Mary Kay Gill

Course of subthreshold bipolar disorder in youth: diagnostic progression from bipolar disorder not otherwise specified.

OBJECTIVE To determine the rate of diagnostic conversion from an operationalized diagnosis of bipolar disorder not otherwise specified (BP-NOS) to bipolar I disorder (BP-I) or bipolar II disorder (BP-II) in youth over prospective follow-up and to identify factors associated with conversion. METHOD Subjects were 140 children and adolescents recruited from clinical referrals or advertisement who met operationalized criteria for BP-NOS at intake and participated in at least one follow-up evaluation (91% of initial cohort). Diagnoses were assessed at follow-up interviews using the Longitudinal Interval Follow-Up Evaluation. The mean duration of follow-up was 5 years and the mean interval between assessments was 8.2 months. RESULTS Diagnostic conversion to BP-I or BP-II occurred in 63 subjects (45%): 32 (23%) to BP-I (nine of whom had initially converted to BP-II) and 31 to only BP-II (22%). Median time from intake to conversion was 58 weeks. First- or second-degree family history of mania or hypomania was the strongest baseline predictor of diagnostic conversion (p = .006). Over follow-up, conversion was associated with greater intensity of hypomanic symptoms and with greater exposure to specialized, intensive outpatient psychosocial treatments. There was no association between conversion and exposure to treatment with particular medication classes. CONCLUSIONS Children and adolescents referred with mood symptoms that meet operationalized criteria for BP-NOS, particularly those with a family history of BP, frequently progress to BP-I or BP-II. Efforts to identify these youth and effectively intervene may have the potential to curtail the progression of mood disorders in this high-risk population.

Psychosocial Functioning Among Bipolar Youth

BACKGROUND Evidence indicates that children and adolescents with bipolar disorder (BP) experience significant functional impairment. However, little is known about the association between psychosocial functioning and episodes of illness, demographic, and clinical variables in this population. METHODS Subjects included 446 patients aged 7 to 17 diagnosed with DSM-IV bipolar disorder via the K-SADS for the Course and Outcome of Bipolar Youth (COBY) study. The Psychosocial Functioning Schedule of the Adolescent Longitudinal Interval Follow-Up Assessment (A-LIFE) was administered at study intake. RESULTS Mild to moderate levels of psychosocial impairment were evident in work (includes academics), interpersonal, and overall domains of functioning among BP youth. Multivariate analyses indicated that the strongest predictors of psychosocial impairment were adolescence (regardless of age of onset), current mood episode, current affective symptom severity, current psychotic symptoms, and current comorbid conduct disorder. Bipolar youth in-episode were significantly more impaired than those in partial remission/recovery in every functional domain examined and were less satisfied with their functioning. Yet, BP youth in partial remission/recovery reported significant psychosocial impairment. LIMITATIONS Limitations include the reliance on patient and parent retrospective report of psychosocial functioning. Additionally, we did not account for the impact of psychosocial and pharmacological interventions on functioning. CONCLUSIONS Findings suggest pediatric BP is associated with significant impairment in psychosocial functioning during and between episodes, with greater impairment during mood episodes than during partial remission/recovery. Additionally, functional impairment in BP appears to increase during adolescence regardless of age of onset. Clinicians should carefully assess and address psychosocial impairment during and between mood episodes, with particular attention to the functioning of BP adolescents.

Examining the Proposed Disruptive Mood Dysregulation Disorder Diagnosis in Children in the Longitudinal Assessment of Manic Symptoms Study

