Quantification of lateral ventricular subdivisions in schizophrenia by high-resolution three-dimensional magnetic resonance imaging

In vivo brain imaging and postmortem investigations have demonstrated ventricular enlargement in the brains of schizophrenic patients. However, the extent of changes in the volume of discrete ventricle subdivisions has not been clearly established. We conducted high-resolution three-dimensional magnetic resonance imaging in 40 schizophrenic patients (20 males and 20 females) and 40 healthy volunteers (20 males and 20 females). The lateral ventricle in each hemisphere was divided into the anterior horn, body, posterior horn and temporal horn. The volumes of the hemispheres, four subdivisions of the lateral ventricles and the third ventricle were measured. Compared to the control subjects, the bilateral hemisphere volumes were significantly lower in the patients than in the control subjects. In the lateral ventricular subdivisions of the male patients, the most substantial volume increase was in the left temporal horn, and volume increases were also observed in the bilateral anterior horns and the right body. The male patients also had a significantly increased volume of the third ventricle. The female patients showed similar patterns with less statistical significance. Thus, the schizophrenia patients showed ventricular enlargement, particularly in the left temporal horn, being more severely affected in the male than in the female.     

A quantitative magnetic resonance imaging study of patients with schizophrenia

Summary Twenty patients with schizophrenia and ten normal control subjects underwent magnetic resonance imaging of the brain. The volumes of several brain structures were measured using a computer image analysing system. The schizophrenic patients had significantly smaller left parahippocampal volume and larger left temporal horn volume than the control subjects. A larger body of the right lateral ventricle could be estimated in the schizophrenics, but this difference was not significant. In the patient group a non-significant negative corrlation was established between the presence of positive symptoms and the left temporal horn volume. There was no signieficant correlation between the temporal horn and temporal lobe or medial temporal structures. Our results indicate that the left medial temporal structure or left temporal lobe may be involved in schizophrenia and that temporal horn enlargement does not simply represent volume loss of the surrounding tissue.     

Inefficient neural activity in patients with schizophrenia and nonpsychotic relatives of schizophrenic patients: Evidence from a working memory task

Studies of schizophrenia with functional MRI have shown hyper- and hypoactivations in various brain regions including the prefrontal cortex. Functional anomalies have also been reported in first-degree relatives of schizophrenic patients. The aim of this study was to examine working memory related brain functions in healthy subjects, schizophrenic patients and unaffected relatives and to determine the influence of psychopathology on these processes. A parametric n-back working memory task and functional MRI were used to examine 61 patients with schizophrenia, 11 nonpsychotic relatives of schizophrenic patients and a comparison group of 61 healthy subjects. The results indicated increased as well as decreased brain functions in schizophrenic patients compared to the control group depending on the task difficulty and the performance: during the attention task (0-back), which served as control condition, behavioral responses of patients and healthy subjects hardly differed but BOLD responses were considerably enhanced in schizophrenic patients. With increasing task difficulty differences between groups in BOLD responses diminished whereas behavioral deficits of patients increased. The examination of attention-independent working memory-functions (2- vs. 0-back) produced hypoactivations in patients, especially in frontal, temporal and subcortical brain regions. Furthermore, positive symptoms were associated with parietal dysfunctions. Behavioral performance and neural responses of unaffected relatives of schizophrenic patients were intermediate between schizophrenic patients and controls indicating slight brain dysfunctions. In addition, compensatory strategies were demonstrated. These findings suggest that the genetic risk for schizophrenia is accompanied by neural inefficiency which is associated with cognitive deficits, especially in difficult tasks.     

Enlargement of the Anterior Horn of the Lateral Ventricle in Schizophrenic Patients: Chronological and Morphometrical Studies

Abstract: The anterior horn and lateral ventricular sizes of the brain CT were selected for measurement and comparison between 47 schizophrenic patients and 48 neurotic cases, which constituted the control subjects. The ventricular brain ratio (VBR) and the linear ratio (LR 1–6) in multiple age groups were calculated, analyzed and compared using the Student's t test, the two-way ANOVA and Bonferroni's methods. It was found that the VBR of the anterior horn and modified bicaudate cerebroventricular index of the teenage schizophrenics were significantly greater than those of the teenage controls (p < 0.01) and the ventricular sizes were not associated with the different stages of age except for the cases of the teenage group. These results support the hypothesis of previous investigators that the ventricular enlargement is present early in the course of schizophrenia and provide additional evidence that in teenage schizophrenic patients there is a tendency of the enlargement of the anterior horn of the lateral ventricle which may be related with a morphological vulnerability in the prefrontal cortex.     

