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Suicide is a major, preventable public health problem. The general factor of psychopathology ("p" factor) might help improve detection and prediction of individuals at risk for suicide. This cross-sectional proof-of-concept study tests whether the p-factor score is associated with suicidal thoughts and behaviors (STB) better than a depression scale alone. Youth (N = 841; mean age 18.02

Inflammatory processes are associated with mood disorders, but data on pediatric patients are scarce. The aim of this study was to investigate a possible association between elevated neutrophil/lymphocyte ratio (NLR) - a marker of inflammation and mood polarity (manic/depressed) in adolescents, admitted between 2010 and 2015 due to a mood disorder episode and to an adolescent inpatient ward. Electronic medical records of 305 patients (aged 10-19 years, 60.6% males) admitted during the study period due to a mood disorder episode were reviewed. Of these, 63 were diagnosed with manic episodes and 242 with depressive episodes. Multivariate analyses were used to compare NLR between and within the two groups, covarying for age, sex, and antipsychotic use. NLR was significantly higher in the manic episode group compared with the depression one. Moreover, in inpatients with multiple hospitalizations, the NLR was higher during their manic episodes than that during their nonmanic states. These results suggest that, as has been reported in adults with bipolar disorder, inflammatory mechanisms may be involved in adolescents' mood disorders as well, particularly in the manic episodes. Thus, clinicians may consider adding anti-inflammatories as part of the treatment of these patients.

To provide a detailed description of the sonographic appearance and development of various fetal structures of the midbrain and hindbrain (MBHB) during the early second trimester, and to evaluate the impact of the frequency of the transvaginal sonography (TVS) transducer on the early recognition of these structures.This was a retrospective analysis of three-dimensional volumetric datasets of the MBHB from apparently normal fetuses at 14-19 gestational weeks, acquired by TVS in the midsagittal view through the posterior fontanelle. Using a multiplanar approach, we measured the tectal thickness and length, aqueductal thickness, tegmental thickness and width and height of the Blake's pouch (BP) neck. In addition, we assessed the existence of early vermian fissures, the linear shape of the brainstem and the components of the fastigium. The correlation between gestational age according to last menstrual period and sonographic measurements of MBHB structures was evaluated using Pearson's correlation (r). A subanalysis was performed to assess the performance of a 5-9-MHz vs a 6-12-MHz TVS transducer in visualizing the MBHB structures in the early second trimester.Sixty brain volumes were included in the study, obtained at a mean gestational age of 16.2 weeks (range, 14.1-19.0 weeks), with a transverse cerebellar diameter range of 13.0-19.8 mm. We found a strong correlation between gestational age and all MBHB measurements, with the exception of the tectal, tegmental and aqueductal thicknesses, for which the correlation was moderate. There was good-to-excellent intraobserver and moderate-to-good interobserver correlation for most MBHB measurements. We observed that the BP neck was patent in all fetuses between 14 and 18 weeks with decreasing diameter, and that the aqueductal thickness was significantly smaller at ≥ 18 weeks compared with at 16 weeks. The early vermian fissures and the linear shape of the brainstem were present in all fetuses from 14 weeks. We found that, in the early second trimester, the horizontal arm of the presumed 'fastigium' evolves from the fourth ventricular choroid plexus and not the posterior vermis, indicating that this is not the fastigium. Standard- and high-resolution TVS transducers performed similarly in the assessment of MBHB anatomy.Detailed early second-trimester assessment of the MBHB is feasible by transvaginal neurosonography and provides reference data which may help in the early detection of brain pathology involving the MBHB. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

The COVID-19 pandemic has been linked to increased risk for perinatal anxiety and depression among parents, as well as negative consequences for child development. Less is known about how worries arising from the pandemic during pregnancy are related to later child development, nor if resilience factors buffer negative consequences. The current study addresses this question in a prospective longitudinal design. Data was collected from a sub-study (n = 184) of a longitudinal study of pregnant individuals (total n = 1,173). During pregnancy (April 17-July 8, 2020) and the early postpartum period (August 11, 2020-March 2, 2021), participants completed online surveys. At 12 months postpartum (June 17, 2021-March 23, 2022), participants completed online surveys and a virtual laboratory visit, which included parent-child interaction tasks. We found more pregnancy-specific pandemic worries were prospectively related to lower levels of child socioemotional development based on parent report (B=-1.13, SE = .43, p = .007) and observer ratings (B=-0.13, SE = .07, p = .045), but not to parent-reported general developmental milestones. Parental emotion regulation in the early postpartum period moderated the association between pregnancy-specific pandemic worries and child socioemotional development such that pregnancy-specific pandemic worries did not related to worse child socioemotional development among parents with high (B=-.02, SE = .10, t=-.14, p = .89) levels of emotion regulation. Findings suggest the negative consequences of parental worry and distress during pregnancy on the early socioemotional development of children in the context of the COVID-19 pandemic. Results highlight that parental emotion regulation may represent a target for intervention to promote parental resilience and support optimized child development.

Acute stress during pregnancy can have adverse effects on maternal health and increase the risk for postpartum depression and impaired mother-infant bonding. The COVID-19 pandemic represents an acute environmental stressor during which it is possible to explore risk and resilience factors that contribute to postpartum outcomes. To investigate prenatal risk and resilience factors as predictors of postpartum depression and impaired mother-infant bonding, this study recruited a diverse cohort of 833 pregnant women from an urban medical center in Philadelphia, Pennsylvania, and assessed them once during pregnancy in the early phase of the COVID-19 pandemic (April-July 2020) and again at approximately twelve weeks postpartum. Adverse childhood experiences, prenatal depression and anxiety, and COVID-19-related distress predicted a greater likelihood of postpartum depression. Prenatal depression was the only unique predictor of impaired maternal-infant bonding after postpartum depression was controlled for. Women reporting greater emotion regulation, self-reliance, and nonhostile relationships had healthier postpartum outcomes. Policies to increase the number of nonspecialty providers providing perinatal mental health services as well as reimbursement for integrated care and access to mental health screening and care are needed to improve lifelong outcomes for women and their children.

