Kegeles Lawrence S, Abi-Dargham Anissa, Frankle W Gordon, Gil Roberto, Cooper Thomas B, Slifstein Mark, Hwang Dah-Ren, Huang Yiyun, Haber Suzanne N, Laruelle Marc
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, New York, USA.
Arch Gen Psychiatry. 2010 Mar;67(3):231-9. doi: 10.1001/archgenpsychiatry.2010.10.
A long-standing version of the dopamine hypothesis of schizophrenia postulates that hyperactivity of dopaminergic transmission at D(2) receptors in the limbic striatum is associated with the illness and that blockade of mesolimbic D(2) receptors is responsible for the antipsychotic action of D(2) receptor antagonists.
To localize dopaminergic hyperactivity within the striatum in schizophrenia.
Case-control study.
Inpatient research unit.
Eighteen untreated patients with schizophrenia and 18 healthy control subjects matched for age, sex, ethnicity, parental socioeconomic status, cigarette smoking, and weight.
Percentage change in dopamine D(2) receptor availability in striatal subregions within each subject measured by positron emission tomography with carbon 11-labeled raclopride before and during pharmacologically induced dopamine depletion.
In the associative striatum, acute dopamine depletion resulted in a larger increase in D(2) receptor availability in patients with schizophrenia (mean [SD], 15% [7%]) than in control subjects (10% [7%], P = .045), suggesting higher synaptic dopamine concentration. Within the associative striatum, this effect was most pronounced in the precommissural dorsal caudate (15% [8%] in patients vs 9% [8%] in controls, P = .03). No between-group differences were observed in the limbic and sensorimotor striatum.
These findings suggest that schizophrenia is associated with elevated dopamine function in associative regions of the striatum. Because the precommissural dorsal caudate processes information from the dorsolateral prefrontal cortex, this observation also suggests that elevated subcortical dopamine function might adversely affect performance of the dorsolateral prefrontal cortex in schizophrenia. On the other hand, the absence of a group difference in the limbic striatum brings into question the therapeutic relevance of the mesolimbic selectivity of second-generation antipsychotic drugs.
精神分裂症多巴胺假说的一个长期版本假定，边缘纹状体中D(2)受体处多巴胺能传递亢进与该疾病相关，且中脑边缘D(2)受体的阻断是D(2)受体拮抗剂抗精神病作用的原因。
在精神分裂症患者的纹状体内定位多巴胺能亢进。
病例对照研究。
住院研究单位。
18例未经治疗的精神分裂症患者和18名年龄、性别、种族、父母社会经济地位、吸烟情况及体重相匹配的健康对照者。
在药理学诱导的多巴胺耗竭之前和期间，通过使用碳11标记的雷氯必利的正电子发射断层扫描测量每个受试者纹状体亚区域中多巴胺D(2)受体可用性的百分比变化。
在联合纹状体中，急性多巴胺耗竭导致精神分裂症患者的D(2)受体可用性增加幅度（均值[标准差]，15%[7%]）大于对照者（10%[7%]，P = 0.045），提示突触多巴胺浓度更高。在联合纹状体内，这种效应在连合前背侧尾状核最为明显（患者为15%[8%]，对照者为9%[8%]，P = 0.03）。在边缘和感觉运动纹状体中未观察到组间差异。
这些发现提示精神分裂症与纹状体联合区域中多巴胺功能升高有关。由于连合前背侧尾状核处理来自背外侧前额叶皮质的信息，该观察结果还提示皮质下多巴胺功能升高可能对精神分裂症患者背外侧前额叶皮质的功能产生不利影响。另一方面，边缘纹状体中无组间差异对第二代抗精神病药物中脑边缘选择性的治疗相关性提出了质疑。
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