The genetic architecture of youth anxiety: a study protocol.

BACKGROUND: Anxiety disorders are the most common psychiatric problems among Canadian youth and typically have an onset in childhood or adolescence. They are characterized by high rates of relapse and chronicity, often resulting in substantial impairment across the lifespan. Genetic factors play an important role in the vulnerability toward anxiety disorders. However, genetic contribution to anxiety in youth is not well understood and can change across developmental stages. Large-scale genetic studies of youth are needed with detailed assessments of symptoms of anxiety disorders and their major comorbidities to inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. METHODS: The Genetic Architecture of Youth Anxiety (GAYA) study is a Pan-Canadian effort of clinical and genetic experts with specific recruitment sites in Calgary, Halifax, Hamilton, Toronto, and Vancouver. Youth aged 10-19 (n = 13,000) will be recruited from both clinical and community settings and will provide saliva samples, complete online questionnaires on demographics, symptoms of mental health concerns, and behavioural inhibition, and complete neurocognitive tasks. A subset of youth will be offered access to a self-managed Internet-based cognitive behavioral therapy resource. Analyses will focus on the identification of novel genetic risk loci for anxiety disorders in youth and assess how much of the genetic risk for anxiety disorders is unique or shared across the life span. DISCUSSION: Results will substantially inform early intervention or preventative strategies and suggest novel targets for therapeutics and personalization of care. Given that the GAYA study will be the biggest genomic study of anxiety disorders in youth in Canada, this project will further foster collaborations nationally and across the world.

Childhood exposure to pyrethroids and neurodevelopment in Canadian preschoolers.

BACKGROUND: Pyrethroid insecticides are used both residentially and agriculturally and their toxicity targets the nervous system of insects. They might also interfere with development and function of the human brain. A few epidemiological studies suggest that exposure to pyrethroids may be associated with neurobehavioral problems in children but there is little data on potential associations with cognitive outcomes. Furthermore, many studies showed that the neurotoxic effects of several pesticides are modified by sex, hence, considerations of potential sex-differences are important to investigate. OBJECTIVE: To study the cross-sectional association between urinary levels of pyrethroid metabolites and neurodevelopment, including neurobehavioral and cognitive outcomes, in preschool-age children, and to examine whether sex might modify these associations. METHODS: We used data from a follow-up examination of the Maternal-Infant Research on Environmental Chemicals (MIREC), the MIREC Child Development study (MIREC-CD Plus) on children at age 3-4 years living in 6 Canadian cities. For each participant, we collected a urine sample for measurements of pyrethroids metabolites (cis-DBCA, cis-DCCA, trans-DCCA, 3-PBA, 4-F-3-PBA). We assessed neurodevelopment with the Wechsler Primary and Preschool Scale of Intelligence-III (WPPSI-III) and two scales of the Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P). Parents reported children's behavior using the Behavior Assessment System for Children-2 (BASC-2) and the Social Responsiveness Scale-2 (SRS-2). We examined associations between children's urinary pyrethroid metabolite concentrations and neurodevelopmental scores with multiple linear regression models, adjusting for confounders, in boys and girls separately. RESULTS: The study included 179 children (mean age: 3.2 y, range 2.8-4.0). The detection frequencies were high for most pyrethroid metabolites (83-100%), but lower for 4-F-3-PBA (36%). Higher concentrations of cis-DBCA were significantly associated with lower verbal, performance and full-scale IQ scores in boys (e.g., for a 2-fold increase in cis-DBCA, ß = -2.0; 95% CI: -3.4, -0.6 for full-scale IQ). In girls, the only metabolite associated with cognitive scores was 3-PBA, which was associated with lower verbal IQ scores (ß = -1.3, 95% CI: -2.6, -0.1). For neurobehavioral outcomes in boys, there were associations between poorer BASC-2 Adaptive Skills scores with higher concentrations of cis-DCCA (ß = -1.6, 95% CI: -2.3, -0.9), trans-DCCA (ß = -1.5, 95% CI: -2.2, -0.8), 3-PBA (ß = -1.7, 95% CI: -2.5, -0.9), and sum of pyrethroid metabolites (ß = -1.8, 95% CI: -2.6, -0.9). In girls, we observed a significant association between higher concentration of cis-DCCA and better BASC-2 Adaptive Skills score (ß = 1.0; 95% CI, 0.2, 1.8), but not with other urinary pyrethroids metabolites. Scores on the SRS-2 and BRIEF-P were not associated with pyrethroid metabolites. CONCLUSION: There were associations between some pyrethroid pesticide metabolites and indicators of neurodevelopmental disorder, especially among boys. These associations are in agreement with previous studies and could suggest that exposure to pyrethroid pesticides represents a risk of potential toxicity for the cognitive development of children, and a risk for behavioral development. However, the cross-sectional nature of this study limits causal inferences.

