Faculty Bibliography

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.

OBJECTIVE:To test whether rates of bipolar disorder (BD) have changed over time or vary across geographic regions after adjusting for design features meta-analyzing epidemiologic studies reporting BD prevalence in adults worldwide. DATA SOURCES:Searches in PubMed and PsycINFO using the terms (epidemiology OR community OR prevalence) AND (mania OR "bipolar disorder" OR cyclothymi*) AND adult and backward searches from published reviews were conducted. STUDY SELECTION:Eighty-five epidemiologic studies published in English from 1980 onward that reported prevalence rates for BD or mania for subjects ≥ 18 years old were included. DATA EXTRACTION:We coded BD prevalence, method of data collection, diagnostic criteria, year of study, country, and quality of study design and data reporting. Meta-regression tested whether sample characteristics influenced prevalence rates using the metafor package in R. RESULTS:Eighty-five effect sizes, from 44 countries, from studies spanning the years 1980-2012, included 67,373 people with BD. Lifetime prevalence for BD spectrum was 1.02% (95% CI, 0.81%-1.29%). Prevalence was moderated by the inclusion of BD not otherwise specified (P = .009) and by geographic region; rates from Africa and Asia were less than half of those from North and South America. Rates did not change significantly over 3 decades after controlling for design features. CONCLUSIONS:The overall prevalence rate is consistent with historical estimates, but rates vary significantly across studies. Differences in methodology contribute to the perception that rates of BD have increased over time. Rates varied markedly by geographic region, even after controlling for all other predictors. Research using consistent definitions and methods may expose specific factors that confer risk for BD.

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.

Research on positive emotion disturbance has gained increasing attention, yet it is not clear which specific positive emotions are affected by mood symptoms, particularly during the critical period of adolescence. This is especially pertinent for identifying potential endophenotypic markers associated with mood disorder onset and course. The present study examined self-reported discrete positive and negative emotions in association with clinician-rated manic and depressive mood symptoms in a clinically and demographically diverse group of 401 outpatient adolescents between 11-18 years of age. Results indicated that higher self reported joy and contempt were associated with increased symptoms of mania, after controlling for symptoms of depression. Low levels of joy and high sadness uniquely predicted symptoms of depression, after controlling for symptoms of mania. Results were independent of age, ethnicity, gender and bipolar diagnosis. These findings extend work on specific emotions implicated in mood pathology in adulthood, and provide insights into associations between emotions associated with goal driven behavior with manic and depressive mood symptom severity in adolescence. In particular, joy was the only emotion associated with both depressive and manic symptoms across adolescent psychopathology, highlighting the importance of understanding positive emotion disturbance during adolescent development.

OBJECTIVES:Epidemiological studies suggest that cyclothymic disorder is the most prevalent subtype of bipolar disorder (BD). However, it is rarely diagnosed, especially in youth. This may be because it can be difficult to ascertain whether a youth meets diagnostic criteria. Clearer, easy-to-apply criteria could reduce misdiagnosis. The objective oftable this study was to determine whether proposed research diagnostic criteria for cyclothymic disorder (RDCyc), based on DSM-5 criteria, could be quantified and validated in youth. METHODS:Participants from the Longitudinal Assessment of Manic Symptoms (LAMS) study were recruited based on symptoms of mania and followed prospectively. RDCyc criteria were: 1) At least one core symptom each of mania and depression; 2) one additional symptom of mania and of depression; 3) persistence over two consecutive six-month periods, and 4) impairment. Exclusionary criteria were having a [hypo]manic or depressive episode. Outcomes at the two-year follow-up were compared between RDCyc youth and other diagnostic groups (BD I/II, BD NOS/non-RDCyc cyclothymic disorder, disruptive behavior disorders [DBD], depression). RESULTS:Thirty-seven youth met RDCyc criteria. There were no consistent differences between the RDCyc youth and youth with other BD subtypes (ps=0.001-0.960, with all-but-one p value >0.02). RDCyc youth had higher depression (p<0.0005) and mania scores (p=0.001), lower functioning (p=0.012), and higher suicide risk than DBD youth (p=0.001). They had higher mania scores than depressed youth (p.018). LIMITATIONS:The majority of youth in the sample were recruited due to elevated symptoms of mania, which may limit the generalizability of the results. Youth were followed for two years, which may not be long enough to determine whether or not they will eventually develop a manic or depressive episode. CONCLUSIONS:Applying RDCyc criteria identified youth who were similar to others with BD and were more impaired than those with DBD. Using these criteria could reduce misdiagnosis and increase our understanding of this prevalent, but largely ignored, diagnosis.

