Cerebroventricular size and cerebrospinal fluid monoamine metabolites in schizophrenic patients and healthy volunteers

Computed tomography (CT) measures and cerebrospinal fluid (CSF) levels of the monoamine metabolites homovanillic acid (HVA), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were determined in 43 healthy volunteers and in 26 patients with an acute psychosis of the schizophrenic type. There were no differences in the mean CSF levels of monoamine metabolites between the two groups. However, the patients had significantly wider lateral and third ventricles as compared to the volunteers. In the volunteers there were no significant correlations between ventricular sizes and monoamine metabolite levels, whereas in the patients a significant negative correlation was obtained between the size of the lateral ventricles and the levels of HVA and 5-HIAA in the CSF. These results may indicate that the enlargements of the brain ventricles found in a subgroup of schizophrenic patients may be associated with deficiencies in central monoamine transmission mechanisms.     

Transcranial brain sonography findings related to neuropsychological impairment in multiple sclerosis

Cognitive dysfunction, fatigue and mood disorder contribute to the neuropsychological impairment that is common in multiple sclerosis (MS). The present paper reviews application of transcranial brain sonography (TCS) in MS patients and TCS findings related to neuropsychological dysfunction. TCS is a new neuroimaging method displaying tissue echogenicity of the brain through the intact skull. Whereas the cortex can not be discriminated from the subcortical white matter with TCS, subcortical brain structures such as ventricles and basal ganglia can be adequately displayed. Even though TCS proved sensitive and reliable in measuring widths of third and lateral ventricles in a number of neurodegenerative diseases, relatively few TCS studies on MS patients have been reported. Data of these studies suggest a good correlation of cognitive dysfunction and width of third ventricle which can be measured reliably with TCS. Moreover, abnormal TCS findings of basal ganglia were associated with cognitive impairment. However, TCS findings of midbrain structures, basal ganglia and ventricles did not correlate with fatigue or depression in MS patients. TCS has the advantages of low costs, short investigation times and unlimited repeatability. The use of third-ventricle and basalganglia TCS for predicting and monitoring neuropsychological impairment in MS patients, however, needs to be elucidated in further studies.     

Brain metabolism in Alzheimer''s dementia: studies of 11C-deoxyglucose accumulation, CSF monoamine metabolites and neuropsychological test performance in patients and healthy subjects.

Thirteen patients with dementia of Alzheimer type and nine age-matched control subjects were examined by a battery of neuropsychological tests and by positron emission tomography (PET) with 11C-deoxyglucose as a tracer for regional glucose metabolism in the brain. Concentrations of the monoamine metabolites HVA, MHPG and 5-HIAA were determined in the CSF from patients and controls. In the patients there was a diminished glucose metabolism in posterior parietal and superior temporal cortex areas to 60% of control levels. Other cortical areas showed similar changes, whereas the pre- and postcentral area, the cerebellum, the hippocampus and the basal ganglia showed less or no change. The decline in cortical metabolism in the patients was symmetrical but the variation in the left/right ratio was greater than in the controls. The CSF levels of monoamine metabolites did not differ between patients and controls. High levels of the metabolites were associated with low rates of glucose metabolism, possibly due to inhibitory influences of monoaminergic pathways upon cortical and subcortical neurons. The rate of glucose metabolism correlated positively with the neuropsychological test performance in both patients and controls. Verbal and memory performances were associated with greater left hemisphere metabolism in the patients, but not in the controls, whereas non-verbal abilities tended to be associated with right hemisphere metabolic dominance.     

Neuropsychological deficit in newly diagnosed patients with schizophrenia or schizophreniform disorder

Forty-six patients with schizophrenia or schizophreniform disorder admitted to hospital for the first time were compared with 21 healthy volunteers on neuropsychological tests reflecting prefrontal and left respectively right hemisphere function. The patients with schizophrenia or schizophreniform disorder had a poorer performance on neuropsychological tests (such as Wisconsin Card Sorting) compared with healthy volunteers. Both left and right hemisphere seemed to be involved. Especially poor performance was found on somewhat complicated tests requiring ability of analysis, abstraction and memory, thus indicating dysfunction of prefrontal and temporohippocampal regions. Signs of sulcal enlargement and size of lateral ventricles on computed tomographic scan correlated with poor test performance on some tests both in patients and in healthy volunteers. No correlations were found between performance on neuropsychological test and negative symptoms.     

