Tuominen Lauri, Armio Reetta-Liina, Hansen Justine Y, Walta Maija, Koutsouleris Nikolaos, Laurikainen Heikki, Salokangas Raimo K R, Misic Bratislav, Hietala Jarmo
University of Ottawa Institute of Mental Health Research, Ottawa, ON, Canada.
Department of Psychiatry, Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada.
Transl Psychiatry. 2025 Apr 6;15(1):129. doi: 10.1038/s41398-025-03336-0.
Use of antipsychotic medication is related to thinning of the cerebral cortex, but the underlying mechanisms of this effect remain largely unknown. Here, we investigated potential mechanisms across multiple levels of description by comparing antipsychotic medication related cortical thinning to atlases of normative neurotransmitter distributions, structural and functional organization of the brain, and meta-analyses of functional activation from the Neurosynth database. We first analyzed a single-site discovery sample of patients (N = 131) with early psychosis for whom antipsychotic related cortical thinning was estimated based on lifetime exposure to antipsychotics. Findings were replicated using data from a large (N ≥ 2168) ENIGMA meta-analysis on schizophrenia patients. We discovered that antipsychotic related cortical thinning is associated with a number of neurotransmitter systems, most notably the serotonin system, as well as physiological measures, functional networks and neural oscillatory power distributions typical for regions subserving higher cognition. At the functional level, antipsychotic related cortical thinning affects regions involved in executive function and motivation, but not perception. These results show how molecular, physiological, and large-scale functional patterns may underlie antipsychotic related cortical thinning.
抗精神病药物的使用与大脑皮层变薄有关，但其潜在机制在很大程度上仍不清楚。在这里，我们通过将抗精神病药物相关的皮层变薄与规范性神经递质分布图谱、大脑的结构和功能组织以及来自Neurosynth数据库的功能激活元分析进行比较，在多个描述层面研究了潜在机制。我们首先分析了一个早期精神病患者的单中心发现样本（N = 131），根据其终生服用抗精神病药物的情况估计与抗精神病药物相关的皮层变薄情况。使用来自一项关于精神分裂症患者的大型（N≥2168）ENIGMA元分析的数据对结果进行了重复验证。我们发现，与抗精神病药物相关的皮层变薄与多种神经递质系统有关，最显著的是血清素系统，以及与支持高级认知的区域典型的生理指标、功能网络和神经振荡功率分布有关。在功能层面，与抗精神病药物相关的皮层变薄会影响执行功能和动机相关区域，但不影响感知区域。这些结果表明了分子、生理和大规模功能模式如何可能是抗精神病药物相关皮层变薄背后的原因。
