Post-mortem volume measurements of limbic system and basal ganglia structures in chronic schizophrenics. Initial results from a new brain collection

Volumes of the hippocampal formation, external and internal pallidum, caudate, putamen, and nucleus accumbens were measured in both hemispheres of recently collected post-mortem brains of 18 chronically ill schizophrenics and 21 control subjects. In the schizophrenic group, the hippocampal formation and the internal pallidum were significantly smaller in the right and left hemisphere, whereas external pallidum, putamen, caudate and accumbens were not significantly changed. Volumes of the hippocampus and of all evaluated parts of the basal ganglia were in the male schizophrenics more reduced than in the female patients. The right and left hemispheres were equally affected in both sexes. Since the mean brain weight was in patients and controls nearly identical, the volume differences can not be explained by a general brain atrophy or hypoplasia but rather indicate a more focal lack of brain tissue, by which some clinical features of the disease might be explained.     

Limbic pathology in schizophrenia: the entorhinal region--a morphometric study

The volume of the entorhinal region is significantly reduced in postmortem brains of schizophrenics compared with controls (p less than 0.017). In addition, a significant reduction of neurons (p less than 0.017), but no significant increase in absolute glial cell numbers, is found. These results are consistent with the hypothesis that structural changes in the medial temporal lobe of schizophrenics may be developmental in origin.     

Basal ganglia volumes in first-episode schizophrenia and healthy comparison subjects.

BACKGROUND: Previous studies suggest that dysfunction of cortico-striato-pallido-thalamic (CSPT) circuitry may be involved in the pathophysiology of schizophrenia but also show that basal ganglia structure is highly plastic and may be influenced by antipsychotic treatments. Controversy remains about whether basal ganglia pathology can be detected in vivo among treatment-na?ve patients. We conducted a magnetic resonance imaging (MRI) study to examine basal ganglia structures and the limbic forebrain in first episode schizophrenia and healthy comparison subjects. METHODS: Fifty-one patients with first-episode schizophrenia and 28 healthy comparison subjects participated in the study. A high-resolution, special contrast (white matter nulling) MRI sequence was used to measure the caudate nucleus, nucleus accumbens, putamen, and subcommissural limbic forebrain. RESULTS: Volumes of the basal ganglia regions of interest (adjusted for total brain volume and age) did not differ significantly between the groups. Age correlated significantly with caudate and putamen volumes bilaterally in the healthy comparison group, but not among patients. CONCLUSIONS: The findings suggest that there are no volumetric abnormalities in basal ganglia before treatment in first-episode schizophrenia. The lack of a negative correlation between age and striatal volume among patients may implicate illness-associated factors that alter normal age-related changes in basal ganglia size.     

Hippocampal pathologic findings in schizophrenia. A morphometric study

We studied hippocampal sections from 13 schizophrenic patients, 9 nonschizophrenic patients, and 16 normal controls from the Yakovlev brain collection. The three groups were similar in age, gender distribution, and brain weight. Most patients had never received neuroleptics, and the two patient groups had had similar types of leukotomies. We used a semiautomated image analysis system to compute volume and pyramidal-cell density in each of the four sectors of the cornu ammonis, Ca1 through CA4, in the right and left hippocampi. Sections from schizophrenic patients had almost consistently the lowest volume and pyramidal-cell density in all sectors. The differences were greatest in left CA4, with schizophrenic patients having significantly lower pyramidal-cell density than normal controls and significantly lower volume than leukotomy controls. Our findings confirm the results of several recent studies showing hippocampal pathologic features in schizophrenia. Our study suggests, however, that the hippocampal neuropathologic findings in schizophrenia may be more subtle and more localized than those reported previously.     

Basal ganglia volume in unmedicated patients with schizophrenia is associated with treatment response to antipsychotic medication

We investigated the relationship between basal ganglia volume and treatment response to the atypical antipsychotic medication risperidone in unmedicated patients with schizophrenia. Basal ganglia volumes included the bilateral caudate, putamen, and pallidum and were measured using the Freesurfer automated segmentation pipeline in 23 subjects. Also, baseline symptom severity, duration of illness, age, gender, time off medication, and exposure to previous antipsychotic were measured. Treatment response was significantly correlated with all three regions of the bilateral basal ganglia (caudate, putamen, and pallidum), baseline symptom severity, duration of illness, and age but not gender, time off antipsychotic medication, or exposure to previous antipsychotic medication. The caudate volume was the basal ganglia region that demonstrated the strongest correlation with treatment response and was significantly negatively correlated with patient age. Caudate volume was not significantly correlated with any other measure. We demonstrated a novel finding that the caudate volume explains a significant amount of the variance in treatment response over the course of 6 weeks of risperidone pharmacotherapy even when controlling for baseline symptom severity and duration of illness.     

Basal ganglia shrinkage without remarkable hippocampal atrophy in chronic aviremic HIV-positive patients

Conventional magnetic-resonance (MR) imaging is not sensitive enough in depicting subtle neurodegenerative changes that occur during chronic HIV infection with good peripheral viral suppression. The aim of this study was to compare brain volumes in HIV-positive subjects with age- and education-matched healthy controls with regard to influence of aging and immunologic parameters. An overall of 65 subjects (40 HIV-positive and 25 age-, gender-, and education-matched healthy subjects) underwent conventional MR imaging with three-dimensional sequence adequate for volumetric measurements. Volumes of specific brain regions were measured and compared between HIV-positive and healthy subjects using Student t test. Correlations between obtained brain volumes and immunologic parameters were determined using Pearson’s correlation test. Influence of age as a covariate was determined using ANCOVA test. Statistical value was set at p?<?0.05. Volumes of nucleus accumbens (p?=?0.003), putamen (p?=?0.003), and thalamus (p?=?0.046) were significantly decreased in HIV-positive subjects compared with healthy, while volumes of lateral ventricles were significantly increased (p?=?0.043). However, influence of age on atrophy was greater than presence of HIV infection in all observed volumes. Positive correlation of nadir CD4+ count and nucleus accumbens volume was obtained, as well as of therapy with lateral ventricle volumes. Volumes of putamen correlated negatively with duration of therapy. HIV-associated atrophic changes are visible in nucleus accumbens, putamen, and thalamus in neurocognitively asymptomatic stage, while no changes can be observed in the hippocampus, affected by other types of dementias. Under therapy, the influence of physiological aging on HIV-associated atrophy is greater than the presence of HIV infection per se.     

