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The brainstem reticular formation in schizophrenia
90A
BIOL PSYCHIATRY 1991 ;29:43A-185A
Schizophrenia il
103 SEROTONIN INNERVATION AND RECEPTOR CHANGES IN STRIATUM AND CORTEX OF SCHIZOPHRENICS Jeffrey N. Joyce, Ph.D., Manuel Casanova, M.D., Joel Kleinman, M.D. Departments of P6,chiatry and Pharmacology, Universa2: of Pennsyivania School of Medicine Philadelphia, PA 191~--6141. Quantitative autc,radiography was used to visualize high-affinity uptake sites on serotonin temfinals ([3H]CNMI) and 5-HTla ([aH]8-OHDPAT) alid 5-HT2 (|I~I]LSD) receptors in eight control cases and six schizophrenic cases, Labeling of serotonin terminals was densest in the ventral striamm with distinct patches of heightened binding. There was heightened binding in the limbic striatum of the schizophrenic cases. In cortex, [3HICNM! binding ~as even across all laminae, higher binding was evident in the lateral occipital temporal gyms (OTG) and entorhinal cortex (EC) and lower in hippocampus. In contrast to the swiatum of schizophrenics, ['8]CNMI binding showed decreased densities in outer and middle layers of the cingulate and frontal cortex and smaller reductions within the PHtl. This loss was not evident in the OTG of either hemisphere. [3H]CNMi binding showed decreased densities in the hippocampus of the schizephl'enics in all layers of CA2, CA3. CA4, and DG but not in CA 1. Receptor density was also altered in schizophrenia. The density of 5-1V.': receptor was elevated bvofold in limbic regions of striamva bat 5-HT~a receptor density was not changed. In cortex of control cases, 5-HTI, receptor density showed a complementary pattern to [3HICNMI sites and 5-HT: receptors. The density of 5-HT2 receptors was increa:~d by more than 100% in all cortical regions of both hemispheres, the density of 5-HT1A receptors is increased to a smaller degree. Increased densities of 5-HT~A receptors were noted in most ~gions of hippocampus but the density of 5-HT~, receptors was .or. lhese effects are ~mlikely to be due to neuroleptic useage and may reflect a primary defect in schizophrenia.
104 THE BRAINSTEM RETICULAR FORMATION IN
SCHIZOPHRENIA Craig N. Karson, M.D., Edgar Garcia-Rill, Ph.D., W. Sue Griffin, Ph.D., Robert Mrak, Ph.D., Muhammad Husain, M.D., Manuel Casanova, M.D. Universi~ of Arkansas for Medical Science, Little Rock, AR 72205-7199. Cholinergic cells in the pe.dunculopontine nucleus (PPN) were stained using NADPH diaphorase histochemistry in elderly schizophrenics, normals, and psychiatric controls (n = 5 for each group). The mean of 17,751 _+ 7,214 cholinergic cells in PPN in the patients with schizophrenia exceeded that of either control group by 190% (F~2.m = 6.09, p < 0.015, with the mean value specifically increased for the patients with schizophrenia according to the Scheffe test). Western immunoblot analyses of GFAP frozen brain tissue from younger subjects do not lend support for the notion of schizophrenia as a neurodegenerative process. Furthermore, in the pontine RF there are alterations in beta-tubulin, a protein expressed in development. A diathesis involving maldevelopment of the RF in at least some schizophrenics is proposed.
BIOL PSYCHIATRY 1991 ;29:43A-185A
Schizophrenia il
103 SEROTONIN INNERVATION AND RECEPTOR CHANGES IN STRIATUM AND CORTEX OF SCHIZOPHRENICS Jeffrey N. Joyce, Ph.D., Manuel Casanova, M.D., Joel Kleinman, M.D. Departments of P6,chiatry and Pharmacology, Universa2: of Pennsyivania School of Medicine Philadelphia, PA 191~--6141. Quantitative autc,radiography was used to visualize high-affinity uptake sites on serotonin temfinals ([3H]CNMI) and 5-HTla ([aH]8-OHDPAT) alid 5-HT2 (|I~I]LSD) receptors in eight control cases and six schizophrenic cases, Labeling of serotonin terminals was densest in the ventral striamm with distinct patches of heightened binding. There was heightened binding in the limbic striatum of the schizophrenic cases. In cortex, [3HICNM! binding ~as even across all laminae, higher binding was evident in the lateral occipital temporal gyms (OTG) and entorhinal cortex (EC) and lower in hippocampus. In contrast to the swiatum of schizophrenics, ['8]CNMI binding showed decreased densities in outer and middle layers of the cingulate and frontal cortex and smaller reductions within the PHtl. This loss was not evident in the OTG of either hemisphere. [3H]CNMi binding showed decreased densities in the hippocampus of the schizephl'enics in all layers of CA2, CA3. CA4, and DG but not in CA 1. Receptor density was also altered in schizophrenia. The density of 5-1V.': receptor was elevated bvofold in limbic regions of striamva bat 5-HT~a receptor density was not changed. In cortex of control cases, 5-HTI, receptor density showed a complementary pattern to [3HICNMI sites and 5-HT: receptors. The density of 5-HT2 receptors was increa:~d by more than 100% in all cortical regions of both hemispheres, the density of 5-HT1A receptors is increased to a smaller degree. Increased densities of 5-HT~A receptors were noted in most ~gions of hippocampus but the density of 5-HT~, receptors was .or. lhese effects are ~mlikely to be due to neuroleptic useage and may reflect a primary defect in schizophrenia.
104 THE BRAINSTEM RETICULAR FORMATION IN
SCHIZOPHRENIA Craig N. Karson, M.D., Edgar Garcia-Rill, Ph.D., W. Sue Griffin, Ph.D., Robert Mrak, Ph.D., Muhammad Husain, M.D., Manuel Casanova, M.D. Universi~ of Arkansas for Medical Science, Little Rock, AR 72205-7199. Cholinergic cells in the pe.dunculopontine nucleus (PPN) were stained using NADPH diaphorase histochemistry in elderly schizophrenics, normals, and psychiatric controls (n = 5 for each group). The mean of 17,751 _+ 7,214 cholinergic cells in PPN in the patients with schizophrenia exceeded that of either control group by 190% (F~2.m = 6.09, p < 0.015, with the mean value specifically increased for the patients with schizophrenia according to the Scheffe test). Western immunoblot analyses of GFAP frozen brain tissue from younger subjects do not lend support for the notion of schizophrenia as a neurodegenerative process. Furthermore, in the pontine RF there are alterations in beta-tubulin, a protein expressed in development. A diathesis involving maldevelopment of the RF in at least some schizophrenics is proposed.