Faculty Bibliography

BACKGROUND:Bipolar Disorder (BD) is a recurrent illness associated with high morbidity and mortality. The frequency of mood episode recurrence in BD is highly heterogeneous and significantly impacts the person's psychosocial functioning and well-being. Understanding the factors associated with mood recurrences could inform the prognosis and treatment. The objective of this review is to summarize the literature on factors, present during childhood, that influence recurrence. METHODOLOGY:A systematic review of PubMed (1946-2017) and PsycINFO (1884-2017) databases was conducted to identify candidate studies. Search terms included bipolar disorder, episodes, predictors, recurrences, and course. Study characteristics, risk for bias, and factors associated with recurrence were coded by two raters according to predetermined criteria. RESULTS:Twenty child studies and 28 adult studies that retrospectively evaluated childhood variables associated with mood recurrences were included. Early age of onset, low socioeconomic status, comorbid disorders, inter-episode subsyndromal mood symptoms, BD-I/II subtypes, presence of stressors, and family history of BD were associated with higher number of recurrences. LIMITATIONS:Risk factors and mood recurrences were assessed and defined in different ways, limiting generalizability. CONCLUSION:Multiple factors are associated with increased risk of mood episode recurrence in BD. Interventions targeting modifiable factors could reduce the impact of BD. For example, treatment of comorbid disorders and subsyndromal mood symptoms, coupled with appropriate cognitive behavioral and family-focused therapies could ameliorate risk related to many clinical factors. When coupled with social services to address environmental factors, the number of episodes could be reduced and the course of BD significantly improved.

OBJECTIVE:Mood and anxiety disorders typically begin in adolescence or early adulthood, but those at the age of highest risk are among those least likely to access mental health services. However, they may be more likely than other demographic groups to seek help online. The goal of the present study was to investigate the online help- and information-seeking activity of young people newly diagnosed with mood and anxiety disorders in order to better understand how digital resources might serve this population. METHOD:Participants, aged 15 to 35, with a diagnosis of a mood or anxiety disorder were eligible if they had received their first mental health diagnosis within 24 months. Participants were interviewed with the Pathways to Care Questionnaire, which inquires about online activity prior to one's first interaction with mental healthcare providers. RESULTS:Forty people participated (depression n = 30, bipolar disorder n = 5, generalized anxiety disorder n = 5); average age 21 years (SD=3.2), 60% female. Eighty-one percent reported seeking help and/or information about their symptoms online. The gap between symptom onset and in-person help seeking was 91.90 weeks (SD=133.7). Most participants (85%) reported they would be open to communicating with a mental health professional online. CONCLUSION:A majority of young people experiencing clinically-significant symptoms seek help online. However, the gap between symptom onset and treatment initiation remains unacceptably long. Better strategies are needed to translate young people's interest in online resources into meaningful care, whether through web-based services or facilitated pathways to traditional treatment.

Suicide is the second leading cause of death among young people. Both mental illness and social factors are associated with suicide in adolescents, and youth with mental disorders often experience social deficits, which may compound risk. The cumulative effects of mental disorders and social factors on suicidal ideation and behaviors (SIB) in adolescents have not previously been explored. Adolescents 13-18 years of age (N = 6,447; 49% female, 65% non-Hispanic White) participated in the National Comorbidity Survey Replication Adolescent Supplement. Adolescents were interviewed to assess mental health diagnoses, history of SIB, and relationship quality. Parents completed self-reports about adolescent mental health and family characteristics. Logistic regression estimated associations of friend, sibling, and family relationships with 12-month SIB and lifetime suicide attempt (SA); associations between relationships, SIB, and SA were compared across classes of mental disorders. Friendship negativity (odds ratio [OR] = 1.20, 95% confidence interval (CI) [1.04, 1.40]), and family conflict (OR = 1.26, 95% CI [1.13, 1.41]), were positively associated with SIB, beyond the risk conferred by mental disorders, particularly mood disorders (OR = 4.75, 95% CI [3.20, 7.05]). Friendship positivity (OR = 0.89, 95% CI [0.80, 0.99]); sibling relationship positivity (OR = 0.79, 95% CI [0.68, 0.91]); family cohesion (OR = 0.77, 95% CI [0.69, 0.87]); maternal care (OR = 0.76, 95% CI [0.69, 0.84]); and paternal care (OR = 0.68, 95% CI [0.59, 0.78]), were inversely associated with SIB. Sibling relationship positivity, family conflict, and paternal care were similarly associated with SA. Self-reported adolescent friend and family relationship characteristics are associated with SIB and SA beyond the risk conferred by mental disorders. This suggests that perceptions of friend and family relationships may be an appropriate target to reduce suicide risk among adolescents.