Basal ganglia/limbic striatal and thalamocortical involvement in craving and loss of control in alcoholism

The authors explore the possible role of basal ganglia/limbic striatal and thalamocortical circuits in craving and loss of control in alcohol abuse and dependence. Alcoholics may suffer from a defect in the neuronal systems within basal ganglia/limbic striatal and thalamocortical neuronal circuits, especially within the striatoaccumbal-ventral pallidal portion of this circuit or its dopaminergic nigrotegmental modulation. Alcoholic craving may result from a neurophysiologically driven obsession resulting from overactivity within the fronto-thalamic neuronal loop, and loss of control of alcohol consumption may be a neurophysiologically driven compulsion resulting from further impairment of the basal ganglia/limbic striatal portion of this circuit caused by the acute dopaminergic effects of intoxication.     

A three-dimensional morphometric study of craniofacial shape in schizophrenia

BACKGROUND: Subtle dysmorphogenesis of the craniofacial region constitutes important corroborating evidence of the neurodevelopmental origins of schizophrenia. Advances in facial visualization now allow for three-dimensional anthropometric evaluations of potentially greater discriminatory power in examining the complex geometric relationships of facial topography. METHOD: Sixty-five anthropometrically derived landmarks were identified from three-dimensional facial images collected from 14 patients with schizophrenia and 11 comparison subjects, imaged with a high-resolution, portable laser scanner. RESULTS: Using the Procrustes morphometric approach for shape analysis, the difference in mean shapes was highly significant, with patients exhibiting superoinferior elongation of the face. CONCLUSIONS: The topography of craniofacial anomalies in schizophrenia is not random and points to midline deformation.     

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.     

The telencephalic limbic system and experimental gastric pathology: A review

The effects of lesions and stimulations of the telencephalic limbic system on experimental gastric ulcers and erosions are reviewed. It is concluded that the centromedial amygdala and the anterior cingulate gyrus are facilitatory structures, whereas the medial prefrontal cortex, posterior cingulate cortex, entorhinal cortex, hippocampus and posterolateral amygdala are inhibitory areas during stressful experiences, e.g., immobilization. Both the centromedial amygdala and the anterior cingulate gyrus may be part of an “ancillary” pain system, mediating the affective components of aversive experiences. The inhibitory structures, on the other hand, are assumed to be part of a “preventive” mechanism which is initiated by the selective nuclear binding of glucocorticoids when under stress.     

Basal ganglia calcification and psychosis in mongolism.

An 18-year-old mongoloid girl (trisomy 21) of Asian descent presented two symptoms rarely associated with mongolism (Down's syndrome). (1) Brain stem calcification; the first case diagnosed in vivo in mongolism on computerized axial tomography. (2) Hallucinatory psychotic depression; the first case successfully treated, to full recovery from the psychosis, in a mongoloid child with known brain stem calcification. The psychotic depression was related to moderate environmental stress. While being treated in her parent's home, in their native land, for more than 1 year, the psychosis remained unresponsive to tranquilizers. Following hospital admission in the USA, rapid improvement was obtained within a few weeks through intensive milieu therapy.     

Reduction of brain volume in MS. MRI and pathology findings

Atrophy is one of the hallmarks in multiple sclerosis (MS), especially in the advanced stage. Modern magnetic resonance (MR) techniques can reliably measure brain volume and changes therein. Depending on the technique used, changes of about 1% may be detected. Clinicoradiological studies show good correlation between atrophy measures, both in brain and spinal cord, and clinical measures. The exact relationship between focal MS lesions and global atrophy has yet to be established. Number of lesions early in the disease seems to predict later atrophy. The exact pathomechanism of atrophy in MS probably may be explained by both demyelination and axonal loss--which may occur independently from each other.     

Basal ganglia calcification in Down''s syndrome.

The basal ganglia from 33 patients (all over one year of age) with Down's syndrome were examined pathologically. Forty-five per cent had calcification. Basal ganglia calcification was localised to a constant area of globus pallidus and became more prominent with increased age. Calcification and amyloid degeneration of the adjacent blood vessels were present. The proximity of abnormal blood vessels to basal ganglia calcification suggests a pathogenetic relationship.     

Cerebellar pathology in schizophrenia? A neuronometric study

We have reviewed clinical, neuroradiological, and neuropathological studies of cerebellar pathology in schizophrenia. The literature suggests that a proportion of schizophrenic patients may have possible cerebellar pathology, but the specificity and exact nature of any such pathology are open to question. We conducted a neuronometric study of principal efferent neurons in cerebella from the brains of 23 leucotomized schizophrenic patients, 23 leucotomized controls, and 37 normal controls in the Yakovlev Collection. There were no significant differences among the three groups in Purkinje cell density in anterior vermis, posterior vermis, or hemispheres; size of the Purkinje cell or its nucleus in anterior vermis; or multipolar cell density in dentate nucleus. Various possible explanations for our findings are considered.