The effects of ziprasidone on prefrontal and amygdalar activation in manic youth with bipolar disorder.
BACKGROUND
Prior research has found that manic adolescents with bipolar disorder exhibit neurofunctional changes in the amygdala and prefrontal cortex following treatment with some pharmacological agents. We examined the neurofunctional effects of ziprasidone in manic adolescents.


METHODS
Manic adolescents with bipolar disorder (n=23) participated in a placebo-controlled study of ziprasidone and underwent a functional magnetic resonance imaging scanning session while performing a task of sustained attention at baseline, prior to treatment as well as on days 7 and 28 (or early termination) of treatment. A comparison group of healthy adolescents (n=10) participated in a single scanning session. Region of interest analyses were performed to assess activation changes associated with treatment in Brodmann Areas (BA) 10, 11 and 47 and in the amygdala.


RESULTS
Compared with placebo, treatment with ziprasidone was associated with greater increases over time in right BA 11 and 47 activation. These effects were not associated with differences in symptom improvement between the treatment groups. Patients who subsequently responded to ziprasidone showed significantly greater deactivation in the right Brodmann area 47 at baseline than those who did not respond to ziprasidone. Similarly, among the bipolar adolescents who were treated with ziprasidone, baseline activation in right BA 47 was negatively correlated with improvement in Young Mania Rating Scale (YMRS) score.


CONCLUSIONS
The small sample size limits the ability to detect significant group differences in other regions of interest. Healthy comparison subjects were scanned only at a single timepoint, which limits the interpretation of the results. Ziprasidone is not currently approved by the United States Food and Drug Administration for the treatment of adolescents with mania, and, therefore, the clinical relevance of these results is limited.


CONCLUSIONS
The increases in right BA 11 and 47 activation observed during sustained attention tasks following ziprasidone treatment and the association identified between lower baseline BA 47 activation and ziprasidone treatment response suggests that ziprasidone may correct prefrontal dysfunction in manic adolescents with bipolar disorder.
Physician Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio, U.S.A.
Marguerite Reid
MR
Schneider
Caleb M
CM
Adler
Rachel
R
Whitsel
Wade
W
Weber
Neil P
NP
Mills
Samantha M
SM
Bitter
James
J
Eliassen
Stephen M
SM
Strakowski
Melissa P
MP
DelBello
D000293:Adolescent; D000679:Amygdala / Q000187:drug effects*; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001714:Bipolar Disorder / Q000188:drug therapy*; D002648:Child; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects*; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*
D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone