Magnetic resonance imaging of the thalamic mediodorsal nucleus and pulvinar in schizophrenia and schizotypal personality disorder

BACKGROUND: The importance of neuronal interactions in development, the cortical dependence of many thalamic nuclei, and the phenomenon of transsynaptic degeneration suggest possible abnormalities in thalamic nuclei with connections to other brain regions implicated in schizophrenia. Because frontal and temporal lobe volumes are diminished in schizophrenia, volume loss could characterize their primary thalamic relay nuclei (mediodorsal nucleus [MDN] and pulvinar). METHODS: Tracers delineated the thalamus, MDN, and pulvinar on contiguous 1.2-mm magnetic resonance images in 12 schizophrenic patients, 12 with schizotypal personality disorder (SPD), and 12 normal control subjects. The MDN and pulvinar were rendered visible by means of a Sobel intensity-gradient filter. RESULTS: Pixel overlap for delineation of all structures by independent tracers was at least 80%; intraclass correlations were r = 0.78 for MDN and r = 0.83 for pulvinar. Pulvinar volume was smaller in schizophrenic (1.22 +/- 0.24 cm(3)) and SPD (1.20 +/- 0.23 cm(3)) patients than controls (1.37 +/- 0.25 cm(3)). Differences for MDN were not statistically significant; however, when expressed as percentage of total brain volume, pulvinar and MDN together were reduced in SPD (0.14%) and schizophrenic (0.15%) patients vs controls (0.16%). Reductions were more prominent in the left hemisphere, with MDN reduced only in the schizophrenic group, and pulvinar in both patient groups. Total thalamic volume did not differ among the 3 groups. CONCLUSIONS: Measurement of MDN and pulvinar in magnetic resonance images is feasible and reproducible. Schizophrenic and SPD patients have volume reduction in the pulvinar, but only schizophrenic patients show reduction relative to brain volume in MDN.     

N-acetylaspartate reductions in the mediodorsal and anterior thalamus in men with schizophrenia verified by tissue volume corrected proton MRSI

OBJECTIVE: Deficits in the mediodorsal and anterior nuclei of the thalamus may contribute to the psychopathological symptoms of schizophrenia. These thalamic nuclei have been found to be abnormal in schizophrenia and have close connections with other brain structures implicated in the disorder. We therefore examined schizophrenia-related alterations in brain metabolite levels specifically in the mediodorsal and anterior thalamic subregions. METHOD: We used in vivo proton magnetic resonance spectroscopic imaging ((1)H MRSI) to measure N-acetylaspartate (NAA), choline-containing compounds (Cho), and creatine+phosphocreatine (Cr) in the mediodorsal and anterior thalamus in 22 male patients with schizophrenia and 22 male controls. Magnetic resonance imaging (MRI) tissue segmentation and thalamic volume mask techniques were performed to distinguish the thalamus, extrathalamic gray and white matter, and CSF within the spectroscopic voxels. RESULTS: Compared to healthy subjects, patients with schizophrenia had significantly lower NAA in the mediodorsal and anterior thalamus bilaterally. No significant differences in Cho or Cr levels were seen. NAA was significantly higher in the left thalamus relative to the right in both groups. We found a strong negative correlation between left thalamic NAA and duration of illness, even after partialling out the effect of age. Tissue segmentation and thalamic volume mask techniques detected no group or lateralized differences in tissue type or CSF percentages, demonstrating that the metabolite reductions were not an artifact of spectroscopic voxel heterogeneity. CONCLUSIONS: These findings suggest diminished function and/or structure in the mediodorsal and anterior thalamus in male patients with schizophrenia and support earlier research demonstrating schizophrenia-related abnormalities in the thalamus and its circuitry.     