ImportanceMany states in the United States enforce restrictions to reproductive care, with access to abortion remaining a highly divisive issue. Denial of abortion is linked with heightened stress and anxiety among reproductive-aged women. However, no studies have tested whether access to reproductive care is linked to suicide.ObjectiveTo evaluate whether state-level restrictions in access to reproductive care in the United States were associated with suicide rates among reproductive-aged women from 1974 to 2016.Design, Setting, and ParticipantsA longitudinal ecologic study with a difference-in-differences analysis assessed whether annual changes in the enforcement of state-level restrictions to reproductive care were related to annual state-level suicide rates vs rates of death due to motor vehicle crashes. Duration of follow-up varied between different states (range, 4-40 years), contingent on the first year that restrictions were implemented. Models controlled for year and state fixed effects and other relevant demographic and economic factors. Analyses were conducted between December 2021 and January 2022.ExposuresTargeted Regulation of Abortion Providers (TRAP) laws index measuring state-year–level restrictions to reproductive care.Main Outcomes and MeasuresAnnual state-level suicide rates and motor vehicle crash death rates among reproductive-aged women (ages 20-34 years; target group) vs women of postreproductive age (ages 45-64 years; control group).ResultsTwenty-one US states enforced at least 1 TRAP law between 1974 and 2016. Annual rates of death by suicide ranged from 1.4 to 25.6 per 100 000 women of reproductive age to 2.7 to 33.2 per 100 000 women of postreproductive age during the study period (1974-2016). Annual motor vehicle crash death rates among women of reproductive age ranged from 2.4 to 42.9 per 100 000. Enforcement of TRAP laws was associated with higher suicide rates among reproductive-aged women (β = 0.17; 95% CI, 0.03 to 0.32; P = .02) but not women of postreproductive age (β = 0.06; 95% CI, –0.11 to 0.24; P = .47) nor to deaths due to motor vehicle crashes (β = 0.03, 95% CI, –0.04 to 0.11; P = .36). Among reproductive-aged women, the weighted average annual-state level suicide death rate when no TRAP laws were enforced was 5.5 per 100 000. Enforcement of a TRAP law was associated with a 5.81% higher annual rate of suicide than in pre-enforcement years. Findings remained significant when using alternative, broader indices of reproductive care access and different age categorizations.Conclusions and RelevanceIn this study with a difference-in-differences analysis of US women, restrictions on access to reproductive care from 1974 to 2016 were associated with suicide rates among reproductive-aged women. Given the limitations of the ecologic design of this study, further research is needed to assess whether current factors affecting access to reproductive care services are related to suicide risk among women of reproductive age and to inform suicide prevention strategies.

Individual differences in cognition during childhood are associated with important social, physical, and mental health outcomes in adolescence and adulthood. Given that cortical surface arealization during development reflects the brain’s functional prioritization, quantifying variation in the topography of functional brain networks across the developing cortex may provide insight regarding individual differences in cognition. We test this idea by defining personalized functional networks (PFNs) that account for interindividual heterogeneity in functional brain network topography in 9-10 year olds from the Adolescent Brain Cognitive DevelopmentSMStudy. Across matched discovery (n=3,525) and replication (n=3,447) samples, the total cortical representation of fronto-parietal PFNs positively correlated with general cognition. Cross-validated ridge regressions trained on PFN topography predicted cognition across domains, with prediction accuracy increasing along the cortex’s sensorimotor-association organizational axis. These results establish that functional network topography heterogeneity is associated with individual differences in cognition before the critical transition into adolescence.

Background COVID-19 pandemic has major ramifications for global health and economy, with growing concerns about economic recession and implications for mental health. Here we investigated the associations between pandemic-related income loss with financial strain and mental health trajectories over a 1-month course, in two independent cohorts. Methods Two independent studies were conducted in the U.S and in Israel at the beginning of the outbreak (March-April 2020, T1; study I: N = 2904, study II: N = 1267) and at a 1-month follow-up (T2; study I: N = 1318, study II: N = 241). Mixed-effects models were applied to assess associations among COVID-19-related income loss, financial strain, and pandemic-related worries about health, with anxiety and depression, controlling for multiple covariates including pre-COVID-19 income. Results In both studies, income loss and financial strain were associated with greater depressive symptoms at T1, above and beyond T1 anxiety, worries about health, and pre-COVID-19 income. Worsening of income loss was associated with exacerbation of depression at T2 in both studies. Worsening of subjective financial strain was associated with exacerbation of depression at T2 in one study (US). Conclusions Income loss and financial strain were uniquely associated with depressive symptoms and their exacerbation over time, above and beyond pandemic-related anxiety. In times when a myriad of stressors are affecting mental health worldwide, our findings reveal specific links between the economic impact of COVID-19 and psychiatric outcomes.

Background Traumatic stressful events (TSEs) are among the most studied risk factors for subsequent schizotypal symptoms. However, specificity and aggregate effects of trauma exposure on schizotypal symptoms remain unclear. This study investigates these relationships among a community-based sample of US adolescents. Material and methods A sub-sample of 426 adolescents (51.6% female) from the Philadelphia Neurodevelopmental Cohort study were selected for longitudinal follow-up based on presence (n = 209) or absence (n = 217) of psychosis spectrum symptoms (PSS). At baseline, they completed assessments of demographic, TSEs, other psychopathology (e.g., PSS, anxiety, depression, and behavioral disorder) and family history of psychopathology. Schizotypal symptom dimensions (cognitive-perceptual, interpersonal and disorganized) were evaluated approximately two years later. Results More than half of adolescents experienced at least one type of TSE. Adolescents with assaultive trauma reported about 1.5 times as many symptoms on all three schizotypal symptom dimensions, compared to adolescents with non-assaultive TSE, adjusting for demographic and family history variables. No statistical significance was found after further adjusting for other baseline psychopathology (p > 0.05). There was a significant aggregate effect of TSEs on cognitive-perceptual symptoms with small effect size (p Conclusions We found evidence of an association between aggregate TSEs and cognitive-perceptual symptoms, but trauma type was not associated with schizotypal symptom dimensions when controlling for potential confounders. Our findings highlight the importance of considering aggregate TSE effects and potential confounds when examining associations between TSEs and schizotypy. Trauma and psychosis spectrum screening may be important in the effort to provide trauma-informed care.

OBJECTIVES To provide evidence to support the hypothesis that the midline cyst-like fluid collection that is frequently observed on fetal brain ultrasound (US) imaging during the early second trimester represents a normal transient cavum veli interpositi (CVI). METHODS This was a retrospective analysis of 89 three-dimensional normal fetal brain volumes, acquired by transvaginal US imaging in 87 pregnant women between 14 and 17 gestational weeks. The midsagittal view was studied using multiplanar imaging, and the maximum length of the fluid collection located over (dorsal to) the tela choroidea of the third ventricle was measured. We calculated the correlation of the transverse cerebellar diameter (TCD) and of the maximum length of the fluid collection with gestational age according to last menstrual period. Color Doppler images were analyzed to determine the location of the internal cerebral veins with respect to the location of the fluid collection. Reports of the second-trimester anatomy scan at 22-24 weeks were also reviewed. RESULTS Interhemispheric fluid collections of various sizes were found in 55% (49/89) of the volumes (mean length, 5 (range, 3.0-7.8) mm). There was a strong correlation between TCD and gestational age (Pearson's correlation, 0.862; P

Individual differences in cognitive abilities emerge early during development, and children with poorer cognition are at increased risk for adverse outcomes as they enter adolescence. Caregiving plays an important role in supporting cognitive development, yet it remains unclear how specific types of caregiving behaviors may shape cognition, highlighting the need for large-scale studies. In the present study, we characterized replicable yet specific associations between caregiving behaviors and cognition in two large sub-samples of children ages 9-10 years old from the Adolescent Brain Cognitive Development Study

