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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.

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, puncorr = .0042, pfdr = .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, puncorr = .0336, pfdr = .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.

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.

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.

Adolescence is a key developmental period for developing and strengthening brain circuits that underlie effective decision-making skills, which profoundly impact lifelong health and academic, professional, and economic achievement. But decision-making skills are learned rather than inherent. School presents an ideal environment for the direct instruction and frequent practice of decision-making skills, however, finding time in the school day is a challenge for contemporary educators. We have developed a learning curriculum that involves active student participation to strengthen decision-making skills that is sufficiently flexible and adaptable to be utilized in a wide variety of content-specific classwork. Using this curriculum, students show evidence of improved decision-making skills, including increased consideration of the number of factors that are relevant to their decision, the resources needed to make a particular decision, and both the short-term and long-term consequences of decisions.

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, Mage = 11.14, SDage = 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.

BackgroundTo identify prospectively ascertained individual and family factors that are associated with improvement in Bipolar Disorder (BD) among youths who initially presented with poor course.Methods82 youths with BD with persistent poor mood symptomatology ("predominantly ill course") were compared to 70 youths with BD who at intake had poor course, but showed improvement during the follow-up ("ill with improving course"), (ages 12.3 ± 3.3, vs. 11.7 ± 3.3 years old, at intake). Improvement was measured by the percentage of time euthymic during a mean follow-up of 12.8 years. Youths and parents were interviewed to assess psychopathology, functioning, treatment, and familial functioning and psychopathology.ResultsCompared to the ill group, since intake, the improving group showed significantly lower subthreshold depression and hypo/mania, Attention Deficit Hyperactivity Disorder, and Disruptive Behavior Disorders. Parental Socioeconomic Status (SES) remained unchanged over time in the ill group, but progressively increased in the improving group. Importantly, the change in SES predated the improvement in the mood trajectory. The most influential variables that predicted improvement were higher SES, and absence of parental BD and Substance Use Disorder (SUD). Parental SUD also negatively affected the parental SES, which was directly associated with worse mood course.LimitationsPredominantly self-reported White samples may limit generalizability; other factors potentially associated with outcome (e.g., treatment adherence), were not ascertained.ConclusionsIn addition to treating mood/comorbid psychopathology in symptomatic BD youths, to improve their prognosis, it is crucial to address their parent's BD and SUD and promote parental education/employment.

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.

Study objectivesStructural 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.MethodsWe 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.ResultsShorter 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.ConclusionsIn 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.

ObjectivesWhile 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.MethodsCOBY 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 (

BackgroundYouth 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.MethodsWe 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.ResultsPoorer 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.ConclusionsAmong 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.

ObjectiveIdentifying 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.MethodsA 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.ResultsResponders, 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.ConclusionsStriatal 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.

BackgroundPediatric 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.MethodsThis 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).ResultsA 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.LimitationsDepression symptom ratings at each assessment were subject to retrospective recall bias despite the longitudinal design. Cognitive assessments were administered at different ages across youths.ConclusionsDepressive 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.

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: 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 individuals recurrence risk of depression and/or hypo/mania in BD youths and for developing personalized interventions and informing research. Replication studies are warranted.

ObjectiveLithium 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.MethodCOBY 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.ResultsA 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

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

OBJECTIVES: Compare longitudinal trajectories of youth with Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Bipolar Disorder (BD), grouped at baseline by presence/absence of increased energy during their worst lifetime mood episode (required for DSM-5). METHODS: Participants from the parent Course and Outcome of Bipolar Youth study (N = 446) were assessed utilizing The Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS), KSADS Mania Rating Scale (KMRS), and KSADS Depression Rating Scale (KDRS). Youth were grouped at baseline into those with increased energy (meeting DSM-5 Criteria A for mania) vs. without increased energy (meeting DSM-IV, but not DSM-5, Criteria A for mania), for those who had worst lifetime mood episode recorded (n = 430). Youth with available longitudinal data had the presence/absence of increased energy measured, as well as psychiatric symptomatology/clinical outcomes (evaluated via the Adolescent Longitudinal Interval Follow-Up Evaluation), at each follow-up for 12.5 years (n = 398). RESULTS: At baseline, the increased energy group (based on endorsed increased energy during worst lifetime mood episode; 86% of participants) vs. the without increased energy group, were more likely to meet criteria for BD-I and BD Not Otherwise Specified, had higher KMRS/KDRS total scores, and displayed poorer family/global psychosocial functioning. However, frequency of increased energy between groups was comparable after 5 years, and no significant group differences were found on clinical/psychosocial functioning outcomes after 12.5 years. LIMITATIONS: Secondary data limited study design; groupings were based on one time point. CONCLUSIONS: Results indicate no clinically relevant longitudinal group differences.

