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AimComorbid anxiety disorder is related to greater illness severity among individuals at clinical high risk (CHR) for psychosis, but its potential role in moderating response to Family Focused Therapy (FFT) for CHR is unexamined. We investigated whether comorbid anxiety disorder in CHR individuals is associated with less constructive communication during family problem-solving interactions, whether their communication skills differentially improve after FFT, and whether FFT is effective in reducing anxiety in this population.MethodsIndividuals recruited into the second phase of the 8-site North American Prodrome Longitudinal Study (NAPLS2) participated (N = 129). They were randomly assigned to 18-sessions of FFT-CHR or three-sessions of Enhanced Care (EC). Participants completed a diagnostic interview at pre-treatment, a family interaction task at pre-treatment and 6-months, and a self-report anxiety measure at pretreatment, 6 and 12-months.ResultsIndividuals at CHR with comorbid anxiety engaged in more negative and fewer positive behaviours during family problem-solving interactions at pre-treatment than did those without comorbid anxiety. There was a significant interaction between anxiety diagnosis and time on interactional behaviour scores, such that individuals at CHR with an anxiety diagnosis showed a greater decrease in negative behaviours and increase in positive behaviours from baseline to 6-months than those without anxiety disorder(s) regardless of treatment condition. However, individuals' self-reported anxiety symptoms decreased more in FFT-CHR than in EC from pre-treatment to 12-month follow-up, regardless of anxiety diagnoses.ConclusionsIndividuals at CHR with symptoms of anxiety benefit from family interventions in showing reductions in anxiety and improvements in family communication.

Adolescence is critical period of neurocognitive development as well as increased prevalence of mood pathology. This cross-sectional study replicated developmental patterns of neurocognition and tested whether mood symptoms moderated developmental effects. Participants were 419 adolescents (n=246 with current mood disorders) who completed reward learning and executive functioning tasks, and reported on age, puberty, and mood symptoms. Structural equation modeling revealed a quadratic relationship between puberty and reward learning performance that was moderated by symptom severity: in early puberty, adolescents reporting higher manic symptoms exhibited heightened reward learning performance (better maximizing of rewards on learning tasks), whereas adolescents reporting elevated anhedonia showed blunted reward learning performance. Models also showed a linear relationship between age and executive functioning that was moderated by manic symptoms: adolescents reporting higher mania showed poorer executive functioning at older ages. Findings suggest neurocognitive development is altered in adolescents with mood pathology and suggest directions for longitudinal studies.

Psychotherapy is an important part of managing bipolar depression and its associated impairments. There is considerable evidence that psychotherapies are effective adjuncts to pharmacotherapy in delaying or preventing episodes of bipolar depression. Individuals with bipolar depression may be reticent to consider these treatments. This paper surveys the utility, evidence base, effective treatment components, and controversies surrounding adjunctive psychosocial interventions.

BackgroundWe examined whether digital phenotyping of spontaneous speech, such as the use of specific word categories during speech samples, was associated with depressive symptoms in youth who were at familial and clinical risk for mood disorders.MethodsParticipants (ages 13-19) had active mood symptoms, mood instability, and at least one parent with bipolar or major depressive disorder. During a randomized trial of family-focused therapy, participants were instructed to make weekly calls to a central voice server and leave speech samples in response to automated prompts. We coded youths' speech samples with the Linguistic Inquiry and Word Count system and used machine learning to identify the combination of speech features that were most closely associated with the course of depressive symptoms over 18 weeks.ResultsA total of 253 speech samples were collected from 44 adolescents (mean age = 15.8 years; SD = 1.6) over 18 weeks. Speech containing affective processes, social processes, drives toward risk or reward, nonfluencies, and time orientation words were correlated with depressive symptoms at concurrent time periods (ps

Bipolar disorder is heterogeneous in phenomenology, illness trajectory, and response to treatment. Despite evidence for the efficacy of multimodal-ity interventions, the majority of persons affected by this disorder do not achieve and sustain full syndromal recovery. It is eagerly anticipated that combining datasets across various information sources (e.g., hierarchical "multi-omic" measures, electronic health records), analyzed using advanced computational methods (e.g., machine learning), will inform future diagnosis and treatment selection. In the interim, identifying clinically meaningful subgroups of persons with the disorder having differential response to specific treatments at point-of-care is an empirical priority. This paper endeavours to synthesize salient domains in the clinical characterization of the adult patient with bipolar disorder, with the overarching aim to improve health outcomes by informing patient management and treatment considerations. Extant data indicate that characterizing select domains in bipolar disorder provides actionable information and guides shared decision making. For example, it is robustly established that the presence of mixed features - especially during depressive episodes - and of physical and psychiatric comorbidities informs illness trajectory, response to treatment, and suicide risk. In addition, early environmental exposures (e.g., sexual and physical abuse, emotional neglect) are highly associated with more complicated illness presentations, inviting the need for developmentally-oriented and integrated treatment approaches. There have been significant advances in validating subtypes of bipolar disorder (e.g., bipolar I vs. II disorder), particularly in regard to pharmacological interventions. As with other severe mental disorders, social functioning, interpersonal/family relationships and internalized stigma are domains highly relevant to relapse risk, health outcomes, and quality of life. The elevated standardized mortality ratio for completed suicide and suicidal behaviour in bipolar disorder invites the need for characterization of this domain in all patients. The framework of this paper is to describe all the above salient domains, providing a synthesis of extant literature and recommendations for decision support tools and clinical metrics that can be implemented at point-of-care.

ObjectiveMood instability is associated with the onset of bipolar disorder (BD) in youth with a family history of the illness. In a clinical trial with youth at high risk for BD, we examined the association between mood instability and symptomatic, psychosocial, and familial functioning over an average of 2 years.MethodYouth (aged 9-17 years) with major depressive disorder or other specified BD, current mood symptoms, and a family history of BD were rated by parents on a mood instability scale. Participants were randomly assigned to 4 months of family-focused therapy or enhanced care psychoeducation, both with medication management as needed. Independent evaluators rated youth every 4-6 months for up to 4 years on symptom severity and psychosocial functioning, whereas parents rated mood instability of the youth and levels of family conflict.ResultsHigh-risk youth (N = 114; mean age 13.3 ± 2.6 years; 72 female) were followed for an average of 104.3 ± 65.8 weeks (range, 0-255 weeks) after randomization. Youth with other specified BD (vs major depressive disorder), younger age, earlier symptom onset, more severe mood symptoms, lower psychosocial functioning, and more familial conflict over time had higher mood instability ratings throughout the study period. Mood instability mediated the association between baseline diagnosis and mother/offspring conflict at follow-up (Z = 2.88, p = .004, αβ = 0.19, 95% CI = 0.06-0.32). Psychosocial interventions did not moderate these associations.ConclusionA questionnaire measure of mood instability tracked closely with symptomatic, psychosocial, and family functioning in youth at high risk for BD. Interventions that are successful in reducing mood instability may enhance long-term outcomes among high-risk youth.Clinical trial registration informationEarly Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.

