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Background Due to the high prevalence of nutrient deficiencies in patients with inflammatory bowel disease (IBD), routine monitoring of nutrient status and supplementation are recommended. Objective This preliminary study was implemented to prospectively identify potential effects of a nutrition support formula on blood nutrient parameters in adults with IBD. Methods Ten adults with Crohn’s disease or ulcerative colitis were recruited from the Portland, Oregon, metropolitan area into a single-arm, open-label pilot study. Participants consumed a nutrition support beverage twice daily for 12 weeks. The formula contained a mixture of micronutrients (including methylated forms of folate and vitamin B12), macronutrients, and phytonutrients (including curcumin, xanthohumol, ginger compounds, and quercetin). Primary measures were the following parameters: folate, vitamin B12, red blood cell (RBC) count, hemoglobin, hematocrit, electrolytes, and albumin. Exploratory measures included a food frequency questionnaire, circulating blood cell counts, and inflammatory markers. Results Nine participants completed the study and one withdrew. Adherence was 98%. Serum folate increased 48.7% ( P = .029), serum vitamin B12 increased 17.4% but did not reach statistical significance ( P = .053), and red cell distribution width (RDW) decreased 9.2% ( P = .012) over the 12-week study period. There were minimal shifts in total white blood cell (WBC) counts (−1.0%, P = .845), but percent neutrophils decreased 10.4% ( P = .042) and absolute lymphocyte count increased 18.6% ( P = .048). RBC count, hemoglobin, hematocrit, electrolytes, albumin, and inflammatory markers did not change significantly. Post hoc analysis demonstrated that neutrophil–lymphocyte ratio (NLR) decreased 18.4% (not significant, P = .061). Conclusion Serum folate and RDW improved in adults with IBD after 12 weeks. Modulation of leukocyte subtypes was also observed, including a decrease in neutrophils and an increase in lymphocytes, with no change in total WBC count. A randomized, controlled study to further examine effects of the nutrition support formula will be initiated to follow up on this promising, but preliminary investigation.

Objective: The authors sought to identify predictors of self-harm adverse events in treatment-resistant, depressed adolescents during the first 12 weeks of treatment.Method: Depressed adolescents (N=334) who had not responded to a previous trial with an SSRI antidepressant were randomized to a switch to either another SSRI or venlafaxine, with or without cognitive behavior therapy. Self-harm events, i.e., suicidal and non-suicidal self-injury adverse events were assessed by spontaneous report for the first 181 participants, and by systematic weekly assessment for the last 153 participants.Results: Higher rates of suicidal (20.8% vs. 8.8%) and nonsuicidal self-injury (17.6% vs. 2.2%), but not serious adverse events (8.4% vs. 7.3%) were detected with systematic monitoring. Median time to a suicidal event was 3 weeks, predicted by high baseline suicidal ideation, family conflict, and drug and alcohol use. Median time to nonsuicidal self-injury was 2 weeks, predicted by previous history of nonsuicidal self-injury. While there were no main effects of treatment, venlafaxine treatment was associated with a higher rate of self-harm adverse events in those with higher suicidal ideation. Adjunctive use of benzodiazepines, while in a small number of participants (N=10) was associated with higher rate of both suicidal and nonsuicidal self-injury adverse events.Conclusions: Since predictors of suicidal adverse events also predict poor response to treatment, and many of these events occurred early in treatment, improving the speed of response to depression, by targeting of family conflict, suicidal ideation, and drug use may help to reduce their incidence. The relationship of venlafaxine and of benzodiazepines to self-harm events requires further study and clinical caution. [ABSTRACT FROM AUTHOR]

Objective: Sleep problems are a cardinal symptom of depression in children and adolescents and caffeine use is a prevalent and problematic issue in youth; yet little is known about caffeine use and its effects on sleep in youth with depression. We examined caffeine use and its relation to sleep and affect in youth's natural environments.Methods: Thirty youth with major depressive disorder (MDD) and 23 control youth reported on caffeine use, sleep, and affect in their natural environment using ecological momentary assessment at baseline and over 8 weeks, while MDD youth received treatment.Results: Youth with MDD reported more caffeine use and sleep problems relative to healthy youth. Youth with MDD reported more anxiety on days they consumed caffeine. Caffeine use among youth with MDD decreased across treatment, but sleep complaints remained elevated.Conclusions: Findings suggest that both sleep quality and caffeine use are altered in pediatric depression; that caffeine use, but not sleep problems, improves with treatment; and that caffeine may exacerbate daily anxiety among youth with depression. [ABSTRACT FROM AUTHOR]

Objective: Changes in reward-related behavior are an important component of normal adolescent affective development. Understanding the neural underpinnings of these normative changes creates a foundation for investigating adolescence as a period of vulnerability to affective disorders, substance use disorders, and health problems. Studies of reward-related brain function have revealed conflicting findings regarding developmental change in the reactivity of the striatum and medial prefrontal cortex (mPFC) and have not considered puberty. The current study focused on puberty-specific changes in brain function and their association with mood.Method: A sample of 77 healthy adolescents (26 pre-/early pubertal, 51 mid-/late pubertal) recruited in a narrow age range (mean = 11.94 years, SD = 0.75) were assessed for sexual maturation and circulating testosterone, completed a functional magnetic resonance imaging (fMRI) guessing task with monetary reward, and underwent experience sampling of mood in natural environments. For comparison, 19 healthy adults completed the fMRI assessment.Results: Adolescents with more advanced pubertal maturation exhibited less striatal and more mPFC reactivity during reward outcome than similarly aged adolescents with less advanced maturation. Testosterone was positively correlated with striatal reactivity in boys during reward anticipation and negatively correlated with striatal reactivity in girls and boys during reward outcome. Striatal reactivity was positively correlated with real-world subjective positive affect and negatively correlated with depressive symptoms. mPFC reactivity was positively correlated with depressive symptoms.Conclusions: Reward-related brain function changes with puberty and is associated with adolescents' positive affect and depressive symptoms. Increased reward-seeking behavior at this developmental point could serve to compensate for these changes. [ABSTRACT FROM AUTHOR]