Cognitive and brain function in schizotypal personality disorder

Schizotypal personality disorder, a diagnosis defined partially in terms of a genetic relatedness to schizophrenia, has begun to receive extensive investigative study. While the exact etiologic relationship between schizotypal personality disorder and schizophrenia remains to be determined, three models have been considered: (1) the two may be distinct disorders, (2) they may be essentially identical disorders but expressed with different degrees of severity, or (3) they may be related disorders with a partially overlapping etiology that might account for the many similarities yet the lack of psychosis or severe deficits in schizotypal individuals. Some of the recent research in the structural and functional neuroanatomy, neurochemistry, cognitive function, and pharmacology of schizotypal personality disorder is reviewed with citation of the most recent findings from our laboratory and others. Both schizotypal and schizophrenic subjects appear to show abnormalities in temporal lobe volume, but schizotypal subjects do not appear to show the volumetric decreases in frontal cortex that schizophrenic patients evidence. Abnormalities in thalamic nuclei parallel these findings-the pulvinar, which projects to temporal association and sensory cortices, is reduced in both disorders, but the mediodorsal nucleus, which projects extensively to the frontal cortex, is reduced in schizophrenic patients but not in schizotypal patients. Functional imaging studies suggest that there may be abnormalities in frontal activation in both disorders, but that schizotypal individuals can recruit alternative regions to accomplish tasks requiring frontal lobe activation that may help compensate. Imaging studies of the subcortex including FDG/PET imaging of metabolic activity during a verbal learning task, SPECT imaging studies which measure binding of IBZM and its displacement following amphetamine administration, and plasma HVA determinations following 2-deoxyglucose administration all suggest the possibility of relatively reduced dopaminergic subcortical activity in schizotypal individuals compared to schizophrenic patients. Cognitive function is also impaired in the areas of working memory, verbal learning, and attention in schizotypal patients, as in schizophrenic patients, and they may be particularly susceptible to cognitive tasks with high context dependence, as in schizophrenia. Preliminary trials of catecholaminergic agents suggest that these agents may be able to improve these impaired cognitive functions.     

Lower concentration of thalamic n-acetylaspartate in patients with schizophrenia: a replication study

OBJECTIVE: Using proton magnetic resonance spectroscopic imaging, the authors measured thalamic N-acetylaspartate (NAA) concentrations in patients with schizophrenia. METHOD: The study included 15 schizophrenic patients on a stable medication regimen and 15 age-matched healthy comparison subjects. Concentrations of NAA, creatine plus phosphocreatine, and choline-containing compounds in bilateral thalamic regions were determined. RESULTS: Previous findings of lower NAA concentration in the left and right mediodorsal region of the thalamus and significant correlations between left and right thalamic NAA measures in patients with schizophrenia were corroborated. Furthermore, the concentrations of choline-containing compounds were significantly lower in the schizophrenic patients. No group differences in creatine plus phosphocreatine were found. CONCLUSIONS: There is strong evidence for neuronal dysfunction or loss in the mediodorsal region of the thalamus in patients with schizophrenia.     

Postmortem assessment of thalamic nuclear volumes in subjects with schizophrenia.

OBJECTIVE: The authors assessed schizophrenia-associated changes in volume and neuronal number in the mediodorsal nucleus and the pulvinar regions of the thalamus. METHOD: Right-hemisphere thalami obtained at autopsy from 14 schizophrenic and eight comparison subjects were examined. Computer-assisted morphometric techniques were used to determine volumes for the mediodorsal nucleus, pulvinar, and the anterior and centromedian nuclei as well as the parvocellular, magnocellular, and caudodorsal subdivisions of the mediodorsal nucleus. Neurons in the mediodorsal nucleus and pulvinar were counted and measured by using a stereology-based sampling strategy. RESULTS: Four schizophrenic and three comparison subjects had Alzheimer's type pathology, leaving 10 schizophrenic and five comparison subjects without other documented neuropathological changes. In analyses that included either the full cohort or only the subjects without Alzheimer's type pathology, volumes of the mediodorsal nucleus and pulvinar, but not the anterior or centromedian nuclei, were significantly smaller in the schizophrenic subjects. For the schizophrenic subjects, neuronal number in the mediodorsal nucleus, parvocellular subdivision, and pulvinar was significantly lower, and neuronal size in the mediodorsal nucleus, caudodorsal subdivision, and pulvinar was significantly smaller. CONCLUSIONS: Schizophrenia is associated with volume and neuronal changes in the mediodorsal nucleus and pulvinar, the major association nuclei of the thalamus, whereas total thalamic volume and the volumes of anterior and centromedian nuclei were not significantly altered.     

