc la sensibilité maternelle n'a pas testée comme mécanisme intermédiaire liant la santé mentale maternelle aux résultats du nourrisson. Les implications pour la promotion de la santé mentale maternelle dans la période périnatale afin de soutenir la santé socio-émotionnelle et physique des nourrissons sont discutées.

Maternal witness to intimate partner violence during childhood and prenatal family functioning alter newborn cortisol reactivity.

Witnessing intimate partner violence (IPV) during childhood is a risk factor for mental health problems across the lifespan. Less is known about the intergenerational consequences of witnessing IPV, and if the current family climate buffers intergenerational effects of witnessing violence. The mother's experience of witnessing IPV against her own mother during childhood, prenatal family dysfunction, and prenatal perceived stress were examined as predictors of offspring cortisol in the first month of life (N = 218 mother-infant dyads). Mothers reported on witnessing IPV in their childhoods, prenatal family dysfunction, and prenatal perceived stress in pregnancy. At 2 days and again at 1 month postpartum, infants engaged in a neurobehavioral exam to assess infant cortisol reactivity. Infants whose mothers witnessed IPV in childhood exhibited alterations in their baseline cortisol and their cortisol reactivity at 1 month of age, whereas family dysfunction during pregnancy was associated with baseline cortisol and cortisol reactivity at 2 days of age. Prenatal perceived stress was not associated with infant cortisol at 2 days or 1 month. Prenatal family dysfunction and perceived stress did not moderate effects of the mother's experience of witnessing IPV. Results support the view that maternal experiences in childhood and during pregnancy exert intergenerational effects on the HPA stress response system.

Family Context Moderates the Association of Maternal Postpartum Depression and Stability of Infant Temperament.

Maternal postpartum depression, maternal sensitivity, and family functioning were examined as predictors of the stability of observed infant temperament over the first 30 months of life (N = 147 families). Eight observations at 8, 15, and 30 months postpartum were used to assess infant temperament. Structured clinical interviews were used to assess maternal depression, and observational assessments were used to assess family functioning and maternal sensitivity. Family context moderated the effect of maternal depression on change in infant temperament. Maternal depression was associated with change in infant temperament when maternal sensitivity was low but not when maternal sensitivity was high. Family functioning similarly moderated these links. Results underscore the centrality of the family context in shaping child behavior over time.

Stress exposure and psychopathology alter methylation of the serotonin receptor 2A (HTR2A) gene in preschoolers.

Serotonin signaling pathways play a key role in brain development, stress reactivity, and mental health. Epigenetic alterations in the serotonin system may underlie the effect of early life stress on psychopathology. The current study examined methylation of the serotonin receptor 2A (HTR2A) gene in a sample of 228 children including 119 with child welfare documentation of moderate to severe maltreatment within the last 6 months. Child protection records, semistructured interviews in the home, and parent reports were used to assess child stress exposure, psychiatric symptoms, and behavior. The HTR2A genotype and methylation of HTR2A were measured at two CpG sites (-1420 and -1224) from saliva DNA. HTR2A genotype was associated with HTR2A methylation at both CpG sites. HTR2A genotype also moderated associations of contextual stress exposure and HTR2A methylation at site -1420. Contextual stress was positively associated with -1420 methylation among A homozygotes, but negatively associated with -1420 methylation among G homozygotes. Posttraumatic stress disorder and major depressive disorder symptoms were negatively associated with methylation at -1420, but positively associated with methylation at -1224. Results support the view that the serotonin system is sensitive to stress exposure and psychopathology, and HTR2A methylation may be a mechanism by which early adversity is biologically encoded.

Dynamic stress-related epigenetic regulation of the glucocorticoid receptor gene promoter during early development: The role of child maltreatment.

Epigenetics processes may play a vital role in the biological embedding of early environmental adversity and the development of psychopathology. Accumulating evidence suggests that maltreatment is linked to methylation of the glucocorticoid receptor gene, nuclear receptor subfamily 3, group C, member 1 (NR3C1), which is a key regulator of the hypothalamus-pituitary-adrenal axis. However, prior work has been exclusively cross-sectional, greatly constraining our understanding of stress-related epigenetic processes over time. In the current study, we examined the effect of maltreatment and other adversity on change in NR3C1 methylation among at-risk preschoolers to begin to characterize within-child epigenetic changes during this sensitive developmental period. Participants were 260 preschoolers (3-5 years old, 53.8% female), including 51.5% with moderate to severe maltreatment in the past 6 months. Child protection records, semistructured interviews, and parent reports were used to assess child stress exposure. Methylation of exons 1D and 1F of NR3C1 via saliva DNA were measured at two time points approximately 6 months apart. Results indicate that maltreated children evidence higher baseline levels of NR3C1 methylation, significant decreases in methylation over time, and then at follow-up, lower levels of methylation, relative to nonmaltreated preschoolers. Findings from the current study highlight the complex nature of stress-related epigenetic processes during early development.