BackgroundAlthough transdiagnostic forms of cognitive-behavioral therapy (CBT) have been evaluated in individuals with depressive and anxiety disorders, few studies have examined their suitability for more severe disorders, such as recurrent or persistent major depressive disorder, bipolar disorder, or psychotic spectrum disorders. This study examined the acceptability and initial efficacy of an app-enhanced Unified Protocol for Adolescents [UP-A] when including youth with more severe mood disorders or psychotic spectrum disorders.MethodsWe first adapted a mobile application (app), based on user-centered feedback from adolescents and their parents, to assist participants in reviewing session content, practicing skills learned in previous treatment sessions, and monitoring symptomatic progress. A total of 24 adolescents (M age = 15.2 years, SD = 1.6) with mood or psychotic spectrum disorders and their parents then participated in an open trial of the app-enhanced group treatment given over 9 weekly sessions.ResultsAdolescent participants and their parents rated the group treatment and mobile app as acceptable and useful. We observed significant improvements over the 9-week treatment in adolescents' depressive symptoms, attenuated psychotic symptoms, and global functioning. The frequency with which adolescents used the mobile app between sessions was positively related to symptomatic and functional gains.ConclusionsInitial findings suggest the acceptability and feasibility of a mobile app that enabled adolescent participants and their parents to review session content and practice treatment skills. Findings also indicated improvements in psychiatric and functional outcomes among the adolescent participants over the course of the app-enhanced treatment. Randomized clinical trials are needed to evaluate the efficacy of app-enhanced CBT in improving symptoms and functioning in adolescents with mood or psychotic spectrum disorders.

AimsYoung people with attenuated psychotic symptoms (APS), brief intermittent psychosis, and/or genetic risk and functional deterioration are at high risk for developing psychotic disorders. In a prior trial, family-focused therapy for clinical high risk youth (FFT-CHR) was more effective than brief psychoeducation in reducing APS severity over 6 months. This 7-site trial will compare the efficacy of FFT-CHR to a psychoeducational and supportive intervention (enhanced care) on APS and social functioning in CHR individuals over 18 months.MethodsParticipants (N = 220, ages 13-25 years) with a CHR syndrome will be randomly assigned to FFT-CHR (18 1-h sessions of family psychoeducation and communication/problem-solving skills training) or enhanced care (3 1-h family psychoeducational sessions followed by 5 individual support sessions), both given over 6 months. Participants will rate their weekly progress during treatment using a mobile-enhanced online platform. Family communication will be assessed in a laboratory interactional task at baseline and post-treatment. Independent evaluators will assess APS (primary outcome) and psychosocial functioning (secondary outcome) every 6 months over 18 months.ResultsWe hypothesize that, compared to enhanced care, FFT-CHR will be associated with greater improvements in APS and psychosocial functioning over 18 months. Secondarily, improvements in family communication over 6 months will mediate the relationship between treatment condition and primary and secondary outcomes over 18 months. The effects of FFT-CHR are predicted to be greater in individuals with higher baseline risk for psychosis conversion.ConclusionsResults of the trial will inform treatment guidelines for individuals at high risk for psychosis.

BackgroundFamily-focused therapy (FFT) is associated with longer intervals between mood episodes and reductions in suicidal ideation among adolescents at risk for bipolar disorders. However, the mediating processes underlying the efficacy of FFT are not well understood. In an open trial of an 18-week FFT program, we explored the association between the therapeutic alliance of adolescents/parents with their therapists and the symptomatic outcomes of adolescents over 18 weeks.MethodParticipants were enrolled in a treatment development trial of FFT supplemented with a mobile app. We used the System for Observing Family Therapeutic Alliances (SOFTA) to rate alliance between adolescents, parents, and therapists using videotaped FFT sessions from the beginning and end of treatment. Pearson correlations were computed between SOFTA alliance ratings and changes in Children's Depression Rating Scale, Revised (CDRS-R) scores over 18 weeks of treatment.ResultsSOFTA ratings were obtained from sessions conducted with 17 adolescents (mean age 14.9+/-2.0 years; 41.2% female) and 22 parents. CDRS-R ratings were obtained from 16 adolescents at baseline and 18 weeks. Parents had significantly higher levels of engagement and emotional connection with therapists than their offspring. Adolescents' therapeutic engagement scores were significantly correlated with reductions in CDRS scores over 18 weeks (r(14) = -0.58, p = 0.018; N = 16).LimitationsWe could not draw conclusions about the causal relationship between therapeutic alliance and improvement in depression.ConclusionsAmong high-risk adolescents undergoing FFT, therapeutic alliance is associated with clinical improvement over 4 months. Strategies to enhance adolescent engagement may strengthen the long-term effects of family interventions.

ObjectivesFamily-focused therapy (FFT) is associated with reduced rates of mood episodes among youth at high risk for bipolar disorder (BD). In a randomized trial of FFT compared to a psychoeducation-only treatment (enhanced care, EC), we sought to determine if changes in psychosocial functioning mediate mood improvements among high-risk youth.Method119 youths with active mood symptoms and a family history of BD were randomized to either 4 months of FFT or EC. Participants were rated on mood symptom severity and provided self-ratings of psychosocial functioning across domains of family, social-emotional, and school functioning. Repeated measures mixed modeling and bootstrapped mediational analyses evaluated the effects of treatment conditions and psychosocial functioning on mood improvements immediately posttreatment and over 2 years of follow-up.ResultsYouths in FFT reported greater improvements in family functioning over 24 months compared to those in EC, F(5, 76.8) = 3.1, p < .05. Improvements in family functioning partially mediated participants' improvements in depressive symptoms, B = -0.22, p < .01; 95% CI [-0.55, -0.02]. The effects of FFT versus EC on family functioning were stronger among youth with comorbid anxiety and externalizing disorders than among youth without these comorbid disorders.ConclusionsThe findings suggest a temporal link between changes in youths' perceptions of family functioning and improvements in depressive symptoms among high-risk youth in FFT. Family conflict and cohesion are important treatment targets for youth who present with early signs of BD. Future studies should examine whether changes in observational measures of family interaction precede improvements in mood among high-risk youth. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

AimSocial impairment is common in individuals with bipolar disorder (BD), although its role in youths at high-risk for BD (i.e., mood symptoms in the context of a family history of BD) is not well understood. Social impairment takes many forms including social withdrawal, relational aggression, physical aggression, and victimization. The aim of this study was to explore the links between social impairment and clinical symptoms in youth at high-risk for BD.MethodsThe sample included 127 youths with elevations in mood symptoms (depression or hypomania) and at least one first and/or second degree relative with BD. Measures of youths' current psychopathology (i.e., depressive and manic severity, suicidality, anxiety, and attention-deficit/hyperactivity disorder [ADHD]) were regressed onto youths' self-reports of social impairment (i.e., social withdrawal, relational aggression, physical aggression, and victimization).ResultsDepressive symptoms, suicidal ideation, and anxiety symptoms were related to social withdrawal. Suicidal ideation was also related to reactive aggression. ADHD symptoms related to reactive and proactive aggression as well as relational victimization. Manic symptoms were not associated with social impairment in this sample.ConclusionsAlthough cross-sectional, study findings point to potential treatment targets related to social functioning. Specifically, social withdrawal should be a target for treatment of childhood depressive and anxiety symptoms. Treatments that focus on social skills and cognitive functioning deficits associated with BD may also have clinical utility.

