Immune and oxidative stress biomarkers in pediatric psychosis and psychosis-risk: Meta-analyses and systematic review.

OBJECTIVE: While genetic and cohort studies suggest immune and reduction/oxidation (redox) alterations occur in psychosis, less is known about potential alterations in children and adolescents. METHODS: We conducted a systematic review to identify immune and redox biomarker studies in children and adolescents (mean age ≤ 18 years old) across the psychosis spectrum: from psychotic like experiences, which are common in children, to threshold psychotic disorders like schizophrenia. We conducted meta-analyses when at least three studies measured the same biomarker. RESULTS: The systematic review includes 38 pediatric psychosis studies. The meta-analyses found that youth with threshold psychotic disorders had higher neutrophil/lymphocyte ratio (Hedge's g = 0.40, 95 % CI 0.17 - 0.64), tumor necrosis factor (Hedge's g = 0.38, 95 % CI 0.06 - 0.69), C-reactive protein (Hedge's g = 0.38, 95 % CI 0.05 - 0.70), interleukin-6 (Hedge's g = 0.35; 95 % CI 0.11 - 0.64), and total white blood cell count (Hedge's g = 0.29, 95 % CI 0.12 - 0.46) compared to youth without psychosis. Other immune and oxidative stress meta-analytic findings were very heterogeneous. CONCLUSION: Results from several studies are consistent with the hypothesis that signals often classified as "proinflammatory" are elevated in threshold pediatric psychotic disorders. Data are less clear for immune markers in subthreshold psychosis and redox markers across the subthreshold and threshold psychosis spectrum. Immune and redox biomarker intervention studies are lacking, and research investigating interventions targeting the immune system in threshold pediatric psychosis is especially warranted.

Traumatic stress load and stressor reactivity score associated with accelerated gray matter maturation in youths indexed by normative models.

Understanding how traumatic stress affects typical brain development during adolescence is critical to elucidate underlying mechanisms related to both maladaptive functioning and resilience after traumatic exposures. The current study aimed to map deviations from normative ranges of brain gray matter for youths with traumatic exposures. For each cortical and subcortical gray matter region, normative percentiles of variations were established using structural MRI from typically developing youths without any traumatic exposure (n = 245; age range = 8-23) from the Philadelphia Neurodevelopmental Cohort (PNC). The remaining PNC participants with neuroimaging data (n = 1129) were classified as either within the normative range (5-95%), delayed (>95%) or accelerated (<5%) maturational ranges for each region using the normative model. An averaged quantile regression index was calculated across all regions. Mediation models revealed that high traumatic stress load was positively associated with poorer cognitive functioning and greater psychopathology, and these associations were mediated by accelerated gray matter maturation. Furthermore, higher stressor reactivity scores, which represent a less resilient response under traumatic stress, were positively correlated with greater acceleration of gray matter maturation (r = 0.224, 95% CI = [0.17, 0.28], p < 0.001), suggesting that more accelerated maturation was linked to greater stressor response regardless of traumatic stress load. We conclude that traumatic stress is a source of deviation from normative brain development associated with poorer cognitive functioning and more psychopathology in the long run.

Associations between neighborhood socioeconomic status, parental education, and executive system activation in youth.

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.

The Ethics of Risk Prediction for Psychosis and Suicide Attempt in Youth Mental Health.

OBJECTIVE: To identify potential clinical utility of polygenic risk scores (PRS) and exposomic risk scores (ERS) for psychosis and suicide attempt in youth and assess the ethical implications of these tools. STUDY DESIGN: We conducted a narrative literature review of emerging findings on PRS and ERS for suicide and psychosis as well as a literature review on the ethics of PRS. We discuss the ethical implications of the emerging findings for the clinical potential of PRS and ERS. RESULTS: Emerging evidence suggests that PRS and ERS may offer clinical utility in the relatively near future but that this utility will be limited to specific, narrow clinical questions, in contrast to the suggestion that population-level screening will have sweeping impact. Combining PRS and ERS might optimize prediction. This clinical utility would change the risk-benefit balance of PRS, and further empirical assessment of proposed risks would be necessary. Some concerns for PRS, such as those about counseling, privacy, and inequities, apply to ERS. ERS raise distinct ethical challenges as well, including some that involve informed consent and direct-to-consumer advertising. Both raise questions about the ethics of machine-learning/artificial intelligence approaches. CONCLUSIONS: Predictive analytics using PRS and ERS may soon play a role in youth mental health settings. Our findings help educate clinicians about potential capabilities, limitations, and ethical implications of these tools. We suggest that a broader discussion with the public is needed to avoid overenthusiasm and determine regulations and guidelines for use of predictive scores.