Background Individuals with autism spectrum disorder (ASD) are challenged not only by the defining features of social-communication deficits and restricted repetitive behaviors, but also by a myriad of psychopathology varying in severity. Different cognitive deficits underpin these psychopathologies, which could be subjected to intervention to alter the course of the disorder. Understanding domain-specific mediating effects of cognition is essential for developing targeted intervention strategies. However, the high degree of inter-correlation among different cognitive functions hinders elucidation of individual effects. Methods In the Philadelphia Neurodevelopmental Cohort, 218 individuals with ASD were matched with 872 non-ASD controls on sex, age, race, and socioeconomic status. Participants of this cohort were deeply and broadly phenotyped on neurocognitive abilities and dimensional psychopathology. Using structural equation modeling, inter-correlation among cognitive domains were adjusted before mediation analysis on outcomes of multi-domain psychopathology and functional level. Results While social cognition, complex cognition, and memory each had a unique pattern of mediating effect on psychopathology domains in ASD, none had significant effects on the functional level. In contrast, executive function was the only cognitive domain that exerted a generalized negative impact on every psychopathology domain (p factor, anxious-misery, psychosis, fear, and externalizing), as well as functional level. Conclusions Executive function has a unique association with the severity of comorbid psychopathology in ASD, and could be a target of interventions. As executive dysfunction occurs variably in ASD, our result also supports the clinical utility of assessing executive function for prognostic purposes.

Background The presentation of neurogenetic disorders such as 22q11.2 Deletion Syndrome (22q11.2DS) includes broad neuropsychiatric phenotypes that impact functioning and require assessment and treatment. Like in non-syndromal neuropsychiatric disorders, there is heterogeneity in symptom severity and illness course. The study of risk and resilience in the general population has benefited from measurement tools that parse heterogeneity and guide treatment. Suitability of such tools in neurogenetic disorders has not been examined and is essential to establish as prerequisite for examining whether similar processes modulate psychopathology in these populations. Method We applied the Risk & Resilience Battery assessing intrapersonal, interpersonal, and environmental domains, to 80 patients with 22q11.2DS, 30 from Philadelphia, USA and 50 from Tel-Aviv, Israel. We also evaluated global functioning and obtained self-reports of anxiety and depression. We examined the Risk & Resilience Battery reliability for each factor and used partial correlations to examine relations between the Risk & Resilience Battery factors and clinical measures. Results Across samples, items within each risk and resilience factor showed good to excellent internal consistency. Higher scores on peer victimization, emotion dysregulation, and hostile close relationships were related to reports of anxiety and depression. Higher levels of self-reliance related to lower anxiety while greater security in close relationships related to lower depression. Conclusion The Risk & Resilience Battery can be applied to 22q11.2DS samples and advance Gene X Environment research and interventions.

Objective: Use of risperidone in preschool-aged children is growing, with rising concerns of adverse metabolic consequences. Longitudinal data on risperidone-related weight gain in preschoolers are scarce. We aimed to evaluate changes in body mass index (BMI) that are associated with risperidone treatment in preschoolers. Method: We analyzed naturalistic, longitudinal data on 141 preschool children (112 boys, 29 girls) receiving psychiatric care. Mean patient age at baseline was 5.0 years (SD=0.8) and average follow-up period was 1.3 years (SD=0.8), with >8 mean BMI measurements per patient. We studied the effect of risperidone exposure ( n=78) on age-and-sex-standardized BMI (BMI Z-score) implementing mixed models with random subject intercepts to account for repeated measures, covarying for multiple confounders including demographics, stimulant treatment and psychiatric diagnoses. We employed similar models to study dose and duration effects. Results: Risperidone treatment was significantly associated with an increase in BMI (effect size of exposure=0.45 SD (SE=0.06), t (949)=7.7, pConclusion: Similar to older populations, risperidone treatment in preschoolers is associated with significant weight gain, with evidence for dose effects. Findings provide critical data that can inform clinicians.

OBJECTIVE: Deliberate self-harm (DSH) is a major health concern among adolescents, and is often associated with the need for inpatient psychiatric hospitalization. The aim of this study was to identify clinical and demographic characteristics associated with DSH behavior among adolescents admitted to an acute psychiatric inpatient unit. METHOD: We retrospectively analyzed data from the electronic medical records of consecutive admittances to a single acute adolescent inpatient unit (N=703, mean age 15.2). We compared inpatients with DSH to inpatients without DSH, and further compared within DSH group based on the presence of suicidal intent. RESULTS: Compared to Non-DSH inpatients (N=497), youths admitted following DSH (N=206) were more likely to be female (OR=2.6, 95%CI 1.7–4), currently in depressive exacerbation (OR=2.4, 95%CI 1.6–3.6), with concurrent suicidal ideation (OR=3.9, 95%CI 2.5–5.9), and history of alcohol use (OR=5.6, 95%CI 3.2–9.5). Within DSH youths, no significant clinical differences were identified between those admitted following suicide attempt (N=102) compared to non-suicidal-self-injury (N=104), who were generally younger. CONCLUSIONS: Findings suggest that early detection and intervention of DSH and depressive crisis is warranted, regardless of the self-harm subtype.

Adolescent suicidality (ie, suicidal ideation or attempts) is a major public health concern. Cyberbullying experiences and perpetration have become increasingly prevalent and are associated with mental health burden, but their roles as independent suicidality risk factors remain unclear. Data are needed to clarify their contribution to teen suicidality to inform suicide prevention efforts.To examine whether cyberbullying experiences and perpetration are distinct stressors divergent from other forms of peer aggression experiences in their association with suicidality in early adolescence.This cross-sectional analysis used data collected between July 2018 and January 2021 from the Adolescent Brain Cognitive Development (ABCD) study, a large, diverse sample of US children aged 10 to 13 years.Youth reports of cyberbullying experiences or perpetration.The main outcome was youth-reported suicidality (past or present, as reported in the ABCD 2-year follow-up assessment). Covariates included demographics, established environmental risk and protective factors for youth suicidality, psychopathology, and experiences or perpetration of offline peer aggression.A total of 10 414 ABCD participants were included in this study. Participants had a mean (SD) age of 12.0 (0.7) years and 4962 (47.6%) were female; 796 (7.6%) endorsed suicidality. A total of 930 (8.9%) reported experiencing cyberbullying and 96 (0.9%) reported perpetrating cyberbullying. Of the perpetrators, 66 (69.0%) also endorsed experiencing cyberbullying. Controlling for demographics, experiencing cyberbullying was associated with suicidality (odds ratio [OR], 4.2 [95% CI, 3.5-5.1]; P .001), whereas perpetrating cyberbullying was not (OR, 1.3 [95% CI, 0.8-2.3]; P = .30). Experiencing cyberbullying remained associated with suicidality when accounting for negative life events, family conflict, parental monitoring, school environment, and racial and ethnic discrimination (OR, 2.5 [95% CI, 2.0-3.0]; P .001) and when further covarying for internalizing and externalizing psychopathology (OR, 1.8 [95% CI, 1.4-2.4]; P .001). Both being a target and being a perpetrator of offline peer aggression were associated with suicidality (OR, 1.5 [95% CI, 1.1-2.0] for both), controlling for all covariates described earlier. Cyberbullying experiences remained associated with suicidality (OR, 1.7 [95% CI, 1.3-2.2]; P .001, controlling for all covariates) when included with offline peer aggression experiences and perpetration.In this cross-sectional study, experiencing-but not perpetrating-cyberbullying was associated with suicidality in early adolescence. This association was significant over and above other suicidality risk factors, including offline peer aggression experiences or perpetration. These findings can inform adolescent suicide prevention strategies, and they suggest that clinicians and educational staff working with this population should routinely evaluate for adolescents' experience with cyberbullying.