Cortical sulcal enlargement in catatonic schizophrenia: a planimetric CT study.

To determine whether patients with catatonic schizophrenia have specific alterations in brain morphology, internal (ventricles) and external (frontal, temporal, parieto-occipital) components of the cerebrospinal fluid (CSF) spaces were examined morphometrically. Planimetric measurements of computed tomographic (CT) scans from 37 patients with catatonic schizophrenia, 28 patients with hebephrenic schizophrenia, and 39 patients with paranoid schizophrenia, all diagnosed according to DSM-III-R criteria, were compared with separate age- and sex-matched non-psychiatric control groups, respectively. The areas of the frontal sulci, the parieto-occipital sulci, the inter-hemispheric fissure, and the lateral and third ventricles were measured separately for the right and left hemispheres. Catatonic patients showed significant enlargements in almost all CSF spaces, especially in the left fronto-temporal area which, in addition, correlated significantly with illness duration. Hebephrenic patients showed selective enlargements in left temporal and left/right lower frontal cortical sulci, whereas paranoid schizophrenic patients showed no enlargements but significant correlations between left temporal cortical sulcal volume and illness duration. Alterations in temporal cortical areas were present in all three sub-types of schizophrenia. In addition to temporal alterations, hebephrenic schizophrenia was characterised by lower frontal (i.e. orbitofrontal) enlargement. Catatonic schizophrenia, the most severe sub-type with regard to clinical symptomatology and brain pathology, showed fronto-parietal cortical alterations.     

Third-ventricle enlargement and neuropsychological deficit in schizophrenia.

Cerebral ventricular enlargement is present in a substantial subgroup of schizophrenic patients. Most, but not all studies examining neuropsychological performance and ventricular size in schizophrenics show more severe cognitive impairment in those patients with greatest ventricular enlargement. Inconsistencies in this literature have been attributed to different neuroimaging techniques, variation in patient characteristics across studies, and the variety of neuropsychological batteries used. In the present study, schizophrenic patients (n = 49 men, n = 23 women) and normal controls (n = 13 men, n = 18 women) underwent magnetic resonance (MR) imaging of the brain and extensive neuropsychological testing including measures of frontal and temporal lobe function. A complete coronal set of MR images was used to calculate volumetric estimates of lateral and third cerebral ventricles. Highly significant associations were found between cognitive deficits and third-ventricle volume, with measures of frontal functioning, attention, and concentration showing the most robust correlations. In contrast, neuropsychological performance was not highly associated with lateral ventricular size. These findings further support the pathophysiological relevance of ventricular enlargement in schizophrenia. More specifically, third, but not lateral, ventricular enlargement was associated with greater cognitive disturbance in this sample. Results are consistent with pathological involvement of periventricular diencephalic structures resulting in dysfunctional frontal and limbic processing in a subgroup of patients.     

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.     

Computed tomography of the brain in patients with acute psychosis and in healthy volunteers

Evidence has been obtained by computed tomography (CT) that some chronic schizophrenic patients have enlarged cerebral ventricles and other brain abnormalities when compared to other patient groups and to healthy controls (Johnstone et al. (1976), Weinberger et al. (1979)). In order to investigate whether structural brain abnormalities can be demonstrated also in younger patients with acute psychosis we have undertaken a CT study in 46 patients and 46 healthy volunteers. Twenty-eight of the patients fulfilled the Research Diagnostic Criteria for schizophrenia. Nineteen had not been hospitalized for psychiatric reasons before. The lateral and third ventricles were significantly wider in the patients than in the volunteers. In the volunteers there was a significant positive correlation between age and size of the lateral ventricles, whereas in the patients, particularly those fulfilling the criteria for schizophrenia, no such correlation was obtained. These results indicate that schizophrenia may be associated with pathophysiological processes which interfere with the normal age-related enlargement of the ventricles. Signs of cortical atrophy, CSF circulation disturbances and reversed asymmetry of the occipital lobes were more frequent in the patient group than among the controls. These results are in accordance with previously published findings and indicate that structural brain abnormalities can be found in relatively young patients with acute psychosis.     