Assessing the feasibility of an intervention for adolescents and parents transitioning out of paediatric eating disorder services: A mixed methods study.

OBJECTIVE: To assess the feasibility of a new intervention designed to support adolescents and parents in the transition from paediatric eating disorder (ED) treatment to adult mental health services. METHOD: Pre-transition adolescents with EDs, and their parents, were invited to complete up to five transition intervention components over 3 months. A mixed methods design was used to assess intervention feasibility, comprised of acceptability and preliminary effectiveness. A single-arm pre-post design was used to collect and analyse quantitative survey and feasibility data. Individual qualitative interviews and written reflections were collected and analysed using content analysis. RESULTS: This study yielded a 33% (10/31) recruitment rate and 68% (13/19) retention rate. On average, participants completed 75% of the expected components in under 3 months, with varied completion of each expected intervention component (40%-100%). Participants found the intervention convenient and helpful. Parents reported a significant decrease in guilt (Z = -2.02, p = 0.04, d = -0.83). By 1-month post-transition, three adolescents transitioned to interim supports and none started specialist adult treatment. CONCLUSIONS: Although this transition intervention did not demonstrate adequate feasibility, its acceptability and effectiveness should be evaluated after an update based on participant feedback. Other solutions to bridge the transition gap for adolescents with EDs should continue to be identified. CLINICAL TRIAL REGISTRATION NUMBER: NCT04888273.

Acute mental health service use in adolescents with suicidal thoughts and behaviours: Impact on outpatient care.

INTRODUCTION: Youth with suicidal thoughts and behaviours often present to acute emergency care settings for assessment. Timely outpatient follow up may reduce return acute care visits. The primary aim of our study was to describe clinical and contextual differences between youth who do and do not use acute care once connected to outpatient services. METHODS: A 24-month retrospective chart review of suicidal youth aged 13-16 (n = 45) presenting for outpatient mental health treatment. Youth who used acute services during the study period (ASU) or did not (non-ASU) were compared on demographic, risk profile, and mental health service use. RESULTS: The mean age of participants was 14.6 years (73% female). Suicide risk profile at baseline did not differ between groups, but was significantly higher in ASU youth at 24 months. There were more youth in service at the end of the study period in the ASU group compared to the non-ASU group (11% vs 55%). CONCLUSION: Youth who do continue to access acute services may be at higher risk of suicidality even after outpatient treatment. Although it is unclear whether this is linked to outpatient engagement, it raises further questions about this population and how they respond to community based mental healthcare.

Frontal EEG asymmetry moderates the relation between borderline personality disorder features and feelings of social rejection in adolescents.