ObjectiveThe authors used multimodal data collected during pre/early-adolescence in research settings to predict self-report of past suicide attempt (SA) by mid-late adolescence in pediatric care settings. The study further aimed to determine types of data that contribute to the prediction; and to test generalizability of the prediction in an independent sample.MethodsThe authors applied machine learning methods on clinical, neurocognitive and geocoded neighborhood environmental data from the Philadelphia Neurodevelopmental Cohort study (PNC, Mean age 11.1, SD=2.2, 52.3% female and 51.4% Black participants) to predict SA reported ∼5 years later in a community pediatric clinic (n=922, 5.3% SA) or emergency department (n=497, 8.2% SA). The authors compared prediction performance when using all data versus individual data types, then used feature selection algorithms (Lasso, Relief and Random Forest) to identify important predictors and compared performance of models relying on feature subsets.ResultsIn the training dataset, SA prediction was good, reaching AUC=0.75, sensitivity/specificity 0.76/0.77 when relying on feature subsets identified using feature selection pipelines. Use of highest-ranking feature subsets from the training dataset yielded similar prediction in the testing dataset with AUC=0.74, sensitivity/specificity 0.66/0.70. Different algorithms showed different high-ranking features, but overall multiple data domains were represented among the highest-ranking predictors selected by each algorithm.ConclusionsThese findings provide evidence for feasibility of predicting youth SA using data collected at a single timepoint early in life in a diverse cohort. Results encourage incorporation of multiple data types including neurocognitive and geocoded environmental measures in machine learning SA prediction pipelines.

Individual differences in cognitive abilities emerge early during development, and children with poorer cognition are at increased risk for adverse outcomes as they enter adolescence. Caregiving plays an important role in supporting cognitive development, yet it remains unclear how specific types of caregiving behaviors may shape cognition, highlighting the need for large-scale studies. In the present study, we characterized replicable yet specific associations between caregiving behaviors and cognition in two large sub-samples of children ages 9-10 years old from the Adolescent Brain and Cognitive Development (ABCD) study. Across both discovery and replication sub-samples, we found that child reports of caregiver monitoring (supervision or regular knowledge of the child’s whereabouts) were positively associated with general cognition abilities, after covarying for age, sex, household income, neighborhood deprivation, and parental education. This association was specific to the type of caregiving behavior (caregiver monitoring, but not caregiver warmth), and was most strongly associated with a broad domain of general cognition (but not executive function or learning/memory). Additionally, we found that caregiver monitoring partially mediated the association between household income and cognition, furthering our understanding of how socioeconomic disparities may contribute to disadvantages in cognitive development. Together, these findings underscore the influence of subtle differences in caregiving behavior in shaping youth cognition.

BackgroundAdolescent suicide is a major health problem in the US marked by a recent increase in Black/African American youth suicide trends. While genetic factors partly account for familial transmission of suicidal behavior, it is not clear whether polygenic risk scores of suicide attempt have clinical utility in youth suicide risk classification.ObjectivesTo evaluate the contribution of a polygenic risk score for suicide attempt (PRS-SA) in explaining variance in suicide attempt by early adolescence.MethodsWe studied N=5,214 non-related Black and White youth from the Adolescent Brain Cognitive Development (ABCD) Study (ages 8.9-13.8 years) who were evaluated between 2016 and 2021. Regression models tested associations between PRS-SA and parental history of suicide attempt/death with youth-reported suicide attempt. Covariates included age, sex, and race.ResultsOver three waves of assessments, 182 youth (3.5%) reported a past suicide attempt, with Black youth reporting significantly more suicide attempts than their White counterparts (6.1% vs 2.8%, PConclusionsFindings suggest that PRS-SA may be useful for suicide risk classification in diverse youth.Contribution to the Field StatementAdolescent suicidal behavior is a major health problem, with suicide being the 2nd leading cause of death in youth. Research that improves our understanding regarding drivers of suicide risk in youth can inform youth suicide prevention strategies. Family history of suicide is an established risk factor for youth suicidal behavior. Current methods in psychiatric genetics allow calculation of polygenic risk scores that represent genetic liability to specific conditions. It is not clear whether polygenic risk score of suicide attempt can assist in risk classification, beyond family history. In this work, we show that in a sample of 5,214 youth ages 9-13, of which 3.5% reported past suicide attempt, polygenic score of suicide attempt was associated with youth suicide attempt. This association additively explained variance over and above parental history of suicide attempt/death. Findings make a case for the potential utility of incorporating polygenic risk scores as part of suicide attempt risk classification in youth, and suggest that polygenic scores may reveal genetic liability that is not captured by family history of suicide.

Understanding biological mechanisms underlying traumatic stress resilience is critical and can advance preventive psychiatry. Brain phenotypes of stress resilience have been investigated in animals, but such data in humans is scarce. Here we characterize cross-sectional brain correlates of traumatic stress resilience and susceptibility to mood and anxiety psychopathology (MAP) in community youth with substantial trauma exposure. Philadelphia Neurodevelopmental Cohort youths with high-quality structural neuroimaging data were included (N = 1392, mean age ~ 15). MAP was quantified using a dimensional factor score. Resilience and susceptibility were ascertained retrospectively and defined as low/high MAP (respectively) in relation to trauma exposure. This resilience-susceptibility construct was operationalized as the interaction term between trauma exposure and MAP. Clinical functioning level was quantified with the Children Global Assessment Scale. Statistical models examined association of volume, cortical thickness, and gray matter density with resilience, covarying for age, sex, race, socioeconomic status, and image quality. Resilience was associated with better clinical functioning and with specific neural correlates, such that in extensive traumatic stress exposure, smaller brain volume was associated with low MAP; while in low trauma exposure, smaller volumes were correlated with higher MAP. This pattern was evident in total brain volume (trauma by MAP interaction, F(1, 1383), p

Background Anxiety symptoms are common in adolescence and are often considered developmentally benign. Yet for some, anxiety presents with serious comorbid nonanxiety psychopathology. Early identification of such "malignant" anxiety presentations is a major challenge. We aimed to characterize anxiety symptoms suggestive of risk for depression and suicidal ideation (SI) in community youths. Methods Cross-sectional associations were evaluated in community youths (n = 7,054, mean age: 15.8) who were assessed for anxiety, depression, and SI. We employed factor and latent class analyses to identify anxiety clusters and subtypes. Longitudinal risk of anxiety was evaluated in a subset of 330 youths with longitudinal data on depression and SI (with baseline mean age of 12.3 years and follow-up mean age of 16.98 years). Outcomes Almost all (92%) adolescents reported anxiety symptoms. Data-driven approaches revealed anxiety factors and subtypes that were differentially associated with depression and SI. Cross-sectional analyses revealed that panic and generalized anxiety symptoms show the most robust associations with depression and SI. Longitudinal, multivariate analyses revealed that panic symptoms during early adolescence, not generalized anxiety symptoms, predict depression and SI for later adolescent years, particularly in males. Interpretation Anxiety is common in youths, with certain symptom clusters/subtypes predicting risk for depression and SI. Panic symptoms in early adolescence, even below disorder threshold, predict high risk for late adolescent depression and SI.

