Patterns of Adverse Childhood Experiences and Neurocognitive Development.

Importance: Early life adversity is associated with higher risk of many adult health problems, including mental illness, substance abuse, suicide attempt, and chronic diseases. Many previous studies investigated adversities one at a time or investigated the health toll associated with the cumulative number of adversities. Objective: To examine the co-occurrence of adversities among children and how specific patterns of adversities are associated with neurocognitive development. Design, Setting, and Participants: This cohort study used data from the Collaborative Perinatal Project (CPP), which enrolled a national sample of women during pregnancy and followed their offspring to ages 7 to 8 years, between 1959 and 1974. The CPP was a community-based study conducted in 12 US medical centers. The CPP sample was ascertained through prenatal clinics and is diverse with respect to race and socioeconomic status. Data analysis was performed from August 2023 to March 2024. Exposures: A latent class analysis was conducted of 12 adverse childhood experiences that occurred between birth and 7 years to identify common patterns of childhood adversities. Main Outcomes and Measures: Five neurocognitive tests were used to measure children's visual-motor, sensory-motor, auditory-vocal, intelligence quotient, and academic skills. Results: The analysis sample included 49 853 offspring (25 226 boys [50.6%]); 24 436 children (49.0%) had low probability of experiencing any adversity, whereas the remaining half were classified into 5 groups reflecting distinct patterns of childhood adversities: parental harshness and neglect, 1625 children (3.3%); parental separation and poverty, 8731 children (17.5%); family instability, 3655 children (7.3%); family loss, instability, and poverty, 1505 children (3.0%); and crowded housing and poverty, 9901 children (19.9%). Children in 4 of these groups had lower neurocognitive scores than children with a low probability of experiencing adversity, with standardized mean differences ranging from -0.07 (95% CI, -0.11 to -0.03) to -0.86 (95% CI, -1.06 to -0.65). Conclusions and Relevance: These findings suggest that adverse childhood experiences are associated with deficits in children's neurocognitive functions. It is important to understand the complexity in children's exposure to adversity and the resulting developmental consequences, as well as the underlying mechanisms, to help support children exposed to adversity and foster healthier and resilient trajectories of development.

Adolescent Substance Use Patterns and Risk for Suicidal Thoughts and Behaviors in Young Adulthood.

OBJECTIVE: There is strong evidence that substance use is a risk factor for suicidality. Prior studies have focused on the suicide risk associated with using individual substances, even though substance users often use more than one substance. This study investigates the association between patterns of adolescent substance use and suicidality in young adulthood. METHOD: Participants were U.S. adolescents (n = 2,111, 58.9% female, mean age = 16.31 years) from the NEXT Generation Health Study, which followed tenth graders for 7 years (2009/2010-2016) and collected data via yearly surveys. Longitudinal latent class analysis was used to identify high school patterns of substance use, and logistic regression was used to relate these patterns to risk of suicidality in young adulthood. RESULTS: We identified two groups of adolescents: "non-/infrequent users" (71%) and "multiple substance users" (29%). Multiple substance users had higher odds of making a suicide plan or attempt in young adulthood (odds ratio [OR] = 2.41, 95% CI [1.05, 5.53]), but not suicidal ideation (OR = 1.55, 95% CI [0.80, 2.99]), than non-/infrequent users, adjusting for sociodemographic factors and depressive symptoms. Multiple substance users with suicidal ideation were not more likely to progress to a later plan or attempt (OR = 1.41, 95% CI [0.41, 4.84]) than non-/infrequent users. CONCLUSIONS: Adolescents who use substances in high school are at higher risk for making a suicide plan or attempt in young adulthood. Early identification of these adolescents may help inform interventions to mitigate risk for suicidal behaviors in young adulthood.

Relationships between early-life family poverty and relative socioeconomic status with gestational diabetes, preeclampsia, and hypertensive disorders of pregnancy later in life.