Abnormalities of thalamic volume and shape in schizophrenia

OBJECTIVE: Postmortem and neuroimaging studies of schizophrenia have reported deficits in the volume of the thalamus and its component nuclei. However, the pattern of shape change associated with such volume loss has not been investigated. In this study, alterations in thalamic volume, shape, and symmetry were compared in subjects with and without schizophrenia. METHOD: T(1)-weighted magnetic resonance scans were collected in 52 schizophrenia and 65 comparison subjects matched for age, gender, race, and parental socioeconomic status. High-dimensional (large-deformation) brain mapping was used to assess thalamic morphology. RESULTS: Significant differences in thalamic volume, deformities of thalamic shape at the anterior and posterior extremes of the structure, and a significant exaggeration of thalamic asymmetry (i.e., left smaller than right) were found in the schizophrenia subjects. After covarying for total cerebral volume, the difference in thalamic volume became insignificant. When information about thalamic shape was combined with previously collected information about hippocampal shape, the discrimination between schizophrenia patients and comparison subjects was improved. CONCLUSIONS: Thalamic volume was smaller than normal in schizophrenia patients, but only proportionate to reductions in reduced total cerebral volume. The presence of changes in thalamic shape and asymmetry suggest greater pathologic involvement of individual nuclei at its anterior and posterior extremes of the thalamic complex.     

Volumetric magnetic resonance imaging study of the anterior cingulate gyrus in schizotypal disorder

Lack of normal structural asymmetry of the anterior cingulate gyrus (ACG) in patients with schizophrenia has been reported in our previous study. However, to our knowledge, no morphological studies of the brain have examined changes in ACG volume in patients with schizotypal features. We investigated the volume of the gray matter and the white matter of the ACG by three-dimensional magnetic resonance imaging (MRI) in 24 patients who met the ICD-10 criteria for schizotypal disorder (12 males, 12 females) in comparison with 48 age- and gender-matched healthy control subjects (24 males, 24 females) and 40 patients with schizophrenia (20 males, 20 females). As we reported previously, right ACG gray matter volume was significantly reduced in the female patients with schizophrenia compared with the female controls. On the other hand, the gray and white matter volume of the ACG in the patients with schizotypal disorder did not differ significantly from the values in the healthy controls or the patients with schizophrenia. However, the female patients with schizotypal disorder showed a lack of right-greater-than-left asymmetry of the ACG gray and white matter found in the female controls. These results suggest that both schizotypal and schizophrenic subjects share, at least in part, the same cerebral asymmetry abnormalities. Received: 28 May 2002 / Accepted: 30 October 2002 Correspondence to T. Takahashi     

Abnormal glucose metabolism in the mediodorsal nucleus of the thalamus in schizophrenia

OBJECTIVE: Three thalamic nuclei--the mediodorsal nucleus, pulvinar, and centromedian nucleus--each have unique reciprocal circuitry with cortical and subcortical areas known to be affected in schizophrenia. To determine if the disorder is also associated with dysfunction in the mediodorsal nucleus, pulvinar, and centromedian nucleus, relative glucose metabolism in these regions was measured in a large group of unmedicated patients with schizophrenia. METHOD: [18F]-deoxyglucose positron emission tomography (PET) and matching T1-weighted magnetic resonance imaging (MRI) scans were obtained for 41 unmedicated patients with schizophrenia and 60 age- and sex-matched healthy subjects. The PET and MRI images for each subject were coregistered, and the whole thalamus, mediodorsal nucleus, pulvinar, and centromedian nucleus were traced on the MRI image. Relative glucose metabolism in these regions was assessed. RESULTS: Patients with schizophrenia showed significantly lower relative glucose metabolism in the mediodorsal nucleus and the centromedian nucleus and significantly higher relative glucose metabolism in the pulvinar, compared with the healthy subjects. Lower relative glucose metabolism in the total thalamus, mediodorsal nucleus, and pulvinar was associated with greater overall clinical symptoms as measured by the Brief Psychiatric Rating Scale. Lower relative glucose metabolism in the pulvinar was associated with more hallucinations and more positive symptoms, while lower relative glucose metabolism in the mediodorsal nucleus was associated with more negative symptoms. CONCLUSIONS: The findings suggest that patients with schizophrenia exhibit dysfunction in thalamic subdivisions with distinct cortical connections and that these thalamic subdivisions have specific associations with clinical symptoms.     

