Search

Objectives: Studies have primarily focused on adverse life events (ALEs) as potential causes rather than as outcomes of pediatric depression. The current study prospectively examines ALEs in a sample of youth with attention-deficit/hyperactivity disorders (ADHD) to determine whether having a major depressive disorder (MDD) at baseline (T1) predicts counts of child-dependent or child-independent ALEs at a second assessment (T2) ≈ 8 months later.Methods: Subjects with ADHD 11-18 years old were drawn mostly from a tertiary mental health clinic and evaluated with semi-structured diagnostic interviews, and parent and teacher questionnaires of ADHD severity. Eighteen with and 61 without initial MDD at T1 were compared at T2 regarding counts of subsequent overall, child-dependent, and child-independent ALEs reported on life events questionnaires by the child or parent.Results: The group initially with MDD had higher overall ALEs (p=0.01) and child-dependent ALEs (p ≤ 0.001) but not child-independent ALEs (p=0.12) at T2 relative to the nondepressed group, although only 3 of 18 continued to meet full criteria for MDD. The group initially with MDD also had a higher baseline ADHD severity (p=0.04) and proportion of oppositional or conduct disorders (p=0.004). In multivariate analyses, the group initially having MDD had a higher adjusted mean at T2 of child-dependent ALEs (p=0.02), but not of overall ALEs (p=0.06), after controlling for other T1 variables, including ALEs of the same type, ADHD severity, externalizing disorders, and the interaction of externalizing disorders with MDD.Conclusions: These findings suggest that child-dependent ALEs are potentially an important outcome after youth with ADHD have an episode of MDD. Youth with ADHD who develop comorbid MDD should be closely monitored and offered interventions to address the potential burden of child-dependent ALEs lingering after a depressive episode. [ABSTRACT FROM AUTHOR]

Background: Previous work indicates that polygenic risk scores (PRS) for bipolar disorder (BD) are elevated in adults and youth with BD, but whether BD-PRS can inform person-level diagnostic prediction is unknown. Here, we test whether BD-PRS improves performance of a previously published risk calculator (RC) for BD., Methods: 156 parents with BD-I/II and their offspring ages 6-18 were recruited and evaluated with standardized diagnostic assessments every two years for >12 years. DNA was extracted from saliva samples, genotyping performed, and BD-PRS calculated based on a 2021 meta-analysis. Using a bootstrapped and cross-validated penalized Cox regression, we assessed whether BD-PRS (alone and interacting with clinical variables) improved RC performance., Results: Of 227 offspring, 38 developed BD during follow-up. The penalized regression selected BD-PRS and interactions between BD-PRS and parental age at mood disorder onset (AAO), depression, and anxiety. The resulting RC discriminated offspring who developed BD (vs. those that did not) with good accuracy (AUC = 0.81); removing BD-PRS and its interaction terms was associated with a significant decrement to the AUC (decrement = 0.07, p = 0.039). Further exploration of selected interaction terms indicated that all were significant (p-values<0.02), indicating that BD-PRS has a larger effect on the outcome in offspring with depression and anxiety, whose affected parent had a younger AAO., Conclusions: The addition of BD-PRS to clinical/demographic predictors in the RC significantly improved its accuracy. BD-PRS predicted BD on the person-level, particularly in offspring of parents with earlier AAO who already had symptoms of anxiety and depression at intake., Competing Interests: Declaration of competing interest Dr. Hafeman reports grants from NIMH and the Brain and Behavior Research Foundation. Dr. Birmaher reports grants from NIMH and royalties from Random House, UpToDate and Lippincott, Williams & Wilkins. 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. Axelson reports grants from NIMH, during the conduct of the study; and royalties from Wolters-Kluwer/UpToDate, outside the submitted work. Dr. Diler has received research support from NIMH. Dr. B. Goldstein reports grant funding from Brain Canada, Canadian Institutes of Health Research, Heart & Stroke Foundation, National Institute of Mental Health, and the departments of psychiatry at the University of Toronto, and acknowledges salary support from the RBC Investments Chair, held at the Centre for Addiction and Mental Health and the University of Toronto department of psychiatry. Dr. Sakolsky reports grant support from NIMH. Mr. Merranko, Dr. Zwicker, and Dr. Uher reports no financial relationships with commercial interests., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Importance: Early-onset bipolar disorder conveys substantial risk for suicide. No psychosocial intervention for this population expressly targets suicidal behavior., Objective: To determine whether dialectical behavior therapy (DBT) for adolescents with bipolar spectrum disorder is more effective than standard of care (SOC) psychotherapy in decreasing suicide attempts over 1 year., Design, Settings, and Participants: Adolescents aged 12 to 18 years diagnosed with bipolar spectrum disorder were recruited from a specialty outpatient psychiatric clinic between November 2014 and September 2019. Independent evaluators conducted quarterly assessments over 1 year with participants and parents. Data were analyzed from March 2021 to November 2022., Interventions: Participants were randomly assigned to 1 year of DBT (36 sessions; n = 47) or SOC psychotherapy (schedule clinically determined; n = 53). All youth received medication management via a flexible algorithm., Main Outcomes and Measures: Primary outcomes included suicide attempts over 1 year and mood symptoms and states (depression and hypomania/mania). Secondary analyses included moderation of DBT effects by history of suicide attempt and mediation through emotion dysregulation., Results: Of 100 included participants, 85 (85%) were female, and the mean (SD) age was 16.1 (1.6) years. Participants were followed up over a mean (SD) of 47 (14) weeks. Both treatment groups demonstrated significant and similar improvement in mood symptoms and episodes over 1 year (standardized depression rating scale slope, -0.17; 95% CI, -0.31 to -0.03; standardized mania rating scale slope, -0.24; 95% CI, -0.34 to -0.14). DBT and SOC participants reported similar suicide attempt rates at intake as measured on the Adolescent Longitudinal Follow-Up Evaluation (ALIFE; mean [SD] attempts, 2.0 [4.5] vs 1.8 [3.9], respectively; P = .80). DBT participants reported slightly more suicide attempts at intake as measured on the Columbia-Suicide Severity Rating Scale Pediatric Version (C-SSRS; mean [SD] attempts, 1.4 [3.6] vs 0.6 [0.9]; P = .02). DBT participants reported significantly fewer suicide attempts over follow-up compared with SOC participants via the ALIFE (mean [SD] attempts per follow-up period, 0.2 [0.4] vs 1.1 [4.3], controlling for baseline attempts: P = .03) and the C-SSRS (mean [SD] attempts per follow-up period, 0.04 [0.2] vs 0.10 [0.3], controlling for baseline attempts; P = .03). DBT was significantly more effective than SOC psychotherapy at decreasing suicide attempts over 1 year (ALIFE: incidence rate ratio [IRR], 0.32; 95% CI, 0.11-0.96; C-SSRS: IRR, 0.13; 95% CI, 0.02-0.78). Decreased rate of suicide attempts in DBT was moderated by presence of lifetime history of suicide attempt and time (IRR, 0.23; 95% CI, 0.13-0.44) and mediated by improvement in emotion dysregulation (IRR, 0.61; 95% CI, 0.42-0.89), particularly for those with high baseline emotion dysregulation (standardized β, -0.59; 95% CI, -0.92 to -0.26)., Conclusions and Relevance: In this randomized clinical trial, DBT demonstrated efficacy in decreasing suicide attempts among the high-risk population of adolescents with bipolar spectrum disorder., Trial Registration: ClinicalTrials.gov Identifier: NCT02003690.