Is adolescent major depressive disorder (MDD) associated with difficulties in young adult psychosocial functioning?METHODS:Design: Prospective cohort study.Follow up period: One year, and when participants were aged 24.Setting: Nine high schools in two urban and three rural communities in Oregon, USA; recruitment from 1987 to 1989.People: 1709 people recruited in high school, of whom 941 completed assessments at baseline, 1 year follow up, and at age 24. At 1 year follow up, 351 people with a history of MDD, 293 people with a history of non-affective disorder, and 457 people with no history of mental disorder, were selected. Average age of participants at final follow up was 24.2 years. 89% of participants were white, 1% black, 3% Hispanic, 3% American Indian, 3% Asian, and 2% 'other'. 61% of participants were single, 34% married, 3% divorced, and 2% separated. 97% had graduated high school or received a general educational development diploma, and 31% had received at least a bachelors degree.Risk factors: Baseline assessment and 1 year assessment were by face-to-face diagnostic interview and questionnaire, while final follow up (at age 23-25 years) was by mailed questionnaire and diagnostic telephone interview. At baseline, a modified Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS) interview was used to derive a DSM-III-R diagnosis. At 1 year and final follow up, the Longitudinal Interval Follow-Up Evaluation (LIFE) interview was used and diagnosis made according to DSM-IV criteria.Outcomes: Young adult psychosocial functioning (YAPF) variables assessed at final follow up were marital status, parenting, mental health use, smoking habits, global level of functioning (DSM-III-R/DSM-IV), years of school completed, unemployment history, income, relationships with friends and family, social network, minor daily hassles (based on Unpleasant Events Schedule), major adversity (based on Social Readjustment Rating Scale and Psychiatric Epidemiology Research Inventory), physical health, and life satisfaction.MAIN RESULTS:Adolescent MDD was significantly associated with low global functioning (p<0.001), low quality of relations with family (p<0.01), small social network (p<0.01), minor daily hassles (p<0.001), major adversity (p<0.001), low life satisfaction (p<0.001), and mental health treatment use (OR 1.78, 99% CI 1.11 to 2.87; analyses adjusted for comorbid non-affective disorder and demographic variables significantly associated with adolescent MDD). Low life satisfaction was the only YAPF variable more strongly associated with adolescent MDD than adolescent non-affective disorder (p<0.001). After further adjustment for stability of psychosocial functioning, and depressive symptomatology at the time of young adult assessment, no significant association remained between adolescent MDD and any YAPF measure. 24 participants who did not complete the mailed questionnaire were excluded from analysis.CONCLUSIONS:Young adults who have experienced an episode of adolescent MDD experience impairments in many areas of psychosocial functioning. [ABSTRACT FROM AUTHOR]

Background: Extracting research of domain criteria (RDoC) from high-risk populations like those with post-traumatic stress disorder (PTSD) is crucial for positive mental health improvements and policy enhancements. The intricacies of collecting, integrating, and effectively leveraging clinical notes for this purpose introduce complexities., Methods: In our study, we created a natural language processing (NLP) workflow to analyze electronic medical record (EMR) data and identify and extract research of domain criteria using a pre-trained transformer-based natural language model, all-mpnet-base-v2. We subsequently built dictionaries from 100,000 clinical notes and analyzed 5.67 million clinical notes from 38,807 PTSD patients from the University of Pittsburgh Medical Center. Subsequently, we showcased the significance of our approach by extracting and visualizing RDoC information in two use cases: (i) across multiple patient populations and (ii) throughout various disease trajectories., Results: The sentence transformer model demonstrated high F1 macro scores across all RDoC domains, achieving the highest performance with a cosine similarity threshold value of 0.3. This ensured an F1 score of at least 80% across all RDoC domains. The study revealed consistent reductions in all six RDoC domains among PTSD patients after psychotherapy. We found that 60.6% of PTSD women have at least one abnormal instance of the six RDoC domains as compared to PTSD men (51.3%), with 45.1% of PTSD women with higher levels of sensorimotor disturbances compared to men (41.3%). We also found that 57.3% of PTSD patients have at least one abnormal instance of the six RDoC domains based on our records. Also, veterans had the higher abnormalities of negative and positive valence systems (60% and 51.9% of veterans respectively) compared to non-veterans (59.1% and 49.2% respectively). The domains following first diagnoses of PTSD were associated with heightened cue reactivity to trauma, suicide, alcohol, and substance consumption., Conclusions: The findings provide initial insights into RDoC functioning in different populations and disease trajectories. Natural language processing proves valuable for capturing real-time, context dependent RDoC instances from extensive clinical notes., (© 2024. The Author(s).)