Objective To provide an in-vivo description of early corpus callosum (CC) development. Methods We reviewed 3D US volumes acquired transvaginally (TVUS) through the anterior fontanelle, between 14 to 17 weeks. The following landmarks were recognized: tela-choroidea (TC), foramina of Moro, early CC and the evolving cavum septi pellucidi. The following measurements were taken: total, anterior and posterior sections, and height of the CC (referenced to the anterior TC border). All measurements were correlated to both the gestational age and the transverse cerebellar diameter (TCD). Results Eighty nine volumes were included in the study (mean 15.1 weeks ± 0.84, TCD range, 13.1-18.4 mm) with high inter and intra observer correlation of the measurements. We found high correlation between CC length and height, and TCD. The anterior segment of the CC appear earlier than the posterior one, and growth continues bi-directionally. Initially, the posterior elongation is significantly larger than the anterior one. Association of all CC measurements with TCD remained significant when co-varying for maternal age and fetal sex. Conclusions imaging the fetal CC is feasible from 14 weeks by TVUS, by following the suggested insonation approach. The early CC develops bi-directionally, and the posterior elongation is more significant than the anterior one.

The coronavirus disease 2019 (COVID-19) pandemic resulted in significant increases in insomnia, with up to 60% of people reporting increased insomnia. However, it is unclear whether exposure to risk factors for the virus or worries about COVID-19 are more strongly associated with insomnia. Using a three-part survey over the course of the first 6 months of the pandemic, we evaluated associations between COVID-19 exposures, COVID-19 worries, and insomnia. We hypothesised that COVID-19-related worries and exposure to risk of COVID-19 would predict increases in insomnia. Participants (N = 3,560) completed a survey at three time-points indicating their exposures to COVID-19 risk factors, COVID-19-related worries, and insomnia. COVID-19 worry variables were consistently associated with greater insomnia severity, whereas COVID-19 exposure variables were not. COVID-19 worries decreased significantly over time, and there were significant interactions between change in COVID-19 worries and change in insomnia severity over time. Individuals who experienced increases in COVID-19 worries also experienced increases in insomnia severity. Changes in worry during the COVID-19 pandemic were associated with changes in insomnia; worries about COVID-19 were a more consistent predictor of insomnia than COVID-19 exposures. Evidence-based treatments targeting virus-related worries may improve insomnia during this and future calamities.

Childbirth trauma is common and increases risk for postpartum depression (PPD). However, we lack brief measures to reliably identify individuals who experience childbirth trauma and who may be at greater prospective risk for PPD. To address this gap, we used data from a racially diverse prospective cohort (n=1082). We collected survey data during pregnancy and at 12 weeks postpartum, as well as clinician-reported data from medical records. A new three-item measure of patient-reported childbirth trauma was a robust and independent risk factor for PPD, above and beyond other known risk factors for PPD, including prenatal anxiety and depression. Cesarean birth, greater blood loss, and preterm birth were each associated with greater patient-reported childbirth trauma. Finally, there were prospective indirect pathways whereby cesarean birth and higher blood loss were related to higher patient-reported childbirth trauma, in turn predicting greater risk for PPD. Early universal postpartum screening for childbirth trauma, targeted attention to individuals with childbirth complications, and continued screening for depression and anxiety can identify individuals at risk for PPD. Such efforts can inform targeted interventions to improve maternal mental health, which plays a vital role in infant development.

Childhood adversity places youth at risk for multiple negative outcomes. The current study aimed to understand how a constellation of risk and resilience factors influenced mental health outcomes as a function of adversities: socioeconomic status (SES) and traumatic stressful events (TSEs). Specifically, we examined outcomes related to psychosis and mood disorders, as well as global clinical functioning. The current study is a longitudinal follow up of 140 participants from the Philadelphia Neurodevelopmental Cohort (PNC) assessed for adversities at Time 1 (Mean age: 14.11 years) and risk, resilience, and clinical outcomes at Time 2 (mean age: 21.54 years). In the context of TSE, a limited set of predictors emerged as important; a more diverse set of moderators emerged in the context of SES. Across adversities, social support was a unique predictor of psychosis spectrum diagnoses and global functioning; emotion dysregulation was an important predictor for mood diagnoses. The current findings underscore the importance of understanding effects of childhood adversity on maladaptive outcomes within a resilience framework.

The prenatal period, early childhood, and adolescence are considered sensitive periods for brain and behavior development, when environmental exposures may have long-lasting effects on mental health. Psychosis spectrum disorder (PSD) is a developmental disorder that often manifests with nonspecific clinical presentations long before full-blown PSD is diagnosed. Genetic factors only partly explain PSD. Multiple early-life environmental exposures are associated with PSD. In this review, we describe the conceptual framework of the exposome and its relevance to PSD research in developmental cohorts and beyond and discuss key challenges for the field as it attempts to move beyond studying environment (in the sense of "searching under the lamppost because this is where the light is") to a more comprehensive assessment of environment and its contribution to PSD. We then suggest that the field should aspire to studying environmental origins of PSD through a developmental lens focusing on young cohorts and using multilevel phenotyping of environment, adopting an exposome framework that embraces the dynamic complex nature of environment and acknowledges the effect of additive and interactive environmental exposures alongside the genome. Furthermore, we highlight the need for a developmental perspective when studying exposome effects on psychopathology, accepting the nonspecificity of child/adolescent psychopathology and encouraging the study of trans-syndromal manifestations, shifting the research paradigm from categorical outcomes (e.g., schizophrenia) and going beyond clinical settings to investigate trajectories of risk and resilience.

Racial health disparities in the United States are a major concern, with Black or African Americans experiencing more morbidity and mortality at earlier ages compared to White Americans. More data is needed on the biological underpinnings of this phenomenon. One potential explanation for racial health disparities is that of accelerated aging, which is associated with increased stress exposure. Black Americans face disproportionate levels of environmental stress, specifically racial/ethnic discrimination. Here we investigated associations between self-reported experiences of discrimination and pubertal development (PD) in a diverse sample of young American adolescents (N = 11,235, mean age 10.9 years, 20.5% Black participants) from the Adolescent Brain Cognitive Development (ABCD) Study. Compared to their non-Black counterparts, Black youth experienced more racial/ethnic discrimination in the past year (10.4% vs 3.1%) and had a greater likelihood of being in late/post-pubertal status (3.6% vs 1.5% in boys, 21.3% vs 11.4% in girls). In both sexes, multivariable regression models run in the full sample revealed a cross-sectional association of experiences of racial/ethnic discrimination with pubertal development (boys: standardized beta [β]=0.123, P .001; girls: β = 0.110, P .001) covarying for demographics, BMI, and dietary habits. Associations remained significant when controlling for multiple other environmental confounders including other forms of (non-racial/ethnic) discrimination and other environmental adversities including poverty and negative life events, and when using parent-reported assessment of pubertal development. Furthermore, racial/ethnic discrimination was associated with elevated estradiol levels in girls (β = 0.057, P = .002). Findings suggest an association between experiences of discrimination and pubertal development that is independent of multiple environmental stressors. Future longitudinal studies are warranted to establish causal mechanism.