Executive function as a generalized determinant of psychopathology and functional outcome in school-aged autism spectrum disorder: a case-control 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.

Caregiver monitoring, but not caregiver warmth, is associated with general cognition in two large sub-samples of youth.

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® (ABCD). 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 differences in caregiving behavior in shaping youth cognition. RESEARCH HIGHLIGHTS: Caregiver monitoring, but not caregiver warmth, is associated with cognitive performance in youth Caregiver monitoring partially mediates the association between household income and cognition Results replicated across two large matched samples from the Adolescent Brain Cognitive Development Study® (ABCD).

The impact of postpartum social support on postpartum mental health outcomes during the COVID-19 pandemic.

Social support is an influential component of postpartum recovery, adjustment, and bonding, which was disrupted by social distancing recommendations related to the COVID-19 pandemic. This study reports on changes in the availability of social support for postpartum women during the pandemic, investigates how those changes may have contributed to postpartum mental health, and probes how specific types of social support buffered against poor postpartum mental health and maternal-infant bonding impairment. Participants were 833 pregnant patients receiving prenatal care in an urban USA setting and using an electronic patient portal to access self-report surveys at two time points, during pregnancy (April-July 2020) and at ~12 weeks postpartum (August 2020-March 2021). Measures included an assessment of COVID-19 pandemic-related change in social support, sources of social support, ratings of emotional and practical support, and postpartum outcomes including depression, anxiety, and maternal-infant bonding. Overall self-reported social support decreased during the pandemic. Decreased social support was associated with an increased risk of postpartum depression, postpartum anxiety, and impaired parent-infant bonding. Among women reporting low practical support, emotional support appeared to protect against clinically significant depressive symptoms and impaired bonding with the infant. Decreases in social support are associated with a risk for poor postpartum mental health outcomes and impaired maternal-infant bonding. Evaluation and promotion of social support are recommended for healthy adjustment and functioning of postpartum women and families.

Hoarding behavior and its association with mental health and functioning in a large youth sample.

Hoarding behavior is prevalent in children and adolescents, yet clinicians do not routinely inquire about it and youth may not spontaneously report it due to stigma. It is unknown whether hoarding behavior, over and above obsessive-compulsive symptoms (OCS), is associated with major clinical factors in a general youth population. This observational study included N = 7054 youth who were not seeking help for mental health problems (ages 11-21, 54% female) and completed a structured interview that included evaluation of hoarding behavior and OCS, as a part of the Philadelphia Neurodevelopmental Cohort between November 2009 and December 2011. We employed regression models with hoarding behavior and OCS (any/none) as independent variables, and continuous (linear regression) or binary (logistic regression) mental health measures as dependent variables. All models covaried for age, sex, race, and socioeconomic status. A total of 374 participants endorsed HB (5.3%), most of which reported additional OCS (n = 317). When accounting for OCS presence, hoarding behavior was associated with greater dimensional psychopathology burden (i.e., higher P-factor) (ß = 0.19, p < .001), and with poorer functioning (i.e., lower score on the child global assessment scale) (ß = - 0.07, p < .001). The results were consistent when modeling psychopathology using binary variables. The results remained significant in sensitivity analyses accounting for count of endorsed OCS and excluding participants who met criteria for obsessive-compulsive disorder (n = 210). These results suggest that hoarding behavior among youth is associated with poorer mental health and functioning, independent of OCS. Brief hoarding-behavior assessments in clinical settings may prove useful given hoarding behavior's stigma and detrimental health associations.

Risk and Resilience Measures Related to Psychopathology in Youth.

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 Influence of Pandemic-Related Worries During Pregnancy on Child Development at 12 Months.

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 = 1173). 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 relate 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.