Enlargement of the anterior horn of the lateral ventricle in schizophrenic patients: chronological and morphometrical studies

The anterior horn and lateral ventricular sizes of the brain CT were selected for measurement and comparison between 47 schizophrenic patients and 48 neurotic cases, which constituted the control subjects. The ventricular brain ratio (VBR) and the linear ratio (LR 1-6) in multiple age groups were calculated, analyzed and compared using the Student's t test, the two-way ANOVA and Bonferroni's methods. It was found that the VBR of the anterior horn and modified bicaudate cerebroventricular index of the teenage schizophrenics were significantly greater than those of the teenage controls (p less than 0.01) and the ventricular sizes were not associated with the different stages of age except for the cases of the teenage group. These results support the hypothesis of previous investigators that the ventricular enlargement is present early in the course of schizophrenia and provide additional evidence that in teenage schizophrenic patients there is a tendency of the enlargement of the anterior horn of the lateral ventricle which may be related with a morphological vulnerability in the prefrontal cortex.     

Brain morphology in first-episode schizophrenia: a meta-analysis of quantitative magnetic resonance imaging studies

BACKGROUND: A number of meta-analytic reviews of structural brain imaging studies have shown that multiple subtle brain abnormalities are consistently found in schizophrenia. However, quantitative reviews till now published have included mainly studies performed on chronic schizophrenic patients but have failed to provide clear information on specific, possibly different, findings in first-episode schizophrenia. METHODS: We performed a systematic search for MRI studies that reported quantitative measurements of volumes of brain regions in first-episode schizophrenic patients and in healthy controls. Twelve meta-analyses were performed for 6 cerebral regions. RESULTS: Twenty-one studies were identified as suitable for analysis. Significant overall effect sizes were demonstrated for lateral and third ventricular volume increase, and for volume reduction of whole brain and hippocampus, but not for temporal lobe, amygdala and total intracranial volumes. CONCLUSIONS: The available literature data strongly indicate that some brain abnormalities are already present in first-episode schizophrenic patients. However, unlike the results of published meta-analyses conducted primarily on samples of chronic schizophrenic patients, the present study did not confirm a significant reduction of temporal lobe or amygdala volumes in first-episode schizophrenia. These findings support the hypothesis of different patterns of involvement of various cerebral areas over the time course of schizophrenia.     

晚发性精神分裂症的磁共振对照研究

目的：了解晚发生性精神分裂症患者脑共振的变化特征。方法：选择１７例晚发性精神分裂症病人,和正常对照组１７例检测脑的磁共振,以第三脑室宽距,侧脑室间距,侧脑室体部最大间距、左、右颞角宽度,额叶脑兆宽度及顶叶脑沟宽度为观察点。结果：发现病例组异常率为５２．９４％,海马异常诲为４１．１８％,与正常对照组相比,第三脑室、左颞角宽度、额叶脑沟宽度和顶叶脑沟宽度有显著差异。结论：晚发性精神分裂症病人的海马、左     

精神分裂症的脑萎缩及其相关因素的分析

探讨精神分裂症患者脑萎缩的发生率及其相关因素。方法对１４２例精神分裂症患者和４６例正常人进行了脑部磁共振检查,对其临床相关因素进行了分批发裂症患者的脑萎缩发生率为３１．７％;两组脑萎缩发生率和脑空评分、第三脑室最大宽度、前角指数、脑室脑比率的值均有显著性差异;     

Computerized tomography of the brain in schizophrenic patients

Computer tomography (CT) of the brain was carried out in 49 schizophrenic patients and 38 controls in order to study the organic characteristics of the brain in schizophrenia. Between the schizophrenic and control groups aged 21 to 40 years, there was no marked difference in ventricular size or cortical atrophy. In the groups aged 41 to 60 years, however, enlargement of the ventricular system and cortical atrophy were highly significant in the schizophrenic group. Positive correlation was observed (P < 0.05) between enlargement of the third ventricle and duration of illness. There was a high frequency of cortical atrophy in the frontal and temporal lobes in the schizophrenic group.     

Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms

OBJECTIVE: Imaging studies of schizophrenia have repeatedly demonstrated global abnormalities of cerebral and ventricular volumes. However, pathological changes at more local levels of brain organization have not yet been so clearly characterized because of the few brain regions of interest heretofore included in morphometric analyses as well as heterogeneity of patient samples. METHOD: Dual echo magnetic resonance imaging (MRI) data were acquired at 1.5 T from 27 right-handed patients who met DSM-IV criteria for schizophrenia with enduring negative symptoms and from 27 healthy comparison subjects. Between-group differences in gray and white matter volume were estimated at each intracerebral voxel after registration of the images in standard space. The relationship between clinical symptom scores and brain structure was also examined within the patient group. Spatial statistics and permutation tests were used for inference. RESULTS: Significant deficits of gray matter volume in the patient group were found at three main locations: 1) the left superior temporal gyrus and insular cortex, 2) the left medial temporal lobe (including the parahippocampal gyrus and hippocampus), and 3) the anterior cingulate and medial frontal gyri. The volume of these three regions combined was 14% lower in the patients relative to the comparison subjects. White matter deficits were found in similar locations in the left temporal lobe and extended into the left frontal lobe. The patient group showed a relative excess of gray matter volume in the basal ganglia. Within the patient group, basal ganglia gray matter volume was positively correlated with positive symptom scores. CONCLUSIONS: Anatomical abnormalities in these schizophrenic patients with marked negative symptoms were most evident in left hemispheric neocortical and limbic regions and related white matter tracts. These data are compatible with models that depict schizophrenia as a supraregional disorder of multiple, distributed brain regions and the axonal connections between them.     

Superior temporal gyrus volume abnormalities and thought disorder in left-handed schizophrenic men.

OBJECTIVE: Studies of schizophrenia have not clearly defined handedness as a differentiating variable. Moreover, the relationship between thought disorder and anatomical anomalies has not been studied extensively in left-handed schizophrenic men. The twofold purpose of this study was to investigate gray matter volumes in the superior temporal gyrus of the temporal lobe (left and right hemispheres) in left-handed schizophrenic men and left-handed comparison men, in order to determine whether thought disorder in the left-handed schizophrenic men correlated with tissue volume abnormalities. METHOD: Left-handed male patients (N = 8) with DSM-III-R diagnoses of schizophrenia were compared with left-handed comparison men (N = 10) matched for age, socioeconomic status, and IQ. Magnetic resonance imaging (MRI) with a 1.5-T magnet was used to obtain scans, which consisted of contiguous 1.5-mm slices of the whole brain. MRI analyses (as previously defined by the authors) included the anterior, posterior, and total superior temporal gyrus in both the left and right hemispheres. RESULTS: There were three significant findings regarding the left-handed schizophrenic men: 1) bilaterally smaller gray matter volumes in the posterior superior temporal gyrus (16% smaller on the right, 15% smaller on the left); 2) a smaller volume on the right side of the total superior temporal gyrus; and 3) a positive correlation between thought disorder and tissue volume in the right anterior superior temporal gyrus. CONCLUSIONS: These results suggest that expression of brain pathology differs between left-handed and right-handed schizophrenic men and that the pathology is related to cognitive disturbance.     