Objective: Suicide is a leading cause of death in adolescents and young adults and has increased substantially in the past 15 years. Accurate suicide risk stratification based on rapid screening can help reverse these trends. This study aimed to assess the ability of the Kiddie Computerized Adaptive Test Suicide Scale (K-CAT-SS), a brief computerized adaptive test of suicidality, to predict suicide attempts (SAs) in high-risk youth., Method: A total of 652 participants (age range, 12-24 years), 78% of whom presented with suicidal ideation or behavior, were recruited within 1 month of mental health care contact. The K-CAT-SS, scaled from 0 to 100, was administered at baseline, and participants were assessed at about 1, 3, and 6 months after intake. Weekly incidence of SAs was assessed using the Adolescent Longitudinal Interval Follow-up Evaluation and Columbia-Suicide Severity Rating Scale. A secondary outcome was suicidal behavior, including aborted, interrupted, and actual SAs., Results: The K-CAT-SS showed a 4.91-fold increase in SAs for every 25-point increase in the baseline score (95% CI 2.83-8.52) and a 3.51-fold increase in suicidal behaviors (95% CI 2.32-5.30). These relations persisted following adjustment for prior attempts; demographic variables including age, sex, gender identity, sexual orientation, and race/ethnicity; and other measures of psychopathology. No moderating effects were identified. At 3 months, area under the receiver operating characteristic curve was 0.83 (95% CI 0.72-0.93) for 1 or more SAs., Conclusion: The K-CAT-SS is an excellent tool for suicide risk stratification, particularly in higher-risk populations where other measures have shown lower predictive validity., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To understand adolescent, parent, and provider perceptions of a machine learning algorithm for detecting adolescent suicide risk prior to its implementation primary care., Methods: We conducted semi-structured, qualitative interviews with adolescents (n = 9), parents (n = 12), and providers (n = 10; mixture of behavioral health and primary care providers) across two major health systems. Interviews were audio recorded and transcribed with analyses supported by use of NVivo. A codebook was developed combining codes derived inductively from interview transcripts and deductively from implementation science frameworks for content analysis., Results: Reactions to the algorithm were mixed. While many participants expressed privacy concerns, they believed the algorithm could be clinically useful for identifying adolescents at risk for suicide and facilitating follow-up. Parents' past experiences with their adolescents' suicidal thoughts and behaviors contributed to their openness to the algorithm. Results also aligned with several key Consolidated Framework for Implementation Research domains. For example, providers mentioned barriers inherent to the primary care setting such as time and resource constraints likely to impact algorithm implementation. Participants also cited a climate of mistrust of science and health care as potential barriers., Conclusions: Findings shed light on factors that warrant consideration to promote successful implementation of suicide predictive algorithms in pediatric primary care. By attending to perspectives of potential end users prior to the development and testing of the algorithm, we can ensure that the risk prediction methods will be well-suited to the providers who would be interacting with them and the families who could benefit., Competing Interests: Declaration of Competing Interest The authors declare there are no conflicts of interest relevant to the current manuscript. This work is funded by the National Institute of Mental Health. Authors receive additional funding from the National Institute of Mental Health and other federal granting agencies. Dr. Young receives royalties from Oxford University Press. Dr. Brent receives royalties from Guilford Press, eRT, and UpToDate and consulting fees from HealthWise. Dr. Brent also receives funding from the American Foundation for Suicide Prevention, the Beckwith Institute, and the Once Upon A Time Foundation. Dr. Melhem received an honorarium from Oakstone Publishing for providing a lecture for one of their courses., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Depression is associated with diminished positive affect (PA), postulated to reflect frontostriatal reward circuitry disruptions. Depression has consistently been associated with higher dorsomedial prefrontal cortex (dmPFC) activation, a region that regulates PA through ventral striatum (VS) connections. Low PA in depression may reflect dmPFC's aberrant functional connectivity (FC) with the VS. To test this, we applied theta burst stimulation (TBS) to dmPFC in 29 adults with depression (79% female, M age  = 21.4, SD = 2.04). Using a randomized, counterbalanced design, we administered 3 types of TBS at different sessions: intermittent (iTBS; potentiating), continuous (cTBS; depotentiating), and sham TBS (control). We used neuronavigation to target personalized dmPFC targets based on VS-dmPFC FC. PA and negative affect (NA), and resting-state fMRI were collected pre- and post-TBS. We found no changes in PA or NA with time (pre/post), condition (iTBS, cTBS, sham), or their interaction. Functional connectivity (FC) between the nucleus accumbens and dmPFC showed a significant condition (cTBS, iTBS, and sham) by time (pre-vs. post-TBS) interaction, and post-hoc testing showed decreased pre-to post-TBS for cTBS but not iTBS or sham. For cTBS only, reduced FC pre/post stimulation was associated with increased PA (but not NA). Our findings lend support to the proposed mechanistic model of aberrant FC between the dmPFC and VS in depression and suggest a way forward for treating depression in young adults. Future studies need to evaluate multi-session TBS to test clinical effects., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Anhedonia is a transdiagnostic symptom of severe mental illness (SMI) and emerges during adolescence. Possible subphenotypes and neural mechanisms of anhedonia in adolescents at risk for SMI are understudied., Methods: Adolescents at familial risk for SMI (N = 81) completed anhedonia (e.g., consummatory, anticipatory, social), demographic, and clinical measures and one year prior, a subsample (N = 46) completed fMRI scanning during a monetary reward task. Profiles were identified using k-means clustering of anhedonia type and differences in demographics, suicidal ideation, impulsivity, and emotional processes were examined. Moderation analyses were conducted to investigate whether levels of brain activation of reward regions moderated the relationships between anhedonia type and behaviors., Results: Two-clusters emerged: a high anhedonia profile (high-anhedonia), characterized by high levels of all types of anhedonia, (N = 32) and a low anhedonia profile (low-anhedonia), characterized by low levels of anhedonia types (N = 49). Adolescents in the high-anhedonia profile reported more suicidal ideation and negative affect, and less positive affect and desire for emotional closeness than low-anhedonia profile. Furthermore, more suicidal ideation, less positive affect, and less desire for emotional closeness differentiated the familial high-risk, high-anhedonia profile adolescents from the familial high-risk, low-anhedonia profile adolescents. Across anhedonia profiles, moderation analyses revealed that adolescents with high dmPFC neural activation in response to reward had positive relationships between social, anticipatory, and consummatory anhedonia and suicidal ideation., Limitations: Small subsample with fMRI data., Conclusion: Profiles of anhedonia emerge transdiagnostically and vary on clinical features. Anhedonia severity and activation in frontostriatal reward areas have value for clinically important outcomes such as suicidal ideation., Competing Interests: Declaration of competing interest Over the past 3 years, Dr. Pizzagalli has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Karla Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Otsuka, Sage Therapeutics, Sunovion, and Takeda; he has received honoraria from the Psychonomic Society and American Psychological Association (for editorial work) and from Alkermes; he has received research funding from the Brain and Behavior Research Foundation, Dana Foundation, Wellcome Leap, Millennium Pharmaceuticals, and NIMH; he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Identifying co-occurring mental disorders and elevated risk is vital for optimization of healthcare processes. In this study, we will use DeepBiomarker2, an updated version of our deep learning model to predict the adverse events among patients with comorbid post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD), a high-risk population., Methods: We analyzed electronic medical records of 5565 patients from University of Pittsburgh Medical Center to predict adverse events (opioid use disorder, suicide related events, depression, and death) within 3 months at any encounter after the diagnosis of PTSD+AUD by using DeepBiomarker2. We integrated multimodal information including: lab tests, medications, co-morbidities, individual and neighborhood level social determinants of health (SDoH), psychotherapy and veteran data., Results: DeepBiomarker2 achieved an area under the receiver operator curve (AUROC) of 0.94 on the prediction of adverse events among those PTSD+AUD patients. Medications such as vilazodone, dronabinol, tenofovir, suvorexant, modafinil, and lamivudine showed potential for risk reduction. SDoH parameters such as cognitive behavioral therapy and trauma focused psychotherapy lowered risk while active veteran status, income segregation, limited access to parks and greenery, low Gini index, limited English-speaking capacity, and younger patients increased risk., Conclusions: Our improved version of DeepBiomarker2 demonstrated its capability of predicting multiple adverse event risk with high accuracy and identifying potential risk and beneficial factors., Competing Interests: Declaration of Competing Interest Neal David Ryan is the Treasurer, of the American Academy of Child and Adolescent Psychiatry and also a member of the Scientific Advisory Board of the Child Mind Institute. He reported financial honorarium from the Scientific Advisory Board of the Child Mind Institute. Thomas R Kosten reports funding from the Department of Defense. LiRong Wang reports sub-award from Pharmacotherapies for Alcohol and Substance Use Disorders Alliance (PASA) funded by the Department of Defense. No other disclosures were reported., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Prediction of high-risk events amongst patients with mental disorders is critical for personalized interventions. We developed DeepBiomarker2 by leveraging deep learning and natural language processing to analyze lab tests, medication use, diagnosis, social determinants of health (SDoH) parameters, and psychotherapy for outcome prediction. To increase the model's interpretability, we further refined our contribution analysis to identify key features by scaling with a factor from a reference feature. We applied DeepBiomarker2 to analyze the EMR data of 38,807 patients from the University of Pittsburgh Medical Center diagnosed with post-traumatic stress disorder (PTSD) to determine their risk of developing alcohol and substance use disorder (ASUD). DeepBiomarker2 predicted whether a PTSD patient would have a diagnosis of ASUD within the following 3 months with an average c-statistic (receiver operating characteristic AUC) of 0.93 and average F1 score, precision, and recall of 0.880, 0.895, and 0.866 in the test sets, respectively. Our study found that the medications clindamycin, enalapril, penicillin, valacyclovir, Xarelto/rivaroxaban, moxifloxacin, and atropine and the SDoH parameters access to psychotherapy, living in zip codes with a high normalized vegetative index, Gini index, and low-income segregation may have potential to reduce the risk of ASUDs in PTSD. In conclusion, the integration of SDoH information, coupled with the refined feature contribution analysis, empowers DeepBiomarker2 to accurately predict ASUD risk. Moreover, the model can further identify potential indicators of increased risk along with medications with beneficial effects.

