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Cerebral venticular enlargement in young manic males
Jourrml of Affective Elsevier Biomedical
Disorders, 4 Press
(I 982) 15- 19
Cerebral Ventricular
15
Enlargement A Controlled
in Young Manic Males
CT Study
Henry A. Nasrallah ‘, Mona McCalley-Whitters Charles G. Jacoby 2
’
and
’ VA Medicul Center und Depurtment OJ Psych&v,
und -’ Department of Rudiologv, Unioersiiy of Iowu, College of Medicine, Iowu Cicv, IA 52240 (U.S.A.) (Received (Accepted
1I September, 30 September,
1981) 198 1)
Summary and Conclusions Computerized tomographic (CT) head scans of 24 young manic males were compared with those of 27 matched control subjects and 55 chronic schizophrenic patients. Cerebral ventricular size was significantly larger in the manic and schizophrenic patients compared to the control group. There was no difference in cerebral ventricular size between the manic and schizophrenic groups, suggesting that cerebral ventricular enlargement may be a nonspecific neuroanatomical correlate of psychotic disorders.
Introduction Schizophrenia and mania are two major psychotic disorders which have many clinical similarities that frequently lead to diagnostic confusion (Pope and Lipinski 1978). Although the development of operational criteria as in the DSM-III has greatly improved diagnostic reliability, the ultimate diagnostic tool will eventually have to include specific biological markers. Recently, several reports have shown that many chronic schizophrenic patients have structural brain abnormalities on computerized tomography (CT) such as enlarged lateral cerebral ventricles (Johnstone et al. 1976; Weinberger et al. 1979a; Correspondence: IA 52240, U.S.A.
Henry
0165-0327/82/0000-0000/$02.75
A. Nasrallah,
M.D., Chief, Psychiatry
0 1982 Elsevier Biomedical
Service, VA Medical
Press
Center,
Iowa City,
16
Golden et al. 1980), cerebral atrophy (Reider et al. 1979; Weinberger et al. 1979b) and cerebellar atrophy (Heath et al. 1979; Weinberger et al. 1979~). Very little is known, however, whether such brain abnormalities occur in mania and if they do at what frequency and to what extent. This report addresses the issue of whether cerebral ventricular enlargement is specific to the schizophrenic psychoses or possibly associated with manic psychosis as well.
Method Over a period of 1 year, 24 manic and 55 schizophrenic patients consented to participate in a CT study of the brain. All patients were males between 20 and 45 years of age who fulfilled the DSM-III criteria for mania or chronic schizophrenia. The mean age for the manic group was 31.8 years and for the schizophrenic group 29.9 years. For ethical reasons a prospective volunteer group for a CT study involving unnecessary radiation was not done. Instead a control group of 27 age- and sex-matched males was selected from consecutive victims of motor vehicle accidents who had a normal CT scan as part of their neurological workup. Control subjects were excluded if they had (a) a history of psychotic illness or (b) gross sensory-motor localizing signs and symptoms even if the CT was read as normal. The mean age for the control group was 28.7 years. CT scans were done on a Model 1005 EM1 scanner. Sections were made at g-mm intervals and most patients received 12 cuts. The films were then coded and the area of the cerebral ventricles was measured by a research technician using a mechanical Planimeter (Keuffler and Esser compensating polar planimeter, catalog No. 6620005) which integrates surface area when the periphery is traced. The area of the ventricles was measured on the cut that comes closes to passing through the body of the lateral ventricles. The area of the ventricles was divided by the area of the brain at that level so that ventricular size was expressed as the ventricle to brain ratio (VBR = area of ventricles X loo/area of brain) which has been shown to correlate well with ventricular volume (Penn et al. 1978). The method used here is similar to that used by Weinberger et al. (1979a).