PURPOSE: Low early-life absolute and relative socioeconomic status (SES) may contribute to socioeconomic disparities in pregnancy complications (i.e., gestational diabetes mellitus [GDM], preeclampsia/eclampsia [PE], hypertensive disorders of pregnancy [HDP; preeclampsia/eclampsia, gestational hypertension, chronic hypertension]), but their independent associations with pregnancy complications have not been studied. This study investigated associations of early-life poverty and relative SES with risks of GDM, PE, and HDP. METHODS: National Longitudinal Study of Adolescent to Adult Health data were used (GDM n = 802; PE n = 813; HDP n = 801). Objective poverty was defined as wave I low-income or receipt of federal nutrition assistance benefits. Relative SES was self-reported at wave V (ages 33-39) by asking whether the participant's family was financially worse off than average when growing up. Logistic regressions assessed relationships between poverty, relative SES, and self-reported lifetime diagnoses of GDM, PE, or HDP. RESULTS: Lifetime prevalences of GDM, PE, and HDP were 9.23%, 12.00%, and 21.93%, respectively. Low relative SES (odds ratio: 2.04 [1.07, 3.89]) and poverty (odds ratio: 1.81 [0.97, 3.38]) were independently associated with GDM but not with PE or HDP. CONCLUSIONS: Early-life poverty and relative SES are associated with GDM; understanding the mechanisms underlying these associations may help identify novel intervention targets to reduce socioeconomic disparities in GDM.

Associations between prenatal maternal stress, maternal inflammation during pregnancy, and children's internalizing and externalizing symptoms throughout childhood.

BACKGROUND: Maternal immune activation is a potential mechanism underlying associations between maternal stress during pregnancy and offspring mental health problems. This study examined associations between prenatal maternal stress, maternal inflammation during pregnancy, and children's internalizing and externalizing symptoms from 3 to 10 years of age, and whether maternal inflammation mediated the associations between prenatal maternal stress and children's internalizing and externalizing symptoms. METHODS: This study comprised 4,902 mother-child dyads in the Generation R study. Prenatal maternal stress was assessed using self-reported data collected during pregnancy and analyzed as a latent variable consisting of four stress domains. Maternal inflammation during pregnancy was assessed using serum concentrations of C-reactive protein (CRP) measured at a median of 13.5 weeks' gestation. Child internalizing and externalizing symptoms were assessed using the Child Behavior Checklist (CBCL) by maternal report at ages 3 years, 5 years, and 10 years; paternal-reported CBCL data were also available at 3 years and 10 years. RESULTS: Prenatal maternal stress was associated with maternal-reported internalizing and externalizing symptoms of the child at 3, 5, and 10 years of age, and with paternal-reported internalizing and externalizing symptoms at 3 and 10 years. Prenatal maternal stress was associated with maternal CRP concentrations prior to, but not after, covariate adjustment. Maternal CRP concentrations during pregnancy were associated with paternal-reported internalizing symptoms of offspring at 10 years of age prior to, but not after, covariate adjustment. There was no evidence that CRP concentrations mediated the associations between prenatal maternal stress and children's internalizing or externalizing symptoms. CONCLUSIONS: Maternal stress during pregnancy is associated with higher levels of internalizing and externalizing symptoms in children, but this association is not because of differences in maternal immune activation linked to maternal stress. Replication of these findings in other cohorts is required; examination of other biomarkers or variation in immune activity during pregnancy would also benefit from further exploration.

Children's cognitive performance and suicide risk through middle adulthood.