Study Objectives: Healthy sleep is important for adolescent neurodevelopment, and relationships between brain structure and sleep can vary in strength over this maturational window. Although cortical gyrification is increasingly considered a useful index for understanding cognitive and emotional outcomes in adolescence, and sleep is also a strong predictor of such outcomes, we know relatively little about associations between cortical gyrification and sleep. We aimed to identify developmentally invariant (stable across age) or developmentally specific (observed only during discrete age intervals) gyrification-sleep relationships in young people., Methods: A total of 252 Neuroimaging and Pediatric Sleep Databank participants (9-26 years; 58.3% female) completed wrist actigraphy and a structural MRI scan. Local gyrification index (lGI) was estimated for 34 bilateral brain regions. Naturalistic sleep characteristics (duration, timing, continuity, and regularity) were estimated from wrist actigraphy. Regularized regression for feature selection was used to examine gyrification-sleep relationships., Results: For most brain regions, greater lGI was associated with longer sleep duration, earlier sleep timing, lower variability in sleep regularity, and shorter time awake after sleep onset. lGI in frontoparietal network regions showed associations with sleep patterns that were stable across age. However, in default mode network regions, lGI was only associated with sleep patterns from late childhood through early-to-mid adolescence, a period of vulnerability for mental health disorders., Conclusions: We detected both developmentally invariant and developmentally specific ties between local gyrification and naturalistic sleep patterns. Default mode network regions may be particularly susceptible to interventions promoting more optimal sleep during childhood and adolescence., (© The Author(s) 2023. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: Positive associations between therapeutic alliance and outcome (e.g. youth symptom severity) have been documented in the youth anxiety literature; however, little is known about the conditions under which early alliance contributes to positive outcomes in youth. The present study examined the relations between therapeutic alliance, session attendance, and outcomes in youths ( N  = 135; 55.6% female) who participated in a randomized clinical trial testing the efficacy of cognitive-behavioral therapy or client-centered therapy for anxiety., Method: We evaluated a conceptual model wherein: (1) early alliance indirectly contributes to positive outcomes by improving session attendance; (2) alliance-outcome associations differ by intervention type, with stronger associations in cognitive-behavioral therapy compared to client-centered therapy; and (3) alliance-outcome associations vary across outcome measurement timepoints, with the effect of early alliance on outcomes decaying over time., Results: Contrary to hypotheses, provider ratings of early alliance predicted greater youth-rated anxiety symptom severity post-treatment (i.e. worse treatment outcomes). Session attendance predicted positive youth-rated outcomes, though there was no indirect effect of early alliance on outcomes through session attendance., Conclusions: Results show that increasing session attendance is important for enhancing outcomes and do not support early alliance as a predictor of outcomes.

Objective: The goal of this study was to examine whether neural sensitivity to negative peer evaluation conveys risk for depression among youth with a history of anxiety. We hypothesized that brain activation in regions that process affective salience in response to rejection, relative to acceptance, from virtual peers would predict depressive symptoms 1 year later and would be associated with ecological momentary assessment (EMA) reports of peer connectedness., Method: Participants were 38 adolescents ages 11-16 (50% female) with a history of anxiety, recruited from a previous clinical trial. The study was a prospective naturalistic follow-up of depressive symptoms assessed 2 years (Wave 2) and 3 years (Wave 3) following treatment. At Wave 2, participants completed the Chatroom Interact Task during neuroimaging and 16 days of EMA., Results: Controlling for depressive and anxiety symptoms at Wave 2, subgenual anterior cingulate (sgACC; β  = .39, p = .010) activation to peer rejection (vs. acceptance) predicted depressive symptoms at Wave 3. SgACC activation to rejection (vs. acceptance) was highly negatively correlated with EMA reports of connectedness with peers in daily life ( r = - .71, p < .001)., Conclusion: Findings suggest that elevated sgACC activation to negative, relative to positive, peer evaluation may serve as a risk factor for depressive symptoms among youth with a history of anxiety, perhaps by promoting vigilance or reactivity to social evaluative threats. SgACC activation to simulated peer evaluation appears to have implications for understanding how adolescents experience their daily social environments in ways that could contribute to depressive symptoms.

The goal of this study was to examine the relation between real-world socio-emotional measures and neural activation to parental criticism, a salient form of social threat for adolescents. This work could help us understand why heightened neural reactivity to social threat consistently emerges as a risk factor for internalizing psychopathology in youth. We predicted that youth with higher reactivity to parental criticism (vs neutral comments) in the subgenual anterior cingulate cortex (sgACC), amygdala and anterior insula would experience (i) less happiness in daily positive interpersonal situations and (ii) more sadness and anger in daily negative interpersonal situations. Participants (44 youth aged 11-16 years with a history of anxiety) completed a 10-day ecological momentary assessment protocol and a neuroimaging task in which they listened to audio clips of their parents' criticism and neutral comments. Mixed-effects models tested associations between neural activation to critical (vs neutral) feedback and emotions in interpersonal situations. Youth who exhibited higher activation in the sgACC to parental criticism reported less happiness during daily positive interpersonal situations. No significant neural predictors of negative emotions (e.g. sadness and anger) emerged. These findings provide evidence of real-world correlates of neural reactivity to social threat that may have important clinical implications., (© The Author(s) 2023. Published by Oxford University Press.)