Current overview of structural magnetic resonance imaging in schizophrenia

Non-invasive morphologic imaging (computer tomography, magnetic resonance imaging, MRT) has contributed significantly to our understanding of schizophrenic disorders as diseases of the brain. Improved MRT techniques enable us to analyse anatomical substructures. The present overview evaluates peer-reviewed MRT studies published between 1994 and July 2000 and provides a comparison with our own results. Chronic schizophrenic patients most frequently show an enlargement in the ventricular system along with a reduction in grey matter. A more detailed subdivision into cortical and subcortical regions additionally shows the noted volume reduction to be limited to specific areas within the brain rather than being distributed equally throughout the brain. Within the area of the temporal lobes the two most frequently affected areas are the hippocampus and the gyrus temporalis superior. Alterations within these areas correlate with clinical symptoms such as hallucinations or thought disorders. Within the frontal cortex nearly 70% of all studies show a decrease in overall volume, while 63% note a reduction in size within the thalamus and 60% in the cerebellum. Morphologically speaking these structures therefore play the greatest role in the pathophysiology of schizophrenia and the onset of clinical symptoms. More recent studies also showed a specific progression in subgroups of patients pointing toward a neurodegenerative process. Additionally there are a number of differential antipsychotic effects following longterm treatment with typical neuroleptics as compared to atypical antipsychotics. Based on these findings future longitudinal studies should examine to what extent such a progressive decrease in volume might be influenced by treatment with modern antipsychotics.     

Lack of association between duration of untreated illness and severity of cognitive and structural brain deficits at the first episode of schizophrenia

OBJECTIVE: The purpose of the study was to determine whether the duration of illness before antipsychotic drug treatment for schizophrenia was associated with the severity of cognitive deficits and volumetric brain structure anomalies observed in some patients with a first episode of schizophrenia. METHOD: Duration of psychotic symptoms and of other symptoms marking a behavioral change was estimated from structured interviews with 50 patients who had a first episode of schizophrenia and their family members. Interviews were conducted within a month of the patients' hospitalization. Duration of untreated psychotic symptoms and of behavioral change was correlated with neuropsychological summary scores from a comprehensive cognitive battery and with measurements of lateral ventricular, temporal lobe, and cerebral hemispheric volumes. RESULTS: No significant correlations were observed between measures of untreated illness and the severity of either cognitive or structural brain deficits at baseline. CONCLUSIONS: The duration of untreated symptoms of schizophrenia, for which an association with an uncontrolled toxic brain process has been proposed, is unlikely to explain why first-episode patients with schizophrenia have widespread deficits in cognitive functioning and have detectable ventricular enlargement and some loss of cortical mass.     

Volumetric measure of the frontal and temporal lobe regions in schizophrenia: relationship to negative symptoms

BACKGROUND: Previous research has provided evidence for brain abnormalities in schizophrenia, but their relationship to specific clinical symptoms and syndromes remains unclear. METHODS: With an all-male demographically similar sample of 53 schizophrenic patients and 29 normal control subjects, cerebral gray and white matter volumes (adjusted for intracranial volume and age were determined for regions in the prefrontal lobe and in the superficial and mesial temporal lobe using T1-weighted magnetic resonance imaging with 2.8-mm coronal slices. RESULTS: As a group, schizophrenic patients had wide-spread bilateral decrements in gray matter in the pre-frontal (7.4%) and temporal lobe regions (8.9%), but not in white matter in these regions. In the temporal lobe, gray matter reductions were found bilaterally in the superior temporal gyrus (6.0%), but not in the hippocampus and parahippocampus. While there were no overall group differences in white matter volumes, widespread decrements in prefrontal white matter in schizophrenic patients (n = 53) were related to higher levels of negative symptoms (partial r[49] = -0.42, P = .002), as measured by the Scale for the Assessment of Negative Symptoms. A post hoc analysis revealed that schizophrenic patients with high negative symptoms had generalized prefrontal white matter reductions (11.4%) that were most severe in the orbitofrontal subregion (15.1%). CONCLUSIONS: These results suggest that gray matter deficits may be a fairly common structural abnormality of schizophrenia, whereas reductions in prefrontal white matter may be associated with schizophrenic negative symptoms.     