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.)

Importance: Establishing genetic contributions to the transmission of bipolar disorder (BD) from parents to offspring may inform the risk of developing this disorder and further serve to validate BD in youth., Objective: To evaluate the specific association of BD polygenic risk scores (PRSs) on the familial transmission and validity of pediatric BD., Design, Setting, and Participants: This community-based case-control longitudinal study (Pittsburgh Biological Offspring Study) included parents with BD I/II and their offspring and parents without BD (healthy or non-BD psychopathology) and their offspring. Participants were recruited between March 2001 and May 2007, and analysis took place from December 2020 to September 2021., Exposures: PRSs for BD, major depressive disorder, schizophrenia, and attention-deficit/hyperactivity disorder., Main Outcomes and Measures: Participants were prospectively evaluated using standardized interviews blind to parental diagnosis. DNA was extracted from saliva and genotyped. PRSs were constructed based on independent large-scale genome-wide association studies., Results: A total of 156 parents with BD I/II and 180 parents without BD (mean [SD] age, 39.6 [7.9] years; 241 female [72%]) as well as 251 offspring of parents with BD and 158 offspring of parents without BD (mean [SD] age, 10.4 [4.7] years; 213 female [52%]) of European ancestry were analyzed. Participants were assessed a mean of 6.7 times during a mean (SD) of 13 (3.4) years of follow-up (84% retention). More offspring of parents with BD developed BD (58 [23.1%] vs 8 [5.1%]; P < .001) and depression (126 [50.2%] vs 52 [32.9%]; P < .001) compared with offspring of parents without BD. BD PRS was higher in both parents and offspring with BD than parents and offspring without BD (parents: odds ratio, 1.50; 95% CI, 1.19-1.89; P < .001; explained 4.8% of the phenotypic variance vs offspring: hazard ratio, 1.34; 95% CI, 1.03-1.7; P = .02; explained 5.0% of the phenotypic variance). BD PRS did not differ across BD subtypes. In a model combining parental and offspring BD PRS, the parental BD PRS association with offspring BD was fully mediated by offspring BD PRS (hazard ratio, 1.40; 95% CI, 1.05-1.86; P = .02). Parental BD had a stronger direct association than parental or offspring BD PRS with offspring BD risk (hazard ratio, 5.21; 95% CI, 1.86-14.62; P = .002), explaining 30% of the variance. Parental and offspring BD PRS explained 6% of the BD onset variance beyond parental diagnosis. There were no significant between-group differences in PRSs for major depressive disorder, schizophrenia, and attention-deficit/hyperactivity disorder in parents or offspring and they were not significantly associated with BD onset., Conclusions and Relevance: The findings of this study add to the extant clinical validation of BD in youth. Parental BD and offspring BD PRS independently associated with the risk of BD in offspring. Although this is promising, the association of BD PRS was relatively small and cannot be used alone to determine BD risk until further developments occur.