Purpose: We examined whether interindividual differences in naturalistic sleep patterns correlate with any deviations from typical brain aging., Methods: Our sample consisted of 251 participants without current psychiatric diagnoses (9-25 years; mean [standard deviation] = 17.4 ± 4.52 yr; 58% female) drawn from the Neuroimaging and Pediatric Sleep Databank. Participants completed a T1-weighted structural magnetic resonance imaging scan and 5-7 days of wrist actigraphy to assess naturalistic sleep patterns (duration, timing, continuity, and regularity). We estimated brain age from extracted structural magnetic resonance imaging indices and calculated brain age gap (estimated brain age-chronological age). Robust regressions tested cross-sectional associations between brain age gap and sleep patterns. Exploratory models investigated moderating effects of age and biological gender and, in a subset of the sample, links between sleep, brain age gap, and depression severity (Patient-Reported Outcomes Measurement Information System Depression)., Results: Later sleep timing (midsleep) was associated with more advanced brain aging (larger brain age gap), β = 0.1575, p uncorr  = .0042, p fdr  = .0167. Exploratory models suggested that this effect may be driven by males, although the interaction of gender and brain age gap did not survive multiple comparison correction (β = 0.2459, p uncorr  = .0336, p fdr  = .1061). Sleep duration, continuity, and regularity were not significantly associated with brain age gap. Age did not moderate any brain age gap-sleep relationships. In this psychiatrically healthy sample, depression severity was also not associated with brain age gap or sleep., Discussion: Later midsleep may be one behavioral cause or correlate of more advanced brain aging, particularly among males. Future studies should examine whether advanced brain aging and individual differences in sleep precede the onset of suboptimal cognitive-emotional outcomes in adolescents., (Copyright © 2022 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Poor sleep and anxiety disorders are highly comorbid in youth, and each predicts altered ventral striatum (VS) response to rewards, which may impact mental health risk. Contrasting evidence suggests previously reported negative associations between sleep health and VS response may be stronger or weaker in youth with anxiety, indicating sensitivity to win/loss information or blunted reward processing, respectively. We cross-sectionally examined the role of sleep in VS response to rewards among youth with anxiety versus a no-psychiatric-diagnosis comparison (ND) group. We expected a group*sleep interaction on VS response to rewards but did not hypothesize directionality., Methods: As part of the pretreatment battery for a randomized clinical trial, 74 youth with anxiety and 31 ND youth (ages 9-14 years; n = 55 female) completed a monetary reward task during fMRI. During the same pretreatment window, actigraphy and diary-estimated sleep were collected over 5 days, and participants and their parents each reported participants' total sleep problems. We examined group*sleep interactions on VS response to monetary rewards versus losses via three mixed linear models corresponding to actigraphy, diary, and questionnaires, respectively., Results: Each model indicated group*sleep interactions on VS response to rewards. Actigraphy and diary-estimated time awake after sleep onset predicted reduced VS response in youth with anxiety but not ND youth. Parent-reported sleep problems similarly interacted with group, but simple slopes were nonsignificant., Conclusions: Wake after sleep onset was associated with blunted reward response in youth with anxiety. These data suggest a potential pathway through which sleep could contribute to perturbed reward function and reward-related psychopathology (e.g., depression) in youth with anxiety., (© 2022 Association for Child and Adolescent Mental Health.)

Pediatric anxiety disorders are characterized by potentiated threat responses and maladaptive emotion regulation (ER). The Late Positive Potential (LPP) is a neural index of heightened attention to emotional stimuli. Anxious individuals typically exhibit a larger LPP to unpleasant stimuli, but the LPP may also be blunted to unpleasant and pleasant stimuli for those with co-morbid depression. While a larger LPP is thought to reflect greater emotional reactivity, it is unknown to what extent variation in the LPP to laboratory stimuli corresponds to daily emotional functioning. We assessed the LPP in the laboratory in response to unpleasant, pleasant, and neutral images in combination with ecological momentary assessment of emotional reactivity and regulation in daily life among youth (9-14 years old; 55 % female) with anxiety disorders (ANX, N = 130) and no psychiatric diagnoses (ND, N = 47). We tested whether LPP amplitudes to unpleasant and pleasant stimuli (vs. neutral) are greater in ANX (vs. ND) youth and whether LPP amplitudes inversely correlate with co-morbid depression symptoms. We also examined associations between the LPP and daily life emotional functioning among ANX and ND youth. We found no group-by-valence effects on LPP amplitudes. Within ANX youth, higher depression symptoms were associated with smaller LPP amplitudes to unpleasant, but not pleasant, stimuli relative to neutral stimuli. Larger LPP amplitudes to emotional (relative to neutral) stimuli were correlated with use of specific ER strategies among ANX and ND youth but not emotional reactivity. While the LPP may reflect initial emotional reactivity to laboratory stimuli, it is associated with ER behaviors, and not emotional reactivity, in daily life., Competing Interests: Declaration of competing interest The authors have declared that they have no competing or potential conflicts of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Excessive monitoring of one's performance is a characteristic of anxiety disorders that has been linked to alterations in implicit emotion regulation (ER), including elevations in neural measures of performance monitoring (i.e., error- and correct-related negativity; ERN and CRN). Elevations in ERN and CRN amplitudes have been reported consistently in anxiety disorders, suggesting that an overactive performance monitoring system is linked to ER difficulties in anxiety. Yet, the relevance of these lab-based neural measures for day-to-day emotional functioning remains poorly understood. This study examined the degree to which ERN and CRN amplitudes are associated with measures of daily ER difficulties in youth with anxiety disorders. Youth (N = 100, M age  = 11.14, SD age  = 1.46) completed a computerized flanker task assessing the ERN and CRN. They then completed a 5-day ecological momentary assessment (EMA) protocol assessing their daily ER (i.e., intensity of momentary and peak negative affect, intensity of worry, reliance on maladaptive ER strategies). Results showed that more negative mean CRN amplitudes were associated with higher levels of negative emotional reactivity and more intense worries. There were no significant associations between ERN amplitude and EMA measures. Furthermore, elevations in CRN were linked to more frequent use of maladaptive ER strategies (i.e., rumination, physiological reactivity, avoidance). Together, results indicate that among youth with anxiety, individual differences in CRN, but not ERN, amplitudes are related to daily ER difficulties. Findings highlight the clinical utility of a lab-based neural measure of ER, suggesting that the CRN, rather than the ERN, reflects individual ER differences in the context of daily life among youth with pediatric anxiety disorders. As such, the CRN might serve as an important dimensional index of a treatment target that can be tracked with a validated, multi-method measure., (Copyright © 2022. Published by Elsevier B.V.)