OBJECTIVE To examine the proposed disruptive mood dysregulation disorder (DMDD) diagnosis in a child psychiatric outpatient population. Evaluation of DMDD included 4 domains: clinical phenomenology, delimitation from other diagnoses, longitudinal stability, and association with parental psychiatric disorders. METHOD Data were obtained from 706 children aged 6-12 years who participated in the Longitudinal Assessment of Manic Symptoms (LAMS) study (sample was accrued from November 2005 to November 2008). DSM-IV criteria were used, and assessments, which included diagnostic, symptomatic, and functional measures, were performed at intake and at 12 and 24 months of follow-up. For the current post hoc analyses, a retrospective diagnosis of DMDD was constructed using items from the K-SADS-PL-W, a version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children, which resulted in criteria closely matching the proposed DSM-5 criteria for DMDD. RESULTS At intake, 26% of participants met the operational DMDD criteria. DMDD+ vs DMDD- participants had higher rates of oppositional defiant disorder (relative risk [RR] = 3.9, P < .0001) and conduct disorder (RR = 4.5, P < .0001). On multivariate analysis, DMDD+ participants had higher rates of and more severe symptoms of oppositional defiant disorder (rate and symptom severity P values < .0001) and conduct disorder (rate, P < .0001; symptom severity, P = .01), but did not differ in the rates of mood, anxiety, or attention-deficit/hyperactivity disorders or in severity of inattentive, hyperactive, manic, depressive, or anxiety symptoms. Most of the participants with oppositional defiant disorder (58%) or conduct disorder (61%) met DMDD criteria, but those who were DMDD+ vs DMDD- did not differ in diagnostic comorbidity, symptom severity, or functional impairment. Over 2-year follow-up, 40% of the LAMS sample met DMDD criteria at least once, but 52% of these participants met criteria at only 1 assessment. DMDD was not associated with new onset of mood or anxiety disorders or with parental psychiatric history. CONCLUSIONS In this clinical sample, DMDD could not be delimited from oppositional defiant disorder and conduct disorder, had limited diagnostic stability, and was not associated with current, future-onset, or parental history of mood or anxiety disorders. These findings raise concerns about the diagnostic utility of DMDD in clinical populations.

Substance Use Disorders among Adolescents with Bipolar Spectrum Disorders

OBJECTIVE We set out to examine the prevalence and correlates of substance use disorders (SUD) in a large sample of adolescents with bipolar disorder (BP). METHODS Subjects were 249 adolescents ages 12 to 17 years old who fulfilled DSM-IV criteria for bipolar I disorder [(BPI), n = 154], or bipolar II disorder [(BPII), n = 25], or operationalized criteria for BP not otherwise specified [(BP NOS), n = 70], via the Schedule for Affective Disorders and Schizophrenia for School-Aged Children (K-SADS). As part of the multi-site Course and Outcome of Bipolar Youth study, demographic, clinical, and family history variables were measured via intake clinical interview with the subject and a parent/guardian. RESULTS The lifetime prevalence of SUD among adolescents with BP was 16% (40/249). Results from univariate analyses indicated that subjects with, as compared to without, SUD were significantly less likely to be living with both biological parents, and that there was significantly greater lifetime prevalence of physical abuse, sexual abuse, suicide attempts, conduct disorder, and posttraumatic stress disorder among subjects with SUD. Subjects with SUD reported significantly greater 12-month prevalence of trouble with police, and females with SUD reported significantly greater 12-month prevalence of pregnancy and abortion. Significant predictors of SUD in a logistic regression model included living with both biological parents (lower prevalence), conduct disorder and suicide attempts (increased prevalence). In logistic regression analyses controlling for demographic differences and conduct disorder, SUD remained significantly associated with trouble with police, whereas the association of SUD with pregnancy and abortion was reduced to a statistical trend. The prevalence of SUD was not significantly different among child- versus adolescent-onset BP subjects. CONCLUSIONS SUD among adolescents with BP is associated with profound hazards including suicide attempts, trouble with police, and teenage pregnancy and abortion.

Schedule for Affective Disorders and Schizophrenia for School- Age Children (K-SADS-PL) for the Assessment of Preschool Children- A Preliminary Psychometric Study

OBJECTIVE To assess the psychometrics of the schedule for affective disorders and schizophrenia for school-age children present and lifetime version (K-SADS-PL) in diagnosing DSM-IV psychiatric disorders and subsyndromal symptomatology in preschool children. METHOD Parents were interviewed about their children using the K-SADS-PL, and they completed the early childhood inventory-4 (ECI-4) and child behavior checklist for ages 1(1/2)-5 years (CBCL). Discriminant, divergent, and convergent validity of the K-SADS-PL were evaluated in 204 offspring ages 2-5 years old of parents from an ongoing study. Inter-rater reliability as well as predictive validity of intake diagnoses at second assessment approximately two years after intake were evaluated. Fourteen children were also assessed by the preschool age psychiatric assessment (PAPA). RESULTS Children who were diagnosed with oppositional defiant disorder, attention deficit hyperactivity disorder, anxiety, mood, or elimination disorders had significantly higher scores on the ECI-4 than children without these disorders. Significant correlations were found for all convergent CBCL scales. Divergent validity was acceptable for emotional disorders. Inter-rater kappa coefficients for all diagnoses were good. Above noted results were similar for children with at least one positive K-SADS-PL key screen symptom. A significantly higher percentage of children with an intake diagnosis had a diagnosis approximately two years after intake compared to those without an intake disorder. Overall, there was consistency between the PAPA and the K-SADS-PL. CONCLUSIONS Pending further testing, the K-SADS-PL may prove useful for the assessment of psychopathology in preschoolers.

