Martin B. Keller’s research while affiliated with University of Miami and other places

Objective To assess medication adherence and factors associated with poor adherence in youth with bipolar disorder followed from adolescence through young adulthood. Method Participants with bipolar disorder recruited through the Course and Outcome of Bipolar Youth (COBY) study were included in this study if they were prescribed psychotropic medications and had at least 3 follow-up assessments of medication adherence (N = 179, ages 12-36). Medication adherence had been evaluated for a median of 8 years using a questionnaire derived from the Coronary Artery Risk Development in Young Adults (CARDIA) study. For the longitudinal evaluation, adherence was measured as the percentage of follow-up assessments in which the participants did not endorse any of the nonadherence items included in the questionnaire. Concurrent and future predictors of poor adherence were assessed using both univariate and multivariate longitudinal analyses. Results Among the participants, 51% reported poor adherence in more than 50% of their follow-up assessments. Younger age, family conflicts, polypharmacy, lower functioning, greater severity of mood symptoms, and comorbid disorders were associated with poor adherence in the univariate analyses. In the multivariate analyses, comorbid attention-deficit/hyperactivity disorder was the single most influential factor associated with concurrent and future poor adherence in all age groups. Participants’ most reported reasons for poor adherence were forgetfulness (56%), negative attitudes toward medication treatment (10.5%), and disturbed daily routine (7%). Conclusion Poor medication adherence is a significant problem in youth with bipolar disorder, with the most influential factor being the presence of comorbid attention-deficit/hyperactivity disorder. Thus, it is important to identify and appropriately treat comorbid attention-deficit/hyperactivity disorder to improve medication adherence and prognosis of patients. Providers should also recommend tools to enhance consistent medication intake and address patients’ concerns and negative beliefs about their illness and treatment.

Objectives: To build a one-year risk calculator (RC) to predict individualized risk for suicide attempt in early-onset bipolar disorder. Methods: 394 youth with bipolar disorder who completed >2 follow-up assessments (median follow-up length=13.1 years) in the longitudinal Course and Outcome of Bipolar Youth (COBY) study were included. Suicide attempt over follow-up was assessed via the A-LIFE Self-Injurious/Suicidal Behavior scale. Predictors from the literature on suicidal behavior in bipolar disorder that are readily assessed in clinical practice were selected and trichotomized as appropriate (presence past 6 months/lifetime history only/no lifetime history). The RC was trained via boosted multinomial classification trees; predictions were calibrated via Platt scaling. Half of the sample was used to train, and the other half to independently test the RC. Results: There were 249 suicide attempts among 106 individuals. Ten predictors accounted for >90% of the cross-validated relative influence in the model (AUC=0.82; in order of relative influence): 1) age of mood disorder onset; 2) non-suicidal self-injurious behavior (trichotomized); 3) current age; 4) psychosis (trichotomized); 5) socioeconomic status; 6) most severe depressive symptoms in past 6 months (trichotomized none/subthreshold/threshold); 7) history of suicide attempt (trichotomized); 8) family history of suicidal behavior; 9) substance use disorder (trichotomized); 10) lifetime history of physical/sexual abuse. For all trichotomized variables, presence in the past 6 months reliably predicted higher risk than lifetime history. Conclusions: This RC holds promise as a clinical and research tool for prospective identification of individualized high-risk periods for suicide attempt in early-onset bipolar disorder.

Neurocognitive deficits, such as cognitive flexibility impairments, are common in bipolar disorder (BD) and predict poor academic, occupational, and functional outcomes. However, the association between neurocognition and illness trajectory is not well understood, especially across developmental transitions. This study examined cognitive flexibility and subsequent mood symptom and suicidal ideation (SI) course in young adults with childhood-onset BD-I (with distinct mood episodes) vs. BD-not otherwise specified (BD-NOS) vs. typically-developing controls (TDCs). Sample included 93 young adults (ages 18–30) with prospectively verified childhood-onset DSM-IV BD-I (n = 34) or BD-NOS (n = 15) and TDCs (n = 44). Participants completed cross-sectional neuropsychological tasks and clinical measures. Then participants with BD completed longitudinal assessments of mood symptoms and SI at 6-month intervals (M = 39.18 ± 16.57 months of follow-up data). Analyses included ANOVAs, independent-samples t tests, chi-square analyses, and multiple linear regressions. Participants with BD-I had significant deficits in cognitive flexibility and executive functioning vs. BD-NOS and TDCs, and impaired spatial working memory vs. TDCs only. Two significant BD subtype-by-cognitive flexibility interactions revealed that cognitive flexibility deficits were associated with subsequent percentage of time depressed and with SI in BD-I but not BD-NOS, regardless of other neurocognitive factors (full-scale IQ, executive functioning, spatial working memory) and clinical factors (current and prior mood and SI symptoms, age of BD onset, global functioning, psychiatric medications, comorbidity). Thus, cognitive flexibility may be an important etiological brain/behavior mechanism, prognostic indicator, and intervention target for childhood-onset BD-I, as this deficit appears to endure into young adulthood and is associated with worse prognosis for subsequent depression and SI.