Neurofunctional Correlates of Response to Quetiapine in Adolescents with Bipolar Depression.

OBJECTIVES: Prior studies have shown that youth with bipolar disorder demonstrate neurofunctional changes in key prefrontal and subcortical brain regions implicated in emotional regulation following treatment with pharmacological agents. We recently reported a large response rate (>60%) to quetiapine (QUET) for treating depressive symptoms in adolescents with bipolar depression. This study investigates the neurofunctional effects of QUET using functional magnetic resonance imaging (fMRI). METHODS: Thirty-three unmedicated subjects, 10-17 years of age, with a current depressive episode (Children's Depression Rating Scale-Revised [CDRS-R] > 40) associated with bipolar I or II disorder were recruited in a two-site randomized, placebo (PBO)-controlled trial of QUET monotherapy for treatment of bipolar depression in adolescents. Twenty-three of these participants (nine male) underwent an MRI scan at baseline, then were randomized to QUET or PBO, followed for 8 weeks, and at the end of their study participation underwent another MRI scan. During the fMRI scan, subjects viewed negative and neutral pictures and rated the valence of each picture. RESULTS: Sixteen subjects had usable data at both time points: 10 subjects randomized to QUET, and 6 randomized to PBO. For QUET subjects, lower baseline activation in the left dorsolateral prefrontal cortex (p < 0.005) and higher baseline activation in the left ventrolateral prefrontal cortex (p = 0.0024) predicted greater improvement in CDRS-R scores from baseline to follow-up. When QUET and PBO groups were combined (n = 16), region-of-interest activation did not significantly predict change in CDRS-R. CONCLUSIONS: Baseline activation patterns in dorsal and ventral portions of the prefrontal cortex that are critical for the regulation of emotion-predicted response, but only within the QUET group. Thus, specific medications may be more effective in the context of specific prefrontal activation patterns in youth with bipolar depression. Larger studies of these youth would help to clarify the effects of QUET on brain activation.

Neurometabolite effects of response to quetiapine and placebo in adolescents with bipolar depression.

OBJECTIVE: Mood stabilizers have been reported to affect brain concentrations of myo-inositol (mI) and N-acetylaspartate (NAA). We examined the effects of quetiapine (QUET), an atypical antipsychotic, on these neurochemicals, and potential predictors of response to QUET in adolescents with bipolar depression. METHODS: Twenty-six adolescents with bipolar depression participated in an 8-week placebo-controlled trial of QUET monotherapy. Subjects were scanned at baseline and after 8 weeks with proton magnetic resonance spectroscopy (1H-MRS) at 3T and 4T at two sites, with 8 cm(3) voxels placed in the right and left dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC). LCModel was used to calculate absolute concentrations of NAA and mI. RESULTS: Twenty-six subjects had pre- and posttreatment scans (mean age=15.6 years, 9 boys). Of these subjects, 5 out of 16 subjects receiving QUET and 5 out of 10 receiving placebo (PBO) were responders (50% decrease in Children's Depression Rating Scale [CDRS] score). Although baseline ACC mI did not predict responder status, responders had significantly lower posttreatment ACC mI values than did nonresponders (3.27±.71 vs. 4.23±.70; p=0.004). There were no significant differences in the changes in ACC and DLPFC NAA levels in the QUET group compared with the PBO group (ACC: -0.55±1.3 vs.+0.25±1.5, p=0.23; right-DLPFC: -0.55±1.3 vs. 0.33±0.89, p=0.13; left-DLPFC: -0.04±0.91 vs.+0.29±0.61, p=0.41). CONCLUSION: We found that posttreatment, not baseline, ACC mI levels were associated with response to QUET in adolescents with bipolar depression. There were no differences in NAA concentration changes between the QUET and PBO groups. Larger studies including different brain regions would help to clarify the effects of QUET on neurochemistry in patients with bipolar disorder.