Antidepressants are standardly used to treat moderate to severe symptoms of depression and/or anxiety in youth but may also be associated with rare but serious psychiatric adverse events such as irritability, agitation, aggression, or suicidal ideation. Adverse events are especially common in youth with a family history of bipolar disorder (BD) who are at heightened risk for dysfunction in neurobiological systems that regulate emotion and arousal. To further understand this phenomenon, this study will examine (a) baseline risk factors associated with dysfunctional arousal in a sample of youth at high-risk for BD treated with or without an antidepressant, (b) whether antidepressant-related changes in arousal are mediated by changes in prefrontal-limbic circuitry, and (c) whether pharmacogenetic factors influence antidepressant-related changes in arousal. High-risk youth (aged 12-17 years with moderate to severe depressive and/or anxiety symptoms and at least one first-degree relative with bipolar I disorder) will be randomized to receive psychotherapy plus escitalopram or psychotherapy plus placebo. Neuroimaging and behavioral measures of arousal will be collected prior to randomization and at 4 weeks. Samples for pharmacogenetic analysis (serum escitalopram concentration, CYP2C19 metabolizer phenotype, and HTR2A and SLC6A4 genotypes) will be collected at 8 weeks. Youth will be followed for up to 16 weeks to assess change in arousal measures.

Parents of a child with a mood disorder report significant levels of distress and burden from caregiving. This study examined whether maternal distress varies over time with levels of mood symptoms in youth with mood disorders, and whether expressed emotion (EE) and family functioning moderate these associations. We recruited youth (ages 9-17 years) with mood disorders and familial risk for bipolar disorder (BD) for a randomized trial of family-focused therapy compared to standard psychoeducation. Participants were assessed every 4-6 months for up to 4 years. Using repeated-measures mixed effects modeling, we examined the longitudinal effects of youths' mood symptoms and maternal distress concurrently, as well as whether each variable predicted the other in successive study intervals. Secondary analyses examined the moderating effects of EE and ratings of family cohesion and adaptability on maternal distress. In sample of 118 youth-mother dyads, levels of self-reported parental distress decreased over time, with no differences between treatment conditions. Youths' depressive symptoms and, most strongly, mood lability were associated with greater maternal distress longitudinally; however, maternal distress did not predict youths' mood symptoms or lability. The effect of youth symptoms on maternal distress was greater among mothers who were high EE. Family cohesion was associated with reduced concurrent ratings of maternal distress, whereas family adaptability was associated with reduced maternal distress at successive follow-ups. While maternal distress decreases over time as youths' symptoms decrease, mothers of youth with mood disorders experience significant distress that is directly linked to the youths' depressive symptom severity and lability. Improved family functioning appears to be an important mechanism by which to intervene.

BackgroundStress is a risk factor for unipolar and bipolar mood disorders, but the mechanisms linking stress to specific symptoms remain elusive. Behavioral responses to stress, such as impulsivity and social withdrawal, may mediate the associations between stress and particular mood symptoms.MethodsThis study evaluated behavioral mediators of the relationship between self-reported intensity of daily stress and mood symptoms over up to eight weeks of daily diary surveys. The sample included individuals with unipolar or bipolar disorders, or with no psychiatric history (n = 113, ages 15-25).ResultsResults showed that higher daily stress was related to higher severity of mania, and this pathway was mediated by impulsive behaviors. Higher stress also predicted higher severity of anhedonic depression, and social withdrawal mediated this relationship. A k-means clustering analysis revealed six subgroups with divergent profiles of stress-behavior-symptom pathways.LimitationsGiven the observational study design, analyses cannot determine causal relationships amongst these variables. Further work is needed to determine how relationships between these variables may vary based on stressor type, at different timescales, and within different populations.ConclusionsFindings support a theoretical model in which impulsivity and social withdrawal act as behavioral mediators of the relationship between stress and mood symptoms. Additionally, distinct patterns of reactivity distinguished subgroups of people vulnerable to particular types of mood symptoms. These results provide novel information about how stress-reactive behaviors relate to specific mood symptoms, which may have clinical relevance as targets of intervention.

BackgroundPatients with mood disorders may benefit from psychosocial interventions through changes in brain networks underlying emotion processing. In this study, we used functional magnetic resonance imaging (fMRI) to investigate treatment-related changes in emotion processing networks in youth at familial high risk for bipolar disorder (BD).MethodsYouth, ages 9-17, were randomly assigned to family-focused therapy for high-risk youth (FFT-HR) or an active comparison treatment, Enhanced Care (EC). Before and after these 4-month treatments, participants underwent fMRI while viewing happy, fearful, and calm facial expressions. Twenty youth in FFT-HR and 20 in EC were included in analyses of pre- to post-treatment changes in activation across the whole brain. Significant clusters were assessed for correlation with mood symptom improvement.ResultsIn the dorsolateral prefrontal cortex (DLPFC), activation increased from pre- to post-treatment in the FFT-HR group and decreased in the EC group. Insula activation decreased in the FFT-HR group and did not change in the EC group. Across both treatments, decreasing activation in the hippocampus and amygdala was correlated with pre- to post-treatment improvement in hypomania, while increasing activation in the DLPFC was correlated with pre- to post-treatment improvement in depression.DiscussionPsychosocial treatment addresses abnormalities in emotion regulation networks in youth at high risk for BD. Increased prefrontal cortex activation suggests enhanced emotion regulation from pre- to post-treatment with FFT-HR. Improvements in family interactions may facilitate the development of prefrontal resources that provide protection against future mood episodes.

The implementation of evidence-based psychotherapies often requires significant commitments of time and expense from mental health providers. Psychotherapy protocols with rapid and efficient training and supervision requirements may have higher levels of uptake in publicly funded clinics. Family-focused therapy (FFT) is a 4-month, 12-session treatment for bipolar and psychosis patients consisting of psychoeducation, communication training, and problem-solving skills training. In a pilot randomized trial, we compared two methods of training community clinicians in FFT: (a) high intensity (n = 24), consisting of a 6-hour in-person didactic workshop followed by telephone supervision for every session with training cases; or (b) low-intensity training (n = 23), consisting of a 4-hour online workshop covering the same material as the in-person workshop followed by telephone supervision after every third session with training cases. Of 47 clinician participants, 18 (11 randomly assigned to high intensity, 7 to low) enrolled 34 patients with mood or psychotic disorders (mean age 16.5 ± 2.0 years; 44.1% female) in an FFT implementation phase. Expert supervisors rated clinicians' fidelity to the FFT manual based on taped family sessions. We detected no differences in fidelity scores between clinicians in the two training conditions, nor did patients treated by clinicians in high- versus low-intensity training differ in end-of-treatment depression or mania symptoms. Levels of parent/offspring conflict improved in both conditions. Although based on a pilot study, the results suggest that low-intensity training of community clinicians in FFT is feasible and can result in rapid achievement of fidelity benchmarks without apparent loss of treatment efficacy.