Objective: To compare the prevalence of psychopathology, particularly bipolar disorder (BD), between preschool offspring of parents with BD and community controls., Method: A total of 116 offspring of BD-I/II parents and 98 controls (53 parents with non-BD psychopathology and 45 healthy parents) were recruited at ages 2 to 5 years and followed on average 9.6 years (on average: 2-5: 1.6 times; after age 5: 4 times) (average ages at intake/last follow-up: 3.8/13.4, retention: 98%). Participants were evaluated with standardized instruments blinded to parental diagnoses., Results: After adjusting for confounders, offspring of BD parents only showed more attention-deficit/hyperactivity disorder (ADHD) during ages 2 to 5 years than the other 2 groups. After age 5, offspring of BD parents did not differ from offspring of parents with non-BD psychopathology, but they had more anxiety, ADHD, and behavior problems than offspring of healthy parents. Only offspring of BD parents developed BD-I/II: 3.4% (n = 4) and BD-not-otherwise-specified (BD-NOS): 11.2% (n = 13), with mean onset ages 11.4 and 7.4, respectively. About 70% of offspring with BD had non-BD disorders before BD. Only ADHD, diagnosed before age 6 years, and early-onset parental BD were significantly associated with BD risk., Conclusion: Most offspring of BD parents did not develop BD, but they were at specific high risk for developing BD, particularly those with preschool ADHD and early-onset parental BD. BD symptoms were scarce during the preschool years and increased throughout the school age, mainly in the form of BD-NOS, a disorder that conveys poor prognosis and high risk to develop BD-I/II. Developing early interventions to delay or, ideally, to prevent its onset are warranted., (Copyright © 2021 American Academy of Child & Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: To evaluate the efficacy in reduction of depressive symptoms, and safety and tolerability of second-generation antipsychotics (SGAs) to manage pediatric bipolar depression (PBD). Methods: We conducted a systematic review for randomized clinical trials (RCTs) for PBD in MEDLINE, Scopus, and EMBASE. Four (quetiapine: 2, lurasidone: 1, olanzapine-fluoxetine combination [OFC]: 1) out of 569 studies met the criteria for inclusion in meta-analysis. RevMan was used for statistical analysis, and the mean difference (MD) between mean children's depression rating scale-revised (CDRS-R) score was used to measure treatment difference between SGA and placebo. Results: Lurasidone displayed a significant reduction in depressive symptoms (MD -5.70, 95% confidence interval [CI] -8.67 to -2.73) in PBD, followed by OFC (MD -5.00, 95% CI -8.64 to -1.36) and quetiapine (MD -2.30, 95% CI -6.80 to 2.20; MD 1.00, 95% CI -9.88 to 11.88). The response was significantly higher for lurasidone (59.5% vs. 36.5%; p  < 0.001) and OFC (78.2% vs. 59.2%, p  = 0.003) compared with placebo. There was no statistically significant MD in treatment and response rates between quetiapine and placebo in all RCTs. The weighted mean CDRS-R total score difference was -4.58 (95% CI -6.59 to -2.56) and overall effect was significant ( p  < 0.00001). Importantly, the p value for heterogeneity was 0.46, which indicated that there was no heterogeneity between outcomes of the studies. The number needed to treat (NNT) for lurasidone was 4.3, followed by OFC (NNT = 5.3) and quetiapine (NNT = 12.5; NNT = 25). Conclusion: Our findings showed lurasidone and OFC were more efficacious than placebo for acute depressive episodes in PBD. RCTs of treatments for PBD remain scarce pressing the need for more research.

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.)

Bipolar disorder (BD) is common and debilitating and confounding effects of depression history on neural activity in BD are unknown. We aimed to dissociate neural activity reflecting past depression-load vs. present symptom severity using the Course and Outcome of Bipolar Youth (COBY), a prospective longitudinal cohort study of pediatric-onset BD. In n = 54 COBY (18-32 years), we modeled depression scores over time (up to 17.5 years) using a standardized autoregressive moving average (ARMA) model, followed by k-means cluster analysis. N = 36 healthy participants (HC, 20-36 years) were included. Using two factorial analyses, we parsed the impact of ARMA-defined past depression-load on neural activity from the impact of current symptoms on neural activity (p < 0.001, k > 30) and examined relationships with past and present symptoms (ps FDR-corrected). ARMA identified three COBY groups based on past depression-load. ARMA-defined COBY participants with the greatest past depression-load vs. other groups showed greater activity in right temporoparietal junction, thalamus, insula, premotor cortex, left fusiform gyrus, bilateral precuneus and cerebellum. In contrast, BD-COBY participants vs. HC showed greater activity in left hippocampus, dorsolateral prefrontal cortex, and right somatosensory cortex, plus the above thalamus, premotor cortex and cerebellum; activity positively correlated with present symptom severity in most regions. Past depression-load was related to social cognition and salience perception network activity, potentially reflecting heightened attention to socially relevant distracters, while present symptoms were associated with emotion processing and reappraisal network activity, potentially reflecting abnormal emotional experience and regulation. Differentiating aberrant neural activity related to long-term depression vs. present affective symptoms can help target interventions to networks associated with pathophysiological processes, rather than long-term illness effects.

Objective: Lithium is the mainstay for bipolar disorder (BD) treatment in adults, but evidence in youths is limited. We used data from the Course and Outcome of Bipolar Youth (COBY) study to assess whether lithium vs other mood-stabilizing medication (OMS) was associated with improved outcomes, including mood symptoms and suicidality., Method: COBY is a naturalistic, longitudinal study of 413 youths, 7 to 17.11 years old at intake, with BD. At each visit, medication exposure, psychiatric symptoms, and psychosocial function over the preceding follow-up period were assessed using the Adolescent Longitudinal Interval Follow-Up Evaluation. Using mixed models, we determined whether participants taking lithium vs OMS (but not lithium) differed regarding mood symptoms, suicidality, psychosocial function, hospitalization, aggression, and substance use., Results: A total of 340 participants contributed 2,638 six-month follow-up periods (886 lithium, 1,752 OMS), over a mean follow-up of 10 years. During lithium (vs OMS) follow-up periods, participants were older, less likely to have lifetime anxiety, and less likely to be on antidepressants (p values<.005). After covariate adjustment, the lithium group (vs OMS) had half as many suicide attempts (p = .03), fewer depressive symptoms (p = .004), less psychosocial impairment (p = .003), and less aggression (p = .0004). Similar findings were observed in the subgroup of follow-up periods in which participants were <18 years old., Conclusion: Findings are consistent with adult studies, showing that lithium is associated with decreased suicidality, less depression, and better psychosocial functioning. Given the paucity of evidence regarding lithium in children and adolescents, these findings have important clinical implications for the pharmacological management of youths with BD., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: With each recurrence the prognosis of bipolar disorder (BD) worsens, indicating the need to identify the factors associated with increased recurrence risk. The course of BD is heterogenous and although risk factors for recurrence for the group as a whole have been reported in the literature, identification of risk factors for a specific individual are crucial for developing personalized treatments., Method: A total of 363 recovered BD youths/young adults from the Course and Outcome of Bipolar Youth (COBY) study were included. Participants were evaluated on average every 7 months for a median of 12.5 years and interviewed with standard instruments. Risk factors of recurrence from the literature were used to build a risk calculator (RC) to predict recurrence risk at different time intervals., Results: Approximately 80% of participants had at least one syndromal recurrence and 60% had ≥2 recurrences, particularly depressions. The 6-month and 1-, 2-, 3-, and 5-year RC showed an accuracy between 72% and 82% for predicting any mood recurrences, and up to 80% for depression and 89% for hypo/mania (sensitivity/specificity both 0.74). The most influential recurrence risk factors were shorter recovery lengths, younger age at assessment, earlier mood onset, and more severe prior depression. Although important, other factors associated with recurrence risk, such as interepisodic subsyndromal mood symptoms and comorbidities, did not influence the RC score beyond factors noted above., Conclusion: The RC provides a useful tool for predicting an individual's recurrence risk of depression and/or hypo/mania in BD youths and for developing personalized interventions and informing research. Replication studies are warranted., (Copyright © 2020 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

