Neurobiology of schizophrenia

Current Opinion in Psychiatry

Volumn 9, Issue 1, 1996, Pages 50-56

  Deakin, J F W ^a  

^a MANCHESTER ROYAL INFIRMARY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 AMINOBUTYRIC ACID; AMINO ACID; GLUTAMATE RECEPTOR; GLUTAMIC ACID; NEUROTRANSMITTER;

BASAL GANGLION; BRAIN ASYMMETRY; BRAIN CORTEX; BRAIN REGION; COMPUTER ASSISTED TOMOGRAPHY; GRAY MATTER; HEMISPHERIC DOMINANCE; HIPPOCAMPUS; HUMAN; IMAGE ANALYSIS; NEUROBIOLOGY; NEUROCHEMISTRY; NUCLEAR MAGNETIC RESONANCE IMAGING; POSITRON EMISSION TOMOGRAPHY; SCHIZOPHRENIA; SHORT SURVEY; SINGLE PHOTON EMISSION COMPUTER TOMOGRAPHY;

EID: 0030041474     PISSN: 09517367     EISSN: None     Source Type: Journal    
DOI: 10.1097/00001504-199601000-00010     Document Type: Short Survey

References (66)

1. Chua SE, McKenna PJ: Schizophrenia - a brain disease? A critical review of structural and functional cerebral abnormality in the disorder. Br J Psychiatry 1995, 166:563-582. Required reading. Scientific equivalent of a cold shower.
2. Schlaepfer TE, Harris GJ, Tien AY, Peng LW, Lee S, Federman EB, Chase GA, Barta PE, Pearlson GD: Decreased regional cortical gray matter volume in schizophrenia. Am J Psychiatry 1994, 151:842-848. Important magnetic resonance study of 46 patients with schizophrenia, 27 bipolar and 60 control individuals. Hypothesis-driven analysis showed a significant decrease in volume of heteromodal association cortex (aggregate of dorsolateral prefrontal cortex, inferior parietal lobule and superior temporal gyrus volumes) in a group with schizophrenia but not of visual plus sensorimotor cortex. Bipolars showed no differences supporting specificity of reduced heteromodal cortex volume for schizophrenia
3. Zipursky RB, Marsh L, Lim KO, Dement S, Shear PK, Sullivan EV, Murphy GM, Csernansky JG, Pfefferbaum A: Volumetric MRI assessment of temporal lobe structures in schizophrenia. Biol Psychiatry 1994, 35: 501-516. An important and carefully performed study of 22 patients and matched control individuals. Every cortical area was smaller and each region of the ventricular system was larger in patients than in controls. Hippocampi were not smaller in the patients.
4. Harvey I, Persaud R, Ron MA, Baker G, Murray RM: Volumetric MRI measurements in bipolars compared with schizophrenics and healthy controls. Psychol Med 1994, 24:689-699. Compares magnetic resonance regional brain volumetric measures in bipolar individuals with volumes in patients with schizophrenia and in control individuals which had been determined with the same scanner two years previously. The study used thick 5 mm slices and truncated coverage of brain but automatic grey-white segmentation. Bipolar individuals showed few of the changes previously determined in the group with schizophrenia. The latter showed a generalized loss of grey matter, sulcal atrophy and enlargement of the sytvian fissure which was more marked on the left. Suggests that changes in schizophrenia are specific for the condition.
5. Andreasen NC, Arndt S, Swayze V, Cizadlo T, Flaum M, Oleary D, Ehrhardt JC, Yuh WTC: Thalamic abnormalities in schizophrenia visualized through magnetic resonance Image averaging. Science 1994, 266: 294-298. An important study involving a novel image analysis technique to average the three dimensional structure of a group of magnetic resonance scans from patients and control individual and then to show the significance of the group differences. The main difference was a smaller thalamic volume in patients with no significant differences in the temporal lobe or other cortical region. The possibility of artefact of smaller variation in thalamic volumes exists because they are central and close to the reference points.
6. Andreasen NC, Rashman L, Flaum M, Arndt S, Swayze V, Oleary DS, Ehrhardt JC, Yuh WTC: Regional brain abnormalities in schizophrenia measured with magnetic resonance imaging. JAMA 1994, 272: 1763-1769. An important large magnetic resonance study of 52 patients and 92 control individuals using high resolution 1.5 mm slices and sophisticated automatic image analysis. Selective loss of frontal grey matter was observed although was evidence of more widespread loss in males.