ObjectiveWe compared intrinsic network connectivity in symptomatic youths at high risk (HR) for bipolar disorder (BD) and healthy comparison (HC) youths. In HR youths, we also investigated treatment-related changes in intrinsic connectivity after family-focused therapy for high-risk youths (FFT-HR) vs standardized family psychoeducation.MethodHR youths (N = 34; age 9-17 years; mean 14 years, 56% girls and 44% boys) with depressive and/or hypomanic symptoms and at least 1 first- or second-degree relative with BD I or II were randomly assigned to 4 months of FFT-HR (12 sessions of psychoeducation, communication, and problem-solving skills training) or enhanced care (EC; 3 family and 3 individual psychoeducation sessions). Before and after 4 months of treatment, participants underwent resting state functional magnetic resonance imaging (rs-fMRI). A whole-brain independent component analysis compared rs-fMRI networks in HR youths and 30 age-matched HC youths at a pretreatment baseline. Then we identified pretreatment to posttreatment (4-month) changes in network connectivity in HR youths receiving FFT-HR (n = 16) or EC (n = 18) and correlated these changes with depression improvement.ResultsAt baseline, HR youths had greater connectivity between the ventrolateral prefrontal cortex (VLPFC) and the anterior default mode network (aDMN) than did HCs (p = .004). Over 4 months of treatment, FFT-HR-assigned HR youths had increased VLPFC-aDMN connectivity from pre- to posttreatment (p = .003), whereas HR youths in EC showed no significant change over time (p = .11) (treatment by time interaction, t31 = 3.33, 95% CI = 0.27-1.14, p = .002]. Reduction in depression severity over 4 months inversely correlated with enhanced anterior DMN (r = -0.71) connectivity in the FFT-HR but not in the EC (r = -0.07) group (z = -2.17, p = .015).ConclusionCompared to standard psychoeducation, FFT-HR is associated with stronger connectivity between the VLPFC and aDMN, suggesting possible enhancements of self-awareness, illness awareness, and emotion regulation.Clinical trial registration informationEarly Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.

Expressed emotion (EE), a measure of attitudes among caregivers towards a patient with a psychiatric disorder, is a robust predictor of relapse across mood and psychotic disorders. Because the measurement of EE is time-intensive and costly, its use in clinical settings has been limited. In an effort to automate EE classification, we evaluated whether machine learning (ML) applied to lexical features of speech samples can accurately categorize parents as high or low in EE and in its subtypes (criticism, overinvolvement, and warmth). The sample was 123 parents of youth who had active mood symptoms and a family history of bipolar disorder. Using ML algorithms, we achieved 75.2-81.8% accuracy (sensitivities of ~0.7 and specificities of ~0.8) in classifying parents as high or low in EE and EE subtypes. Additionally, machine-derived EE classifications and observer-rated EE classifications had simiar relationships with youth mood symptoms, parental distress, and family conflict. Of note, criticism related to greater manic severity, parental distress, and family conflict. Study findings indicate that EE classification can be automated through lexical analysis and suggest potential for facilitating larger-scale applications in clinical settings. The results also provide initial indications of the digital phenotypes that underlie EE and its subtypes.

AimIntegrating psychosocial interventions with mobile apps may increase treatment engagement among adolescents. We examined the user experience, uptake, and clinical effects of a mobile-enhanced family-focused therapy (FFT) among adolescents at risk for mood disorders.MethodWe created a mobile app containing 12 lesson plans corresponding to content of weekly FFT sessions, with modules concerning mood management, family communication and problem-solving. We pilot tested the app in an open trial of FFT (12 sessions in 18 weeks) for adolescents who had active depressive or hypomanic symptoms, a parent with mood disorder, and at least one parent who expressed high levels of criticism. Teens and parents made daily and weekly ratings of youths' moods, amount of parent/offspring criticism, and practice of FFT psychoeducational, communication or problem-solving skills. Independent evaluators interviewed adolescents at baseline and every 9 weeks over 27 weeks to measure symptom trajectories.ResultsParticipants were adolescents (n=22; mean age 15.4 ± 1.8 years; 45.5% female) and their 34 parents. Completion of requested app assessment and skill practices averaged 46%-65% among adolescents and parents over 18 weeks of treatment. Adolescents showed significant improvement in clinician-rated depression scores over 27 weeks (Cohen's d=1.58, 95% CI, 0.83 to 2.32) and reported reductions in the amount of perceived criticism expressed by parents.LimitationsThe uncontrolled design limits inferences about whether the mobile app augmented the effects of FFT on moods or family relationships.ConclusionsMobile applications may enhance users' responses to family therapy and provide clinicians with information regarding clinical status. Clinicaltrials.gov NCT03913013.

AimRecent findings suggest that family-focused therapy (FFT) is effective for individuals at clinical high-risk for psychosis (CHR-P). As outcomes of CHR-P individuals are quite varied, certain psychosocial interventions may be differentially effective in subgroups. The present study examined change in positive symptoms for CHR-P individuals at different levels of predicted risk for conversion to psychosis who received either FFT, a brief form of family education termed enhanced care (EC) or treatment as usual.MethodsParticipants were drawn from the North American Prodromal Longitudinal Study (NAPLS2). A subset of NAPLS2 participants completed a randomized study involving FFT or EC. The present study includes participants from the FFT-CHR sub-study and non-randomized NAPLS2 participants. Predicted risk of conversion was calculated using the Individualized Risk Calculator for Psychosis. Robust linear regressions evaluated whether the association between predicted risk of conversion and positive symptom change differed across intervention groups.ResultsA total of 94 participants from the FFT-CHR sub-study (FFT-CHR n = 50, EC n = 44) and 401 non-randomized NAPLS2 participants were included in this study. There was a treatment group by predicted risk of conversion interaction that predicted positive symptom improvement: higher risk individuals improved more with FFT-CHR than EC or the non-randomized NAPLS group, whereas lower-risk individuals did not differ in positive symptom improvement across treatment groups (FFT-CHR vs EC: P = .03, β = 20.27; FFT-CHR vs NAPLS2: P

BackgroundLittle is known about the longitudinal course of mood symptoms and functioning in youth who are at high risk for bipolar disorder (BD). Identifying distinct course trajectories and predictors of those trajectories may help refine treatment approaches.MethodsThis study examined the longitudinal course of mood symptoms and functioning ratings in 126 youth at high risk for BD based on family history and early mood symptoms. Participants were enrolled in a randomized trial of family-focused therapy and followed longitudinally (mean 2.0 years, SD = 53.6 weeks).ResultsUsing latent class growth analyses (LCGA), we observed three mood trajectories. All youth started the study with active mood symptoms. Following the index mood episode, participants were classified as having a "significantly improving course" (n = 41, 32.5% of sample), a "moderately symptomatic course" (n = 21, 16.7%), or a "predominantly symptomatic course" (n = 64, 50.8%) at follow-up. More severe depression, anxiety, and suicidality at the study's baseline were associated with a poorer course of illness. LCGA also revealed three trajectories of global functioning that closely corresponded to symptom trajectories; however, fewer youth exhibited functional recovery than exhibited symptomatic recovery.LimitationsMood trajectories were assessed within the context of a treatment trial. Ratings of mood and functioning were based on retrospective recall.ConclusionsThis study suggests considerable heterogeneity in the course trajectories of youth at high risk for BD, with a significant proportion (32.5%) showing long-term remission of symptoms. Treatments that enhance psychosocial functioning may be just as important as those that ameliorate symptoms in youth at risk for BD.

