Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England2Fundación para la Investigación y Docencia Maria Angustias Giménez Germanes Hospitalàries, Centro de Investigación Biomédica en R.
Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, England3Department of Psychiatry, University of Basel, Basel, Switzerland.
JAMA Psychiatry. 2015 Dec;72(12):1243-51. doi: 10.1001/jamapsychiatry.2015.2196.
Abnormal reward processing is suggested to underlie the formation of psychotic symptoms, likely driven by elevated ventral striatal (VS) dopamine levels. Functional magnetic resonance imaging studies reveal alterations of VS activity during reward processing in patients with chronic psychosis and first episode of psychosis, as well as individuals at high risk for psychosis, but findings are inconclusive, conflicting, and difficult to subject to meta-analysis without introducing bias because several studies reported that findings were not statistically significant but did not report statistics.
To assess the differences between patients with schizophrenia spectrum disorders and healthy controls in VS activation during reward processing.
Web of Knowledge database (incorporating Web of Science and MEDLINE) until July 2015, including references of eligible articles and reviews.
Functional magnetic resonance imaging studies comparing VS activity during monetary reward processing between patients with schizophrenia spectrum disorders or clinical or genetic high-risk state for psychosis and healthy controls.
Statistics and thresholds related to the main outcome measures and potential moderators were independently retrieved by 2 investigators. Effect sizes were analyzed using MetaNSUE, a random-effects method that enables the unbiased inclusion of nonstatistically significant unreported effects.
Effect size of the group differences in VS activity, and correlation between VS activity and negative and positive symptom scores in patients.
The meta-analysis included 23 studies (917 patients) for reward anticipation, 9 studies (358 patients) for reward feedback, and 8 studies (314 patients) for reward prediction error. We found significant bilateral VS hypoactivation during reward anticipation (23 studies, n = 917) in patients compared with healthy controls (left/right Cohen d, -0.50/-0.70; P < .001). Left VS abnormality was more severe in patients with high scores of negative symptoms during reward anticipation (r = -0.41; P < .001). Patients also showed hypoactivation during reward feedback (left/right d, -0.57/-0.56; P < .001). Simulations showed that exclusion of studies with nonstatistically significant unreported effects was associated with a strong bias (d bias = 0.22), whereas estimations using MetaNSUE were unbiased even when statistics were seldom reported (d bias < 0.001).
This meta-analysis provides evidence that patients with psychosis demonstrate VS hypoactivation during reward anticipation. The assessment of VS prediction errors seems to be promising, but more studies are needed to draw valid conclusions.
异常的奖励处理被认为是精神病症状形成的基础，可能是由腹侧纹状体（VS）多巴胺水平升高驱动的。功能磁共振成像研究表明，在慢性精神病和首发精神病患者以及精神病高危个体中，VS 在奖励处理过程中的活动发生了改变，但研究结果尚无定论，相互矛盾，并且由于一些研究报告说研究结果没有统计学意义但没有报告统计数据，因此很难进行荟萃分析而不会引入偏差。
评估精神分裂症谱系障碍患者与健康对照组在奖励处理过程中 VS 激活方面的差异。
Web of Knowledge 数据库（包括 Web of Science 和 MEDLINE），直至 2015 年 7 月，包括符合条件的文章和综述的参考文献。
比较精神分裂症谱系障碍患者或精神病临床或遗传高危状态与健康对照组在金钱奖励处理过程中 VS 活动的功能磁共振成像研究。
两名研究人员独立提取与主要结局指标和潜在调节因素相关的统计数据和阈值。使用 MetaNSUE 分析效应大小，这是一种随机效应方法，可以公正地纳入未报告的非统计学显著效应。
VS 活动的组间差异的效应大小，以及患者 VS 活动与阴性和阳性症状评分之间的相关性。
荟萃分析纳入了 23 项研究（917 名患者）用于奖励预期，9 项研究（358 名患者）用于奖励反馈，8 项研究（314 名患者）用于奖励预测错误。我们发现，与健康对照组相比，患者在奖励预期期间双侧 VS 活动明显减弱（23 项研究，n=917；左/右 Cohen d，-0.50/-0.70；P<0.001）。在奖励预期期间，左侧 VS 异常在高阴性症状评分的患者中更为严重（r=-0.41；P<0.001）。患者在奖励反馈期间也表现出活动减弱（左/右 d，-0.57/-0.56；P<0.001）。模拟表明，排除无统计学意义但未报告的效应的研究与强烈的偏差相关（d 偏差=0.22），而即使很少报告统计数据，使用 MetaNSUE 进行估计也没有偏差（d 偏差<0.001）。
这项荟萃分析提供了证据表明，精神病患者在奖励预期期间表现出 VS 活动减弱。评估 VS 预测错误似乎很有前途，但需要更多的研究来得出有效的结论。