Although associations among borderline personality disorder (BPD), social rejection, and frontal EEG alpha asymmetry scores (FAA, a neural correlate of emotion regulation and approach-withdrawal motivations) have been explored in different studies, relatively little work has examined these relations during adolescence in the same study. We examined whether FAA moderated the relation between BPD features and rejection sensitivity following a validated social exclusion paradigm, Cyberball. A mixed, clinical-community sample of 64 adolescents (females = 62.5%; Mage = 14.45 years; SD = 1.6; range = 11-17 years) completed psychodiagnostic interviews and a self-report measure of BPD (Time 1). Approximately two weeks later (Time 2), participants completed a resting EEG recording followed by Cyberball. FAA moderated the relation between BPD features and overall feelings of rejection following Cyberball: individuals with greater relative left FAA had the highest and lowest feelings of social rejection depending on whether they had high and low BPD feature scores, respectively. Results remained after controlling for age, sex, gender, depression, and BPD diagnosis. These results suggest that FAA may moderate the relation between BPD features and social rejection, and that left frontal brain activity at rest may be differentially associated with those feelings in BPD. Findings are discussed in terms of the link between left frontal brain activity in the regulation and dysregulation of social approach behaviors, characteristic of BPD.

Maternal pregnancy diet, postnatal home environment and executive function and behavior in 3- to 4-y-olds.

BACKGROUND: Optimal maternal nutrition during pregnancy has been linked to better cognitive and behavioral development in children. However, its influence on the effects of suboptimal postnatal exposures like reduced stimulation and support in the home is not known. OBJECTIVES: To examine the effect of maternal pregnancy diet on executive function and/or behavioral development in children raised in suboptimal home environments. METHODS: Data were provided by 808 mother-infant dyads from the Canadian Maternal-Infant Research on Environmental Chemicals-Child Development study. Maternal pregnancy diet was self-reported using the Healthy Eating Index 2010 questionnaire. Stimulation and support in the home was assessed using the Home Observation for Measurement of the Environment (HOME) when children were 3-4 y old. Child executive function was reported by mothers at this age using the Behavior Rating Inventory of Executive Functioning-Preschool Edition, and child behavior was assessed using the Behavior Assessment System for Children-2nd Edition. We examined the interaction of maternal pregnancy diet and postnatal HOME scores on child executive function and behavior using linear regression adjusted for maternal education, postpartum depression, prepregnancy BMI, and smoking. RESULTS: Maternal pregnancy diet was associated with an increasingly positive association with child working memory (ß: 0.21; 95% CI: 0.82, 3.41; P = 0.001), planning (ß: 0.17; 95% CI: 0.38, 2.84; P = 0.007), and adaptability (ß: -0.13; 95% CI: -1.72, -0.08; P = 0.032) as levels of postnatal stimulation decreased. CONCLUSIONS: The positive association of maternal pregnancy diet quality and executive function and adaptability in 3- to 4-y-olds appeared to increase with decreasing levels of postnatal stimulation and support. These results suggest that overall maternal pregnancy diet could be linked to better child neurodevelopment in families experiencing barriers to providing stimulation and support to children in their home.

External validation of a bifactor model of oppositional defiant disorder.

Dimensions of irritability and defiant behavior, though correlated within the structure of ODD, convey separable developmental risks through adolescence and adulthood. Irritability predicts depression and anxiety, whereas defiant behavior is a precursor to antisocial outcomes. Previously we demonstrated that a bifactor model comprising irritability and defiant behavior dimensions, in addition to a general factor, provided the best-fitting structure of ODD symptoms in five large datasets. Herein we extend our previous work by externally validating the bifactor model of ODD using multiple regression and multivariate behavior genetic analyses. We used parent ratings of DSM IV ODD symptoms, and symptom dimensions for ADHD (i.e., inattention and hyperactivity-impulsivity), conduct disorder (CD), depression/dysthymia, and generalized anxiety disorder (GAD) from 846 6-18-year-old twin pairs. We found that the ODD irritability factor was associated only with depression/dysthymia and GAD and the ODD defiant behavior factor was associated only with inattention, hyperactivity-impulsivity, and CD, whereas the ODD general factor was associated with all five symptom dimensions. Multivariate behavior genetic analyses found all five symptom dimensions shared genetic influences in common with the ODD general, irritability, and defiant behavior factors. In contrast, the defiant behavior factor shared genetic influences uniquely with inattention and hyperactivity-impulsivity, whereas the irritability factor shared genetic influences uniquely with depression/dysthymia and GAD, but not vice versa. This suggests that genes that influence irritability in early childhood also predispose to depression and anxiety in adolescence and adulthood. These multivariate genetic findings also support the external validity of the three ODD dimensions at the etiological level. Our study provides additional support for subtyping ODD based on these symptom dimensions, as in the revisions in the ICD-11, and suggests potential mechanisms underlying the development from ODD to behavioral or affective disorders.