BackgroundSuicidal thoughts and behavior (STB) in children are a growing health concern, and more data is needed regarding their biological underpinnings. Immune processes such as inflammation have been associated with STB, primarily in adults. Asthma is a common chronic inflammatory disorder in children and has been associated with STB in adolescent and adult populations, but data in children is lacking. We wished to study associations of asthma with childhood STB given asthma’s potential as a clinically relevant model for childhood chronic immune dysregulation.MethodsUsing data from the Adolescent Brain Cognitive Development (ABCD) Study (N=11,878, 52% males, mean age 9.9 years at baseline assessment and 10.9 years at 1-year follow up), we assessed associations between asthma and STB at both baseline and 1-year follow up.ResultsWe found that asthma at baseline assessment (n=2,214, 18.6%) is associated with STB, controlling for multiple confounders including demographics, socioeconomic factors and environmental confounders such as air pollution (odds ratio (OR)=1.2, 95%CI 1.01-1.42, P=0.039). Indicators of recently active asthma were not significantly associated with suicidality at baseline assessment (currently taking asthma medication: OR=1.22, 95%CI 0.93-1.60, P=0.146), or at 1-year follow up (past year asthma-related clinical visit: OR=1.13, 95%CI 0.87-1.47, P=0.357). Proxy-measures of asthma severity (number of asthma medications or clinical visits) did not reveal a significant dose response relationship with STB.ConclusionsFindings suggest an association between history of asthma and STB in children, which may not be related to asthma disease state. Further research is needed to investigate mechanisms underlying this relationship.

BackgroundThe COVID-19 pandemic is a rapidly evolving stressor with significant mental health consequences. We aimed to delineate distinct anxiety-response trajectories during the early stages of the pandemic and to identify baseline risk and resilience factors as predictors of anxiety responses.MethodsUsing a crowdsourcing website, we enrolled 1,362 participants, primarily from the United States (n = 1064) and Israel (n = 222) over three time-points from April-September 2020. We used latent growth mixture modeling to identify anxiety trajectories over time. Group comparison and multivariate regression models were used to examine demographic and risk and resilience factors associated with class membership.ResultsA four-class model provided the best fit. The resilient trajectory (stable low anxiety) was the most common (n = 961, 75.08%), followed by chronic anxiety (n = 149, 11.64%), recovery (n = 96, 7.50%) and delayed anxiety (n = 74, 5.78%). While COVID-19 stressors did not differ between trajectories, resilient participants were more likely to be older, living with another person and to report higher income, more education, fewer COVID-19 worries, better sleep quality, and more dispositional resilience factors at baseline. Multivariate analyses suggested that baseline emotion regulation capabilities and low conflictual relationships uniquely distinguished participants in distinct trajectories.ConclusionsConsistent with prior resilience research following major adversities, a majority of individuals showed stable low levels of low anxiety in response to the COVID-19 pandemic. Knowledge about dispositional resilience factors may prospectively inform mental health trajectories early in the course of ongoing adversity.

Acute stress during pregnancy can have adverse effects on maternal health and increase the risk for postpartum depression and impaired mother-infant bonding. The COVID-19 pandemic represents an acute environmental stressor during which it is possible to explore risk and resilience factors that contribute to postpartum outcomes. To investigate prenatal risk and resilience factors as predictors of postpartum depression and impaired mother-infant bonding, this study recruited a diverse cohort of 833 pregnant women from an urban medical center in Philadelphia, Pennsylvania, and assessed them once during pregnancy in the early phase of the COVID-19 pandemic (April–July 2020) and again at approximately twelve weeks postpartum. Adverse childhood experiences, prenatal depression and anxiety, and COVID-19-related distress predicted a greater likelihood of postpartum depression. Prenatal depression was the only unique predictor of impaired maternal-infant bonding after postpartum depression was controlled for. Women reporting greater emotion regulation, self-reliance, and nonhostile relationships had healthier postpartum outcomes. Policies to increase the number of nonspecialty providers providing perinatal mental health services as well as reimbursement for integrated care and access to mental health screening and care are needed to improve lifelong outcomes for women and their children.

The COVID-19 pandemic and associated responses have induced a host of crises worldwide, including an economic recession and a global mental health crisis. The specific effects of recession on youth mental health are understudied. We aimed to examine the mechanisms by which pandemic-related financial strain may affect mental health in a diverse sample of American adolescents.We analyzed data from the Adolescent Brain Cognitive Development Study (ABCD Study®), a large, longitudinal study of diverse US adolescents which collected data before and during the pandemic (N = 9,720, mean age 12.9 years, 18.2% Black). Linear mixed-effects models tested associations of financial strain (parent-reported household wage loss and youth-reported financial stress) with depressive symptomatology over time, covarying for multiple confounders including pre-pandemic socioeconomic status and psychopathology, and pandemic-related environmental factors. Longitudinal mediation analyses examined potential mechanisms leading from wage loss to youth mental health.Financial strain was highly prevalent, especially among low-income participants, with70% of the total sample reporting lost wages. Both wage loss and subjective financial stress were associated with depressive symptomatology over time (Estimate = 0.04, P = 0.014; Estimate = 0.17, P 0.001; respectively). The association between financial stress and depressive symptomatology was robust to the addition of multiple environmental confounders (Estimate = 0.16, P 0.001). Both family-level (family conflict) and individual-level (financial stress) factors mediated the relationship between wage loss and depressive symptomatology.The financial effects of COVID-19 (and worldwide responses to it) have taken a significant toll on youth mental health. In families that lost wages, youth-reported financial stress and familial factors mediated the relationship between wage loss and mental health over time. Findings highlight financial stress as a key driver of youth mental health burden and identify familial factors as critical targets for intervention to mitigate mental health risks in periods of economic crises.This study was supported by the National Institute of Mental Health [grant numbers K23MH120437 (RB), R01MH117014 (TMM)]; the Lifespan Brain Institute of Children's Hospital of Philadelphia and Penn Medicine, University of Pennsylvania.

Low socioeconomic status has been shown to have detrimental effects on cognitive performance, including working memory (WM). As executive systems that support WM undergo functional neurodevelopment during adolescence, environmental stressors at both individual and community levels may have a particularly strong impact on cognitive outcomes. Here, we sought to examine how neighborhood socioeconomic status (SES) impacts task-related activation of the executive system during adolescence, and to determine whether this effect mediates the relationship between neighborhood SES and WM performance. To address these questions, we studied 1,158 youths (age 8-22) that completed a fractal n-back WM task during fMRI at 3T as part of the Philadelphia Neurodevelopmental Cohort. We found that higher neighborhood SES was associated with greater activation of the executive system to WM load, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and precuneus. These associations remained significant when controlling for related factors like parental education and exposure to traumatic events. Furthermore, high dimensional multivariate mediation analysis identified two distinct patterns of brain activity within the executive system that significantly mediated the relationship between neighborhood SES and task performance. Together, these findings underscore the importance of the neighborhood environment in shaping executive system function and WM in youth.

