Schlagenhauf Florian, Juckel Georg, Koslowski Michael, Kahnt Thorsten, Knutson Brian, Dembler Theresa, Kienast Thorsten, Gallinat Jürgen, Wrase Jana, Heinz Andreas
Department of Psychiatry and Psychotherapy, Charité University Medical Center, Campus Charité Mitte, Charitéplatz 1, 10117 Berlin, Germany.
Psychopharmacology (Berl). 2008 Mar;196(4):673-84. doi: 10.1007/s00213-007-1016-4. Epub 2007 Dec 21.
High blockade of dopamine D2 receptors in the ventral striatum including the nucleus accumbens may interfere with reward anticipation and cause secondary negative symptoms such as apathy or anhedonia. This may not be the case with newer neuroleptics such as olanzapine, which show less dopamine D2 receptor blockade and a faster off-rate from the receptor.
We used functional magnetic resonance imaging to assess the blood oxygenation level dependent response in the ventral striatum of schizophrenics medicated with typical neuroleptics (T1) and after switching them to olanzapine (T2) and of healthy control subjects at corresponding time points during reward anticipation.
Ten schizophrenics, while medicated with typical neuroleptics (T1) and after having been switched to olanzapine (T2), and ten matched healthy volunteers participated in a monetary incentive delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain or have no consequence.
During reward anticipation, healthy volunteers showed significantly higher ventral striatal activation compared to schizophrenic patients treated with typical neuroleptics but not olanzapine, which was reflected in a significant interaction between group and session. In patients treated with typical neuroleptics, but not with olanzapine, decreased left ventral striatal activation was correlated with negative symptoms.
Failure to activate the ventral striatum during reward anticipation was pharmacologically state-dependent and observed only in patients treated with typical neuroleptics but not with olanzapine, which may indicate that this drug did not induce secondary negative symptoms via interference with reward anticipation.
伏隔核等腹侧纹状体中多巴胺D2受体的高度阻断可能会干扰奖赏预期，并导致继发性阴性症状，如冷漠或快感缺失。而奥氮平这类新型抗精神病药物可能并非如此，它们对多巴胺D2受体的阻断作用较小，且从受体上解离的速度更快。
我们使用功能磁共振成像来评估在奖赏预期期间，服用典型抗精神病药物（T1）的精神分裂症患者、换用奥氮平治疗后（T2）的精神分裂症患者以及健康对照者在相应时间点腹侧纹状体的血氧水平依赖反应。
10名精神分裂症患者，在服用典型抗精神病药物时（T1）以及换用奥氮平后（T2），和10名匹配的健康志愿者参与了一项金钱激励延迟任务，其中视觉线索预示着对随后目标刺激的快速反应要么会带来金钱收益，要么没有结果。
在奖赏预期期间，与服用典型抗精神病药物而非奥氮平的精神分裂症患者相比，健康志愿者的腹侧纹状体激活显著更高，这反映在组间和阶段之间的显著交互作用上。在服用典型抗精神病药物而非奥氮平的患者中，左侧腹侧纹状体激活降低与阴性症状相关。
在奖赏预期期间未能激活腹侧纹状体在药理学状态上是依赖的，且仅在服用典型抗精神病药物而非奥氮平的患者中观察到，这可能表明该药物不会通过干扰奖赏预期诱发继发性阴性症状。