Background: Childhood abuse negatively impacts the course of Bipolar Disorder (BD). Yet, no study has examined risk factors associated with prospectively evaluated physical/sexual abuse, specifically, those preceding first abuse among BD youth. We investigate past/intake/follow-up factors preceding first physical/sexual abuse among BD youth., Methods: Childhood-onset BD participants (n = 279 youth, mean age at intake = 12, mean length of follow-up = 12 years) enrolled in the Course and Outcome of Bipolar Youth (COBY) study. Demographic, clinical and family history variables were assessed every 7 months on average using Longitudinal Interval Follow-up Evaluation and Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS-PL). Abuse was evaluated at intake using the K-SADS-PL, over follow-up with a Traumatic Events Screen. Family psychopathology was assessed using Family History Screen/Structured Clinical Interview for Diagnostic Statistical Manual-IV., Results: Fifteen-percent of youth reported new-onset abuse during follow-up (62% physical, 26% sexual; 12% both). Intake predictors included more severe depressive symptoms (HR = 1.29), low socioeconomic-status (SES) in families with substance abuse (HR = 0.84) (physical abuse), and female sex (HR = 2.41) (sexual abuse). Follow-up predictors preceding physical abuse included: older age (HR = 1.42), disruptive disorders (HR = 1.39), and the interaction between low SES and family substance abuse (HR = 0.86). For sexual abuse, female sex (HR = 4.33) and a non-biologically related father presence in the household (HR = 2.76). Good relationships with friends (prospectively evaluated) protected against physical/sexual abuse (HR = 0.72/0.70, respectively)., Limitations: Prospective data was gathered longitudinally but assessed retrospectively at every follow-up; perpetrator information and abuse severity were not available., Conclusions: Identifying factors temporally preceding new onset physical/sexual abuse may hold promise for identifying high-risk youth with BD., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Limited research has simultaneously focused on sociodemographic differences in who receives recommended adolescent depression screening in primary care and who endorses elevated depression and suicide risk on these screeners. We describe screening and risk rates in a large pediatric primary care network in the United States after the network expanded its universal depression screening guideline to cover all well-visits (i.e., annual medical checkups) for adolescents ages 12 and older., Methods: Between November 15, 2017 and February 1, 2020, there were 122,682 well-visits for adolescents ages 12-17 (82,531 unique patients). The Patient Health Questionnaire - Modified for Teens (PHQ-9-M) was administered to screen for depression., Results: A total of 99,961 PHQ-9-Ms were administered (screening rate=81.48%). The likelihood of screening was higher among adolescents who were female, 12-14 years of age at their first well-visit during the study, White, Hispanic/Latino, or publicly-insured (i.e., Medicaid-insured). Additionally, 5.92% of adolescents scored in the threshold range for depression symptoms and 7.19% endorsed suicidality. Heightened depression and suicide risk were observed among adolescents who were female, 15-17 years of age at their first well-visit during the study, Black, Hispanic/Latino, attending urban primary care practices, or Medicaid-insured. Odds of endorsing suicidality were also higher among teens who identified as other races., Limitations: Limitations related to data available in the electronic health record and reliance on data from a single hospital system are noted., Conclusions: Findings highlight misalignments in screening and risk status that are important to address to ensure more equitable screening implementation and health outcomes., (Copyright © 2021. Published by Elsevier B.V.)

Study Objectives: Structural brain maturation and sleep are complex processes that exhibit significant changes over adolescence and are linked to many physical and mental health outcomes. We investigated whether sleep-gray matter relationships are developmentally invariant (i.e. stable across age) or developmentally specific (i.e. only present during discrete time windows) from late childhood through young adulthood., Methods: We constructed the Neuroimaging and Pediatric Sleep Databank from eight research studies conducted at the University of Pittsburgh (2009-2020). Participants completed a T1-weighted structural MRI scan (sMRI) and 5-7 days of wrist actigraphy to assess naturalistic sleep. The final analytic sample consisted of 225 participants without current psychiatric diagnoses (9-25 years). We extracted cortical thickness and subcortical volumes from sMRI. Sleep patterns (duration, timing, continuity, regularity) were estimated from wrist actigraphy. Using regularized regression, we examined cross-sectional associations between sMRI measures and sleep patterns, as well as the effects of age, sex, and their interaction with sMRI measures on sleep., Results: Shorter sleep duration, later sleep timing, and poorer sleep continuity were associated with thinner cortex and altered subcortical volumes in diverse brain regions across adolescence. In a discrete subset of regions (e.g. posterior cingulate), thinner cortex was associated with these sleep patterns from late childhood through early-to-mid adolescence but not in late adolescence and young adulthood., Conclusions: In childhood and adolescence, developmentally invariant and developmentally specific associations exist between sleep patterns and gray matter structure, across brain regions linked to sensory, cognitive, and emotional processes. Sleep intervention during specific developmental periods could potentially promote healthier neurodevelopmental outcomes., (© Sleep Research Society 2021. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: While adults with bipolar disorder (BD) often report symptoms starting in childhood, continuity of mania and/or hypomania (mania/hypomania) from childhood to adulthood has been questioned. Using longitudinal data from the Course and Outcome of Bipolar Youth (COBY) study, we assessed threshold mania/hypomania in young adults who manifested BD as youth., Methods: COBY is a naturalistic, longitudinal study of 446 youth with BD (84% recruited from outpatient clinics), 7-17 years old at intake, and over 11 years of follow-up. Focusing on youth with BD-I/II (n = 297), we examined adult mania/hypomania risk (>18 years old; mean 7.9 years of follow-up) according to child (<13 years old) versus adolescent (13-17 years old) onset. We next used penalized regression to test demographic and clinical predictors of young adult mania/hypomania., Results: Most participants (64%) had child-onset mania/hypomania, 57% of whom also experienced mania/hypomania in adolescence. Among those who experienced an episode in adolescence, over 40% also had mania/hypomania during adulthood; the risk did not differ according to child versus adolescent onset. In contrast, 7% with mania/hypomania in childhood, but not adolescence, experienced mania/hypomania in adulthood. Family history (of mania and suicide attempts) predicted mania/hypomania in young adulthood (p-values <0.05); age of onset was not a significant predictor. Among participants with no mania/hypomania during adulthood, 53% (105/198) still experienced subthreshold manic episodes., Discussion: We find substantial continuity across developmental stage indicating that, in this carefully characterized sample, children who experience mania/hypomania-particularly those who also experience mania/hypomania in adolescence-are likely to experience mania/hypomania in young adulthood., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Youth with bipolar disorder (BD) are at high risk for suicidal thoughts and behaviors and frequently experience interpersonal impairment, which is a risk factor for suicide. Yet, no study to date has examined the longitudinal associations between relationship quality in family/peer domains and suicidal thoughts and behaviors among youth with BD. Thus, we investigated how between-person differences - reflecting the average relationship quality across time - and within-person changes, reflecting recent fluctuations in relationship quality, act as distal and/or proximal risk factors for suicidal ideation (SI) and suicide attempts., Methods: We used longitudinal data from the Course and Outcome of Bipolar Youth Study (N = 413). Relationship quality variables were decomposed into stable (i.e., average) and varying (i.e., recent) components and entered, along with major clinical covariates, into separate Bayesian multilevel models predicting SI and suicide attempt. We also examined how the relationship quality effects interacted with age and sex., Results: Poorer average relationship quality with parents (β = -.33, 95% Bayesian highest density interval (HDI) [-0.54, -0.11]) or friends (β = -.33, 95% HDI [-0.55, -0.11]) was longitudinally associated with increased risk of SI but not suicide attempt. Worsening recent relationship quality with parents (β = -.10, 95% HDI [-0.19, -0.03]) and, to a lesser extent, friends (β = -.06, 95% HDI [-0.15, 0.03]) was longitudinally associated with increased risk of SI, but only worsening recent relationship quality with parents was also associated with increased risk of suicide attempt (β = -.15, 95% HDI [-0.31, 0.01]). The effects of certain relationship quality variables were moderated by gender but not age., Conclusions: Among youth with BD, having poorer average relationship quality with peers and/or parents represents a distal risk factor for SI but not suicide attempts. Additionally, worsening recent relationship quality with parents may be a time-sensitive indicator of increased risk for SI or suicide attempt., (© 2020 Association for Child and Adolescent Mental Health.)

