Matrone Marta, Kotzalidis Georgios D, Romano Andrea, Bozzao Alessandro, Cuomo Ilaria, Valente Francesca, Gabaglio Chiara, Lombardozzi Ginevra, Trovini Giada, Amici Emanuela, Perrini Filippo, De Persis Simone, Iasevoli Felice, De Filippis Sergio, de Bartolomeis Andrea
Section of Psychiatry Laboratory of Molecular and Translational Psychiatry, Unit of Treatment Resistant Psychosis, Department of Neuroscience, Reproductive Science, and Odontostomatology, University of Naples Federico II, 80131 Naples, Italy; Clinica Neuropsichiatrica Villa von Siebenthal, Department of Neuropsychiatry, Via della Madonnina 1, 00045 Genzano di Roma, RM, Italy.
NESMOS (Neurosciences, Mental Health, and Sensory Organs) Department, Sapienza University of Rome, Faculty of Medicine and Psychology, Via di Grottarossa 1035-1039, 00189 Rome, Italy.
Prog Neuropsychopharmacol Biol Psychiatry. 2022 Mar 2;114:110493. doi: 10.1016/j.pnpbp.2021.110493. Epub 2021 Dec 7.
Treatment-resistance in schizophrenia is 30-40%. Its neurobiology remains unclear; to explore it, we conducted a combined spectrometry/tractography/cognitive battery and psychopathological rating study on patients with treatment-resistant schizophrenia (TRS), dividing the sample into early-onset (N = 21) and adult-onset TRS (N = 20). Previous studies did not differentiate between early- (onset 13-18 years) and adult-onset (>18 years at formal diagnosis of schizophrenia) TRS.
We evaluated cross-sectionally 41 TRS patients (26 male and 15 female) and 20 matched healthy controls (HCs) with psychopathological and cognitive testing prior to participating in brain imaging scanning using magnetic resonance spectroscopy and diffusion tensor imaging to determine the relationship between their symptoms and their glutamate levels and white matter integrity.
TRS patients scored lower than HCs on all cognitive domains; early-onset patients performed better than adult-onset patients only on the Symbol Coding domain. TRS correlated with symptom severity, especially negative symptoms. Glutamate levels and glutamate/creatine were increased in anterior cingulate cortex. Diffusion tensor imaging showed low fractional anisotropy in TRS patients in specific white matter tracts compared to HCs (bilateral anterior thalamic radiation, cortico-spinal tract, forceps minor, inferior fronto-occipital fasciculus, inferior longitudinal fasciculus, superior longitudinal fasciculus, and right uncinate fasciculus).
We identified specific magnetic resonance spectroscopy and diffusion tensor imaging alterations in TRS patients. Adult-onset TRS differed little from early-onset TRS on most measures; this points to alterations being present since the outset of schizophrenia and may constitute a biological signature of treatment-resistance.
精神分裂症的治疗抵抗率为30%-40%。其神经生物学机制仍不清楚；为了探究这一问题，我们对治疗抵抗性精神分裂症（TRS）患者进行了一项光谱分析、纤维束成像和认知测试组合以及精神病理学评定研究，将样本分为早发型（N = 21）和成年型TRS（N = 20）。以往的研究没有区分早发型（发病年龄13-18岁）和成年型（精神分裂症正式诊断时年龄>18岁）TRS。
我们对41例TRS患者（26例男性和15例女性）和20例匹配的健康对照者（HCs）进行了横断面评估，在使用磁共振波谱和扩散张量成像进行脑成像扫描之前，先进行精神病理学和认知测试，以确定他们的症状与谷氨酸水平和白质完整性之间的关系。
TRS患者在所有认知领域的得分均低于HCs；早发型患者仅在符号编码领域的表现优于成年型患者。TRS与症状严重程度相关，尤其是阴性症状。前扣带回皮质的谷氨酸水平和谷氨酸/肌酸水平升高。扩散张量成像显示，与HCs相比，TRS患者特定白质束的分数各向异性较低（双侧丘脑前辐射、皮质脊髓束、小钳、额枕下束、下纵束、上纵束和右侧钩束）。
我们在TRS患者中发现了特定的磁共振波谱和扩散张量成像改变。在大多数指标上，成年型TRS与早发型TRS差异不大；这表明这些改变在精神分裂症发病之初就已存在，可能构成治疗抵抗的生物学特征。