Change in FK506 binding protein 5 (FKBP5) methylation over time among preschoolers with adversity.

FK506 binding protein 5 (FKBP5) alters stress response system functioning, and childhood maltreatment is associated with methylation of the FKBP5 gene. Yet it is unknown if maltreatment contributes to change in FKBP5 methylation over time. The current study draws upon a sample of 231 preschoolers, including 123 with child welfare documentation of moderate to severe maltreatment in the past 6 months, to understand if maltreatment contributes to change in FKBP5 methylation over a 6-month period. Review of child protection records and semistructured interviews in the home were used to assess maltreatment and exposure to other contextual stressors, as well as service utilization. Methylation of FKBP5 at two CpG sites in intron 7 was measured from saliva DNA at the time of initial study enrollment, and 6 months following enrollment. Child maltreatment was associated with change in FKBP5 methylation over time, but only when children were exposed to high levels of other contextual stressors. Service utilization was associated with increases in methylation over time, but only among children with the FKPB5 rs1360780 protective CC genotype. Methylation of FKBP5 is sensitive to stress exposure and may be a mechanism linking early adversity to long-term health and developmental outcomes.

Prenatal Major Depressive Disorder, Placenta Glucocorticoid and Serotonergic Signaling, and Infant Cortisol Response.

OBJECTIVES: Extending prior studies of prenatal adversity and depressive symptoms, we tested associations between maternal prenatal major depressive disorder (MDD) and infant cortisol regulation. Based on prior findings by our group, we also tested placenta glucocorticoid (HSD11B2 methylation) and serotonin (SLC6A4 gene expression) signaling as moderators of links between prenatal MDD and infant cortisol. METHODS: Participants were 153 mother-infant pairs from a low-income, diverse sample (M [SD] age = 26 [6] years). Repeated structured diagnostic interviews were used to identify mothers with (a) prenatal MDD, (b) preconception-only MDD, and (c) controls. Placenta samples were assayed for HSD11B2 methylation and SLC6A4 gene expression. Infant salivary cortisol response to a neurobehavioral examination was assessed at 1 month. RESULTS: Daughters of prenatal MDD mothers had 51% higher baseline (ratio = 1.51; 95% confidence interval [CI] = 1.01-2.27; p = .045) and 64% higher stress responsive cortisol (ratio = 1.64; 95% CI = 1.05-2.56; p = .03) than daughters of controls and 75% higher stress-responsive cortisol (ratio = 1.75; 95% CI = 1.04-2.94; p = .04) than daughters of preconception-only MDD mothers. HSD11B2 methylation moderated links between prenatal MDD and baseline cortisol (p = .02), with 1% methylation decreases associated with 9% increased baseline cortisol in infants of prenatal MDD mothers (ratio = 1.09; 95% CI = 1.01-1.16). SLC6A4 expression moderated links between prenatal MDD and cortisol response among boys alone (p = .007), with 10-fold increases in expression associated with threefold increases in stress-responsive cortisol (ratio = 2.87; 95% CI = 1.39-5.93) in sons of control mothers. CONCLUSIONS: Results highlight specificity of associations between prenatal versus preconception MDD and cortisol regulation and the importance and complexity of placenta glucocorticoid and serotonergic pathways underlying the intergenerational transmission of risk from maternal adversity.

Methylation of the Glucocorticoid Receptor Gene Promoter in Preschoolers: Links With Internalizing Behavior Problems.

