首次发病未治疗精神分裂症患者大脑皮质复杂度改变

目的探讨首次发病未治疗精神分裂症患者大脑皮质复杂度的异常特征及其与临床症状的相关性。方法使用Philip 3.0 T磁共振成像系统采集77例首次发病未治疗精神分裂症患者(患者组)及84名健康对照者(对照组)的高分辨率3D脑结构图像,采用基于SPM12的计算解剖学工具包计算分形维度(fractal dimension,FD)值表征皮质形态复杂度,2组间FD值比较采用t检验;采用偏相关分析对患者组FD值与临床症状严重程度进行相关分析。结果与对照组相比,患者组左侧上额叶皮质复杂度下降(MNI:x=-5,y=22,z=58,体素水平P<0.001,簇水平经family-wise error校正后P<0.05)。女性患者左侧上额叶皮质复杂度与PANSS总分(r=-0.357,P=0.028)、阴性症状分(r=-0.373,P=0.021)呈负相关,男性患者皮质复杂度与临床特征均无相关性。结论首次发病未治疗精神分裂症患者左侧上额叶皮质复杂度下降,女性患者阴性症状与皮质复杂度下降相关,提示精神分裂症存在早期神经发育异常,进一步支持精神分裂症的神经发育假说。     

Gyrification in first-episode schizophrenia: a morphometric study.

BACKGROUND: A number of studies have found localized differences in the appearance and extent of cortical folding between the brains of schizophrenic patients and healthy control subjects. This study aimed to determine whether there are differences in gyral folding in schizophrenia by conducting a detailed analysis of magnetic resonance images. METHODS: Thirty-four young adults in their first episode of schizophrenia and 36 age-matched, healthy control subjects were studied. The gyrification index (GI), the ratio of the inner and outer cortical surface contours, was measured bilaterally on every second 1.88-mm image slice in four specifically defined lobar regions. Independent t tests were conducted for each region, followed by post hoc analysis of variance testing for the effects of laterality. RESULTS: Gyrification index values between groups corresponded closely in the occipital and parietal regions but were significantly increased in the right temporal lobe of the schizophrenic patients. Calculating the GI by two different methods (used in previous studies) notably affected results. Gyrification index values were significantly lateralized in the frontal and temporal regions, with no group x side interactions. CONCLUSIONS: Differences in the temporal lobe GI of first-episode schizophrenic patients might reflect disturbed or abnormal connectivity. Further examination of specific sources of sulco-gyral difference in schizophrenia is required to clarify this.     

Developmental abnormalities of the hippocampus in first-episode schizophrenia.

BACKGROUND: The human hippocampus becomes visible during the first trimester and folds to form the hippocampal fissure (HF) in the second trimester. The walls of this fissure fuse by 30 weeks, although small residual cavities can occur if development is disrupted. The primary purpose of this study was to determine if hippocampal fissures are evident in schizophrenia. A second goal was to assess the association between HF size and premorbid and clinical features of the illness. METHODS: Magnetic resonance imaging scans were obtained on 33 patients with first-episode schizophrenia and 19 healthy volunteers. Hippocampal fissures were measured using semi-automated procedures, and hippocampi were manually traced. Birth history and premorbid functioning were assessed using maternal report. RESULTS: Patients had a significantly larger mean HF volume and a nonsignificantly smaller hippocampal volume. Hippocampal fissure size was significantly associated with poor educational achievement and with anxiety-depression symptoms during the onset of illness. Smaller hippocampal size was associated with poor premorbid adjustment. CONCLUSIONS: Larger HF size and an association between low educational achievement and enlarged HFs suggest abnormal neurodevelopment in schizophrenia. The association between HF size and anxiety-depression symptoms suggests that hippocampal abnormalities underlying HF dilatation may be a predisposing factor for increased stress sensitivity.     

Planum temporale asymmetry to the right hemisphere in first-episode schizophrenia

In schizophrenia patients reduced cerebral asymmetry is an important finding and this may reflect a disturbance in cortical development. We investigated planum temporale (PT) volume and asymmetry in 23 first-episode schizophrenia patients compared to healthy controls and found for the first time an in vivo volume asymmetry of PT to the right hemisphere.     

Gyrification abnormalities in childhood- and adolescent-onset schizophrenia.

