Abnormal white matter microstructure in drug-naive first episode schizophrenia patients before and after eight weeks of antipsychotic treatment.

Abnormal white matter integrity has been reported among first episode schizophrenia patients. However, findings on whether it can be reversed by short-term antipsychotic medications are inconsistent. Diffusion tensor imaging (DTI) was obtained from 55 drug-naive first episode schizophrenia patients and 61 healthy controls, and was repeated among 25 patients and 31 controls after 8 weeks during which patients were medicated with antipsychotics. White matter integrity is measured using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). These measures showing a group difference by Tract-based spatial statistics (TBSS) at baseline were extracted for longitudinal comparisons. At baseline, patients exhibited lower FA, higher MD and higher RD versus controls in forceps, left superior longitudinal fasciculus, inferior fronto-occipital fasciculus, left corticospinal tract, left uncinate fasciculus, left anterior thalamic radiation, and bilateral inferior longitudinal fasciculi. FA values of schizophrenia patients correlated with their negative symptoms (r=-0.412, P=0.002), working memory (r=0.377, P=0.005) and visual learning (r=0.281, P=0.038). The longitudinal changes in DTI indices in these tracts did not differ between patients and controls. However, among the patients the longitudinal changes in FA values in left superior longitudinal fasciculus correlated with the change of positive symptoms (r=-0.560, p=0.004), and the change of processing speed (r=0.469, p=0.018). White matter deficits were validated in the present study by a relatively large sample of medication naïve and first episode schizophrenia patients. They could be associated with negative symptoms and cognitive impairment, whereas improvement in white matter integrity of left superior longitudinal fasciculus correlated with improvement in psychosis and processing speed. Further examination of treatment-related changes in white matter integrity may provide clues to the mechanism of antipsychotic response and provide a biomarker for clinical studies.

Zeng B ，Ardekani BA ，Tang Y ，Zhang T ，Zhao S ，Cui H ，Fan X ，Zhuo K ，Li C ，Xu Y ，Goff DC ，Wang J ... -  《-》

Frontal fasciculi and psychotic symptoms in antipsychotic-naive patients with schizophrenia before and after 6 weeks of selective dopamine D2/3 receptor blockade.

Ebdrup BH ，Raghava JM ，Nielsen MØ ，Rostrup E ，Glenthøj B ... -  《-》

Effect of clozapine on white matter integrity in patients with schizophrenia: a diffusion tensor imaging study.

Several diffusion tensor imaging (DTI) studies have reported disturbed white matter integrity in various brain regions in patients with schizophrenia, whereas only a few studied the effect of antipsychotics on DTI measures. The aim of this study was to investigate the effect of 12 weeks of clozapine treatment on DTI findings in patients with schizophrenia, and to compare the findings with those in unaffected controls. The study included 16 patients with schizophrenia who were assessed with the Positive and Negative Syndrome Scale, a neurocognitive test battery, and DTI at baseline and 12 weeks after the initiation of clozapine treatment. Eight unaffected controls were assessed once with the neurocognitive test battery and DTI. Voxel-wise analysis of DTI data was performed via tract-based spatial statistics (TBSS). Compared with the control group, the patient group exhibited lower fractional anisotropy (FA) in 16 brain regions, including the bilateral superior longitudinal fasciculi, inferior fronto-occipital fasciculi, superior and inferior parietal lobules, cingulate bundles, cerebellum, middle cerebellar peduncles, and left inferior longitudinal fasciculus, whereas the patients had higher FA in six regions, including the right parahippocampus, left anterior thalamic radiation, and right posterior limb of the internal capsule before clozapine treatment. After 12 weeks of treatment with clozapine, white matter FA was increased in widespread brain regions. In two of the regions where FA had initially been lower in patients compared with controls (left inferior fronto-occipital fasciculus and superior parietal lobule), clozapine appeared to increase FA. An improvement in semantic fluency was correlated with the increase in FA value in the left inferior fronto-occipital fasciculus. An increase in FA following 12 weeks of treatment with clozapine suggests that this treatment alters white matter microstructural integrity in patients with schizophrenia previously treated with typical and/or atypical antipsychotics and, in some locations, reverses a previous deficit.

