Race/ethnicity and socioeconomic status as predictors of outcome following family therapy in youth at clinical high risk for psychosis.

AIM: There is limited research on the effects of sociodemographic and socioeconomic factors on treatment outcomes in youth at clinical high risk for psychosis (CHRp). This study examined sociodemographic factors that may affect functional outcomes within this population. Specifically, we investigated the influence of race/ethnicity (dichotomized as non-Hispanic whites [NHW] vs. people of colour [POC]), socioeconomic status (SES; operationalized as parental years of education), and their interaction on change in psychosocial functioning and symptoms over 6 months in a randomized trial of family-focused therapy. METHODS: CHRp youth (N = 128) participated in a randomized trial of family therapy (18 sessions of family therapy vs. 3 sessions of family psychoeducation). Sixty-four participants who self-identified as POC and 64 self-identified NHW participants completed baseline and 6-month follow-up measures of positive and negative symptoms and psychosocial (global, role, and social) functioning. Multiple regression models were conducted to test the main effect of race/ethnicity on changes in positive and negative symptoms and functioning, and whether this effect was moderated by parental education. RESULTS: There was a significant interaction between race/ethnicity and parental education, such that higher parental education was associated with greater improvement in global functioning in NHW participants, but there was no relationship between parental education and global functioning in POC. Additionally, higher parental education was associated with a decrease in negative symptoms in NHW participants but not in POC. There were no significant effects of race/ethnicity or parental education on positive symptoms, nor on social or role functioning. CONCLUSIONS: Clinicians may consider tailoring psychosocial treatments according to the needs of diverse families who vary in sociodemographic factors such as educational attainment and race/ethnicity.

An ERP Study of Face Processing in Schizophrenia, Bipolar Disorder, and Socially Isolated Individuals from the Community.

People with schizophrenia (SCZ) and bipolar disorder (BD) have impairments in processing social information, including faces. The neural correlates of face processing are widely studied with the N170 ERP component. However, it is unclear whether N170 deficits reflect neural abnormalities associated with these clinical conditions or differences in social environments. The goal of this study was to determine whether N170 deficits would still be present in SCZ and BD when compared with socially isolated community members. Participants included 66 people with SCZ, 37 with BD, and 125 community members (76 "Community-Isolated"; 49 "Community-Connected"). Electroencephalography was recorded during a face processing task in which participants identified the gender of a face, the emotion of a face (angry, happy, neutral), or the number of stories in a building. We examined group differences in the N170 face effect (greater amplitudes for faces vs buildings) and the N170 emotion effect (greater amplitudes for emotional vs neutral expressions). Groups significantly differed in levels of social isolation (Community-Isolated > SCZ > BD = Community-Connected). SCZ participants had significantly reduced N170 amplitudes to faces compared with both community groups, which did not differ from each other. The BD group was intermediate and did not differ from any group. There were no significant group differences in the processing of specific emotional facial expressions. The N170 is abnormal in SCZ even when compared to socially isolated community members. Hence, the N170 seems to reflect a social processing impairment in SCZ that is separate from level of social isolation.

Social cognition and social motivation in schizophrenia and bipolar disorder: are impairments linked to the disorder or to being socially isolated?

BACKGROUND: People with schizophrenia on average are more socially isolated, lonelier, have more social cognitive impairment, and are less socially motivated than healthy individuals. People with bipolar disorder also have social isolation, though typically less than that seen in schizophrenia. We aimed to disentangle whether the social cognitive and social motivation impairments observed in schizophrenia are a specific feature of the clinical condition v. social isolation generally. METHODS: We compared four groups (clinically stable patients with schizophrenia or bipolar disorder, individuals drawn from the community with self-described social isolation, and a socially connected community control group) on loneliness, social cognition, and approach and avoidance social motivation. RESULTS: Individuals with schizophrenia (n = 72) showed intermediate levels of social isolation, loneliness, and social approach motivation between the isolated (n = 96) and connected control (n = 55) groups. However, they showed significant deficits in social cognition compared to both community groups. Individuals with bipolar disorder (n = 48) were intermediate between isolated and control groups for loneliness and social approach. They did not show deficits on social cognition tasks. Both clinical groups had higher social avoidance than both community groups. CONCLUSIONS: The results suggest that social cognitive deficits in schizophrenia, and high social avoidance motivation in both schizophrenia and bipolar disorder, are distinct features of the clinical conditions and not byproducts of social isolation. In contrast, differences between clinical and control groups on levels of loneliness and social approach motivation were congruent with the groups' degree of social isolation.

Protocol for teen inflammation glutamate emotion research (TIGER): Toward predictors of treatment response and clinical course in depressed adolescents.

