Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan.
Department of Psychiatry, Gakuji-kai Kimura Hospital, Chiba, Japan.
J Psychopharmacol. 2020 May;34(5):540-547. doi: 10.1177/0269881119900982. Epub 2020 Jan 21.
Patients with first-episode psychosis respond well to initial antipsychotic treatment, but among patients experiencing a relapse of psychosis, the response rate falls to approximately 30%. The mechanism of this discrepancy has not been clarified, but the development of dopamine supersensitivity psychosis with the underlying up-regulation of post-synaptic dopamine D2 receptors could be involved in this lesser response. It is uncertain whether elevated dopamine synthesis and release occurs in patients with dopamine supersensitivity psychosis, in contrast to those with first-episode psychosis.
We examined a first-episode psychosis group (=6) and a chronic schizophrenia group, i.e. patients experiencing relapse (=23) including those who relapsed due to dopamine supersensitivity psychosis (=18). Following the initiation of treatment, we measured the patients' blood concentrations of homovanillic acid and 3-methoxy-4-hydroxyphenylglycol at two weeks and four weeks after the baseline measurements.
The first-episode psychosis group tended to show decreased homovanillic acid, accompanied by an improvement of symptoms. The chronic schizophrenia group showed no alteration of homovanillic acid or 3-methoxy-4-hydroxyphenylglycol over the treatment period. These results were the same in the dopamine supersensitivity psychosis patients alone.
Our findings suggest that unlike first-episode psychosis, the release of dopamine from presynaptic neurons did not increase in relapse episodes in the patients with dopamine supersensitivity psychosis. This indirectly indicates that the development of supersensitivity of post-synapse dopamine D2 receptor is involved in relapse in dopamine supersensitivity psychosis patients.
首发精神病患者对初始抗精神病药物治疗反应良好，但在精神病复发患者中，反应率降至约 30%。这种差异的机制尚不清楚，但潜在的突触后多巴胺 D2 受体上调导致的多巴胺超敏性精神病的发展可能与此反应降低有关。目前尚不确定多巴胺超敏性精神病患者是否存在多巴胺合成和释放增加，而首发精神病患者则不然。
我们检查了首发精神病组（=6）和慢性精神分裂症组，即包括因多巴胺超敏性精神病（=18）而复发的患者（=23）在内的复发患者。在开始治疗后，我们在基线测量后的两周和四周测量了患者的血液中高香草酸和 3-甲氧基-4-羟基苯乙二醇的浓度。
首发精神病组的高香草酸倾向于降低，同时症状改善。慢性精神分裂症组在治疗期间未改变高香草酸或 3-甲氧基-4-羟基苯乙二醇。多巴胺超敏性精神病患者也有相同的结果。
我们的发现表明，与首发精神病不同，多巴胺超敏性精神病患者在复发发作时，来自突触前神经元的多巴胺释放没有增加。这间接表明，突触后多巴胺 D2 受体超敏的发展与多巴胺超敏性精神病患者的复发有关。