ObjectivesCompare longitudinal trajectories of youth with Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV Bipolar Disorder (BD), grouped at baseline by presence/absence of increased energy during their worst lifetime mood episode (required for DSM-5).MethodsParticipants from the parent Course and Outcome of Bipolar Youth study (N = 446) were assessed utilizing The Schedule for Affective Disorders and Schizophrenia for School-Age Children (KSADS), KSADS Mania Rating Scale (KMRS), and KSADS Depression Rating Scale (KDRS). Youth were grouped at baseline into those with increased energy (meeting DSM-5 Criteria A for mania) vs. without increased energy (meeting DSM-IV, but not DSM-5, Criteria A for mania), for those who had worst lifetime mood episode recorded (n = 430). Youth with available longitudinal data had the presence/absence of increased energy measured, as well as psychiatric symptomatology/clinical outcomes (evaluated via the Adolescent Longitudinal Interval Follow-Up Evaluation), at each follow-up for 12.5 years (n = 398).ResultsAt baseline, the increased energy group (based on endorsed increased energy during worst lifetime mood episode; 86% of participants) vs. the without increased energy group, were more likely to meet criteria for BD-I and BD Not Otherwise Specified, had higher KMRS/KDRS total scores, and displayed poorer family/global psychosocial functioning. However, frequency of increased energy between groups was comparable after 5 years, and no significant group differences were found on clinical/psychosocial functioning outcomes after 12.5 years.LimitationsSecondary data limited study design; groupings were based on one time point.ConclusionsResults indicate no clinically relevant longitudinal group differences.

OBJECTIVES: Few studies have examined domain-specific psychosocial functioning in Bipolar Disorder (BD) youths. This prospective study examines (1) Interpersonal Relationships with Family; (2) Interpersonal Relationships with Friends; (3) School/Work; (4) Recreation; (5) Life Satisfaction, in BD youths. METHOD: A Course and Outcome of Bipolar Youth subsample (n = 367; mean intake age = 12.6 years, SD = 3.3; 46.6% female) was previously grouped into 4 Classes based on their illness trajectories and percentage of time euthymic using Latent Class Growth Analysis: Class 1 Predominantly Euthymic; Class 2 Moderately Euthymic; Class 3 Ill with Improving Course; Class 4 Predominantly Ill. Psychosocial functioning within the domains were examined for greater than 10 years using the Adolescent Longitudinal Interval Follow-Up Evaluation. RESULTS: Class 1 demonstrated better functioning across all domains; Class 4 demonstrated worse functioning across all domains. Class 2 showed worsening relationships and recreation, and improvement in work/schoolwork. Class 3 showed variable domain declines and improvements. Despite symptomatic remission, 13%-20% of Class 1 and 20-47% of Classes 1/3 still had impairments across different domains. Early age of BD onset impacted impairment across most domains, and low SES significantly predicted impairment in family relationships. LIMITATIONS: The study does not have a healthy control group to compare functioning findings. CONCLUSIONS: Participants with more symptomatic mood trajectories had greater impairment across domains. Moreover, even with symptomatic remission, participants still exhibited impairment. Each Class and domain had different trajectories for impairment. Results suggest the importance of examining specific (vs. global) domains for targeted treatment, even when symptomatically remitted.