Notes from the graveyard: neuropathology and schizophrenia

Schizophrenia is commonly regarded as a 'functional' psychosis, the implication being that the delusions, hallucinations and cognitive impairment characteristic of the disease have no organic basis. This view is due in no small way to the failure of pathologists to find convincing pathological changes associated with the disease in the first seven decades of the century. Over the last 10 years things have changed considerably. Recent CT and MRI scan studies have provided convincing evidence of significant ventricular enlargement in the brains of schizophrenics and post-mortem studies have shown that schizophrenic brains are about 6% lighter than controls and have a reduced volume and reduced antero-posterior length. Planimetric studies on post-mortem material and a recent MRI study show that medial temporal lobe structures (parahippocampal gyrus, hippocampus and amygdala) are preferentially affected. Although other brain regions (e.g. cingulate gyrus, frontal cortex) also show alterations they appear to be 'downstream' from the regions primarily affected. Morphological studies show that there is a loss of neurons from medial temporal lobe structures and indicate irregularities in their cytoarchitectonic arrangement. The alterations in structure are not associated with degenerative, inflammatory, or abnormal vascular processes. There has been much debate as to the possible causes of the structural changes and whether they are limited to particular 'types' or sub-groups of schizophrenics. At present it seems simpler to suppose that all schizophrenics have a degree of structural abnormality which may differ in degree but not in kind. It has been proposed that the changes in brain structure in schizophrenia are the result of an anomaly of brain development. In the last year CT and MRI studies have shown that ventricular enlargement precedes clinical symptoms and is not progressive. These studies support the developmental interpretation. Future studies will need to focus on (a) the mechanisms (probably genetic) which can cause such developmental anomalies, (b) the neurochemical perturbations occurring as a result of such anomalies and (c) how both relate to clinical symptoms.     

Structural brain abnormalities in bipolar affective disorder. Ventricular enlargement and focal signal hyperintensities

Structural brain abnormalities were examined in a sample of 48 patients with bipolar affective disorder who were compared with 54 schizophrenic patients and 47 normal controls. As in our previous work using computed tomographic scanning, lateral ventricular enlargement was due to a diagnostic effect. In this study, the effect was more prominent in the schizophrenic men, while a trend was seen in the bipolar men. Women in both groups did not differ significantly from normal subjects. This finding is possibly consistent with the fact that men have a higher frequency of birth anomalies such as hydrocephalus. Since one cause of such birth anomalies might be periventricular hemorrhage or infarction, we also evaluated all scans for the presence of small focal regions of signal hyperintensity. A significant increase in the number of focal signal hyperintensities was noted in the bipolar patients, in comparison with normal subjects, but not in the schizophrenics. The bipolar patients with focal signal hyperintensities had a trend toward larger ventricular size than those without. The pathophysiological significance of these findings is unclear.     

Influence of genetic loading,obstetric complications and premorbid adjustment on brain morphology in schizophrenia: a MRI study

Cerebrospinal fluid (CSF) space enlargement in schizophrenia is a prominent finding. This study was initiated to examine the influence of genetic loading, obstetric complications and premorbid adjustment on the extent of this enlargement. The sample of this MRI study consisted of 40 schizophrenic patients, 24 psychiatric and 40 healthy family members from 10 uniaffected and 19 multiple affected families with schizophrenia, such as 27 control subjects from non-affected families. The ventricle-to-brain-ratio (VBR), and the areas of the third ventricle, sylvian fissure, temporal horn and interhemispheric fissure at the slice where these structures reached their maximum were examined relatively to the corresponding total brain areas. The sum of CSF areas was calculated as a parameter for global atrophy. From MANCOVA adjusted for intervening variables the right VBR and the sum of CSF areas revealed significant differences between diagnostic groups. For these areas schizophrenic patients showed an increase compared to control subjects and family members with psychiatric disorder. Genetic loading influenced the interhemispheric fissure, enlarged in multiple affected compared to uniaffected families, and the temporal horn asymmetry, which was right sided (right > left) in control subjects and multiple affected families, but inverted in uniaffected families. Neonatal obstetric complications influenced only the size of the VBR, while premorbid adjustment predicted various CSF areas. In conclusion, schizophrenic subjects from multiple and uniaffected families showed a global atrophy, which was most pronounced in the VBR. Genetic loading seems to have an impact on frontal regions as the interhemispheric fissure and on the temporal horn. Received: 14 February 2002 / Accepted: 17 February 2003 Correspondence to Peter Falkai, MD     