BACKGROUND: Longitudinal studies show that lower cognitive performance in adolescence and early adulthood is associated with higher risk of suicide death throughout adulthood. However, it is unclear whether this cognitive vulnerability originates earlier in childhood since studies conducted in children are scarce and have inconsistent results. METHODS: Vital status of 49,853 individuals born between 1959 and 1966 to participants in the Collaborative Perinatal Project cohort was determined by a probabilistic linkage to the National Death Index, covering all US deaths occurring from 1979 through 2016. Cox proportional hazard models were used to examine associations of general, verbal, and non-verbal intelligence at ages 4 and 7, and academic skills at age 7 with suicide death coded according to ICD-9/10 criteria, while accounting for sociodemographic and pregnancy factors previously associated with suicide in this sample. RESULTS: By the end of 2016, 288 cohort members had died by suicide. Cognitive performance at 7 years on tests with verbal components was associated with suicide risk (average vs. high verbal intelligence, HR = 1.97, 95% CI 1.05-3.71; low vs. high spelling skills, HR = 2.02, 95% CI 1.16-3.51; low vs. high reading skills, HR = 2.01, 95% CI 1.27-3.17). Associations were still evident, especially for verbal intelligence and reading skills, but hazard ratios were attenuated after adjusting for prenatal and sociodemographic factors at birth (verbal intelligence, HR = 1.97, 95% CI 1.03-3.78; spelling, HR = 1.61, 95% CI 0.90-2.88; reading, HR = 1.67, 95% CI 1.02-2.72). CONCLUSIONS: Childhood neurocognitive performance is associated with vulnerability to suicide mortality through middle-adulthood, suggesting that there might be a cognitive diathesis for suicide originating in early childhood. Future studies should examine how multiple domains of childhood cognitive performance contribute to vulnerability to suicide risk, including by increasing risk for social and environmental factors that are associated not only with suicide but also with many types of psychiatric disorders.

Prenatal maternal stress, child internalizing and externalizing symptoms, and the moderating role of parenting: findings from the Norwegian mother, father, and child cohort study.

BACKGROUND: Few studies have examined how parenting influences the associations between prenatal maternal stress and children's mental health. The objectives of this study were to examine the sex-specific associations between prenatal maternal stress and child internalizing and externalizing symptoms, and to assess the moderating effects of parenting behaviors on these associations. METHODS: This study is based on 15 963 mother-child dyads from the Norwegian Mother, Father, and Child Cohort Study (MoBa). A broad measure of prenatal maternal stress was constructed using 41 self-reported items measured during pregnancy. Three parenting behaviors (positive parenting, inconsistent discipline, and positive involvement) were assessed by maternal report at child age 5 years. Child symptoms of internalizing and externalizing disorders (depression, anxiety, attention-deficit hyperactivity disorder, conduct disorder, and oppositional-defiant disorder) were assessed by maternal report at age 8. Analyses were conducted using structural equation modeling techniques. RESULTS: Prenatal maternal stress was associated with child internalizing and externalizing symptoms at age 8; associations with externalizing symptoms differed by sex. Associations between prenatal maternal stress and child depression, and conduct disorder and oppositional-defiant disorder in males, became stronger as levels of inconsistent discipline increased. Associations between prenatal maternal stress and symptoms of attention-deficit hyperactivity disorder in females were attenuated as levels of parental involvement increased. CONCLUSIONS: This study confirms associations between prenatal maternal stress and children's mental health outcomes, and demonstrates that these associations may be modified by parenting behaviors. Parenting may represent an important intervention target for improving mental health outcomes in children exposed to prenatal stress.

Uncertainty in Developmental Origins of Health and Disease research: commentary on Nomura et al. (2023).

Nomura et al. (Journal of Child Psychology and Psychiatry, 2023) reported that children whose mothers were pregnant when Superstorm Sandy struck the Eastern Seaboard of the United States had elevated risk of psychopathology. Their study leverages data from a unique cohort of children established prior to Sandy that enabled researchers to investigate children's mental health depending on their prenatal exposure to the storm. Their findings add to mounting evidence that various types of prenatal stressors instigate stress responses that are transmitted to the developing fetus and impart enduring risk for neuropsychiatric disorders.

A Nationally Representative Study of Sexual Orientation and High-Risk Drinking From Adolescence to Young Adulthood.