BackgroundYouth who are at clinical and familial risk for bipolar disorder (BD) often have significant suicidal ideation (SI). In a randomized trial, we examined whether family-focused therapy (FFT) is associated with reductions in SI and suicidal behaviors in high-risk youth.MethodsParticipants (ages 9-17 years) met diagnostic criteria for unspecified BD or major depressive disorder with active mood symptoms and had at least one relative with BD type I or II. Participants were randomly allocated to 12 sessions in 4 months of FFT or 6 sessions in 4 months of psychoeducation (enhanced care, EC), with pharmacotherapy as needed. Clinician- and child-rated assessments of mood, suicidal thoughts and behaviors, and family conflict were obtained at baseline and 4-6 month intervals over 1-4 years.ResultsParticipants (N=127; mean 13.2±2.6 yrs., 82 female) were followed over an average of 105.9±64.0 weeks. Youth with high baseline levels of SI who received FFT had lower levels of (and fewer weeks with) SI at follow-up compared to youth with high baseline SI who received EC. Participants in FFT had longer intervals without suicidal behaviors than participants in EC. Youths' ratings of family conflict significantly mediated the effects of treatment on SI at follow-up.LimitationsFamily conflict was based on questionnaires rather than observer ratings of family interactions.ConclusionsFamily psychoeducation with skill training can be an effective deterrent to suicidal thoughts and behaviors in youth at high risk for BD. Reducing parent/offspring conflict should be a central objective of psychosocial interventions for high-risk youth with SI.

BackgroundThe association between illness perceptions and the effectiveness of patients' illness-management strategies has been supported across a range of medical and psychiatric disorders. Few studies have examined these variables or their association in bipolar disorder (BD). This study examined the main and interactive associations between illness perceptions and one important illness management strategy - social rhythms stability on mood symptom severity in adults with BD.MethodsA cross-sectional study with 131 patients with BD in Taiwan was conducted using clinician- and patient-rated mood symptoms, self-reported illness perceptions, and a measure of daily and nightly social rhythms.ResultsIllness perceptions were associated with mood symptom severity, but social rhythms were not. Unfavorable illness perceptions (e.g., beliefs of experiencing more BD symptoms, having stronger emotional responses to the illness) were associated with more severe mood symptoms. Favorable illness perceptions (e.g., beliefs of being able to understand and control the illness) were associated with less severe mood symptoms, with personal control as the strongest correlate of mood symptom severity. Finally, social rhythm stability moderated the relationship between unfavorable illness perceptions and clinician-rated manic symptoms.LimitationsThe cross-sectional design limits our ability to make causal conclusions. Also, the effects pertain to patients in remission and may not generalize to more severely ill or hospitalized bipolar patients.ConclusionsThis study indicates that in patients with BD, illness perceptions are associated with symptom severity. Interventions to enhance favorable IPs and reduce unfavorable IPs may improve mood outcomes, particularly when patients have adopted regular social rhythms.

BackgroundDespite the well-documented negative impact of untreated bipolar illness, approaches to early intervention in childhood-onset bipolar and related disorders are not well delineated.MethodsWe reviewed the extant treatment literature on children at high risk for bipolar disorder, with definitions based on family history, childhood adversity, and prodromal symptoms.ResultsA panoply of approaches have been described, but most interventions are based on an inadequate database to support their routine implementation. We classify early stage interventions as a function of their safety and tolerability with the hope that these might generate more rigorous study and a stronger database.LimitationsCritics may rightly argue that identifying viable treatment methods is premature given our lack of ability to reliably predict illness trajectory in very young children. However, many of the psychosocial and pharmacological interventions we present could have nonspecific positive effects across a variety of symptoms, syndromes, and diagnoses, further enhancing the rationale for more rigorous study.ConclusionsEarly stage interventions have the potential to improve functioning in prodromal illness and exert long-term positive effects on the course of illness. Many of the safest interventions deserve consideration for implementation and dissemination studies.

Impairments in family functioning are associated with more severe depressive and manic symptoms, earlier recurrences, and more suicidal behaviors in early-onset bipolar disorder. This study examined whether family-focused treatment for adolescents (FFT-A) with BD I or II disorder led to greater increases in family cohesion and adaptability and decreases in conflict over 2 years compared to a briefer psychoeducational treatment (enhanced care, EC). Participants were 144 adolescents (mean age: 15.6 ± 1.4 years) with BD I or II with a mood episode in the previous 3 months. Adolescents and parents were randomized to either FFT-A (21 sessions) or EC (three sessions). Patients received guideline-based pharmacotherapy throughout the 2-year study. Trajectories of adolescent- and parent-rated family cohesion, adaptability, and conflict were analyzed over 2 years. FFT-A had greater effects on adolescent-rated family cohesion compared to EC over 2 years. Participants in FFT-A and EC reported similar improvements in family conflict across the 2 years. In the FFT-A group, low-conflict families had greater adolescent-rated family cohesion throughout the study compared to high-conflict families. High-conflict families in both treatment groups tended to show larger reductions in conflict over 2 years than low-conflict families. Family psychoeducation and skills training may improve family cohesion in the early stages of BD. Measuring levels of family conflict at the start of treatment may inform treatment responsiveness among those receiving FFT-A.

ImportanceBehavioral high-risk phenotypes predict the onset of bipolar disorder among youths who have parents with bipolar disorder. Few studies have examined whether early intervention delays new mood episodes in high-risk youths.ObjectiveTo determine whether family-focused therapy (FFT) for high-risk youths is more effective than standard psychoeducation in hastening recovery and delaying emergence of mood episodes during the 1 to 4 years after an active period of mood symptoms.Design, settings, and participantsThis multisite randomized clinical trial included referred youths (aged 9-17 years) with major depressive disorder or unspecified (subthreshold) bipolar disorder, active mood symptoms, and at least 1 first- or second-degree relative with bipolar disorder I or II. Recruitment started from October 6, 2011, and ended on September 15, 2016. Independent evaluators interviewed participants every 4 to 6 months to measure symptoms for up to 4 years. Data analysis was performed from March 13 to November 3, 2019.InterventionsHigh-risk youths and parents were randomly allocated to FFT (12 sessions in 4 months of psychoeducation, communication training, and problem-solving skills training; n = 61) or enhanced care (6 sessions in 4 months of family and individual psychoeducation; n = 66). Youths could receive medication management in either condition.Main outcomes and measuresThe coprimary outcomes, derived using weekly psychiatric status ratings, were time to recovery from prerandomization symptoms and time to a prospectively observed mood (depressive, manic, or hypomanic) episode after recovery. Secondary outcomes were time to conversion to bipolar disorder I or II and longitudinal symptom trajectories.ResultsAll 127 participants (82 [64.6%] female; mean [SD] age, 13.2 [2.6] years) were followed up for a median of 98 weeks (range, 0-255 weeks). No differences were detected between treatments in time to recovery from pretreatment symptoms. High-risk youths in the FFT group had longer intervals from recovery to the emergence of the next mood episode (χ2 = 5.44; P = .02; hazard ratio, 0.55; 95% CI, 0.48-0.92;), and from randomization to the next mood episode (χ2 = 4.44; P = .03; hazard ratio, 0.59; 95% CI, 0.35-0.97) than youths in enhanced care. Specifically, FFT was associated with longer intervals to depressive episodes (log-rank χ2 = 6.24; P = .01; hazard ratio, 0.53; 95% CI, 0.31-0.88) but did not differ from enhanced care in time to manic or hypomanic episodes, conversions to bipolar disorder, or symptom trajectories.Conclusions and relevanceFamily skills-training for youths at high risk for bipolar disorder is associated with longer times between mood episodes. Clarifying the relationship between changes in family functioning and changes in the course of high-risk syndromes merits future investigation.Trial registrationClinicalTrials.gov identifier: NCT01483391.

