Association of maternal fish consumption and ω-3 supplement use during pregnancy with child autism-related outcomes: results from a cohort consortium analysis.

BACKGROUND: Prenatal fish intake is a key source of omega-3 (ω-3) polyunsaturated fatty acids needed for brain development, yet intake is generally low, and studies addressing associations with autism spectrum disorder (ASD) and related traits are lacking. OBJECTIVE: This study aimed to examine associations of prenatal fish intake and ω-3 supplement use with both autism diagnosis and broader autism-related traits. METHODS: Participants were drawn from 32 cohorts in the Environmental influences on Child Health Outcomes Cohort Consortium. Children were born between 1999 and 2019 and part of ongoing follow-up with data available for analysis by August 2022. Exposures included self-reported maternal fish intake and ω-3/fish oil supplement use during pregnancy. Outcome measures included parent report of clinician-diagnosed ASD and parent-reported autism-related traits measured by the Social Responsiveness Scale (SRS)-second edition (n = 3939 and v3609 for fish intake analyses, respectively; n = 4537 and n = 3925 for supplement intake analyses, respectively). RESULTS: In adjusted regression models, relative to no fish intake, fish intake during pregnancy was associated with reduced odds of autism diagnosis (odds ratio: 0.84; 95% confidence interval [CI]: 0.77, 0.92), and a modest reduction in raw total SRS scores (ß: -1.69; 95% CI: -3.3, -0.08). Estimates were similar across categories of fish consumption from "any" or "less than once per week" to "more than twice per week." For ω-3 supplement use, relative to no use, no significant associations with autism diagnosis were identified, whereas a modest relation with SRS score was suggested (ß: 1.98; 95% CI: 0.33, 3.64). CONCLUSIONS: These results extend previous work by suggesting that prenatal fish intake, but not ω-3 supplement use, may be associated with lower likelihood of both autism diagnosis and related traits. Given the low-fish intake in the United States general population and the rising autism prevalence, these findings suggest the need for better public health messaging regarding guidelines on fish intake for pregnant individuals.

Examining the association between prenatal cannabis exposure and child autism traits: A multi-cohort investigation in the environmental influences on child health outcome program.

This study examined the association between prenatal cannabis exposure and autism spectrum disorder (ASD) diagnoses and traits. A total sample of 11,570 children (ages 1-18; 53% male; 25% Hispanic; 60% White) from 34 cohorts of the National Institutes of Health-funded environmental influences on child health outcomes consortium were included in analyses. Results from generalized linear mixed models replicated previous studies showing that associations between prenatal cannabis exposure and ASD traits in children are not significant when controlling for relevant covariates, particularly tobacco exposure. Child biological sex did not moderate the association between prenatal cannabis exposure and ASD. In a large sample and measuring ASD traits continuously, there was no evidence that prenatal cannabis exposure increases the risk for ASD. This work helps to clarify previous mixed findings by addressing concerns about statistical power and ASD measurement.

Self-reported neighborhood stressors and sleep quality among Puerto Rican young adults.

OBJECTIVE: To examine the association between changes in self-reported neighborhood stressors and sleep quality and determine whether this varied by sociocultural context among Puerto Rican young adults. METHODS: Data come from the Boricua Youth Study Health Assessment, a sample of Puerto Rican young adults from San Juan, Puerto Rico, and South Bronx, New York (n = 818; mean age=22.9years). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). Neighborhood social stressors (disorder, social cohesion, and safety) were parent-reported in childhood and self-reported in young adulthood and categorized into: low in childhood/young adulthood (reference group), high in childhood/low in young adulthood, low in childhood/high in young adulthood, and high in childhood/young adulthood. Sociocultural context was based on participant residence during childhood (San Juan vs. South Bronx). RESULTS: Adjusting for sociodemographic factors, living with high neighborhood stressors in both childhood and young adulthood (prevalence ratios=1.30, 95% CI: 1.01, 1.66) was associated with overall poor sleep (PSQI score >5). Among PSQI components, living with high neighborhood stressors in young adulthood only or in both time periods was associated with worse subjective sleep quality and daytime dysfunction. Additionally, there were various associations between the neighborhood stressor measures and PSQI components. Results did not differ by sociocultural context. CONCLUSION: Findings suggest that living with high levels of neighborhood stressors during childhood and young adulthood may have a cumulative adverse impact on sleep quality in young adulthood.

Demographic and health characteristics associated with fish and n-3 fatty acid supplement intake during pregnancy: results from pregnancy cohorts in the ECHO programme.

