Abstract
We present an evaluation of the contribution of structural and functional brain imaging to our understanding of schizophrenia. Methodological influences on the validity of the data generated by these new technologies include problems with measurement and clinical and anatomic heterogeneity. These considerations greatly affect the interpretation of the data generated by these technologies. Work in these fields to date, however, has produced strong evidence which suggests that schizophrenia is a disease which involves abnormalities in the structure and function of many brain areas. Structural brain imaging studies of schizophrenia using computed tomography (CT) and magnetic resonance imaging (MRI) are reviewed and their contribution to current theories of the pathogenesis of schizophrenia are discussed. Positron emission tomography (PET) studies of brain metabolic activity and dopamine receptor binding in schizophrenia are summarized and the critical questions raised by these studies are outlined. Future studies in these fields have the potential to yield critical insights into the pathophysiology of schizophrenia; new directions for studies of schizophrenia using these technologies are identified.
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- Alexander G. E., Crutcher M. D. Functional architecture of basal ganglia circuits: neural substrates of parallel processing. Trends Neurosci. 1990 Jul;13(7):266–271. doi: 10.1016/0166-2236(90)90107-l. [DOI] [PubMed] [Google Scholar]
- Andersson U., Eckernäs S. A., Hartvig P., Ulin J., Långström B., Häggström J. E. Striatal binding of 11C-NMSP studied with positron emission tomography in patients with persistent tardive dyskinesia: no evidence for altered dopamine D2 receptor binding. J Neural Transm Gen Sect. 1990;79(3):215–226. doi: 10.1007/BF01245132. [DOI] [PubMed] [Google Scholar]
- Andreasen N. C., Ehrhardt J. C., Swayze V. W., 2nd, Alliger R. J., Yuh W. T., Cohen G., Ziebell S. Magnetic resonance imaging of the brain in schizophrenia. The pathophysiologic significance of structural abnormalities. Arch Gen Psychiatry. 1990 Jan;47(1):35–44. doi: 10.1001/archpsyc.1990.01810130037006. [DOI] [PubMed] [Google Scholar]
- Andreasen N., Nasrallah H. A., Dunn V., Olson S. C., Grove W. M., Ehrhardt J. C., Coffman J. A., Crossett J. H. Structural abnormalities in the frontal system in schizophrenia. A magnetic resonance imaging study. Arch Gen Psychiatry. 1986 Feb;43(2):136–144. doi: 10.1001/archpsyc.1986.01800020042006. [DOI] [PubMed] [Google Scholar]
- Bahn M. M., Huang S. C., Hawkins R. A., Satyamurthy N., Hoffman J. M., Barrio J. R., Mazziotta J. C., Phelps M. E. Models for in vivo kinetic interactions of dopamine D2-neuroreceptors and 3-(2'-[18F]fluoroethyl)spiperone examined with positron emission tomography. J Cereb Blood Flow Metab. 1989 Dec;9(6):840–849. doi: 10.1038/jcbfm.1989.118. [DOI] [PubMed] [Google Scholar]
- Baron J. C., Martinot J. L., Cambon H., Boulenger J. P., Poirier M. F., Caillard V., Blin J., Huret J. D., Loc'h C., Maziere B. Striatal dopamine receptor occupancy during and following withdrawal from neuroleptic treatment: correlative evaluation by positron emission tomography and plasma prolactin levels. Psychopharmacology (Berl) 1989;99(4):463–472. doi: 10.1007/BF00589893. [DOI] [PubMed] [Google Scholar]
- Barta P. E., Pearlson G. D., Powers R. E., Richards S. S., Tune L. E. Auditory hallucinations and smaller superior temporal gyral volume in schizophrenia. Am J Psychiatry. 1990 Nov;147(11):1457–1462. doi: 10.1176/ajp.147.11.1457. [DOI] [PubMed] [Google Scholar]
- Bartlett E. J., Brodie J. D., Wolf A. P., Christman D. R., Laska E., Meissner M. Reproducibility of cerebral glucose metabolic measurements in resting human subjects. J Cereb Blood Flow Metab. 1988 Aug;8(4):502–512. doi: 10.1038/jcbfm.1988.91. [DOI] [PubMed] [Google Scholar]
- Berman K. F., Illowsky B. P., Weinberger D. R. Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. IV. Further evidence for regional and behavioral specificity. Arch Gen Psychiatry. 1988 Jul;45(7):616–622. doi: 10.1001/archpsyc.1988.01800310020002. [DOI] [PubMed] [Google Scholar]
- Blin J., Baron J. C., Cambon H., Bonnet A. M., Dubois B., Loc'h C., Mazière B., Agid Y. Striatal dopamine D2 receptors in tardive dyskinesia: PET study. J Neurol Neurosurg Psychiatry. 1989 Nov;52(11):1248–1252. doi: 10.1136/jnnp.52.11.1248. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bogerts B., Ashtari M., Degreef G., Alvir J. M., Bilder R. M., Lieberman J. A. Reduced temporal limbic structure volumes on magnetic resonance images in first episode schizophrenia. Psychiatry Res. 1990 Apr;35(1):1–13. doi: 10.1016/0925-4927(90)90004-p. [DOI] [PubMed] [Google Scholar]
- Bogerts B., Meertz E., Schönfeldt-Bausch R. Basal ganglia and limbic system pathology in schizophrenia. A morphometric study of brain volume and shrinkage. Arch Gen Psychiatry. 1985 Aug;42(8):784–791. doi: 10.1001/archpsyc.1985.01790310046006. [DOI] [PubMed] [Google Scholar]
- Borison R. L., Hitri A., Blowers A. J., Diamond B. I. Antipsychotic drug action: clinical, biochemical, and pharmacological evidence for site specificity of action. Clin Neuropharmacol. 1983 Jun;6(2):137–150. [PubMed] [Google Scholar]