Results Figure 1 shows a scattergram of VBR values for the controlled schizophrenic and manic groups. The ventricular size data was analyzed in two ways. (a) The difference between the means was analyzed by a two-tailed f-test. The mean VBR of the bipolar manic group (7.5 * 3.2) is significantly larger (t = 3.785, P < 0.005) than the mean control VBR (4.5 + 2.6). The mean VBR of the schizophrenic group (8.7 -C 4.0) is also significantly larger than the control group (t = 5.735, P
VENTRICLE
TO BRAIN RATIO ON C.T. SCANS
26 . 24 1 22
20
.
18 . .
16 ti 14 ai 5 12 IO 8
i 8 .
l
T
2 SD
8
4.5_+2.6
4
.
2
rc % 8
7.5t3.2
I SD 6
0
.
0
ERoLS $gZOPHRENIA
BIPOLAR ~~F&ZJI&E N=24
Fig. 1. A scattergram distribution control groups. The meankstandard
of the ventricle to brain ratio (VBR) in manic, schizophrenic deviation for each population is shown for comparison.
and
(b) A comparison was made between the manic and the schizophrenic groups as to how many patients in each group had a VBR that exceeded 2 standard deviations (SD) above the control mean VBR i.e. above 4.5 * (2 X 2.6) = 9.7. 19/55 (34.5%) of schizophrenic patients and 7/24 (29.2%) of manic patients exceeded 2 SD. There is no statistical difference between the two groups.
Discussion The data in this study indicate that there is no statistical difference in cerebral ventricular size between young manic males and young chronic schizophrenic males. The mean VBR value for the manic group is comparable to that of the schizophrenic graup, and the VBR distribution is similar in both patient groups. When compared to a normal control group, the manic and schizophrenic groups have significantly larger cerebral ventricular size. In a recent communication, Pearlson and Veroff (198 1) reported findings that validate the results of this study. They reported no significant difference in the mean
VBR of 16 manic-depressive patients when compared to 22 schizophrenic patients. The main implication of the findings is that enlarged cerebral ventricles on CT scans is not specific to chronic schizophrenia, but occurs in mania as well, at least in young male manic patienis who comprised the sample in this study. Further studies in young manic females are needed to validate the findings here, which suggest that enlarged cerebral ventricles is a neuroanatomical abnormality that is associated with psychosis rather than with a specific psychotic disorder. Additional support for this notion comes from reports indicating that cerebral ventricular enlargement on CT scans is present in patients with psychosis secondary to lupus erythematosus (Bilaniuk et al. 1977; Gonzales-Scarano et al. 1979). Studies in various psychotic conditions are necessary to confirm that cerebral ventricular size is a nonspecific finding. There is also the possibility that cerebral ventricular enlargement is a product of the drug treatment of psychosis. All the manic and schizophrenic patients in this study received neuroleptic drugs repeatedly since the onset of their illness. As for the effect of ECT on VBR, no significant difference was found between the mean VBR of manic patients with a history of ECT treatment (N = 4, mean VBR = 5.8) and the mean VBR of patients who had never received ECT (mean VBR = 8.2). This suggests that a history of ECT treatment is not associated with an increase in cerebral ventricular size. Finally, a note should be made of the fact that while the mean VBRs of the manic and schizophrenic patients are significantly larger than the mean VBR of the control group, there are many manic and schizophrenic patients with VBR values well within the range of the controls, while others are totally outside that range. It is possible that a subgroup of both manic (Kadrmas and Winokur 1979) and schizophrenic (Hays 1977) patients are associated with an organic etiology, while others are the result of genetic transmission. For this reason, the family history of psychosis, past history of perinatal brain injury, infantile encephalitis or head injury, and EEG abnormalities should be recorded on all patients with mania and schizophrenia. It may be that patients with negative family history and positive history of organic brain disease have larger VBR values than patients with a positive family history and negative organic findings. Such a study is currently underway to help elucidate the etiology of cerebral ventricular enlargement in mania and schizophrenia.
