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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.

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.

Both unipolar and bipolar depression have been linked with impairments in executive functioning (EF). In particular, mood symptom severity is associated with differences in common EF, a latent measure of general EF abilities. The relationship between mood disorders and EF is particularly salient in adolescence and young adulthood when the ongoing development of EF intersects with a higher risk of mood disorder onset. However, it remains unclear if common EF impairments have associations with specific symptom dimensions of mood pathology such as blunted positive affect, mood instability, or physiological arousal, or if differences in common EF more broadly relate to what is shared across various symptom domains, such as general negative affect or distress. To address this question, bifactor models can be applied to simultaneously examine the shared and unique contributions of particular mood symptom dimensions. However, no studies to our knowledge have examined bifactor models of mood symptoms in relation to measures of common EF. This study examined associations between common EF and general vs. specific symptom dimensions (anhedonia, physiological arousal, and mania) using structural equation modeling in adolescents and young adults with varying severity of mood symptoms (n = 495, ages = 13–25 years, 68.69% female). A General Depression factor capturing shared variance across symptoms statistically predicted lower Common EF. Additionally, a factor specific to physiological arousal was associated with lower Common EF. Anhedonia-specific and Mania-specific factors were not significantly related to Common EF. Altogether, these results indicate that deficits in common EF are driven by, or reflect, general features of mood pathology that are shared across symptom dimensions but are also specifically associated with physiological arousal.

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.

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.

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.

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.

Aim The peak onset of psychotic disorders occurs during adolescence and early adulthood, yet treatments for youth at clinical high risk (CHR) for psychosis are generally designed for adults. CHR youth, despite poor academic and social engagement, spend hours each day playing complicated videogames. The aim of this study was to test the feasibility of integrating biofeedback and cooperative videogame play within family therapy as a means of engaging and enhancing this population's resilience. Methods We conducted a feasibility trial of an innovative 12-week family therapy for CHR ages 12-30 (clinicaltrials.gov NCT02531243). We report feasibility outcomes and preliminary effect sizes for pre-post changes and youth-parent differences. Results Of 88 individuals referred to the centre who met age and CHR criteria, 11 (13%) youth-parent pairs met full criteria and engaged in treatment. Ten (91%) completed at least six sessions. Youth found CALMS initially credible, but parents tended to find it more credible and to be more satisfied over time. Surprisingly, parents reported a better game experience than youth. As a group, youth and parent participants reported experiencing reduced stress and perceiving each other as less critical by the end of treatment. Youth were rated as having significantly improved social, but not role or global functioning by the end of treatment. Conclusions Multiuser videogames may have a role to play in engaging youth at risk for psychosis in therapy and reducing stress and familial risk factors. A number of key developments are needed to enhance the appeal, effectiveness and practicality of this approach.

Objective The 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. Method A 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. Results Latent 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. Conclusion A 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 information Effectiveness of Family-Focused Treatment Plus Pharmacotherapy for Bipolar Disorder in Adolescents; https://clinicaltrials.gov/ ; NCT00332098 .

Bipolar disorder is characterized by recurrent mood episodes and severe functional impairments. Earlier onsets of bipolar disorder are associated with a more severe course of the illness. Treatment guidelines across age groups include pharmacotherapy plus bipolar disorder–specific psychotherapies. Evidence supporting the use of adjunctive psychotherapies is strongest for long-term maintenance of bipolar disorder, including relapse prevention and restoring function and quality of life, for youths and adults with bipolar disorder. When given in combination with pharmacotherapy, family-focused treatment (FFT) and group psychoeducation (including functional remediation methods) have the strongest support among adults. Individual psychotherapies (interpersonal and social rhythm therapy [IPSRT] and cognitive-behavioral therapy [CBT]) are associated with improvements in clinical functioning similar to intensive psychoeducational or supportive therapies. For adolescent bipolar patients there is evidence for FFT and dialectical behavior therapy in stabilizing symptoms and enhancing quality of life, whereas in younger-age patients (i.e., ages 7–14), there is evidence for multifamily group formats that combine psychoeducation with CBT strategies. Finally, there is preliminary evidence that FFT, multifamily psychoeducation, and IPSRT have effects on symptom control in youths at high risk for bipolar disorder. Future research directions include identifying mechanisms of change in current psychotherapies, establishing best-practice treatments for more severe forms of bipolar disorder, examining clinically significant outcomes (e.g., suicidal behaviors, school dropout, unemployment), and developing technology-driven treatment strategies.

This chapter surveys the literature on the pharmacological and psychological management of bipolar disorder. Lithium, valproate, and several dopamine antagonists/partial agonists—in monotherapy or in combination—are the first-line treatments for acute mania. For bipolar depression, lithium, lamotrigine, and quetiapine monotherapy remain the first-line options. The topic of antidepressants in bipolar disorder is controversial. Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, risperidone, and long-acting antipsychotic formulations represent the principal strategies for maintenance treatment of bipolar disorder. The use of medication in bipolar disorder may benefit from a combined psychological approach in stabilizing symptoms and preventing relapses. Three strategies have shown consistent empirical evidence: group psychoeducation, family-focused therapy, and interpersonal and social rhythm therapy. The evidence supporting cognitive behavioural therapy (CBT) as an adjunctive psychosocial intervention is inconsistent, although ‘third-wave’ CBT approaches are promising. There is preliminary evidence for functional remediation in bipolar disorder patients with neurocognitive impairment.

Objective: Up 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. Method: We 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. Results: Current 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. Conclusion: Contrary 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.