- Brown R., Colter N., Corsellis J. A., Crow T. J., Frith C. D., Jagoe R., Johnstone E. C., Marsh L. Postmortem evidence of structural brain changes in schizophrenia. Differences in brain weight, temporal horn area, and parahippocampal gyrus compared with affective disorder. Arch Gen Psychiatry. 1986 Jan;43(1):36–42. doi: 10.1001/archpsyc.1986.01800010038005. [DOI] [PubMed] [Google Scholar]
- Bruton C. J., Crow T. J., Frith C. D., Johnstone E. C., Owens D. G., Roberts G. W. Schizophrenia and the brain: a prospective clinico-neuropathological study. Psychol Med. 1990 May;20(2):285–304. doi: 10.1017/s0033291700017608. [DOI] [PubMed] [Google Scholar]
- Buchsbaum M. S., DeLisi L. E., Holcomb H. H., Cappelletti J., King A. C., Johnson J., Hazlett E., Dowling-Zimmerman S., Post R. M., Morihisa J. Anteroposterior gradients in cerebral glucose use in schizophrenia and affective disorders. Arch Gen Psychiatry. 1984 Dec;41(12):1159–1166. doi: 10.1001/archpsyc.1984.01790230045007. [DOI] [PubMed] [Google Scholar]
- Buchsbaum M. S., Ingvar D. H., Kessler R., Waters R. N., Cappelletti J., van Kammen D. P., King A. C., Johnson J. L., Manning R. G., Flynn R. W. Cerebral glucography with positron tomography. Use in normal subjects and in patients with schizophrenia. Arch Gen Psychiatry. 1982 Mar;39(3):251–259. doi: 10.1001/archpsyc.1982.04290030001001. [DOI] [PubMed] [Google Scholar]
- Buchsbaum M. S., Mirsky A. F., DeLisi L. E., Morihisa J., Karson C. N., Mendelson W. B., King A. C., Johnson J., Kessler R. The Genain Quadruplets: electrophysiological, positron emission, and X-ray tomographic studies. Psychiatry Res. 1984 Sep;13(1):95–108. doi: 10.1016/0165-1781(84)90121-5. [DOI] [PubMed] [Google Scholar]
- Buchsbaum M. S., Nuechterlein K. H., Haier R. J., Wu J., Sicotte N., Hazlett E., Asarnow R., Potkin S., Guich S. Glucose metabolic rate in normals and schizophrenics during the Continuous Performance Test assessed by positron emission tomography. Br J Psychiatry. 1990 Feb;156:216–227. doi: 10.1192/bjp.156.2.216. [DOI] [PubMed] [Google Scholar]
- Buchsbaum M. S. The frontal lobes, basal ganglia, and temporal lobes as sites for schizophrenia. Schizophr Bull. 1990;16(3):379–389. doi: 10.1093/schbul/16.3.379. [DOI] [PubMed] [Google Scholar]
- Buchsbaum M. S., Wu J. C., DeLisi L. E., Holcomb H. H., Hazlett E., Cooper-Langston K., Kessler R. Positron emission tomography studies of basal ganglia and somatosensory cortex neuroleptic drug effects: differences between normal controls and schizophrenic patients. Biol Psychiatry. 1987 Apr;22(4):479–494. doi: 10.1016/0006-3223(87)90170-3. [DOI] [PubMed] [Google Scholar]
- Cleghorn J. M., Garnett E. S., Nahmias C., Brown G. M., Kaplan R. D., Szechtman H., Szechtman B., Franco S., Dermer S. W., Cook P. Regional brain metabolism during auditory hallucinations in chronic schizophrenia. Br J Psychiatry. 1990 Oct;157:562–570. doi: 10.1192/bjp.157.4.562. [DOI] [PubMed] [Google Scholar]
- Cleghorn J. M., Garnett E. S., Nahmias C., Firnau G., Brown G. M., Kaplan R., Szechtman H., Szechtman B. Increased frontal and reduced parietal glucose metabolism in acute untreated schizophrenia. Psychiatry Res. 1989 May;28(2):119–133. doi: 10.1016/0165-1781(89)90040-1. [DOI] [PubMed] [Google Scholar]
- Cohen R. M., Semple W. E., Gross M., Nordahl T. E., DeLisi L. E., Holcomb H. H., King A. C., Morihisa J. M., Pickar D. Dysfunction in a prefrontal substrate of sustained attention in schizophrenia. Life Sci. 1987 May 18;40(20):2031–2039. doi: 10.1016/0024-3205(87)90295-5. [DOI] [PubMed] [Google Scholar]
- Crawley J. C., Owens D. G., Crow T. J., Poulter M., Johnstone E. C., Smith T., Oldland S. R., Veall N., Owen F., Zanelli G. D. Dopamine D2 receptors in schizophrenia studied in vivo. Lancet. 1986 Jul 26;2(8500):224–225. doi: 10.1016/s0140-6736(86)92525-0. [DOI] [PubMed] [Google Scholar]
- Cross A. J., Crow T. J., Owen F. 3H-Flupenthixol binding in post-mortem brains of schizophrenics: evidence for a selective increase in dopamine D2 receptors. Psychopharmacology (Berl) 1981;74(2):122–124. doi: 10.1007/BF00432676. [DOI] [PubMed] [Google Scholar]
- Crow T. J., Ball J., Bloom S. R., Brown R., Bruton C. J., Colter N., Frith C. D., Johnstone E. C., Owens D. G., Roberts G. W. Schizophrenia as an anomaly of development of cerebral asymmetry. A postmortem study and a proposal concerning the genetic basis of the disease. Arch Gen Psychiatry. 1989 Dec;46(12):1145–1150. doi: 10.1001/archpsyc.1989.01810120087013. [DOI] [PubMed] [Google Scholar]
- Crow T. J. Molecular pathology of schizophrenia: more than one disease process? Br Med J. 1980 Jan 12;280(6207):66–68. doi: 10.1136/bmj.280.6207.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crow T. J. Temporal lobe asymmetries as the key to the etiology of schizophrenia. Schizophr Bull. 1990;16(3):433–443. doi: 10.1093/schbul/16.3.433. [DOI] [PubMed] [Google Scholar]
- D'Antona R., Baron J. C., Samson Y., Serdaru M., Viader F., Agid Y., Cambier J. Subcortical dementia. Frontal cortex hypometabolism detected by positron tomography in patients with progressive supranuclear palsy. Brain. 1985 Sep;108(Pt 3):785–799. doi: 10.1093/brain/108.3.785. [DOI] [PubMed] [Google Scholar]
- DeLisi L. E., Buchsbaum M. S., Holcomb H. H., Langston K. C., King A. C., Kessler R., Pickar D., Carpenter W. T., Jr, Morihisa J. M., Margolin R. Increased temporal lobe glucose use in chronic schizophrenic patients. Biol Psychiatry. 1989 Apr 1;25(7):835–851. doi: 10.1016/0006-3223(89)90263-1. [DOI] [PubMed] [Google Scholar]