OBJECTIVE: n-3 fatty acid consumption during pregnancy is recommended for optimal pregnancy outcomes and offspring health. We examined characteristics associated with self-reported fish or n-3 supplement intake. DESIGN: Pooled pregnancy cohort studies. SETTING: Cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) consortium with births from 1999 to 2020. PARTICIPANTS: A total of 10 800 pregnant women in twenty-three cohorts with food frequency data on fish consumption; 12 646 from thirty-five cohorts with information on supplement use. RESULTS: Overall, 24·6 % reported consuming fish never or less than once per month, 40·1 % less than once a week, 22·1 % 1-2 times per week and 13·2 % more than twice per week. The relative risk (RR) of ever (v. never) consuming fish was higher in participants who were older (1·14, 95 % CI 1·10, 1·18 for 35-40 v. <29 years), were other than non-Hispanic White (1·13, 95 % CI 1·08, 1·18 for non-Hispanic Black; 1·05, 95 % CI 1·01, 1·10 for non-Hispanic Asian; 1·06, 95 % CI 1·02, 1·10 for Hispanic) or used tobacco (1·04, 95 % CI 1·01, 1·08). The RR was lower in those with overweight v. healthy weight (0·97, 95 % CI 0·95, 1·0). Only 16·2 % reported n-3 supplement use, which was more common among individuals with a higher age and education, a lower BMI, and fish consumption (RR 1·5, 95 % CI 1·23, 1·82 for twice-weekly v. never). CONCLUSIONS: One-quarter of participants in this large nationwide dataset rarely or never consumed fish during pregnancy, and n-3 supplement use was uncommon, even among those who did not consume fish.

Prenatal sleep health and risk of offspring ADHD symptomatology and associated phenotypes: a prospective analysis of timing and sex differences in the ECHO cohort.

Background: Sleep difficulties are common in pregnancy, yet poor prenatal sleep may be related to negative long-term outcomes for the offspring, including risk for attention-deficit/hyperactivity disorder (ADHD). Existing studies are few and have not examined timing of exposure effects or offspring sex moderation. We thus aimed to test the hypotheses that poor sleep health in pregnancy is associated with increased risk for ADHD symptoms and offspring sleep problems at approximately 4 years of age. Methods: Participants were 794 mother-child dyads enrolled in the NIH Environmental Influences on Child Health Outcomes Study (ECHO). Participants self-reported on sleep duration, quality, and disturbances during pregnancy and on children's ADHD symptoms and sleep problems on the Child Behaviour Checklist. Findings: Pregnant participants were 32.30 ± 5.50 years and children were 46% female. 44 percent of pregnant participants identified as Hispanic or Latine; 49% identified as White. Second-trimester sleep duration was associated with offspring ADHD symptoms (b = -0.35 [95% CI = -0.57, -0.13], p = 0.026), such that shorter duration was associated with greater symptomatology. Poorer sleep quality in the second trimester was also associated with increased ADHD symptomatology (b = 0.66 [95% CI = 0.18, 1.14], p = 0.037). Greater sleep disturbances in the first trimester were associated with offspring ADHD (b = 1.03 [95% CI = 0.32, 1.03], p = 0.037) and in the second trimester with sleep problems (b = 1.53 [95% CI = 0.42, 2.92], p = 0.026). We did not document substantial offspring sex moderation. Interpretation: Poor prenatal sleep health, particularly quality and duration in the second trimester, may be associated with offspring risk of neurodevelopmental disorders and sleep problems in early childhood. Further research is needed to understand mechanisms, yet our study suggests that prenatal maternal sleep may be a modifiable target for interventions aimed at optimizing early neurodevelopment. Funding: NIH grants U2COD023375, U24OD023382, U24OD023319, UH3OD023320, UH3OD023305, UH3OD023349, UH3OD023313, UH3OD023272, UH3OD023328, UH3OD023290, K08MH117452 and NARSAD Young Investigator Award 28545.

Mental Health in a Changing Planet.

This Viewpoint discusses climate change and its effect on mental health.

Maternal childhood maltreatment: associations to offspring brain volume and white matter connectivity.

