Evidence for disruption in prefrontal cortical functions in juvenile bipolar disorder.

OBJECTIVES: Systematic parsing of executive function processes is critical for the development of more specific models of neurobiological processes mediating disturbed cognition in youth with bipolar disorder (BPD). METHODS: A sample of 33 children and adolescents with bipolar I disorder (BPD I) (mean age 12.1 +/- 3.0 years, 39% female) and 44 demographically matched healthy participants (mean age 12.9 +/- 2.8 years, 50% female) completed a neurocognitive battery including measures aimed at detection of disruption in prefrontal cortical circuitry (i.e., working memory, set shifting, and rule attainment). RESULTS: Compared to healthy controls, BPD I children exhibited significant deficits in spatial working memory, visual sequencing and scanning, verbal fluency and abstract problem solving, particularly when a memory component was involved. In our spatial delayed response task, memory set size was parametrically varied; the performance pattern in BPD I children suggested deficits in short-term memory encoding and/or storage, rather than capacity limitations in spatial working memory. Earlier age at onset of illness and antipsychotic medication usage were associated with poorer performance on speeded information-processing tasks; however, severity of mood symptomatology and comorbidity with disruptive behavior disorders were not associated with task performance. CONCLUSIONS: These results suggest impairment in measures of prefrontal cortical function in juvenile BPD I that are similar to those seen in the adult form of the illness, and implicate both the ventral and dorsolateral prefrontal cortex as loci of pathology in juvenile BPD. As these deficits were not associated with clinical state or comorbidity with other disorders, they may reflect trait-related impairments, a hypothesis that will be pursued further in longitudinal studies.

Declarative memory impairment in pediatric bipolar disorder.

OBJECTIVES: Impaired verbal declarative memory has been proposed as a trait marker for adult bipolar disorder. However, similar impairments in juvenile-onset bipolar disorder have not been yet documented. Here, we assessed declarative memory in a large sample of clinically well-characterized children with bipolar disorder. METHODS: Forty-one children and adolescents with bipolar disorder [21 bipolar I disorder (BP-I), 10 bipolar II disorder (BP-II), and 10 bipolar disorder, not otherwise specified (BP-NOS)] and 17 demographically matched healthy participants completed a standardized learning and memory test. RESULTS: BP-I children recalled and recognized significantly fewer words than healthy subjects, whereas children with BP-II and BP-NOS did not differ from controls. However, individuals with BP-NOS made more perseverative errors and intrusions than the other groups. Severity of mood symptomatology was not associated with memory performance in any bipolar subtype. CONCLUSIONS: Findings suggest that declarative memory impairments in juvenile BP-I are similar to those seen in the adult form of the illness. These impairments do not appear to be secondary to clinical state; rather, they may reflect trait-related impairments. Distinct performance patterns in BP-I, BP-II, and BP-NOS suggest that the broadly defined phenotype is significantly heterogeneous, and may not be informative for pathogenetic investigations of bipolar disorder.

A feasibility study of the childhood depression medication algorithm: the Texas Children's Medication Algorithm Project (CMAP).

OBJECTIVE: To evaluate the feasibility and impact on clinical response and function associated with the use of an algorithm-driven disease management program (ALGO) for children and adolescents treated for depression with or without attention-deficit/hyperactivity disorder (ADHD) in community mental health centers. METHOD: Interventions included (1). medication algorithms, (2). clinical and technical support for the physician, (3). uniform chart documentation of outcomes, and (4). a patient/family psychoeducation program. Children eligible for entry into the study were referred to the child psychiatrist for initiation or change in medicine. Outcomes of treatment with the ALGO for up to 4 months are presented. Measures of change included clinical symptoms, functioning, and global improvement (Clinical Global Impression Scale). A historical chart cohort from the same clinics was used as a quasi-control. RESULTS: Thirty-nine individuals (depression = 24; comorbid depression with ADHD = 15) were enrolled for treatment with ALGO. One hundred fourteen children were in the control cohort (74 depressed, 40 comorbid). For the ALGO groups, Children's Depression Rating Scale-Revised depression severity scores decreased from 48.2 to 32.5 and Child Adolescent Functioning Assessment Scale function scores improved from 70.3 to 40.9 (all p < or =.0005). Clinical Global Impression Scale severity scores decreased from 5.7 to 3.7 in ALGO compared to only 5.8 to 4.8 in the control (p <.003). CONCLUSIONS: There was clear improvement in clinical symptoms, functioning, and global response with ALGO treatment. The magnitude of the improvement was greater in children and adolescents treated with the ALGO program compared with a historical cohort. These data support the need for controlled studies in larger populations examining the effects of algorithm-driven disease management programs on the clinical outcomes of children with mental illness.