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 speci.c 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 signi.cant de.cits in spatial working memory, visual sequencing and scanning, verbal.uency 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 de.cits 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 isruptive behavior disorders were not associated with task performance. Conclusions: These results suggest impairment in measures of prefrontalcortical 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 de.cits were not associated with clinical state or comorbidity with other disorders, they may re.ect trait-related impairments, a hypothesis that will be pursued further in longitudinal studies.