Examining the predictive association of irritability with borderline personality disorder in a clinical sample of female adolescents.

OBJECTIVES: Borderline personality disorder (BPD) is a disorder associated with emotion dysregulation and is common in clinical samples of adolescents. The identification and delineation of BPD from other disorders is important, yet methods for effectively screening for BPD are lacking. Here, we examine whether irritability can be used as a screening item for BPD in adolescents at risk for the disorder. METHODS: We assessed Diagnostic Interview for Borderline-Revised and Development of Well-Being Assessment scores in a clinical sample of female adolescents ages 12-17 (n = 78) to identify BPD and group cases into 'irritable' and 'non-irritable' mood types, respectively. We then examined the prevalence of irritability and its predictive association with BPD. RESULTS: The prevalence of BPD was 26% (n = 20). There was a significant association between irritable mood and BPD, specifically (χ2 (1) = 17.740, p < 0.001). Irritability was endorsed in all (n = 20) BPD cases (sensitivity: 100%), while in non-BPD cases (n = 58), irritability was endorsed in 27 (specificity: 53%; positive predictive value: 0.33; and negative predictive value: 1.0). CONCLUSION: Irritability is a highly sensitive screening item for BPD in adolescents. The absence of irritability in an adolescent may be an important clinical tool to rule out BPD. © 2020 John Wiley & Sons, Ltd.

Maternal Pregnancy Diet Quality Is Directly Associated with Autonomic Nervous System Function in 6-Month-Old Offspring.

BACKGROUND: Many pregnant women are consuming diets of poor overall quality. Although many studies have linked poor prenatal diet quality to an increased risk of specific diseases in offspring, it is not known if exposure to poor prenatal diet affects core neurophysiological regulatory systems in offspring known to lie upstream of multiple diseases. OBJECTIVE: We aimed to examine the association between prenatal diet quality and autonomic nervous system (ANS) function in infants at 6 mo of age. METHODS: Data from 400 women (aged >18 y, with uncomplicated pregnancies) and their infants participating in the Maternal-Infant Research on Environmental Chemicals-Infant Development cohort were used to investigate links between prenatal diet quality and infant ANS function at 6 mo of age. Prenatal diet quality was assessed using the Healthy Eating Index (2010), calculated from a validated FFQ completed by women during the first trimester. Infant ANS function was measured using 2 assessments of heart rate variability (HRV) including root mean square of successive differences (RMSSD) and SD of N-N intervals (SDNN). Associations were analyzed before and after adjustment for socioeconomic status, maternal depression symptoms, maternal cardiometabolic dysfunction, breastfeeding, and prenatal smoking. RESULTS: Poorer prenatal diet quality was associated with lower infant HRV assessed using RMSSD (B: 0.07; 95% CI: 0.01, 0.13; R2 = 0.013) and SDNN (B: 0.18; 95% CI: 0.02, 0.35; R2 = 0.011). These associations remained significant after adjustment for confounding variables [RMSSD: B: 0.09; 95% CI: 0.003, 0.18; squared semipartial correlation (sp2) = 0.14 and SDNN B: 0.24; 95% CI: 0.0, 0.49; sp2 = 0.13]. CONCLUSIONS: In a large cohort study, poorer prenatal diet quality was associated with lower offspring HRV, a marker of decreased capacity of the ANS to respond adaptively to challenge. Therefore, poor prenatal diet may play a significant role in the programming of multiple organ systems and could increase general susceptibility to disease in offspring.