PURPOSE: To determine whether peer drunkenness, parental knowledge about their adolescent's whereabouts and behaviors, and depressive symptoms contribute to sexual orientation disparities in high-risk drinking behaviors; if they do, they would be potential intervention targets. METHODS: Longitudinal survey data from 2,051 adolescents who participated in the NEXT Generation Health Study were analyzed. Latent growth curve and longitudinal path analyses were used to test for indirect effects linking sexual orientation in 11th grade (3.4% males and 8.4% females were sexual minorities) to past 30-day heavy episodic drinking (HED) over 6 years and past year high-intensity binge drinking at 4 years after high school. RESULTS: Sexual minority males were not more likely to engage in high-risk drinking than heterosexual males. In contrast, sexual minority females were more likely than heterosexual females to engage in HED when they were in 11th grade (Odds Ratio = 2.83, 95% confidence interval = 1.43, 5.61), in part because of lower parental knowledge. Sexual minority females also had higher depressive symptoms during the transition from adolescence to young adulthood, which in turn was associated with greater risk of high-intensity binge drinking in young adulthood. Peer drunkenness was a strong risk factor for HED and high-intensity binge drinking among both males and females. DISCUSSION: Sexual minority females reported lower levels of parental knowledge during adolescence and higher levels of depressive symptoms during the transition to young adulthood than heterosexual females. Both factors were associated with high-risk drinking behavior, suggesting developmentally sensitive opportunities to mitigate sexual orientation disparities in high-risk drinking.

Positive maternal mental health attenuates the associations between prenatal stress and children's internalizing and externalizing symptoms.

Positive maternal mental health can improve perceptions of stressful situations and promote the use of adaptive coping strategies. However, few studies have examined how positive maternal mental health affects children's development. The aims of this study were to examine the associations between positive maternal mental health and children's internalizing and externalizing symptoms, and to ascertain whether positive maternal mental health moderated the associations between prenatal stress and children's internalizing and externalizing symptoms. This study is based on the Norwegian Mother, Father, and Child Cohort Study (MoBa), and comprised 36,584 mother-child dyads. Prenatal stress was assessed using 41 self-reported items measured during pregnancy. Positive maternal mental health (self-efficacy, self-esteem, and enjoyment) was assessed by maternal report during pregnancy and postpartum. Child internalizing and externalizing symptoms were assessed by maternal report at age 5. Structural equation modeling was used for analysis. Maternal self-efficacy, self-esteem, and enjoyment were negatively associated with internalizing and externalizing symptoms in males and females. The association between prenatal stress and internalizing symptoms in males was stronger at low than at high levels of maternal self-esteem and enjoyment, whereas for females, the association was stronger at low than at high levels of maternal self-esteem and self-efficacy. This study provides evidence of associations between positive maternal mental health and children's mental health, and suggests that higher positive maternal mental health may buffer against the impacts of prenatal stress. Positive maternal mental health may represent an important intervention target to improve maternal-child well-being and foster intergenerational resilience.

Adverse childhood experiences and premature mortality through mid-adulthood: A five-decade prospective study.

Background: Adverse childhood experiences (ACEs) can have lasting effects on adult health and survival. In this study, we aimed to examine how the cumulative number and clustering patterns of ACEs were related to premature mortality. Methods: Participants (N=46 129; 45% White, 48% Black; 49·5% females) were offspring (born in 1959-1966) of participants enrolled in the Collaborative Perinatal Project (CPP). We conducted latent class analysis to examine the clustering patterns of ACEs assessed between children's birth and age seven. We also calculated the cumulative ACE scores of 13 individual ACEs. Cox regression models were used to examine the associations of ACE clusters and scores with risk of premature mortality from adolescence to mid-adulthood. Findings: At the start of the follow-up for mortality in 1979, participants were 12-20 years old (Mean=15·99 years), and within the 38-year follow-up through 2016, 3 344 deaths were observed among the 46 129 CPP offspring. Five latent classes of ACEs were identified. Compared to children with Low Adversity (48% of the sample), children in Family Instability (9%, HR=1·28, 95%CI 1·07-1·53), Poverty & Crowded Housing (21%, HR=1·41, 95%CI 1·24-1·62), and Poverty & Parental Separation (19%, HR=1·50, 95%CI 1·33-1·68) classes had higher hazards of premature mortality. In addition, children with 2 (HR=1·27, 95%CI 1·14-1·41), 3 (HR=1·29, 95%CI 1·15-1·45), and 4+ (HR=1·45, 95%CI 1·30-1·61) ACEs had higher hazards of mortality than those with no ACE. The clusters of Poverty & Crowded Housing (HR=1·28, 95%CI 1·10-1·49) and Poverty & Parental Separation (HR=1·23, 95%CI 1·02-1·48) remained associated with higher risk of premature mortality, beyond the cumulative risk of higher number of ACEs (HR=1·05, 95%CI 1·01-1·08). Interpretation: About half of the CPP cohort experienced early life adversities that clustered into four distinct patterns, which were associated with different risk of premature mortality. It is important to deepen our understanding of how specific clusters of childhood adversities affect health and premature mortality to better inform approaches to prevention and interventions.