References Bilaniuk, L.T., Patel, S. and Zimmerman, R.A., Computed tomography of systemic lupus erythematosus. Radiology, 124 (I 977) 119- I2 1. Golden, C.J., Moses, J.A., Zelazowski, M.A. et al., Cerebral ventricular size and neuropsychological impairment in young chronic schizophrenics, Arch. Gen. Psychiat.. 37 (1980) 619-623. Gonzales-Scarano, F., Lisak, R.P., Bilaniuk, L.T. et al., Cranial computed tomography in the diagnosis of systemic lupus erythematosus, Ann. Neural., 5 (1979) 158- 165. Hays, P., Electroencephalic variant and genetic predisposition to schizophrenia, J. Neurol. Neurosurg. Psychiat., 40 (1977) 753-755.
19
Heath, R.G., Franklyn, D.E. and Shraberg, D., Gross pathology of the cerebellum in patients diagnosed and treated as functional psychiatric disorders, J. Nerv. Ment. Dis.. 167 (1979) 585-592. Johnstone, E.C., Crow, T.J., Frith, CD. et al., Cerebral ventricular size and cognitive impairment in chronic schizophrenia, Lancet, ii (1976) 924-926. Kadrmas, A.K. and Winokur, G., Manic depressive illness and EEG abnormalities, J. Clin. Psychiat., 40 (1979) 306-307. Pearlson, G.D. and Veroff, A.E., Computerized tomographic scan changes in manic-depressive illness, Lancet, ii ( I98 I) 470. Penn, R.D., Belanger, M.G. and Yasnoff, W.A., Ventricular volume in man computed from CAT scans, Ann. Neurol., 3 (1978) 216-223. Pope, H.G. and Lipinski, J.F., Diagnosis in schizophrenia and manic-depressive illness-A reassessment of the specificity of ‘schizophrenic’ symptoms in the light of current research, Arch. Gen. Psychiat., 35 (1978) 81 l-828. Rieder, R.O., Donnelly, E.F., Herdt, J.R. and Waldman, IN., Sulcal prominence in young chronic schizophrenic patients-CT scan findings associated with impairment on neuropsychological tests, Psychiat. Res., I (1979) 1-8. Weinberger, D.R., Torrey, E.F., Neophytides, A.N. et al.. Lateral cerebral ventricular enlargement in chronic schizophrenia, Arch. Gen. Psychiat., 36 (1979a) 735-739. Weinberger, D.R., Torrey, E.F., Neophytides, A.N. and Wyatt, R.J., Structural abnormalities of the cerebral cortex in chronic schizophrenia, Arch. Gen. Psychiat., 36 (1979b) 935-939. Weinberger, D.R., Torrey, E.F. and Wyatt, R.J., Cerebellar atrophy in chronic schizophrenia, Lancet, i (1979~) 718-719.
Disorders, 4 Press
(I 982) 15- 19
Cerebral Ventricular
15
Enlargement A Controlled
in Young Manic Males
CT Study
Henry A. Nasrallah ‘, Mona McCalley-Whitters Charles G. Jacoby 2
’
and
’ VA Medicul Center und Depurtment OJ Psych&v,
und -’ Department of Rudiologv, Unioersiiy of Iowu, College of Medicine, Iowu Cicv, IA 52240 (U.S.A.) (Received (Accepted
1I September, 30 September,
1981) 198 1)
Summary and Conclusions Computerized tomographic (CT) head scans of 24 young manic males were compared with those of 27 matched control subjects and 55 chronic schizophrenic patients. Cerebral ventricular size was significantly larger in the manic and schizophrenic patients compared to the control group. There was no difference in cerebral ventricular size between the manic and schizophrenic groups, suggesting that cerebral ventricular enlargement may be a nonspecific neuroanatomical correlate of psychotic disorders.
