Dept. of Psychiatry and Psychotherapy III, University of Ulm, Leimgrubenweg 12, 89075 Ulm, Germany.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Oct 1;34(7):1215-22. doi: 10.1016/j.pnpbp.2010.06.022. Epub 2010 Jun 30.
In delusional infestation (DI), as with other non-schizophrenic psychotic disorders, little is known about the neural basis and the mechanisms of antipsychotic treatment. We aimed at investigating the brain circuitry involved in DI and the role of postsynaptic D2 receptors in mediating the effects of antipsychotics by means of multimodal neuroimaging.
In Case 1, a patient with DI (initially drug-induced), cerebral glucose metabolism and dopaminergic neurotransmission were studied in the untreated state (FDG-PET, FDOPA-PET, 123I-FP-CIT-SPECT, and IBZM-SPECT) and after effective aripiprazole treatment (FDG-PET and IBZM-SPECT), with negative drug screenings at both imaging sessions. In Case 2 (DI secondary to mild vascular encephalopathy) cerebral perfusion and gray matter volume changes were investigated in the untreated state and compared to N=8 [corrected] age-matched healthy controls (MRI-based CASL and VBM).
In Case 1, before treatment, glucose metabolism was left-dominant in the thalamus and the putamen. Pre- and postsynaptic dopaminergic neurotransmissions were altered in the striatum, again mainly the left putamen. Full remission to aripiprazole was associated with 63 to 78% striatal D2 receptor occupancy and glucose metabolism changes in the bilateral thalamus. In Case 2, significant perfusion and GMV changes were observed in the bilateral putamen, frontal and parietal somatosensory cortices as compared to controls. Symptoms partially remitted to ziprasidone therapy.
DISCUSSION/CONCLUSION: Six imaging techniques were first used to study the neural basis of DI and mechanisms of antipsychotic therapy. The study provides first low-level evidence in vivo evidence of fronto-striato-thalamo-parietal network to mediate core symptoms of DI, i.e. a priori brain regions involved in judgment (frontal cortex), sensory gating (thalamus) and body perception (dorsal striatum, thalamus and somatic cortices). This is also the first report of effective treatment with aripiprazole in drug-induced DI and with ziprasidone in organic DI, adding to existing limited evidence that SGAs are helpful in various forms of DI. Effective antipsychotic treatment seems to depend on blocking striatal D2 receptors with similar occupancy rates as in schizophrenia. Larger samples are needed to confirm our preliminary findings and further evaluate their relevance for the different forms of DI.
在妄想性寄生虫病(DI)中,与其他非精神分裂症性精神病障碍一样,人们对神经基础和抗精神病治疗机制知之甚少。我们旨在通过多模态神经影像学研究参与 DI 的大脑回路以及突触后 D2 受体在介导抗精神病药物作用中的作用。
在案例 1 中,一名患有 DI(最初为药物诱导)的患者在未治疗状态下(FDG-PET、FDOPA-PET、123I-FP-CIT-SPECT 和 IBZM-SPECT)和有效阿立哌唑治疗后(FDG-PET 和 IBZM-SPECT)研究了大脑葡萄糖代谢和多巴胺能神经传递,两次影像学检查均进行了阴性药物筛查。在案例 2 中(DI 继发于轻度血管性脑病),在未治疗状态下研究了大脑灌注和灰质体积变化,并与 8 名年龄匹配的健康对照者(基于 MRI 的 CASL 和 VBM)进行了比较。
在案例 1 中,治疗前,丘脑和壳核的葡萄糖代谢呈左优势。纹状体中的前突触和后突触多巴胺能神经传递发生改变,主要是左壳核。阿立哌唑完全缓解与双侧丘脑 63%至 78%的纹状体 D2 受体占有率和葡萄糖代谢变化有关。在案例 2 中,与对照组相比,双侧壳核、额顶体感皮质的灌注和 GMV 变化显著。症状部分缓解至齐拉西酮治疗。
讨论/结论:首次使用六种成像技术研究 DI 的神经基础和抗精神病治疗机制。该研究提供了 DI 核心症状的体内神经基础的初步证据,即预先存在的大脑区域参与判断(额叶皮层)、感觉门控(丘脑)和身体感知(背侧纹状体、丘脑和躯体皮质)。这也是阿立哌唑治疗药物诱导性 DI 和齐拉西酮治疗器质性 DI 的首次有效治疗报告,这增加了现有的有限证据,表明 SGA 有助于各种形式的 DI。有效的抗精神病治疗似乎依赖于用与精神分裂症相似的占有率阻断纹状体 D2 受体。需要更大的样本量来证实我们的初步发现,并进一步评估它们对不同形式的 DI 的相关性。