OBJECTIVE:Depression and bipolar disorder (negative mood disorders, NMD) are associated with dysregulated hypothalamic-pituitary-adrenal (HPA)-axis function and disrupted emotion processing. The neural networks involved in attenuation of HPA-axis reactivity overlap with the circuitry involved in perception and modulation of emotion; however, direct links between these systems are understudied. This study investigated whether cortisol activity prior to undergoing fMRI was related to neural processing of emotional information in participants with NMD. METHODS:=36.43, SD=17.33) provided salivary cortisol samples prior to completing a facial emotion perception test during 3-Tesla fMRI. RESULTS:Overall, pre-scan cortisol level was positively associated with greater engagement of the dorsal anterior cingulate (dACC), inferior parietal lobule, insula, putamen, precuneus, middle and medial frontal and postcentral gyri, posterior cingulate, and inferior temporal gyrus during emotion processing of all faces. NMD status moderated this effect; in NMD participants' pre-scan cortisol was associated with attenuated activation of the insula, postcentral gyrus, precuneus, and putamen for fearful faces and the medial frontal gyrus for angry faces relative to HCs. Cortisol-related attenuation of activation among NMD participants was also observed for facial identification in the dACC, putamen, middle temporal gyrus, precuneus, and caudate. CONCLUSIONS:Across all participants, cortisol was associated with greater activation in several regions involved in the perception and control of emotion. However, cortisol responsivity was associated with hypoactivation of several of these regions in the NMD group, suggesting that HPA-axis activity may selectively interfere with the potentially adaptive recruitment of circuits supporting emotion perception, processing and/or regulation in mood disorders.

OBJECTIVE: The aim of this study was to meta-analyze the prevalence of symptoms before an initial mood episode of bipolar disorder (BD) and the prevalence of subthreshold symptoms before a BD mood episode recurrence, to facilitate early identification and prevention. METHOD: Systematic literature reviews were conducted in PsycINFO and PubMed for prospective or retrospective studies reporting on the prevalence and longest duration of symptoms before an initial or recurrent mood episode of BD. Random effects meta-regression explored whether geographic location, age, percentage of female individuals, and study quality moderated the overall prevalence. RESULTS: In 11 studies (n = 1,078), the prodrome preceding an initial mood episode lasted 27.1 +/- 23.1 months (range, 4.6-130 months). In 10 studies (n = 1,000), the subthreshold symptoms preceding a recurrent mood episode lasted 1.0 +/- 0.9 months (range, 0.5-1.3 months). The most common symptoms were largely consistent with diagnostic criteria symptoms associated with the subsequent mood polarity for both the initial prodrome and the period prior to a recurrent mood episode. Few moderators of symptom prevalences emerged, and significant heterogeneity remained. CONCLUSION: The initial prodromal period is sufficiently long and characterized by symptoms of the subsequent mood episode to make early identification and intervention programs feasible. Conversely, the period of subthreshold symptoms before a recurrent mood episode is short, mandating adequate psychoeducation of patients and families, monitoring of changes in sleep and activity, plus sufficiently frequent follow-up visits to identify patients before a mood episode recurrence. Future prospective investigations, designed to address the identified shortcomings in the extant literature, are needed to identify more clinically applicable information.

OBJECTIVES/OBJECTIVE:The phenomenology and diagnosis of pediatric bipolar disorder has been controversial. We aimed to update a 2005 meta analysis of the prevalence of manic symptoms in youth, in order to determine whether the picture of pediatric mania has changed as research on pediatric bipolar disorder has grown. METHODS:We conducted literature reviews in PsycINFO and PubMed; studies with the prevalence of manic symptoms in youth were included. Two raters coded each study; kappa was 0.86-1.0. RESULTS:Twenty studies were meta-analyzed (N = 2,226 youths). The most common symptoms across bipolar subtypes, using a random-effects model, were: increased energy 79%, irritability 77%, mood lability 76%, distractibility 74%, goal-directed activity 72%, euphoric/elated mood 64%, pressured speech 63%, hyperactive 62%, racing thoughts 61%, poor judgment 61%, grandiosity 57%, inappropriate laughter 57%, decreased need for sleep 56%, and flight of ideas 54%. Symptom rates were heterogeneous across samples; potential predictors were explored but no clear patterns were found. CONCLUSIONS:Debate continues about the definitions of pediatric bipolar disorder; the results of this meta-analysis suggest that there is significant heterogeneity of symptom prevalence between studies, and that symptoms vary widely across individuals. Understanding the roots of this heterogeneity could broaden understanding of the complex clinical presentation of pediatric mania, and aid in diagnosis.