We aimed to identify markers of future affective lability in youth at bipolar disorder risk from the Pittsburgh Bipolar Offspring Study (BIOS) (n = 41, age = 14, SD = 2.30), and validate these predictors in an independent sample from the Longitudinal Assessment of Manic Symptoms study (LAMS) (n = 55, age = 13.7, SD = 1.9). We included factors of mixed/mania, irritability, and anxiety/depression (29 months post MRI scan) in regularized regression models. Clinical and demographic variables, along with neural activity during reward and emotion processing and gray matter structure in all cortical regions at baseline, were used to predict future affective lability factor scores, using regularized regression. Future affective lability factor scores were predicted in both samples by unique combinations of baseline neural structure, function, and clinical characteristics. Lower bilateral parietal cortical thickness, greater left ventrolateral prefrontal cortex thickness, lower right transverse temporal cortex thickness, greater self-reported depression, mania severity, and age at scan predicted greater future mixed/mania factor score. Lower bilateral parietal cortical thickness, greater right entorhinal cortical thickness, greater right fusiform gyral activity during emotional face processing, diagnosis of major depressive disorder, and greater self-reported depression severity predicted greater irritability factor score. Greater self-reported depression severity predicted greater anxiety/depression factor score. Elucidating unique clinical and neural predictors of future-specific affective lability factors is a step toward identifying objective markers of bipolar disorder risk, to provide neural targets to better guide and monitor early interventions in bipolar disorder at-risk youth.

Objective: To compare the longitudinal course of family functioning in offspring of parents with bipolar disorder (BD), offspring of parents with non-BD psychopathology, and offspring of healthy control (HC) parents., Method: Offspring of parents with BD (256 parents and 481 offspring), parents without BD (82 parents and 162 offspring), and HC parents (88 parents and 175 offspring) 7 to 18 years of age at intake, from the Bipolar Offspring Study (BIOS), were followed for an average of 4.3 years. Family functioning was evaluated using the child- and parent-reported Family Adaptability and Cohesion Scale-II and the Conflict Behavior Questionnaire. The data were analyzed using multivariate multilevel regression, generalized linear estimating equation models, and path analysis., Results: Families of parents with BD and parents with non-BD psychopathology showed lower cohesion and adaptability and higher conflict compared with HC families. There were no significant differences in cohesion and adaptability between families of parents with psychopathology. The effect of parental psychopathology on family functioning was mediated by parental psychosocial functioning and, to a lesser extent, offspring disorders. In all 3 groups, parent-reported family conflict was significantly higher than child-reported conflict. Across groups, family cohesion decreased over follow-up, whereas conflict increased., Conclusion: Any parental psychopathology predicted family impairment. These results were influenced by the offspring's age and were mediated by parental psychosocial functioning and, to a lesser degree, by offspring psychopathology. These findings emphasize the need to routinely assess family functioning in addition to psychopathology and provide appropriate interventions to parents and offspring., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Sleep disturbance may be involved in symptom progression across multiple domains of psychopathology and could represent a target for treatment development in youth. Our objective was to identify sleep patterns that longitudinally change in conjunction with psychiatric symptom severity in at-risk youth., Method: The study included 484 Pittsburgh Bipolar Offspring Study (BIOS) youth with at least 2 sleep assessments occurring between 10 and 18 years of age: 267 offspring of parents with bipolar I or II disorder and 217 community comparison offspring. Assessments occurred approximately every 2 years (mean number of assessments, 2.8 ± 0.8; mean follow-up duration, 3.8 ± 1.6 years). Offspring had a range of psychiatric diagnoses at baseline. Multivariate lasso regression was implemented to select offspring-reported sleep patterns associated with changes in five psychiatric symptom measures from baseline through last follow-up (mania, depression, mood lability, anxiety, inattention/externalizing). Analyses accounted for parent psychiatric diagnoses and offspring demographics, psychiatric diagnoses, and medications., Results: Follow-up duration, baseline socioeconomic status, parental history of bipolar disorder, offspring attention-deficit/hyperactivity disorder, and disruptive behavior disorder, and five sleep patterns were identified as predictors of change in all five psychiatric symptom measures. Decreasing sleep duration, later sleep timing preference, longer sleep latency, increasing nighttime awakenings, and greater sleepiness over follow-up were associated with increasing severity the five psychiatric symptom outcomes over follow-up. These 10 predictors explained 16% of the variance in longitudinal psychiatric symptom change, 33% of which was accounted for by sleep predictors., Conclusion: A constellation of sleep features were associated with psychiatric symptom changes in youth, and may represent viable targets for future interventions., (Copyright © 2019 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the prevalence and risk factors associated with psychotic-like experiences (PLE) in offspring of parents with bipolar disorder (BP) and offspring of community control parents., Method: Delusional and hallucinatory subclinical psychotic experiences were evaluated at intake and longitudinally in a cohort study of 390 offspring of BP parents and 247 offspring of control parents; all offspring were between 6 and 18 years of age. The sample was followed up every 2.5 years on average for 8.3 years. Of the sample, 91.7% completed at least one follow-up. Risk factors at intake and at each assessment until the onset of PLE were analyzed using survival models., Results: In all, 95 offspring (14.9%) reported PLE at some point of the study, 16.9% of BP parents and 11.7% of controls, without statistically significant differences. Psychotic disorders were less frequent, with 16 (2.5%) in both groups. During follow-up, three variables remained as the most significant associated with PLE in the multivariate models: (1) presence of any psychiatric disorder (hazard ratio [HR] = 3.1; p = .01); (2) low psychosocial functioning (HR = 2.94; p < .0001); and (3) current or past history of physical or sexual abuse (HR = 1.85; p = .04). There were no effects of any subtype of BP, IQ, history of medical illnesses, exposure to medications, or perinatal complications., Conclusion: In line with previous studies, PLE in our sample were relatively common, and were associated with higher morbidity during the follow-up. Contrary to the literature, neither family risk for bipolar nor early neurodevelopmental insults were associated with PLE., (Copyright © 2018 American Academy of Child and Adolescent Psychiatry. All rights reserved.)