Characteristics of children with elevated symptoms of mania: The Longitudinal Assessment of Manic Symptoms (LAMS) study

OBJECTIVE The aim of the Longitudinal Assessment of Manic Symptoms (LAMS) study is to examine differences in psychiatric symptomatology, diagnoses, demographics, functioning, and psychotropic medication exposure in children with elevated symptoms of mania (ESM) compared to youth without ESM. This article describes the initial demographic information, diagnostic and symptom prevalence, and medication exposure for the LAMS cohort that will be followed longitudinally. METHOD Guardians of consecutively ascertained new outpatients 6 to 12 years of age presenting for treatment at one of 10 university-affiliated mental health centers were asked to complete the Parent General Behavior Inventory-10-Item Mania Scale (PGBI-10M). Patients with scores ≥ 12 on the PGBI-10M (ESM+) and a matched sample of patients who screened negative (ESM-) were invited to participate. Patients were enrolled from December 13, 2005, to December 18, 2008. RESULTS 707 children (621 ESM+, 86 ESM-; mean [SD] age = 9.4 [2.0] years) were evaluated. The ESM+ group, compared to the ESM- group, more frequently met DSM-IV criteria for a mood disorder (P < .001), bipolar spectrum disorders (BPSD; P < .001), and disruptive behavior disorders (P < .01). Furthermore, they showed poorer overall functioning and more severe manic, depressive, attention-deficit/hyperactivity, disruptive behavioral, and anxiety symptoms. Nevertheless, rates of BPSD were relatively low in the ESM+ group (25%), with almost half of these BPSD patients (12.1% of ESM+ patients) meeting DSM-IV criteria for bipolar disorder not otherwise specified. ESM+ children with BPSD had significantly more of the following: current prescriptions for antipsychotics, mood stabilizers, and anticonvulsants (P < .001 for each); psychiatric hospitalizations (P < .001); and biological parents with elevated mood (P = .001 for mothers, P < .013 for fathers). ESM+ children with BPSD were also lower functioning compared to ESM+ children without BPSD. CONCLUSIONS Although ESM+ was associated with higher rates of BPSD than ESM-, 75% of ESM+ children did not meet criteria for BPSD. Results suggest that longitudinal assessment is needed to examine which factors are associated with diagnostic evolution to BPSD in children with elevated symptoms of mania.

Prevalence and correlates of physical and sexual abuse in children and adolescents with bipolar disorder

OBJECTIVE Adult bipolar disorder (BP) has been associated with lifetime history of physical and sexual abuse. However, there are no reports of the prevalence of abuse in BP youth. The objective of this study was to examine the prevalence and correlates of physical and/or sexual abuse among youth with BP spectrum disorders. METHODS Four hundred forty-six youths, ages 7 to 17 years (12.7+/-3.2), meeting DSM-IV criteria for BP-I (n=260), BP-II (n=32) or operationalized definition of BP-NOS (n=154) were assessed using the Schedule for Affective Disorders and Schizophrenia for School Age Children-Present and Lifetime version (K-SADS-PL). Abuse was ascertained using the K-SADS. RESULTS Twenty percent of the sample experienced physical and/or sexual abuse. The most robust correlates of any abuse history were living with a non-intact family (OR=2.6), lifetime history of posttraumatic stress disorder (PTSD) (OR=8.8), psychosis (OR=2.1), conduct disorder (CD) (OR=2.3), and first-degree family history of mood disorder (OR=2.2). After adjusting for confounding demographic factors, physical abuse was associated with longer duration of BP illness, non-intact family, PTSD, psychosis, and first-degree family history of mood disorder. Sexual abuse was associated with PTSD. Subjects with both types of abuse were older, with longer illness duration, non-intact family, and greater prevalence of PTSD and CD as compared with the non-abused group. LIMITATIONS Retrospective data. Also, since this is a cross-sectional study, no inferences regarding causality can be made. CONCLUSION Sexual and/or physical abuse is common in youth with BP particularly in subjects with comorbid PTSD, psychosis, or CD. Prompt identification and treatment of these youth is warranted.