Reduced number of mediodorsal and anterior thalamic neurons in schizophrenia.

BACKGROUND: The thalamus is a brain region of interest in the study of schizophrenia because it provides critical input to brain regions such as the prefrontal, cingulate, and temporal cortices, where abnormalities have been repeatedly observed in patients with schizophrenia. Postmortem anatomic studies have rarely investigated the thalamus in this population. METHODS: Postmortem tissue was obtained from the left hemisphere of eight male schizophrenic patients and eight male age-matched control subjects. The optical dissector stereologic procedure was used to count neurons in the mediodorsal (MD) and anteroventral/anteromedial (AV/AM) nuclei of the thalamus. RESULTS: The number of neurons and volume of the MD were significantly reduced by 35% and 24%, respectively. The MD cell number reduction was a consistent finding; every control subject had more and every schizophrenic subject had fewer than 3.5 million neurons. Neuron number was also significantly reduced (16%) in the AV/AM nuclei. CONCLUSIONS: The present data indicate that schizophrenia is associated with robust reductions in nerve cell numbers in nuclei that communicate with the prefrontal cortex and limbic system. These thalamic anatomic deficits may be responsible, in part, for previous reports of such prefrontal cortical abnormalities as reduced synaptic density, reduced volume, and metabolic hypofunction.     

Eye tracking impairment in clinically identified patients with schizotypal personality disorder

Eye tracking accuracy, which has been found to be impaired in schizophrenic patients and their relatives, was assessed in 26 patients with schizotypal personality disorder, 17 control subjects with other non-schizophrenia-related personality disorders, 29 normal control subjects, and 44 schizophrenic patients. Both schizotypal and schizophrenic patients, but not control subjects with other personality disorders, demonstrated significantly more impaired tracking than the normal control subjects. These results suggest that patients with clinically defined schizotypal personality disorder may be biologically related to schizophrenic patients as part of a spectrum of schizophrenia-related disorders.     

Cingulate gyrus volume and metabolism in the schizophrenia spectrum

BACKGROUND: The cingulate gyrus, which is involved in affect, attention, memory and higher executive functions, has been implicated as a dysfunctional region in schizophrenia. Postmortem studies report cytoarchitectural changes in the anterior cingulate gyrus (ACG) and functioning imaging studies show correlations between the degree of hypometabolism of the anterior cingulate and clinical symptoms in schizophrenia. METHODS: Unmedicated patients with schizophrenia (n=27) and schizotypal personality disorder (SPD) (n=13), as well as sex- and age-matched control subjects (n=32), were studied with (18)F-fluorodeoxyglucose positron emission tomography (PET) scans and magnetic resonance imaging (MRI). As a control over mental activity, all subjects performed a verbal working memory task during the PET protocol. The cingulate gyrus was first outlined on the MRI scans and, after coregistration, the coordinates were applied to the PET scans to yield a three-dimensional metabolic map of the cingulate gyrus for each subject. A statistical resampling method was used to analyze the metabolic differences between groups. RESULTS: Compared with controls, patients with schizophrenia had lower relative glucose metabolic rates in the left anterior cingulate and the right posterior cingulate gyrus (PCG) assessed by 3-D significance probability mapping. SPD patients had higher glucose metabolic rates (GMRs) in the left posterior cingulate than did controls. Furthermore, volumetric measurement with MRI showed the left anterior cingulate and Brodmann area 24' to be smaller in schizophrenic patients than controls. CONCLUSIONS: Compared with controls, patients with schizophrenia have metabolic and volumetric reductions in a cingulate gyrus area that is related to higher executive functions. Schizotypal patients rely more on sensory association areas to perform a cognitive task than do controls and seem to be a group that is partially distinct in its physiological and functional characteristics.     