Adolescent-onset depression is a prevalent and debilitating condition commonly associated with treatment refractory depression and non-response to first-line antidepressants. There are, however, no objective tests to determine who may or may not respond to antidepressants. As depressed adolescents are especially vulnerable to the lifelong consequences of ineffectively-treated depression, it is critical to identify neurobiological predictors of treatment non-response in this population. Here, we describe the scientific rationale and protocol for the Teen Inflammation Glutamate Emotion Research (TIGER) study, a prospective 18-month investigation of 160 depressed adolescents who will be assessed before and after treatment with selective serotonin reuptake inhibitors. TIGER will be using ultra-high field imaging to test the effects of acute stress and antidepressant treatment on inflammatory and glutamatergic processes hypothesized to underlie depression maintenance. Results from this work will motivate future studies testing alternative therapeutics for depressed adolescents at risk for treatment resistant depression. ClinicalTrials.gov Identifier: NCT05329441.

Neurocognitive risk phenotyping to predict mood symptoms in adolescence.

Predicting mood disorders in adolescence is a challenge that motivates research to identify neurocognitive predictors of symptom expression and clinical profiles. This study used machine learning to test whether neurocognitive variables predicted future manic or anhedonic symptoms in two adolescent samples risk-enriched for lifetime mood disorders (Sample 1, n = 73, ages = 13-25, M [SD] = 19.22 [2.49] years, 68% lifetime mood disorder) or familial mood disorders (Sample 2, n = 154, ages = 13-21, M [SD] = 16.46 [1.95] years, 62% first-degree family history of mood disorder). Participants completed cognitive testing and functional magnetic resonance imaging at baseline, for behavioral and neural measures of reward processing and executive functioning. Next, participants completed a daily diary procedure for 8-16 weeks. Penalized mixed-effects models identified neurocognitive predictors of future mood symptoms and stress-reactive changes in mood symptoms. Results included the following. In both samples, adolescents showing ventral corticostriatal reward hyposensitivity and lower reward performance reported more severe stress-reactive anhedonia. Poorer executive functioning behavior was associated with heightened anhedonia overall in Sample 1, but lower stress-reactive anhedonia in both samples. In Sample 1, adolescents showing ventral corticostriatal reward hypersensitivity and poorer executive functioning reported more severe stress-reactive manic symptoms. Clustering analyses identified, and replicated, five neurocognitive subgroups. Adolescents characterized by neural or behavioral reward hyposensitivities together with average-to-poor executive functioning reported unipolar symptom profiles. Adolescents showing neural reward hypersensitivity together with poor behavioral executive functioning reported a bipolar symptom profile (Sample 1 only). Together, neurocognitive phenotypes may hold value for predicting symptom expression and profiles of mood pathology. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A Randomized Clinical Trial of Technology-Enhanced Family-Focused Therapy for Youth in the Early Stages of Mood Disorders.

Objective: Family-focused therapy (FFT) is associated with enhanced outcomes in youth with bipolar and depressive disorders, but has not been evaluated in conjunction with mobile health tools. In symptomatic adolescents whose parents had histories of mood disorders, we examined whether the effects of telehealth-based FFT were augmented by mobile health apps that emphasized mood tracking and family coping skills. Method: Participants (aged 13-19 years) had active mood symptoms and a parent with major depressive or bipolar disorder. Participants received 12 sessions in 18 weeks of telehealth FFT, with random assignment to (1) a mobile app (MyCoachConnect, MCC) that enabled mood tracking, reviews of session content, and text reminders to practice mood management and family communication skills (FFT-MCC); or (2) a mobile app that enabled mood tracking only (FFT-Track). Independent evaluators assessed youth every 9 weeks over 6 months on depressive symptoms (primary outcome), anxiety, and psychosocial functioning. Results: Participants (N = 65; mean age 15.8 ± 1.6 years) significantly improved in depressive symptoms over 6 months (F1,170 = 45.02, p < .0001; ή2 = 0.21, 95% CI = 0.11-0.31), but there were no effects of treatment condition or treatment by time interactions on depression scores. When secondary outcome measures were considered, the subgroup of youth with bipolar spectrum disorders showed greater improvements in anxiety and global functioning in FFT-MCC compared with FFT-Track. Conclusion: Youth in the early stages of mood disorder may benefit from FFT enhanced by mobile health apps. Collaborations between researchers and information technologists on mobile app design and user experience may lead to increases in engagement among adolescents. Clinical trial registration information: Technology Enhanced Family Treatment; https://clinicaltrials.gov/; NCT03913013.

In-person versus remote CBT groups during COVID-19 for adolescents with mood disorders or psychosis-risk syndromes.

BACKGROUND: Since the COVID-19 pandemic, psychosocial therapies have been provided in varying formats, including remote, in-person, and hybrid services. It is unclear whether varying formats are similarly efficacious in improving psychiatric symptoms and functioning, lead to similar rates of treatment retention, and are equally acceptable to patients. This study compared youth with mood disorders and/or psychosis-risk syndromes who participated in a group cognitive behavioral therapy (CBT) in-person prior to COVID-19, to youth in the same treatment given remotely during the pandemic. METHODS: Adolescents ages 13-17 years participated in 9 sessions of group-based CBT given in-person (2018-2019) or remotely (2020-2021). Youth participants provided self-report ratings of psychiatric symptoms, psychosocial functioning, and emotional regulation at the study baseline and post-treatment and ratings of treatment satisfaction and burden at post-treatment. RESULTS: There were no differences between in-person and remote treatment improvements in psychiatric symptoms, psychosocial functioning or emotional regulation. However, youth in remote treatment had increased retention compared to youth who received treatment in person. Youth in the remote treatment reported similar levels of satisfaction but reported lower burden compared to those who received in-person treatment. LIMITATIONS: Participants were not randomized into remote or in-person treatment. Participants prior to COVID did not have the same frame of reference for alternative treatment delivery options as those during or post-COVID. CONCLUSIONS: Remote group treatment can provide similar levels of psychiatric benefit but less burden than in-person treatment for youth with mood disorders and/or psychosis-risk syndromes.