- DeLisi L. E., Goldin L. R., Hamovit J. R., Maxwell M. E., Kurtz D., Gershon E. S. A family study of the association of increased ventricular size with schizophrenia. Arch Gen Psychiatry. 1986 Feb;43(2):148–153. doi: 10.1001/archpsyc.1986.01800020058007. [DOI] [PubMed] [Google Scholar]
- DeLisi L. E., Holcomb H. H., Cohen R. M., Pickar D., Carpenter W., Morihisa J. M., King A. C., Kessler R., Buchsbaum M. S. Positron emission tomography in schizophrenic patients with and without neuroleptic medication. J Cereb Blood Flow Metab. 1985 Jun;5(2):201–206. doi: 10.1038/jcbfm.1985.26. [DOI] [PubMed] [Google Scholar]
- Farde L., Eriksson L., Blomquist G., Halldin C. Kinetic analysis of central [11C]raclopride binding to D2-dopamine receptors studied by PET--a comparison to the equilibrium analysis. J Cereb Blood Flow Metab. 1989 Oct;9(5):696–708. doi: 10.1038/jcbfm.1989.98. [DOI] [PubMed] [Google Scholar]
- Farde L., Halldin C., Stone-Elander S., Sedvall G. PET analysis of human dopamine receptor subtypes using 11C-SCH 23390 and 11C-raclopride. Psychopharmacology (Berl) 1987;92(3):278–284. doi: 10.1007/BF00210831. [DOI] [PubMed] [Google Scholar]
- Farde L., Pauli S., Hall H., Eriksson L., Halldin C., Högberg T., Nilsson L., Sjögren I., Stone-Elander S. Stereoselective binding of 11C-raclopride in living human brain--a search for extrastriatal central D2-dopamine receptors by PET. Psychopharmacology (Berl) 1988;94(4):471–478. doi: 10.1007/BF00212840. [DOI] [PubMed] [Google Scholar]
- Farde L., Wiesel F. A., Hall H., Halldin C., Stone-Elander S., Sedvall G. No D2 receptor increase in PET study of schizophrenia. Arch Gen Psychiatry. 1987 Jul;44(7):671–672. doi: 10.1001/archpsyc.1987.01800190091013. [DOI] [PubMed] [Google Scholar]
- Farde L., Wiesel F. A., Halldin C., Sedvall G. Central D2-dopamine receptor occupancy in schizophrenic patients treated with antipsychotic drugs. Arch Gen Psychiatry. 1988 Jan;45(1):71–76. doi: 10.1001/archpsyc.1988.01800250087012. [DOI] [PubMed] [Google Scholar]
- Farde L., Wiesel F. A., Stone-Elander S., Halldin C., Nordström A. L., Hall H., Sedvall G. D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C]raclopride. Arch Gen Psychiatry. 1990 Mar;47(3):213–219. doi: 10.1001/archpsyc.1990.01810150013003. [DOI] [PubMed] [Google Scholar]
- Farkas T., Wolf A. P., Jaeger J., Brodie J. D., Christman D. R., Fowler J. S. Regional brain glucose metabolism in chronic schizophrenia. A positron emission transaxial tomographic study. Arch Gen Psychiatry. 1984 Mar;41(3):293–300. doi: 10.1001/archpsyc.1984.01790140083010. [DOI] [PubMed] [Google Scholar]
- Feinberg I. Schizophrenia: caused by a fault in programmed synaptic elimination during adolescence? J Psychiatr Res. 1982;17(4):319–334. doi: 10.1016/0022-3956(82)90038-3. [DOI] [PubMed] [Google Scholar]
- Feinberg T. E., Rifkin A., Schaffer C., Walker E. Facial discrimination and emotional recognition in schizophrenia and affective disorders. Arch Gen Psychiatry. 1986 Mar;43(3):276–279. doi: 10.1001/archpsyc.1986.01800030094010. [DOI] [PubMed] [Google Scholar]
- Fox P. T., Mintun M. A., Reiman E. M., Raichle M. E. Enhanced detection of focal brain responses using intersubject averaging and change-distribution analysis of subtracted PET images. J Cereb Blood Flow Metab. 1988 Oct;8(5):642–653. doi: 10.1038/jcbfm.1988.111. [DOI] [PubMed] [Google Scholar]
- Fox P. T., Perlmutter J. S., Raichle M. E. A stereotactic method of anatomical localization for positron emission tomography. J Comput Assist Tomogr. 1985 Jan-Feb;9(1):141–153. doi: 10.1097/00004728-198501000-00025. [DOI] [PubMed] [Google Scholar]
- Fried I., Mateer C., Ojemann G., Wohns R., Fedio P. Organization of visuospatial functions in human cortex. Evidence from electrical stimulation. Brain. 1982 Jun;105(Pt 2):349–371. doi: 10.1093/brain/105.2.349. [DOI] [PubMed] [Google Scholar]
- Fried I., Ojemann G. A., Fetz E. E. Language-related potentials specific to human language cortex. Science. 1981 Apr 17;212(4492):353–356. doi: 10.1126/science.7209537. [DOI] [PubMed] [Google Scholar]
- Friedman A. M., DeJesus O. T., Woolverton W. L., van Moffaert G., Goldberg L. I., Prasad A., Barnett A., Dinerstein R. J. Positron tomography of a radio-brominated analog of the D1/DA1 antagonist, SCH 23390. Eur J Pharmacol. 1985 Feb 5;108(3):327–328. doi: 10.1016/0014-2999(85)90459-5. [DOI] [PubMed] [Google Scholar]
- Friston K. J., Frith C. D., Liddle P. F., Dolan R. J., Lammertsma A. A., Frackowiak R. S. The relationship between global and local changes in PET scans. J Cereb Blood Flow Metab. 1990 Jul;10(4):458–466. doi: 10.1038/jcbfm.1990.88. [DOI] [PubMed] [Google Scholar]
- Friston K. J., Passingham R. E., Nutt J. G., Heather J. D., Sawle G. V., Frackowiak R. S. Localisation in PET images: direct fitting of the intercommissural (AC-PC) line. J Cereb Blood Flow Metab. 1989 Oct;9(5):690–695. doi: 10.1038/jcbfm.1989.97. [DOI] [PubMed] [Google Scholar]
- Funahashi S., Bruce C. J., Goldman-Rakic P. S. Mnemonic coding of visual space in the monkey's dorsolateral prefrontal cortex. J Neurophysiol. 1989 Feb;61(2):331–349. doi: 10.1152/jn.1989.61.2.331. [DOI] [PubMed] [Google Scholar]