BACKGROUND: Gyrification is an important index of brain development. We used magnetic resonance scanning technology to compare brain surface morphology and measures of gyrification in children and adolescents with a schizophrenia spectrum disorder and in age-equivalent healthy controls. METHODS: Magnetic resonance scans were obtained from 42 patients and 24 healthy controls, mean age 17.7 years for both groups. We employed novel quantitative measures of brain morphology, including cortical thickness and a variety of indices of sulcal and gyral curvature. We examined these measures in the whole brain and in the frontal, temporal, parietal, and occipital lobes. RESULTS: There were significant decreases in cortical thickness in the patients. This was most pronounced in the cortical tissue that underlies the sulci. The patient group had significantly more flattened curvature in the sulci and more steeped or peaked curvature in the gyri. CONCLUSIONS: This study quantitatively examines cortical thickness and surface morphology in children and adolescents with schizophrenia. Patients with schizophrenia demonstrated patterns of brain morphology that were distinctly different from healthy controls. In light of current theories of the formation of gyri and sulci, these changes may reflect aberrations in cerebral and subcortical connectivity.     

Prefrontal gyral folding and its cognitive correlates in bipolar disorder and schizophrenia

Objective: We sought to address whether dorsal or ventral prefrontal gyrification is abnormal in bipolar disorder and to determine its diagnostic specificity and cognitive associations. Method: Forty‐two out‐patients with bipolar disorder, 28 with schizophrenia and 37 controls underwent magnetic resonance imaging. All subjects also underwent IQ and executive assessments using tasks whose performance has been localized to the ventral or dorsal prefrontal cortex. Cortical folding was quantified using the gyrification index (GI) and related to the cognitive measures. Results: Patients with bipolar disorder showed reduced prefrontal gyrification compared with controls but did not differ from patients with schizophrenia. Neither ventral nor dorsal GI was preferentially affected in either disorder. Current IQ was positively and significantly correlated with GI. Conclusion: Patients with bipolar disorder and patients with schizophrenia have reduced prefrontal gyrification affecting both ventral and dorsal subregions. These reductions were significantly associated with cognitive impairments occurring in both disorders.     

Internal capsule size associated with outcome in first-episode schizophrenia

Subtle structural brain abnormalities are an established finding in first-episode psychosis. Nevertheless their relationship to the clinical course of schizophrenia is controversially discussed. In a multicentre study 45 first-episode schizophrenia patients (FE-SZ) underwent standardized MRI scanning and were followed up to 1 year. In 32 FE-SZ volumetric measurement of three regions of interests (ROIs) potentially associated with disease course, hippocampus, lateral ventricle and the anterior limb of the internal capsule (ALIC) could be performed. The subgroups of FE-SZ with good (12 patients) and poor outcome (11 patients), defined by a clinically relevant change of the PANSS score, were compared with regard to these volumetric measures. Multivariate analysis of covariance revealed a significant reduced maximal cross sectional area of the left ALIC in FE-SZ with clinically relevant deterioration compared to those with stable psychopathology. There were no differences in the other selected ROIs between the two subgroups. In conclusion, reduced maximal area of ALIC, which can be interpreted as a disturbance of fronto-thalamic connectivity, is associated with poor outcome during the 1 year course of first-episode schizophrenia.     

Cortical surface complexity in frontal and temporal areas varies across subgroups of schizophrenia

Schizophrenia is assumed to be a neurodevelopmental disorder, which might involve disturbed development of the cerebral cortex, especially in frontal and medial temporal areas. Based on a novel spherical harmonics approach to measuring complexity of cortical folding, we applied a measure based on fractal dimension (FD) to investigate the heterogeneity of regional cortical surface abnormalities across subgroups of schizophrenia defined by symptom profiles. A sample of 87 patients with DSM‐IV schizophrenia was divided into three subgroups (based on symptom profiles) with predominantly negative (n = 31), disorganized (n = 23), and paranoid (n = 33) symptoms and each compared to 108 matched healthy controls. While global FD measures were reduced in the right hemisphere of the negative and paranoid subgroups, regional analysis revealed marked heterogeneity of regional FD alterations. The negative subgroup showed most prominent reductions in left anterior cingulate, superior frontal, frontopolar, as well as right superior frontal and superior parietal cortices. The disorganized subgroup showed reductions in bilateral ventrolateral/orbitofrontal cortices, and several increases in the left hemisphere, including inferior parietal, middle temporal, and midcingulate areas. The paranoid subgroup showed only few changes, including decreases in the right superior parietal and left fusiform region, and increase in the left posterior cingulate cortex. Our findings suggest regional heterogeneity of cortical folding complexity, which might be related to biological subgroups of schizophrenia with differing degrees of altered cortical developmental pathology. Hum Brain Mapp 35:1691–1699, 2014. © 2013 Wiley Periodicals, Inc.     