Given the chronic and deleterious course of serious mental illness (SMI; schizophrenia and bipolar disorder), significant efforts have been undertaken to improve prediction of SMI and provide treatment for adolescents in the early, putatively prodromal stage of these illnesses. While risk assessments and disorder-specific treatments for adolescents at risk for SMI have shown some efficacy, significant issues remain around disorder-specific treatments for these youth. There is substantial heterogeneity of psychopathology within adolescents at high risk for SMI that leads to many false-positives and varying diagnostic outcomes. As a result, initial treatment focusing on broad symptoms and skills has been proposed in place of disorder-specific treatments. We discuss the rationale for providing an already-developed and empirically supported transdiagnostic treatment for emotional disorders (termed the Unified Protocol) as a first-line staging of treatment for adolescents experiencing early SMI symptoms. Additionally, we outline the open trial we are piloting using this transdiagnostic treatment in adolescents between the ages of 13 - 17 who have begun experiencing distressing yet subsyndromal psychosis or bipolar mood symptoms. Preliminary findings suggest feasibility and acceptability as well as initial efficacy in improving psychiatric symptoms, quality of life, and difficulties regulating emotions. We also present case studies from our open trial. A unified, cognitive-behavioral treatment for early presentations of SMI has important clinical and public health benefits, including streamlining treatment and providing broad skills that are applicable to a wide range of psychopathology.

Significant efforts have been undertaken to characterize the phenomenology of the high-risk period for bipolar disorder (BD) through the examination of youth at familial risk (i.e., having a first- or second-degree relative with BD) or clinical high risk for the disorder (i.e., youth with BD Not Otherwise Specified [NOS] or major depressive disorder [MDD]). However, little is known about the phenomenology of youth at both familial and clinical high risk for BD. In this study, we examined the clinical and psychosocial characteristics of youth at familial and clinical high risk (HR) for BD, and compared these characteristics to those of youth with BD I and II. Both groups were recruited based on current, active mood symptoms from separate randomized trials of family therapy. A total of 127 HR youth were evaluated: 52 (40.9%) were diagnosed with BD-NOS and 75 (59.1%) were diagnosed with MDD. Compared to adolescents with BD I and II (n = 145), HR youth had higher rates of anxiety disorders, and comparable rates of attention-deficit/hyperactivity disorder and oppositional defiant disorder/conduct disorder. Manic symptom severity and psychosocial functioning were progressively more impaired consistent with diagnostic severity: BD I > BD II > BD-NOS > MDD. Nonetheless, HR youth exhibited depressive symptom severity that was comparable to adolescents with BD I. These results provide further support for the high rates of anxiety disorders and premorbid dysfunction in addition to active mood symptoms for youth at risk for BD, and suggest anxiety is an important phenomenological characteristic and treatment target in the high-risk period.

ObjectivesNetwork analyses of psychopathology examine the relationships between individual symptoms in an attempt to establish the causal interactions between symptoms that may give rise to episodes of psychiatric disorders. We conducted a network analysis of mood symptoms in adolescents with or at risk for bipolar spectrum disorders.MethodsThe sample consisted of 272 treatment-seeking adolescents with or at high risk for bipolar disorder who had at least subsyndromal depressive or (hypo)manic symptoms. Based on symptom scores assessed via semi-structured interviews, we constructed the network of depressive and manic symptoms and identified the most central symptoms and symptom communities within the network. We used bootstrapping analyses to determine the reliability of network parameters.ResultsSymptoms within the depressive and manic mood poles were more related to each other than to symptoms of the opposing mood pole. Four communities were identified, including a depressive symptom community and three manic symptom communities. Fatigue and depressed mood were the strongest individual symptoms within the overall network (ie the most highly correlated with other symptoms), followed by motor hyperactivity. Mood lability and irritability were found to be "bridge" symptoms that connected the two mood poles.ConclusionsSymptoms of activity/energy (ie fatigue and hyperactivity) and depressed mood are the most prominent mood symptoms among youth with bipolar spectrum disorders. Mood lability and irritability represent potential warning signs of emergent episodes of either polarity. Targeting these central and bridge symptoms would lead to more efficient assessments and therapeutic interventions for bipolar disorder.

ObjectiveThe Course and Outcome of Bipolar Youth study found that children and adolescents with bipolar spectrum disorders followed 1 of 4 distinct mood trajectories over 8 years of follow-up, with as many as 25% of participants showing a predominantly euthymic course. We evaluated whether similar patterns of illness course are observed in adolescents with bipolar I and II disorder who participated in a 2-year clinical trial.MethodA total of 144 adolescents with bipolar I or II disorder, identified shortly after a mood episode, were assessed over a 2-year period. Participants were randomly assigned to one of 2 psychosocial family treatments during the first 9 months of the study, and pharmacotherapy was provided throughout the 2 years. Using latent class growth analyses, we classified participants into distinct courses of illness based on mood ratings collected over the 2 years. We examined demographic and illness variables as predictors of these course classifications.ResultsLatent class growth analyses indicated four mood trajectories: "predominantly euthymic" (29.9% of sample), "ill with significantly improving course" (11.1%), "moderately euthymic" (26.4%), and "ill with moderately improving course" (32.6%). Adolescents in these classes were euthymic 77.7%, 53.6%, 44.1%, and 18.6% of the weeks of follow-up, respectively. Psychosocial treatment condition and baseline medication exposure were not associated with trajectories. However, youth with more severe baseline depressive symptoms, suicidality, lower quality of life scores, and minority race/ethnicity had more symptomatic courses of illness over time.ConclusionA substantial proportion (25%-30%) of youth with bipolar I or II disorder maintain euthymic states over extended periods of follow-up. Identifying youth who are more and less likely to remain stable over time may help guide psychosocial and pharmacological treatments after an illness episode.Clinical trial registration informationEffectiveness of Family-Focused Treatment Plus Pharmacotherapy for Bipolar Disorder in Adolescents; https://clinicaltrials.gov/; NCT00332098.

Individuals with serious mental illness experience changes in their clinical states over time that are difficult to assess and that result in increased disease burden and care utilization. It is not known if features derived from speech can serve as a transdiagnostic marker of these clinical states. This study evaluates the feasibility of collecting speech samples from people with serious mental illness and explores the potential utility for tracking changes in clinical state over time. Patients (n = 47) were recruited from a community-based mental health clinic with diagnoses of bipolar disorder, major depressive disorder, schizophrenia or schizoaffective disorder. Patients used an interactive voice response system for at least 4 months to provide speech samples. Clinic providers (n = 13) reviewed responses and provided global assessment ratings. We computed features of speech and used machine learning to create models of outcome measures trained using either population data or an individual's own data over time. The system was feasible to use, recording 1101 phone calls and 117 hours of speech. Most (92%) of the patients agreed that it was easy to use. The individually-trained models demonstrated the highest correlation with provider ratings (rho = 0.78, p

ObjectiveTo 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.MethodOffspring 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.ResultsFamilies 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.ConclusionAny 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.