ObjectivesFew studies have examined domain-specific psychosocial functioning in Bipolar Disorder (BD) youths. This prospective study examines (1) Interpersonal Relationships with Family; (2) Interpersonal Relationships with Friends; (3) School/Work; (4) Recreation; (5) Life Satisfaction, in BD youths.MethodA Course and Outcome of Bipolar Youth subsample (n = 367; mean intake age = 12.6 years, SD = 3.3; 46.6% female) was previously grouped into 4 Classes based on their illness trajectories and percentage of time euthymic using Latent Class Growth Analysis: Class 1 Predominantly Euthymic; Class 2 Moderately Euthymic; Class 3 Ill with Improving Course; Class 4 Predominantly Ill. Psychosocial functioning within the domains were examined for greater than 10 years using the Adolescent Longitudinal Interval Follow-Up Evaluation.ResultsClass 1 demonstrated better functioning across all domains; Class 4 demonstrated worse functioning across all domains. Class 2 showed worsening relationships and recreation, and improvement in work/schoolwork. Class 3 showed variable domain declines and improvements. Despite symptomatic remission, 13%-20% of Class 1 and 20-47% of Classes 1/3 still had impairments across different domains. Early age of BD onset impacted impairment across most domains, and low SES significantly predicted impairment in family relationships.LimitationsThe study does not have a healthy control group to compare functioning findings.ConclusionsParticipants with more symptomatic mood trajectories had greater impairment across domains. Moreover, even with symptomatic remission, participants still exhibited impairment. Each Class and domain had different trajectories for impairment. Results suggest the importance of examining specific (vs. global) domains for targeted treatment, even when symptomatically remitted.

This study examines how relationship quality in family and peer domains are associated with suicidal ideation (SI) in youth with bipolar disorder (BP). We assessed 404 Course and Outcome of Bipolar Youth study participants for psychiatric disorders and SI at intake and for family/peer relationships the month after intake. Multivariate logistic regression examined associations between relationships and SI, controlling for significant covariates. There were 144 youth (36%) who reported SI at intake; bivariate analyses indicated they had significantly worse family/peer relationships. Multivariate analyses showed that family/peer relationships were associated with current SI, controlling for significant covariates. Results support associations between poor relationships and SI in BP youth, regardless of current mood symptom severity. Clinicians should assess relationships when completing risk assessments with BP youth.

Suicidal ideation increases in adolescence, especially for anxious youth, and is a frequent precursor to suicide. This study examined whether neural processing of social rejection interacted with negative social experiences to predict suicidal ideation. Thus, to our knowledge this is the first study to examine how brain function may interact with the environment to contribute to suicidal ideation in youth, consistent with a developmental psychopathology perspective. Thirty-six anxious youth (ages 11 to 16) completed diagnostic interviews and questionnaires, an ecological momentary assessment (EMA) protocol, and a functional magnetic resonance imaging paradigm. Results showed that youth experienced greater severity of suicidal ideation when they exhibited heightened activation to social rejection in the right anterior insula and also experienced high levels of peer victimization or EMA-measured daily negative social experiences. Findings provide preliminary evidence that alterations in neural processing of social rejection interacts with exposure to negative social experiences to contribute to suicidal ideation.

OBJECTIVES: To compare the longitudinal clinical course of youths with bipolar disorder (BD) spectrum with lifetime (past, intake, and/or follow-up) psychosis (BDP+) to youths with BD without lifetime psychosis (BDP-). Also, to identify risk factors associated with increased risk of first onset of psychosis during prospective follow-up. METHOD: Bipolar disorder youths (BDP+ = 137, BDP- = 233), aged 7-17 years old, were followed on average every 7 months for 11.7 years and were evaluated using standardized instruments. Data were analyzed using linear and generalized linear models for the full sample, as well as for youths who developed first period of psychosis (n = 55). RESULTS: After adjusting for confounders, BDP+ youths with one, and in particular ≥2 lifetime psychotic episodes, had higher rates and more severe mood and anxiety symptoms, higher rates of suicidality, psychiatric hospitalizations, and sexual/physical abuse, and poorer psychosocial functioning than BDP- youths. Even before the first onset of psychosis during follow-up, BDP+ youths showed more psychopathology and had more family history of psychiatric illness than those who never developed psychosis. First-onset psychosis was associated with low socioeconomic status (SES), living with one parent, bipolar disorder type one and type two, comorbid anxiety, history of hospitalizations, and family history of mania and suicidality. CONCLUSION: BDP+ is associated with poor prognosis and worse clinical picture, even before the onset of psychosis, indicating the need for prompt identification and treatment of these youths. Studies aimed to treat acute symptoms of psychosis, as well as prevent the onset of psychosis, including risk factors amenable to change, are warranted.

