Hostname: page-component-586b7cd67f-rdxmf Total loading time: 0 Render date: 2024-11-25T19:13:38.089Z Has data issue: false hasContentIssue false
  • English
  • Français

Altered cerebral perfusion measured by SPECT in relatives of patients with schizophrenia

Correlations with memory and P300

Published online by Cambridge University Press:  31 January 2018

Douglas H. R. Blackwood ,
Mike F. Glabus ,
Julie Dunan ,
Ronan E. O'Carroll ,
Walter J. Muir  and
Klaus P. Ebmeier
Douglas H. R. Blackwood*
Affiliation:
Edinburgh University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh
Mike F. Glabus
Affiliation:
Edinburgh University Department of Medical Physics, Royal Infirmary, Edinburgh and MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh
Julie Dunan
Affiliation:
Department of Clinical Psychology, Stobhill Hospital, Glasgow
Ronan E. O'Carroll
Affiliation:
Department of Psychology, University of St Andrews
Walter J. Muir
Affiliation:
Edinburgh University Department of Psychiatry, Royal Edinburgh Hospital, Edinburgh
Klaus P. Ebmeier
Affiliation:
Edinburgh University Department of Psychiatry and MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Edinburgh
*
Professor D. H. R. Blackwood, Edinburgh University Department of Psychiatry, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF. Tel: 0131 537 6000; Fax: 0131 537 6259; e-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Genetic studies in schizophrenia are hampered by the complex heterogeneous clinical phenotype. Biological variables identified as trait markers of risk could clarify the mode of inheritance, define clinical subgroups and provide clues about aetiology.

Aims

To use single photon emission computed tomography (SPECT) to compare brain perfusion maps in patients with schizophrenia (n=19), their asymptomatic ‘high-risk’ relatives (n=36) and control subjects (n=34) and to examine the relationships between imaging, memory and P300 event-related potential.

Method

SPECT, memory tests and P300 recording were carried out.

Results

In the patients with schizophrenia and their relatives, perfusion was reduced in left inferior prefrontal and anterior cingulate cortex and increased bilaterally in a subcortical region. Perfusion significantly correlated with verbal memory and P300 amplitude in left inferior prefrontal cortex and with P300 latency in anterior cingulate cortex.

Conclusions

Medication– and symptom-free relatives had altered regional perfusion intermediate between subjects with schizophrenia and controls. Impaired perfusion, verbal memory and P300 appear to be related traits associated with an increased risk of illness.

Type
Papers
Information
The British Journal of Psychiatry , Volume 175 , Issue 4 , October 1999 , pp. 357 - 366
Copyright
Copyright © 1999 The Royal College of Psychiatrists 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

Declaration of interest

Funded by the Medical Research Council and the Scottish Office.

