Department of Psychology, Simon Fraser University, Burnaby, British Columbia.
J Int Neuropsychol Soc. 2012 Jul;18(4):717-27. doi: 10.1017/S1355617712000343. Epub 2012 Apr 4.
Antipsychotic medications can contribute to neurocognitive and motor impairments, but specific links to individualized pharmacological treatment regimens are unclear. In 68 participants with stabilized first-episode psychosis (FEP), we investigated the links between neuropsychological functions and an established anticholinergic potency index and a new D(2) antagonist potency index developed in our lab. Each participant's psychiatric medication regimen was converted into estimated receptor antagonist loads based upon specific medication dosage(s) and reported in vitro brain muscarinic cholinergic and D(2) receptor antagonism. In addition to the global neuropsychological impairments of FEP participants, the findings supported the hypothesized links between receptor antagonist loads and specific deficits. Higher anticholinergic load was associated with poorer delayed verbal memory but was not related to motor functioning. In contrast, higher D(2) load was associated with poorer motor functioning but not verbal memory. These selective antagonist load associations explained 19% of the variance in motor functioning and 17% of the variance in delayed verbal memory. Evidently, some of the neuropsychological impairments found in persons with FEP are selectively related to the specific pharmacodynamics and the dosing of their medication regimens. Moreover, these effects can be readily estimated from practical and inexpensive indices.
抗精神病药物可能导致神经认知和运动损伤，但与个体化药物治疗方案的具体联系尚不清楚。在 68 名稳定的首发精神病（FEP）患者中，我们研究了神经心理学功能与我们实验室开发的既定抗胆碱能效力指数和新的 D2 拮抗剂效力指数之间的联系。根据特定药物剂量和报告的体外脑毒蕈碱胆碱能和 D2 受体拮抗作用，将每位参与者的精神药物治疗方案转换为估计的受体拮抗剂负荷。除了 FEP 参与者的整体神经心理学损伤外，研究结果还支持了受体拮抗剂负荷与特定缺陷之间的假设联系。较高的抗胆碱能负荷与较差的延迟言语记忆有关，但与运动功能无关。相比之下，较高的 D2 负荷与较差的运动功能有关，但与言语记忆无关。这些选择性拮抗剂负荷关联解释了运动功能的 19%和延迟言语记忆的 17%的方差。显然，在 FEP 患者中发现的一些神经心理学损伤与他们的药物治疗方案的特定药效动力学和剂量有关。此外，这些影响可以从实用且廉价的指标中轻易估计。