Blunted neural responses to reward in an EEG paradigm (RewP) are associated with vulnerability to depression, but the pathways linking this biomarker to depressive symptoms are unclear. We examined whether the relationship between reward response (RewP mean amplitude and latency) and depression was in part explained by approach-motivated behaviors in adolescents with varying levels of depression. EEG was collected during a game rigged to provide win/loss trials. Longer RewP latency was associated with depression symptoms only when scores on a measure of avoidance motivation were included. These results suggest that treatments targeting avoidance may decrease vulnerability to depressive episodes.

AimsDespite the considerable public health impact of bipolar disorder (BD), no psychosocial interventions have been systematically evaluated in its early prodromal stages. We describe the rationale, design and analytic methods for a 3-site randomized trial of family-focused treatment for youth at high risk (FFT-HR) for BD.MethodsParticipants (ages 9-17 years) have a diagnosis of unspecified BD or major depressive disorder, current mood symptoms and at least one first- or second-degree relative with a lifetime history of BD I or II. Participants are randomly assigned to FFT-HR (12 sessions in 4 months of family psychoeducation and skills training) or enhanced care (EC; 6 individual and family sessions over 4 months), with pharmacotherapy provided as needed. A subset of participants undergo pre- and post-treatment functional MRI (fMRI) scans while performing face-rating and family problem-solving tasks designed to activate corticolimbic circuitry. Independent evaluators assess participants' status every 4 to 6 months for up to 4 years.ResultsWe hypothesize that FFT-HR will be more effective than EC in reducing the severity of mood symptoms (primary outcome) and the hazard of a first manic episode (secondary) over 4 years. Secondarily, we will explore whether FFT-HR is associated with greater decreases in amygdala activation and increases in dorsolateral, ventrolateral or anterior medial prefrontal cortex activation from pre- to post-treatment. Clinical characteristics of 133 subjects enrolled at baseline are described.ConclusionsThis study will test a novel intervention to reduce the early symptoms of BD, and identify neural and behavioural mechanisms that may help refine future treatments.

BackgroundWhile family interventions have shown efficacy in improving mood symptoms and family functioning in pediatric bipolar disorder, few studies have examined the effects of comorbid psychiatric conditions on patients' symptomatic or functional responses to treatment.Methods145 adolescents with bipolar I or II disorder were randomly assigned to family-focused therapy (FFT-A) or a brief psychoeducational therapy (enhanced care; EC) and followed over 2 years. Participants received pharmacotherapy for the study's duration. We examined whether comorbid anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and disruptive behavior disorders (DBDs; i.e., oppositional defiant and conduct disorder) predicted the proportion of weeks that participants experienced mood symptoms during follow-up, and whether comorbid disorders moderated the effects of treatment assignment on mood symptoms and family conflict.ResultsComorbid anxiety was associated with a greater proportion of weeks with depressive symptoms, more severe (hypo)manic symptoms during follow-up, and greater family conflict over the 2-year study. Comorbid ADHD was associated with a greater proportion of weeks with (hypo)manic symptoms, more severe (hypo)manic symptoms, and greater family conflict. Additionally, youth with comorbid ADHD who received FFT-A had more favorable trajectories of (hypo)manic symptoms and family functioning than youth with comorbid ADHD who received EC. Comorbid DBDs were consistently associated with more severe depressive symptoms and greater family conflict throughout the study.LimitationsRandomization to treatments was not stratified on comorbid disorders. The longitudinal trajectories of anxiety, attentional, and disruptive behavior symptoms were not examined.ConclusionsThe course of bipolar disorder in adolescents is strongly affected by comorbid disorders. Future research should examine whether adolescents with more complex presentations of bipolar disorder should be treated with different or more intensive psychosocial protocols than adolescents without these presentations.

Parental expressed emotion (EE) attitudes are important prognostic indicators in the course of bipolar disorder (BD) in adolescents and adults. This study examined the hypothesis that parents' own susceptibility to affective disturbances contributes to their likelihood of high-EE attitudes. We examined past-week levels of emotional distress, lifetime affective diagnoses, and family histories of affective disorder among high- and low-EE parents of 86 adolescents with bipolar I or II disorder who were recovering from an episode of depression or (hypo) mania. High EE parents endorsed higher concurrent levels of depression, anxiety, and anger/hostility than low EE parents, and reported a greater familial history of depression and BD. No differences between high and low EE parents were found in concurrent levels of interpersonal sensitivity, lifetime rates of affective disorders, or familial loading of anxiety disorder. Parents' distress at the time of the EE assessment was the strongest correlate of EE. The results suggest that susceptibility to affective psychopathology may be an important contributor to the development of EE attitudes among parents of adolescents with BD.

ObjectiveUp to 60% of patients with bipolar disorder develop a substance use disorder during their lifetime. The purpose of this paper was to assess the impact of substance use disorders on depression recovery among bipolar patients randomly assigned to different psychotropic medications and psychosocial interventions. We hypothesized that patients with a comorbid substance use disorder would benefit less from psychotherapy regardless of treatment intensity/length compared to patients without a comorbid substance use disorder.MethodWe conducted post hoc analyses among bipolar disorder patients ( n = 270) with and without comorbid substance use disorders enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder randomized psychosocial intervention trial. All patients entered during or shortly after the onset of a bipolar depressive episode. Logistic regression and Cox proportional hazard models were used to assess whether current or past substance use disorders moderated the response of patients to intensive psychosocial intervention or brief psychoeducation with collaborative care, operationalized as full recovery from an episode of bipolar depression.ResultsCurrent comorbid substance use disorders significantly predicted likelihood of recovery (odds ratio = 2.25, p = 0.025) and time to recovery (odds ratio = 1.71, p = 0.006) from bipolar depression. We found that 74.5% of patients with a current substance use disorder, compared to 56.5% without a current substance use disorder, recovered from bipolar depression. Past substance use disorders did not predict likelihood of recovery or time to recovery. Current substance use disorders did not significantly moderate response to intensive psychotherapy versus collaborative care.ConclusionContrary to our hypotheses, bipolar disorder participants with a current comorbid substance use disorder were more likely to recover from psychosocial treatment for bipolar depression than patients without a current comorbid substance use disorder. If this finding is replicated, it has implications for the ordering of treatment for patients with comorbid bipolar disorder and substance use disorders.