Modulation of the startle response and startle laterality in relatives of schizophrenic patients and in subjects with schizotypal personality disorder: evidence of inhibitory deficits

OBJECTIVE: Patients with schizophrenia spectrum disorders have been shown to have deficits in sensorimotor gating as assessed by prepulse inhibition of the startle response. The authors hypothesized that nonschizophrenic relatives of patients with schizophrenia would also have prepulse inhibition deficits, thereby reflecting a genetically transmitted susceptibility to sensorimotor gating deficits. METHOD: Twenty-five comparison subjects, 23 patients with schizophrenia, 34 relatives of the schizophrenic patients, and 11 subjects with schizotypal personality disorder were assessed in an acoustic startle paradigm. The eye-blink component of the startle response was assessed bilaterally by using electromyographic recordings of orbicularis oculi. RESULTS: The patients with schizophrenia, their relatives, and subjects with schizotypal personality disorder all had reduced prepulse inhibition relative to comparison subjects, and these deficits were more evident in measures of right eye-blink prepulse inhibition. Comparison subjects demonstrated greater right versus left eye-blink prepulse inhibition, whereas the probands, their relatives, and subjects with schizotypal personality disorder showed less asymmetry of prepulse inhibition. CONCLUSIONS: These data suggest a genetically transmitted deficit in prepulse inhibition (sensorimotor gating) in patients with schizophrenia spectrum disorders, including subjects with schizotypal personality disorder and relatives of patients with schizophrenia.     

Fiber tracking of white matter integrity connecting the mediodorsal nucleus of the thalamus and the prefrontal cortex in schizophrenia: A diffusion tensor imaging study

The goal of this study was to detect abnormalities in white matter integrity connecting the mediodorsal nucleus of the thalamus and the prefrontal cortex using fiber-tracking technique. Diffusion tensor imaging was acquired in 20 patients with schizophrenia and 20 normal comparison subjects. Fiber tracking was performed on the anterior thalamic peduncle, and the tractography was used to determine the cross-sectional area, mean fractional anisotropy, and standard deviation of fractional anisotropy for every step separately in the right and left hemispheres. Compared with normal subjects, patients showed a significant reduction in the cross-sectional area of the left anterior thalamic peduncle. There were no significant differences for the mean fractional anisotropy bilaterally between the two groups, but significant differences for the standard deviation of fractional anisotropy in both hemispheres. Reduction in the cross-sectional area of the left anterior thalamic peduncle suggests the presence of the failure of left-hemisphere lateralization. In schizophrenic patients a significant increase of the standard deviation of fractional anisotropy raise the possibility that the inhomogeneity of white matter integrity, which is densely or sparsely distributed by site. These findings might provide further evidence for disruption of white matter integrity between the thalamus and the prefrontal cortex in schizophrenia.     

Pathology of the thalamus and schizophrenia--an overview

Since the beginning of the 20 (th) century, the thalamus was regarded as a brain region which may be involved in the pathogenesis of schizophrenia. Distinct thalamic nuclei were morphologically analyzed with qualitative methods with an emphasis on the mediodorsal nucleus. However, the reported results were inconsistent. After the introduction of quantitative neuroanatomical methods, it became obvious that the volume and cell reductions are not only present in the association nuclei, but also in the limbic (N. anteroventralis) and motor thalamic nuclei (N. ventrolateralis posterior). The involvement of distinct thalamic nuclei is supported by structural MRI studies which have shown a moderate but significant volume reduction of the whole thalamus in this disease. The majority of fMRI and PET studies reported a reduction of the metabolic activity or blood flow in the thalamus in patients with schizophrenia. The similarity between the structural changes in animal models of thalamic plasticity and the structural thalamic alterations in schizophrenia suggest an involvement of neuroplasticity mechanisms in the pathogenesis of these alterations. Post-mortem studies and In-vivo receptor studies suggest altered glutamatergic, dopaminergic and membrane-associated mechanisms within thalamic pathology in schizophrenia. On the psychopathological level, there is a similarity between some of the psychic manifestations of thalamic lesions and symptoms of the schizophrenic disease. There are also reports on volume reduction of the whole thalamus in first-episode neuroleptic-free patients. It appears unlikely that the neuroleptic medication plays an etiological important role, since no significant correlations were found between the volume and cell reductions and the neuroleptic treatment period. The reviewed data suggest that distinct thalamic nuclei and therefore distinct neuronal circuits are involved in the pathogenesis of schizophrenia.     

