| Objective: There is mounting evidence for the involvement of cerebral white matter in the pathophysiology of schizophrenia based on neuropathological and neuroimaging studies, suggesting the onset of schizophrenia is associated with anatomical or functional dysconnectivity between varies brain regions, especially, the abnormal connectivity between temporal and frontal regions (frontotemporal dysconnectivity) has been thought to play an important role in the neuropathology of schizophrenia. The external capsule (EC) conveys fibers from the ventral and medial prefrontal cortex, ventral premotor cortex, precentral gyrus, to the rostral superior temporal region, and the inferotemporal and preoccipital regions. The extreme capsule (EmC) extends between the inferior frontal gyrus (IFG) and the middle-posterior portion of the superior temporal gyrus. A few DTI studies reported that schizophrenia patients had significantly lower FA values in the area of EC, which directly support the notion of frontotemporal dysconnectivity. However, whether there exists an anatomic substrate for this functional dysconnectivity remains unclear. On the other hand, there has been enormous heterogeneity in schizophrenia and the limited phenotypic characterization of clinical samples in most previous studies. This is true not only for the presence or absence of specific symptoms within a disorder (diagnostic heterogeneity), but also for etiological pathways involved in disorders (etiological heterogeneity). In view of the above backgrounds, with a pure sample of first-episode paranoid schizophrenia, the present study examined white matter volumes of EC, EmC) and IFG using MRI-based volumetric analysis, as well as the relations between volumetric measures and clinical symptoms. Methods: Thirty-eight (18 males and 20 females) patients with first-episode paranoid schizophrenia and 42 (20 males and 22 females) healthy comparison subjects were included in this study. The patients were recruited from the No7 People's Hospital of Dalian during 2007 to 2008, all patients fulfilled the criteria of paranoid schizophrenia in ICD-10 and schizophrenia, paranoid type in DSM-IV. The imagines were acquired on a 1.5T GE Signa MR scanner. A three-dimensional fast spoiled gradient-recalled sequence (3D-FSPGR) was used for acquisition of sagittal T1-weighted images. After that, the images were processed on a Unix workstation (Silicon Graphics, Mountain View, CA, USA) with the software package Dr View 2.0. EC, EmC and IFG were manually traced on consecutive coronal 1-mm-thick slices, from anterior to posterior, with the corresponding sagittal and axial planes simultaneously presented as references. Brief Psychiatric Rating Scale (BPRS), Scale for Assessment of Negative Symptoms (SANS), Scale for Assessment of Positive Symptoms (SAPS) were used to evaluate clinical manifestations. Statistical differences in the regional volume measures were analyzed using repeated measures multivariate analysis of covariance (MANCOVA). Pearson's partial correlation coefficients were calculated to examine the relationship between volumetric measure and the severity of symptoms.Results: Compared with normal controls, patients with first-episode paranoid schizophrenia had significantly decreased volumes in whole cerebral volume (p=0.019) and whole cerebral gray matter volume (post hoc test, p<0.001), while significant volume decrease in whole cerebral white matter was shown only in male patients (post hoc test, p<0.001). There was no significant difference between patients and normal controls in the volume of EC (p=0.497), EmC (p=0.973), whole IFG (p=0.528), and gray matter of IFG (p=0.109). However, patients had significantly increased volumes in the white matter of left IFG (p=0.013). The EC volume was significantly negatively correlated with poverty of thought (left: p=0.050, right: p=0.040), the right EmC volume was significantly negatively correlated with ToSANS (p=0.048), abulia (p=0.050) and attention deficit (p=0.010), and the right IFG white matter was significantly negatively correlated with hallucination (p=0.047).Conclusions: 1. Patients with first-episode paranoid schizophrenia had significantly volume reductions in whole cerebrum, whole cerebral gray matter and whole cerebral white matter, which suggests that anatomical brain damage has already existed in the early stage of disease. 2. There was no significant difference either in the external capsule or in the extreme capsule between the patients and controls, suggests that the impaired long-range neural connections relevant to EC and EmC in paranoid schizophrenia seem to have a functional rather than an anatomical origin, at least in the early stages of this disorder. 3. Compared with the controls, the patients had significantly increased volume in the white matter of left IFG, which support the notion of neurodevelopment hypothesis. 4. In patient group, the external capsule volume and extreme capsule volume was significantly negatively correlated with negative symptoms, and inferior frontal gyrus white matter volume might be relevant to mechanism of hallucination. |
PDF Full Text Request