Objective: This study aims to document rates of sexual activity among youth with bipolar spectrum disorder (BD) and to examine demographic and clinical factors associated with first sexual activity and sexual risk behavior during follow-up., Method: The sample was drawn from the Course and Outcome of Bipolar Youth (COBY) study of 413 youth 7 to 17 years at baseline who met criteria for bipolar spectrum disorder according to the Schedule for Affective Disorders and Schizophrenia for School-Aged Children. Psychiatric symptoms during follow-up were assessed using the Adolescent Longitudinal Interview Follow-Up Evaluation (ALIFE). Sexual behavior and level of sexual risk (e.g., unprotected sex, multiple partners, and/or partners with known sexually transmitted infections) were assessed by trained evaluators using the ALIFE Psychosocial Functioning Scale. Analyses were conducted in relation to first sexual behavior during follow-up and then to subsequent sexual behaviors (mean 9.7 years, standard deviation 3.2)., Results: Sexually active COBY youth (n = 292 of 413; 71%) were more likely females, using substances, and not living with both parents. Consistent with findings among healthy youth, earlier first sexual activity in the sample was significantly associated with low socioeconomic status, female sex, comorbid disruptive behavior disorder, and substance use. As with healthy youth, sexual risk behavior during follow-up was significantly associated with non-Caucasian race, low socioeconomic status, substance use, and history of sexual abuse. Of those COBY youth who were sexually active, 11% reported sexual assault or abuse, 36% reported becoming pregnant (or the significant other becoming pregnant), and 15% reported having at least 1 abortion (or the significant other having an abortion) during follow-up. Hypomanic symptoms during follow-up were temporally associated with the greatest risk for sexual risk behavior., Conclusion: Demographic and clinical factors could help identify youth with bipolar spectrum disorder at significantly greatest risk for sexual activity and sexual risk behavior. Attending to sexual risk behaviors in this population is warranted., (Copyright © 2017 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Importance: Early identification of individuals at high risk for the onset of bipolar spectrum disorder (BPSD) is key from both a clinical and research perspective. While previous work has identified the presence of a bipolar prodrome, the predictive implications for the individual have not been assessed, to date., Objective: To build a risk calculator to predict the 5-year onset of BPSD in youth at familial risk for BPSD., Design, Setting, and Participants: The Pittsburgh Bipolar Offspring Study is an ongoing community-based longitudinal cohort investigation of offspring of parents with bipolar I or II (and community controls), recruited between November 2001 and July 2007, with a median follow-up period of more than 9 years. Recruitment has ended, but follow-up is ongoing. The present analysis included offspring of parents with bipolar I or II (aged 6-17 years) who had not yet developed BPSD at baseline., Main Outcomes and Measures: This study tested the degree to which a time-to-event model, including measures of mood and anxiety, general psychosocial functioning, age at mood disorder onset in the bipolar parent, and age at each visit, predicted new-onset BPSD. To fully use longitudinal data, the study assessed each visit separately, clustering within individuals. Discrimination was measured using the time-dependent area under the curve (AUC), predicting 5-year risk; internal validation was performed using 1000 bootstrapped resamples. Calibration was assessed by comparing observed vs predicted probability of new-onset BPSD., Results: There were 412 at-risk offspring (202 [49.0%] female), with a mean (SD) visit age of 12.0 (3.5) years and a mean (SD) age at new-onset BPSD of 14.2 (4.5) years. Among them, 54 (13.1%) developed BPSD during follow-up (18 with BD I or II); these participants contributed a total of 1058 visits, 67 (6.3%) of which preceded new-onset BPSD within the next 5 years. Using internal validation to account for overfitting, the model provided good discrimination between converting vs nonconverting visits (AUC, 0.76; bootstrapped 95% CI, 0.71-0.82). Important univariate predictors of outcome (AUC range, 0.66-0.70) were dimensional measures of mania, depression, anxiety, and mood lability; psychosocial functioning; and parental age at mood disorder., Conclusions and Relevance: This risk calculator provides a practical tool for assessing the probability that a youth at familial risk for BPSD will develop new-onset BPSD within the next 5 years. Such a tool may be used by clinicians to inform frequency of monitoring and treatment options and for research studies to better identify potential participants at ultra high risk of conversion.