Accumulating evidence suggests that early adversity is linked to methylation of the glucocorticoid receptor (GR) gene, NR3C1, which is a key regulator of the hypothalamic-pituitary-adrenal axis. Yet no prior work has considered the contribution of methylation of NR3C1 to emerging behavior problems and psychopathology in childhood. This study examined the links between methylation of NR3C1 and behavior problems in preschoolers. Data were drawn from a sample of preschoolers with early adversity (n = 171). Children ranged in age from 3 to 5 years, were racially and ethnically diverse, and nearly all qualified for public assistance. Seventy-one children had child welfare documentation of moderate to severe maltreatment in the past 6 months. Structured record review and interviews in the home were used to assess early adversity. Parents reported on child internalizing and externalizing behavior problems. Methylation of NR3C1 at exons 1D , 1F , and 1H were measured via sodium bisulfite pyrosequencing from saliva DNA. Methylation of NR3C1 at exons 1D and 1F was positively associated with internalizing (r = .21, p < .01 and r = .23, p < .01, respectively), but not externalizing, behavior problems. Furthermore, NR3C1 methylation mediated effects of early adversity on internalizing behavior problems. These results suggest that methylation of NR3C1 contributes to psychopathology in young children, and NR3C1 methylation from saliva DNA is salient to behavioral outcomes.

Childhood adversity and epigenetic regulation of glucocorticoid signaling genes: Associations in children and adults.

Early childhood experiences have lasting effects on development, including the risk for psychiatric disorders. Research examining the biologic underpinnings of these associations has revealed the impact of childhood maltreatment on the physiologic stress response and activity of the hypothalamus-pituitary-adrenal axis. A growing body of literature supports the hypothesis that environmental exposures mediate their biological effects via epigenetic mechanisms. Methylation, which is thought to be the most stable form of epigenetic change, is a likely mechanism by which early life exposures have lasting effects. We present recent evidence related to epigenetic regulation of genes involved in hypothalamus-pituitary-adrenal axis regulation, namely, the glucocorticoid receptor gene (nuclear receptor subfamily 3, group C, member 1 [NR3C1]) and FK506 binding protein 51 gene (FKBP5), after childhood adversity and associations with risk for psychiatric disorders. Implications for the development of interventions and future research are discussed.

Childhood maltreatment and methylation of FK506 binding protein 5 gene (FKBP5).

A growing body of evidence suggests that alterations of the stress response system may be a mechanism by which childhood maltreatment alters risk for psychopathology. FK506 binding protein 51 (FKBP5) binds to the glucocorticoid receptor and alters its ability to respond to stress signaling. The aim of the present study was to examine methylation of the FKBP5 gene (FKBP5), and the role of an FKBP5 genetic variant, in relation to childhood maltreatment in a sample of impoverished preschool-aged children. One hundred seventy-four families participated in this study, including 69 with child welfare documentation of moderate to severe maltreatment in the past 6 months. The children, who ranged in age from 3 to 5 years, were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors; and a composite variable assessed the number exposures to these adversities. Methylation of two sites in intron 7 of FKBP5 was measured via sodium bisulfite pyrosequencing. Maltreated children had significantly lower levels of methylation at both CpG sites (p < .05). Lifetime contextual stress exposure showed a trend for lower levels of methylation at one of the sites, and a trend for an interaction with the FKBP5 polymorphism. A composite adversity variable was associated with lower levels of methylation at one of the sites as well (p < .05). FKBP5 alters glucocorticoid receptor responsiveness, and FKBP5 gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.

Adversity in preschool-aged children: Effects on salivary interleukin-1ß.

Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary interleukin (IL)-1ß and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records. Contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1ß and CRP were obtained before and after participation in four emotion-eliciting tasks. The number of past-month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1ß. Baseline IL-1ß was positively associated with each of the significant main-effect adversities. Postchallenge IL-1ß displayed positive associations with each adversity variable, but these were not significant. CRP was not significantly associated with any of the adversity variables. Given the evidence suggesting the involvement of IL-1ß in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes.

Methylation of exons 1D, 1F, and 1H of the glucocorticoid receptor gene promoter and exposure to adversity in preschool-aged children.

Epigenetic modifications to the genome are a key mechanism involved in the biological encoding of experience. Animal studies and a growing body of literature in humans have shown that early adversity is linked to methylation of the gene for the glucocorticoid receptor (GR), which is a key regulator of the hypothalamic-pituitary-adrenal axis as well as a broad range of physiological systems including metabolic and immune function. One hundred eighty-four families participated, including n = 74 with child welfare documentation of moderate-severe maltreatment in the past 6 months. Children ranged in age from 3 to 5 years, and were racially and ethnically diverse. Structured record review and interviews in the home were used to assess a history of maltreatment, other traumas, and contextual life stressors, and a composite variable assessed the number exposures to these adversities. Methylation of regions 1(D), 1(F), and 1(H) of the GR gene was measured via sodium bisulfite pyrosequencing. The composite measure of adversity was positively correlated with methylation at exons 1(D) and 1(F) in the promoter of the GR gene. Individual stress measures were significantly associated with a several CpG sites in these regions. GR gene methylation may be a mechanism of the biobehavioral effects of adverse exposures in young children.

