Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, 1601 23rd Avenue South, Nashville, TN, 37212, USA.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
Cerebellum. 2024 Jun;23(3):1215-1220. doi: 10.1007/s12311-023-01591-9. Epub 2023 Aug 4.
Psychomotor disturbance has been identified as a key feature of psychotic disorders, with motor signs observed in upwards of 66% of unmedicated, first-episode patients. Aberrations in the cerebellum have been directly linked to sensorimotor processing deficits including processing speed, which may underly psychomotor disturbance in psychosis, though these brain-behavior-symptom relationships are unclear, in part due to within-diagnosis heterogeneity across these levels of analysis. In 339 psychosis patients (242 schizophrenia-spectrum, 97 bipolar with psychotic features) and 217 controls, we evaluated the relationship between cerebellar grey matter volume in the Yeo sensorimotor network and psychomotor disturbance (mannerisms and posturing, retardation, excitement of the Positive and Negative Syndrome Scale [PANSS]), as mediated by processing speed (assessed via the SCIP). Models included intracranial volume, age, sex, and chlorpromazine equivalents as covariates. We observed significant mediation by processing speed, with a small positive effect of the cerebellum on processing speed (ß = 0.172, p = 0.029, d = 0.24) and a medium negative effect of processing speed on psychomotor disturbance (ß = -0.254, p < 0.001, d = 0.60), with acceptable specificity and sensitivity suggesting this model is robust against unmeasured confounding. The current findings suggest a critical role of cerebellar circuitry in a well-established sensorimotor aberration in psychosis (processing speed) and the presentation of related psychomotor phenotypes within psychosis. Establishing such relationships is critical for intervention research, such as TMS. Future work will employ more dimensional measures of psychomotor disturbance and cognitive processes to capture normative and aberrant brain-behavior-symptom relationships and may also determine the magnitude of these relationships within subtypes of psychosis (e.g., disorganized behavior, catatonia).
精神运动障碍已被确定为精神病性障碍的一个关键特征，在未经治疗的首发患者中，超过 66%的患者存在运动体征。小脑的异常与感觉运动处理缺陷直接相关，包括处理速度，这可能是精神病性精神运动障碍的基础，尽管这些大脑-行为-症状关系尚不清楚，部分原因是在这些分析水平上存在诊断内异质性。在 339 名精神病患者（242 名精神分裂症谱系，97 名伴有精神病特征的双相障碍）和 217 名对照者中，我们评估了 Yeo 感觉运动网络中的小脑灰质体积与精神运动障碍（怪癖和姿势、迟滞、阳性和阴性症状量表 [PANSS] 的兴奋）之间的关系，由处理速度（通过 SCIP 评估）介导。模型包括颅内体积、年龄、性别和氯丙嗪当量作为协变量。我们观察到处理速度的显著中介作用，小脑对处理速度有轻微的正效应（ß=0.172，p=0.029，d=0.24），处理速度对精神运动障碍有中度负效应（ß=-0.254，p<0.001，d=0.60），特异性和敏感性均可接受，表明该模型对未测量的混杂具有稳健性。目前的研究结果表明，小脑回路在精神病中已确立的感觉运动异常（处理速度）和相关精神运动表型的表现中起着关键作用。建立这种关系对于干预研究（如 TMS）至关重要。未来的工作将采用更具维度的精神运动障碍和认知过程测量方法，以捕捉正常和异常的大脑-行为-症状关系，并且还可能确定这些关系在精神病的亚型（例如，思维紊乱、紧张症）中的程度。
