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Background: There is substantial evidence that bipolar disorder (BD) manifests on a spectrum rather than as a categorical condition. Detection of people with subthreshold manifestations of BD is therefore important. The Hypomania Checklist-32 (HCL-32) was developed as a tool to identify such people., Purpose: The aims of this paper were to: (1) investigate the factor structure of HCL-32; (2) determine whether the HCL-32 can discriminate between mood disorder subtypes; and (3) assess the familial aggregation and cross-aggregation of hypomanic symptoms assessed on the HCL with BD., Procedures: Ninety-six probands recruited from the community and 154 of their adult first-degree relatives completed the HCL-32. Diagnosis was based on semi-structured interviews and family history reports. Explanatory factor analysis and mixed effects linear regression models were used., Findings: A four-factor ("Activity/Increased energy," "Distractibility/Irritability", "Novelty seeking/Disinhibition, "Substance use") solution fit the HCL-32, explaining 11.1% of the total variance. The Distractibility/Irritability score was elevated among those with BP-I and BP-II, compared to those with depression and no mood disorders. Higher HCL-32 scores were associated with increased risk of BD-I (OR = 1.22, 95%CI 1.14-1.30). The "Distractibility/Irritability" score was transmitted within families (β = 0.15, p = 0.040). However, there was no familial cross-aggregation between mood disorders and the 4 HCL factors., Conclusions: Our findings suggest that the HCL-32 discriminates the mood disorder subtypes, is familial and may provide a dimensional index of propensity to BD. Future studies should explore the heritability of symptoms, rather than focusing on diagnoses., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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 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.

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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: Forty-one adults (M age =40.33, SD=15.57) with major depression (n=29) or bipolar disorder (n=12) and 23 healthy control comparisons (M age =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., Competing Interests: M. G. M. is on the Speakers Bureau for Merck Pharmaceuticals., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objectives: 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., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Learning more about how biological traits, like temperament and sensitivity in the behavioral inhibition (BIS) and behavioral activation (BAS) systems, relate to mood pathology is consistent with the Research Domain Criteria initiative׳s goal of investigating mechanisms of risk., Method: Korean young adults (n=128) and American young adults (n=630, of whom 23 has recent treatment for bipolar disorder, and 21for depression) completed self-report questionnaires, including the TEMPS-A, the BIS/BAS scales, Beck Depression Inventory (BDI), and Hypomanic Checklist (HCL-32). Linear regression quantified relations between mood symptoms, sample characteristics, temperament, and BIS/BAS., Results: Temperament styles explained 49% of the variance in BDI scores. BIS explained an additional 1% of the variance in BDI scores. BAS Fun and Reward (p<.01), in addition to cyclothymic and hyperthymic temperaments (p<.001) explained 21% of the variance in HCL-32 scores. Sample characteristics were not significant predictors in the full model., Limitations: Differences in sample size, the cross-sectional study design, and lack of collateral report or behavioral measures of constructs are limitations., Conclusions: Affective temperament and BIS/BAS are complementary but distinct constructs. Affective temperament, particularly cyclothymic, may represent a stronger diathesis for mood pathology, and seems potent irrespective of culture or diagnosis. Assessing temperament may help overcome some challenges in diagnosing mood disorders., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Suicidality among youth with bipolar disorder is an extreme, but largely unaddressed, public health problem. The current study examined the psychosocial characteristics differentiating youth with varying severities of suicidal ideation that may dictate targets for suicide prevention interventions., Methods: Participants included 72 youth aged 7-13 (M=9.19, SD=1.61) with DSM-IV-TR bipolar I, II, or NOS and a parent/caregiver. Current suicidal ideation and correlates were assessed at intake, including: demographics and clinical factors (diagnosis, symptom severity, psychiatric comorbidity); child factors (cognitive risk and quality of life); and family factors (parenting stress, family cohesion, and family rigidity)., Results: Current ideation was prevalent in this young sample: 41% endorsed any ideation, and 31% endorsed active forms. Depression symptoms, quality of life, hopelessness, self-esteem, and family rigidity differentiated youth with increasing ideation severity. Separate logistic regressions examined all significant child- and family-level factors, controlling for demographic and clinical variables. Greater family rigidity and lower self-esteem remained significant predictors of current planful ideation. Diagnosis, index episode, comorbidity, and mania severity did not differentiate non-ideators from those with current ideation., Limitations: Limitations include the small sample to examine low base-rate severe ideation, cross-sectional analyses and generalizability of findings beyond the outpatient clinical sample., Conclusions: Findings underscore the importance of assessing and addressing suicidality in preadolescent youth with bipolar disorder, before youth progress to more severe suicidal behaviors. Results also highlight child self-esteem and family rigidity as key treatment targets to reduce suicide risk in pediatric bipolar disorder., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: In the pediatric bipolar disorder literature, mania has eclipsed depression as the mood state of most interest. Though depressive episodes tend to be more prevalent and persisting than manic episodes, research about the associated consequences is limited. The goal of the present study was to compare the influences of depressive and manic symptoms on domains of functioning in which youth with bipolar disorder often demonstrate deficits., Method: Youth meeting DSM-IV-TR criteria for bipolar spectrum disorders (I, II, and NOS) between the ages of seven and 13 were recruited from a clinic in a large Midwestern city (N=54). Both parent and clinician report of manic and depressive symptoms were used in regression analyses to determine how each set of symptoms was related to child functioning., Results: Parent-rated child depression symptoms were associated with problem behaviors (p<0.05), and lower quality of life (p<0.001). Clinician-rated child depression was associated with greater psychiatric illness (p<0.05), lower child self-concept (p<0.001), lower quality of life (p<0.05), hopelessness (p<0.05), and suicidal ideation (p<0.05). Parent-rated mania was associated with better self-esteem (p<0.05) and physical wellbeing (p<0.05). Clinician-rated mania was associated with greater psychiatric illness (p<0.05) and physical wellbeing (p<0.05)., Limitations: The specific outcomes predicted by parent and clinician-rated symptoms vary. Though the overall story told--that bipolar depression is associated with significant impairment in youth--is consistent, further research is necessary to more fully understand the impact of each mood state., Conclusion: Mania is undoubtedly destructive, but this study provides evidence to suggest that depression may be more deleterious to youths' psychosocial functioning and quality of life; more attention to understanding and ameliorating the effects of bipolar depression on youth is warranted., (© 2013 Elsevier B.V. All rights reserved.)