References

American Psychiatric Association (1994) Diagnostic and Statistical Manual of Mental Disorders (4th edn) (DSM–IV). Washingon, DC: APA.Google Scholar
Andreasen, N. C., O'Leary, D. S., Flaum, M., et al (1997) Hypofrontality in schizophrenia: distributed dysfunctional circuits in neuropleptic naïve patients. Lancet, 349, 1730–1734.Google Scholar
Annett, M. (1970) A classification of hand preference by association analysis. British Journal of Psychology, 62, 303–321.Google Scholar
Blackwood, D. H. R., Whalley, L. J., Christie, J. E., et al (1987) Changes in auditory P3 event-related potentials in schizophrenia and depression. British Journal of Psychiatry, 150, 154–160.Google Scholar
Blackwood, D. H. R., St Clair, D. M., Muir, W. J., et al (1991a) Auditory P300 and eye tracking dysfunction in schizophrenic pedigrees. Archives of General Psychiatry, 48, 899–909.Google Scholar
Blackwood, D. H. R., Young, A. H., McQueen, J. K., et al (1991b) Magnetic resonance imaging in schizophrenia; altered brain morphology associated with P300 abnormalities and eye tracking dysfunction. Biological Psychiatry, 30, 753–769.Google Scholar
Blackwood, D. H. R., Ebmeier, K. P., Muir, W. J., et al (1994) Correlation of regional cerebral blood flow measured by single photon emission tomography with P300 latency and eye movement abnormality in schizophrenia. Acta Psychiatrica Scandinavica, 90, 157–166.Google Scholar
Borowski, J., Benton, A. & Spreen, O. (1967) Word fluency and brain damage. Neuropsychologic, 5, 135–140.Google Scholar
Buchsbaum, M. S., Wu, J. C., DeLisi, L. E., et al (1987) Positron emission tomography studies of basal ganglia and somatosensory cortex: neuroleptic drug effects: differences between normal controls and schizophrenic patients. Biological Psychiatry, 22, 479–494.Google Scholar
Cannon, T. D., Mednick, S. A., Pirnas, J., et al (1993) Developmental brain abnormalities in the offspring of schizophrenic mothers. I: Contributions of genetic and perinatal factors. Archives of General Psychiatry, 50, 551–564.Google Scholar
Chua, S. E. & McKenna, P. J. (1995) Schizophrenia – a brain disease? A critical review of structural and functional cerebral abnormality in the disorder. British Journal of Psychiatry, 166, 563–582.Google Scholar
Delis, D. C., Kramer, J. H., Kaplan, E., et al (1987) California Verbal Learning Test (CVLT) Manual. New York: Psychological Corporation.Google Scholar
Early, T. S., Reiman, E. M., Rachle, M. E., et al (1987) Left globus pallidus abnormality in never-medicated patients with schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 84, 561–563.Google Scholar
Ebmeier, K. P., Blackwood, D. H. R., Murray, C., et al (1993) Single photon emission tomography with 99mTc-Exametazime in unmedicated schizophrenic patients. Biological Psychiatry, 33, 487–495.Google Scholar
Ebmeier, K. P., Lawrie, S. M., Blackwood, D. H. R., et al (1995a) Hypofrontality revisited: a high resolution single photon emission computed tomography study in schizophrenia. Journal of Neurology, Neurosurgery and Psychiatry, 58, 452–456.Google Scholar
Ebmeier, K. P., Steele, J. D., Mackenzie, D. M., et al (1995b) Cognitive brain potentials and regional cerebral blood flow equivalents during two- and three-sound auditory “oddball tasks”. Electroencephalography and Clinical Neurophysiology, 95, 434–443.Google Scholar
Endicott, J. & Spitzer, R. L. (1978) A diagnostic interview: the schedule for affective disorders and schizophrenia. Archives of General Psychiatry, 35, 837–844.Google Scholar
Erlenmeyer-Kimling, L., Comblatt, B. A., Rock, D., et al (1993) The New York High-Risk Project: anhedonia, attentional deviance and psychopathology. Schizophrenia Bulletin, 19, 141–153.CrossRefGoogle ScholarPubMed
Fletcher, P., McKenna, P. J., Fristen, K. J., et al (1999) Abnormal cingulate modulation of fronto-temporal connectivity in schizophrenia. Neuroimage, 9, 337–342.Google Scholar
Frangou, S., Sharma, T., Alarcon, G., et al (1997) The Maudsley Family Study, 2: endogenous event-related potentials in familial schizophrenia. Schizophrenia Research, 23, 45–53.Google Scholar
Frazier, J. A., Giedd, J. N., Hamburger, S. D., et al (1996) Brain anatomic magnetic resonance in childhood-onset schizophrenia. Archives of General Psychiatry, 53, 617–624.CrossRefGoogle ScholarPubMed
Freedman, P., Coon, H., Myles-Worsley, M., et al (1997) Linkage of a neurophysiological deficit in schizophrenia to a chromosome 15 locus. Proceedings of the National Academy of Sciences of the United States of America, 94, 587–592.Google Scholar
Friedman, D., Cornblatt, B., Vaughan, H. G., et al (1988) Auditory event-related potentials in children at risk for schizphrenia: the complete initial sample. Psychiatry Research, 26, 202–221.Google Scholar
Frith, C. D., Friston, K. J., Liddle, P. F., et al (1991) A PET study of word finding. Neuropsychologia, 29, 1137–1148.Google Scholar