ObjectiveDespite 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.MethodsA 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.ResultsFemales 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.ConclusionsContrasting 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.

During adolescence, youth may experience heightened attention bias to socially relevant stimuli; however, it is unclear if attention bias toward social threat may be exacerbated for adolescents with a history of anxiety. This study evaluated attentional bias during the Chatroom-Interact task with 25 adolescents with a history of anxiety (18F, Mage = 13.6) and 22 healthy adolescents (13F, Mage = 13.8). In this task, participants received feedback from fictional, virtual peers who either chose them (acceptance) or rejected them (rejection). Overall, participants were faster to orient toward and spent longer time dwelling on their own picture after both rejection and acceptance compared to non-feedback cues. Social feedback was associated with greater pupillary reactivity, an index of cognitive and emotional neural processing, compared to non-feedback cues. During acceptance feedback (but not during rejection feedback), anxious youth displayed greater pupil response compared to healthy youth, suggesting that positive feedback from peers may differentially influence youth with a history of an anxiety disorder.

Sleep disturbance is prevalent in anxious youth and prospectively predicts poor emotional adjustment in adolescence. Study 1 examined whether anxiety treatment improves subjective and objective sleep disturbance in anxious youth. Study 2 examined whether a sleep intervention called Sleeping TIGERS can further improve sleep following anxiety treatment. Study 1 examined 133 youth (ages 9-14; 56% female; 11% ethnic/racial minority) with generalized, social, or separation anxiety over the course of anxiety treatment (cognitive behavioral treatment or client-centered treatment). Sleep-related problems (parent-, child-report) and subjective (diary) and objective (actigraphy) sleep patterns were assessed across treatment in an open trial design. Study 2 included 50 youth (ages 9-14; 68% female; 10% ethnic/racial minority) who continued to report sleep-related problems after anxiety treatment and enrolled in an open trial of Sleeping TIGERS. Pre- and postassessments duplicated Study 1 and included the Focal Interview of Sleep to assess sleep disturbance. Study 1 demonstrated small reductions in sleep problems and improvements in subjective sleep patterns (diary) across anxiety treatment, but outcomes were not deemed clinically significant, and 75% of youth stayed above clinical cutoff. Study 2 showed clinically significant, large reductions in sleep problems and small changes in some subjective sleep patterns (diary). Anxiety treatment improves, but does not resolve, sleep disturbance in peri-pubertal youth, which may portend risk for poor emotional adjustment and mental health. The open trial provides preliminary support that Sleeping TIGERS can improve sleep in anxious youth to a clinically significant degree.

ObjectivesIn a sample of participants diagnosed with Bipolar Disorder (BD) in youth, we aim: (1) to examine longitudinal psychosocial functioning; (2) to determine whether psychosocial impairment remains in those who remitted from mood disorders during later periods of follow-up; (3) to examine predictors of psychosocial impairment despite symptomatic remission.MethodA Course and Outcome of Bipolar Youth subsample of 367 (≥ 4 years follow-up data) were grouped into mood trajectories: Class 1 Predominantly Euthymic; Class 2 Moderately Euthymic; Class 3 Ill with Improving Course; Class 4 Predominantly Ill. Psychosocial functioning was assessed via Children's Global Assessment Scale (C-GAS) for those under age 22; Global Assessment of Functioning (GAF) scale after 22. Current school, employment, and disability status were examined. Established predictors of symptomatic impairment were analyzed.ResultsThe Predominantly Euthymic Class had better psychosocial functioning, and were more likely to be in school/employed. The Persistently Ill Class had worse psychosocial functioning, and were more likely to receive disability. However, 44% of Predominantly Euthymic and 93% of Ill with Improving Course participants continued to experience current psychosocial impairment. Early BD onset, low Socioeconomic Status (SES), and current comorbidity, predicted poor psychosocial functioning. Low SES, and current comorbidity, predicted no school enrollment/unemployment.LimitationsThe study does not have a healthy control group to compare functioning findings.ConclusionsIn general, youth with persistent mood symptoms had worse psychosocial functioning, moreover, those with remitted symptoms still exhibited current psychosocial functioning deficits. High risk individuals with predictors of impairment should be targeted for functioning interventions.

