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Background: The impairing neurodevelopmental course of bipolar disorder (BD) suggests the importance of early intervention for youth in the beginning phases of the illness. Objective: We report the results of a 3-site randomized trial of family-focused therapy for youth at high-risk (FFT-HR) for BD, and explore psychosocial and neuroimaging variables as mediators of treatment effects. Methods: High-risk youth ( Results: Among 127 youth (mean 13.2+2.6 years) over a median of 98 weeks, FFT-HR was associated with longer intervals prior to new mood episodes and lower levels of suicidal ideation than enhanced care. Reductions in perceived family conflict mediated the effects of psychosocial interventions on the course of mood symptoms. Among 34 participants with pre- /post-treatment fMRI scans, youth in FFT-HR had (a) stronger resting state connectivity between ventrolateral PFC and anterior default mode network, and (b) increased activity of dorsolateral and medial PFC in emotion processing and problem-solving tasks, compared to youth in enhanced care. Conclusion: FFT-HR may delay new mood episodes in symptomatic youth with familial liability to BD. Putative treatment mechanisms include neural adaptations suggestive of improved emotion regulation.

Severe mental illnesses (SMI) such as schizophrenia, major depressive disorder, and bipolar disorder are prevalent, debilitating, and chronic conditions that come with significant costs to families, public health systems, and communities. Research indicates that emotional qualities within the family environment of the person with SMI (e.g., whether members are highly supportive, critical, or emotionally overinvolved) can either protect against or increase the risk for psychiatric relapse. Dovetailing this work is research indicating that family-based psychosocial interventions, which can increase family functioning through psychoeducation and skill building, can promote positive outcomes for individuals with SMI. Unfortunately, social barriers such as financial strain, inaccessibility of specialized care, stigma, and social marginalization may impede a patient's or family's ability to initiate and/or continue family services. We propose that improving treatment engagement requires a combination of state and federal policy initiatives supporting community resources, integrated health care, and partnerships with national organizations.

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. [ Psychiatr Ann . 2023;53(2):58–62.]

Adolescence is a critical period of neurocognitive development and increased prevalence of mood pathology. In this cross-sectional study, we 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.

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 18weeks.ResultsA total of 253 speech samples were collected from 44 adolescents (mean age=15.8years; SD=1.6) over 18weeks. 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&nbsp

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.

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.

Aims Young 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. Methods Participants (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. Results We 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. Conclusions Results of the trial will inform treatment guidelines for individuals at high risk for psychosis.

Severe irritability and temper outbursts are risk factors for the onset of serious and lifelong mood disorders. In treating children and adolescents with severe irritability, clinicians should evaluate and address safety issues before acute stabilization of symptoms. Then, clinicians can initiate interventions to prevent the onset or relapses of the undesired behavior and its functional consequences. This review summarizes primary, secondary, and tertiary relapse prevention strategies, with an emphasis on strategies that build resilience in youth that mitigate the onset, recurrence, and progression of emotion dysregulation.

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=15.2years, 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.

