A Pharmacological Functional Magnetic Resonance Imaging Study Probing the Interface of Cognitive and Emotional Brain Systems in Pediatric Bipolar Disorder

Objective: This functional magnetic resonance imaging (fMRI) study investigated the effects of pharmacotherapy on brain function underlying affect dysregulation and cognitive function in pediatric bipolar disorder (PBD). Method: Healthy controls (HC) (n¼14; mean age¼14.1±2.4 years) and unmedicated PBD patients with manic or hypomanic episodes (n¼17; mean age¼14.3±1.1 years) were matched on intelligence quotient (IQ) and demographic factors. The fMRI studies were performed at baseline and after 14 weeks, during which PBD patients were treated initially with second-generation antipsychotics (SGAs) followed by lamotrigine monotherapy. The pediatric affective color-matching task was used where subjects matched the color of a positive, negative, or neutral word with one of the two colored circles below in each of the trials. There were five blocks of each emotional word type, with 10 trials per block. Results: Behavioral data showed that the PBD group was modestly slower and less accurate than the HC, regardless of condition or treatment status. The blood oxygen level-dependent (BOLD) signal activity was reduced with treatment in the PBD group relative to the HC group during the negative versus neutral condition in bilateral dorsolateral prefrontal cortex (DLPFC), right posterior cingulate gyrus, parahippocampal gyrus, and inferior parietal lobule, but increased in left ventromedial prefrontal cortex (VMPFC). Similarly, during the positive versus neutral condition, the PBD group, relative to HC, showed reduced activity in right DLPFC, precuneus, and inferior parietal lobule and increased activity in the right VMPFC. However, within thePBD group, there was treatment related decrease inVMPFC and DLPFC. Improvement on Young Mania Rating Scale (YMRS) score significantly correlated with the decreased activity in VMPFC within the patient group. Conclusions: Pharmacotherapy in PBD patients led to differential effort with persistently increased activity in the affective regions and decreased activity in the cognitive regions relative to HC, demonstrating altered mechanisms of affective and cognitive systems of brain function, regardless of symptom response.