OBJECTIVE:Research on adults with cyclothymic disorder (CycD) suggests that irritability and impulsive aggression (IA) are highly prevalent among this population. Less is known about whether these behaviors might also distinguish youth with CycD from youth without CycD. Additionally, little is known about how irritability and IA relate to one another, and whether they are associated with different outcomes. This study aimed to compare irritability and IA across diagnostic subtypes to determine whether CycD is uniquely associated with these behaviors, and to assess how irritability and IA relate to youth social and general functioning. METHODS:Participants (n = 459), 11-18 years of age, were recruited from an urban community mental health center and an academic outpatient clinic; 25 had a diagnosis of CycD. Youth and caregivers completed measures of IA and irritability. Youth and caregivers also completed an assessment of youth friendship quality. Clinical interviewers assessed youth social, family, and school functioning. RESULTS:Youth with CycD had higher scores on measures of irritability and IA than youth with nonbipolar disorders, but scores were not different from other youth with bipolar spectrum disorders. Measures of irritability and IA were correlated, but represented distinct constructs. Regression analyses indicated that irritability was related to friendship quality (p < 0.005). Both IA and irritability were related to social impairment (ps < 0.05-0.0005) and Child Global Assessment Scale (C-GAS) scores (ps = 0.05-0.005). CycD diagnosis was associated with poorer caregiver-rated friendship quality and social functioning (ps < 0.05). CONCLUSIONS:We found that irritability and aggression were more severe among youth with CycD than among youth with nonbipolar diagnoses, but did not differ across bipolar disorder subtypes. Among youth seeking treatment for mental illness, irritability and IA are prevalent and nonspecific. Irritability and IA were uniquely related to our outcomes of social and general functioning, suggesting that it is worthwhile to assess each separately, in order to broaden our understanding of the characteristics and correlates of each.

OBJECTIVE:Compare the accuracy, agreement, internal consistency, and interrater reliability of 3 interviews to assess suicidal ideation and behavior in accordance with US Food and Drug Administration guidance about reporting categories. METHOD/METHODS:Adults admitted to a psychiatric inpatient unit (N = 199) completed 3 assessments of past month and lifetime suicidal ideation and behavior-the Columbia Suicide Severity Rating Scale (C-SSRS), the Suicide Tracking Scale (STS), and the Sheehan Suicidality Tracking Scale (S-STS)-in randomized, counterbalanced order. "Missing gold standard" latent class analyses defined categories for ideation and behavior. Analyses also evaluated the S-STS mapping to C-SSRS categories. Three trained judges re-rated 89 randomly selected interview videotapes. Cohen κ, the primary outcome measure, quantified agreement above chance. Data were collected between November 2011 and June 2013. RESULTS:All 3 assessments showed excellent accuracy for suicidal ideation (κ = 0.72 to 1.00) and attempts (κ = 0.82 to 0.95) calibrated against latent classes. Interrater agreement ranged from κ = 0.52 to 1.00. Interrater agreement about more granular C-SSRS categories varied more widely (κ = 0.48 to 1.00), and the C-SSRS and S-STS assigned significantly different numbers of cases to many categories. Cronbach α was < 0.55 for the C-SSRS ideation and between 0.78 and 0.92 for the other scales. CONCLUSIONS:All 3 assessments showed good accuracy for broad categories of suicidal ideation and behavior. More granular, specific categories usually were rated reliably, but the C-SSRS and S-STS differed significantly in regard to which patients were assigned to these subcategories. Using any of these interviews would improve reliability over unstructured assessment in evaluating suicidal ideation and behavior. Clinical predictive validity of these interviews, and particularly the more granular categories, remains to be shown.