Background: Sleep disturbances are a prominent feature of bipolar disorder (BP). However, it remains unclear how sleep phenotypes may evolve among at-risk youth, and their relevance to BP onset., Methods: Pittsburgh Bipolar Offspring Study (BIOS) offspring (ages 10-18) and their parents completed assessments approximately every two years pertaining to current psychopathology and offspring sleep habits. A latent transition analysis (LTA) identified latent sleep groups within offspring based on their ratings of six sleep domains using the School Sleep Habits Survey. Demographic and clinical characteristics were compared between sleep groups. Logistic regression tested links between sleep group and BP onset at the subsequent assessment., Results: The LTA model identified latent groups of good, poor, and variable sleepers. We observed an overall trend of good sleep becoming variable, and then poor, as youth age. Offspring in the poor sleep group were more likely to have psychopathology. Adjusting for age and depression, poor sleepers had nearly twice the odds of developing BP relative to good (OR=1.99, CI=0.45-8.91) or variable (OR=2.03, CI=0.72-5.72) sleepers., Limitations: Limitations include the use of proximal sleep phenotypes to predict BP onset, and a self-report measure of sleep CONCLUSIONS: We found three non-overlapping sleep phenotype groups in a large sample of offspring of bipolar probands and offspring of demographically-matched community control parents. Clinicians should consider that youth will likely experience variable and/or poor sleep as they age, and that at-risk youth with poor sleep may be at increased risk of developing MDD and BP at their next assessment., (Copyright © 2017. Published by Elsevier B.V.)

Objective: There is substantial interest in delineating the course of cognitive functioning in bipolar (BP) youth. However, there are no longitudinal studies aimed at defining subgroups of BP youth based on their distinctive cognitive trajectories and their associated clinical variables., Method: Cognitive functioning was measured in 135 participants from the Course and Outcome of BP Youth (COBY) study using several subtests of the Cambridge Neuropsychological Test Automated Battery (CANTAB). Youth were prospectively evaluated three times on average every 13.75 months over 2.5 years. Clinical and functional outcomes were assessed using the Longitudinal Interval Follow-Up Evaluation (LIFE)., Results: Latent class growth analysis identified three longitudinal patterns of cognitive functioning based on a general cognitive index: class 1, "persistently high" (N=21; 15.6%); class 2, "persistently moderate" (N=82; 60.74%); and class 3, "persistently low" (N=32; 23.7%). All classes showed normal cognitive functioning when compared with the CANTAB normative data. After adjustment for confounders, youth from class 3 had a significantly greater percentage of time with overall, manic, and depressive syndromal symptoms than youth in the other two classes. Also, after adjustment for confounders, youth from class 3 had significantly poorer global, academic, and social functioning than youth from class 1., Conclusions: BP youth showed normal overall cognitive functioning that remained stable during the follow-up within each class. However, 24% of BP youth showed poorer cognitive functioning than the other BP youth. This subgroup had poorer mood course and functioning, and may benefit from cognitive remediation and early management with evidence-based pharmacological treatments., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Hypothalamic-Pituitary-Adrenal (HPA) axis dysregulation is associated with increased risk for suicidal behavior. However, it is not clear whether such dysregulation exists prior to or is a consequence of attempt. Studies also show an activation of inflammatory responses in suicidal behavior but often combine attempters with those with ideation., Methods: The sample consisted of psychiatric inpatients, aged 15-30 years, admitted for suicide attempt (SA, n=38), inpatients admitted for suicidal ideation with no prior history of attempts (SI, n=40), and healthy controls (n=37). We compared SA, SI, and controls on hair cortisol concentrations (HCC), which provides retrospective levels of cortisol and thus prior to the attempt in SA. We also compared them on the expression of genes in the HPA axis and inflammatory pathways previously implicated in suicidal behavior (GR or NR3C1, SKA2, FKBP5, IL-1β, TNF-α); plasma C-Reactive Protein (CRP); and cellular measures of glucocorticoid receptor (GR) sensitivity and stimulated production of IL-6., Results: We found lower HCC [β=-0.55, 95% CI (-0.96, -0.13), p=0.01, ES=-0.54] in first-time SA compared to SI and controls. In addition, SA showed lower GR or NR3C1 (α isoform) mRNA [β=-5.11, 95% CI (-10.9, 0.73), p=0.09, ES=-0.46], higher CRP [β=0.94, 95% CI (-0.004, 1.9), p=0.05, ES=0.60], and higher TNF-α mRNA [β=26.4, 95% CI (7.7, 45.2), p=0.006, ES=0.73]., Conclusions: This is the first study to differentiate youth who attempt suicide from those with suicidal ideation on HCC and to show that low HCC precedes suicide attempt. Suicide attempters also showed a distinct biological profile on several markers in both the HPA axis and inflammatory pathways. Future longitudinal studies are needed to examine the ability of these biomarkers to predict suicidal behavior., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: Treatment-refractory depression is a devastating condition with significant morbidity, mortality, and societal cost. At least 15% of cases of major depressive disorder remain refractory to treatment. The authors previously identified a young adult with treatment-refractory depression and multiple suicide attempts with an associated severe deficiency of CSF tetrahydrobiopterin, a critical cofactor for monoamine neurotransmitter synthesis. Treatment with sapropterin, a tetrahydrobiopterin analogue, led to dramatic and long-lasting remission of depression. This sentinel case led the authors to hypothesize that the incidence of metabolic abnormalities contributing to treatment-refractory depression is underrecognized., Method: The authors conducted a case-control, targeted, metabolomic evaluation of 33 adolescent and young adult patients with well-characterized histories of treatment-refractory depression (at least three maximum-dose, adequate-duration medication treatments), and 16 healthy comparison subjects. Plasma, urine, and CSF metabolic profiling were performed by coupled gas chromatography/mass spectrometry and high-performance liquid chromatography electrospray ionization tandem mass spectrometry., Results: CSF metabolite abnormalities were identified in 21 of the 33 participants with treatment-refractory depression. Cerebral folate deficiency (N=12) was most common, with normal serum folate levels and low CSF 5-methyltetrahydrofolate (5-MTHF) levels. All patients with cerebral folate deficiency, including one with low CSF levels of 5-MTHF and tetrahydrobiopterin intermediates, showed improvement in depression symptom inventories after treatment with folinic acid; the patient with low tetrahydrobiopterin also received sapropterin. None of the healthy comparison subjects had a metabolite abnormality., Conclusions: Examination of metabolic disorders in treatment-refractory depression identified an unexpectedly large proportion of patients with potentially treatable abnormalities. The etiology of these abnormalities remains to be determined.

