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October 1995, Vol 52, No. 10 >
Article | October 1995

Neocortical Abnormalities in Schizophrenia

Stanley J. Watson, PhD, MD; James H. Meador-Woodruff, MD
Arch Gen Psychiatry. 1995;52(10):819-820. doi:10.1001/archpsyc.1995.03950220029006
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The HISTORY of the study of brains of individuals with schizophrenia is replete with novel, fragmentary, and even occasionally enticing findings, if any positive results were obtained at all. Most of these findings have proved to be elusive when replications have been attempted. In fact, the most consistent finding in studies of the brains of persons with schizophrenia is that they are usually not distinguishable from the brains of normal individuals. However, over the last 15

See also page 805 years, a literature has been slowly accumulating in two scientific arenas, structural brain imaging and functional brain imaging. Studies of the structure of schizophrenic brains (via computed tomographic or magnetic resonance imaging scans) have produced a subtle but increasingly reliable set of observations. Such studies have often pointed toward ventricular enlargement, sulcal widening, and cortical atrophy, with occasional suggestions of left temporal lobe, frontal lobe, and thalamic atrophy.1-4 Functional

REFERENCES

1 +
Shenton ME, Kikinis R, Jolesz FA, Pollak SD, LeMay M, Wible CG, Hokama H, Martin J, Metcalf D, Coleman M, McCarley RW.  Abnormalities of the left temporal lobe and thought disorder in schizophrenia: a quantitative magnetic resonance imaging study . N Engl J Med . 1992;;327:604-612.
2 +
Breier A, Buchanan RW, Elkashef A, Munson RC, Kirkpatrick B, Gellad F.  Brain morphology and schizophrenia: a magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures . Arch Gen Psychiatry . 1992;;49:921-926.
3 +
Jernigan TL, Zisook S, Heaton RK, Moranville JT, Hesselink J, Braff DL.  Magnetic resonance imaging abnormalities in lenticular nuclei and cerebral cortex in schizophrenia . Arch Gen Psychiatry . 1991;;48:881-890.
4 +
Harvey I, Ron MA, DuBoulay G, Wicks D, Lewis SW, Murray RM.  Reduction of cortical volume in schizophrenia on magnetic resonance imaging . Psychol Med . 1993;;23:591-604.
5 +
Berman KF, IIIowsky BP, Weinberger DR.  Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia, IV: further evidence for regional and behavioral specificity . Arch Gen Psychiatry . 1988;;45:616-622.
6 +
Weinberger DR, Berman KF, IIIowsky BP.  Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia, III: a new cohort and evidence for a monoaminergic mechanism . Arch Gen Psychiatry . 1988;;45:609-615.
7 +
Tamminga CA, Thaker GK, Buchanan R, Kirkpatrick B, Alphs LD, Chase TN, Carpenter WT.  Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome . Arch Gen Psychiatry . 1992;;49:522-530.
8 +
Friston KJ, Liddle PF, Frith CD, Hirsch SR, Frackowiak RSJ.  The left medial temporal region and schizophrenia: a PET study . Brain . 1992;;115:367-382.
9 +
Pettegrew JW, Keshavan MS, Panchalingam K, Strychor S, Kaplan DB, Tretta MG, Allen M.  Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive schizophrenics: a pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy . Arch Gen Psychiatry . 1991;;48:563-568.
10 +
Fugimoto T, Nakano T, Hokazono Y, Asakura T, Tsuji T.  Study of chronic schizophrenics using 31P magnetic resonance chemical shift imaging . Acta Psychiatr Scand . 1992;;86:455-462.
11 +
Selemon LD, Rajkowska G, Goldman-Rakic PS.  Abnormally high neuronal density in the schizophrenic cortex: a morphometric analysis of prefrontal area 9 and occipital area 17 . Arch Gen Psychiatry . 1995;;52:805-818.
12 +
Feinberg I.  Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiatr Res . 1982-83;;17:319-334.
13 +
Andreasen NC, Arndt S, Swayze V II, Cizadlo T, Flaum M, O'Leary D, Ehrhardt JC, Yuh WTC.  Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging . Science . 1994;;266:294-298.
14 +
Zipursky RB, Lim KO, Sullivan EV, Brown BW, Pfefferbaum A.  Widespread cerebral gray matter volume deficits in schizophrenia . Arch Gen Psychiatry . 1992;;49:195-205.
15 +
Raine A, Lencz T, Reynolds GP, Harrison G, Sheard C, Medley I, Reynolds LM, Cooper JE.  An evaluation of structural and functional prefrontal deficits in schizophrenia: MRI and neuropsychological measures . Psychiatry Res . 1992;;45:123-137.
16 +
Glantz LA, Lewis DA.  Synaptic immunoreactivity is selectively deceased in the prefrontal cortex of schizophrenic subjects . Soc Neurosci Abst . 1993;;19:201.
17 +
Benes FM, McSparren J, Bird ED, Sangiovanni JP, Vincent SL.  Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients . Arch Gen Psychiatry . 1991;;48:996-1001.
18 +
Akbarian S, Bunney WE Jr, Potkin SC, Wigal SB, Hagman JO, Sandman CA, Jones EG.  Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development . Arch Gen Psychiatry . 1993;;50:169-177.
19 +
Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE Jr, Jones EG.  Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics . Arch Gen Psychiatry . 1995;;52:258-278.