Worry about COVID-19 as a predictor of future insomnia.

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.

Clinician-reported childbirth outcomes, patient-reported childbirth trauma, and risk for postpartum depression.

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.

Association between family history of suicide attempt and neurocognitive functioning in community youth.

BACKGROUND: Suicidal behavior is highly familial. Neurocognitive deficits have been proposed as an endophenotype for suicide risk that may contribute to the familial transmission of suicide. Yet, there is a lack of research on the neurocognitive functioning of first-degree biological relatives of suicide attempters. The aim of the present study is to conduct the largest investigation to date of neurocognitive functioning in community youth with a family history of a fatal or nonfatal suicide attempt (FH). METHODS: Participants aged 8-21 years from the Philadelphia Neurodevelopmental Cohort completed detailed clinical and neurocognitive evaluations. A subsample of 501 participants with a FH was matched to a comparison group of 3,006 participants without a family history of suicide attempt (no-FH) on age, sex, race, and lifetime depression. RESULTS: After adjusting for multiple comparisons and including relevant clinical and demographic covariates, youth with a FH had significantly lower executive function factor scores (F[1,3432] = 6.63, p = .010) and performed worse on individual tests of attention (F[1,3382] = 7.08, p = .008) and language reasoning (F[1,3387] = 5.12, p = .024) than no-FH youth. CONCLUSIONS: Youth with a FH show small differences in executive function, attention, and language reasoning compared to youth without a FH. Further research is warranted to investigate neurocognitive functioning as an endophenotype for suicide risk. Implications for the prevention and treatment of suicidal behaviors are discussed.

The Impact of the COVID-19 Pandemic on Children's Conduct Problems and Callous-Unemotional Traits.

The COVID-19 pandemic has dramatically altered family life, but whether family exposures to and worries about the COVID-19 pandemic has impacted child conduct problems (CP) and callous-unemotional (CU) traits is unknown. Thus, we evaluated 303 parents (Mage = 38.04; SD = 5.21; 92.4% biological mothers) and children (Mage = 6.43; SD = 2.13; 51.8% female) during a four-month period early in the pandemic. We examined associations between parental exposures to COVID-19, parental worries about the pandemic, harsh and warm parenting practices, and child CP and CU traits. Although more parental worries were not directly related to parenting practices, more worry about COVID-19 was specifically related to higher levels of child CP, particularly parental worries about themselves or family members contracting the virus. Our findings add to a growing literature demonstrating the burden that the pandemic has placed on families and its implications for children's mental health.

Association of anxiety phenotypes with risk of depression and suicidal ideation in community youth.

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.

The early pattern of human corpus callosum development: A transvaginal 3D neurosonographic study.

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.

Association between prenatal exposure to a 1-month period of repeated rocket attacks and neuropsychiatric outcomes up through age 9: a retrospective cohort study.

Exposure to gestational stress is implicated in increased risk for neuropsychiatric disorders in offspring. We assessed association between prenatal exposure to a 1-month period of repeated rocket attacks during the 2006 Second Lebanon War in Northern Israel and emergence of childhood neuropsychiatric disorders from birth through 9 years of age. Children born to women who were pregnant during the war (N = 6999) were identified and compared to children in the same district born a year later (N = 7054), whose mothers were not exposed to rocket attacks during pregnancy. Multivariable regression models assessed risk for attention deficit hyperactivity disorder, autism, epilepsy, depression and/or anxiety, or any of these disorders (composite outcome) in offspring. Models controlled for multiple confounders including parents' demographics, parity, maternal use of psychotropic medications during pregnancy, post-partum depression and parental psychiatric history. Results show that exposed and comparison groups did not differ with respect to demographics, parity or psychiatric history. Exposed and comparison groups were similar with regard to gestational age and weight at birth. Multivariable models did not demonstrate an association between exposure to rocket attacks during pregnancy and neuropsychiatric outcomes by age 9. No interactions were found between exposure and gestational trimester at exposure or child's sex. Our findings suggest that in utero exposure to isolated, 1-month repeated rocket attacks on a civilian population was not associated with major neuropsychiatric outcomes in children by age 9. Future studies should evaluate whether this exposure is associated with psychiatric and/or other health-related outcomes later in life.

