Rasim Somer Diler

The Child Behavior Checklist (CBCL) and the CBCL-Bipolar Phenotype Are Not Useful in Diagnosing Pediatric Bipolar Disorder

OBJECTIVES Previous studies have suggested that the sum of Attention, Aggression, and Anxious/Depressed subscales of Child Behavior Checklist (CBCL-PBD; pediatric bipolar disorder phenotype) may be specific to pediatric bipolar disorder (BP). The purpose of this study was to evaluate the usefulness of the CBCL and CBCL-PBD to identify BP in children <12 years old. METHODS A sample of children with BP I, II, and not otherwise specified (NOS) (n = 157) ascertained through the Course and Outcome for Bipolar Disorder in Youth (COBY) study were compared with a group of children with major depressive/anxiety disorders (MDD/ANX; n = 101), disruptive behavior disorder (DBD) (n = 127), and healthy control (HC) (n = 128). The CBCL T-scores and area under the curve (AUC) scores were calculated and compared among the above-noted groups. RESULTS Forty one percent of BP children did not have significantly elevated CBCL-PBD scores (>or=2 standard deviations [SD]). The sensitivity and specificity of CBCL-PBD >or= 2 SD for diagnosis of BP was 57% and 70-77%, respectively, and the accuracy of CBCL-PBD for identifying a BP diagnosis was moderate (AUC = 0.72-0.78). CONCLUSION The CBCL and the CBCL-PBD showed that BP children have more severe psychopathology than HC and children with other psychopathology, but they were not useful as a proxy for Diagnostic and Statistical Manual of Mental Disorders, 4(th) edition (DSM-IV) diagnosis of BP.

Concerns Regarding the Inclusion of Temper Dysregulation Disorder With Dysphoria in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition

Though we understand the incredibly difficult work required in order to revise the Diagnostic and Statistical Manual of Mental Disorders (DSM) and appreciate the efforts of those serving to develop it, we as a group are strongly against including temper dysregulation disorder with dysphoria (TDD) as an official diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We believe that currently there is insufficient scientific support to include TDD as a unique diagnostic entity. Furthermore, we believe that the inclusion of TDD will have an adverse impact on patient care, research, and the general public’s perception of child psychiatry. Our concerns are outlined below, and then we offer some alternative strategies to improve diagnostic classification of chronically irritable youths for the DSM-5 Work Groups to consider.

Does pharmacotherapy for attention-deficit/hyperactivity disorder predict risk of later major depression?

OBJECTIVE This studys goal was to determine among youths with attention-deficit/hyperactivity disorder (ADHD) how the history of ADHD pharmacotherapy influenced the risk of developing major depressive disorder (MDD), compared to other commonly reported predictors. METHOD Diagnostic and treatment history data were analyzed retrospectively in 75 youths 11-18 years old with definite or probable ADHD, enrolled in an observational study at a tertiary mental health clinic. Subjects with histories of MDD (H/o MDD) (n = 36) were compared to others who had never been depressed (Never-Depressed) (n = 39) regarding histories of ADHD pharmacotherapy, psychopathology and other potential covariates of MDD risk. RESULTS H/o MDD subjects reported longer delays before initiating ADHD pharmacotherapy, were more often female, reported having experienced more traumatic event types, and had higher rates of early anxiety and externalizing disorders. With all covariates allowed to enter a backward stepwise Cox regression of survival time till first episodes of MDD, only two variables remained in the model. The time-dependent variable, ADHD pharmacotherapy, prolonged survival times (p = .012), while having experienced more traumatic event types shortened them (p = .001). CONCLUSIONS This study provides preliminary evidence that pharmacotherapy for ADHD may have a protective effect in ADHD youths, reducing the risk of later MDD.

Psychosocial functioning in offspring of parents with bipolar disorder

BACKGROUND Offspring of parents with bipolar disorder are at increased risk for a range of psychopathology, including bipolar disorder. It is not clear if they also have impairments in their psychosocial functioning. METHODS We compared the psychosocial functioning of three groups of children enrolled in the Pittsburgh Bipolar Offspring Study (BIOS): offspring of probands with bipolar disorder (n=388), offspring of probands with other types of psychopathology (n=132), and offspring of healthy probands (n=118). Psychosocial functioning was assessed at study intake using the schedule of the Adolescent Longitudinal Interval Follow-Up Evaluation (A-LIFE), the Child Behavior Check List (CBCL) and the Childrens Global Assessment Scale (CGAS). RESULTS Offspring of probands with bipolar disorder exhibited impairments in various aspects of psychosocial functioning. On all measures, they had worse functioning in comparison with offspring of healthy probands. Offspring of probands with bipolar disorder generally exhibited more impairment than offspring of probands with nonbipolar psychopathology. After adjusting for proband parent functioning and the childs Axis I psychopathology, functioning of offspring of probands with bipolar disorder was similar to that of offspring of healthy probands. LIMITATIONS Data are cross-sectional and therefore do not allow for causal conclusions about the association between parental psychopathology, child psychopathology and offspring psychosocial functioning. CONCLUSIONS Offspring of parents with bipolar disorder exhibit impairments in psychosocial functioning which appear largely attributable to proband parent functional impairment and the childs own psychopathology. As such, interventions to improve parental functioning, as well as early interventions to treat the childs psychopathology may help reduce the risk for long-term functional impairment in offspring.