DSM-IV-TR defines four subtypes of bipolar disorder (BP): bipolar I, bipolar II, cyclothymic disorder and bipolar not otherwise specified (NOS). However, cyclothymic disorder in children is rarely researched, or often subsumed in an "NOS" category. The present study tests the replicability of findings from an earlier study, and expands on the criterion validity of cyclothymic disorder in youth. Using the Robins and Guze (1970) framework we examined the validity of cyclothymic disorder as a subtype of BP. Using a youth (ages 5-17) outpatient clinical sample (N = 894), participants with cyclothymic disorder (n = 53) were compared to participants with other BP spectrum disorders (n = 399) and to participants with non-bipolar disorders (n = 442). Analyses tested differences in youth with cyclothymic disorder and bipolar disorder not otherwise specified who do, and those who do not, have a parent with BP. Compared to youth with non-bipolar disorders, youth with cyclothymic disorder had higher irritability (p < 0.001), more comorbidity (p < 0.001), greater sleep disturbance (p < 0.005), and were more likely to have a family history of BP (p < 0.001). Cyclothymic disorder was associated with a younger age of onset compared to depression (p < 0.001) and bipolar II (p = 0.05). Parental BP status was not significantly associated with any variables. Results support that cyclothymic disorder belongs on the bipolar spectrum. Epidemiological studies indicate that cyclothymic disorder is not uncommon and involves significant impairment. Failing to differentiate between cyclothymic disorder and bipolar NOS limits our knowledge about a significant proportion of cases of bipolarity.

Cyclothymic disorder is a subtype of bipolar disorder included in the Diagnostic and Statistical Manual of Mental Disorders since 1980, but largely neglected in research. Additionally, it is rarely diagnosed clinically, in spite of evidence that it may be the most prevalent form of bipolar disorder. Neglect has contributed to confusion about the diagnosis and clinical presentation of cyclothymic disorder. Its status as a mood disorder is also ambiguous due to overlap in terminology and symptoms with temperament and personality disorders. Subthreshold bipolar disorder appears more prevalent among young people than previously thought, and follows a range of trajectories from remission to escalation-raising questions about risk factors and traits associated with the varied course. Cyclothymic disorder may be an important diathesis for major mood disorders. Constructs such as cyclothymic disorder link major mood disorder and peri-clinical fluctuations of mood, thus warranting a prominent role in dimensional models of mood and psychopathology. Current evidence indicates that cyclothymic disorder is a prevalent and highly impairing disorder on the bipolar spectrum, with the potential to make unique contributions to our understanding of the risk factors and outcomes associated with bipolar disorder. The inclusion of cyclothymic disorder in future research studies is essential to accurate diagnosis and effective treatment for the full spectrum of bipolar disorder, as well as understanding the developmental trajectory of bipolar spectrum disorders., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Four subtypes of bipolar disorder (BP) - bipolar I, bipolar II, cyclothymia and bipolar not otherwise specified (NOS) - are defined in DSM-IV-TR. Though the diagnostic criteria for each subtype are intended for both adults and children, research investigators and clinicians often stray from the DSM when diagnosing pediatric bipolar disorder (PBD) (Youngstrom, 2009), resulting in a lack of agreement and understanding regarding the PBD subtypes., Methods: The present study uses the diagnostic validation method first proposed by Robins and Guze (1970) to systematically evaluate cyclothymic disorder as a distinct diagnostic subtype of BP. Using a youth (ages 5-17) outpatient clinical sample (n=827), participants with cyclothymic disorder (n=52) were compared to participants with other BP spectrum disorders and to participants with non-bipolar disorders., Results: Results indicate that cyclothymic disorder shares many characteristics with other bipolar subtypes, supporting its inclusion on the bipolar spectrum. Additionally, cyclothymia could be reliably differentiated from non-mood disorders based on irritability, sleep disturbance, age of symptom onset, comorbid diagnoses, and family history., Limitations: There is little supporting research on cyclothymia in young people; these analyses may be considered exploratory. Gaps in this and other studies are highlighted as areas in need of additional research., Conclusions: Cyclothymic disorder has serious implications for those affected. Though it is rarely diagnosed currently, it can be reliably differentiated from other disorders in young people. Failing to accurately diagnose cyclothymia, and other subthreshold forms of bipolar disorder, contributes to a significant delay in appropriate treatment and may have serious prognostic implications., (Copyright © 2011 Elsevier B.V. All rights reserved.)