Validation of a youth suicide risk calculator in an adult sample with bipolar disorder.

BACKGROUND: Bipolar disorder (BD) conveys the highest risk of suicide of all mental disorders. We sought to externally validate a risk calculator (RC) of suicide attempts developed in youth with BD from the Course and Outcome of Bipolar Youth (COBY) study in an adult sample. METHODS: A prospective cohort of adults with BD from the National Institute of Mental Health Collaborative Depression Study (CDS; N = 427; mean (+/- SD) age at intake (36 +/- 13 years)) was secondarily analyzed to validate the COBY RC for one-year risk of suicide attempts/deaths. Nine of the ten predictor variables from the COBY RC were available in the CDS and used: age, age of mood disorder onset, first and second (partial) degree family history of suicide, history of psychotic symptoms, substance use disorder, prior suicide attempt, socioeconomic status, and non-suicidal self-injury (prospectively, incompletely at baseline). RESULTS: Over a mean (SD) follow-up of 19 (10) years, 29 % of the CDS sample attempted suicide. The RC predicted suicide attempts/deaths over one-year follow-up with an area under the receiver operating characteristic curve (AUC) of 0.78 (95 % CI 0.75-0.80). The RC performed slightly better in those with a younger age of mood disorder onset. LIMITATIONS: Clinical samples may limit generalizability; the RC does not assess more acute suicide risk. CONCLUSIONS: One-year risk of suicide attempts/deaths can be predicted with acceptable accuracy in youth and adults with BD, comparable to commonly used RCs to predict cardiovascular risk. This RC may help identify higher-risk individuals with BD for personalized treatment and research. https://cobysuicideattemptsrc.shinyapps.io/Shiny.

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.

Polygenic Scores and Onset of Major Mood or Psychotic Disorders Among Offspring of Affected Parents.

OBJECTIVE: Family history is an established risk factor for mental illness. The authors sought to investigate whether polygenic scores (PGSs) can complement family history to improve identification of risk for major mood and psychotic disorders. METHODS: Eight cohorts were combined to create a sample of 1,884 participants ages 2-36 years, including 1,339 offspring of parents with mood or psychotic disorders, who were prospectively assessed with diagnostic interviews over an average of 5.1 years. PGSs were constructed for depression, bipolar disorder, anxiety, attention deficit hyperactivity disorder (ADHD), schizophrenia, neuroticism, subjective well-being, p factor, and height (as a negative control). Cox regression was used to test associations between PGSs, family history of major mental illness, and onsets of major mood and psychotic disorders. RESULTS: There were 435 onsets of major mood and psychotic disorders across follow-up. PGSs for neuroticism (hazard ratio=1.23, 95% CI=1.12-1.36), schizophrenia (hazard ratio=1.15, 95% CI=1.04-1.26), depression (hazard ratio=1.11, 95% CI=1.01-1.22), ADHD (hazard ratio=1.10, 95% CI=1.00-1.21), subjective well-being (hazard ratio=0.90, 95% CI=0.82-0.99), and p factor (hazard ratio=1.14, 95% CI=1.04-1.26) were associated with onsets. After controlling for family history, neuroticism PGS remained significantly positively associated (hazard ratio=1.19, 95% CI=1.08-1.31) and subjective well-being PGS remained significantly negatively associated (hazard ratio=0.89, 95% CI=0.81-0.98) with onsets. CONCLUSIONS: Neuroticism and subjective well-being PGSs capture risk of major mood and psychotic disorders that is independent of family history, whereas PGSs for psychiatric illness provide limited predictive power when family history is known. Neuroticism and subjective well-being PGSs may complement family history in the early identification of persons at elevated risk.

Mood Instability in Youth at High Risk for Bipolar Disorder.

OBJECTIVE: Mood 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. METHOD: Youth (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. RESULTS: High-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, αß = 0.19, 95% CI = 0.06-0.32). Psychosocial interventions did not moderate these associations. CONCLUSION: A 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 INFORMATION: Early Intervention for Youth at Risk for Bipolar Disorder; https://clinicaltrials.gov/; NCT01483391.

Effects of family intervention on psychosocial functioning and mood symptoms of youth at high risk for bipolar disorder.

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 psychoeducation-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 family, social-emotional, and school functioning. Repeated measures mixed modeling and bootstrapped mediational analyses evaluated the effects of treatment conditions and psychosocial functioning on mood improvements immediately posttreatment and over 2 years of follow-up. 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 < .05. Improvements in family functioning partially mediated participants' improvements in depressive symptoms, B = -0.22, p < .01; 95% CI [-0.55, -0.02]. The effects of FFT versus EC on family functioning were stronger among youth with comorbid anxiety and externalizing disorders than among youth without these comorbid disorders. 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. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Higher socioeconomic status and less parental psychopathology improve prognosis in youths with bipolar disorder.