Introduction Schizophrenia and mania are two major psychotic disorders which have many clinical similarities that frequently lead to diagnostic confusion (Pope and Lipinski 1978). Although the development of operational criteria as in the DSM-III has greatly improved diagnostic reliability, the ultimate diagnostic tool will eventually have to include specific biological markers. Recently, several reports have shown that many chronic schizophrenic patients have structural brain abnormalities on computerized tomography (CT) such as enlarged lateral cerebral ventricles (Johnstone et al. 1976; Weinberger et al. 1979a; Correspondence: IA 52240, U.S.A.
Henry
0165-0327/82/0000-0000/$02.75
A. Nasrallah,
M.D., Chief, Psychiatry
0 1982 Elsevier Biomedical
Service, VA Medical
Press
Center,
Iowa City,
16
Golden et al. 1980), cerebral atrophy (Reider et al. 1979; Weinberger et al. 1979b) and cerebellar atrophy (Heath et al. 1979; Weinberger et al. 1979~). Very little is known, however, whether such brain abnormalities occur in mania and if they do at what frequency and to what extent. This report addresses the issue of whether cerebral ventricular enlargement is specific to the schizophrenic psychoses or possibly associated with manic psychosis as well.
Method Over a period of 1 year, 24 manic and 55 schizophrenic patients consented to participate in a CT study of the brain. All patients were males between 20 and 45 years of age who fulfilled the DSM-III criteria for mania or chronic schizophrenia. The mean age for the manic group was 31.8 years and for the schizophrenic group 29.9 years. For ethical reasons a prospective volunteer group for a CT study involving unnecessary radiation was not done. Instead a control group of 27 age- and sex-matched males was selected from consecutive victims of motor vehicle accidents who had a normal CT scan as part of their neurological workup. Control subjects were excluded if they had (a) a history of psychotic illness or (b) gross sensory-motor localizing signs and symptoms even if the CT was read as normal. The mean age for the control group was 28.7 years. CT scans were done on a Model 1005 EM1 scanner. Sections were made at g-mm intervals and most patients received 12 cuts. The films were then coded and the area of the cerebral ventricles was measured by a research technician using a mechanical Planimeter (Keuffler and Esser compensating polar planimeter, catalog No. 6620005) which integrates surface area when the periphery is traced. The area of the ventricles was measured on the cut that comes closes to passing through the body of the lateral ventricles. The area of the ventricles was divided by the area of the brain at that level so that ventricular size was expressed as the ventricle to brain ratio (VBR = area of ventricles X loo/area of brain) which has been shown to correlate well with ventricular volume (Penn et al. 1978). The method used here is similar to that used by Weinberger et al. (1979a).
Results Figure 1 shows a scattergram of VBR values for the controlled schizophrenic and manic groups. The ventricular size data was analyzed in two ways. (a) The difference between the means was analyzed by a two-tailed f-test. The mean VBR of the bipolar manic group (7.5 * 3.2) is significantly larger (t = 3.785, P < 0.005) than the mean control VBR (4.5 + 2.6). The mean VBR of the schizophrenic group (8.7 -C 4.0) is also significantly larger than the control group (t = 5.735, P
VENTRICLE
TO BRAIN RATIO ON C.T. SCANS
26 . 24 1 22
20
.
18 . .
16 ti 14 ai 5 12 IO 8
i 8 .
l
T
2 SD
8
4.5_+2.6
4
.
2
rc % 8
7.5t3.2
I SD 6
0
.
0
ERoLS $gZOPHRENIA
BIPOLAR ~~F&ZJI&E N=24
Fig. 1. A scattergram distribution control groups. The meankstandard
of the ventricle to brain ratio (VBR) in manic, schizophrenic deviation for each population is shown for comparison.
and
(b) A comparison was made between the manic and the schizophrenic groups as to how many patients in each group had a VBR that exceeded 2 standard deviations (SD) above the control mean VBR i.e. above 4.5 * (2 X 2.6) = 9.7. 19/55 (34.5%) of schizophrenic patients and 7/24 (29.2%) of manic patients exceeded 2 SD. There is no statistical difference between the two groups.