The developmental origins of suicide mortality: a systematic review of longitudinal studies.

Suicide prevention efforts generally target acute precipitants of suicide, though accumulating evidence suggests that vulnerability to suicide is partly established early in life before acute precipitants can be identified. The aim of this systematic review was to synthesize evidence on early life vulnerability to suicide beginning in the prenatal period and extending through age 12. We searched PubMed, Embase, PsycNet, Web of Science, Scopus, Social Services Abstracts, and Sociological Abstracts for prospective studies published through January 2021 that investigated early life risk factors for suicide mortality. The search yielded 13,237 studies; 54 of these studies met our inclusion criteria. Evidence consistently supported the link between sociodemographic (e.g., young maternal age at birth, low parental education, and higher birth order), obstetric (e.g., low birth weight), parental (e.g., exposure to parental death by external causes), and child developmental factors (e.g., exposure to emotional adversity) and higher risk of suicide death. Among studies that also examined suicide attempt, there was a similar profile of risk factors. We discuss a range of potential pathways implicated in these associations and suggest that additional research be conducted to better understand how early life factors could interact with acute precipitants and increase vulnerability to suicide.

Association of Maternal Caffeine Consumption During Pregnancy With Child Growth.

Importance: Greater caffeine consumption in pregnancy is associated with reduced birth size, but potential associations with childhood growth are unclear. Objective: To evaluate the associations of pregnancy caffeine and paraxanthine measures with child growth in a contemporary cohort with low caffeine consumption and a historical cohort with high caffeine consumption. Design, Setting, and Participants: The Environmental Influences on Child Health Outcomes cohort of the National Institute of Child Health and Human Development Fetal Growth Studies (ECHO-FGS; 10 sites, 2009-2013) was a pregnancy cohort with 1 child measurement between ages 4 and 8 years (follow-up in 2017-2019). The Collaborative Perinatal Project (CPP) was a pregnancy cohort (12 sites, 1959-1965) with child follow-up through 8 years (1960-1974). The current secondary analysis was conducted in 2021 and 2022. Exposures: Concentrations of caffeine and its primary metabolite, paraxanthine, were quantified from plasma (ECHO-FGS) and serum (CPP) collected in the first trimester. Cut points for analyses were defined by quartiles in ECHO-FGS and quintiles in CPP. Main Outcomes and Measures: Child z scores for body mass index, weight, and height were evaluated, as well as fat mass index and percentage and obesity risk measured at 1 time between age 4 and 8 years in ECHO-FGS. In a secondary analysis of the CPP cohort, child z scores and obesity risk longitudinally through age 8 years were evaluated. Results: In ECHO-FGS (median caffeine intake <50 mg/d), 788 children (mean [SD] age, 6.8 [1.0] years; 411 boys [52.2%]) of women in the fourth vs first quartile of plasma caffeine concentrations had lower height z scores (ß = -0.21; 95% CI, -0.41 to -0.02), but differences in weight z scores were only observed in the third quartile (ß = -0.27; 95% CI, -0.47 to -0.07). In CPP, beginning at age 4 years, 1622 children (805 boys [49.7%]) of women in the highest caffeine quintile group had lower height z scores than their peers from the lowest group, with the gap widening with each successive year of age (ß = -0.16 [95% CI, -0.31 to -0.01] at 4 years; ß = -0.37 [95% CI, -0.57 to -0.16] at 8 years). There were slight reductions in weight at ages 5 to 8 years for children in the third vs first caffeine quintile (ß = -0.16 to -0.22). Results were consistent for paraxanthine concentrations in both cohorts. Conclusions and Relevance: Intrauterine exposure to increasing levels of caffeine and paraxanthine, even in low amounts, was associated with shorter stature in early childhood. The clinical implication of reductions in height and weight is unclear; however, the reductions were apparent even with levels of caffeine consumption below clinically recommended guidelines of less than 200 mg per day.

