Anomalous prefrontal-subcortical activation in familial pediatric bipolar disorder: a functional magnetic resonance imaging investigation.
BACKGROUND
The neurobiological features of pediatric bipolar disorder (BD) are largely unknown. Children and adolescents with BD may be important to study with functional neuroimaging techniques because of their unique status of early-onset BD and high familial loading for the disorder. Neuroimaging studies of adults with BD have implicated the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in the development of this disorder.


OBJECTIVE
To study children and adolescents with BD via functional magnetic resonance imaging using cognitive and affective tasks and to examine possible abnormalities in the DLPFC and ACC, as well as selected subcortical areas, in pediatric familial BD.


METHODS
We evaluated 12 male subjects aged 9 to 18 years with BD who had at least 1 parent with BD as well as 10 age- and IQ-matched healthy male controls. Stimulants were discontinued for at least 24 hours; other medications were continued. Subjects underwent functional magnetic resonance imaging at 3 T while performing a 2-back visuospatial working memory task and an affective task involving the visualization of positively, neutrally, or negatively valenced pictures.


METHODS
An academic referral setting, drawing from the Bay Area of San Francisco, Calif.


RESULTS
Compared with controls, for the visuospatial working memory task, subjects with BD had greater activation in several areas including the bilateral ACC, left putamen, left thalamus, left DLPFC, and right inferior frontal gyrus. Controls had greater activation in the cerebellar vermis. In viewing negatively valenced pictures, subjects with BD had greater activation in the bilateral DLPFC, inferior frontal gyrus, and right insula. Controls had greater activation in the right posterior cingulate gyrus. For positively valenced pictures, subjects with BD had greater activation in the bilateral caudate and thalamus, left middle/superior frontal gyrus, and left ACC, whereas controls had no areas of greater activation.


CONCLUSIONS
Children and adolescents with BD may have underlying abnormalities in the regulation of prefrontal-subcortical circuits. Further functional magnetic resonance imaging studies of attention and mood with greater sample sizes are needed.
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5540, USA. kchang@stanford.edu
Kiki
K
Chang
Nancy E
NE
Adleman
Kimberly
K
Dienes
Diana I
DI
Simeonova
Vinod
V
Menon
Allan
A
Reiss
D000293:Adolescent; D000339:Affect / Q000502:physiology; D000367:Age Factors; D001288:Attention / Q000502:physiology; D001714:Bipolar Disorder / Q000235:genetics / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D005190:Family; D007839:Functional Laterality / Q000502:physiology; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000706:statistics & numerical data*; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D017397:Prefrontal Cortex / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000502:physiology