Volumetric MRI study of the short and long insular cortices in schizophrenia spectrum disorders

We have previously reported volume reductions of the insular cortex in schizophrenia, but it is still not clear whether insular cortex volume loss preferentially involves the anterior (short insular cortex) or posterior (long insular cortex) portion. On the other hand, no volumetric studies of the brain have examined changes in insular cortex volume in subjects with schizotypal features. In this study, we separately investigated the volumes of the short and long insular cortex portions using magnetic resonance imaging in 37 schizotypal disorder patients (24 males, 13 females), 62 schizophrenia patients (32 males, 30 females), and 69 healthy controls (35 males, 34 females). While the volumes of the short and long insular cortex were significantly reduced in schizophrenia patients compared with schizotypal disorder patients and control subjects, there was no difference between schizotypal disorder patients and control subjects. These results suggest that the volume reduction of the insular cortex may be specific to overt schizophrenia without topographically specific localization.     

Smaller left Heschl's gyrus volume in patients with schizotypal personality disorder

OBJECTIVE: Individuals with schizophrenia spectrum disorders evince similar genetic, neurotransmitter, neuropsychological, electrophysiological, and structural abnormalities. Magnetic resonance imaging (MRI) studies have shown smaller gray matter volume in patients with schizotypal personality disorder than in matched comparison subjects in the left superior temporal gyrus, an area important for language processing. In a further exploration, the authors studied two components of the superior temporal gyrus: Heschl's gyrus and the planum temporale. METHOD: MRI scans were acquired from 21 male, neuroleptic-naive subjects recruited from the community who met DSM-IV criteria for schizotypal personality disorder and 22 male comparison subjects similar in age. Eighteen of the 21 subjects with schizotypal personality disorder had additional comorbid, nonpsychotic diagnoses. The superior temporal gyrus was manually delineated on coronal images with subsequent identification of Heschl's gyrus and the planum temporale. Exploratory correlations between region of interest volumes and neuropsychological measures were also performed. RESULTS: Left Heschl's gyrus gray matter volume was 21% smaller in the schizotypal personality disorder subjects than in the comparison subjects, a difference that was not associated with the presence of comorbid axis I disorders. There were no between-group volume differences in right Heschl's gyrus or in the right or left planum temporale. Exploratory analyses also showed a correlation between poor logical memory and smaller left Heschl's gyrus volume. CONCLUSIONS: Smaller left Heschl's gyrus gray matter volume in subjects with schizotypal personality disorder may help to explain the previously reported abnormality in the left superior temporal gyrus and may be a vulnerability marker for schizophrenia spectrum disorders.     

Temporal lobe gray matter in schizophrenia spectrum: a volumetric MRI study of the fusiform gyrus, parahippocampal gyrus, and middle and inferior temporal gyri

Although several brain morphologic studies have suggested abnormalities in the temporal regions to be a common indicator of vulnerability for the schizophrenia spectrum, less attention has been paid to temporal lobe structures other than the superior temporal gyrus or the medial temporal region. In this study, we investigated the volume of gray matter in the fusiform gyrus, the parahippocampal gyrus, the middle temporal gyrus, and the inferior temporal gyrus using magnetic resonance imaging in 39 schizotypal disorder patients, 65 schizophrenia patients, and 72 age and gender matched healthy control subjects. The anterior fusiform gyrus was significantly smaller in the schizophrenia patients than the control subjects but not in the schizotypal disorder patients, while the volume reduction of the posterior fusiform gyrus was common to both disorders. Volumes for the middle and inferior temporal gyri or the parahippocampal gyrus did not differ between groups. These findings suggest that abnormalities in the posterior region of the fusiform gyrus are, as have been suggested for the superior temporal gyrus or the amygdala/hippocampus, prominent among the temporal lobe structures as a common morphologic substrate for the schizophrenia spectrum, whereas more widespread alterations involving the anterior region might be associated with the development of full-blown schizophrenia.     