Prenatal origins of suicide mortality: A prospective cohort study in the United States.

Most suicide research focuses on acute precipitants and is conducted in high-risk populations. Yet, vulnerability to suicide is likely established years prior to its occurrence. In this study, we aimed to investigate the risk of suicide mortality conferred by prenatal sociodemographic and pregnancy-related factors. Offspring of participants (N = 49,853) of the Collaborative Perinatal Project, a U.S. population-based cohort of pregnancies enrolled between 1959 and 1966, were linked to the U.S. National Death Index to determine their vital status by the end 2016. We examined associations between sociodemographic factors during pregnancy, pregnancy complications, labor and delivery complications, and neonatal complications with suicide death coded according to ICD-9/10 criteria. By the end of 2016, 3,555 participants had died. Of these, 288 (214 males, 74 females) died by suicide (incidence rate = 15.6 per 100,000 person-years, 95% Confidence Interval [CI] = 13.9-17.5). In adjusted models, male sex (Hazard Ratio [HR] = 2.98, CI: 2.26-3.93), White race (HR = 2.14, CI = 1.63-2.83), low parental education (HR = 2.23, CI = 1.38-3.62), manual parental occupation (HR = 1.38, CI = 1.05-1.82), being a younger sibling (HR = 1.52, CI = 1.10-2.11), higher rates of pregnancy complications (HR = 2.36, CI = 1.08-5.16), and smoking during pregnancy (HR = 1,28, CI = 0.99-1.66) were independently associated with suicide risk, whereas birth and neonatal complications were not. Consistent with the developmental origins of psychiatric disorders, vulnerability to suicide mortality is established early in development. Both sociodemographic and pregnancy factors play a role in this risk, which underscores the importance of considering life course approaches to suicide prevention, possibly including provision of high-quality prenatal care, and alleviating the socioeconomic burdens of mothers and families.

Gestational age at term delivery and children's neurocognitive development.

BACKGROUND: Preterm birth is associated with lower neurocognitive performance. However, whether children's neurodevelopment improves with longer gestations within the full-term range (37-41 weeks) is unclear. Given the high rate of obstetric intervention in the USA, it is critical to determine whether long-term outcomes differ for children delivered at each week of term. METHODS: This secondary analysis included 39 199 live-born singleton children of women who were admitted to the hospital in spontaneous labour from the US Collaborative Perinatal Project (1959-76). At each week of term gestation, we evaluated development at 8 months using the Bayley Scales of Infant Development, 4 years using the Stanford-Binet IQ (SBIQ) domains and 7 years using the Wechsler Intelligence Scales for Children (WISC) and Wide-Range Achievement Tests (WRAT). RESULTS: Children's neurocognitive performance improved with each week of gestation from 37 weeks, peaking at 40 or 41 weeks. Relative to those delivered at 40 weeks, children had lower neurocognitive scores at 37 and 38 weeks for all assessments except SBIQ and WISC Performance IQ. Children delivered at 39 weeks had lower Bayley Mental (ß = -1.18; confidence interval -1.77, -0.58) and Psychomotor (ß = -1.18; confidence interval -1.90, -0.46) scores. Results were similar for within-family analyses comparing siblings, with the addition of lower WRAT scores at 39 weeks. CONCLUSIONS: The improvement in development scores across assessment periods indicates that each week up to 40 or 41 weeks of gestation is important for short- and long-term cognitive development, suggesting 40-41 weeks may be the ideal delivery window for optimal neurodevelopmental outcomes.

Advancing the Social Epidemiology Mission of the American Journal of Epidemiology.

Social epidemiology is concerned with how social forces influence population health. Rather than focusing on a single disease (as in cancer or cardiovascular epidemiology) or a single type of exposure (e.g., nutritional epidemiology), social epidemiology encompasses all the social and economic determinants of health, both historical and contemporary. These include features of social and physical environments, the network of relationships in a society, and the institutions, politics, policies, norms and cultures that shape all of these forces. This commentary presents the perspective of several editors at the Journal with expertise in social epidemiology. We articulate our thinking to encourage submissions to the Journal that: 1) expand knowledge of emerging and underresearched social determinants of population health; 2) advance new empirical evidence on the determinants of health inequities and solutions to advance health equity; 3) generate evidence to inform the translation of research on social determinants of health into public health impact; 4) contribute to innovation in methods to improve the rigor and relevance of social epidemiology; and 5) encourage critical self-reflection on the direction, challenges, successes, and failures of the field.