Background: Concomitant pharmacotherapy has become increasingly common in the treatment of youth, including in psychiatric residential treatment facilities (PRTF) despite limited efficacy and safety data. Research is reported on the prevalence of any class and interclass concomitant pharmacotherapy, specific class combinations of psychotropics, and changes in number of medications from admission to discharge for Medicaid insured youth treated in PRTFs in one mid-Atlantic state. Methods: Medicaid administrative claims data were examined for youth under age 18 years who were discharged from one of 21 PRTFs during calendar year 2019. Descriptive statistics were calculated to examine patterns of service utilization 90 days prior to admission. The rates of concomitant psychotropic use at admission were compared to the rates at discharge. Logistic regression models were used to examine covariates associated with discharging on 4 or more medications. Results: Fifty-four % of youth were admitted on either two or three psychotropics, while 25% were admitted on four or more psychotropics. The proportion of youth admitting and discharging on 2 or 3 medications was stable. There was a 27% increase in number of youth discharging on 4 medications with a 24% decrease in those on a 5- drug regimen. Only the number of medications prescribed at admission was found to be significant ( p < 0.001), with more medications at admission contributing to probability of discharging on 4 or more medications. Conclusions: Concomitant pharmacotherapy is common in PRTFs. These findings support the practice of deprescribing and underscore the need for further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Edelsohn, Eren, Parthasarathy, Ryan and Herschell.)

Objective: Identifying neural correlates of response to psychological treatment may inform targets for interventions designed to treat psychiatric disorders. This study examined the extent to which baseline functioning in reward circuitry is associated with response to psychotherapy in youths with anxiety disorders., Methods: A randomized clinical trial of cognitive-behavioral therapy compared with supportive therapy was conducted in youths with anxiety disorders. Before treatment, 72 youths (9-14 years old) with anxiety disorders and 37 group-matched healthy comparison youths completed a monetary reward functional MRI task. Treatment response was defined categorically as at least a 35% reduction in diagnostician-rated anxiety severity from pre- to posttreatment assessment. Pretreatment neural activation in the striatum and medial prefrontal cortex (mPFC) during monetary wins relative to losses was examined in relation to treatment response., Results: Responders, nonresponders, and healthy youths differed significantly in mPFC activation to rewards versus losses at baseline. Youths with anxiety exhibited higher mPFC activity relative to healthy youths, although this may have been driven by differences in depressive symptoms. Planned comparisons between treatment responders (N=48) and nonresponders (N=24) also revealed greater pretreatment neural activation in a cluster encompassing the subgenual anterior cingulate cortex and nucleus accumbens among responders., Conclusions: Striatal activation to reward receipt may not differentiate youths with anxiety from healthy youths. However, higher striatal responsivity to rewards may allow youths with anxiety to improve during treatment, potentially through greater engagement in therapy. Function in reward circuitry may guide development of treatments for youths with anxiety.

Objective: Limited research exists in predicting first-time suicide attempts that account for two-thirds of suicide decedents. We aimed to predict first-time suicide attempts using a large data-driven approach that applies natural language processing (NLP) and machine learning (ML) to unstructured (narrative) clinical notes and structured electronic health record (EHR) data., Methods: This case-control study included patients aged 10-75 years who were seen between 2007 and 2016 from emergency departments and inpatient units. Cases were first-time suicide attempts from coded diagnosis; controls were randomly selected without suicide attempts regardless of demographics, following a ratio of nine controls per case. Four data-driven ML models were evaluated using 2-year historical EHR data prior to suicide attempt or control index visits, with prediction windows from 7 to 730 days. Patients without any historical notes were excluded. Model evaluation on accuracy and robustness was performed on a blind dataset (30% cohort)., Results: The study cohort included 45 238 patients (5099 cases, 40 139 controls) comprising 54 651 variables from 5.7 million structured records and 798 665 notes. Using both unstructured and structured data resulted in significantly greater accuracy compared to structured data alone (area-under-the-curve [AUC]: 0.932 vs. 0.901 P  < .001). The best-predicting model utilized 1726 variables with AUC = 0.932 (95% CI, 0.922-0.941). The model was robust across multiple prediction windows and subgroups by demographics, points of historical most recent clinical contact, and depression diagnosis history., Conclusions: Our large data-driven approach using both structured and unstructured EHR data demonstrated accurate and robust first-time suicide attempt prediction, and has the potential to be deployed across various populations and clinical settings., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

Background: Pediatric bipolar disorders are often characterized by disruptions in cognitive functioning, and exposure to child maltreatment (e.g., physical and sexual abuse) is associated with a significantly poorer course of illness. Although clinical and developmental research has shown maltreatment to be robustly associated with poorer cognitive functioning, it is unclear whether maltreatment and cognitive function jointly influence the clinical course of bipolar symptoms., Methods: This secondary analysis examined moderating effects of lifetime childhood physical and sexual abuse, and cognitive disruptions (sustained attention, affective information processing), on longitudinal ratings of depression symptom severity in youths from the Course and Outcome of Bipolar Youth (COBY) study, examined from intake (M = 12.24 years) through age 22 (N = 198; 43.9% female; Mean age of bipolar onset = 8.85 years)., Results: A significant moderating effect was detected for sustained attention and maltreatment history. In the context of lower sustained attention, maltreatment exposure was associated with higher depression symptom severity during childhood, but not late adolescence. There was no association between maltreatment and symptom severity in the context of higher sustained attention, and no association between attention and depression symptom severity for non-maltreated youths., Limitations: Depression symptom ratings at each assessment were subject to retrospective recall bias despite the longitudinal design. Cognitive assessments were administered at different ages across youths., Conclusions: Depressive symptoms in pediatric bipolar may be jointly moderated by impairments in attention and exposure to maltreatment. Assessment of these risks, particularly in childhood, may be beneficial for considering risk of recurrence or chronicity of depressive symptoms., (Copyright © 2020. Published by Elsevier B.V.)

