Quantitative changes in mesial temporal volume, regional cerebral blood flow, and cognition in Alzheimer's disease.

Twenty-six patients with moderately severe Alzheimer's disease (AD) and 16 normal control subjects were studied using either quantitative magnetic resonance imaging (MRI) measures of mesial temporal atrophy (15 patients with AD and 16 normal control subjects) and/or quantitative radioactive iodine 123-N-isopropyl-iodoamphetamine single-photon emission computed tomography (SPECT) assessment of regional cerebral blood flow (20 patients with AD and eight normal control subjects). Nine individuals with AD and eight normal control subjects underwent both structural and functional imaging. On MRI, patients and controls were best discriminated using left amygdala and entorhinal cortex volumes, and on SPECT they were best discriminated by relative left temporoparietal cortex blood flow. Combining these MRI and SPECT measures yielded 100% discrimination. Relative left temporoparietal SPECT regional cerebral blood flow and left superior temporal gyral MRI volume correlated best with severity of cognitive deficit in patients with AD. Mesial temporal MRI atrophy exceeded generalized cerebral shrinkage. Both SPECT and MRI regional changes accorded with areas known to be affected by AD neuropathology.

Cortical gyral anatomy and gross brain dimensions in monozygotic twins discordant for schizophrenia.

BACKGROUND: This study combines recent advances in three-dimensional neuroimaging technology and the genetic constraints inherent in monozygotic (MZ) twins to examine surface gyral anatomy and gross brain dimensions in monozygotic twin pairs discordant for schizophrenia. Results are presented and evaluated with respect to prior observations of cortical anomalies in schizophrenia and the hypothesis that schizophrenia involves cortical maldevelopment. DESIGN: Three-dimensional renderings from volumetric magnetic resonance imaging (MRI) data of 13 MZ twin pairs discordant for schizophrenia and nine normal MZ pairs were studied. Qualitative assessments of left and right hemisphere surfaces were made by raters blind to diagnosis in an effect to identify developmental gyral abnormalities such as vertical temporal gyri or microgyria. Measurement of brain hemisphere length, area, and volume were also determined. These data were compared within discordant MZ schizophrenia pairs, within normal MZ pairs, and between matched unaffected discordant and normal MZ groups. RESULTS: Raters did not identify qualitatively abnormal gyri in the schizophrenia subjects to enable distinction from their unaffected co-twins or from normal controls. Brain hemisphere volumes in the affected DS were significantly smaller bilaterally by about 3% compared with their unaffected DS co-twins, who did not differ from normals on this measure. CONCLUSIONS: We were unable to confirm previous reports of vertical gyri or localized gyral thinning as being characteristic of the cortical anatomy of schizophrenia. If cortical maldevelopment is associated with schizophrenia it does not appear to disrupt gross gyral pattern formation in these ways. The quantitative results of diminished hemisphere volume and length in the twins with schizophrenia are consistent with previous reports of smaller brain size in schizophrenia. Our results suggest that this is a bilateral phenomenon that may be dependent, at least in part, on environmental factors.

A volumetric magnetic resonance imaging study of monozygotic twins discordant for bipolar disorder.

Six monozygotic (MZ) twin pairs discordant for bipolar disorder were compared with normal MZ twins with magnetic resonance imaging (MRI) on volumes of basal ganglia (BG), amygdala-hippocampus (AH), and cerebral hemisphere. Caudate nuclei were larger in both affected and unaffected bipolar twins than in normal MZ twins. The right hippocampus was smaller in the sick vs. well bipolar twins. The hippocampus was also less asymmetric in the affected bipolar twins than in the well cotwins and the normal MZ twins. These anatomical structures continue to be of interest in bipolar disorder research.

Cingulate gyrus in schizophrenic patients and normal volunteers.

Comparable magnetic resonance imaging (MRI) sections of right and left anterior and posterior cingulate gyrus were measured blindly with a method developed by the authors in 14 patients with schizophrenia (by DSM-III-R criteria) and 14 normal volunteers individually matched to the patients for age, sex, education, and parental socioeconomic status. Interrater reliability met or exceeded 0.92 (k) on all cingulate structures measured. Brain volume in the two groups differed by 2% (normal > schizophrenia), but the difference was not significant. All cingulate gyri measures were nonsignificantly smaller in the patient group by 3-5%. There was an inverse correlation between left anterior cingulate size and severity of hallucinations that was, however, not significant after Bonferroni correction. Lateral asymmetry of the cingulate regions measured was the same in both groups, with the left being nonsignificantly smaller than the right for all regions. We demonstrate a reliable method, unreported thus far in the literature, to measure the cingulate gyrus on MRI; the results suggest that left cingulate gyrus size may be inversely related to severity of hallucinations in schizophrenia.

Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and control brains.

INTRODUCTION: Previous postmortem studies of glutamate receptors and uptake sites have shown decreased D-aspartate (D-Asp) (a marker for the high affinity glutamate uptake site) and elevated (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate (MK-801) binding in the putamen in schizophrenia and elevated alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor binding in the caudate nucleus of schizophrenics who committed suicide. The relative effects of schizophrenia, suicide, and neuroleptic treatment in these findings is unclear. This study further explores binding to glutamate receptors (NMDA, kainic acid, and AMPA) and uptake sites in postmortem striatal structures in schizophrenics relative to three control groups (normal controls, neuroleptic-treated controls, and nonpsychotic suicides). METHODS: We compared the binding densities of tritium-labeled ligands 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), kainic acid (KA), MK-801, and D-Asp, which target the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), KA, and N-methyl-D-aspartic acid (NMDA) ionotropic receptor sites and the glutamate uptake site, respectively, in postmortem striatal/accumbens tissue from six DSM-III-R schizophrenics, eight normal controls, eight neuroleptic-treated controls, and eight suicide victims using standard receptor autoradiographic methods. RESULTS: Binding of [3H] CNQX (AMPA receptors) was significantly different among the four groups across the subdivisions of the striatum: caudate, putamen, and nucleus accumbens (ANOVA P = .0007, .002, and .004, respectively). The schizophrenia group had higher mean CNQX binding in the caudate nucleus than normal (P = .005) and neuroleptic controls (P = .006) but not suicides (P = .6), who were also higher than normals and neuroleptic-treated controls (P = .05). The binding densities of tritiated MK-801, KA, and D-Asp were not significantly different among the four groups of subjects in any of the striatal regions examined. CONCLUSIONS: The data suggest there may be an increased density of AMPA receptor sites in the caudate nucleus in schizophrenia that is not apparently due to neuroleptic treatment. A similar increase was also seen the suicide group. Although these data do not confirm previous reports of an increase in [3H]MK-801 or a decrease in [3H]D-Asp binding in the basal ganglia in schizophrenia, the increased caudate AMPA binding observed here could reflect decreased cortical glutamatergic innervation of the caudate. Its implication for suicide is unclear.