Sexual Minority Status and Age of Onset of Adolescent Suicide Ideation and Behavior.

OBJECTIVES: To determine if sexual minority adolescents have earlier onset of suicidality and faster progressions from ideation to plan and attempt than heterosexual adolescents. METHODS: A population-based longitudinal cohort of 1771 adolescents participated in the NEXT Generation Health Study. Participants reported sexual minority status (defined by sexual attraction) in 2010-2011 and retrospectively reported age at onset of suicidality in 2015-2016. RESULTS: Sexual minority adolescents (5.8% of weighted sample) had higher lifetime risk of suicide ideation (26.1% vs 13.0%), plan (16.6% vs 5.4%), and attempt (12.0% vs 5.4%) than heterosexual adolescents. Survival analyses adjusted for demographic characteristics and depressive symptoms revealed positive associations of sexual minority status with time to first onset of suicide ideation (hazard ratio [HR] = 1.77; 95% confidence interval [CI] 1.03-3.06) and plan (HR = 2.69; 95% CI 1.30-5.56). The association between sexual minority status and age at onset of suicide attempt was stronger at age <15 (HR = 3.26; 95% CI 1.25-8.47) than age ≥15 (HR = 0.59; 95% CI 0.21-1.66). The association between sexual minority status and progression from ideation to plan was stronger in the same year of first ideation (HR = 2.01; 95% CI 1.07-3.77) than ≥1 year after first ideation (HR = 1.33; 95% CI 0.26-6.77). CONCLUSIONS: Sexual minority adolescents had earlier onset of suicidality and faster progression from suicide ideation to plan than heterosexual adolescents. The assessment of sexual minority status in routine pediatric care has the potential to inform suicide risk screening, management, and intervention efforts among early sexual minority adolescents.

Impact of prenatal maternal cytokine exposure on sex differences in brain circuitry regulating stress in offspring 45 years later.

Stress is associated with numerous chronic diseases, beginning in fetal development with in utero exposures (prenatal stress) impacting offspring's risk for disorders later in life. In previous studies, we demonstrated adverse maternal in utero immune activity on sex differences in offspring neurodevelopment at age seven and adult risk for major depression and psychoses. Here, we hypothesized that in utero exposure to maternal proinflammatory cytokines has sex-dependent effects on specific brain circuitry regulating stress and immune function in the offspring that are retained across the lifespan. Using a unique prenatal cohort, we tested this hypothesis in 80 adult offspring, equally divided by sex, followed from in utero development to midlife. Functional MRI results showed that exposure to proinflammatory cytokines in utero was significantly associated with sex differences in brain activity and connectivity during response to negative stressful stimuli 45 y later. Lower maternal TNF-α levels were significantly associated with higher hypothalamic activity in both sexes and higher functional connectivity between hypothalamus and anterior cingulate only in men. Higher prenatal levels of IL-6 were significantly associated with higher hippocampal activity in women alone. When examined in relation to the anti-inflammatory effects of IL-10, the ratio TNF-α:IL-10 was associated with sex-dependent effects on hippocampal activity and functional connectivity with the hypothalamus. Collectively, results suggested that adverse levels of maternal in utero proinflammatory cytokines and the balance of pro- to anti-inflammatory cytokines impact brain development of offspring in a sexually dimorphic manner that persists across the lifespan.

Associations between depression subtype and functional impairment and treatment utilization in a national sample of adolescents.