Longitudinal Assessment of Manic Symptoms (LAMS) Study: Background, Design and Initial Screening Results

OBJECTIVE To describe the design of a longitudinal study of youth with elevated symptoms of mania (ESM), as well as the prevalence and correlates of manic symptoms. Bipolar disorder in youth is serious and is surrounded by controversy about its phenomenology, course, and treatment. Yet, there are no longitudinal studies of youth selected only for ESM, the phenomenological hallmark. The studys objective is to document the rate and sociodemographic correlates of ESM in children attending outpatient psychiatric clinics. METHOD Parents of 3,329 children aged 6-12 years visiting 10 outpatient clinics were asked to complete the Parent General Behavior Inventory 10-Item Mania Scale (PGBI-10M). Children with PGBI-10M scores ≥ 12 (ESM positive-screen [ESM+]) and a matched sample of ESM screen-negative (ESM-) children were invited to enroll in the longitudinal study. The sample was accrued from November 14, 2005, to November 28, 2008. RESULTS Most of the children whose parents filled out the PGBI-10M (N = 2,622, 78.8%) participated in the study. Nonparticipants were slightly younger (mean age = 9.1 years [SD = 2.0 years] versus 9.4 years [SD = 2.0 years] for participants; t3327 = 4.42, P < .001). Nearly half of the participants (43%) were ESM+; these were more likely to be Latino (4.2% versus 2.5% for ESM-; χ(2)1 = 5.45, P = .02), younger (mean age = 9.3 years [SD = 2.0 years] versus 9.6 years [SD = 1.9 years] for ESM-; t2620 = 3.8, P < .001), and insured by Medicaid (48.4% versus 35.4% for ESM-; χ(2)1 = 45.00, P < .001). There were no sociodemographic differences between those who did versus did not agree to enroll in the longitudinal portion (yes to enrollment: n = 621, 55.2%; no to enrollment: n = 503, 44.8%). Four items best discriminated ESM+ children from ESM- children. Three of the 4 items were not the most commonly endorsed items, but all were indicative of behavioral extremes. CONCLUSIONS Data suggest that ESM+ is not rare in 6- to 12-year-olds. Children who are ESM+ show behavioral extremes, including rapid mood shifts, compared to ESM- children.

Significance of cigarette smoking among youths with bipolar disorder

Cigarette smoking among adults with bipolar disorder (BP) correlates with psychosis, substance use disorders (SUD), and suicidality. Little is known regarding smoking among youths with BP. Youths with BP (n = 441) were divided into three smoking groups: Never, Ever, and Daily. Twenty-five percent reported any smoking (11% daily, 14% ever). Ever and Daily subjects had significantly greater lifetime prevalence of suicide attempts, physical abuse, conduct disorder, and SUD compared to Never subjects. Daily heavy smokers had greater prevalence of SUD and suicide attempts, and worse depression versus daily light smokers. Smoking among youths with BP is independently associated with suicide attempts and SUD.

Comorbid anxiety in children and adolescents with bipolar spectrum disorders: prevalence and clinical correlates.

OBJECTIVE Anxiety disorders are among the most common comorbid conditions in youth with bipolar disorder. We aimed to examine the prevalence and correlates of comorbid anxiety disorders among youth with bipolar disorder. METHOD As part of the Course and Outcome of Bipolar Youth study, 446 youth, ages 7 to 17 years, who met DSM-IV criteria for bipolar I disorder (n = 260) or bipolar II disorder (n = 32) or met operationalized criteria for bipolar disorder not otherwise specified (n = 154) were included. Subjects were evaluated for current and lifetime Axis I psychiatric disorders at intake using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Aged Children-Present and Lifetime version, and standardized instruments were used to assess functioning and family history. RESULTS Forty-four percent (n = 194) of the sample met DSM-IV criteria for at least 1 lifetime anxiety disorder, most commonly separation anxiety (24%) and generalized anxiety disorders (16%). Nearly 20% met criteria for 2 or more anxiety disorders. Overall, anxiety disorders predated the onset of bipolar disorder. Subjects with bipolar II disorder were more likely than subjects with bipolar I disorder or bipolar disorder not otherwise specified to have a comorbid anxiety disorder. After adjusting for confounding factors, youth with bipolar disorder with anxiety were more likely to have bipolar II disorder; longer duration of mood symptoms; more severe ratings of depression; and family history of depression, hopelessness, and somatic complaints during their worst lifetime depressive episode than those without anxiety. CONCLUSIONS Comorbid anxiety disorders are common in youth with bipolar disorder, and they most often predate bipolar disorder onset. Bipolar II disorder, a family history of depression, and more severe lifetime depressive episodes distinguish youth with bipolar disorder with comorbid anxiety disorders from those without. Careful consideration should be given to the assessment of comorbid anxiety in youth with bipolar disorder.