Exposures to perinatal, familial, social, and physical environmental stimuli can have substantial effects on human development. Yet the complex network structure of the environment (i.e., exposome) makes it challenging to investigate. Here, we analyze the exposome using data from the Adolescent Brain Cognitive Development Study (ABCD, N = 11,235, mean age = 10.9, 52% male) and replicate key findings in an age and sex matched sample from the Philadelphia Neurodevelopmental Cohort (PNC, N = 4,993). Both these cohorts are large, diverse samples of US adolescents with phenotyping at multiple levels of environmental exposure. In ABCD, applying data-driven iterative factor analyses and bifactor modeling, we reduced dimensionality from n=798 exposures to six exposome subfactors and a general (adverse) exposome factor. These factors revealed quantitative differences among racial and ethnic groups. Exposome factors increased variance explained in mental health by 10-fold (from 38%), over and above other commonly used sociodemographic factors. The general exposome factor was associated with psychopathology (β=0.28, 95%CI 0.26-0.3) and key health-related outcomes: obesity (OR=1.4, 95%CI 1.3-1.5) and advanced pubertal development (OR=1.3, 95%CI 1.2-1.5). In PNC, using substantially fewer available environmental exposures (n=29), analyses yielded consistent associations of the general exposome factor with psychopathology (β =0.15, 95%CI 0.13-0.17), obesity (OR=1.4, 95%CI 1.3-1.6) and advanced pubertal development (OR=1.3, 95%CI 1-1.6). Findings demonstrate how incorporating the exposome framework can be useful to study the role of environment in human development.

Socioeconomic status (SES) can impact cognitive performance, including working memory (WM). As executive systems that support WM undergo functional neurodevelopment during adolescence, environmental stressors at both individual and community levels may influence cognitive outcomes. Here, we sought to examine how SES at the neighborhood and family level impacts task-related activation of the executive system during adolescence and determine whether this effect mediates the relationship between SES and WM performance. To address these questions, we studied 1,150 youths (age 8–23) that completed a fractal n-back WM task during functional magnetic resonance imaging at 3T as part of the Philadelphia Neurodevelopmental Cohort. We found that both higher neighborhood SES and parental education were associated with greater activation of the executive system to WM load, including the bilateral dorsolateral prefrontal cortex, posterior parietal cortex, and precuneus. The association of neighborhood SES remained significant when controlling for task performance, or related factors like exposure to traumatic events. Furthermore, high-dimensional multivariate mediation analysis identified distinct patterns of brain activity within the executive system that significantly mediated the relationship between measures of SES and task performance. These findings underscore the importance of multilevel environmental factors in shaping executive system function and WM in youth.

BackgroundAlthough there are extensive data on clinical psychopathology in youth with suicidal ideation, data are lacking regarding their neurocognitive function.AimsTo characterise the cognitive profile of youth with suicidal ideation in a community sample and evaluate gender differences and pubertal status effects.MethodParticipants (N = 6151, age 11–21 years, 54.9% females) from the Philadelphia Neurodevelopmental Cohort, a non-help-seeking community sample, underwent detailed clinical evaluation. Cognitive phenotyping included executive functioning, episodic memory, complex reasoning and social cognitive functioning. We compared participants with suicidal ideation (N = 672) and without suicidal ideation (N = 5479). Regression models were employed to evaluate differences in cognitive performance and functional level, with gender and pubertal status as independent variables. Models controlled for lifetime depression or general psychopathology, and for covariates including age and socioeconomic status.ResultsYouth with suicidal ideation showed greater psychopathology, poorer level of function but better overall neurocognitive performance. Greater functional impairment was observed in females with suicidal ideation (suicidal ideation × gender interaction, t = 3.091, P = 0.002). Greater neurocognition was associated with suicidal ideation post-puberty (suicidal ideation × puberty interaction, t = 3.057, P = 0.002). Exploratory analyses of specific neurocognitive domains showed that suicidal ideation-associated cognitive superiority was more prominent in post-pubertal males compared with females (Cohen's d = 0.32 and d = 0.11, respectively) across all cognitive domains.ConclusionsSuicidal ideation was associated with poorer functioning yet better cognitive performance, especially in post-pubertal males, as measured by a comprehensive cognitive battery. Findings point to gender and pubertal-status specificity in the relationship between suicidal ideation, cognition and function in youth.Declaration of interestR.B. serves on the scientific board and reports stock ownership in ‘Taliaz Health’, with no conflict of interest relevant to this work. M.A.O. receives royalties for the commercial use of the Columbia-Suicide Severity Rating Scale from the Research Foundation for Mental Hygiene. Her family owns stock in Bristol-Myers Squibb. All other authors declare no potential conflict of interest.

Psychiatric and cognitive phenotypes have been associated with a range of specific, rare copy number variants (CNVs). Moreover, IQ is strongly associated with CNV risk scores that model the predicted risk of CNVs across the genome. But the utility of CNV risk scores for psychiatric phenotypes has been sparsely examined.To determine how CNV risk scores, common genetic variation indexed by polygenic scores (PGSs), and environmental factors combine to associate with cognition and psychopathology in a community sample.The Philadelphia Neurodevelopmental Cohort is a community-based study examining genetics, psychopathology, neurocognition, and neuroimaging. Participants were recruited through the Children's Hospital of Philadelphia pediatric network. Participants with stable health and fluency in English underwent genotypic and phenotypic characterization from November 5, 2009, through December 30, 2011. Data were analyzed from January 1 through July 30, 2021.The study examined (1) CNV risk scores derived from models of burden, predicted intolerance, and gene dosage sensitivity; (2) PGSs from genomewide association studies related to developmental outcomes; and (3) environmental factors, including trauma exposure and neighborhood socioeconomic status.The study examined (1) neurocognition, with the Penn Computerized Neurocognitive Battery; (2) psychopathology, with structured interviews based on the Schedule for Affective Disorders and Schizophrenia for School-Age Children; and (3) brain volume, with magnetic resonance imaging.Participants included 9498 youths aged 8 to 21 years; 4906 (51.7%) were female, and the mean (SD) age was 14.2 (3.7) years. After quality control, 18 185 total CNVs greater than 50 kilobases (10 517 deletions and 7668 duplications) were identified in 7101 unrelated participants genotyped on Illumina arrays. In these participants, elevated CNV risk scores were associated with lower overall accuracy on cognitive tests (standardized β = 0.12; 95% CI, 0.10-0.14; P = 7.41 × 10-26); lower accuracy across a range of cognitive subdomains; increased overall psychopathology; increased psychosis-spectrum symptoms; and higher deviation from a normative developmental model of brain volume. Statistical models of developmental outcomes were significantly improved when CNV risk scores were combined with PGSs and environmental factors.In this study, elevated CNV risk scores were associated with lower cognitive ability, higher psychopathology including psychosis-spectrum symptoms, and greater deviations from normative magnetic resonance imaging models of brain development. Together, these results represent a step toward synthesizing rare genetic, common genetic, and environmental factors to understand clinically relevant outcomes in youth.