BACKGROUND: Prior studies have characterized distinct major depressive episode (MDE) subtypes among adults, yet limited evidence exists regarding variation in MDE during adolescence. METHODS: Using 2008-2016 National Survey of Drug Use and Health data, latent class analysis (LCA) was used to characterize depression subtypes (based on symptom presentation) among 9,896 youth ages 12-17 with recent first-onset MDE. Logistic regression was used to estimate associations of MDE subtype with functional outcomes and treatment utilization, adjusting for demographic characteristics and depression severity (i.e., number of MDE diagnostic criteria and recurrence status) RESULTS: A 5-class LCA model provided optimal fit. Three distinct categories of MDE symptoms generally clustered together, which we termed "somatic," "cognitive," and "self-worth;" classes were differentiated by distinct combinations of symptoms across these 3 categories. Subtypes were characterized as: Highly Symptomatic (39% of youth); Somatic & Cognitive (24%), Somatic (22%), Diffuse Symptoms (8%), and Somatic & Self-Worth (6%). The majority of youth reported at least moderate impairment across multiple domains; subtype was a significant predictor of functional impairment. Only 34% of youth received any past-year depression-related treatment; treatment utilization was significantly higher for MDE subtypes with the highest prevalences of suicidal ideation. LIMITATIONS: Due to cross-sectional data, we cannot establish causal directionality. CONCLUSIONS: Subtype was significantly predictive of functional impairment and treatment utilization, above and beyond number of MDE diagnostic criteria or recurrence status. Understanding distinct profiles of adolescent depression, as well as potential differential associations with impairment, can inform prevention, diagnosis, and treatment of depression among youth.

Childhood disadvantage, neurocognitive development and neuropsychiatric disorders: Evidence of mechanisms.

PURPOSE OF REVIEW: Children living in socioeconomically disadvantaged households have excess risks of neurodevelopmental and neuropsychiatric problems. The purpose of this review is to synthesize evidence for mechanisms that may contribute to these excess risks. RECENT FINDINGS: The majority of the 60 studies included in our review focused on children's neurocognitive development and behavioural problems. About half conducted mediation analyses of factors in the family and neighbourhood environments, including access to resources (e.g. cognitive inputs within the home environment) and exposure to stressors (e.g. negative parenting practices), as well as neurobiological embedding of childhood disadvantage. In addition, many studies conducted moderation analyses of factors that were hypothesized to interact with (i.e. exacerbate or mitigate) the harmful effects of childhood disadvantage. SUMMARY: Many of the factors that contribute to the excess risk of neurodevelopmental and neuropsychiatric problems among children in disadvantaged households are potentially modifiable (e.g. cognitively stimulating materials, parental language input, cultural resources, parental stress and psychopathology, negative parenting, neighbourhood violence). If their causality is ultimately established, they could be targets for the prevention and reduction of disparities. The continued search for mechanisms should not detract from work to reduce and hopefully eliminate children's exposure to disadvantage.

Resilience Factors in the Association Between Depressive Symptoms and Suicidality.

PURPOSE: To investigate whether life satisfaction and optimism might reduce the risk of suicidal thoughts and behaviors among adolescents with depressive symptoms. METHODS: Participants were 1,904 youth from the NEXT Generation Health Study, a national sample of U.S. adolescents, followed over 7 years from 2009/2010 to 2015/2016. Longitudinal latent profile analysis and logistic regressions were conducted. RESULTS: We identified three subgroups of adolescents with different patterns of depressive symptoms across the first six waves: "Low" (40%), "Mild" (42%), and "Moderate to Severe" (18%). The Moderate to Severe (OR = 14.47, 95% CI [6.61, 31.66]) and Mild (OR = 3.90, 95% CI [2.22, 6.86]) depression profiles had significantly higher odds of developing suicidality than the Low depression profile. Both life satisfaction and optimism moderated the association between depressive symptom profile and suicidality. The difference in suicidality risk between the Mild and Low depression profiles was significantly attenuated at high versus low levels of life satisfaction, with a difference of -.08, 95% CI [-.14, -.03]. In addition, the difference in suicidality risk between the Moderate to Severe and Low depression profiles was attenuated at high versus low levels of optimism, with a difference of -.11, 95% CI [-.21, -.01]. CONCLUSIONS: For adolescents transitioning to young adulthood, resilience factors such as life satisfaction and optimism may buffer against suicidality risk in the face of mild or moderate to severe depressive symptoms.