7. Flaum M, Swayze II VW, O'Leary DS, Yuh WTC, Ehrhardt JC, Arndt SV, Andreasen NC: Effects of diagnosis, laterality and gender on brain morphology in schizophrenia. Am J Psychiatry 1995, 152:704-714. A magnetic resonance study of 102 patients and 87 control individuals. The study showed that in the patients the ventricles were bigger, and the thalamus, hippocampus and superior temporal gyrus were smaller. Temporal lobe, caudates and temporal horns were individuals not different. No laterality or sex effects were observed
8. Elkashef AM, Buchanan RW, Gellad F, Munson RC, Breier A: Basal ganglia pathology in schizophrenia and tardive dyskinesia: an MRI quantitative study. Am J Psychiatry 1994, 151:752-755. The authors of this magnetic resonance study in 25 patients and matched control individuals found increased volumes of globus pallidus, caudate and putamen and less asymmetry in the patients. The authors speculate that either a failure of neuronal pruning in development or neuroleptic action is the mechanism. A combination of increased volume and loss of asymmetry is exactly the pattern predicted by an arrest of the development of asymmetry.
9. Chakos MH, Lieberman JA, Bilder RM, Borenstein M, Lerner G, Bogerts B, Wu HW, Kinon B, Ashtari M: Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. Am J Psychiatry 1994, 151:1430-1436.
10. Keshaven et al.: Lancet 1994, 344:1434.
11. Vita A, Giobbio GM, Dieci M, Garbarini M, Morganti C, Comazzi M, Invernizzi G: Stability of cerebral ventricular size from the appearance of the first psychotic symptoms to the later diagnosis of schizophrenia. Biol Psychiatry 1994, 35:960-962.
12. Jaskiw GE, Julioano DM, Goldberg TE, Hertzman M, Urow-Hamell E, Weinberger DR: Cerebral ventricular enlargement in schizophreniform disorder does not progress. A seven year follow-up study. Schizophr Res 1994, 14:23-28.
13. Rossi A, Stratta P, Mancini F, Gallucci M, Mattei P, Dimichele V, Casacchia M, Core L: Magnetic resonance imaging findings of amygdala anterior hippocampus shrinkage in male patients with schizophrenia. Psychiatry Res 1994, 52:43-53.
14. Arnold SE, Franz BR, Gur RC, Gur RE, Shapiro RM, Moberg PJ, Trojanowski JQ: Smaller neuron size in schizophrenia in hippocampal subfields that mediate cortical-hippocampal interactions. Am J Psychiatry 1995, 152:738-748. A post-mortem brain study. Pyramidal cells were 10% smaller in hippocampal subfields but not in control individuals in the visual or motor neocortex. No reductions in density or orientation were observed. Somewhat greater reduction in subicular and other regions related to afferent and efferent connections of hippocampus but statistics do not strongly support this specificity.
15. Zaidel DW, Esiri MM, Eastwood SL, Harrison PJ: Asymmetrical hippocampal circuitry and schizophrenia [letter]. Lancet 1995, 345: 656-657.
16. Goldsmith SK, Joyce JN: Alterations in hippocampal mossy fiber pathway in schizophrenia and Alzheimer's disease. Biol Psychiatry 1995, 37: 122-126. In post-mortem samples of the hippocampus, increased Timm's staining reveals sprouting of Mossy fibres to replace degenerated entorhinal afferents in Alzheimers disease. No evidence has been found of sprouting and, therefore, of loss of entorhinal afferents in schizophrenia.
17. Bilder RM, Wu HW, Bogerts B, Degreef G, Ashtari M, Alvir JMJ, Snyder PJ, Lieberman JA: Absence of regional hemispheric volume asymmetries in first-episode schizophrenia. Am J Psychiatry 1994, 151:1437-1447. Normal brain asymmetry on coronal sections is that posterior regions are larger on the right than on left, whereas frontal regions are larger on the left. This was shown in 51 control individuals and was more marked in males but asymmetries were significantly less in 71 patients in their first episode. This was true of each cortical area studied and suggests pervasive developmental disturbance
18. Petty RG, Barta PE, Pearlson GD, McGilchrist IK, Lewis RW, Tien AY, Pulver A, Vaughn DD, Casanova MF, Powers RE: Reversal of asymmetry of the planum temporale in schizophrenia. Am J Psychiatry 1995, 152: 715-721. This study showed a clear reversal of normal asymmetry in patients with schizophrenia using sophisticated image analysis techniques.