Objective: Accumulating evidence suggests cross-national differences in adults with bipolar disorder (BD), but also in the susceptibility of their offspring (bipolar offspring). This study aims to explore and clarify cross-national variation in the prevalence of categorical and dimensional psychopathology between bipolar offspring in the US and The Netherlands., Methods: We compared levels of psychopathology in offspring of the Pittsburgh Bipolar Offspring Study (n=224) and the Dutch Bipolar Offspring Study (n=136) (age 10-18). Categorical psychopathology was ascertained through interviews using the Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS-PL), dimensional psychopathology by parental reports using the Child Behavior Checklist (CBCL)., Results: Higher rates of categorical psychopathology were observed in the US versus the Dutch samples (66% versus 44%). We found no differences in the overall prevalence of mood disorders, including BD-I or -II, but more comorbidity in mood disorders in US versus Dutch offspring (80% versus 34%). The strongest predictors of categorical psychopathology were maternal BD (OR: 1.72, p<.05), older age of the offspring (OR: 1.19, p<.05), and country of origin (US; OR: 2.17, p<.001). Regarding comorbidity, only country of origin (OR: 7.84, p<.001) was a significant predictor. In general, we found no differences in dimensional psychopathology based on CBCL reports., Limitations: Preliminary measure of inter-site reliability., Conclusions: We found cross-national differences in prevalence of categorical diagnoses of non-mood disorders in bipolar offspring, but not in mood disorder diagnoses nor in parent-reported dimensional psychopathology. Cross-national variation was only partially explained by between-sample differences. Cultural and methodological explanations for these findings warrant further study., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: The authors sought to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorders in youths at familial risk of bipolar disorder ("at-risk" youths)., Method: Offspring 6-18 years old of parents with bipolar I or II disorder (N=359) and community comparison offspring (N=220) were recruited. At baseline, 8.4% of the offspring of bipolar parents had a bipolar spectrum disorder. Over 8 years, 14.7% of offspring for whom follow-up data were available (44/299) developed a new-onset bipolar spectrum disorder (15 with bipolar I or II disorder). Measures collected at baseline and follow-up were reduced using factor analyses, and factors (both at baseline and at the visit prior to conversion or last contact) were assessed as predictors of new-onset bipolar spectrum disorders., Results: Relative to comparison offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsyndromal manic, and affective lability symptoms. The strongest predictors of new-onset bipolar spectrum disorders were baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p<0.05). While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed a bipolar spectrum disorder, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesis that affective lability at baseline predicts a new-onset bipolar spectrum disorder in part through increased manic symptoms at the visit prior to conversion; earlier parental age at mood disorder onset was also significantly associated with an increased risk of conversion. While youths without anxiety/depression, affective lability, and mania (and with a parent with older age at mood disorder onset) had a 2% predicted chance of conversion to a bipolar spectrum disorder, those with all risk factors had a 49% predicted chance of conversion., Conclusions: Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of new-onset bipolar spectrum disorders in at-risk youths. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings.

Objectives: Disruptions in sleep and dysregulation in circadian functioning may represent core abnormalities in the pathophysiology of bipolar disorder (BP). However, it is not clear whether these dysfunctions are state or trait markers of BP. This report compared sleep and circadian phenotypes among three groups: offspring of parents with BP diagnosed with BP at intake (BP/OB; n = 47), offspring of parents with BP without BP at intake (non-BP/OB; n = 386), and offspring of matched control parents who did not have BP (controls; n = 301). We also examined the association of baseline sleep parameters with subsequent development of BP among the non-BP/OB group., Methods: Pittsburgh Bipolar Offspring Study youth (ages 6-18 years) and their parents completed assessments every two years pertaining to the child's sleep and circadian phenotypes and current psychopathology. Mixed-effects models examined differences in baseline sleep and circadian variables among the three groups., Results: BP/OB offspring who were in a mood episode differed significantly on sleep parameters from the non-BP/OB and the offspring of controls, such as having inadequate sleep. Mixed logistic regression procedures showed that baseline sleep and circadian variables, such as frequent waking during the night, significantly predicted the development of BP among non-BP/OB over longitudinal follow-up., Conclusions: While lifetime diagnostic status accounted for differences among the groups in sleep and circadian disturbances, psychopathology explained the differences even further. Additionally, sleep disturbance may be a prognostic indicator of the development of BP in high-risk youth. Future studies are required to further disentangle whether sleep and circadian disruption are state or trait features of BP., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Despite burgeoning literature in middle-aged adults, little is known regarding proinflammatory markers (PIMs) among adolescents and young adults with bipolar disorder. Similarly, few prior studies have considered potential confounds when examining the association between PIMs and bipolar disorder characteristics. We therefore retrospectively examined these topics in the Course and Outcome of Bipolar Youth (COBY) study., Method: Subjects were 123 adolescents and young adults (mean [SD] = 20.4 ± 3.8 years; range, 13.4-28.3 years) in COBY, enrolled between October 2000 and July 2006. DSM-IV diagnoses were determined using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). Clinical characteristics during the preceding 6 months, including mood, comorbidity, and treatment, were evaluated using the Longitudinal Interval Follow-Up Evaluation (LIFE). Serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP) were assayed. Primary analyses examined the association of PIMs with bipolar disorder characteristics during the preceding 6 months., Results: Several lifetime clinical characteristics were significantly associated with PIMs in multivariable analyses, including longer illness duration (P = .005 for IL-6; P = .0004 for hsCRP), suicide attempts (P = .01 for TNF-α), family history of suicide attempts or completion (P = .01 for hsCRP), self-injurious behavior (P =.005 for TNF-α), substance use disorder (SUD) (P < .0001 for hsCRP), and family history of SUD (P = .02 for TNF-α; P = .01 for IL-6). The following bipolar disorder characteristics during the preceding 6 months remained significantly associated with PIMs in multivariable analyses that controlled for differences in comorbidity and treatment: for TNF-α, percentage of weeks with psychosis (χ(2) = 5.7, P =.02); for IL-6, percentage of weeks with subthreshold mood symptoms (χ(2)= 8.3, P = .004) and any suicide attempt (χ(2) = 6.1, P = .01); for hsCRP, maximum severity of depressive symptoms (χ(2) = 8.3, P =.004)., Conclusion: Proinflammatory markers may be relevant to bipolar disorder characteristics as well as other clinical characteristics among adolescents and young adults with bipolar disorder. Traction toward validating PIMs as clinically relevant biomarkers in bipolar disorder will require repeated measures of PIMs and incorporation of relevant covariates., (© Copyright 2015 Physicians Postgraduate Press, Inc.)