Incidental radiological findings on brain magnetic resonance imaging in first-episode psychosis and chronic schizophrenia

OBJECTIVE: To investigate whether patients with first-episode psychosis or chronic schizophrenia have an increased incidence of magnetic resonance imaging (MRI) brain abnormalities compared with control subjects. METHOD: Totally 340 clinical MRI reports [Controls (n=98), first-episode psychoses (n=152), chronic schizophrenia (n=90)] were reported by a neuroradiologist blind to diagnosis and subsequently categorized using referral criteria (immediate, urgent, routine or no referral). RESULTS: Thirty percent of all scans were reported by a neuroradiologist as abnormal, but the majority required no referral. Patients with chronic schizophrenia were more likely to have clinically significant abnormal scans than patients with first episode psychosis or control subjects. In four patients the MRI findings led to the discovery of previously unsuspected pathology. CONCLUSION: Patients with chronic schizophrenia have an increased prevalence of incidental brain abnormalities. A small proportion of patients with chronic schizophrenia and first-episode psychosis benefitted directly from MRI scanning.     

Abnormal cortical folding in high-risk individuals: a predictor of the development of schizophrenia?

BACKGROUND: A number of studies have found localized differences in the appearance and extent of cortical folding between the brains of schizophrenic patients and healthy control subjects. This study aimed to determine whether, within individuals at genetic high risk for schizophrenia, there are pre-existing differences in gyral folding between those who subsequently develop the disease and those who remain unaffected. METHODS: Assessment was conducted on baseline magnetic resonance imaging scans of 30 young adults grouped into 14 who remained unaffected and 16 who subsequently developed schizophrenia. The gyrification index (GI), the ratio of the inner and outer cortical surface contours, was measured bilaterally on every second 1.88-mm image slice in four specifically defined lobar regions. Independent t tests and volume and genetic liability correlations were conducted for each region, followed by a post hoc examination. RESULTS: Right prefrontal lobe GI values were significantly increased in individuals who subsequently developed schizophrenia. Post hoc examination suggested that the areas of greatest increase lay anteriorly and laterally in Brodmann areas 9 and 10. Correlations with volume and analysis of covariance suggested some overlap between GI and volume measures. CONCLUSIONS: Differences in frontal lobe GI might reflect disturbed or abnormal connectivity predictive of subsequent schizophrenia.     

A magnetic resonance imaging study in first-episode disorganized-type patients with schizophrenia

Abstract Although a number of radiological studies have suggested that brains of patients suffering from schizoprenia have morphological abnormalities, the results are inconsistent. In the present study, in order to examine the brain, morphological features of homogeneous schizophrenics' brain magnetic resonance imagings (MRI) were taken, before neuroleptic treatment, from subjects suffering from disorganized-type schizophrenia, (DOS) during their first episodes. Results showed that DOS had significantly smaller indices for bilateral frontal gray matter (GM), left hippocampal formation (HF), left parahippocampal gray matter (PHGM) and left cingulate gyrus gray matter (CGM) than normal controls. These findings support the previous computed tomography (CT) and MRI studies on schizophrenic brains, although the subjects were not defined as disorganized-type, and may suggest the involvement of a neurocircuit between the bilateral frontal lobe and the left side of limbic system in the first-episode DOS group.     

Altered cortical gyrification patterns in panic disorder: Deficits and potential compensation

Abnormal gyrification patterns may reflect aberrant cortical connectivity during an early period of brain maturation. We here investigated anatomical distribution of cortical gyrification deficits underlying panic disorder and the relationships of these potential neurodevelopmental markers with panic symptom severity. High-resolution three-dimensional T1-weighted structural images were obtained from 23 patients with panic disorder and 33 matched healthy individuals. Local gyrification indices were measured in each genetically-based parcellated cortical subregion and regional gyrification patterns were compared between groups. Cortical areas in which gyrification patterns were associated with panic symptom severity were also determined. Significant reductions in cortical gyrification were observed in panic patients compared with healthy individuals, which were mainly distributed in the lateral brain extending from the fronto-parietal to the temporal areas. In contrast, hyper-gyrification in the posteromedial cortical regions which exert interconnecting roles in the default mode network, was associated with less severe panic symptoms. Post-hoc analysis for the inter-regional covariance of local gyrification indices revealed that interconnections of the posteromedial cortical regions with other cortical areas which belong to the default mode network were reduced in panic patients with severe symptoms relative to either less severe patients or healthy individuals. Our findings suggest not only substantial perturbation in cortical gyrification patterns in panic disorder but also potential contribution of integrated cortical folding pattern of the default mode network to alleviated panic severity.     