Polygenic scores (PGS) are commonly evaluated in terms of their predictive accuracy at the population level by the proportion of phenotypic variance they explain. To be useful for precision medicine applications, they also need to be evaluated at the individual patient level when phenotypes are not necessarily already known. Hence, we investigated the stability of PGS in European-American (EUR)- and African-American (AFR)-ancestry individuals from the Philadelphia Neurodevelopmental Cohort (PNC) and the Adolescent Brain Cognitive Development (ABCD) cohort using different discovery GWAS for post-traumatic stress disorder (PTSD), type-2 diabetes (T2D), and height. We found that pairs of EUR-ancestry GWAS for the same trait had genetic correlations > 0.92. However, PGS calculated from pairs of sameancestry and different-ancestry GWAS had correlations that ranged from th percentile of PGS overlapping from one height GWAS to another. The degree of overlap decreases sharply as higher quantiles, less heritable traits, and different-ancestry GWAS are considered. PGS computed from different discovery GWAS have only modest correlation at the level of the individual patient, underscoring the need to proceed cautiously with integrating PGS into precision medicine applications.

Suicidal ideation and attempts (i.e., suicidality) are complex behaviors driven by environmental stress, genetic susceptibility, and their interaction. Preadolescent suicidality is a major health problem with rising rates, yet its underlying biology is understudied. Here we studied effects of genetic stress susceptibility, estimated by polygenic risk score (PRS) for post-traumatic-stress-disorder (PTSD), on preadolescent suicidality in participants from the Adolescent Brain Cognitive Development (ABCD) Study®. We further evaluated PTSD-PRS effects on suicidality in the presence of environmental stressors that are established suicide risk factors. Analyses included both European and African ancestry participants using PRS calculated based on summary statistics from ancestry-specific genome-wide association studies. In European ancestry participants (N=4,619, n=378 suicidal), PTSD-PRS was associated with preadolescent suicidality (odds ratio [OR]=1.12, 95%CI 1-1.25, p=0.038). Results in African ancestry participants (N=1,334, n=130 suicidal) showed a similar direction but were not statistically significant (OR=1.21, 95%CI 0.93-1.57, p=0.153). Sensitivity analyses using non-psychiatric polygenic score for height and using cross-ancestry PTSD-PRS did not reveal any association with suicidality, supporting the specificity of the association of ancestry-specific PTSD-PRS with suicidality. Environmental stressors were robustly associated with suicidality across ancestries with moderate effect size for negative life events and family conflict (OR 1.27-1.6); and with large effect size (OR ∼ 4) for sexual-orientation discrimination. When combined with environmental factors, PTSD-PRS showed marginal additive effects in explaining variability in suicidality, with no evidence for G X E interaction. Results support use of cross-phenotype PRS, specifically stress-susceptibility, as a robust genetic marker for suicidality risk early in the lifespan.

Background Obsessive compulsive symptomatology (OCS) is common in adolescence but usually does not meet the diagnostic threshold for obsessive compulsive disorder. Nevertheless, both OCD and subthreshold OCS are associated with increased likelihood of experiencing other serious psychiatric conditions including depression and suicidal ideation. Unfortunately, there is limited information on the neurobiology of OCS. Methods Here we undertook one of the first brain imaging studies of OCS in a large adolescent sample (analyzed n=832) from the Philadelphia Neurodevelopmental Cohort. We investigated resting-state fMRI functional connectivity using complementary analytic approaches that focus on different neuroanatomical scales, from known functional systems to connectome-wide tests. Results We found a robust pattern of connectome-wide, OCS-related differences, as well as evidence of specific abnormalities involving known functional systems, including dorsal and ventral attention, frontoparietal and default mode systems. Analysis of cerebral perfusion imaging and high resolution structural imaging did not show OCS-related differences, consistent with domain specificity to functional connectivity. Conclusions The brain connectomic associations with OCS reported here, together with early studies of its clinical relevance, support the potential for OCS as an early marker of psychiatric risk that may enhance our understanding of mechanisms underlying the onset of adolescent psychopathology.

OBJECTIVE: Youth suicide rates in the United States have been increasing in recent years, especially in Black Americans, the reasons for which are unclear. Environmental adversity is key in youth suicidality; hence there is a need to study stressors that have a disproportionate impact on Black youths. We aimed to disentangle the unique contribution of racial/ethnic discrimination from other adversities associated with childhood suicidal ideation and attempts (suicidality). METHOD: We analyzed data from the Adolescent Brain Cognitive Development (ABCD) Study, which included a large, diverse sample of US children (N = 11,235, mean age 10.9 years, 20.2% Black), assessed for multiple environmental adversities including discrimination. Multivariate regression models tested the association of self-reported racial/ethnic discrimination with suicidality, covarying for multiple confounders including other discrimination types (toward non–US-born individuals, sexual orientation–based, and weight-based). Matched analyses contrasted effects of racial/ethnic discrimination and racial identity on suicidality. RESULTS: Black youths reported more discrimination and higher suicidality rates than non-Black youths. High racial/ethnic discrimination was positively and significantly associated with suicidality, adjusting for other discrimination types (odds ratio = 2.6, 95% CI = 2.1–3.2). Findings remained significant after adjusting for multiple suicidality risk factors. Once experienced, racial/ethnic discrimination was similarly associated with suicidality in White, Black, and Hispanic youths. Matched analyses revealed that racial/ethnic discrimination was associated with suicidality (relative risk = 2.7, 95% CI = 2–3.5), whereas Black race was not (relative risk = 0.9, 95% CI = 0.7–1.2). CONCLUSION: Racial/ethnic discrimination is disproportionately experienced by Black children, and is associated with preadolescent suicidality, over and above other adversities. Findings highlight the need to address discrimination as part of suicide prevention strategies. Cross-sectional design hampers causal inferences. Reprinted from J Am Acad Child Adolesc Psychiatry, Argabright et al., Association Between Discrimination Stress and Suicidality in Preadolescent Children, S0890–8567(21)01355-1, copyright 2021, with permission from Elsevier

Major depressive disorder (MDD) is complex and multifactorial, posing a major challenge of tailoring the optimal medication for each patient. Current practice for MDD treatment mainly relies on trial and error, with an estimated 42–53% response rates for antidepressant use. Here, we sought to generate an accurate predictor of response to a panel of antidepressants and optimize treatment selection using a data-driven approach analyzing combinations of genetic, clinical, and demographic factors. We analyzed the response patterns of patients to three antidepressant medications in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, and employed state-of-the-art machine learning (ML) tools to generate a predictive algorithm. To validate our results, we assessed the algorithm’s capacity to predict individualized antidepressant responses on a separate set of 530 patients in STAR*D, consisting of 271 patients in a validation set and 259 patients in the final test set. This assessment yielded an average balanced accuracy rate of 72.3% (SD 8.1) and 70.1% (SD 6.8) across the different medications in the validation and test set, respectively (p p’s