19. Falkai P, Bogerts B, Schneider T, Greve B, Pfieffer U, Pilz K, Gonsiorzcyk C, Majtenyi C, Ovary I: Disturbed planum temporale asymmetry in schizophrenia. A quantitative post-mortem study. Schizophr Res 1995, 14: 161-176 The planum temporale is located in the superior temporal gyrus and is normally bigger on the left reflecting its specialized function in language as shown in this post-mortem brain study. Twenty-four brains from patients with schizophrenia failed to show normal asymmetry of the planum; asymmetry was absent in females and reversed in males. The findings implicate a disturbance in development of asymmetry in schizophrenia.
20. Kulynych JJ, Vladar K, Fantie BD, Jones DW, Weinberger DR: Normal asymmetry of the planum temporale in patients with schizophrenia. Three-dimensional cortical morphometry with MRI. Br J Psychiatry 1995, 166:742-749. A study of only 12 patients and 12 control individuals. The image analysis was good and no loss of asymmetry of planum temporale was observed in patients.
21. Vita A, Dieci M, Giobbio GM, Capulo A, Ghiringhelli L, Comazzi M, Garbarini M, Mendini AP, Morganti C, Tenconi F, Cesana B, Invemizzi G: Language and thought disorder in schizophrenia: brain morphological correlates. Schizophr Res 1995, 15:243-251. A study showing ventricular-brain ratio but no reduction in frontal, temporal or superior temporal gyral volumes in 19 patients and 15 control individuals. Some relationships were demonstrated between Thought Language and Communication Scale scores and frontal lobe volume and also with lack of split-thickness graft asymmetry. The study involved too few subjects and too many correlations.
22. Seidman U, Yurgelun-Todd O, Kremen WS, Woods BT, Goldstein JM, Faraone SV, Tsuang MT: Relationship of prefrontal and temporal lobe MRI measures to neuropsychological performance in chronic schizophrenia. Biol Psychiatry 1994, 35:235-246. Performance on tests of attention, abstract reasoning and executive function correlated with dorsolateral prefrontal cortex area but not orbital in one section of magnetic resonance scans of 17 patients. This is one of very few studies to subdivide frontal cortex and show relation with frontal lobe function tests. The study involved too few subjects and too many correlations.
23. Goldberg TE, Torrey EF, Berman KF, Weinberger DR: Relations between neuropsychological performance and brain morphological and physiological measures in monozygotic twins discordant for schizophrenia. Psychiatry Res 1994, 55:55-61. A study of monozygotic twins discordant for schizophrenia. Intrapair differences in left hippocamapal volumes correlated with intrapair differences in logical memory performance. Differences in frontal positron emission tomography activation during Wisconsin Card Sort Test also correlated with logical memory. This study adds weight to the Weinberger view that structural abnormalities of the temporal lobe affect functioning of the frontal lobe in schizophrenia.
24. Waldo MC, Cawthra E, Adler LE, Dubester S, Staunton M, Nagamoto H, Baker N, Madison A, Simon J, Scherzinger A et al.: Auditory sensory gating, hippocampal volume, and catecholamine metabolism in schizophrenics and their siblings. Schizophr Res 1994, 12:93-106. A pilot study relating normal versus abnormal 'sensory gating' (P50-an electrophysiological measure of the suppression of an event-related potential to a click by a preceding click stimulus) to plasma homovanillic acid and to hippocampal volume. The study involved 11 schizophrenics, 20 unaffected siblings and 13 control individuals. Schizophrenics had normal hippocampi but siblings with abnormal gating had larger hippocampi. In principle it is a good idea to relate abnormal information processing in relatives to brain morphometry, but the direction of change is unexpected. Such studies require much larger sample sizes. Pilot studies clutter the literature.
25. Vita A, Dieci M, Giobbio GM, Garbarini M, Morganti C, Braga M, Invernizzi G: A reconsideration of the relationship between cerebral structural abnormalities and family history of schizophrenia Psychiatry Res 1994, 53: 41-55 This large (n = 229) but retrospective study found larger ventricles in males without a family history of schizophrenia but no difference in sulcal atrophy. Metaanalysis of eight other studies (total sample = 447) confirmed the ventricular-brain ratio result but with borderline statistical significance. This is a problematic finding since most patients with a negative family history nevertheless transmit risk. This and other studies suggest that sulcal atrophy and increased ventricular-brain ratio may be distinct pathological processes.