A systematic review of interventions for treatment resistant major depressive disorder in adolescents.

To update a comparative effectiveness review (1980-2011) of treatments for adolescents whose depressive episode or disorder (MDE/MDD) did not respond to one or more trials of SSRI antidepressants. MEDLINE, Cochrane Central, PsychINFO, Cochrane Database of Systematic Reviews, EMBASE, CINAHL, and AMED were searched in addition to the grey literature. We spanned May 2011 to September 1, 2017 and included only articles in English. 11 new studies were reviewed based on the criteria of having tested a comparative treatment in adolescents with MDD or MDE who were confirmed to have failed one or more SSRI trials. Data were extracted using standardized forms and a reference guide in DistillerSR; a second reviewer verified the accuracy of the data fields and discrepancies were resolved by consensus. One trial (N = 29) found a small benefit of escalating doses of fluoxetine and the treatment of adolescent depression study (TORDIA, N = 334) found significant benefits of combined SSRI or venlafaxine treatment with CBT for most outcomes. No new studies were identified since the previous review (2012). One trial is currently registered that will be a cross over trial of rTMS; other registered trials are open label. Multiple secondary data analyses of TORDIA have identified important predictors of treatment response and relapse. No new comparative studies were identified since the original review. Trials are desperately needed to identify new treatments for youth with SSRI resistant MDD. These youth should not be deemed as treatment resistant until completing one or two failed trials of SSRI combined with evidence-based psychotherapy.

An evaluation of clinical practice guidelines for self-harm in adolescents: The role of borderline personality pathology.

Borderline personality disorder (BPD) is associated with high rates of self-harm, suicide attempts, and death by suicide in adults and adolescents. Screening and assessment of BPD in self-harming adolescents could be an important clinical intervention. The aim of this article was to identify whether existing clinical practice guidelines (CPGs) for the care of self-harm in adolescents considered the screening, diagnosis, and/or treatment of BPD. Previous work by Courtney, Duda, Szatmari, Henderson, and Bennett (2018) used Preferred Reporting Items for Systematic Reviews and Meta-Analyses methods to identify 10 CPGs relevant to self-harm in children and adolescents. In this study, the 10 CPGs were reviewed for content about screening, assessment, and/or treatment recommendations for adolescents with BPD. Out of the 10 CPGs, 4 acknowledged the association between BPD and self-harm in adolescents. There was minimal to no guidance provided in the CPGs regarding specific screening, assessment, or treatment strategies for BPD. This may be due to the lack of evidence for efficacy and effectiveness of screening for BPD, thereby limiting the development of guideline recommendations. Studies that examine the impact of screening for BPD in clinical settings are needed. In the interim, CPGs should cite the prevalence of BPD in adolescents who self-harm and reference research showing the benefit of treatment with dialectical behavioral therapy for self-harm and suicide attempts in youth with BPD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Borderline Personality Disorder and Disordered Eating Behaviour: The Mediating Role of Rejection Sensitivity.

OBJECTIVE: To examine the relationship between disordered eating behaviour and Borderline Personality Disorder (BPD) in a clinical population of adolescent girls. We hypothesized that BPD and disordered eating would be strongly associated and that this association would be partially mediated by rejection sensitivity. METHOD: Participants were 73 female patients aged 11-18 presenting for mental health treatment at an outpatient psychiatry clinic in a large metropolitan hospital. Measures used in this study include the Diagnostic Interview for Borderline Personality Disorder-Revised, Borderline Personality Questionnaire and The Short Screen for Eating Disorders. RESULTS: Youth with BPD had significantly more disordered eating behaviour compared to controls. Of the nine facets of BPD, eight were highly correlated with disordered eating, suggesting important shared variance between the constructs of BPD and disordered eating. This study also demonstrated that rejection sensitivity significantly mediated the relationship between BPD symptoms and disordered eating. CONCLUSIONS: This paper provides a novel association between a diagnosis of BPD in adolescents and disordered eating and the mediation effect of rejection sensitivity. These findings suggest that disordered eating should be screened in BPD samples and interventions targeting rejection sensitivity may be of clinical use.