OBJECTIVE:Research on pediatric bipolar disorder (PBD) has grown substantially in the past 7 years; updating a 2011 meta-analysis of PBD prevalence could improve understanding of factors that influence prevalence. DATA SOURCES:A literature review of papers published in English was updated in 2018 using PubMed and PsycINFO. Search terms included pediatric, child, "bipolar disorder," bipolar, mania, prevalence, epidemiology, community, adolescent, and youth. STUDY SELECTION:Inclusion criteria were (1) youth epidemiologic sample, (2) number of youth with bipolar spectrum disorders reported, and (3) prevalence rates for youth differentiated from prevalence for those over age 21 years (if both included). Of 2,400 articles retrieved, 44 were evaluated and 8 new were included. DATA EXTRACTION:Prevalence rates for each bipolar subtype were recorded as reported; hypothesized moderators (eg, study characteristics, environmental factors) were also coded. RESULTS:Eight additional studies resulted in a total sample of 19 studies, tripling the sample size to N = 56,103 and n = 1,383 with bipolar disorder. Seven studies were from the United States, and 12 were from South America, Central America, or Europe. Weighted average prevalence of bipolar spectrum disorders was 3.9% (95% CI, 2.6%-5.8%). There was significant heterogeneity across studies (Q = 759.82, df = 32, P < .0005). The pooled rate of bipolar I was 0.6% (95% CI, 0.3%-1.2%); these rates were also heterogeneous (Q = 154.27, df = 13, P < .0001). Predictors of higher bipolar spectrum disorder prevalence were the use of broad bipolar criteria (P < .0001), older minimum age (P = .005), and lifetime prevalence (P = .002). Newer studies were associated with lower rates (P < .0001). CONCLUSIONS:The updated meta-analysis confirms that rates of bipolar spectrum disorders are not higher in the United States than in other Western countries, nor are rates increasing over time. Nonstandard diagnostic criteria result in highly variable prevalence rates, as does focusing on narrow definitions of PBD to the exclusion of the full spectrum. Consistent application of validated criteria could help to settle questions regarding PBD prevalence. Studies from non-Western countries are needed to refine understanding of international prevalence and risk factors.

Over the past two decades, research on pediatric bipolar disorder has grown geometrically. The diagnosis of pediatric bipolar disorder was met with enthusiasm, which in healthy doses catalyzed change, and skepticism, which in good measure pushes for rigor. Skepticism led to productive questions about the phenomenology of pediatric bipolar disorder and how best to diagnose and treat it. With regard to prevalence, key questions included whether it was increasing over time, and whether it was limited to the United States. In 2011, we published a meta-analysis addressing the prevalence questions; results indicated that bipolar disorder manifested at statistically indistinguishable rates in youth community samples across the world. In their recent paper, Parry et al. examine the studies included in the 2011 meta-analysis using a qualitative approach. Their opinion piece represents a step backwards; every study has shortcomings, but in focusing on a dozen individual studies, Parry et al. fail to take into account the preponderance of evidence - literally thousands of articles across countries, cohorts and methodologies - that support the existence of bipolar disorder in both prepubescent youth and adolescents. This commentary addresses misperceptions regarding the diagnosis of bipolar disorder in youth, particularly with regard to cross-informant agreement, to present converging data from international sources regarding the onset of bipolar disorder in childhood, and to correct the false claim that pediatric bipolar disorder is controversial. As clinicians and researchers, we have an obligation to do what we can to improve the lives of youth affected by mental illness. Denying the existence of a serious mood disorder will not serve the best interests of young people and will perpetuate the long delays many experience before getting an accurate diagnosis, appropriate treatment, and a fair chance at a good quality of life.

Depression is the leading cause of disability and a major cause of morbidity worldwide, with societal costs now upwards of 1 trillion dollars across the globe. Hence, extending current efforts to augment prevention outcomes is consistent with global public health interests. Although many prevention programs have been developed and have demonstrated efficacy, studies have yet to demonstrate that CBT is effective in preventing symptoms in populations at risk for developing depression induced by pharmacological substances. Using a randomized, controlled design, this pilot study reports on the feasibility and preliminary effects of a novel, guided symptom exposure augmented cognitive behavioral prevention intervention (GSE-CBT) in a sample diagnosed with Hepatitis C at risk for developing medication induced depression. Results demonstrated that the guided symptom exposure augmented CBT (GSE-CBT) was feasible in this population and was delivered with high integrity. Although not statistically different, we observed a pattern of lower depression levels in the GSE-CBT group versus those in the control group throughout. This pilot study demonstrates that a psychosocial prevention intervention is feasible for use in patients at risk for developing pharmacologically induced depression and that a guided symptom exposure augmented CBT protocol has the potential to prevent symptoms of depression that develop as a side effect to taking these medications. Results are preliminary and future studies should use larger samples and test the intervention in other populations.