Neural activity to intense positive versus negative stimuli can help differentiate bipolar disorder from unipolar major depressive disorder in depressed adolescents: A pilot fMRI study

Failure to distinguish bipolar depression (BDd) from the unipolar depression of major depressive disorder (UDd) in adolescents has significant clinical consequences. We aimed to identify differential patterns of functional neural activity in BDd versus UDd and employed two (fearful and happy) facial expression/ gender labeling functional magnetic resonance imaging (fMRI) experiments to study emotion processing in 10 BDd (8 females, mean age=15.1 ± 1.1) compared to age- and gender-matched 10 UDd and 10 healthy control (HC) adolescents who were age- and gender-matched to the BDd group. BDd adolescents, relative to UDd, showed significantly lower activity to both intense happy (e.g., insula and temporal cortex) and intense fearful faces (e.g., frontal precentral cortex). Although the neural regions recruited in each group were not the same, both BDd and UDd adolescents, relative to HC, showed significantly lower neural activity to intense happy and mild happy faces, but elevated neural activity to mild fearful faces. Our results indicated that patterns of neural activity to intense positive and negative emotional stimuli can help differentiate BDd from UDd in adolescents.

Dimensional psychopathology in offspring of parents with bipolar disorder.

Diler RS, Birmaher B, Axelson D, Obreja M, Monk K, Hickey MB, Goldstein B, Goldstein T, Sakolsky D, Iyengar S, Brent D, Kupfer D. Dimensional psychopathology in offspring of parents with bipolar disorder. Bipolar Disord 2011: 13: 670–678.

The longitudinal course of sleep timing and circadian preferences in adults with bipolar disorder.

To study the longitudinal course of sleep timing and circadian preferences in individuals with bipolar disorder (BP) compared to individuals with non‐BP psychopathology and healthy controls.

Inflammatory Markers Among Adolescents and Young Adults With Bipolar Spectrum Disorders

OBJECTIVE Despite burgeoning literature in middle-aged adults, little is known regarding proinflammatory markers (PIMs) among adolescents and young adults with bipolar disorder. Similarly, few prior studies have considered potential confounds when examining the association between PIMs and bipolar disorder characteristics. We therefore retrospectively examined these topics in the Course and Outcome of Bipolar Youth (COBY) study. METHOD Subjects were 123 adolescents and young adults (mean [SD] = 20.4 ± 3.8 years; range, 13.4-28.3 years) in COBY, enrolled between October 2000 and July 2006. DSM-IV diagnoses were determined using the Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS). Clinical characteristics during the preceding 6 months, including mood, comorbidity, and treatment, were evaluated using the Longitudinal Interval Follow-Up Evaluation (LIFE). Serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP) were assayed. Primary analyses examined the association of PIMs with bipolar disorder characteristics during the preceding 6 months. RESULTS Several lifetime clinical characteristics were significantly associated with PIMs in multivariable analyses, including longer illness duration (P = .005 for IL-6; P = .0004 for hsCRP), suicide attempts (P = .01 for TNF-α), family history of suicide attempts or completion (P = .01 for hsCRP), self-injurious behavior (P =.005 for TNF-α), substance use disorder (SUD) (P < .0001 for hsCRP), and family history of SUD (P = .02 for TNF-α; P = .01 for IL-6). The following bipolar disorder characteristics during the preceding 6 months remained significantly associated with PIMs in multivariable analyses that controlled for differences in comorbidity and treatment: for TNF-α, percentage of weeks with psychosis (χ(2) = 5.7, P =.02); for IL-6, percentage of weeks with subthreshold mood symptoms (χ(2)= 8.3, P = .004) and any suicide attempt (χ(2) = 6.1, P = .01); for hsCRP, maximum severity of depressive symptoms (χ(2) = 8.3, P =.004). CONCLUSION Proinflammatory markers may be relevant to bipolar disorder characteristics as well as other clinical characteristics among adolescents and young adults with bipolar disorder. Traction toward validating PIMs as clinically relevant biomarkers in bipolar disorder will require repeated measures of PIMs and incorporation of relevant covariates.

Mood lability among offspring of parents with bipolar disorder and community controls

Early identification of bipolar disorder (BP) symptomatology is crucial for improving the prognosis of this illness. Increased mood lability has been reported in BP. However, mood lability is ubiquitous across psychiatric disorders and may be a marker of severe psychopathology and not specific to BP. To clarify this issue, this study examined the prevalence of mood lability and its components in offspring of BP parents and offspring of community control parents recruited through the Pittsburgh Bipolar Offspring Study.

Pharmacologic Treatment of Bipolar Disorder in Children and Adolescents

This review focuses mainly on published articles regarding the treatment of school-aged children and adolescents with pediatric bipolar disorder. In light of systematic reviews, large randomized controlled trial data are emphasized wherever possible. This review addresses the treatment of acute manic/mixed episodes, including combination treatment, the preliminary literature regarding bipolar depression among youth, treatment in the face of comorbid conditions, and maintenance treatment. Suggestions regarding future directions are offered. A clinical vignette describing a teen with bipolar disorder is presented and bipolar medications, dosing, efficacy, side effects, contraindications, and succinct comments on each medication are summarized.