The deleterious effects of adversity are likely intergenerational, such that one generation's adverse experiences can affect the next. Epidemiological studies link maternal adversity to offspring depression and anxiety, possibly via transmission mechanisms that influence offspring fronto-limbic connectivity. However, studies have not thoroughly disassociated postnatal exposure effects nor considered the role of offspring sex. We utilized infant neuroimaging to test the hypothesis that maternal childhood maltreatment (CM) would be associated with increased fronto-limbic connectivity in infancy and tested brain-behavior associations in childhood. Ninety-two dyads participated (32 mothers with CM, 60 without; 52 infant females, 40 infant males). Women reported on their experiences of CM and non-sedated sleeping infants underwent MRIs at 2.44 ± 2.74 weeks. Brain volumes were estimated via structural MRI and white matter structural connectivity (fiber counts) via diffusion MRI with probabilistic tractography. A subset of parents (n = 36) reported on children's behaviors at age 5.17 ± 1.73 years. Males in the maltreatment group demonstrated greater intra-hemispheric fronto-limbic connectivity (b = 0.96, p= 0.008, [95%CI 0.25, 1.66]), no differences emerged for females. Fronto-limbic connectivity was related to somatic complaints in childhood only for males (r = 0.673, p = 0.006). Our findings suggest that CM could have intergenerational associations to offspring brain development, yet mechanistic studies are needed.

Maternal Mental Health and Offspring Brain Development: An Umbrella Review of Prenatal Interventions.

The idea that risk for psychiatric disorders may be transmitted intergenerationally via prenatal programming places interest in the prenatal period as a critical moment during which intervention efforts may have a strong impact, yet studies testing whether prenatal interventions also protect offspring are limited. The present umbrella review of systematic reviews and meta-analyses (SRMAs) of randomized controlled trials aimed to synthesize the available evidence and highlight promising avenues for intervention. Overall, the literature provides mixed and limited evidence in support of prenatal interventions. Thirty SRMAs were included. Of the 23 SRMAs that reported on prenatal depression interventions, 16 found a significant effect (average standard mean difference = -0.45, SD = 0.25). Similarly, 13 of the 20 SRMAs that reported on anxiety outcomes documented significant reductions (average standard mean difference = -0.76, SD = 0.95 or -0.53/0.53 excluding one outlier). Only 4 SRMAs reported child outcomes, and only 2 (of 10) analyses showed significant effects of prenatal interventions (massage and telephone support on neonatal resuscitation [relative risk = 0.43] and neonatal intensive care unit admissions [relative risk = 0.91]). Notably missing, perhaps due to our strict inclusion criteria (inclusion of randomized controlled trials only), were interventions focusing on key facets of prenatal health (e.g., whole diet, sleep). Structural interventions (housing, access to health care, economic security) were not included, although initial success has been documented in non-SRMAs. Most notably, none of the SRMAs focused on offspring mental health or neurodevelopmental outcomes. Given the possibility that interventions deployed in this period will positively impact the next generation, randomized trials that focus on offspring outcomes are urgently needed.

Racial/ethnic disparities in subjective sleep duration, sleep quality, and sleep disturbances during pregnancy: an ECHO study.

In the United States, racial/ethnic minoritized groups experience worse sleep than non-Hispanic Whites (nHW), but less is known about pregnant people. This is a key consideration since poor sleep during pregnancy is common and associated with increased risk of adverse perinatal outcomes. This study reports the prevalence of subjective sleep measures in a multi-racial/ethnic pregnant population from the Environmental influences on Child Health Outcomes (ECHO) program. Participants' self-reported race and ethnicity were grouped into: nHW, non-Hispanic Black/African American (nHB/AA), Hispanic, non-Hispanic Asian (nHA). Analyses examined trimester-specific (first (T1), second (T2), third (T3)) nocturnal sleep duration, quality, and disturbances (Pittsburgh Sleep Quality Index and ECHO maternal sleep health questionnaire). Linear or multinomial regressions estimated the associations between race/ethnicity and each sleep domain by trimester, controlling for body mass index and age, with nHW as reference group. We repeated analyses within maternal education strata. nHB/AA participants reported shorter sleep duration (T2: ß = -0.55 [-0.80,-0.31]; T3: ß = -0.65 [-0.99,-0.31]) and more sleep disturbances (T2: ß = 1.92 [1.09,2.75]; T3: ß = 1.41 [0.09,2.74]). Hispanic participants reported longer sleep duration (T1: ß = 0.22 [0.00004,0.44]; T2: ß = 0.61 [0.47,0.76]; T3: ß = 0.46 [0.22,0.70]), better sleep quality (Reference group: Very good. Fairly good T1: OR = 0.48 [0.32,0.73], T2: OR = 0.36 [0.26,0.48], T3: OR = 0.31 [0.18,0.52]. Fairly bad T1: OR = 0.27 [0.16,0.44], T2: OR = 0.46 [0.31, 0.67], T3: OR = 0.31 [0.17,0.55]), and fewer sleep disturbances (T2: ß = -0.5 [-1.0,-0.12]; T3: ß = -1.21 [-2.07,-0.35]). Differences persisted within the high-SES subsample. Given the stark racial/ethnic disparities in perinatal outcomes and their associations with sleep health, further research is warranted to investigate the determinants of these disparities.