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.La implementación de psicoterapias factuales generalmente exige compromisos significativos de tiempo y gastos por parte de los profesionales de salud mental. Los protocolos de psicoterapia con los requisitos de capacitación y supervisión rápidas y eficaces pueden tener niveles más altos de captación en las clínicas financiadas con fondos públicos. La terapia centrada en la familia es un tratamiento de 4 meses y 12 sesiones para pacientes bipolares y con psicosis que consiste en psicoeducación, capacitación en comunicación y capacitación en habilidades de resolución de problemas. En un ensayo aleatorizado piloto, comparamos dos métodos de capacitar a profesionales clínicos de la comunidad en terapia centrada en la familia: (a) la capacitación de alta intensidad (n = 24), que consiste en un taller didáctico presencial de seis horas seguido de supervisión telefónica para cada sesión con casos de capacitación; o (b) la capacitación de baja intensidad (n=23), que consiste en un taller virtual de cuatro horas y cubre el mismo material que el taller presencial seguido de supervisión telefónica después de cada tercera sesión con casos de capacitación. De 47 profesionales clínicos participantes, 18 (11 asignados aleatoriamente a alta intensidad, y 7 a baja intensidad) inscribieron a 34 pacientes con trastornos del estado de ánimo o psicóticos (edad promedio 16.5+2.0 años; el 44.1 % mujeres) en una fase de implementación de la terapia centrada en la familia. Un grupo de supervisores expertos calificó la fidelidad de los profesionales clínicos al manual de la terapia centrada en la familia basándose en sesiones familiares grabadas. No detectamos diferencias en los puntajes de fidelidad entre los profesionales clínicos de las dos condiciones de capacitación, ni los pacientes tratados por profesionales clínicos en las capacitaciones de alta intensidad ni en las de baja intensidad tuvieron diferencias en los síntomas de manía o depresión al final del tratamiento. Los niveles de conflicto entre los padres y los hijos mejoraron en ambas condiciones. Aunque están basados en un estudio piloto, los resultados sugieren que la capacitación de baja intensidad de los profesionales clínicos de la comunidad en la terapia centrada en la familia es viable y puede dar como resultado un logro rápido de referentes de fidelidad sin pérdida aparente de eficacia del tratamiento.循证心理治疗的实施往往需要心理健康提供者投入大量的时间和费用。如果心理治疗方案通过快速和高效的培训和督导能满足要求，这样的方案对公共资助的诊所而言接受水平可能会高得多。以家庭为中心的治疗(FFT)是一项为期4个月，有12个疗程的治疗双相和精神病患者的方法，包括心理教育，沟通培训，解决问题的技能培训。在一项试点随机试验中，我们比较了FFT方法在两种培训社区临床医生的方法: (a)高强度，包括6小时的面对面教学研讨会，然后在每个培训案例的治疗会谈中通过电话方式督导;或者(b)低强度培训(n=23)，包括一个4小时的在线培训，内容与现场培训相同，每三次治疗会谈后进行电话督导。在47名临床参与者中，18名(11名随机分配为高强度，7名随机分配为低强度)登记了34名情绪或精神障碍患者(平均年龄16.5+2.0岁; (44.1%女性)在FFT实施阶段。专家监督员根据家庭治疗会谈录像对临床医生对FFT手册的忠实度进行评分。我们没有发现临床医生在两种训练条件下的忠实度分数有差异，也没有发现接受高强度训练和低强度训练的患者在治疗结束时的抑郁或躁狂症状有差异。在这两种情况下，父母和子女之间的冲突程度都有所改善。虽然这只是一项初步实验性质的研究，但结果表明，对社区临床治疗师进行低强度的FFT培训是可行的，可以迅速达到忠实基准，而不会明显丧失治疗效果。.

Aim Social 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. Methods The 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). Results Depressive 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. Conclusions Although 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.

AIM: Comorbid 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. METHODS: Individuals 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. RESULTS: Individuals 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. CONCLUSIONS: Individuals at CHR with symptoms of anxiety benefit from family interventions in showing reductions in anxiety and improvements in family communication.

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.

Background Youth 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. Methods Participants (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. Results Participants (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. Limitations Family conflict was based on questionnaires rather than observer ratings of family interactions. Conclusions Family 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.

Background The 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. Methods A 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. Results Illness 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. Limitations The 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. Conclusions This 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.

Background Despite the well-documented negative impact of untreated bipolar illness, approaches to early intervention in childhood-onset bipolar and related disorders are not well delineated. Methods We reviewed the extant treatment literature on children at high risk for bipolar disorder, with definitions based on family history, childhood adversity, and prodromal symptoms. Results A 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. Limitations Critics 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. Conclusions Early 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.

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. Mood symptom severity and psychosocial functioning were progressively more impaired consistent with diagnostic severity: BD I>BD II>BD-NOS>MDD. Nonetheless, HR youth exhibited significant depressive symptom severity compared to adolescents with BD I and overall impairment in psychosocial functioning. 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 phenological characteristics and treatment target of the high-risk period.

OBJECTIVES: Family-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 psychoeducational-only treatment (enhanced care, EC), we sought to determine if changes in psychosocial functioning mediate mood improvements among high-risk youth. METHOD: 119 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 social-emotional, family, and school functioning. Repeated measures mixed modeling and bootstrapped mediational analyses determined the effects of treatment conditions and psychosocial functioning on mood improvements immediately post-treatment and over 2 years of follow-up. RESULTS: Youths in FFT reported greater improvements in family functioning over 24 months compared to those in EC, F(5,76.8) = 3.1, p < 0.05. Improvements in family functioning partially mediated participants’ improvements in depressive symptoms, B = −0.22, p < 0.01; 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. CONCLUSIONS: The 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.