- Goetz K. L., van Kammen D. P. Computerized axial tomography scans and subtypes of schizophrenia. A review of the literature. J Nerv Ment Dis. 1986 Jan;174(1):31–41. doi: 10.1097/00005053-198601000-00005. [DOI] [PubMed] [Google Scholar]
- Graybiel A. M. Neurotransmitters and neuromodulators in the basal ganglia. Trends Neurosci. 1990 Jul;13(7):244–254. doi: 10.1016/0166-2236(90)90104-i. [DOI] [PubMed] [Google Scholar]
- Gur R. E., Gur R. C., Skolnick B. E., Caroff S., Obrist W. D., Resnick S., Reivich M. Brain function in psychiatric disorders. III. Regional cerebral blood flow in unmedicated schizophrenics. Arch Gen Psychiatry. 1985 Apr;42(4):329–334. doi: 10.1001/archpsyc.1985.01790270015001. [DOI] [PubMed] [Google Scholar]
- Gur R. E., Resnick S. M., Gur R. C., Alavi A., Caroff S., Kushner M., Reivich M. Regional brain function in schizophrenia. II. Repeated evaluation with positron emission tomography. Arch Gen Psychiatry. 1987 Feb;44(2):126–129. doi: 10.1001/archpsyc.1987.01800140028004. [DOI] [PubMed] [Google Scholar]
- Hall H., Wedel I. Comparisons between the in vitro binding of two substituted benzamides and two butyrophenones to dopamine-D2 receptors in the rat striatum. Acta Pharmacol Toxicol (Copenh) 1986 May;58(5):368–373. doi: 10.1111/j.1600-0773.1986.tb00123.x. [DOI] [PubMed] [Google Scholar]
- Halldin C., Farde L., Högberg T., Hall H., Sedvall G. Carbon-11 labelling of eticlopride in two different positions--a selective high-affinity ligand for the study of dopamine D-2 receptors using PET. Int J Rad Appl Instrum A. 1990;41(7):669–674. doi: 10.1016/0883-2889(90)90082-r. [DOI] [PubMed] [Google Scholar]
- Hat size in schizophrenia. Arch Gen Psychiatry. 1987 Jul;44(7):672–676. [PubMed] [Google Scholar]
- Hat size in schizophrenia. Arch Gen Psychiatry. 1987 Jul;44(7):672–676. [PubMed] [Google Scholar]
- Hatazawa J., Brooks R. A., Di Chiro G., Bacharach S. L. Glucose utilization rate versus brain size in humans. Neurology. 1987 Apr;37(4):583–588. doi: 10.1212/wnl.37.4.583. [DOI] [PubMed] [Google Scholar]
- Heckers S., Heinsen H., Heinsen Y. C., Beckmann H. Limbic structures and lateral ventricle in schizophrenia. A quantitative postmortem study. Arch Gen Psychiatry. 1990 Nov;47(11):1016–1022. doi: 10.1001/archpsyc.1990.01810230032006. [DOI] [PubMed] [Google Scholar]
- Hökfelt T., Ungerstedt U. Electron and fluorescence microscopical studies on the nucleus caudatus putamen of the rat after unilateral lesions of ascending nigro-neostriatal dopamine neurons. Acta Physiol Scand. 1969 Aug;76(4):415–426. doi: 10.1111/j.1748-1716.1969.tb04489.x. [DOI] [PubMed] [Google Scholar]
- Iacono W. G., Smith G. N., Moreau M., Beiser M., Fleming J. A., Lin T. Y., Flak B. Ventricular and sulcal size at the onset of psychosis. Am J Psychiatry. 1988 Jul;145(7):820–824. doi: 10.1176/ajp.145.7.820. [DOI] [PubMed] [Google Scholar]
- Illowsky B. P., Juliano D. M., Bigelow L. B., Weinberger D. R. Stability of CT scan findings in schizophrenia: results of an 8 year follow-up study. J Neurol Neurosurg Psychiatry. 1988 Feb;51(2):209–213. doi: 10.1136/jnnp.51.2.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ingvar D. H., Franzén G. Abnormalities of cerebral blood flow distribution in patients with chronic schizophrenia. Acta Psychiatr Scand. 1974;50(4):425–462. doi: 10.1111/j.1600-0447.1974.tb09707.x. [DOI] [PubMed] [Google Scholar]
- Jernigan T. L., Sargent T., 3rd, Pfefferbaum A., Kusubov N., Stahl S. M. 18Fluorodeoxyglucose PET in schizophrenia. Psychiatry Res. 1985 Dec;16(4):317–329. doi: 10.1016/0165-1781(85)90123-4. [DOI] [PubMed] [Google Scholar]
- Johnstone E. C., Crow T. J., Frith C. D., Husband J., Kreel L. Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet. 1976 Oct 30;2(7992):924–926. doi: 10.1016/s0140-6736(76)90890-4. [DOI] [PubMed] [Google Scholar]
- Johnstone E. C., Owens D. G., Crow T. J., Frith C. D., Alexandropolis K., Bydder G., Colter N. Temporal lobe structure as determined by nuclear magnetic resonance in schizophrenia and bipolar affective disorder. J Neurol Neurosurg Psychiatry. 1989 Jun;52(6):736–741. doi: 10.1136/jnnp.52.6.736. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kelsoe J. R., Jr, Cadet J. L., Pickar D., Weinberger D. R. Quantitative neuroanatomy in schizophrenia. A controlled magnetic resonance imaging study. Arch Gen Psychiatry. 1988 Jun;45(6):533–541. doi: 10.1001/archpsyc.1988.01800300029003. [DOI] [PubMed] [Google Scholar]
- Kishimoto H., Kuwahara H., Ohno S., Takazu O., Hama Y., Sato C., Ishii T., Nomura Y., Fujita H., Miyauchi T. Three subtypes of chronic schizophrenia identified using 11C-glucose positron emission tomography. Psychiatry Res. 1987 Aug;21(4):285–292. doi: 10.1016/0165-1781(87)90011-4. [DOI] [PubMed] [Google Scholar]
- Klawans H. L., Jr The pharmacology of tardive dyskinesias. Am J Psychiatry. 1973 Jan;130(1):82–86. doi: 10.1176/ajp.130.1.82. [DOI] [PubMed] [Google Scholar]
- Kling A. S., Metter E. J., Riege W. H., Kuhl D. E. Comparison of PET measurement of local brain glucose metabolism and CAT measurement of brain atrophy in chronic schizophrenia and depression. Am J Psychiatry. 1986 Feb;143(2):175–180. doi: 10.1176/ajp.143.2.175. [DOI] [PubMed] [Google Scholar]