The Intergenerational Impact of Structural Racism and Cumulative Trauma on Depression.

Depression among individuals who have been racially and ethnically minoritized in the United States can be vastly different from that of non-Hispanic White Americans. For example, African American adults who have depression rate their symptoms as more severe, have a longer course of illness, and experience more depression-associated disability. The purpose of this review was to conceptualize how structural racism and cumulative trauma can be fundamental drivers of the intergenerational transmission of depression. The authors propose that understanding risk factors for depression, particularly its intergenerational reach, requires accounting for structural racism. In light of the profoundly different experiences of African Americans who experience depression (i.e., a more persistent course of illness and greater disability), it is critical to examine whether an emerging explanation for some of these differences is the intergenerational transmission of this disorder due to structural racism.

Neural Activity and Emotion Socialization as Predictors of Later Emotion Regulation Difficulties in Children With and Without Hyperactivity/Impulsivity.

OBJECTIVE: This study examined emotion socialization and neural activity during frustration as predictors of emotion regulation (ER) difficulties, and the interplay of emotion socialization and neural activity, in children with and without hyperactivity/impulsivity (H/I). METHOD: At Time 1, neural activity (P1, N2, P3) during a frustration task, H/I symptoms, and emotion socialization were assessed in 68 children (aged 4-7 years old). At Time 2 (1.5-2 years later), child-report, maternal-report, and observation measures of ER difficulties were assessed. RESULTS: H/I symptoms moderated the relation between predictors and ER difficulties; there were significant relations for children with high, but not low, levels of H/I. Further, as emotion socialization quality increased, relations between event-related potentials and later ER difficulties became weaker. CONCLUSION: The processes underlying ER difficulties differ for children with H/I symptoms. High quality emotion socialization may have a protective effect for children whose neural patterns indicate risk for later ER difficulties.

Association of Comorbid Behavioral and Medical Conditions With Cannabis Use Disorder in Pregnancy.

Importance: Prenatal cannabis use continues to increase, yet studies of the demographic, psychiatric, and medical characteristics associated with cannabis use in pregnancy are limited by size and use of self-report, and often do not consider cannabis use disorder (CUD) or concomitant substance use disorders (SUDs). Understanding the factors associated with CUD in pregnancy is paramount for designing targeted interventions. Objective: To examine the prevalence of co-occurring psychiatric and medical conditions of US pregnant individuals hospitalized with and without CUD by concomitant SUDs. Design, Setting, and Participants: The study analyzed restricted hospital discharge data from the 2010 to 2018 Healthcare Cost and Utilization Project State Inpatient Databases in 35 states. Data were analyzed from January to August 2021. Weighted linear regressions tested whether the prevalence of psychiatric and medical conditions differed between individuals with and without a CUD diagnosis at hospitalization. Inpatient hospitalizations of pregnant patients aged 15 to 44 years with a CUD diagnosis were identified. Pregnant patients aged 15 to 44 years without a CUD diagnosis were identified for comparison. Patients were further stratified based on concomitant SUD patterns: (1) other SUDs, including at least 1 controlled substance; (2) other SUDs, excluding controlled substances; and (3) no other SUDs. Exposures: CUD in pregnancy. Main Outcomes and Measures: Prevalence of demographic characteristics, psychiatric disorders (eg, depression and anxiety), and medical conditions (eg, epilepsy and vomiting). Results: The sample included 20 914 591 hospitalizations of individuals who were pregnant. The mean (SD) age was 28.24 (5.85) years. Of the total number of hospitalizations, 249 084 (1.19%) involved CUD and 20 665 507 (98.81%) did not. The proportion of prenatal hospitalizations involving CUD increased from 0.008 in 2010 to 0.02 in 2018. Analyses showed significant differences in the prevalence of almost every medical and psychiatric outcome examined between hospitalizations with and without CUD diagnoses, regardless of concomitant SUDs. Elevations were seen in depression (0.089; 95% CI, 0.083-0.095), anxiety (0.072; 95% CI, 0.066-0.076), and nausea (0.036; 95% CI, 0.033-0.040]) among individuals with CUD only at hospitalization compared with individuals with no SUDs at hospitalization. Conclusions and Relevance: Considerable growth was observed in the prevalence of CUD diagnoses among individuals hospitalized prenatally and in the prevalence of depression, anxiety, nausea, and other conditions in individuals with CUD at hospitalization. This study highlights the need for more screening, prevention, and treatment, particularly in populations with co-occurring CUD and psychiatric disorders. Research on the determinants and outcomes associated with CUD during pregnancy is needed to guide clinicians, policy makers, and patients in making informed decisions.