Anxious youth often have trouble regulating negative affect (NA) and tend to over-rely on parents when faced with challenges. It is unclear how social interactions with parents or peers actually helps or hinders anxious youths' success in regulating NA. The aim of this study was to examine whether the success of anxious youths' emotion regulation strategies differed according to social context. We compared the effectiveness of co-ruminating, co-problem solving and co-distracting with parents/peers for regulating anxious youth's NA in response to stress in their daily lives. We also examined the benefit of attempting each strategy socially vs. non-socially (e.g., co-ruminating vs. ruminating). One-hundred-seventeen youth (9-14) with a current diagnosis of Separation Anxiety Disorder, Generalized Anxiety Disorder, and/or Social Phobia completed an ecological momentary assessment (14 calls over 5 days), reporting on recent stressors, their affective state, presence of others, and emotion regulation strategies within the prior hour. Mixed linear models revealed that co-distracting was the most effective social strategy for reducing NA, but only for boys. Co-rumination was the least effective social strategy for regulating NA. Regarding social context, only co-distracting was more effective for regulating NA over distracting alone, but only among anxious boys. Results suggest that co-rumination is an ineffective use of social support for regulating NA. Anxious boys may benefit from social support by co-distracting with parents/peers, but improper use may reflect avoidance and contribute to long-term anxiety maintenance. Results extend research on gender differences in interpersonal relationships and emotion regulation.

ObjectiveDespite abundant literature demonstrating increased metabolic syndrome (MetS) prevalence and important clinical correlates of MetS among middle-age adults with bipolar disorder, little is known about this topic among adolescents and young adults early in their course of bipolar disorder. We therefore examined this topic in the Course and Outcome of Bipolar Youth (COBY) study.MethodsA cross-sectional, retrospective study was conducted of 162 adolescents and young adults (mean ± SD age = 20.8 ± 3.7 years; range, 13.6-28.3 years) with bipolar disorder (I, II, or not otherwise specified, based on DSM-IV) enrolled in COBY between 2000 and 2006. MetS measures (blood pressure, glucose, high-density lipoprotein cholesterol [HDL-C], triglycerides, and waist circumference), defined using the International Diabetes Federation criteria, were obtained at a single timepoint. Mood, comorbidity, and treatment over the 6 months preceding the MetS assessment were evaluated using the Longitudinal Interval Follow-Up Evaluation.ResultsThe prevalence of MetS in the sample was 19.8% (32/162). Low HDL-C (56.5%) and abdominal obesity (46.9%) were the most common MetS criteria. MetS was nominally associated with lower lifetime global functioning at COBY intake (odds ratio [OR] = 0.97, P = .06). MetS was significantly associated with percentage of weeks in full-threshold pure depression (OR = 1.07, P = .02) and percentage of weeks receiving antidepressant medications (OR = 1.06, P = .001) in the preceding 6 months. MetS was not associated with manic symptoms or medications other than antidepressants.ConclusionsThe prevalence of MetS in this sample was at least double compared to the general population. Moreover, MetS is associated with increased burden of depression symptoms in this group. Management of early-onset bipolar disorder should integrate strategies focused on modifying MetS risk factors.

BACKGROUND:Vigilant attention to threat is commonly observed in anxiety, undergoes developmental changes in early adolescence, and has been proposed to interfere with sleep initiation and maintenance. We present one of the first studies to use objective measures to examine associations between vigilant attention to threat and difficulties initiating and maintaining sleep in an early adolescent anxious sample. We also explore the moderating role of development (age, puberty) and sex. METHODS:Participants were 66 peripubertal youth (ages 9-14) with a primary anxiety disorder and 24 healthy control subjects. A dot-probe task was used to assess attentional bias to fearful relative to neutral face stimuli. Eye-tracking indexed selective attentional bias to threat, and reaction time bias indexed action readiness to threat. Sleep was assessed via actigraphy (e.g. sleep onset delay, wake after sleep onset, etc.), parent report (Children's Sleep Habits Questionnaire), and child report (Sleep Self-Report). The Pediatric Anxiety Rating Scale assessed anxiety severity. RESULTS:Eye-tracking initial threat fixation bias (β = .33, p = .001) and threat dwell time bias (β = .22, p = .041) were positively associated with sleep onset latency. Reaction time bias was positively associated with wake after sleep onset (β = .24, p = .026) and parent-reported sleep disturbance (β = .25, p = .019). Anxiety (severity, diagnosis) was not associated with these outcomes. Sex (β = -.32, p = .036) moderated the relation between initial threat fixation bias and sleep onset latency, with a positive association for males (p = .005), but not for females (p = .289). Age and pubertal status did not moderate effects. CONCLUSIONS:Vigilant attention to threat is related to longer sleep onset and reduced sleep maintenance. These associations are not stronger in early adolescents with anxiety. Implications for early intervention or prevention that targets vigilant attention to threat to impact sleep disturbance, and vice versa, are discussed.