Unirhinal olfactory identification deficits in young male patients with schizophrenia and related disorders: association with impaired memory function

We have observed discreet subgroups of male patients with psychotic disorders who have unirhinal olfactory identification deficits (microsmia). The purpose of this study was to examine the relationship between left or right nostril microsmia and performance on literalised neuropsychological tests sensitive to lesions in brain areas implicated in the pathogenesis of schizophrenia. Sixty-six male patients diagnosed with schizophrenia or related disorders were assessed with a battery of neuropsychological tests, sensitive to literalised and regional (temporal and frontal lobe) dysfunction. The University of Pennsylvania Smell Identification Test (UPSIT) was administered unirhinally and resultant scores were used to classify patients into olfactory subgroups. Neuropsychological test scores were compared amongst subgroups. A mixed design MANOVA was performed on cognitive domains with olfactory status (right microsmic; RM, n=8, left microsmic; LM, n=20, and normosmic schizophrenic controls; NSzC, n=38) as the between subject factor while hemisphere (left versus right) and domain (executive/fluency versus memory) were within-subject factors. A three-way (olfactory subgroup by hemisphere by region) interaction was observed. Non-verbal memory impairment was observed in the right and left microsmic subgroups. Verbal memory deficits were demonstrated in patients with left nostril microsmia.These results indicate that unirhinal olfactory performance may provide a meaningful manner by which to subtype patients with schizophrenia. Moreover, the data suggest that olfactory deficits in patients with schizophrenia are associated with dysfunction of temporal lobe, rather than frontal lobe abnormalities. The data are consistent with reports linking the right temporal lobe integrity to adequate olfactory processing.     

Neuropsychological relationships in paranoid schizophrenia with and without delusional misidentification syndromes. A comparative study

Delusional misidentification syndromes (DMSs) and schizophrenia are strongly associated, since the former occur predominantly in the context of paranoid schizophrenia. However, the possible underlying neuropsychological relationships between DMSs and paranoid schizophrenia have not been thoroughly investigated. The aim of the present study was to investigate whether DMSs in paranoid schizophrenia are associated with a distinct neuropsychological substrate indicative of differential bilateral frontal and right hemisphere dysfunction. We compared two matched groups of paranoid schizophrenic patients with (N=22) and without (N=22) DMS(s) on a battery of neuropsychological tests assessing mainly frontal and right hemisphere functions. No statistically significant differences were detected between the two groups. Our findings are indicative of a bilateral frontal and right hemisphere dysfunction of equal severity in both DMS and non-DMS patients with paranoid schizophrenia.     

Examining the relationship between computed tomography and neuropsychological measures in normal and demented elderly.

Correlational analysis of CT and neuropsychological measures in patients with dementia revealed more predictive relationships in degenerative and vascular subgroups that in a multi-aetiology group. Normal and dementia patients were then matched for age, sex and educational background, and analysed together. The ventricular/brain ratios of the bodies of the lateral ventricles and of the third ventricle correlated most highly with neuropsychologic performance. Canonical analysis revealed a correlation coefficient of 0.725 between the sets of CT and neuropsychological measures, which increased to 0.78 when a degenerative subgroup only was considered. Discriminant function analysis indicated that the combination of CT and neuropsychological measures was more powerful in discriminating normals from dementia patients than CT or neuropsychological measures alone.     

Atrophy limited to the third ventricle in chronic schizophrenic patients. Report of a controlled series

Computed tomographic scans of 30 chronic schizophrenic patients and 26 matched medical controls were blindly assessed for ventricular brain ratio, cortical atrophy, third-ventricle diameter, and cerebellar atrophy. Schizophrenic patients had significantly larger third ventricles than the medical controls. There was no difference in the other brain morphologic variables. Phenomenology, drug response, CSF levels of 5-hydroxyindoleacetic acid, 3-methoxy-4-hydroxyphenylglycol, homovanillic acid, and a wide variety of clinical variables did not correlate with any measure of brain morphology. Clinicopathologic correlates of brain morphology may be limited to those patients with significant atrophy.     

Magnetic resonance imaging in schizophrenia: altered brain morphology associated with P300 abnormalities and eye tracking dysfunction.