Reversed cerebellar asymmetry in men with first-episode schizophrenia.

BACKGROUND: Abnormalities in cerebellar structure and function have been implicated in the pathophysiology of schizophrenia. In this study, we investigated whether patients experiencing first-episode schizophrenia differed from healthy comparison subjects in regional cerebellar volumes or cerebellar asymmetry. METHODS: Volumes of four cerebellar regions (right, left; anterior, posterior) were measured from contiguous coronal magnetic resonance (MR) images in 69 (37 men, 32 women) patients experiencing first-episode schizophrenia and in 49 (27 men, 22 women) healthy comparison subjects. Patients were rated on the Scale for the Assessment of Negative Symptoms and the Schedule for Affective Disorders and Schizophrenia-Psychosis/Disorganization before the initiation of antipsychotic medication and at the time of the MR imaging exam. RESULTS: Patients and healthy comparison subjects did not differ in regional cerebellar volumes, but male patients demonstrated significantly reversed anterior and posterior asymmetry compared with healthy male subjects. Among male patients, greater reversals in a composite measure of cerebellar asymmetry (i.e., torque) correlated significantly with increased negative symptoms before the initiation of antipsychotic medication. CONCLUSIONS: These findings implicate an aberrant neurodevelopmental process involving the metencephalon in the pathophysiology of schizophrenia and are consistent with prior studies implicating abnormal asymmetry in schizophrenia at the neocortical level.     

青少年精神分裂症首次发病患者脑灰质体积与认知功能的相关性

目的:探讨首发青少年精神分裂症患者脑灰质体积与认知功能的关系。方法:33例首发青少年精神分裂症患者(患者组)和28名性别、年龄、右利手、受教育程度与之相匹配的正常对照组进行神经心理测评,包括连线测验、符号编码、词语流畅性测验、霍普金斯词语学习测验-修订版(HVLT-R)、简易视觉记忆测验-修订版(BVMT-R)、Stroop色词测验(ST-1、ST-2、ST-3)及迷宫测验和结构磁共振扫描(s MRI);用基于体素的形态学方法(VBM))分析比较两组脑灰质体积。结果:患者组除连线测验成绩显著高于正常对照组外(t=2.08,P0.05),符号编码(t=-4.36)、HVLT-R(t=-3.74)、BVMT-R(t=-4.83)、ST-1、ST-2、ST-3(t=-3.08,t=-3.85,t=-3.62)及迷宫测验(t=-3.14)成绩明显低于正常对照组(P0.01或P0.001)。患者组右侧颞上回及右侧颞中回脑灰质体积较正常对照组明显减小(t=-3.868,t=3.964;P均0.001)。Pearson相关分析显示,患者组符号编码(r=0.373,P=0.032)及迷宫测验评分(r=0.356,P=0.042)与右侧颞中回脑灰质体积正相关。结论:首发青少年精神分裂症患者存在脑灰质体积异常;这可能与认知功能广泛损害相关。     

Shortening of the hippocampal formation in first-episode schizophrenic patients

Abstract Shortening of hippocampal formation (HF) in chronic schizophrenic patients have been demonstrated in our previous study. The purpose of the present study is to test if shortening of the HF occurs in schizophrenic patients suffering their initial psychotic episode. We performed contiguous, 1 mm thick, magnetic resonance imaging scans in 20 first-episode schizophrenic patients, 21 chronic schizophrenic patients, and 25 healthy subjects. Both groups of schizophrenic patients demonstrated significant shortening of the HF compared with normal controls (first-episode schizophrenia, 5.3%; chronic schizophrenia, 8.0%). However, the HF length was not significantly different between the first-episode and chronic schizophrenic patients. No significant correlation was seen between the HF length and the duration of illness in chronic schizophrenic patients. These results suggest that the HF shortening observed in schizophrenic patients may be genetic and/or developmental in origin.     