Mood Symptom Dimensions and Developmental Differences in Neurocognition in Adolescence.

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

Psychotherapy in Bipolar Depression: Effective Yet Underused.

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.

Early Family Intervention for Youth at Risk for Bipolar Disorder: Psychosocial and Neural Mediators of Outcome.

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 (<18 years) with major depressive disorder or other specified BD, active mood symptoms, and a family history of BD were randomly assigned to 4 months of FFT-HR (psychoeducation, communication and problem-solving skills training) or 4 months of enhanced care psychoeducation. Adjunctive pharmacotherapy was provided by study psychiatrists. Neuroimaging scans were conducted before and after psychosocial treatments in eligible participants. Independent evaluators interviewed participants every 4-6 months over 1-4 years regarding symptomatic outcomes. 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.

A randomized trial of telehealth mindfulness-based cognitive therapy and cognitive behavioral therapy groups for adolescents with mood or attenuated psychosis symptoms.

OBJECTIVES: There is substantial evidence that cognitive behavioral therapy (CBT) and mindfulness-based cognitive therapy (MBCT) improve symptoms and functioning in adults with mood and psychotic disorders. There has been little work directly comparing these treatments among adolescents with early-onset mood or psychosis symptoms. METHOD: We conducted a randomized controlled trial comparing remotely administered group CBT to group MBCT for adolescents (ages 13-17) with a mood disorder or attenuated psychosis symptoms. Adolescents attended nine sessions over 2 months; their parents attended parallel groups focused on the same skill practices. Participants were assessed for psychiatric symptoms and functioning at posttreatment and 3 months posttreatment. RESULTS: Sixty-six youth (Mage = 15.1 years, SD = 1.4; 44 females [66.7%]) initiated the trial (32 in CBT and 34 in MBCT), with 54 retained at posttreatment and 53 at the 3-month follow-up. The treatments were associated with comparable improvements in adolescents' mood, anxiety, attenuated psychosis symptoms, and psychosocial functioning over 5 months. CBT was associated with greater improvements than MBCT in emotion regulation and well-being during the posttreatment period. MBCT (compared to CBT) was associated with greater improvements in social functioning among adolescents with greater childhood adversity. Both treatments had comparable rates of retention, but youth and parents reported more satisfaction with CBT than MBCT. CONCLUSIONS: The beneficial effect of both treatments in a group telehealth format is encouraging. Due to our limited sample, future research should investigate whether adolescents' history of adversity and treatment preferences replicate as treatment moderators for youth with mood or psychosis symptoms. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Word usage in spontaneous speech as a predictor of depressive symptoms among youth at high risk for mood disorders.

BACKGROUND: We 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. METHODS: Participants (ages 13-19) had active mood symptoms, mood instability, and at least one parent with bipolar or major depressive disorder. During a randomized trial of family-focused therapy, participants were instructed to make weekly calls to a central voice server and leave speech samples in response to automated prompts. We coded youths' speech samples with the Linguistic Inquiry and Word Count system and used machine learning to identify the combination of speech features that were most closely associated with the course of depressive symptoms over 18 weeks. RESULTS: A total of 253 speech samples were collected from 44 adolescents (mean age = 15.8 years; SD = 1.6) over 18 weeks. Speech containing affective processes, social processes, drives toward risk or reward, nonfluencies, and time orientation words were correlated with depressive symptoms at concurrent time periods (ps < 0.01). Machine learning analyses revealed that affective processes, nonfluencies, drives and risk words combined to most strongly predict changes in depressive symptoms over 18 weeks of treatment. LIMITATIONS: Study results were limited by the small sample and the exclusion of paralinguistic or contextual variables in analyzing speech samples. CONCLUSIONS: In youth at high risk for mood disorders, knowledge of speech patterns may inform prognoses during outpatient psychosocial treatment.

Family communication and the efficacy of family focused therapy in individuals at clinical high risk for psychosis with comorbid anxiety.

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.

The clinical characterization of the adult patient with bipolar disorder aimed at personalization of management.

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.

A Double-Blind Randomized Trial to Investigate Mechanisms of Antidepressant-Related Dysfunctional Arousal in Depressed or Anxious Youth at Familial Risk for Bipolar Disorder.

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.

General and Specific Dimensions of Mood Symptoms Are Associated With Impairments in Common Executive Function in Adolescence and Young Adulthood.

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.