BDNF overexpression prevents cognitive deficit elicited by adolescent cannabis exposure and host susceptibility interaction.

Cannabis abuse in adolescence is associated with increased risk of psychotic disorders. Δ-9-tetrahydrocannabinol (THC) is the primary psychoactive component of cannabis. Disrupted-In-Schizophrenia-1 (DISC1) protein is a driver for major mental illness by influencing neurodevelopmental processes. Here, utilizing a unique mouse model based on host (DISC1) X environment (THC administration) interaction, we aimed at studying the pathobiological basis through which THC exposure elicits psychiatric manifestations. Wild-Type and dominant-negative-DISC1 (DN-DISC1) mice were injected with THC (10 mg/kg) or vehicle for 10 days during mid-adolescence-equivalent period. Behavioral tests were conducted to assess exploratory activity (open field test, light-dark box test) and cognitive function (novel object recognition test). Electrophysiological effect of THC was evaluated using acute hippocampal slices, and hippocampal cannabinoid receptor type 1 and brain-derived neurotrophic factor (BDNF) protein levels were measured. Our results indicate that THC exposure elicits deficits in exploratory activity and recognition memory, together with reduced short-term synaptic facilitation and loss of BDNF surge in the hippocampus of DN-DISC mice, but not in wild-type mice. Over-expression of BDNF in the hippocampus of THC-treated DN-DISC1 mice prevented the impairment in recognition memory. The results of this study imply that induction of BDNF following adolescence THC exposure may serve as a homeostatic response geared to maintain proper cognitive function against exogenous insult. The BDNF surge in response to THC is perturbed in the presence of mutant DISC1, suggesting DISC1 may be a useful probe to identify biological cascades involved in the neurochemical, electrophysiological, and behavioral effects of cannabis related psychiatric manifestations.

Neurocognitive functioning in community youth with suicidal ideation: gender and pubertal effects.

BACKGROUND: Although there are extensive data on clinical psychopathology in youth with suicidal ideation, data are lacking regarding their neurocognitive function. AIMS: To characterise the cognitive profile of youth with suicidal ideation in a community sample and evaluate gender differences and pubertal status effects. METHOD: Participants (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. RESULTS: Youth 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. CONCLUSIONS: Suicidal 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 INTEREST: R.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.

Association between traumatic stress load, psychopathology, and cognition in the Philadelphia Neurodevelopmental Cohort.

BACKGROUND: Traumatic stressors during childhood and adolescence are associated with psychopathology, mostly studied in the context of post-traumatic stress disorder (PTSD) and depression. We investigated broader associations of traumatic stress exposure with psychopathology and cognition in a youth community sample. METHODS: The Philadelphia Neurodevelopmental Cohort (N = 9498) is an investigation of clinical and neurobehavioral phenotypes in a diverse (56% Caucasian, 33% African American, 11% other) US youth community population (aged 8-21). Participants were ascertained through children's hospital pediatric (not psychiatric) healthcare network in 2009-2011. Structured psychiatric evaluation included screening for lifetime exposure to traumatic stressors, and a neurocognitive battery was administered. RESULTS: Exposure rate to traumatic stressful events was high (none, N = 5204; one, N = 2182; two, N = 1092; three or more, N = 830). Higher stress load was associated with increased psychopathology across all clinical domains evaluated: mood/anxiety (standardized ß = .378); psychosis spectrum (ß = .360); externalizing behaviors (ß = .311); and fear (ß = .256) (controlling for covariates, all p < 0.001). Associations remained significant controlling for lifetime PTSD and depression. Exposure to high-stress load was robustly associated with suicidal ideation and cannabis use (odds ratio compared with non-exposed 5.3 and 3.2, respectively, both p < 0.001). Among youths who experienced traumatic stress (N = 4104), history of assaultive trauma was associated with greater psychopathology and, in males, vulnerability to psychosis and externalizing symptoms. Stress load was negatively associated with performance on executive functioning, complex reasoning, and social cognition. CONCLUSIONS: Traumatic stress exposure in community non-psychiatric help-seeking youth is substantial, and is associated with more severe psychopathology and neurocognitive deficits across domains, beyond PTSD and depression.