OBJECTIVES/OBJECTIVE:To clarify the clinical features preceding the onset of bipolar disorder (BD) has become a public health priority for the prevention of high morbidity and mortality. BD remains frequently under- or misdiagnosed, and under- or mistreated, often for years. METHODS:We assessed the predictive value of precursors and prodromes of BD. We assessed precursors of first-lifetime manic or hypomanic episodes with/without mixed features in retrospective and prospective studies. The task force evaluated and summarized separately assessments of familial risk, premorbid personality traits, retrospective, and prospective studies. RESULTS:Cyclothymic features, a family history of BD, retrospectively reported attenuated manic symptoms, prospectively identified subthreshold symptoms of hypomania, recurrence of depression, panic anxiety and psychotic features, have been identified as clinical precursors of BD. The prodromal symptoms like [hypo]mania often appears to be long enough to encourage early identification and timely intervention. CONCLUSIONS:The predictive value of any risk factor identified remains largely unknown. Prospective controlled studies are urgently needed for prevention and effective treatment.

BACKGROUND:Accurate assessment of pediatric bipolar disorder (BD) is important for allocating appropriate treatment, but it is complicated by significant heterogeneity in symptom presentation and high rates of comorbidity. Investigating clinical subtypes of the disorder may help to clarify diagnostic boundaries and inform targeted treatment. This study used a full diagnostic instrument to examine symptom patterns among youth with BD. METHOD:Trained interviewers completed the Washington University Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) with 71 children (7 to 13 y of age) and families as part of the baseline assessment for a randomized clinical trial of Child- and Family-focused Cognitive-Behavioral Therapy (CFF-CBT) compared with treatment as usual (TAU) for pediatric BD. All participants met DSM-IV-TR criteria for a bipolar spectrum disorder. Hierarchical and K-means cluster analyses were performed. Resultant clusters were compared on symptom severity and psychosocial functioning at baseline and across treatment. RESULTS:Two distinct symptom profiles emerged: "dysregulated/defiant" and "classic presentation." The dysregulated/defiant cluster was characterized by more externalizing and disruptive behaviors, whereas the classic cluster presented with more severe depression, hallmark manic symptoms, anxiety, and inattention. CFF-CBT consistently promoted psychosocial coping skills, such as problem solving and self-control, for the dysregulated/defiant cluster. TAU also promoted these skills among the individuals in the classic presentation group but not those with symptoms in the dysregulated/defiant cluster. DISCUSSION:Pediatric BD may be characterized by distinct phenotypes with unique etiologies and pathways to impairment. The use of a parametric approach to classify the diverse symptom presentations helped yield valuable insights into how to promote the best prognosis for improved functional outcomes in CFF-CBT versus TAU for youth with pediatric BD.

Background/UNASSIGNED:Late adolescence and early adulthood is a period of highest incidence for onset of mental health problems. Transition to college environment has been associated with many risk factors such as the initial disruption-and subsequent irregularity-of the student's sleep and activity schedule. We tested the feasibility of using blue blocking glasses (BBG) at night in first year higher education students with sleep complaints, to obtain preliminary evidence for the impact of BBG on sleep, activity, and mood. Methods/UNASSIGNED:Participants were 13 first year undergraduates (from 10 different academic courses) living on campus for the first time with sleep complaints/disorders confirmed at screening via the Duke Structured Interview Schedule for Sleep Disorders. We used a 2-week, balanced crossover design (BBG vs placebo glasses; participants were unaware which was the active intervention) with computer-generated random allocation. Exploratory analyses provided descriptive and frequency summaries to evaluate feasibility of the intervention. Results/UNASSIGNED:Preliminary evidence supports the feasibility and acceptability of the trial; almost all screened participants consented and completed the protocol with high adherence; missing data were negligible. Additionally, the effectiveness of BBGs to enhance sleep, mood, and activity levels in young adults was supported. Conclusions/UNASSIGNED:The results of this feasibility trial suggest that BBG have potential as an inexpensive and feasible intervention for reducing sleep and circadian dysregulation in young adult students. A larger trial, following this successfully implemented protocol, is necessary to fully test the efficacy of BBG.