BACKGROUND:Anxiety disorders are associated with an overactive action monitoring system as indexed by a larger error-related negativity (ERN). This study tests whether ERN magnitude changes following treatment, predicts response to treatment, and varies by treatment type. METHODS:The sample included 130 youth (9-14 years): youth with an anxiety disorder (ANX; n = 100) and healthy control (HC; n = 30) youth with no lifetime DSM-IV disorders. ANX youth were randomized to either a manualized cognitive-behavior therapy (CBT) or a comparison child-centered therapy (CCT). The ERN was assessed before and after 16 sessions of treatment and within a comparable interval for HC. Subjective ratings about making errors on the task were obtained following each testing session. The ClinicalTrials.gov identifier is NCT00774150. RESULTS:The ERN was larger in ANX than HC youth but ERN magnitude did not significantly change following treatment in the ANX youth, regardless of treatment type, and baseline ERN did not predict treatment response. Post-task ratings revealed that ANX youth worried more about task performance feedback than HC. Like the ERN, mean ratings did not significantly change following treatment. However, these ratings were not correlated with ERN amplitude. CONCLUSIONS:Findings of greater ERN in pediatric anxiety disorders are replicated in a larger sample. More importantly, findings from this randomized control trial show that a larger ERN and feeling worried about performance feedback remain unchanged following treatment and are unrelated to treatment response. Such findings suggest that action monitoring systems remain overactive in anxious youth treated with psychotherapy, suggesting the need for future investigation of whether novel complimentary cognitive and emotional training programs can modify these systems would be warranted.

ObjectiveMost studies of pediatric bipolar disorder (BP) combine youth who have manic symptoms, but do not meet criteria for BP I/II, into one "not otherwise specified" (NOS) group. Consequently, little is known about how youth with cyclothymic disorder (CycD) differ from youth with BP NOS. The objective of this study was to determine whether youth with a research diagnosis of CycD (RDCyc) differ from youth with operationalized BP NOS.MethodParticipants from the Course and Outcome of Bipolar Youth study were evaluated to determine whether they met RDCyc criteria. Characteristics of RDCyc youth and BP NOS youth were compared at baseline, and over eight-years follow-up.ResultsOf 154 youth (average age 11.96 (3.3), 42% female), 29 met RDCyc criteria. RDCyc youth were younger (p = .04) at baseline. Over follow-up, RDCyc youth were more likely to have a disruptive behavior disorder (p = .01), and were more likely to experience irritability (p = .03), mood reactivity (p = .02), and rejection sensitivity (p = .03). BP NOS youth were more likely to develop hypomania (p = .02), or depression (p = .02), and tended to have mood episodes earlier in the eight-year follow-up period.LimitationsRDCyc diagnoses were made retrospectively and followed stringent criteria, which may highlight differences that, under typical clinical conditions and more vague criteria, would not be evident.ConclusionThere were few differences between RDCyc and BP NOS youth. However, the ways in which the groups diverged could have implications; chronic subsyndromal mood symptoms may portend a severe, but ultimately non-bipolar, course. Longer follow-up is necessary to determine the trajectory and outcomes of CycD symptoms.