Magnetic resonance imaging of mediodorsal, pulvinar, and centromedian nuclei of the thalamus in patients with schizophrenia

BACKGROUND: Postmortem and magnetic resonance imaging (MRI) data have suggested volume reductions in the mediodorsal (MDN) and pulvinar nuclei (PUL) of the thalamus. The centromedian nucleus (CMN), important in attention and arousal, has not been previously studied with MRI. METHODS: A sample of 41 patients with schizophrenia (32 men and 9 women) and 60 healthy volunteers (45 men and 15 women) underwent assessment with high-resolution 1.2-mm thick anatomical MRI. Images were differentiated to enhance the edges and outline of the whole thalamus, and the MDN, PUL, and CMN were outlined on all slices by a tracer masked to diagnostic status. RESULTS: Significantly smaller volumes of the MDN and PUL were found in patients with schizophrenia compared with controls. Volume relative to brain size was reduced in all 3 nuclei; differences in relative reduction did not differ among the nuclei. The remainder of the thalamic volume (whole thalamus minus the volume of the 3 delineated nuclei) was not different between schizophrenic patients and controls, indicating that the volume reduction was specific to these nuclei. Volume relative to brain size was reduced in all 3 nuclei and remained significant when only patients who had never been exposed to neuroleptic medication (n = 15) were considered. For the MDN, women had larger relative volumes than men among controls, but men had larger volumes than women among schizophrenic patients. CONCLUSIONS: Three association regions of the thalamus that have reciprocal connectivity to schizophrenia-associated regions of the cortex have significantly smaller volumes on MRI in patients with schizophrenia.     

A magnetic resonance imaging study of thalamic area in adolescent patients with either schizophrenia or bipolar disorder as compared to healthy controls

The purpose of this study was to compare thalamic size in adolescent patients with either schizophrenia or bipolar disorder and healthy controls. T2-weighted axial magnetic resonance images were used to manually define the area of the thalamus for 20 schizophrenia patients, 15 bipolar patients and 16 normal control subjects, all of whom were adolescents. Two orthogonal planned contrasts were tested: Contrast 1, patients with schizophrenia vs. patients with bipolar disorder; and Contrast 2, both patient groups taken as a single group compared to controls. Contrast 1 was not statistically significant for right or left thalamic area. Contrast 2 was statistically significant and indicated reductions in thalamic area in the patients as compared to controls. The same pattern of results emerged after adjustment for total brain volume. Our results indicate that thalamic abnormalities reported in adult schizophrenic and bipolar patients are also observed in adolescent patients. Our findings also add to the evidence implicating the thalamus in the pathophysiology of schizophrenia and bipolar disorder.     

3H-spiperone binding to lymphocytes in neuroleptic-naive-schizophrenia and the effect of neuroleptic treatment

The aim of this study was to determine whether spiperone binding to lymphocytes could serve as a biological marker of susceptibility to schizophrenia and schizophrenic spectrum disorders or as a measure of response to neuroleptic treatment. Lymphocyte spiperone binding parameters (Bmax, KD) were assessed in 13 patients with schizophrenia and 4 patients with schizotypal personality disorder, all neuroleptic naive, and in 19 age- and sex-matched control subjects. A repeated determination was carried out in 11 of the schizophrenic subjects after several months of neuroleptic treatment. In addition, the binding characteristics of 12 of the schizophrenic/schizotypal patients were compared with those of 13 healthy family members and normal unrelated controls. No significant differences were detected between the schizophrenic subjects and controls before or after neuroleptic treatment or between the patients and their non-affected family members and controls.