OBJECTIF: Examiner la relation entre le trouble du comportement alimentaire et le trouble de la personnalité limite (TPL) dans une population clinique d'adolescentes. Nous avons émis l'hypothèse que le TPL et le trouble alimentaire seraient fortement associés et que cette association serait partiellement soumise à la médiation de la sensibilité au rejet. MÉTHODE: Les participantes étaient 73 patientes âgées de 11 à 18 ans qui consultaient pour un traitement de santé mentale à une clinique psychiatrique ambulatoire d'un grand hôpital métropolitain. Les mesures utilisées dans cette étude comprennent l'entrevue diagnostique pour le trouble de la personnalité limite (révisé), le questionnaire de la personnalité limite et le dépistage rapide des troubles alimentaires. RÉSULTATS: Les adolescentes souffrant du TPL avaient significativement plus de troubles du comportement alimentaire comparativement aux témoins. Sur les 9 dimensions du TPL, 8 étaient fortement corrélées au trouble alimentaire, ce qui suggère une importante variance partagée entre les structures du TPL et du trouble alimentaire, Cette étude a aussi démontré que la sensibilité au rejet est un médiateur significatif de la relation entre les symptômes du TPL et le trouble alimentaire. CONCLUSIONS: Cet article offre une nouvelle association entre un diagnostic de TPL chez des adolescentes et un trouble alimentaire, et l'effet de médiation de la sensibilité au rejet. Ces résultats suggèrent qu'il faudrait dépister les troubles alimentaires dans les échantillons souffrant de TPL, et que des interventions ciblant la sensibilité au rejet pourraient être d'une utilité clinique.

Prevalence and Correlates of Youth Suicidal Ideation and Attempts: Evidence from the 2014 Ontario Child Health Study.

OBJECTIVES: To present the 12-month prevalence and correlates of suicidal ideation and attempts in a sample of youth in Ontario. METHODS: Data come from the 2014 Ontario Child Health Study, a provincially representative survey of families with children in Ontario. Youth aged 14 to 17 y ( n = 2,396) completed a computer-assisted, self-administered questionnaire in their home to assess the occurrence of suicidal ideation, suicidal attempts, and associated correlates, including non-suicidal self-injury, mental disorders, substance use, peer victimization and exposure to child maltreatment. Socio-demographic information was collected from the parent. Logistic regression models were used to identify correlates that distinguished between youth reporting: 1) no suicidal ideation or attempts, 2) suicidal ideation but no attempts, and 3) suicidal ideation and attempts. RESULTS: The 12-month prevalence of suicidal ideation and attempts was 8.1% and 4.3%, respectively. All clinical and behavioural correlates were significantly higher among youth reporting suicidal ideation or attempts, as compared with non-suicidal youth. In adjusted models, depression and non-suicidal self-injury were each independently associated with elevated odds of suicidal ideation (OR = 4.84 and 4.19, respectively) and suicidal attempt (OR = 7.84 and 22.72, respectively). Among youth who reported suicidal ideation, the only variable that differentiated youth who attempted suicide v. those who did not, in adjusted models, was non-suicidal self-injury (OR = 3.89). CONCLUSIONS: Suicidal ideation and attempts are common among youth in Ontario, often co-occurring with mental disorders and high-risk behaviours. These findings underscore the need for effective prevention and intervention strategies, particularly for youth depression and non-suicidal self-injury.

Longitudinal associations between non-suicidal self-injury and borderline personality disorder in adolescents: a literature review.