26. Cannon TD, Mednick SA, Parnas J, Schulsinger F, Praestholm J, Vestergaard A: Developmental brain abnormalities in the offspring of schizophrenic mothers. 2. Structural brain characteristics of schizophrenics and schizotypal personality disorder Arch Gen Psychiatry 1994, 51:955-962. An important study of 60, 72 and 25 individuals with respectively neither one or both parents affected by schizophrenia. Increased ventricular and cortical cerebrospinal fluid spaces were found to have a linear relation to generic risk. This relationship was especially marked in those with perinatal birth complications and argues against ideas that ventricular dilatation indicates a nongenetic route to schizophrenia.
27. Honer WG, Bassett AS, Smith GN, Lapointe JS, Falkai P: Temporal lobe abnormalities in multigenerational families with schizophrenia. Biol Psychiatry 1994, 36:737-743. A computed tomography scan study in patients and unaffected relatives. Temporal lobes were smaller in patients than in relatives, but frontal lobes were not significantly different. No controls were used; therefore, frontal volumes may have been normal in both groups. These findings are compatible with the view that relatives and patients share frontal pathology but only patients have temporal. More family studies in schizophrenia are essential to identify what, if any, brain changes are genetically transmitted.
28. Bullmore E, Brammer M, Harvey I, Persaud R, Murray R, Ron M: Fractal analysis of the boundary between white matter and cerebral cortex in magnetic resonance images: a controlled study of schizophrenic and manic-depressive patients. Psychol Med 1994, 24:771-781. Coastlines, snowflakes, clouds and the grey-white matter boundary on magnetic resonance scans are examples of fractal objects in having perimeters that are similar at different magnifications. The intricacy of the outline is reflected in the fractal number. If schizophrenia is associated with neurodevelopmental impairment, the grey-white matter boundary should be less intricate than in control individuals.
29. Dequardo JR, Tandon R, Goldman R, Meador-Woodruff JH, McGrath-Giroux M, Brunberg JA, Kim L: Ventricular enlargement, neuropsychological status, and premorbid function in schizophrenia. Biol Psychiatry 1994, 35: 517-524.
30. Levitt JJ, Shenton ME, McCarley RW, Faux SF, Ludwig AS: Premorbid adjustment in schizophrenia: implications for psychosocial and ventricular pathology. Schizophr Res 1994, 12:159-168.
31. Breese CR, Freedman R, Leonard SS: Glutamate receptor subtype expression in human postmortem brain tissue from schizophrenics and alcohol abusers. Brain Res 1995, 674:82-90. Messenger RNA for the glutamate receptor subunits R1,2,3 and 5 are not significantly different in the hippocampus or cingulate cortex in patients compared with control individuals who did not have a history of alcohol abuse. Samples from alcohol abusers showed increased GluR2 and 3 expression.
32. Kerwin RW, Harrison PJ: Loss of non NMDA receptors in medial temporal lobe - a robust neurochemical finding: autoradiographic, gene expression and immunocytochemical findings. Schizophr Res 1995, 15:62.
33. Bekewith JP, Stefanis NC, McLaughlin DP, Kerwin RW: The expression of NMDA receptor subunits in schizophrenic post-mortem human hippocampus. Schizophr Res 1995, 15:54.
34. Humphries CR, Virgo L, Mortimer A, Barnes T, Hirsch S, de Belleroche J: The expression of the N-methyl-D-aspartate receptor subunit NR, is decreased in schizophrenia. Schizophr Res 1995, 15:60-61.
35. Nasrallah HA, Skinner TE, Schmalbrock P, Robitaille PM: Proton magnetic resonance spectroscopy (1H MRS) of the hippocampal formation in schizophrenia: a pilot study. Br J Psychiatry 1994, 165:481-485.
36. Renshaw PF, Yurgeluntodd DA, Tohen M, Gruber S, Cohen BM: Temporal lobe proton magnetic resonance spectroscopy of patients with first-episode psychosis. Am J Psychiatry 1995, 152:444-446. A preliminary study showing a 10% reduction in the N-acetyl aspartate: creatine ratio in both temporal lobes of a first episode psychosis group of seven brief reactive or schizophreniform patients and six bipolare. The reduction could be secondary to structural changes.
37. Buckley PF, Moore C, Long H, Larkin C, Thompson P Mulvany F, Redmond O, Stack JP, Ennis JT, Waddington JL: H-1-magnetic resonance spectroscopy of the left temporal and frontal lobes in schizophrenia: clinical, neurodevelopmental, and cognitive correlates. Biol Psychiatry 1994, 36:792-800. A proton spectroscopy study of 28 patients and 20 control individuals in which male patients but not female had reduced N-acetyl aspartate in the frontal region but not in the temporal.
