Ebdrup Bjørn H, Raghava Jayachandra M, Nielsen Mette Ø, Rostrup Egill, Glenthøj Birte
From the Centre for Neuropsychiatric Schizophrenia Research, CNSR & Centre for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Copenhagen University Hospital, Mental Health Centre (Ebdrup, Raghava, Nielsen, Glenthøj); and the Functional Imaging Unit, Department of Diagnostics, Glostrup University Hospital (Raghava, Rostrup), Glostrup, Denmark.
J Psychiatry Neurosci. 2016 Mar;41(2):133-41. doi: 10.1503/jpn.150030.
Psychotic symptoms are core clinical features of schizophrenia. We tested recent hypotheses proposing that psychotic, or positive, symptoms stem from irregularities in long-range white matter tracts projecting into the frontal cortex, and we predicted that selective dopamine D2/3 receptor blockade would restore white matter.
Between December 2008 and July 2011, antipsychotic-naive patients with first-episode schizophrenia and matched healthy controls underwent baseline examination with 3 T MRI diffusion tensor imaging and clinical assessments. We assessed group differences of fractional anisotropy (FA) using voxelwise tract-based spatial statistics (TBSS) and anatomic region of interest (ROI)-based analyses. Subsequently, patients underwent 6 weeks of antipsychotic monotherapy with amisulpride. We repeated the examinations after 6 weeks.
We included 38 patients with first-episode schizophrenia and 38 controls in our analysis, and 28 individuals in each group completed the study. At baseline, whole brain TBSS analyses revealed lower FA in patients in the right anterior thalamic radiation (ATR), right cingulum, right inferior longitudinal fasciculus and right corticospinal tract (CT). Fractional anisotropy in the right ATR correlated with positive symptoms (z = 2.64, p= 0.008). The ROI analyses showed significant associations between positive symptoms and FA of the frontal fasciculi, specifically the right arcuate fasciculus (z = 2.83, p= 0.005) and right superior longitudinal fasciculus (z = -3.31, p= 0.001). At re-examination, all correlations between positive symptoms and frontal fasciculi had resolved. Fractional anisotropy in the ATR increased more in patients than in controls (z = -4.92, p< 0.001). The amisulpride dose correlated positively with FA changes in the right CT (t= 2.52, p= 0.019).
Smoking and a previous diagnosis of substance abuse were potential confounders. Long-term effects of amisulpride on white matter were not evaluated.
Antipsychotic-naive patients with schizophrenia displayed subtle deficits in white matter, and psychotic symptoms appeared specifically associated with frontal fasciculi integrity. Six weeks of amisulpride treatment normalized white matter. Potential remyelinating effects of dopamine D2/3 receptor antagonism warrant further clarification.
精神病性症状是精神分裂症的核心临床特征。我们检验了最近提出的假说，即精神病性（或阳性）症状源于投射至额叶皮质的长程白质纤维束的异常，并且我们预测选择性多巴胺D2/3受体阻断将恢复白质。
在2008年12月至2011年7月期间，未使用过抗精神病药物的首发精神分裂症患者及匹配的健康对照者接受了3T磁共振成像扩散张量成像的基线检查和临床评估。我们使用基于体素的纤维束空间统计分析（TBSS）和基于感兴趣解剖区域（ROI）的分析评估了各向异性分数（FA）的组间差异。随后，患者接受了为期6周的氨磺必利抗精神病单药治疗。6周后我们重复了检查。
我们的分析纳入了38例首发精神分裂症患者和38例对照者，每组各有28例个体完成了研究。在基线时，全脑TBSS分析显示，患者右侧丘脑前辐射（ATR）、右侧扣带、右侧下纵束和右侧皮质脊髓束（CT）的FA较低。右侧ATR的FA与阳性症状相关（z = 2.64，p = 0.008）。ROI分析显示阳性症状与额束的FA之间存在显著关联，特别是右侧弓状束（z = 2.83，p = 0.005）和右侧上纵束（z = -3.31，p = 0.001）。在复查时，阳性症状与额束之间的所有相关性均消失。患者ATR中的FA增加幅度大于对照者（z = -4.92，p < 0.001）。氨磺必利剂量与右侧CT的FA变化呈正相关（t = 2.52，p = 0.019）。
吸烟和既往药物滥用诊断是潜在的混杂因素。未评估氨磺必利对白质的长期影响。
未使用过抗精神病药物的精神分裂症患者存在白质细微缺陷，并且精神病性症状似乎与额束完整性特别相关。6周的氨磺必利治疗使白质恢复正常。多巴胺D2/3受体拮抗的潜在髓鞘再生作用有待进一步阐明。