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1 +
Shenton ME, Kikinis R, Jolesz FA, Pollak SD, LeMay M, Wible CG, Hokama H, Martin J, Metcalf D, Coleman M, McCarley RW.  Abnormalities of the left temporal lobe and thought disorder in schizophrenia: a quantitative magnetic resonance imaging study . N Engl J Med . 1992;;327:604-612.
2 +
Breier A, Buchanan RW, Elkashef A, Munson RC, Kirkpatrick B, Gellad F.  Brain morphology and schizophrenia: a magnetic resonance imaging study of limbic, prefrontal cortex, and caudate structures . Arch Gen Psychiatry . 1992;;49:921-926.
3 +
Jernigan TL, Zisook S, Heaton RK, Moranville JT, Hesselink J, Braff DL.  Magnetic resonance imaging abnormalities in lenticular nuclei and cerebral cortex in schizophrenia . Arch Gen Psychiatry . 1991;;48:881-890.
4 +
Harvey I, Ron MA, DuBoulay G, Wicks D, Lewis SW, Murray RM.  Reduction of cortical volume in schizophrenia on magnetic resonance imaging . Psychol Med . 1993;;23:591-604.
5 +
Berman KF, IIIowsky BP, Weinberger DR.  Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia, IV: further evidence for regional and behavioral specificity . Arch Gen Psychiatry . 1988;;45:616-622.
6 +
Weinberger DR, Berman KF, IIIowsky BP.  Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia, III: a new cohort and evidence for a monoaminergic mechanism . Arch Gen Psychiatry . 1988;;45:609-615.
7 +
Tamminga CA, Thaker GK, Buchanan R, Kirkpatrick B, Alphs LD, Chase TN, Carpenter WT.  Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome . Arch Gen Psychiatry . 1992;;49:522-530.
8 +
Friston KJ, Liddle PF, Frith CD, Hirsch SR, Frackowiak RSJ.  The left medial temporal region and schizophrenia: a PET study . Brain . 1992;;115:367-382.
9 +
Pettegrew JW, Keshavan MS, Panchalingam K, Strychor S, Kaplan DB, Tretta MG, Allen M.  Alterations in brain high-energy phosphate and membrane phospholipid metabolism in first-episode, drug-naive schizophrenics: a pilot study of the dorsal prefrontal cortex by in vivo phosphorus 31 nuclear magnetic resonance spectroscopy . Arch Gen Psychiatry . 1991;;48:563-568.
10 +
Fugimoto T, Nakano T, Hokazono Y, Asakura T, Tsuji T.  Study of chronic schizophrenics using 31P magnetic resonance chemical shift imaging . Acta Psychiatr Scand . 1992;;86:455-462.
11 +
Selemon LD, Rajkowska G, Goldman-Rakic PS.  Abnormally high neuronal density in the schizophrenic cortex: a morphometric analysis of prefrontal area 9 and occipital area 17 . Arch Gen Psychiatry . 1995;;52:805-818.
12 +
Feinberg I.  Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiatr Res . 1982-83;;17:319-334.
13 +
Andreasen NC, Arndt S, Swayze V II, Cizadlo T, Flaum M, O'Leary D, Ehrhardt JC, Yuh WTC.  Thalamic abnormalities in schizophrenia visualized through magnetic resonance image averaging . Science . 1994;;266:294-298.
14 +
Zipursky RB, Lim KO, Sullivan EV, Brown BW, Pfefferbaum A.  Widespread cerebral gray matter volume deficits in schizophrenia . Arch Gen Psychiatry . 1992;;49:195-205.
15 +
Raine A, Lencz T, Reynolds GP, Harrison G, Sheard C, Medley I, Reynolds LM, Cooper JE.  An evaluation of structural and functional prefrontal deficits in schizophrenia: MRI and neuropsychological measures . Psychiatry Res . 1992;;45:123-137.
16 +
Glantz LA, Lewis DA.  Synaptic immunoreactivity is selectively deceased in the prefrontal cortex of schizophrenic subjects . Soc Neurosci Abst . 1993;;19:201.
17 +
Benes FM, McSparren J, Bird ED, Sangiovanni JP, Vincent SL.  Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients . Arch Gen Psychiatry . 1991;;48:996-1001.
18 +
Akbarian S, Bunney WE Jr, Potkin SC, Wigal SB, Hagman JO, Sandman CA, Jones EG.  Altered distribution of nicotinamide-adenine dinucleotide phosphate-diaphorase cells in frontal lobe of schizophrenics implies disturbances of cortical development . Arch Gen Psychiatry . 1993;;50:169-177.
19 +
Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE Jr, Jones EG.  Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics . Arch Gen Psychiatry . 1995;;52:258-278.

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