Friston, K. J. (1995) Commentary and opinion II. Statistical parametric mapping: ontology and current issues. Journal of Cerebral Blood Flow and Metabolism, 15, 361–370.Google Scholar
Ganguli, R., Carter, C., Mintun, M., et al (1997) PET brain mapping study of auditory verbal supraspan memory versus visual fixation in schizophrenia. Biological Psychiatry, 41, 33–42.Google Scholar
Glabus, M. F., Blackwood, D. H. R., Ebmeier, K. P., et al (1994) Methodological considerations in measurement of P300 component of the auditory oddball ERP in schizophrenia. Electroencephalography and Clinical Neurophysiology, 90, 123–134.Google Scholar
Heidrich, A. & Strik, W. K. (1997) Auditory P300 topography and neuropsychological test performance: evidence for left hemispheric dysfunction in schizophrenia. Biological Psychiatry, 41, 327–335.Google Scholar
Holzman, P. S., Proctor, I. R. & Levy, D. L. (1974) Eye tracking dysfunction in schizophrenic patients and their relatives. Archives of General Psychiatry, 31, 143–151.Google Scholar
Honer, W. G., Bassett, A. S., Smith, G. N., et al (1994) Temporal lobe abnormalities in multigenerational families with schizophrenia. Biological Psychiatry, 36, 737–743.Google Scholar
Itil, T., Hsu, W., Saletu, B., et al (1974) Computer EEG and auditory evoked potential investigations in children at risk for schizophrenia. American Journal of Psychiatry, 131, 892–900.Google Scholar
Karayiorgou, M. & Gogos, J. A. (1997) Dissecting the genetic complexity of schizophrenia. Molecular Psychiatry, 2, 211–223.Google Scholar
Keefe, R. S. E., Silverman, J. M., Roitman, S. E. L., et al (1994) Performance of nonpsychotic relatives of schizophrenic patients on cognitive tests. Psychiatric Research, 53, 1–12.Google Scholar
Keefe, R. S. E., Silverman, J. M., Mohs, R. C., et al (1997) Eye tracking, attention and schizotypal symptoms in nonpsychotic relatives of patients with schizophrenia. Archives of General Psychiatry, 54, 169–176.Google Scholar
Kendler, K. S. & Diehl, S. R. (1993) The genetics of schizophrenia: a current genetic epidemiologic perspective. Schizophrenia Bulletin, 19, 261–285.Google Scholar
Kidogami, Y., Yoneda, H., Aaba, H., et al (1992) P300 in first degree relatives of schizophrenics. Schizophrenia Research, 6, 9–13.Google Scholar
Kremen, W. S., Seidman, L. J., Pepple, J. R., et al (1994) Neuropsychological risk indicators for schizophrenia: a review of family studies. Schizophrenia Bulletin, 20, 103–119.Google Scholar
Lawrie, S. M. & Abukmeil, S. S. (1998) Brain abnormality in schizophrenia. A systematic and quantitative review of volumetric magnetic resonance imaging studies. British Journal of Psychiatry, 172, 110–120.Google Scholar
Lawrie, S. M., Whalley, H., Kestelman, J. N., et al (1999) Magnetic resonance imaging of the brain in subjects at high risk of developing schizophrenia. Lancet, 353, 30–33.Google Scholar
McCarley, R. W., Faux, S. F., Shenton, M. E., et al (1991) Event related potentials in schizophrenia: their biological and clinical correlates and a new model of schizophrenic pathophysiology. Schizophrenia Research, 4, 209–231.Google Scholar
McCarley, R. W., Shenton, M. E., O'Donnell, B. F., et al (1993) Auditory P300 abnormalities and the left posterior superior temporal gyrus volume reduction in schizophrenia. Archives of General Psychiatry, 50, 190–197.Google Scholar
Muir, W. J., St Clair, D. M. & Blackwood, D. H. R. (1991) Long-latency auditory event-related potentials in schizophrenia and in bipolar and unipolar affective disorder. Psychological Medicine, 21, 867–879.Google Scholar
Murray, R. M. (1994) Neurodevelopmental schizophrenia: the rediscovery of dementia praecox. British Journal of Psychiatry, 165 (suppl. 25), 6–12.Google Scholar
Nelson, H. E. & Willison, J. R. (1991) The Revised National Adult Reading Test – Test Manual. Windsor: NFER–Nelson.Google Scholar
O'Carroll, R. E., Walker, M., Dunan, J., et al (1992) Selecting controls for schizophrenia research studies: the use of the National Adult Reading Test (NART) as a measure of premorbid ability. Schizophrenia Research, 8, 137–141.Google Scholar
Pearison, G. D., Barta, P. E., Powers, R. E., et al (1997) Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder. Biological Psychiatry, 41, 1–14.CrossRefGoogle Scholar
Pfefferbaum, A., Wingegrat, B. G., Ford, J. M., et al (1984) Clinical application of the P3 component of event related potentials. Dementia, depression and schizophrenia. Electroencephalography and Clinical Neurophysiology, 59, 101–124.Google ScholarPubMed
Ross, C. A. & Pearison, G. D. (1996) Schizophrenia, the heteromodal association neocortex and development: potential for neurogenetic approach. Trends in Neuroscience, 19, 171–176.Google Scholar