精神分裂症首次发病患者额顶网络功能连接与面孔情绪识别能力的关系

目的:探讨首发精神分裂症患者在静息状态下额顶网络的功能连接特点,及其与面孔情绪识别能力的相关性。方法:对37例首发未用药的精神分裂症患者(患者组)和30名年龄、性别、利手、受教育程度与患者相匹配的健康者(正常对照组)进行静息态功能磁共振(f MRI)扫描,收集两组的一般临床特征,并采用面孔情绪测试评价被试的面孔情绪认知功能;以双侧背外侧前额叶(DLPFC)为种子点比较两组间额顶网络功能连接的差异,并分析与面孔情绪认知功能的相关性。结果:与正常对照组相比,患者组DLPFC与左顶下小叶(t=-3.243,Alphasim校正P0.05)、左额下回(t=-3.151,Alphasim校正P0.05)、左额中回(t=-3.151,Alphasim校正P0.05)、双侧尾状核(t=-4.325,Alphasim校正P0.05)、左颞中回(t=-3.120,Alphasim校正P0.05)的功能连接减低;与双侧扣带回中部(t=2.731,Alphasim校正P0.05)、右中央前回(t=3.991,Alphasim校正P0.05)、右岛叶(t=3.991,Alphasim校正P0.05)功能连接增强。患者组额-顶通路的功能连接与面孔情绪认知障碍呈正相关(r=0.501,P0.05)。结论:首发精神分裂症患者额顶网络的功能连接存在异常,其中DLPFC-顶下小叶通路的功能连接降低可能影响患者面孔情绪识别能力。     

Abnormal cerebral cortex structure in children with ADHD

Objective:

Examination of cerebral cortical structure in children with Attention‐Deficit/Hyperactivity Disorder (ADHD) has thus far been principally limited to volume measures. In the current study, an automated surface‐based analysis technique was used to examine the ADHD‐associated differences in additional morphologic features of cerebral cortical gray matter structure, including surface area, thickness, and cortical folding.

Methods:

MPRAGE images were acquired from 21 children with ADHD (9 girls) and 35 typically developing controls (15 girls), aged 8–12 years. Statistical difference maps were used to compare mean cortical thickness between groups along the cortical surface. Cortical volume, surface area, mean thickness, and cortical folding were measured within regions of interest, including the right/left hemispheres, frontal, temporal, parietal, and occipital lobes within each hemisphere, and sub‐lobar regions.

Results:

Children with ADHD showed a decrease in total cerebral volume and total cortical volume of over 7 and 8%, respectively; volume reduction was observed throughout the cortex, with significant reduction in all four lobes bilaterally. The ADHD group also showed a decrease in surface area of over 7% bilaterally, and a significant decrease in cortical folding bilaterally. No significant differences in cortical thickness were detected.

Conclusions:

Results from the present study reveal that ADHD is associated with decreased cortical volume, surface area, and folding throughout the cerebral cortex. The findings suggest that decreased cortical folding is a key morphologic feature associated with ADHD. This would be consistent with onset early in neural development and could help to identify neurodevelopmental mechanisms that contribute to ADHD. Hum Brain Mapp 2009. © 2007 Wiley‐Liss, Inc.     

Reduced cerebellar volume and neurological soft signs in first-episode schizophrenia

Recent studies indicate that morphological and functional abnormalities of the cerebellum are associated with schizophrenia. Since the cerebellum is crucial for motor coordination, one may ask whether the respective changes are associated with motor dysfunction in the disease. To test these hypotheses in a clinical study, we investigated cerebellar volumes derived from volumetric magnetic resonance imaging of 37 first-episode patients with schizophrenia, schizophreniform or schizoaffective disorder and 18 healthy controls matched for age, gender and handedness. To control for potential interindividual differences in head size, intracranial volume was entered as a covariate. Neurological soft signs (NSS) were examined after remission of acute symptoms. Compared with the controls, patients had significantly smaller cerebellar volumes for both hemispheres. Furthermore, NSS in patients were inversely correlated with tissue volume of the right cerebellar hemisphere partialling for intracranial volume. No associations were detected between cerebellar volumes and psychopathological measures obtained at hospital admission when patients were in the acute psychotic state or after remission, treatment duration until remission, treatment response or prognostic factors, respectively. These findings support the hypothesis of cerebellar involvement in schizophrenia and indicate that the respective changes are associated with NSS.