38. Stanley JA, Williamson PC, Drost DJ, Carr TJ, Rylett J, Malla A, Thompson T: An in-vivo study of the prefrontal cortex of schizophrenic patients at different stages of illness via phosphorus magnetic resonance spectroscopy. Arch Gen Psychiatry 1995, 52:399-406.
39. Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzol A, Bunney WEJ, Jones EG: Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics. Arch Gen Psychiatry 1995, 52:258-266. A high resolution in-situ hybridization study in postmortem prefrontal cortex that demonstrated decreased messenger RNA for the SABA synthetic enzyme glutamic acid decarboxylase per cell. No reduction in cell numbers was observed. The authors conclude that the cells are less activated.
40. Delini-Stula A, Berdah-Tordjman D: Benzodiazeprines and the GABA hypothesis of schizophrenia. J Psychopharmacol 1995, 9:57-63.
41. 2-receptor binding was found in the patient group and the male controls had low laterally. This study partially corroborates earlier positron emission tomography laterally findings.
42. 2-receptor binding which may have been due to drug treatment.
43. 2-receptor binding and clinical features in eight drug-naive patients that showed no difference between patients and controls but did show a strong association between less binding and negative symptoms. This prompts the question: what is a correlate in controls with equally less binding? Perhaps lower binding in patients orginates from loss of neuropil but in controls from normal variation.
44. 2 receptor binding in the basal ganglia. Psychol Med 1994, 24:423-429.
45. 2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate. Am J Psychiatry 1995, 192:173-178.
46. 2-dopamine receptor occupancy differs between patients with and without extrapyramidal side effects. Acta Psychiatr Scand 1994, 90: 266-268.
47. 2-dopamine receptor occupancy during treatment with typical and atypical neuroleptics. Biol Psychiatry 1994, 36:627-629.
48. 2 receptor blockade in vivo with the novel antipsychotics risperidone and remoxipride - An I-123-IBZM single photon emission tomography (SPET) study. Psychopharmacology (Berl) 1995, 117:55-61.
49. Bartlett EJ, Brodie JD, Simkowitz P, Dewey SL, Rusinek H, Wolf AP, Fowler JS, Volkow ND, Smith G, Wolkin A, Cancro R: Effects of haloperidol challenge on regional cerebral glucose utilization in normal human subjects. Am J Psychiatry 1994, 151:681-686.
50. Wolkin A, Sanfilipo M, Angrist B, Duncan E, Wieland S, Wolf AP, Brodie JD, Cooper TB, Laska E, Rotrosen JP: Acute d-amphetamine challenge in schizophrenia: effects on cerebral glucose utilization and clinical symptomatology Biol Psychiatry 1994, 36:317-325.
51. 31P MRS study in 20 chronic patients and 16 controls. Increased phosphodiesters were found bilaterally in frontal but not parietal lobes. No decrease in phosphomonoesters was seen.
52. 31P MRS dorsolateral perfrontal cortex study in 11 drug naive first episode patients, eight medicated first episodes and 21 controls demonstrated decreased phosphomonoesters (involved in membrane synthesis) and, only in the drug naive, increased phosphodiesters (breakdown products). The latter was also reported in another study in drug-naive, first episode patients and is suggestive of excessive membrane breakdown early in disease reversed by neuroleptics.
53. Horrobin DF, Glen AIM, Vaddadi K: The membrane hypothesis of schizophrenia. Schizophr Res 1994, 13:195-207.
54. 31P MRS in basal ganglia in 18 patients and 16 controls showing bilateral reduction of ATP but no differences in total phosphorous signal or inorganic phosphate, phospho diesters or creatine. The study involved too many comparisons. The results may be caused by drug effect.
55. Gur RC, Gur RE: Hypofrontality in schizophrenia: RIP. Lancet 1995, 345:1383-1384. A review of SPECT and positron emission tomography data for hypofrontality and find it severely wanting. No good evidence was presented for resting hypofunction and little better for task-related failure of frontal activation in schizophrenia.
56. Ebmeier KP, Lawrie SM, Blackwood DHR, Johnstone EC, Goodwin GM: Hypofrontality revisited: a high resolution single photon emission tomography study in schizophrenia. J Neurol Neurosurg Psychiatry 1995, 58:452-456. This careful study with exametazine SPECT revealed no evidence of hypofrontality. This represents a crucial study destroying the crude hypofrontality hypothesis.