BACKGROUND: To identify prospectively ascertained individual and family factors that are associated with improvement in Bipolar Disorder (BD) among youths who initially presented with poor course. METHODS: 82 youths with BD with persistent poor mood symptomatology ("predominantly ill course") were compared to 70 youths with BD who at intake had poor course, but showed improvement during the follow-up ("ill with improving course"), (ages 12.3 ± 3.3, vs. 11.7 ± 3.3 years old, at intake). Improvement was measured by the percentage of time euthymic during a mean follow-up of 12.8 years. Youths and parents were interviewed to assess psychopathology, functioning, treatment, and familial functioning and psychopathology. RESULTS: Compared to the ill group, since intake, the improving group showed significantly lower subthreshold depression and hypo/mania, Attention Deficit Hyperactivity Disorder, and Disruptive Behavior Disorders. Parental Socioeconomic Status (SES) remained unchanged over time in the ill group, but progressively increased in the improving group. Importantly, the change in SES predated the improvement in the mood trajectory. The most influential variables that predicted improvement were higher SES, and absence of parental BD and Substance Use Disorder (SUD). Parental SUD also negatively affected the parental SES, which was directly associated with worse mood course. LIMITATIONS: Predominantly self-reported White samples may limit generalizability; other factors potentially associated with outcome (e.g., treatment adherence), were not ascertained. CONCLUSIONS: In addition to treating mood/comorbid psychopathology in symptomatic BD youths, to improve their prognosis, it is crucial to address their parent's BD and SUD and promote parental education/employment.

Validation of the youth mood recurrences risk calculator in an adult sample with bipolar disorder.

BACKGROUND: The ability to predict an individual's risk of mood episode recurrence can facilitate personalized medicine in bipolar disorder (BD). We sought to externally validate, in an adult sample, a risk calculator of mood episode recurrence developed in youth/young adults with BD from the Course and Outcome of Bipolar Youth (COBY) study. METHODS: Adult participants from the National Institute of Mental Health Collaborative Depression Study (CDS; N=258; mean(SD) age=35.5(12.0) years; mean follow-up=24.9 years) were utilized as a sample to validate the youth COBY risk calculator for onset of depressive, manic, or any mood episodes. RESULTS: In this older validation sample, the risk calculator predicted recurrence of any episode over 1, 2, 3, or 5-year follow-up intervals, with Area Under the Curves (AUCs) approximating 0.77. The AUC for prediction of depressive episodes was about 0.81 for each of the time windows, which was higher than for manic or hypomanic episodes (AUC=0.72). While the risk calculator was well-calibrated across the range of risk scores, it systematically underestimated risk in the CDS sample by about 20%. The length of current remission was a highly significant predictor of recurrence risk in the CDS sample. LIMITATIONS: Predominantly self-reported White samples may limit generalizability; the risk calculator does not assess more proximal risk (e.g., 1 month). CONCLUSIONS: Risk of mood episode recurrence can be predicted with good accuracy in youth and adults with BD in remission. The risk calculators may help identify higher risk BD subgroups for treatment and research.

Effects of family-focused therapy on suicidal ideation and behavior in youth at high risk for bipolar disorder.

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.

Predicting Personalized Risk of Mood Recurrences in Youths and Young Adults With Bipolar Spectrum Disorder.

OBJECTIVE: With each recurrence the prognosis of bipolar disorder (BD) worsens, indicating the need to identify the factors associated with increased recurrence risk. The course of BD is heterogenous and although risk factors for recurrence for the group as a whole have been reported in the literature, identification of risk factors for a specific individual are crucial for developing personalized treatments. METHOD: A total of 363 recovered BD youths/young adults from the Course and Outcome of Bipolar Youth (COBY) study were included. Participants were evaluated on average every 7 months for a median of 12.5 years and interviewed with standard instruments. Risk factors of recurrence from the literature were used to build a risk calculator (RC) to predict recurrence risk at different time intervals. RESULTS: Approximately 80% of participants had at least one syndromal recurrence and 60% had ≥2 recurrences, particularly depressions. The 6-month and 1-, 2-, 3-, and 5-year RC showed an accuracy between 72% and 82% for predicting any mood recurrences, and up to 80% for depression and 89% for hypo/mania (sensitivity/specificity both 0.74). The most influential recurrence risk factors were shorter recovery lengths, younger age at assessment, earlier mood onset, and more severe prior depression. Although important, other factors associated with recurrence risk, such as interepisodic subsyndromal mood symptoms and comorbidities, did not influence the RC score beyond factors noted above. CONCLUSION: The RC provides a useful tool for predicting an individual's recurrence risk of depression and/or hypo/mania in BD youths and for developing personalized interventions and informing research. Replication studies are warranted.

A Risk Calculator to Predict the Individual Risk of Conversion From Subthreshold Bipolar Symptoms to Bipolar Disorder I or II in Youth.

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

Parsing cyclothymic disorder and other specified bipolar spectrum disorders in youth.