Anxiety is the most prevalent psychological disorder among youth, and even following treatment, it confers risk for anxiety relapse and the development of depression. Anxiety disorders are associated with heightened response to negative affective stimuli in the brain networks that underlie emotion processing. One factor that can attenuate the symptoms of anxiety and depression in high-risk youth is parental warmth. The current study investigates whether parental warmth helps to protect against future anxiety and depressive symptoms in adolescents with histories of anxiety and whether neural functioning in the brain regions that are implicated in emotion processing and regulation can account for this link. Following treatment for anxiety disorder (Time 1), 30 adolescents (M age = 11.58, SD = 1.26) reported on maternal warmth, and 2 years later (Time 2) they participated in a functional neuroimaging task where they listened to prerecorded criticism and neutral statements from a parent. Higher maternal warmth predicted lower neural activation during criticism, compared with the response during neutral statements, in the left amygdala, bilateral insula, subgenual anterior cingulate (sgACC), right ventrolateral prefrontal cortex, and anterior cingulate cortex. Maternal warmth was associated with adolescents' anxiety and depressive symptoms due to the indirect effects of sgACC activation, suggesting that parenting may attenuate risk for internalizing through its effects on brain function.

Objective: Despite substantial literature on sex differences in adults with bipolar disorder (BD), little is known about this topic in youth; this study examines sex differences in mood symptomatology and psychiatric comorbidity in prospectively followed youth with BD., Methods: A subsample of the Course and Outcome of Bipolar Youth study (N = 370; female n = 199, male n = 171) enrolled October 2000-July 2006 (age at intake = 7-17.11 years) who met DSM-IV criteria for bipolar I disorder (BD-I; n = 221), bipolar II disorder (BD-II; n = 26), or operationalized BD not otherwise specified (BD-NOS; n = 123) with ≥ 4 years follow-up was included. Analyses examined sex differences at intake and, prospectively, in mood symptomatology and psychiatric comorbidity for a mean ± SD follow-up of 10.5 ± 1.72 years., Results: Females were older than males at intake (mean ± SD age = 13.33 ± 3.32 vs 12.04 ± 3.16 years; P = .0002) and at age at mood onset (9.33 ± 4.22 vs 7.53 ± 3.74 years; P < .0001). After adjustment for confounders, males spent more time with syndromal ADHD (Padjusted = .001) and females spent more time with syndromal anxiety (Padjusted = .02). There were trends toward males spending more time with substance use disorder and females having more non-suicidal self-injurious behavior (Padjusted = .07 and .09, respectively). There were no sex differences on outcome variables, including rate of or time to recovery and recurrence., Conclusions: Contrasting with adult literature, this study identified minimal sex differences in the course of youth with BD. Longer-term studies are needed to clarify if youth-onset BD remains a "sex neutral" subtype of BD or diverges according to sex in adulthood., (© Copyright 2020 Physicians Postgraduate Press, Inc.)

Background: Exposure to severe Traumatic Events (TEs) has been associated with poor course and outcomes among individuals with Bipolar Disorder (BD). However, there is limited research on TEs among youth with BD, and few studies are longitudinal. This study prospectively followed a large sample of BD youth, examining the associations of lifetime TEs with their mood and functioning., Methods: BD participants (n=375; mean age=17; range 8-25y) were assessed, on average, every 7 months for a median 8.7 years. Psychopathology and lifetime trauma history were prospectively evaluated using the Longitudinal Interval Follow-Up Evaluation, and a traumatic events screening., Results: Accounting for covariates, participants with one or more lifetime TEs (84%) showed earlier BD onset, poorer psychosocial functioning, worse mood symptoms, and more suicidal ideation, comorbidities, and family psychopathology than those without TEs. TEs during recovery periods increased recurrence risk (p<0.02). More TEs were associated with poorer mood course, particularly among victims of violence/abuse (p<0.02). Abused participants (34% physical; 17% sexual) showed earlier onset of substance use disorders, more suicidality and comorbidities compared to those without abuse. Comparisons of mood course before and after abuse occurred, and with participants without abuse, showed worsening mood symptoms after, specifically hypo/mania (p<0.03)., Limitations: Prospective data was gathered longitudinally but assessed retrospectively at every follow-up; given approximate dates causality cannot be inferred; TEs severity was not assessed., Conclusions: Severe TEs, particularly abuse, were associated with poorer course and outcomes among BD youth. Prompt screening of trauma and early intervention may be warranted to minimize TEs impact., Competing Interests: Declaration of Competing Interest Dr. Andreu Pascual has received a grant from the Alicia Koplowitz Foundation. Dr. Levenson receives salary support and grant funding from NICHD, grant funding American Academy of Sleep Medicine Foundation and the University of Pittsburgh, and royalties from American Psychological Association Book. Dr. Birmaher reports grants from NIMH, during the conduct of the study; royalties from Random House, Woltas Kluwer (UpToDate) and Lippincott, Williams & Wilkins, outside of the submitted work. Ms. Hower has received research support from NIMH, and honoraria from the Department of Defense (DOD). Dr. Yen has received research support from NIMH, NCCIH, and the American Foundation for Suicide Prevention. Dr. Strober has received research support from NIMH, and support from the Resnick Endowed Chair in Eating Disorders. Dr. T. Goldstein reports grants from NIMH, The American Foundation for Suicide Prevention, University of Pittsburgh Clinical and Translational Science Institute (CTSI) and The Brain and Behavior Foundation and royalties from Guilford Press, outside the submitted work. Dr. B Goldstein reports grants from Brain & Behavior Research Foundation, Brain Canada, Canadian Institutes of Health Research, Heart & Stroke Foundation, and the departments of psychiatry of Sunnybrook Health Sciences Centre and the University of Toronto Department of Psychiatry. Dr. Ryan reports grants from NIH and Axsome Therapeutics. Dr. Weinstock has received research support from NIMH, NCCIH, the NIH OBSSR, and NIJ. Dr. Keller has received research support from NIMH and the John J. McDonnell and Margaret T. O'Brien Foundation. Dr. Axelson reports grants from NIMH, during the conduct of the study; personal fees from Janssen Research and Development, LLC, and UpToDate, outside the submitted work. Mr. Merranko, Ms. Gill report no financial relationships with commercial interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)