ObjectiveYouth with subthreshold mania are at increased risk of conversion to bipolar disorder (BP) I/II. Predictors for conversion have been published for the group as a whole. However, risk factors are heterogeneous, indicating the need for personalized risk assessment.MethodOne hundred forty youth with BP not otherwise specified (BP-NOS; 6-17 years old) followed through the Course and Outcome of Bipolar Youth (COBY) study with at least 1 follow-up assessment before conversion to BP-I/II were included. Youths were assessed on average every 7 months (median 11.5 years) using standard instruments. Risk predictors reported in the literature were used to build a 5-year risk calculator. Discrimination was measured using the time-dependent area under the curve after 1,000 bootstrap resamples. Calibration was evaluated by comparing observed with predicted probability of conversion. External validation was performed using an independent sample of 58 youths with BP-NOS recruited from the Pittsburgh Bipolar Offspring Study.ResultsSeventy-five (53.6%) COBY youths with BP-NOS converted to BP-I/II, of which 57 (76.0%) converted within 5 years. Earlier-onset BP-NOS, familial hypomania/mania, and high mania, anxiety, and mood lability symptoms were important predictors of conversion. The calculator showed excellent consistency between the predicted and observed risks of conversion, good discrimination between converters and non-converters (area under the curve 0.71, CI 0.67-0.74), and a proportionally increasing rate of converters at each successive risk class. Discrimination in the external validation sample was good (area under the curve 0.75).ConclusionIf replicated, the risk calculator would provide a useful tool to predict personalized risk of conversion from subsyndromal mania to BP-I/II and inform individualized interventions and research.

Background. Flea-borne typhus (FBT), an uncommon illness in the United States, typically presents as a high continuous fever with commonly associated symptoms including headache, myalgias, and rashes on the trunk and extremities. Patients infected with FBT may also present with atypical symptoms. As such, the combination of its relatively low incidence in the United States coupled with its variability in associated symptoms poses a diagnostic challenge for clinicians; early empiric treatment with doxycycline is warranted prior to a definitive diagnosis to reduce the risk of damage to vital organs. Case Report. This case describes a 54-year-old male who presented to an emergency room in Houston, Texas, with one week of constant right upper quadrant abdominal pain and fevers up to 40°C. The patient was initially diagnosed with Grade III severe acute cholangitis after abdominal ultrasound revealed gallbladder sludge and wall thickening without ductal dilatation, but a subsequent endoscopic retrograde cholangiopancreatography was unremarkable. Following intermittent fevers and worsening anemia, the patient was started on oral doxycycline for atypical infection, and an infectious disease workup subsequently returned a positive titer for Rickettsia typhi. He experienced rapid symptomatic and clinical improvement, and the patient was discharged home with a final diagnosis of flea-borne typhus. Conclusion. Albeit uncommon, the presentation of this patient’s symptoms and final diagnosis of flea-borne typhus demonstrates the importance of (1) keeping atypical infections such as FBT in the differential diagnosis and (2) beginning empiric treatment to prevent damage to vital organs if suspicion of FBT is high.

This study compared individual cognitive behavioral therapy (CBT) and a supportive child-centered therapy (CCT) for child anxiety disorders on rates of treatment response and recovery at posttreatment and 1-year follow-up, as well as on real-world measures of emotional functioning. Youth (N = 133; ages 9-14) with anxiety disorders (generalized, separation, and/or social anxiety) were randomized using a 2:1 ratio to CBT (n = 90) or CCT (n = 43), which served as an active comparison. Treatment response and recovery at posttreatment and 1-year follow-up were assessed by Independent Evaluators, and youth completed ecological momentary assessment of daily emotions throughout treatment. The majority of youth in both CBT and CCT were classified as treatment responders (71.1% for CBT, 55.8% for CCT), but youth treated with CBT were significantly more likely to fully recover, no longer meeting diagnostic criteria for any of the targeted anxiety disorders and no longer showing residual symptoms (66.7% for CBT vs. 46.5% for CCT). Youth treated with CBT also reported significantly lower negative emotions associated with recent negative events experienced in daily life during the latter stages of treatment relative to youth treated with CCT. Furthermore, a significantly higher percentage of youth treated with CBT compared to CCT were in recovery at 1-year follow-up (82.2% for CBT vs. 65.1% for CCT). These findings indicate potential benefits of CBT above and beyond supportive therapy on the breadth, generalizability, and durability of treatment-related gains.

ObjectiveThis 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.MethodThe 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).ResultsSexually 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.ConclusionDemographic 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.