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

Longitudinal trajectories of ADHD symptomatology in offspring of parents with bipolar disorder and community controls.

OBJECTIVE: To compare the psychopathology and longitudinal course of attention-deficit/hyperactivity disorder (ADHD) symptomatology and global functioning between the offspring with ADHD of parents with bipolar disorder and the offspring with ADHD of community control parents. METHOD: One hundred twenty-two offspring with ADHD of parents with bipolar disorder and 48 offspring with ADHD of control parents from the Pittsburgh Bipolar Offspring Study (BIOS) were included. DSM-IV lifetime psychiatric disorders were ascertained through the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL). The outcome measures of ADHD symptoms were ascertained at intake and every other year for a period of 6 years using the ADHD section of the K-SADS-PL and the Disruptive Behavior Disorder rating scale (DBD). Global functioning was assessed using the Children's Global Assessment Scale (CGAS). RESULTS: The offspring with ADHD of parents with bipolar disorder showed higher lifetime prevalence of mood and anxiety disorders relative to the offspring with ADHD of control parents (P values ≤ .03). For both groups of offspring with ADHD, the hyperactivity, impulsivity, and total K-SADS-PL ADHD scores decreased over time (P values < .001) without differences between the 2 groups. There were no between- or within-group differences in the inattention scores over time. The DBD ADHD scores decreased with age in both groups (P values < .002) without differences between the 2 groups. For both groups of offspring with ADHD, the global functioning did not improve over time. CONCLUSIONS: Offspring with ADHD of parents with bipolar disorder have more psychopathology relative to offspring with ADHD of control parents. However, there were no differences in the developmental courses of ADHD symptomatology between these 2 groups of ADHD youth.

The longitudinal course of sleep timing and circadian preferences in adults with bipolar disorder.

OBJECTIVES: To study the longitudinal course of sleep timing and circadian preferences in individuals with bipolar disorder (BP) compared to individuals with non-BP psychopathology and healthy controls. METHODS: Individuals with bipolar I and bipolar II disorder (n = 257), non-BP psychopathology (n = 105), and healthy controls (n = 55) (mean age 40.2 years, 21.3% male, 85.1% Caucasian) were followed on average every 27 months for a mean of four years. Sleep timing parameters and circadian preference were reported using the Sleep Timing Questionnaire and The Composite Scale for Morningness. Group comparisons were adjusted for multiple comparisons and between-group differences in demographic variables and psychopharmacological treatment. RESULTS: Regardless of their current mood state, individuals with BP showed more sleep onset latency (SOL), wakening after sleep onset (WASO), and evening preference in comparison to both individuals with non-BP psychopathology and healthy controls. Individuals with BP also showed less stability of bed and awakening times in comparison to the other two groups, though these results were dependent on mood state. Non-BP individuals only showed more WASO and less stability in bed and awakening times before work/school days than healthy controls. Adjusting for comorbid disorders yielded similar results. Within-group analyses found little to no effect of time and BP subtype on sleep timing and circadian preference. CONCLUSIONS: Disturbances of sleep timing are prominent in individuals with BP. These disturbances are worse during mood episodes, but still apparent during euthymic periods. Evening preference was not associated with polarity type, or mood state in BP, suggesting that this characteristic may be a trait marker.

Longitudinal trajectories and associated baseline predictors in youths with bipolar spectrum disorders.

OBJECTIVE: The authors sought to identify and evaluate longitudinal mood trajectories and associated baseline predictors in youths with bipolar disorder. METHOD: A total of 367 outpatient youths (mean age, 12.6 years) with bipolar disorder with at least 4 years of follow-up were included. After intake, participants were interviewed on average 10 times (SD=3.2) over a mean of 93 months (SD=8.3). Youths and parents were interviewed for psychopathology, functioning, treatment, and familial psychopathology and functioning. RESULTS: Latent class growth analysis showed four different longitudinal mood trajectories: "predominantly euthymic" (24.0%), "moderately euthymic" (34.6%), "ill with improving course" (19.1%), and "predominantly ill" (22.3%). Within each class, youths were euthymic on average 84.4%, 47.3%, 42.8%, and 11.5% of the follow-up time, respectively. Multivariate analyses showed that better course was associated with higher age at onset of mood symptoms, less lifetime family history of bipolar disorder and substance abuse, and less history at baseline of severe depression, manic symptoms, suicidality, subsyndromal mood episodes, and sexual abuse. Most of these factors were more noticeable in the "predominantly euthymic" class. The effects of age at onset were attenuated in youths with lower socioeconomic status, and the effects of depression severity were absent in those with the highest socioeconomic status. CONCLUSIONS: A substantial proportion of youths with bipolar disorder, especially those with adolescent onset and the above-noted factors, appear to be euthymic over extended periods. Nonetheless, continued syndromal and subsyndromal mood symptoms in all four classes underscore the need to optimize treatment.