Objectives Caregivers of people with bipolar disorder often have depression and health problems. This study aimed to evaluate the sustained effects of a 12-15 week psychoeducational intervention on the health and mental health of caregivers of persons with bipolar disorder. We also evaluated the effects of the intervention on patients' mood symptoms over 6 months post-treatment. Methods Caregivers of 46 persons with bipolar disorder were randomized to 12-15 weeks of a caregiver-only adaptation of family-focused treatment (FFT), in which caregivers were instructed on self-care strategies and ways to assist the patient in managing the illness, or to 8-12 sessions of standard health education. Independent evaluators assessed caregivers' depression and physical health and patients' mood symptoms before treatment, immediately after the treatment, and at 6 months post-treatment. Results Randomization to FFT was associated with greater decreases in depression for both caregivers and patients over a 6-month follow-up period post-treatment. Reductions in patients' depression scores over 6 months post-treatment were mediated by reductions in caregivers' depression scores (z = -2.74, P Conclusions Interventions that are effective in reducing mood symptoms and improving health behavior in caregivers may have important health and mental health benefits for patients with bipolar disorder. Specifically, a treatment focused on caregiver education about bipolar disorder and the need for the caregiver to attend to his/her own health and mental health can benefit patients, even without their direct participation.

Depression and brief periods of manic symptoms are linked to a significant risk of progression to bipolar disorder (BD) in children who have a first-degree relative with BD I or II. However, little evidence exists to guide the pharmacologic management of children with these high-risk phenotypes. We propose a pharmacological treatment algorithm for high-risk youth and present results on its use in a study of children with a first-degree relative with BD.Subjects were 40 youth (mean 12.7 years, range 9-17 years) who had (1) a first-degree relative with lifetime history of BD I or II, (2) DSM-IV-TR diagnoses of BD not otherwise specified, major depressive disorder or cyclothymic disorder, and (3) active symptoms of depression, mania, or hypomania. Participants and their families were enrolled in a randomized trial examining the effects of two psychosocial interventions on the 1-year course of mood disorder. At study intake, participants received a psychiatric evaluation and were offered medications or had existing medications optimized to decrease symptom severity. During the 1-year study, psychiatrists treated participants using a medication algorithm to treat depressive or manic symptoms as well as comorbid anxiety and/or attention-deficit/hyperactivity disorder.At study entry, 25 of 40 (62.5%) of the participants were taking at least one psychiatric medication. At 1 year, nearly an identical proportion were taking medications (22 of 35, 63%). Independent ratings indicated that in 84.7% of the study visits, physicians maintained adherence to the algorithm. No patients experienced antidepressant- or stimulant-induced mania during the study.An algorithmic approach to pharmacologic interventions may aid in the management of youth (i.e., age18) at high risk for BD. Future studies should compare outcomes in high-risk patients receiving algorithm-prescribed treatment versus those receiving treatment as usual.Early Family-Focused Treatment for Youth at Risk for Bipolar Disorder; www.clinicaltrials.gov/ ; NCT00943085.

Objectives Over 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. Methods An 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. Results Substantial, 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. Conclusions As 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.

BACKGROUND: Bipolar disorder (BD) and schizophrenia (SZ) show substantial overlap. It has been suggested that a subgroup of patients might contribute to these overlapping features. This study employed a cross-diagnostic cluster analysis to identify subgroups of individuals with shared cognitive phenotypes. METHOD: 143 participants (68 BD patients, 39 SZ patients and 36 healthy controls) completed a battery of EEG and performance assessments on perception, nonsocial cognition and social cognition. A K-means cluster analysis was conducted with all participants across diagnostic groups. Clinical symptoms, functional capacity, and functional outcome were assessed in patients. RESULTS: A two-cluster solution across 3 groups was the most stable. One cluster including 44 BD patients, 31 controls and 5 SZ patients showed better cognition (High cluster) than the other cluster with 24 BD patients, 35 SZ patients and 5 controls (Low cluster). BD patients in the High cluster performed better than BD patients in the Low cluster across cognitive domains. Within each cluster, participants with different clinical diagnoses showed different profiles across cognitive domains. LIMITATIONS: All patients are in the chronic phase and out of mood episode at the time of assessment and most of the assessment were behavioral measures. CONCLUSIONS: This study identified two clusters with shared cognitive phenotype profiles that were not proxies for clinical diagnoses. The finding of better social cognitive performance of BD patients than SZ patients in the Lowe cluster suggest that relatively preserved social cognition may be important to identify disease process distinct to each disorder.

Background Most longitudinal or treatment studies in bipolar disorder have used symptomatic or syndromal status as the primary outcome variable. More recently, psychosocial functioning has been highlighted as a key domain of outcome. Patients with bipolar disorder appear to be impaired in all functional domains, although the factors that cause impairment have not been clearly specified. Methods This paper reviews cross-sectional and longitudinal studies on functional impairment and its relationship to symptomatic, neurocognitive, personality, and stress variables in bipolar disorder; and the implications of these relationships for defining treatment targets. 93 articles were located through comprehensive MEDLINE, SCOPUS and Web of Science searches. Results and discussion Functional recovery following a mood episode consistently lags behind symptomatic and syndromal recovery. Longer term functional impairment is only partly explained by the number of manic/hypomanic episodes. Depression (including subsyndromal states) and persistent neurocognitive impairment are the strongest correlates of functional impairment in bipolar disorder, with personality and psychosocial stressors playing secondary roles. Possible treatment options include: more aggressive treatment of subthreshold depressive states, pharmacotherapies that target cognition (e.g., stimulants), and adjunctive psychotherapies including cognitive remediation.

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.

Objective We 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. Method HR 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. Results At 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). Conclusion Compared 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 information Early Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/ ; NCT01483391 .