New perspectives on schizotypal personality disorder

Schizotypal personality disorder is the prototype of the schizophrenia-related personality disorders and has been demonstrated to have phenomenologic, biologic, treatment, and outcome characteristics similar to those of schizophrenic patients. These studies suggest that patients with schizotypal personality disorder, like schizophrenic patients, show cognitive impairment, but the impairment is more focal and involves primarily working memory, verbal learning, and sustained attention rather than generalized intellectual deficits. Schizotypal patients, like schizophrenic patients show reductions in temporal lobe volume, but seem to be spared the frontal volume reductions found in some studies of schizophrenic patients and in our laboratory. Better frontal “buffering” may prevent the more severe cognitive and social deterioration associated with schizophrenia. Furthermore, schizotypal patients appear to show less susceptibility to psychotic symptoms, in part perhaps because of better buffered subcortical dopaminergic activity as suggested by recent data from a SPECT/amphetamine paradigm, glucose metabolic study, and structural studies of basal ganglia. These findings are discussed in terms of a model of schizotypal personality disorder where schizotypal patients have better capacity for compensatory buffering in lateral and subcortical brain regions, protecting them from the more severe symptoms of chronic schizophrenia.     

Abnormal relationships between local and global brain measures in subjects at clinical high risk for psychosis: a pilot study

We examined whether abnormal volumes of several brain regions as well as their mutual associations that have been observed in patients with schizophrenia, are also present in individuals at clinical high-risk (CHR) for developing psychosis. 3T magnetic resonance imaging was acquired in 19 CHR and 20 age- and handedness-matched controls. Volumes were measured for the body and temporal horns of the lateral ventricles, hippocampus and amygdala as well as total brain, cortical gray matter, white matter, and subcortical gray matter volumes. Relationships between volumes as well as correlations between volumes and cognitive and clinical measures were explored. Ratios of lateral ventricular volume to total brain volume and temporal horn volume to total brain volume were calculated. Volumetric abnormalities were lateralized to the left hemisphere. Volumes of the left temporal horn, and marginally, of the body of the left lateral ventricle were larger, while left amygdala but not hippocampal volume was significantly smaller in CHR participants compared to controls. Total brain volume was also significantly smaller and the ratio of the temporal horn/total brain volume was significantly higher in CHR than in controls. White matter volume correlated positively with higher verbal fluency score while temporal horn volume correlated positively with a greater number of perseverative errors. Together with the finding of larger temporal horns and smaller amygdala volumes in the left hemisphere, these results indicate that the ratio of temporal horns volume to brain volume is abnormal in CHR compared to controls. These abnormalities present in CHR individuals may constitute the biological basis for at least some of the CHR syndrome.     

Magnetic Resonance in Schizophrenia

In vivo magnetic resonance imaging (MRI) of schizophrenic patients permits the direct and noninvasive study of brain biochmeistry, structure, and function. During the last decade, a number of morphological abnormalities have been found in schizophrenic brains on the basis of qualitative and quantitative assessment of MRIs. Changes in ventricular volume, cortical volume, temporal lobe structures, and subcortical regions have been reported. The search for a precise and specific location underlying the pathophysiology of schizophrenia has led to the interpretation of imaging results in the context of interrelated systems of brain function, rather than isolated focal brain abnormalities. Furthermore, an important goal of imaging studies is to describe unusual features of schizophrenic brains that represent abnormalities central to the development of the disorder, including abnormalities that may represent vulnerabilities or risk factors, as well as those that are directly related to psychopathology. Identifying brain pathology that distinguishes schizophrenics' brains has proven difficult because it involves detecting rather subtle changes against a background of extensive normal variation. Application of powerful new magnetic resonance techniques continues to increase our understanding of these subtle changes. The importance of magnetic resonance spectroscopy is derived from the information it provides regarding the chemical content of the tissue being studied. Functional MRI provides a method for the assessment of functional architecture by measuring changes in oxidation and regional blood flow in discrete regions of the brain in response to challenge paradigms. These technologies promise to facilitate both the detection of cortical anomalies as well as provide the methods necessary for the systematic exploration of cortical structure and function needed to examine brain dysfunction from a network perspective.