BACKGROUND:Traditional assessment and treatment of bipolar disorder (BD) often overlooks an important feature of the illness, mood instability (MI). MI - the presence of intense, rapidly shifting emotional states - is associated with a number of poor prognostic outcomes. This study examined whether MI among adolescents with BD was cross-sectionally related to bipolar subtype (I vs. II) and prognostically associated with symptoms and functioning over 3 months. METHODS:Participants included 145 adolescents (mean age: 15.6 years ± 1.4) with BD I or II with a mood episode in the previous 3 months. Depression and (hypo)mania instability were computed using the root mean square successive difference (rMSSD) score, reflecting both the size and temporal order of changes in weekly depression and (hypo)mania scores (over 12 weeks) from the Adolescent Longitudinal Interval Follow-Up Evaluation. RESULTS:Greater depression instability was associated with BD II, whereas greater (hypo)mania instability was associated with BD I. Baseline MI, particularly depression, predicted more instability, a higher percentage of weeks in a clinical mood state, and poorer global functioning over 3 months, even when covarying concurrent mood severity scores. LIMITATIONS:The clinical measure of symptoms used retrospective reports of clinically significant symptoms only. We were unable to standardize medication use or adherence. CONCLUSIONS:MI differs by diagnostic subtype, is relatively stable over time, and predicts clinical and functional outcomes. Targeting MI should be considered a clinical focus to augment traditional methods of assessing and treating BD during adolescence to enhance clinical and functional outcomes.

Previous research has found that family problem-solving interactions are more constructive and less contentious when there is a family member with bipolar disorder compared with schizophrenia. The present study extended this research by examining whether family problem-solving interactions differ between clinical high-risk (CHR) stages of each illness. Trained coders applied a behavioral coding system (O'Brien et al., 2014) to problem-solving interactions of parents and their adolescent child, conducted just prior to beginning a randomized trial of family-focused therapy. The CHR for psychosis sample included 58 families with an adolescent with attenuated positive symptoms, brief intermittent psychosis, or genetic risk and functional deterioration; the CHR for bipolar disorder sample included 44 families with an adolescent with "unspecified" bipolar disorder or major depressive disorder and at least one first or second degree relative with bipolar I or II disorder. When controlling for adolescent gender, age, functioning, and parent education, mothers of youth at CHR for psychosis displayed significantly more conflictual and less constructive communication than did mothers of youth at CHR for bipolar disorder. Youth risk classification did not have a significant relationship with youths' or fathers' communication behavior. The family environment among help-seeking adolescents may be more challenging for families with an adolescent at CHR for psychosis compared with bipolar illness. Accordingly, families of adolescents at clinical high-risk for psychosis may benefit from more intensive or focused communication training than is required by families of adolescents at clinical high-risk for bipolar disorder or other mood disorders. (PsycINFO Database Record

ObjectivesOver the past two decades, there has been tremendous growth in research regarding bipolar disorder (BD) among children and adolescents (ie, pediatric BD [PBD]). The primary purpose of this article is to distill the extant literature, dispel myths or exaggerated assertions in the field, and disseminate clinically relevant findings.MethodsAn international group of experts completed a selective review of the literature, emphasizing areas of consensus, identifying limitations and gaps in the literature, and highlighting future directions to mitigate these gaps.ResultsSubstantial, and increasingly international, research has accumulated regarding the phenomenology, differential diagnosis, course, treatment, and neurobiology of PBD. Prior division around the role of irritability and of screening tools in diagnosis has largely abated. Gold-standard pharmacologic trials inform treatment of manic/mixed episodes, whereas fewer data address bipolar depression and maintenance/continuation treatment. Adjunctive psychosocial treatment provides a forum for psychoeducation and targets primarily depressive symptoms. Numerous neurocognitive and neuroimaging studies, and increasing peripheral biomarker studies, largely converge with prior findings from adults with BD.ConclusionsAs data have accumulated and controversy has dissipated, the field has moved past existential questions about PBD toward defining and pursuing pressing clinical and scientific priorities that remain. The overall body of evidence supports the position that perceptions about marked international (US vs elsewhere) and developmental (pediatric vs adult) differences have been overstated, although additional research on these topics is warranted. Traction toward improved outcomes will be supported by continued emphasis on pathophysiology and novel therapeutics.

Self-harm refers to the purposeful destruction of bodily tissue without suicidal intention and for purposes that are not socially sanctioned. Little is known about the associations between a history of self-harm, mood symptoms, and functioning in adults with different types of mood disorders. Lifetime histories of self-harm, current mood symptoms, global functioning, and affective traits were collected on 142 adults with mood disorders. The prevalence of lifetime self-harm was higher in patients with bipolar disorder compared with patients with a unipolar depressive disorder. Self-harm was also more strongly linked to impulsivity in individuals with bipolar disorder compared with unipolar depressive disorder. Across both diagnoses, histories of self-harm were related to lower levels of current global functioning, more severe depressive symptoms, and high self-reported emotional dysregulation and neuroticism. Findings indicate that self-harm is a potent prognostic variable for symptoms, global functioning, and personality functioning in individuals with mood disorders.

BackgroundAdolescents with bipolar disorder (BD) report lower quality of life (QoL) than adolescents with other psychiatric disorders. This study compared the efficacy of family-focused therapy for adolescents (FFT-A) plus pharmacotherapy to brief psychoeducation (enhanced care, or EC) plus pharmacotherapy on self-rated QoL in adolescents with BD over 2 years.MethodsParticipants were 141 adolescents (mean age: 15.6±1.4yr) with BD I or II who had a mood episode in the previous 3 months. Adolescents and parents were randomly assigned to (1) FFT-A, given in 21 sessions in 9 months of psychoeducation, communication enhancement training, and problem-solving skills training, or (2) EC, given in 3 family psychoeducation sessions. Study psychiatrists provided patient participants with protocol-based pharmacotherapy for the duration of the study. QoL was assessed with The KINDLRQuestionnaire (Ravens-Sieberer and Bullinger, 1998) during active treatment (baseline to 9 months) and during a post-treatment follow-up (9-24 months).ResultsThe two treatment groups did not differ in overall QoL scores over 24 months. However, adolescents in FFT-A had greater improvements in quality of family relationships and physical well-being than participants in EC. For quality of friendships, the trajectory during active treatment favored EC, whereas the trajectory during post-treatment favored FFT-A.LimitationsWe were unable to standardize medication use or adherence over time. Quality of life was based on self-report rather than on observable functioning.ConclusionsA short course of family psychoeducation and skills training may enhance relational functioning and health in adolescents with BD. The effects of different psychosocial interventions on peer relationships deserves further study.

Perceived criticism (PC) is a construct that plays a key role in family relationships of persons with psychiatric disorders. It can be assessed in a brief and simple way using the Perceived Criticism Measure. PC ratings made by patients about their caregivers predict adverse clinical outcomes including increases in symptoms and relapse across a broad range of psychiatric diagnoses. Although research supports the concurrent and predictive validity of PC, the measure is not widely used in clinical practice. Here, we describe the construct of PC and review evidence supporting its clinical utility. We then illustrate how criticism and perceptions of criticism can be addressed in a clinical context, describing a family focused treatment approach used with a depressed adolescent at high risk for bipolar disorder.

This study examined whether sleep disturbance predicted or moderated responses to psychotherapy in participants who participated in STEP-BD, a national, multisite study that examined the effectiveness of different treatment combinations for bipolar disorder. Participants received either a brief psychosocial intervention called collaborative care (CC; n = 130) or intensive psychotherapy (IP; n = 163), with study-based pharmacotherapy. Participants (N = 243) were defined as current (past week) short sleepers (