- Kolakowska T., Williams A. O., Jambor K., Ardern M. Schizophrenia with good and poor outcome. III: Neurological 'soft' signs, cognitive impairment and their clinical significance. Br J Psychiatry. 1985 Apr;146:348–357. doi: 10.1192/bjp.146.4.348. [DOI] [PubMed] [Google Scholar]
- Kornhuber J., Riederer P., Reynolds G. P., Beckmann H., Jellinger K., Gabriel E. 3H-spiperone binding sites in post-mortem brains from schizophrenic patients: relationship to neuroleptic drug treatment, abnormal movements, and positive symptoms. J Neural Transm. 1989;75(1):1–10. doi: 10.1007/BF01250639. [DOI] [PubMed] [Google Scholar]
- Kuzniecky R., de la Sayette V., Ethier R., Melanson D., Andermann F., Berkovic S., Robitaille Y., Olivier A., Peters T., Feindel W. Magnetic resonance imaging in temporal lobe epilepsy: pathological correlations. Ann Neurol. 1987 Sep;22(3):341–347. doi: 10.1002/ana.410220310. [DOI] [PubMed] [Google Scholar]
- Lee T., Seeman P., Tourtellotte W. W., Farley I. J., Hornykeiwicz O. Binding of 3H-neuroleptics and 3H-apomorphine in schizophrenic brains. Nature. 1978 Aug 31;274(5674):897–900. doi: 10.1038/274897a0. [DOI] [PubMed] [Google Scholar]
- Lewis S. W. Computerised tomography in schizophrenia 15 years on. Br J Psychiatry Suppl. 1990;(9):16–24. [PubMed] [Google Scholar]
- Liddle P. F., Barnes T. R. Syndromes of chronic schizophrenia. Br J Psychiatry. 1990 Oct;157:558–561. doi: 10.1192/bjp.157.4.558. [DOI] [PubMed] [Google Scholar]
- Liddle P. F. Schizophrenic syndromes, cognitive performance and neurological dysfunction. Psychol Med. 1987 Feb;17(1):49–57. doi: 10.1017/s0033291700012976. [DOI] [PubMed] [Google Scholar]
- Lim K. O., Pfefferbaum A. Segmentation of MR brain images into cerebrospinal fluid spaces, white and gray matter. J Comput Assist Tomogr. 1989 Jul-Aug;13(4):588–593. doi: 10.1097/00004728-198907000-00006. [DOI] [PubMed] [Google Scholar]
- List S. J., Seeman P. Dopamine agonists reverse the elevated 3H-neuroleptic binding in neuroleptic-pretreated rats. Life Sci. 1979 Apr 16;24(16):1447–1452. doi: 10.1016/0024-3205(79)90027-4. [DOI] [PubMed] [Google Scholar]
- List S. J., Seeman P. Resolution of dopamine and serotonin receptor components of [3H]spiperone binding to rat brain regions. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2620–2624. doi: 10.1073/pnas.78.4.2620. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Logan J., Wolf A. P., Shiue C. Y., Fowler J. S. Kinetic modeling of receptor-ligand binding applied to positron emission tomographic studies with neuroleptic tracers. J Neurochem. 1987 Jan;48(1):73–83. doi: 10.1111/j.1471-4159.1987.tb13129.x. [DOI] [PubMed] [Google Scholar]
- Lundberg T., Lindström L. H., Hartvig P., Eckernâs S. A., Ekblom B., Lundqvist H., Fasth K. J., Gullberg P., Långström B. Striatal and frontal cortex binding of 11-C-labelled clozapine visualized by positron emission tomography (PET) in drug-free schizophrenics and healthy volunteers. Psychopharmacology (Berl) 1989;99(1):8–12. doi: 10.1007/BF00634444. [DOI] [PubMed] [Google Scholar]
- Martinot J. L., Huret J. D., Peron-Magnan P., Mazoyer B. M., Baron J. C., Caillard V., Syrota A., Loo H. Striatal D2 dopaminergic receptor status ascertained in vivo by positron emission tomography and 76Br-bromospiperone in untreated schizophrenics. Psychiatry Res. 1989 Sep;29(3):357–358. doi: 10.1016/0165-1781(89)90088-7. [DOI] [PubMed] [Google Scholar]
- Martinot J. L., Paillère-Martinot M. L., Loc'h C., Hardy P., Poirier M. F., Mazoyer B., Beaufils B., Mazière B., Allilaire J. F., Syrota A. The estimated density of D2 striatal receptors in schizophrenia. A study with positron emission tomography and 76Br-bromolisuride. Br J Psychiatry. 1991 Mar;158:346–350. doi: 10.1192/bjp.158.3.346. [DOI] [PubMed] [Google Scholar]
- Meltzer H. Y., Matsubara S., Lee J. C. The ratios of serotonin2 and dopamine2 affinities differentiate atypical and typical antipsychotic drugs. Psychopharmacol Bull. 1989;25(3):390–392. [PubMed] [Google Scholar]
- Mintun M. A., Fox P. T., Raichle M. E. A highly accurate method of localizing regions of neuronal activation in the human brain with positron emission tomography. J Cereb Blood Flow Metab. 1989 Feb;9(1):96–103. doi: 10.1038/jcbfm.1989.13. [DOI] [PubMed] [Google Scholar]
- Nasrallah H. A., Olson S. C., McCalley-Whitters M., Chapman S., Jacoby C. G. Cerebral ventricular enlargement in schizophrenia. A preliminary follow-up study. Arch Gen Psychiatry. 1986 Feb;43(2):157–159. doi: 10.1001/archpsyc.1986.01800020067008. [DOI] [PubMed] [Google Scholar]
- Novic J., Luchins D. J., Perline R. Facial affect recognition in schizophrenia. Is there a differential deficit? Br J Psychiatry. 1984 May;144:533–537. doi: 10.1192/bjp.144.5.533. [DOI] [PubMed] [Google Scholar]
- Ojemann G. A., Creutzfeldt O., Lettich E., Haglund M. M. Neuronal activity in human lateral temporal cortex related to short-term verbal memory, naming and reading. Brain. 1988 Dec;111(Pt 6):1383–1403. doi: 10.1093/brain/111.6.1383. [DOI] [PubMed] [Google Scholar]
- Pakkenberg B. Post-mortem study of chronic schizophrenic brains. Br J Psychiatry. 1987 Dec;151:744–752. doi: 10.1192/bjp.151.6.744. [DOI] [PubMed] [Google Scholar]
- Pardo J. V., Fox P. T., Raichle M. E. Localization of a human system for sustained attention by positron emission tomography. Nature. 1991 Jan 3;349(6304):61–64. doi: 10.1038/349061a0. [DOI] [PubMed] [Google Scholar]