Objective: The authors sought to identify diagnostic risk factors of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder ("high-risk offspring")., Method: High-risk offspring 6-18 years old (N=391) and demographically matched offspring (N=248) of community parents without bipolar disorder were assessed longitudinally with standardized diagnostic instruments by staff blind to parental diagnoses. Follow-up assessments were completed in 91% of the offspring (mean follow-up interval, 2.5 years; mean follow-up duration, 6.8 years)., Results: Compared with community offspring, high-risk offspring had significantly higher rates of subthreshold mania or hypomania (13.3% compared with 1.2%), manic, mixed, or hypomanic episodes (9.2% compared with 0.8%), and major depressive episodes (32.0% compared with 14.9%). They also had higher rates of attention deficit hyperactivity disorder (30.7% compared with 18.1%), disruptive behavior disorders (27.4% compared with 15.3%), anxiety disorders (39.9% compared with 21.8%), and substance use disorders (19.9% compared with 10.1%), but not unipolar major depressive disorder (major depression with no bipolarity; 18.9% compared with 13.7%). Multivariate Cox regressions showed that in the high-risk offspring, subthreshold manic or hypomanic episodes (hazard ratio=2.29), major depressive episodes (hazard ratio=1.99), and disruptive behavior disorders (hazard ratio=2.12) were associated with subsequent manic, mixed, or hypomanic episodes. Only subthreshold manic or hypomanic episodes (hazard ratio=7.57) were associated when analyses were restricted to prospective data., Conclusions: Subthreshold manic or hypomanic episodes were a diagnostic risk factor for the development of manic, mixed, or hypomanic episodes in the offspring of parents with bipolar disorder and should be a target for clinical assessment and treatment research. Major depressive episodes and disruptive behavior disorders are also indications for close clinical monitoring of emergent bipolarity in high-risk offspring.

Objective: The authors evaluated lifetime prevalence and specificity of DSM-IV psychiatric disorders and severity of depressive and manic symptoms at intake in preschool offspring of parents with bipolar I and II disorders., Method: A total of 121 offspring ages 2-5 years from 83 parents with bipolar disorder and 102 offspring of 65 demographically matched comparison parents (29 with non-bipolar psychiatric disorders and 36 without any lifetime psychopathology) were recruited for the study. Parents with bipolar disorder were recruited through advertisements and adult outpatient clinics, and comparison parents were ascertained at random from the community. Participants were evaluated with standardized instruments. All staff were blind to parental diagnoses., Results: After adjustment for within-family correlations and both biological parents' non-bipolar psychopathology, offspring of parents with bipolar disorder, particularly those older than age 4, showed an eightfold greater lifetime prevalence of attention deficit hyperactivity disorder (ADHD) and significantly higher rates of having two or more psychiatric disorders compared to the offspring of the comparison parents. While only three offspring of parents with bipolar disorder had mood disorders, offspring of parents with bipolar disorder, especially those with ADHD and oppositional defiant disorder, had significantly more severe current manic and depressive symptoms than comparison offspring., Conclusions: Preschool offspring of parents with bipolar disorder have an elevated risk for ADHD and have greater levels of subthreshold manic and depressive symptoms than children of comparison parents. Longitudinal follow-up is warranted to evaluate whether these children are at high risk for developing mood and other psychiatric disorders.

Objectives: To assess emotional (depression, anxiety and self-esteem) and behavioural problems in migrant children and to compare them with non-migrant children., Methods: 526 students (60% boys, 40% girls) aged 11.23 +/- 1.05, at five schools in Adana, Turkey in areas with a high migrant population were included in this study. 182 children (35%) were migrants and 344 children (65%) were non-migrants. The Depression Inventory for Children (CDI), the State-Trait Anxiety Inventory for Children (STAI-C) and the Coopersmith Self-Esteem Inventory (CSEI) were administered to the pupils at their school and Rutter's Teachers Rating Scale (RTRS) was administered to their teachers. Sociodemographic variables were recorded on the basis of school records and the children's report., Results: In the migrant group, fathers were less educated and had more employment problems, homes were rented and the children were unsuccessful at school. Migrant children had significantly lower self-esteem with higher depression and anxiety. Behavioural symptoms on RTRS were not significant with regard to migration. No significant correlation was found between psychometric tests and father's education, duration of residence after migration or room density., Conclusions: We found significant emotional but no behavioural problems in Turkish migrant children compared to Turkish non-migrant children. Further prospective studies are needed to clarify the long-term course of the various types of distress and the individual prognosis of migrant adjustment.