BACKGROUND: Borderline personality disorder (BPD) in adolescent samples is similar to BPD in adults concerning clinical characteristics. A notable difference is that adolescents with BPD - and adolescents in general - are more likely than adults to present with acute symptoms such as non-suicidal self-injury (NSSI) and suicidal behaviours. BPD is the only disorder in the Diagnostic and Statistical Manual- 5th Edition that includes a criterion of NSSI. Additionally, NSSI is purported to be a developmental precursor of BPD under the biosocial developmental model. Though much cross-sectional data have illustrated the robust association of adolescent NSSI and BPD, no review to date has summarized the longitudinal associations between these phenomena. The aim of this literature review was to summarize what is known about the longitudinal associations between adolescent NSSI and BPD symptoms. Information on the developmental course of NSSI in relation to BPD would be helpful to clinicians, as the rate of NSSI is high in adolescent populations, and research indicates early, possibly BPD-specific interventions are imperative. METHODS: A literature search was conducted using Embase, MEDLINE, and PsycINFO databases and cited reference searches. Criteria included studies of adolescents (age ≤ 18 at baseline) from either epidemiological or clinical samples, incorporating a longitudinal design, with predictors and outcomes of interest, including both NSSI and BPD diagnosis/symptoms/traits. RESULTS: Six independent samples were identified that matched our search criteria.The articles were grouped and reported on separately by population type (epidemiological vs. clinical), and directionality of relations. We identified two epidemiological and four clinical samples. Five samples examined the longitudinal associations of NSSI preceding BPD, three samples measured BPD in adolescence (baseline age ≤ 18), and two of those samples measured BPD at baseline. Both epidemiological studies revealed significant longitudinal associations between NSSI and later BPD/BPD symptoms; however, they differed notably in their methodologies hindering data synthesis across studies. In the clinical studies, findings of the association or predictive relations were not consistent. This is potentially due to differing methodologies, or differences in treatment effectiveness and responsiveness across the samples. CONCLUSIONS: This review highlights the paucity of data that are available examining the longitudinal association between NSSI and BPD within adolescent samples. Thus, it is not possible to reliably comment on how NSSI and BPD are related over time. Future studies will benefit from the measurement of BPD symptoms in very early adolescence, and concurrent measurement of NSSI as well as other forms of suicidal behaviours across adolescence.

Neurodevelopment in 3-4 year old children exposed to maternal hyperglycemia or adiposity in utero.

BACKGROUND: Prenatal exposure to maternal metabolic complications has been linked to offspring neurodevelopmental problems. However, no studies investigating these links have examined the role of maternal prenatal diet. AIMS: To determine if prenatal exposure to maternal adiposity or hyperglycemia is associated with neurodevelopmental problems in 3-4 year old children, and if links persist following adjustment for confounding variables, including prenatal diet. METHOD: 808 mother-child pairs from the Maternal-Infant Research on Environmental Chemicals-Child Development Plus cohort were used to examine associations between pre-pregnancy body mass index (BMI), hyperglycemia and offspring verbal, performance and full-scale IQ scores, as well as internalizing and externalizing problems. Associations were examined before and after adjustment for prenatal diet along with home environment, maternal depression, education and prenatal smoking. Semi-partial correlations were examined post-hoc to assess the impact of each confounder in the adjusted models. RESULTS: In the unadjusted models, BMI and hyperglycemia predicted lower verbal and full-scale IQ. BMI was also linked to externalizing problems. However, associations were not significant after adjustment. In adjusted models, post-hoc analysis revealed that prenatal diet and home environment accounted for significant variance in verbal and full-scale IQ. The home environment and maternal depression accounted for significant variance in externalizing problems. CONCLUSION: In the adjusted models, maternal metabolic complications were not associated with offspring neurodevelopment. Even while adjusting for well-known risk factors for adverse offspring cognition (home environment, maternal depression), we show for the first time that maternal prenatal diet is an important confounder of the links between maternal metabolic complications and offspring cognition.