Ozcelik-Eroglu E ，Ertugrul A ，Oguz KK ，Has AC ，Karahan S ，Yazici MK ... -  《-》

Reduced white matter integrity and cognitive deficit in never-medicated chronic schizophrenia: a diffusion tensor study using TBSS.

Disrupted white matter (WM) integrity is the pathological hallmark of schizophrenia. Previous studies have reported the cognitive deficits that are associated with WM disruption in schizophrenia with anti-psychiatric treatment. However, no study has yet revealed the correlation between cognition and WM abnormalities in never-medicated chronic schizophrenia. We used the diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) approach to investigate the whole-brain difference in the WM fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) values between 17 schizophrenia patients and 17 healthy controls matched in age, gender and education level. Patients' cognition was assessed through the MATRICS Consensus Cognitive Battery (MCCB). We explored the association between WM reduction and cognitive, clinical characteristics (severity of clinical symptoms, age, age of onset, illness duration). Voxel-wise statistics revealed that schizophrenia patients showed significant FA reduction in left inferior longitudinal fasciculus (ILF) and left inferior fronto-occipital fasciculus (IFOF), and no difference in MD, AD or RD as compared to healthy subjects. Furthermore, in the patients group, lower FA value of the left ILF and left IFOF significantly correlated with worse processing speed, as well as verbal learning and visual learning abilities. There was no correlation between the FA value and the severity of clinical symptoms, age, and age of onset or illness duration. Our results provide evidence to support that the disconnection of WM pathways may contribute to the pathophysiology of schizophrenia and suggest that the disturbance of left ILF and left IFOF integrity may contribute to cognitive deficits in schizophrenia, independent of effects of antipsychotic medication.

Liu X ，Lai Y ，Wang X ，Hao C ，Chen L ，Zhou Z ，Yu X ，Hong N ... -  《-》

White matter microstructural organizations in patients with severe treatment-resistant schizophrenia: A diffusion tensor imaging study.

Previous diffusion tensor imaging (DTI) studies have reported white matter alterations in patients with schizophrenia. Notably, one third of this population does not respond to first-line antipsychotics and is thus referred to as treatment-resistant schizophrenia (TRS). Despite potentially distinct neural bases between TRS and non-TRS, few studies have compared white matter integrity between these groups. In order to reflect clinical picture of TRS, we enrolled TRS patients who had severe symptoms. According to the consensus criteria for TRS. TRS was defined by severe positive symptomatology despite optimal antipsychotic treatment. Fractional anisotropy (FA), an index of white matter integrity, was examined by DTI and analyzed with tract-based spatial statistics in 24 TRS patients (mean PANSS = 108.9), 28 non-TRS patients (mean PANSS = 50.0), and 27 healthy controls (HCs) for group comparison. Additionally, correlation analyses were conducted between FA values and symptomatology. The TRS group had lower FA values in multiple tracts (cerebral peduncle, corona radiata, corpus callosum, external and internal capsules, posterior thalamic radiation, sagittal stratum, superior longitudinal fasciculus, tapetum, and uncinate fasciculus) compared to the HC group as well as the non-TRS group (p < .05; family-wise error-corrected), while no differences were found between the non-TRS and HC groups. In the TRS group, FA values in most of the tracts (other than the left anterior limb of internal capsule, left cerebral peduncle, and right uncinate fasciculus) were negatively correlated with the Positive and Negative Syndrome Scale total scores, and negative and general symptom scores. No such relationships were found in the non-TRS group. The identified white matter integrity deficits may reflect the pathophysiology of TRS.

Ochi R ，Noda Y ，Tsuchimoto S ，Tarumi R ，Honda S ，Matsushita K ，Tsugawa S ，Plitman E ，Masuda F ，Ogyu K ，Wada M ，Miyazaki T ，Fujii S ，Chakravarty MM ，Graff-Guerrero A ，Uchida H ，Mimura M ，Nakajima S ... -  《-》