This study was designed to investigate whether auditory P300 event-related potential and smooth pursuit eye-movement abnormalities in schizophrenia are associated with brain structural changes measured using magnetic resonance imaging (MRI). Serial coronal MRI scans obtained from 31 schizophrenic subjects and 33 volunteer controls were analysed by a rater who had no knowledge of the subjects' diagnoses. The brain areas measured bilaterally were the temporal lobe, hippocampus, amygdala, parahippocampal gyrus, head of caudate, cingulate cortex, frontal cortex, and the lateral ventricles. The area of the third ventricle, the thickness of the corpus callosum, and the intracranial area were also measured. Auditory P300 and eye tracking performance were recorded on all subjects. There was a significant increase in the latency and a reduction in amplitude of the P300 in the schizophrenic group. Only in the schizophrenic group was P300 latency correlated negatively with the area of the right and left cingulate cortex and positively with the difference in size between the right and left amygdala. In the subgroup of schizophrenic subjects whose P300 latency was greater than 2 standard deviations above the control mean, the area of the left cingulate cortex was significantly smaller than in controls, and the absolute right-left difference in the area of the amygdala was significantly increased. Eye tracking dysfunction in schizophrenia was not related to changes in the amygdala or cingulate cortex but was significantly correlated with enlargement of the lateral ventricles. Schizophrenic subjects with poor eye tracking had significantly larger lateral ventricles than controls. Eye tracking dysfunction, but not P300 abnormality, was correlated with the severity of both positive and negative symptom of schizophrenia. These findings demonstrate that psychophysiological abnormalities are associated with altered brain structure in schizophrenia.     

CT scan and MRI findings in a child with schizophrenia

Morphologic brain changes have long been recognized in some adult schizophrenic patients. The ready availability of computed tomographic (CT) scans and the recent advent of magnetic resonance imaging (MRI) now permit noninvasive neuroimaging of schizophrenic patients. We describe a prepubertal schizophrenic child with neuroradiographic findings similar to those found in adult schizophrenic patients: ex vacuo enlargement of the lateral ventricles, dilatation of the third ventricle, and cerebellar abnormalities. This patient appears to be the first schizophrenic child documented to have these morphologic changes of the brain and suggests the need for further neuroradiographic studies to define the frequency and significance of structural changes that may occur in childhood schizophrenia.     

Lateralized brain dysfunction in autism: Evidence from the Halstead-Reitan neuropsychological battery

Selected tests from the Halstead-Reitan neuropsychological battery were administered to 10 male individuals who had been diagnosed as autistic in early childhood. Results from the battery obtained from the autistic group were compared with a group of retarded persons matched for IQ and with a group of patients with demonstrable diffuse brain damage. As a group, the autistic subjects showed a pattern of deficits indicative of a significantly greater degree of left hemisphere dysfunction than either comparison group. Furthermore, within-subject comparisons revealed that the autistic group had a significantly greater left than right hemisphere dysfunction, while neither comparison group showed this lateralized pattern.     

The use of a standardized battery of Luria's tests in the diagnosis of lateralized cerebral dysfunction.

The present study was designed to examine the capability of a standardized battery of Luria's qualitative neuropsychological techniques in discriminating between right, left and diffuse brain-injured subjects. A total of sixty medically confirmed brain-damaged subjects were equally divided among the three groups. Subjects were assigned to two groups (right, left) according to medically proven lateralized brain injury to either the right or left hemisphere in the absence of verifiable insult to the opposite hemisphere. A third group was also selected in which medical evidence confirmed damage to both hemispheres (diffuse group). All three groups were matched for age and education. All subjects were tested on a standardized version of 269 Luria's qualitative neuropsychological test items. The items were divided into 11 sections based upon Luria's theory of brain function. Each of the 11 sections plus a right and a left hemisphere scale as well as an overall impairment scale yielded 14 summary measures of performance representing several areas of neuropsychological ability and overall severity of brain dysfunction. Analysis of variance and discriminant analysis were used to compare the three groups on these 14 summary measures. Analysis of variance revealed on significant difference between the three groups on the Left scale with the left group performing poorest. Discriminant analysis predicted the status of 59 of 60 subjects correctly (98% hit rate). The implication of the lack of significant simple relationships (ANOVA) and the complex interrelationships found using the discriminant analysis were discussed in terms of the support these results provide for Luria's theory of brain function. The specific qualitative aspects of the test battery and their use in the diagnosis of lateralized brain injury were also discussed. Indications for future research were pointed out.     