- Pearlson G. D., Kim W. S., Kubos K. L., Moberg P. J., Jayaram G., Bascom M. J., Chase G. A., Goldfinger A. D., Tune L. E. Ventricle-brain ratio, computed tomographic density, and brain area in 50 schizophrenics. Arch Gen Psychiatry. 1989 Aug;46(8):690–697. doi: 10.1001/archpsyc.1989.01810080020003. [DOI] [PubMed] [Google Scholar]
- Perez M. M., Trimble M. R. Epileptic psychosis--diagnostic comparison with process schizophrenia. Br J Psychiatry. 1980 Sep;137:245–249. doi: 10.1192/bjp.137.3.245. [DOI] [PubMed] [Google Scholar]
- Perlmutter J. S., Kilbourn M. R., Welch M. J., Raichle M. E. Non-steady-state measurement of in vivo receptor binding with positron emission tomography: "dose-response" analysis. J Neurosci. 1989 Jul;9(7):2344–2352. doi: 10.1523/JNEUROSCI.09-07-02344.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perlmutter J. S., Larson K. B., Raichle M. E., Markham J., Mintun M. A., Kilbourn M. R., Welch M. J. Strategies for in vivo measurement of receptor binding using positron emission tomography. J Cereb Blood Flow Metab. 1986 Apr;6(2):154–169. doi: 10.1038/jcbfm.1986.29. [DOI] [PubMed] [Google Scholar]
- Pfefferbaum A., Lim K. O., Rosenbloom M., Zipursky R. B. Brain magnetic resonance imaging: approaches for investigating schizophrenia. Schizophr Bull. 1990;16(3):453–476. doi: 10.1093/schbul/16.3.453. [DOI] [PubMed] [Google Scholar]
- Pfefferbaum A., Zatz L. M., Jernigan T. L. Computer-interactive method for quantifying cerebrospinal fluid and tissue in brain CT scans: effects of aging. J Comput Assist Tomogr. 1986 Jul-Aug;10(4):571–578. doi: 10.1097/00004728-198607000-00004. [DOI] [PubMed] [Google Scholar]
- Pfefferbaum A., Zipursky R. B., Lim K. O., Zatz L. M., Stahl S. M., Jernigan T. L. Computed tomographic evidence for generalized sulcal and ventricular enlargement in schizophrenia. Arch Gen Psychiatry. 1988 Jul;45(7):633–640. doi: 10.1001/archpsyc.1988.01800310037005. [DOI] [PubMed] [Google Scholar]
- Pfefferbaum A., Zipursky R. B. Neuroimaging studies of schizophrenia. Schizophr Res. 1991 Mar-Apr;4(2):193–208. doi: 10.1016/0920-9964(91)90033-n. [DOI] [PubMed] [Google Scholar]
- Posner M. I., Early T. S., Reiman E., Pardo P. J., Dhawan M. Asymmetries in hemispheric control of attention in schizophrenia. Arch Gen Psychiatry. 1988 Sep;45(9):814–821. doi: 10.1001/archpsyc.1988.01800330038004. [DOI] [PubMed] [Google Scholar]
- Raz S., Raz N., Bigler E. D. Ventriculomegaly in schizophrenia: is the choice of controls important? Psychiatry Res. 1988 Apr;24(1):71–77. doi: 10.1016/0165-1781(88)90142-4. [DOI] [PubMed] [Google Scholar]
- Raz S., Raz N. Structural brain abnormalities in the major psychoses: a quantitative review of the evidence from computerized imaging. Psychol Bull. 1990 Jul;108(1):93–108. doi: 10.1037/0033-2909.108.1.93. [DOI] [PubMed] [Google Scholar]
- Raz S., Raz N., Weinberger D. R., Boronow J., Pickar D., Bigler E. D., Turkheimer E. Morphological brain abnormalities in schizophrenia determined by computed tomography: a problem of measurement? Psychiatry Res. 1987 Oct;22(2):91–98. doi: 10.1016/0165-1781(87)90096-5. [DOI] [PubMed] [Google Scholar]
- Reveley A. M., Reveley M. A., Clifford C. A., Murray R. M. Cerebral ventricular size in twins discordant for schizophrenia. Lancet. 1982 Mar 6;1(8271):540–541. doi: 10.1016/s0140-6736(82)92047-5. [DOI] [PubMed] [Google Scholar]
- Reveley M. A. Ventricular enlargement in schizophrenia. The validity of computerised tomographic findings. Br J Psychiatry. 1985 Sep;147:233–240. doi: 10.1192/bjp.147.3.233. [DOI] [PubMed] [Google Scholar]
- Reynolds G. P. Beyond the dopamine hypothesis. The neurochemical pathology of schizophrenia. Br J Psychiatry. 1989 Sep;155:305–316. doi: 10.1192/bjp.155.3.305. [DOI] [PubMed] [Google Scholar]
- Roberts G. W. Schizophrenia: the cellular biology of a functional psychosis. Trends Neurosci. 1990 Jun;13(6):207–211. doi: 10.1016/0166-2236(90)90161-3. [DOI] [PubMed] [Google Scholar]
- Rossi A., Stratta P., D'Albenzio L., Tartaro A., Schiazza G., di Michele V., Bolino F., Casacchia M. Reduced temporal lobe areas in schizophrenia: preliminary evidences from a controlled multiplanar magnetic resonance imaging study. Biol Psychiatry. 1990 Jan 1;27(1):61–68. doi: 10.1016/0006-3223(90)90020-3. [DOI] [PubMed] [Google Scholar]
- Schulz S. C., Koller M. M., Kishore P. R., Hamer R. M., Gehl J. J., Friedel R. O. Ventricular enlargement in teenage patients with schizophrenia spectrum disorder. Am J Psychiatry. 1983 Dec;140(12):1592–1595. doi: 10.1176/ajp.140.12.1592. [DOI] [PubMed] [Google Scholar]
- Seeman P. Brain dopamine receptors in schizophrenia: PET problems. Arch Gen Psychiatry. 1988 Jun;45(6):598–600. doi: 10.1001/archpsyc.1988.01800300096017. [DOI] [PubMed] [Google Scholar]
- Seeman P., Bzowej N. H., Guan H. C., Bergeron C., Reynolds G. P., Bird E. D., Riederer P., Jellinger K., Tourtellotte W. W. Human brain D1 and D2 dopamine receptors in schizophrenia, Alzheimer's, Parkinson's, and Huntington's diseases. Neuropsychopharmacology. 1987 Dec;1(1):5–15. doi: 10.1016/0893-133x(87)90004-2. [DOI] [PubMed] [Google Scholar]
- Seeman P. Dopamine receptors and the dopamine hypothesis of schizophrenia. Synapse. 1987;1(2):133–152. doi: 10.1002/syn.890010203. [DOI] [PubMed] [Google Scholar]
