Psychiatry Neuroimaging Laboratory, Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Psychol Med. 2023 Jul;53(10):4707-4719. doi: 10.1017/S003329172200160X. Epub 2022 Jul 7.
While adolescent-onset schizophrenia (ADO-SCZ) and adolescent-onset bipolar disorder with psychosis (psychotic ADO-BPD) present a more severe clinical course than their adult forms, their pathophysiology is poorly understood. Here, we study potentially state- and trait-related white matter diffusion-weighted magnetic resonance imaging (dMRI) abnormalities along the adolescent-onset psychosis continuum to address this need.
Forty-eight individuals with ADO-SCZ (20 female/28 male), 15 individuals with psychotic ADO-BPD (7 female/8 male), and 35 healthy controls (HCs, 18 female/17 male) underwent dMRI and clinical assessments. Maps of extracellular free-water (FW) and fractional anisotropy of cellular tissue (FA) were compared between individuals with psychosis and HCs using tract-based spatial statistics and FSL's Randomise. FA and FW values were extracted, averaged across all voxels that demonstrated group differences, and then utilized to test for the influence of age, medication, age of onset, duration of illness, symptom severity, and intelligence.
Individuals with adolescent-onset psychosis exhibited pronounced FW and FA abnormalities compared to HCs. FA reductions were spatially more widespread in ADO-SCZ. FW increases, however, were only present in psychotic ADO-BPD. In HCs, but not in individuals with adolescent-onset psychosis, FA was positively related to age.
We observe evidence for cellular (FA) and extracellular (FW) white matter abnormalities in adolescent-onset psychosis. Although cellular white matter abnormalities were more prominent in ADO-SCZ, such alterations may reflect a shared trait, i.e. neurodevelopmental pathology, present across the psychosis spectrum. Extracellular abnormalities were evident in psychotic ADO-BPD, potentially indicating a more dynamic, state-dependent brain reaction to psychosis.
青少年起病精神分裂症（ADO-SCZ）和伴有精神病性症状的青少年起病双相障碍（psychotic ADO-BPD）的临床表现比成人形式更为严重，但它们的病理生理学尚不清楚。在这里，我们研究了青少年起病精神病谱中潜在的与状态和特征相关的白质弥散加权磁共振成像（dMRI）异常，以满足这一需求。
48 名 ADO-SCZ 患者（20 名女性/28 名男性）、15 名伴有精神病性症状的 ADO-BPD 患者（7 名女性/8 名男性）和 35 名健康对照者（HCs，18 名女性/17 名男性）接受了 dMRI 和临床评估。使用基于束流的空间统计学和 FSL 的 Randomise 比较了精神病患者和 HCs 之间细胞外游离水（FW）和细胞组织各向异性分数（FA）的地图。在显示组间差异的所有体素上提取 FA 和 FW 值，然后进行平均值计算，并用于测试年龄、药物、发病年龄、疾病持续时间、症状严重程度和智力的影响。
与 HCs 相比，青少年起病精神病患者表现出明显的 FW 和 FA 异常。与 ADO-SCZ 相比，FA 减少的空间范围更广。然而，FW 增加仅见于伴有精神病性症状的 ADO-BPD。在 HCs 中，而不是在青少年起病精神病患者中，FA 与年龄呈正相关。
我们观察到青少年起病精神病患者存在细胞（FA）和细胞外（FW）白质异常的证据。尽管 ADO-SCZ 中细胞性白质异常更为突出，但这种改变可能反映了精神分裂症谱中存在的共同特征，即神经发育病理学。伴有精神病性症状的 ADO-BPD 中存在细胞外异常，这可能表明对精神病的反应更为动态，与状态相关。