57. Blackwood DHR, Ebmeier KP, Muir WJ, Sharp CW, Glabus M, Walker M, Souza V, Dunan JR, Goodwin GM: Correlation of regional cerebral blood flow equivalents measured by single photon emission computerized tomography with P300 latency and eye movement abnormality in schizophrenia. Acta Psychiatr Scand 1994, 90:157-166. Further analysis of a study which showed hyperfrontality in a Te-exametazine study of 14 drug-free patients with schizophrenia. Latency of P300 correlated with increased left frontal and parietal flow and abnormal eye tracking was associated with increased bifrontal and cingulate flow. The significance for pathogenesis is not clear except that the two physiological markers which run independently in families of patients have a different cerebral basis.
58. Vita A, Bressi S, Perani D, Invernizzi G, Giobbio M, Dieci M, Garbarini M, Del Sole A, Fazio F: High-resolution SPECT study of regional cerebral blood flow in drug-free and drug-naive schizophrenic patients. Am J Psychiatry 1995, 152:876-882. This IIMPAO study of eight drug-free and nine drug-naive patients produced different results depending on whether counts normalized to cerebellum or to whole brain. All significant effects were exclusive to drug-naive patients. General hypoperfusion was found when counts referred to cerebellum but not when they referred to whole brain.
59. Schroeder J, Buchsbaum MS, Siegel BV, Geider FJ, Haier RJ, Lohr J, Wu J, Potkin SG: Patterns of cortical activity in schizophrenia. Psychol Med 1994, 24:947-955. In this factor analytic study of regional glucose metabolic rate relative to whole brain in 83 patients, five factors emerged that roughly corresponded to main cortical regions: parietal, temporal, association, hypofrontal and frontal. Hypofrontal, left temporal and parietal factor scores discriminated between patient and controls. Hypofrontal score also has a loading of almost unity on primary visual cortex metabolism; it is difficult to understand how this relates to pathogenesis. This study requires replication; as with all factor analytic studies it will be interesting if factor scores relate to symptoms.
60. 15O water positron emission study in 13 control individuals and 20 patients with schizophrenia during resting state, reflexive, volitional and memory guided eye movement saccades shared increased regional cerebral blood flow in the visual cortex in both groups and all conditions but no activation of frontal eye fields in patients. There was a problem of greater resting forced expiratory flow in patients with schizophrenia and also a failure of normal dorsolateral prefrontal cortex activation in volitional saccades in patients.
61. Rubin P, Hemmingsen R, Holm S, Mollermadsen S, Hertel C, Povlsen UJ, Karle A: Relationship between brain structure and function in disorders of the schizophrenic spectrum: single position emission computerized tomography, computerized tomography and psychopathology of first episodes Acta Psychiatr Scand 90:281-289. A split dose HMPAO SPECT study with Wisconsin Card Sort activation in 50 first episode patients showing no significant frontal activation and significantly lower regional cerebral blood flow at rest and under activation in the patients. Positive symptoms correlated modestly with activated temporal flow. Thought disorder also correlated positively with frontal regional cerebral blood flow at rest and on activation. Perhaps the more active the hypofunctional circuits, the more productive they are of symptoms and hence the positive correlations with regional cerebral blood flow.
62. Liddle PF, Spence SA, Sharma T, Helliwell J, McGuire P, Deakin W, Murray RM, Friston KJ, Frith C: A PET study of obligate carriers of the predisposition to schizophrenia. Schizophr Res 1995, 15:90.
63. Hellewell JSE, Deakin JFW: Impaired frontal lobe function in schizophrenia is familial. Schizophr Res 1995, 15:121.
64. Busatto GF, Costa DC, Ell PJ, Pilowsky LS, David AS, Kerwin RW: Regional cerebral blood flow (rCBF) in schizophrenia during verbal memory activation: A Tc-99m-HMPAO single photon emission tomography (SPET) study. Psychol Med 1994, 24:463-472.
65. David A, Blamire A, Breiter H: Functional magnetic resonance imaging. A new technique with implications for psychology and psychiatry. Br J Psychiatry 1994, 164:2-7.
66. Renshaw PF, Yurgeluntodd DA, Cohen BM: Greater hemodynamic response to photic stimulation in schizophrenic patients: an echo planar MRI study. Am J Psychiatry 1994, 151:1493-1495. Functional magnetic resonance study showing that photic stimulation caused greater change in signal intensity in primary visual cortex in eight patients with schizophrenia than in control individuals.