Schneider Marguerite Reid, Adler Caleb M, Whitsel Rachel, Weber Wade, Mills Neil P, Bitter Samantha M, Eliassen James, Strakowski Stephen M, DelBello Melissa P
Physician Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, Neuroscience Graduate Program, University of Cincinnati, Cincinnati, Ohio, U.S.A.
Isr J Psychiatry Relat Sci. 2012;49(2):112-20.
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.
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.
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.
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.
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.
先前的研究发现，患有双相情感障碍的躁狂青少年在接受某些药物治疗后，杏仁核和前额叶皮质会出现神经功能变化。我们研究了齐拉西酮对躁狂青少年的神经功能影响。
患有双相情感障碍的躁狂青少年（n = 23）参与了一项齐拉西酮的安慰剂对照研究，并在基线期、治疗前以及治疗第7天和第28天（或提前终止治疗）进行持续注意力任务时接受了功能磁共振成像扫描。一组健康青少年（n = 10）作为对照组参与了单次扫描。进行感兴趣区域分析，以评估与治疗相关的激活变化，这些区域包括布罗德曼区（BA）10、11和47以及杏仁核。
与安慰剂相比，齐拉西酮治疗与右侧BA 11和47激活随时间的更大增加相关。这些效应与治疗组之间症状改善的差异无关。随后对齐拉西酮有反应的患者在基线时右侧布罗德曼区47的失活明显大于对齐拉西酮无反应的患者。同样，在接受齐拉西酮治疗 的双相情感障碍青少年中，右侧BA 47的基线激活与青年躁狂评定量表（YMRS）评分的改善呈负相关。
样本量小限制了在其他感兴趣区域检测显著组间差异的能力。健康对照受试者仅在单个时间点进行扫描，这限制了对结果的解释。齐拉西酮目前未被美国食品药品监督管理局批准用于治疗患有躁狂症的青少年，因此，这些结果的临床相关性有限。
在齐拉西酮治疗后的持续注意力任务中观察到右侧BA 11和47激活增加，以及较低的基线BA 47激活与齐拉西酮治疗反应之间的关联表明，齐拉西酮可能纠正患有双相情感障碍的躁狂青少年的前额叶功能障碍。