Behavioral and Neural Markers of Emotion Competence as Predictors of Later Psychopathology in Children With and Without Hyperactive/Impulsive Symptoms.

Objective: We examined behavioral and neural markers of emotion competence in young children as predictors of psychopathology, and as mediators of the relation between hyperactivity/impulsivity (H/I) and psychopathology. Method: At Time 1 (T1), children (n = 49; ages 4-7 years) with and without H/I symptoms completed a frustration task. Frustration, observed emotion, and neural activity (P1, N2, and P3 event-related potentials) were measured. Symptoms of psychopathology were collected 18 months later (Time 2; T2). Results: T1 lability, negative affect, and frustration predicted T2 depression and aggression symptomatology, controlling for T1 symptoms. Children with difficulty allocating neural resources during and after frustration were at risk for depression, aggression, and anxiety symptoms, controlling for earlier symptoms. P3 amplitudes during recovery mediated the relation between H/I and later depression. Conclusion: Markers of emotion competence contribute to psychopathology symptoms, particularly in children at risk for attention-deficit/hyperactivity disorder (ADHD). Emotion competence skills may be useful intervention targets.

ADHD and risk for subsequent adverse childhood experiences: understanding the cycle of adversity.

BACKGROUND: Children with adverse childhood experiences (ACEs) are more likely to develop Attention-Deficit/Hyperactivity Disorder (ADHD). The reverse relationship - ADHD predicting subsequent ACEs - is vastly understudied, although it may be of great relevance to underserved populations highly exposed to ACEs. METHODS: Participants were 5- to 15-year-olds (48% females) with (9.9%) and without ADHD (DSM-IV criteria except age of onset) in a longitudinal population-based study of Puerto Rican youth. In each wave (3 yearly assessments, W1-3), ten ACEs (covering parental loss and maladjustment and child maltreatment) were examined, plus exposure to violence. Logistic regression models examined ADHD (including subtypes) and subsequent risk for ACEs. Also considered were interactions by age, sex, number of W1 ACEs, and recruitment site. RESULTS: Children with W1 ADHD were more likely to experience subsequent adversity (OR: 1.63; 95% CI: 1.12-2.37) accounting for child age, sex, public assistance, maternal education, site, disruptive behavior disorders, and W1 ACEs. Inattentive (OR: 2.00; 95% CI: 1.09-3.66), but not hyperactive/impulsive or combined ADHD, predicted future ACEs. CONCLUSIONS: ADHD predicts subsequent risk for ACEs, and the inattentive presentation may confer the most risk. Inattentive presentations could pose a bigger risk given differences in symptom persistence, latency to access to treatment, and treatment duration. The present study suggests a pathway for the perpetuation of adversity, where bidirectional relationships between ADHD and ACEs may ensnare children in developmental pathways predictive of poor outcomes. Understanding the mechanism underlying this association can help the development of interventions that interrupt the cycle of adversity exposure and improve the lives of children with ADHD.

Association of Prenatal Acetaminophen Exposure Measured in Meconium With Risk of Attention-Deficit/Hyperactivity Disorder Mediated by Frontoparietal Network Brain Connectivity.

Importance: Despite evidence of an association between prenatal acetaminophen exposure and attention-deficit/hyperactivity disorder (ADHD) in offspring, the drug is not contraindicated during pregnancy, possibly because prior studies have relied on maternal self-report, failed to quantify acetaminophen dose, and lacked mechanistic insight. Objective: To examine the association between prenatal acetaminophen exposure measured in meconium (hereinafter referred to as meconium acetaminophen) and ADHD in children aged 6 to 7 years, along with the potential for mediation by functional brain connectivity. Design, Setting, and Participants: This prospective birth cohort study from the Centre Hospitalier Université de Sherbrooke in Sherbrooke, Québec, Canada, included 394 eligible children, of whom 345 had meconium samples collected at delivery and information on ADHD diagnosis. Mothers were enrolled from September 25, 2007, to September 10, 2009, at their first prenatal care visit or delivery and were followed up when children were aged 6 to 7 years. When children were aged 9 to 11 years, resting-state brain connectivity was assessed with magnetic resonance imaging. Data for the present study were collected from September 25, 2007, to January 18, 2020, and analyzed from January 7, 2019, to January 22, 2020. Exposures: Acetaminophen levels measured in meconium. Main Outcomes and Measures: Physician diagnosis of ADHD was determined at follow-up when children were aged 6 to 7 years or from medical records. Resting-state brain connectivity was assessed with magnetic resonance imaging; attention problems and hyperactivity were assessed with the Behavioral Assessment System for Children Parent Report Scale. Associations between meconium acetaminophen levels and outcomes were estimated with linear and logistic regressions weighted on the inverse probability of treatment to account for potential confounders. Causal mediation analysis was used to test for mediation of the association between prenatal acetaminophen exposure and hyperactivity by resting-state brain connectivity. Results: Among the 345 children included in the analysis (177 boys [51.3%]; mean [SD] age, 6.58 [0.54] years), acetaminophen was detected in 199 meconium samples (57.7%), and ADHD was diagnosed in 33 children (9.6%). Compared with no acetaminophen, detection of acetaminophen in meconium was associated with increased odds of ADHD (odds ratio [OR], 2.43; 95% CI, 1.41-4.21). A dose-response association was detected; each doubling of exposure increased the odds of ADHD by 10% (OR, 1.10; 95% CI, 1.02-1.19). Children with acetaminophen detected in meconium showed increased negative connectivity between frontoparietal and default mode network nodes to clusters in the sensorimotor cortices, which mediated an indirect effect on increased child hyperactivity (14%; 95% CI, 1%-26%). Conclusions and Relevance: Together with the multitude of other cohort studies showing adverse neurodevelopment associated with prenatal acetaminophen exposure, this work suggests caution should be used in administering acetaminophen during pregnancy. Research into alternative pain management strategies for pregnant women could be beneficial.

Differences in brain structure and function in children with the FTO obesity-risk allele.

OBJECTIVE: Noncoding alleles of the fat mass and obesity-associated (FTO) gene have been associated with obesity risk, yet the underlying mechanisms remain unknown. Risk allele carriers show alterations in brain structure and function, but previous studies have not disassociated the effects of genotype from those of body mass index (BMI). METHODS: Differences in brain structure and function were examined in children without obesity grouped by their number of copies (0,1,2) of the FTO obesity-risk single-nucleotide polymorphism (SNP) rs1421085. One hundred five 5- to 10-year-olds (5th-95th percentile body fat) were eligible to participate. Usable scans were obtained from 93 participants (15 CC [homozygous risk], 31 CT [heterozygous] and 47 TT [homozygous low risk]). RESULTS: Homozygous C allele carriers (CCs) showed greater grey matter volume in the cerebellum and temporal fusiform gyrus. CCs also demonstrated increased bilateral cerebellar white matter fibre density and increased resting-state functional connectivity between the bilateral cerebellum and regions in the frontotemporal cortices. CONCLUSIONS: This is the first study to examine brain structure and function related to FTO alleles in young children not yet manifesting obesity. This study lends support to the notion that the cerebellum may be involved in FTO-related risk for obesity, yet replication and further longitudinal study are required.

Family Environment, Neurodevelopmental Risk, and the Environmental Influences on Child Health Outcomes (ECHO) Initiative: Looking Back and Moving Forward.

The family environment, with all its complexity and diverse components, plays a critical role in shaping neurodevelopmental outcomes in children. Herein we review several domains of the family environment (family socioeconomic status, family composition and home environment, parenting behaviors and interaction styles, parental mental health and functioning, and parental substance use) and discuss how these domains influence neurodevelopment, with particular emphasis on mental health outcomes. We also highlight a new initiative launched by the National Institutes of Health, the Environmental influences on Child Health Outcomes (ECHO) program. We discuss the role that ECHO will play in advancing our understanding of the impact of the family environment on children's risk for psychiatric outcomes. Lastly, we conclude with important unanswered questions and controversies in this area of research, highlighting how ECHO will contribute to resolving these gaps in our understanding, clarifying relationships between the family environment and children's mental health.