Interleukin 1B gene (IL1B) variation and internalizing symptoms in maltreated preschoolers.

Evidence now implicates inflammatory proteins in the neurobiology of internalizing disorders. Genetic factors may influence individual responses to maltreatment; however, little work has examined inflammatory genetic variants in adults and none in children. The present study examined the role of an interleukin 1B gene (IL1B) variant in preschoolers exposed to maltreatment and other forms of adversity in internalizing symptom development. One hundred ninety-eight families were enrolled, with one child (age 3-5 years) from each family. Adversity measures included child protective service documentation of moderate-severe maltreatment in the last 6 months and interview-assessed contextual stressors. Internalizing symptoms were measured using the Child Behavior Checklist and the Diagnostic Infant and Preschool Assessment. Maltreated children had higher major depressive disorder (MDD) and posttraumatic stress disorder symptoms and marginally higher internalizing symptoms on the Child Behavior Checklist. Controlling for age, sex, and race, IL1B genotype was associated with MDD symptoms (p = .002). Contextual stressors were significantly associated with MDD and posttraumatic stress disorder and marginally with internalizing symptoms. The IL1B genotype interacted with contextual stress such that children homozygous for the minor allele had more MDD symptoms (p = .045). These results suggest that genetic variants of IL1B may modulate the development of internalizing symptoms in the face of childhood adversity.

Does sleep link child maltreatment to depressive symptoms among incoming first-year college students?

Study Objectives: We examined whether sleep (i.e. quality, regularity, and duration) mediated associations between child maltreatment (CM) and depressive symptoms among emerging adults undergoing the major life transition of starting college. Methods: Students (N = 1400; 44% male; 48% non-Hispanic white, 20% non-Hispanic Asian, 15% Hispanic all races, 7% non-Hispanic black, and 10% non-Hispanic other races) completed daily sleep diaries for 9 weeks, followed by the Childhood Trauma Questionnaire-Short Form, Pittsburgh Sleep Quality Index, and the Center for Epidemiologic Studies Depression Scale (CES-D). DSD data were used to compute participants' Sleep Regularity Index and average 24-hour total sleep time. We used a nonparametric structural equation modeling bootstrap approach and full information maximum likelihood to account for missing data. In model 1, we controlled for sex and race and ethnicity. In model 2, we further adjusted for baseline CES-D scores. Results: The prevalence of self-reported moderate-to-severe CM was 22%. Small but significant indirect effects of CM on greater depressive symptoms through worse sleep quality (ß = 0.06, 95% CI = 0.04, 0.09) and lower sleep regularity (ß = 0.02, 95% CI = 0.005, 0.03) were observed in model 1. In model 2, only the indirect effect of sleep quality remained significant (ß = 0.03, 95% CI = 0.01, 0.06). Conclusions: Poorer sleep quality may partially account for associations between CM and depressive symptoms during the first semester of college. Including sleep as a target in student health interventions on college campuses may not only help buffer against poor mental health outcomes for students with CM, but also poor academic and socioeconomic outcomes long-term.

Maternal perinatal hypertensive disorders and parenting in infancy.

Maternal mental health strongly influences parenting during infancy. However, it is unclear whether maternal physical health conditions in the perinatal period may also impact parenting. Examining the association of hypertensive disorders - a common physical health problem in pregnancy - with subsequent parenting behaviors is an important first step in understanding the connection between maternal physical health and parenting during this critical developmental period. This study evaluated whether hypertensive disorders of pregnancy (HDP) and hypertensive disorders (HD) diagnosed after the birth of the infant were associated with parenting self-efficacy, parenting stress, and observed parental responsiveness during mother-infant interactions at 6 and 12 months postpartum among a sample of racially and ethnically diverse mothers and their infants (N = 295). Results showed that mothers with an HDP or HD diagnosis had lower levels of parenting self-efficacy, higher levels of parenting stress, and lower levels of observed parental responsiveness compared to mothers without an HDP or HD diagnosis. Given that women with childhood adversity are at higher risk for experiencing HDP/HD and may have more difficulties with parenting compared to women without childhood adversity, we utilized a sample of mothers wherein most had experienced at least one form of adversity in their childhoods. Exploratory analyses revealed that HDP/HD moderated the relation between early life experiences and parenting outcomes in all but one model. Associations between HDP/HD and parenting are discussed, with implications for how we understand maternal physical health as a determinant of parenting in the perinatal period.