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.

Aim Given ongoing disagreement about the diagnosis of pediatric bipolar disorder, we sought to illuminate key empirical findings regarding the condition in children and adolescents. Methods We conducted a review of extant studies of the diagnosis, course, and treatment of bipolar disorder in children and adolescents. Results Bipolar disorder is a lifelong, familial condition with frequent onset in childhood or adolescence. Secular trends indicate that globally, the onset of puberty is occurring earlier, which may contribute to increased identification of mood disorders in younger populations. Despite opinions to the contrary, bipolar disorder has been observed in youth around the world, not just in the U.S. Discrete and episodic manic symptoms occur on a continuum/spectrum of severity and duration. Clinicians may be just as likely to miss mania (false negatives) as overcall it (false positives). As is true in adults, periodicity and heterogeneity are defining features of early onset bipolar disorder. Youth who are misdiagnosed and undiagnosed tend to do poorly over the long term. Youth with and at risk for bipolar disorder are frequently exposed to maltreatment, abuse, and bullying. Fortunately, there are now many evidence-based interventions that have been studied in thousands of youth with or at high risk for bipolar disorder, demonstrating large effect sizes for evaluated treatments versus comparative treatments. Conclusion Identifying optimal methods for the evaluation and treatment of bipolar disorder in children and adolescents represents important advances in the field. Recognizing the occurrence of mania symptoms in youth is pivotal for improving outcomes in patients living with bipolar disorder.

Background Stress 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. Methods This 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). Results Results 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. Limitations Given 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. Conclusions Findings 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.

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.

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 or 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. Further, machine-derived EE classifications’ relationships with mood symptoms, parental distress, and family conflict paralleled observer-rated EE classifications’ relationships with the same variables. 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.

Aim. Integrating 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. Method. We 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. Results. Participants 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. Limitations. The uncontrolled design limits inferences about whether the mobile app augmented the effects of FFT on moods or family relationships. Conclusions. Mobile applications may enhance users’ responses to family therapy and provide clinicians with information regarding clinical status. Clinicaltrials.gov NCT03913013

Background Patients 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). Methods Youth, 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. Results In 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. Discussion Psychosocial 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.

Background This first mixed-methods UK trial examined the feasibility and acceptability of a future definitive randomised controlled trial (RCT) to evaluate whether Family Focussed Treatment for Adolescents with Bipolar Disorder (FFT-A) UK version can improve family functioning and well-being as part of the management of Paediatric Bipolar Disorder (PBD). Method The trial used a randomised, parallel group, non-blinded design where participants received FFT-A UK (16 sessions over 6 months) immediately or after 12 months (delayed arm). Measures of family functioning, well-being and quality of life of the young person and the main carer (most commonly a parent) were completed at baseline, 6 and 12-months in both arms. Primary outcome measures included rates of eligibility, consent and retention along with estimates of variability in the measures and assessment of the intervention delivery. Qualitative interviews allowed assessment of participants’ views about FFT-A and the trial processes. Results Twenty-seven of 36 young persons with PBD and their families consented; of these, 14 families were randomised to the immediate and 13 to the delayed arm. Two families from the immediate arm withdrew consent and discontinued participation. Quantitative measures were completed by 22 families (88%) at 6-months and 21 families (84%) at 12-months. Qualitative interviews were conducted with 30 participants (9 young people, 15 parents and 6 other family members). Nine families attended 3 post-trial focus groups. Conclusion It was feasible to recruit and retain to this trial. The results highlighted that trial design and measures were acceptable to participants. A benefit in family relationships was reported by participants which they attributed to the intervention in qualitative interviews. Families recommended that future modifications include definitive trial(s) recruiting participants in the age range 15–25 years as it felt this was the age range with maximum need. Trial registration ISRCTN, ISRCTN59769322. Registered 20 January 2014, http://www.isrctn.com/ISRCTN59769322

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.