Faculty Bibliography

Shifting definitions and differences in the conceptualization of bipolar disorders have contributed to long diagnostic delays, poor reliability, and inconsistent findings. Rating scales are independent of clinical judgment and offer a reliable way to assess manic symptoms, making them good tools to improve both clinical and research diagnoses of bipolar disorder. However, there are dozens of candidates, with few obvious distinguishing characteristics, making it difficult to select one. Our goal was to metaanalyze the diagnostic accuracy of rating scales designed to identify [hypo]manic symptoms. Additionally, we explored potential moderator variables including global region, translation into a different language, and sample composition. Nearly 4000 articles were identified with searches in PubMed and PsycINFO, yielding 127 effect sizes from 103 studies that met the following inclusion criteria: (a) statistics reported by which a standardized effect size could be calculated, (b) participants age 18 + years, (c) reference diagnoses made by semistructured/structured diagnostic interview, (d) results published in English. Multivariate mixed regression models accounted for multiple effect sizes nested within sample. One hundred twenty-seven effect sizes across 14 rating scales were evaluated. There was significant heterogeneity across effect sizes; Cochran's Q(126 df) = 1622.08, p < .00005, and substantial variance components both within (σ2 = .057) and between samples (σ2 = .253). Four measures performed similarly well and significantly better than some competitors after controlling for design and reporting features. The best rating scales offer an inexpensive, efficient way to improve research and clinical diagnostic processes across diverse populations, and could also complement formal diagnoses for examining secular and cultural trends. (PsycINFO Database Record

This study investigated the clinical utility of the Achenbach System of Empirically Based Assessment (ASEBA) for identifying youth at risk for suicide. Specifically, we investigated how well the Total Problems scores and the sum of two suicide-related items (#18 "Deliberately harms self or attempts suicide" and #91 "Talks about killing self") were able to distinguish youth with a history of suicidal behavior. Youth (N = 1117) aged 5-18 were recruited for two studies of mental illness. History of suicidal behavior was assessed by semi-structured interviews (K-SADS) with youth and caregivers. Youth, caregivers, and a primary teacher each completed the appropriate form (YSR, CBCL, and TRF, respectively) of the ASEBA. Areas under the curve (AUCs) from ROC analyses and diagnostic likelihood ratios (DLRs) were used to measure the ability of both Total Problems T scores, as well as the summed score of two suicide-related items, to identify youth with a history of suicidal behavior. The Suicide Items from the CBCL and YSR performed well (AUCs = 0.85 and 0.70, respectively). The TRF Suicide Items did not perform better than chance, AUC = 0.45. The AUCs for the Total Problems scores were poor-to-fair (0.33-0.65). The CBCL Suicide Items outperformed all other scores (ps = 0.04 to <0.0005). Combining the CBCL and YSR items did not lead to incremental improvement in prediction over the CBCL alone. The sum of two questions from a commonly used assessment tool can offer important information about a youth's risk for suicidal behavior. The low burden of this approach could facilitate wide-spread screening for suicide in an increasingly at-risk population.

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.

This study investigated the diagnostic and clinical utility of the parent-rated Screen for Child Anxiety Related Emotional Disorders (SCARED-P) for detecting youth anxiety disorders. Youth ages 6 to 12 years, 11 months were recruited from 9 outpatient mental health clinics (N = 707). Consensus diagnoses were based on semistructured interviews (Schedule for Affective Disorders and Schizophrenia for School-Age Children) with youth and caregivers; 31% were diagnosed with at least one anxiety disorder. Caregivers completed the SCARED-P to describe youth anxiety levels. SCARED-P scores were not considered during the consensus diagnoses. Areas under the curve (AUCs) from receiver operating characteristic analyses and diagnostic likelihood ratios (DLRs) quantified performance of the SCARED-P total score and subscale scores (generalized anxiety disorder and separation anxiety disorder). SCARED-P total scores had variable efficiency (AUCs = .69-.88), and Generalized Anxiety Disorder and Separation Anxiety subscale scores were excellent (AUCs = .86-.89) for identifying specific anxiety disorders. Optimal subscale cutoff scores were computed to help rule in (DLRs = 2.7-5.4) or rule out (DLRs < 1.0) anxiety disorders among youth. Results suggest that the Generalized Anxiety Disorder and Separation Anxiety SCARED-P subscales accurately identify their respective matched diagnoses. DLRs may aid clinicians in screening for youth anxiety disorders and improve accuracy of diagnosis.

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: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.