- Seeman P., Guan H. C., Niznik H. B. Endogenous dopamine lowers the dopamine D2 receptor density as measured by [3H]raclopride: implications for positron emission tomography of the human brain. Synapse. 1989;3(1):96–97. doi: 10.1002/syn.890030113. [DOI] [PubMed] [Google Scholar]
- Seeman P., Niznik H. B., Guan H. C., Booth G., Ulpian C. Link between D1 and D2 dopamine receptors is reduced in schizophrenia and Huntington diseased brain. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10156–10160. doi: 10.1073/pnas.86.24.10156. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Seeman P., Niznik H. B., Guan H. C. Elevation of dopamine D2 receptors in schizophrenia is underestimated by radioactive raclopride. Arch Gen Psychiatry. 1990 Dec;47(12):1170–1172. doi: 10.1001/archpsyc.1990.01810240090014. [DOI] [PubMed] [Google Scholar]
- Shelton R. C., Karson C. N., Doran A. R., Pickar D., Bigelow L. B., Weinberger D. R. Cerebral structural pathology in schizophrenia: evidence for a selective prefrontal cortical defect. Am J Psychiatry. 1988 Feb;145(2):154–163. doi: 10.1176/ajp.145.2.154. [DOI] [PubMed] [Google Scholar]
- Sheppard G., Gruzelier J., Manchanda R., Hirsch S. R., Wise R., Frackowiak R., Jones T. 15O positron emission tomographic scanning in predominantly never-treated acute schizophrenic patients. Lancet. 1983 Dec 24;2(8365-66):1448–1452. doi: 10.1016/s0140-6736(83)90798-5. [DOI] [PubMed] [Google Scholar]
- Smith M., Wolf A. P., Brodie J. D., Arnett C. D., Barouche F., Shiue C. Y., Fowler J. S., Russell J. A., MacGregor R. R., Wolkin A. Serial [18F]N-methylspiroperidol PET studies to measure changes in antipsychotic drug D-2 receptor occupancy in schizophrenic patients. Biol Psychiatry. 1988 Apr 1;23(7):653–663. doi: 10.1016/0006-3223(88)90048-0. [DOI] [PubMed] [Google Scholar]
- Sokoloff P., Giros B., Martres M. P., Bouthenet M. L., Schwartz J. C. Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature. 1990 Sep 13;347(6289):146–151. doi: 10.1038/347146a0. [DOI] [PubMed] [Google Scholar]
- Stevens J. R. Neuropathology of schizophrenia. Arch Gen Psychiatry. 1982 Oct;39(10):1131–1139. doi: 10.1001/archpsyc.1982.04290100011003. [DOI] [PubMed] [Google Scholar]
- Suddath R. L., Casanova M. F., Goldberg T. E., Daniel D. G., Kelsoe J. R., Jr, Weinberger D. R. Temporal lobe pathology in schizophrenia: a quantitative magnetic resonance imaging study. Am J Psychiatry. 1989 Apr;146(4):464–472. doi: 10.1176/ajp.146.4.464. [DOI] [PubMed] [Google Scholar]
- Suddath R. L., Christison G. W., Torrey E. F., Casanova M. F., Weinberger D. R. Anatomical abnormalities in the brains of monozygotic twins discordant for schizophrenia. N Engl J Med. 1990 Mar 22;322(12):789–794. doi: 10.1056/NEJM199003223221201. [DOI] [PubMed] [Google Scholar]
- Sunahara R. K., Guan H. C., O'Dowd B. F., Seeman P., Laurier L. G., Ng G., George S. R., Torchia J., Van Tol H. H., Niznik H. B. Cloning of the gene for a human dopamine D5 receptor with higher affinity for dopamine than D1. Nature. 1991 Apr 18;350(6319):614–619. doi: 10.1038/350614a0. [DOI] [PubMed] [Google Scholar]
- Synek V., Reuben J. R. The ventricular-brain ratio using planimetric measurement of EMI scans. Br J Radiol. 1976 Mar;49(579):233–237. doi: 10.1259/0007-1285-49-579-233. [DOI] [PubMed] [Google Scholar]
- Szechtman H., Nahmias C., Garnett E. S., Firnau G., Brown G. M., Kaplan R. D., Cleghorn J. M. Effect of neuroleptics on altered cerebral glucose metabolism in schizophrenia. Arch Gen Psychiatry. 1988 Jun;45(6):523–532. doi: 10.1001/archpsyc.1988.01800300019002. [DOI] [PubMed] [Google Scholar]
- Taylor M. A., Abrams R. Auditory thresholds in schizophrenics versus normal controls. Compr Psychiatry. 1985 Nov-Dec;26(6):489–492. doi: 10.1016/0010-440x(85)90015-x. [DOI] [PubMed] [Google Scholar]
- Turner S. W., Toone B. K., Brett-Jones J. R. Computerized tomographic scan changes in early schizophrenia--preliminary findings. Psychol Med. 1986 Feb;16(1):219–225. doi: 10.1017/s003329170000266x. [DOI] [PubMed] [Google Scholar]
- Van Tol H. H., Bunzow J. R., Guan H. C., Sunahara R. K., Seeman P., Niznik H. B., Civelli O. Cloning of the gene for a human dopamine D4 receptor with high affinity for the antipsychotic clozapine. Nature. 1991 Apr 18;350(6319):610–614. doi: 10.1038/350610a0. [DOI] [PubMed] [Google Scholar]
- Volkow N. D., Wolf A. P., Van Gelder P., Brodie J. D., Overall J. E., Cancro R., Gomez-Mont F. Phenomenological correlates of metabolic activity in 18 patients with chronic schizophrenia. Am J Psychiatry. 1987 Feb;144(2):151–158. doi: 10.1176/ajp.144.2.151. [DOI] [PubMed] [Google Scholar]
- Waddington J. L., O'Callaghan E., Larkin C., Redmond O., Stack J., Ennis J. T. Magnetic resonance imaging and spectroscopy in schizophrenia. Br J Psychiatry Suppl. 1990;(9):56–65. [PubMed] [Google Scholar]
- Warkentin S., Nilsson A., Risberg J., Karlson S., Flekköy K., Franzén G., Gustafson L., Rodriguez G. Regional cerebral blood flow in schizophrenia: repeated studies during a psychotic episode. Psychiatry Res. 1990 Apr;35(1):27–38. doi: 10.1016/0925-4927(90)90006-r. [DOI] [PubMed] [Google Scholar]
- Weinberger D. R., Berman K. F., Illowsky B. P. Physiological dysfunction of dorsolateral prefrontal cortex in schizophrenia. III. A new cohort and evidence for a monoaminergic mechanism. Arch Gen Psychiatry. 1988 Jul;45(7):609–615. doi: 10.1001/archpsyc.1988.01800310013001. [DOI] [PubMed] [Google Scholar]
