School of Clinical Medicine, Discipline of Psychiatry and Mental Health, University of New South Wales (UNSW), Sydney, NSW, Australia.
Neuroscience Research Australia, Randwick, NSW, Australia.
Eur Arch Psychiatry Clin Neurosci. 2022 Oct;272(7):1205-1218. doi: 10.1007/s00406-022-01450-4. Epub 2022 Jul 6.
Grey matter volume (GMV) may be associated with polygenic risk for schizophrenia (PRS-SZ) and severe cognitive deficits in people with schizophrenia, schizoaffective disorder (collectively SSD), and bipolar disorder (BD). This study examined the interactive effects of PRS-SZ and cognitive subtypes of SSD and BD in relation to GMV. Two-step cluster analysis was performed on 146 clinical cases (69 SSD and 77 BD) assessed on eight cognitive domains (verbal and visual memory, executive function, processing speed, visual processing, language ability, working memory, and planning). Among them, 55 BD, 51 SSD, and 58 healthy controls (HC), contributed to focal analyses of the relationships between cognitive subtypes, PRS-SZ and their interaction on GMV. Two distinct cognitive subtypes were evident among the combined sample of cases: a 'cognitive deficit' group (CD; N = 31, 20SSD/11BD) showed severe impairment across all cognitive indices, and a 'cognitively spared' (CS; N = 75; 31SSD/44BD) group showed intermediate cognitive performance that was significantly worse than the HC group but better than the CD subgroup. A cognitive subgroup-by-PRS-SZ interaction was significantly associated with GMV in the left precentral gyrus. Moderation analyses revealed a significant negative relationship between PRS-SZ and GMV in the CD group only. At low and average (but not high) PRS-SZ, larger precentral GMV was evident in the CD group compared to both CS and HC groups, and in the CS group compared to HCs. This study provides evidence for a relationship between regional GMV changes and PRS-SZ in psychosis spectrum cases with cognitive deficits, but not in cases cognitively spared.
脑灰质体积（GMV）可能与精神分裂症的多基因风险（PRS-SZ）以及精神分裂症、分裂情感障碍（统称为 SSD）和双相情感障碍（BD）患者的严重认知缺陷有关。本研究探讨了 PRS-SZ 与 SSD 和 BD 的认知亚型的交互作用与 GMV 的关系。对 146 例临床病例（69 例 SSD 和 77 例 BD）进行了两步聚类分析，评估了 8 个认知领域（言语和视觉记忆、执行功能、处理速度、视觉处理、语言能力、工作记忆和计划）。其中，55 例 BD、51 例 SSD 和 58 例健康对照组（HC）参与了认知亚型、PRS-SZ 及其对 GMV 的相互作用关系的焦点分析。在病例的综合样本中，有两个明显不同的认知亚型：一个“认知缺陷”组（CD；N=31，20 例 SSD/11 例 BD）在所有认知指标上均表现出严重的损害，另一个“认知未受损”（CS；N=75；31 例 SSD/44 例 BD）组表现出中等认知表现，明显低于 HC 组，但优于 CD 亚组。认知亚组与 PRS-SZ 的交互作用与左侧中央前回的 GMV 显著相关。调节分析显示，PRS-SZ 与 CD 组的 GMV 之间存在显著的负相关关系。仅在 CD 组中，PRS-SZ 较低和中等（但不是较高）时，与 CS 和 HC 组相比，CD 组的中央前回 GMV 较大，与 HC 组相比，CS 组的 GMV 也较大。这项研究为精神病谱病例中 GMV 变化与 PRS-SZ 之间的关系提供了证据，这些病例存在认知缺陷，但不存在认知未受损的病例。