Brain Atrophy and Intellectual Impairment in Tardive Dyskinesia

Abstract: Fourteen chronic schizophrenic patients with tardive dyskinesia (TD) and 13 without TD were given psychological tests and CT scans. The low density rate (LDR), i.e., the ratio of the X-ray absorption (corresponding nearly to that of cerebrospinal fluid) of a brain lesion to the X-ray absorption of the whole brain, was used as an index of brain atrophy (HN-method). The LDR of the left hemisphere of the TD patients was significantly higher than that of non-TD patients in the basal nucleus and lateral ventricle, and the LDR of the right hemisphere for the TD patients was significantly higher than that of non-TD patients in the basal nucleus. The Hasegawa Dementia Rating Scale (HDRS) and Bender-Gestalt Test (BGT) for the TD patients were significantly lower than those for the non-TD patients. Our study revealed that brain atrophy was greater in TD than in non-TD patients and tended to be more pronounced in the left hemisphere, and that the degree of intellectual impairment was greater in the TD patients than in the non-TD group. The results suggest that schizophrenic brains with TD tend to be more easily damaged than those without TD, that this tendency predominates on the left side, and that intellectual impairment in TD is related to brain atrophy.     

Clinical, biological, and neuropsychological features associated with lateral ventricular enlargement in DSM-III schizophrenic disorder

Clinical, historical, neuropsychological, and biological correlates of lateral ventricular enlargement on computed tomography (CT scan) were explored in a sample of DSM-III schizophrenics. Patients with enlarged ventricles, as compared with those whose ventricles were normal, presented a longer duration of illness and mean duration of hospitalization, and higher scores on the subscales alogia, affective flattening, and attentional impairment of the Scale for the Assessment of Negative Symptoms (SANS), on the scales self-care, participation in household activities, work performance, and behavior in crises and emergencies of the Disability Assessment Schedule, on the scales rhythm, writing, reading, arithmetic, and left hemisphere of the Luria-Nebraska Neuropsychological Battery, and on the subtests digit span, digit symbol and block design of the Wechsler Adult Intelligence Scale. Furthermore, on the computerized electroencephalogram, beta relative activity was significantly higher in patients with normal ventricles on the right frontal, left frontal, and right central leads. On stepwise discriminant function analysis, the patient groups with enlarged and normal ventricles could be separated statistically, and duration of illness and summary score on the SANS were found to be the best discriminators.     

Neuropsychological functioning of first-episode schizophreniform patients.

OBJECTIVE AND METHOD: This study compared 32 consecutively admitted first-episode schizophreniform patients, 26 patients with chronic schizophrenia according to the DSM-III-R criteria, and 25 normal comparison subjects on a comprehensive battery of neuropsychological tests to determine the degree of cognitive impairment existing at the onset of schizophrenic illness. Patients were tested within 2 weeks of admission to the hospital, after their medication had been stabilized. RESULTS: With age and education controlled, the first-episode and chronic patients performed significantly worse than the normal subjects on neuropsychological summary measures of executive function, verbal memory, spatial memory, concentration/speed, and global cognitive function and on left and right hemisphere function scales. The first-episode patients were as cognitively impaired as the chronic patients on all summary scales and many of the individual tests. Both groups showed relatively greater left than right hemisphere dysfunction. CONCLUSIONS: These findings suggest that substantial cognitive deficits, comparable to those of chronic patients, are present early in the course of psychotic illness.     

Magnetic resonance brain images in schizophrenic and normal subjects: influence of diagnosis and education

Evidence from computerized tomography (CT) suggests that schizophrenic patients may have smaller brains than normal subjects. Magnetic resonance imaging (MRI), which produces more clearly defined images than CT, was used to measure T1 and brain size of 24 schizophrenic and 24 normal subjects matched for age and sex but not for education. Two transverse images were obtained: slice 1 at the foramina of Monro and slice 2 at the widest part of the lateral ventricles. Adequate T1 instrumental reliability could not be demonstrated. Schizophrenic subjects had smaller right hemispheres (slice 1) and smaller frontal areas (slice 2) than normal subjects. However, when education was taken into account, only the left frontal area (slice 2) was smaller in schizophrenic than in normal subjects. Larger brain areas were associated with better cognitive test scores and fewer neurological signs. Cranial and body size were similar in both diagnostic groups.