- Weinberger D. R., Berman K. F., Zec R. F. Physiologic dysfunction of dorsolateral prefrontal cortex in schizophrenia. I. Regional cerebral blood flow evidence. Arch Gen Psychiatry. 1986 Feb;43(2):114–124. doi: 10.1001/archpsyc.1986.01800020020004. [DOI] [PubMed] [Google Scholar]
- Weinberger D. R., DeLisi L. E., Neophytides A. N., Wyatt R. J. Familial aspects of CT scan abnormalities in chronic schizophrenic patients. Psychiatry Res. 1981 Feb;4(1):65–71. doi: 10.1016/0165-1781(81)90009-3. [DOI] [PubMed] [Google Scholar]
- Weinberger D. R., DeLisi L. E., Perman G. P., Targum S., Wyatt R. J. Computed tomography in schizophreniform disorder and other acute psychiatric disorders. Arch Gen Psychiatry. 1982 Jul;39(7):778–783. doi: 10.1001/archpsyc.1982.04290070014004. [DOI] [PubMed] [Google Scholar]
- Weinberger D. R. Implications of normal brain development for the pathogenesis of schizophrenia. Arch Gen Psychiatry. 1987 Jul;44(7):660–669. doi: 10.1001/archpsyc.1987.01800190080012. [DOI] [PubMed] [Google Scholar]
- Weinberger D. R., Torrey E. F., Neophytides A. N., Wyatt R. J. Structural abnormalities in the cerebral cortex of chronic schizophrenic patients. Arch Gen Psychiatry. 1979 Aug;36(9):935–939. doi: 10.1001/archpsyc.1979.01780090021002. [DOI] [PubMed] [Google Scholar]
- Wienhard K., Coenen H. H., Pawlik G., Rudolf J., Laufer P., Jovkar S., Stöcklin G., Heiss W. D. PET studies of dopamine receptor distribution using [18F]fluoroethylspiperone: findings in disorders related to the dopaminergic system. J Neural Transm Gen Sect. 1990;81(3):195–213. doi: 10.1007/BF01245042. [DOI] [PubMed] [Google Scholar]
- Wiesel F. A. Positron emission tomography in psychiatry. Psychiatr Dev. 1989 Spring;7(1):19–47. [PubMed] [Google Scholar]
- Wiesel F. A., Wik G., Sjögren I., Blomqvist G., Greitz T., Stone-Elander S. Regional brain glucose metabolism in drug free schizophrenic patients and clinical correlates. Acta Psychiatr Scand. 1987 Dec;76(6):628–641. doi: 10.1111/j.1600-0447.1987.tb02933.x. [DOI] [PubMed] [Google Scholar]
- Williamson P. C., Kutcher S. P., Cooper P. W., Snow W. G., Szalai J. P., Kaye H., Morrison S. L., Willinsky R. A., Mamelak M. Psychological, topographic EEG, and CT scan correlates of frontal lobe function in schizophrenia. Psychiatry Res. 1989 Aug;29(2):137–149. doi: 10.1016/0165-1781(89)90028-0. [DOI] [PubMed] [Google Scholar]
- Wolkin A., Angrist B., Wolf A., Brodie J. D., Wolkin B., Jaeger J., Cancro R., Rotrosen J. Low frontal glucose utilization in chronic schizophrenia: a replication study. Am J Psychiatry. 1988 Feb;145(2):251–253. doi: 10.1176/ajp.145.2.251. [DOI] [PubMed] [Google Scholar]
- Wolkin A., Barouche F., Wolf A. P., Rotrosen J., Fowler J. S., Shiue C. Y., Cooper T. B., Brodie J. D. Dopamine blockade and clinical response: evidence for two biological subgroups of schizophrenia. Am J Psychiatry. 1989 Jul;146(7):905–908. doi: 10.1176/ajp.146.7.905. [DOI] [PubMed] [Google Scholar]
- Wolkin A., Jaeger J., Brodie J. D., Wolf A. P., Fowler J., Rotrosen J., Gomez-Mont F., Cancro R. Persistence of cerebral metabolic abnormalities in chronic schizophrenia as determined by positron emission tomography. Am J Psychiatry. 1985 May;142(5):564–571. doi: 10.1176/ajp.142.5.564. [DOI] [PubMed] [Google Scholar]
- Wong D. F., Gjedde A., Wagner H. M., Jr, Dannals R. F., Links J. M., Tune L. E., Pearlson G. D. In reply: elevated d2 dopamine receptors in drug-naive schizophrenics. Science. 1988 Feb 12;239(4841):790–791. doi: 10.1126/science.239.4841.790. [DOI] [PubMed] [Google Scholar]
- Wong D. F., Gjedde A., Wagner H. N., Jr Quantification of neuroreceptors in the living human brain. I. Irreversible binding of ligands. J Cereb Blood Flow Metab. 1986 Apr;6(2):137–146. doi: 10.1038/jcbfm.1986.27. [DOI] [PubMed] [Google Scholar]
- Wong D. F., Wagner H. N., Jr, Tune L. E., Dannals R. F., Pearlson G. D., Links J. M., Tamminga C. A., Broussolle E. P., Ravert H. T., Wilson A. A. Positron emission tomography reveals elevated D2 dopamine receptors in drug-naive schizophrenics. Science. 1986 Dec 19;234(4783):1558–1563. doi: 10.1126/science.2878495. [DOI] [PubMed] [Google Scholar]
- Wood F. B., Flowers D. L. Hypofrontal vs. hypo-Sylvian blood flow in schizophrenia. Schizophr Bull. 1990;16(3):413–424. doi: 10.1093/schbul/16.3.413. [DOI] [PubMed] [Google Scholar]
- Yoshii F., Barker W. W., Chang J. Y., Loewenstein D., Apicella A., Smith D., Boothe T., Ginsberg M. D., Pascal S., Duara R. Sensitivity of cerebral glucose metabolism to age, gender, brain volume, brain atrophy, and cerebrovascular risk factors. J Cereb Blood Flow Metab. 1988 Oct;8(5):654–661. doi: 10.1038/jcbfm.1988.112. [DOI] [PubMed] [Google Scholar]
- Zatz L. M., Jernigan T. L., Ahumada A. J., Jr Changes on computed cranial tomography with aging: intracranial fluid volume. AJNR Am J Neuroradiol. 1982 Jan-Feb;3(1):1–11. [PMC free article] [PubMed] [Google Scholar]
- Zeeberg B. R., Gibson R. E., Reba R. C. Elevated D2 dopamine receptors in drug-naïve schizophrenics. Science. 1988 Feb 12;239(4841 Pt 1):789–791. doi: 10.1126/science.2963379. [DOI] [PubMed] [Google Scholar]
- Zipursky R. B., Lim K. O., Pfefferbaum A. Volumetric assessment of cerebral asymmetry from CT scans. Psychiatry Res. 1990 Apr;35(1):71–89. doi: 10.1016/0925-4927(90)90010-4. [DOI] [PubMed] [Google Scholar]