Roth, W. T. & Cannon, E. H. (1972) Some features of the auditory evoked responses in schizophrenics. Archives of General Psychiatry, 27, 466–477.Google Scholar
Roxborough, H., Muir, W. J., Blackwood, D. H. R., et al (1993) Neuropsychological and P300 abnormalities in schizophrenics and their relatives. Psychological Medicine, 23, 305–314.Google Scholar
Roy, M. A., Flaum, M. A., Arndt, S. V., et al (1994) Magnetic resonance imaging in familial versus sporadic cases of schizophrenia. Psychiatry Research, 54, 25–36.Google Scholar
Sabri, O., Erkwoh, R., Schreckenberger, M., et al (1997) Correlation of positive symptoms exclusively to hyperperfusion or hypoperfusion of cerebral cortex in never treated schizophrenics. Lancet, 349, 1735–1739.Google Scholar
Saitoh, O., Niwa, S. I., Hiramatsu, K. I., et al (1984) Abnormalities in late positive component of event related potentials may reflect a genetic predisposition to schizophrenia, biological Psychiatry, 19, 293–303.Google Scholar
Saykin, A. J., Shtasel, D. L., Gur, R. E., et al (1994) Neuropsychological deficits in neuroleptic naive patients with first episode schizophrenia. Archives of General Psychiatry, 51, 124–131.Google Scholar
Schreiber, H., Stolz-Born, C., Kornhuber, H. H., et al (1992) Event-related potential correlates of impaired selective attention in children at high risk for schizophrenia. Biological Psychiatry, 32, 634–651.Google Scholar
Seidman, L. J., Faraone, S. V., Goldstein, J. M., et al (1997) Reduced subcortical brain volumes in nonpsychotic siblings of schizophrenic patients: a pilot magnetic resonance imaging study. American Journal of Medical Genetics, 74, 507–514.Google Scholar
Shajahan, P. M., O'Carroll, R. E., Glabus, M. F., et al (1997a) Correlation of auditory “oddball’ P300 with verbal memory deficits in schizophrenia. Psychological Medicine, 27, 579–586.Google Scholar
Shajahan, P. M., Glabus, M. F., Blackwood, D. H. R., et al (1997b) Brain activation during an auditory “oddball task” in schizophrenia measured by single photon emission tomography. Psychological Medicine, 27, 587–594.Google Scholar
Sham, P. C., Morton, N. E., Muir, W. J., et al (1994) Segregation analysis of complex phenotypes: an application to schizophrenia and auditory P300 latency. Psychiatric Genetics, 4, 29–38.Google Scholar
Sharma, T, Lancaster, E., Lee, E. X., et al (1998) Brain changes in schizophrenia. Volumetric MRI study of families multiply affected with schizophrenia – the Maudsley Family Study 5. British Journal of Psychiatry, 173, 132–138.Google Scholar
Shediack, K., Lee, G., Sakuma, M., et al (1997) Language processing and memory in ill and well siblings from multiplex families affected with schizophrenia. Schizophrenia Research, 25, 43–52.Google Scholar
Shihabuddin, L, Silverman, J. M., Buchsbaum, M. S., et al (1996) Ventricular enlargement associated with linkage marker for schizophrenia-related disorders in one pedigree. Molecular Psychiatry, 1, 215–222.Google Scholar
Siegel, B. V., Buchsbaum, M. S., Bunney, W. E., et al (1993) Cortical-striatal-thalamic circuits and brain glucose metabolic activity in 70 unmedicated male schizophrenic patients. American Journal of Psychiatry, 150, 1325–1336.Google Scholar
Souza, V. B. N., Muir, W. J., Walker, M. T., et al (1995) Auditory P300 event-related potentials and neuropsychological performance in schizophrenia and bipolar affective disorder. Biological Psychiatry, 37, 300–310.Google Scholar
Talairach, J. & Tournoux, P. (1988) Co-Planar Stereotaxic Atlas of the Human Brain. Stuttgart: Georg Thieme.Google Scholar
Tamminga, C. A., Thaker, G. K., Buchanan, M., et al (1992) Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome. Archives of General Psychiatry, 49, 522–530.Google Scholar
Wechsler, D. (1987) The Wechsler Memory Scale-Revised. New York: Psychological Corporation.Google Scholar
Weinberger, D. R. (1995) From neuropathology to neurodevelopment. Lancet, 346, 552–557.Google Scholar
Weinberger, D. R., De Lisi, L. E., Neophytides, A. N., et al (1981) Familial aspects of CT scan abnormalities in chronic schizophrenic patients. Psychiatry Research, 4, 65–71.Google Scholar
Weinberger, D. R., Berman, K. F., Suddath, R., et al (1992) Evidence of dysfunction of a prefrontal – limbic network in schizophrenia: a magnetic resonance imaging and regional cerebral blood flow study of discordant monozygotic twins. American Journal of Psychiatry, 149, 890–897.Google Scholar
Wible, C. G., Shenton, M. E., Hokama, H., et al (1995) Prefrontal cortex and schizophrenia: a quantitative magnetic resonance imaging study. Archives of General Psychiatry, 52, 279–288.Google Scholar
Wiesel, F. A., Wik, G., Sjogren, I., et al (1987) Regional brain glucose metabolism in drug free schizophrenic patients and clinical correlates. Acta Psychiatrica Scandinavica, 76, 628–641.Google Scholar
Submit a response

eLetters

No eLetters have been published for this article.