Discussion The data in this study indicate that there is no statistical difference in cerebral ventricular size between young manic males and young chronic schizophrenic males. The mean VBR value for the manic group is comparable to that of the schizophrenic graup, and the VBR distribution is similar in both patient groups. When compared to a normal control group, the manic and schizophrenic groups have significantly larger cerebral ventricular size. In a recent communication, Pearlson and Veroff (198 1) reported findings that validate the results of this study. They reported no significant difference in the mean
VBR of 16 manic-depressive patients when compared to 22 schizophrenic patients. The main implication of the findings is that enlarged cerebral ventricles on CT scans is not specific to chronic schizophrenia, but occurs in mania as well, at least in young male manic patienis who comprised the sample in this study. Further studies in young manic females are needed to validate the findings here, which suggest that enlarged cerebral ventricles is a neuroanatomical abnormality that is associated with psychosis rather than with a specific psychotic disorder. Additional support for this notion comes from reports indicating that cerebral ventricular enlargement on CT scans is present in patients with psychosis secondary to lupus erythematosus (Bilaniuk et al. 1977; Gonzales-Scarano et al. 1979). Studies in various psychotic conditions are necessary to confirm that cerebral ventricular size is a nonspecific finding. There is also the possibility that cerebral ventricular enlargement is a product of the drug treatment of psychosis. All the manic and schizophrenic patients in this study received neuroleptic drugs repeatedly since the onset of their illness. As for the effect of ECT on VBR, no significant difference was found between the mean VBR of manic patients with a history of ECT treatment (N = 4, mean VBR = 5.8) and the mean VBR of patients who had never received ECT (mean VBR = 8.2). This suggests that a history of ECT treatment is not associated with an increase in cerebral ventricular size. Finally, a note should be made of the fact that while the mean VBRs of the manic and schizophrenic patients are significantly larger than the mean VBR of the control group, there are many manic and schizophrenic patients with VBR values well within the range of the controls, while others are totally outside that range. It is possible that a subgroup of both manic (Kadrmas and Winokur 1979) and schizophrenic (Hays 1977) patients are associated with an organic etiology, while others are the result of genetic transmission. For this reason, the family history of psychosis, past history of perinatal brain injury, infantile encephalitis or head injury, and EEG abnormalities should be recorded on all patients with mania and schizophrenia. It may be that patients with negative family history and positive history of organic brain disease have larger VBR values than patients with a positive family history and negative organic findings. Such a study is currently underway to help elucidate the etiology of cerebral ventricular enlargement in mania and schizophrenia.
References Bilaniuk, L.T., Patel, S. and Zimmerman, R.A., Computed tomography of systemic lupus erythematosus. Radiology, 124 (I 977) 119- I2 1. Golden, C.J., Moses, J.A., Zelazowski, M.A. et al., Cerebral ventricular size and neuropsychological impairment in young chronic schizophrenics, Arch. Gen. Psychiat.. 37 (1980) 619-623. Gonzales-Scarano, F., Lisak, R.P., Bilaniuk, L.T. et al., Cranial computed tomography in the diagnosis of systemic lupus erythematosus, Ann. Neural., 5 (1979) 158- 165. Hays, P., Electroencephalic variant and genetic predisposition to schizophrenia, J. Neurol. Neurosurg. Psychiat., 40 (1977) 753-755.
19
Heath, R.G., Franklyn, D.E. and Shraberg, D., Gross pathology of the cerebellum in patients diagnosed and treated as functional psychiatric disorders, J. Nerv. Ment. Dis.. 167 (1979) 585-592. Johnstone, E.C., Crow, T.J., Frith, CD. et al., Cerebral ventricular size and cognitive impairment in chronic schizophrenia, Lancet, ii (1976) 924-926. Kadrmas, A.K. and Winokur, G., Manic depressive illness and EEG abnormalities, J. Clin. Psychiat., 40 (1979) 306-307. Pearlson, G.D. and Veroff, A.E., Computerized tomographic scan changes in manic-depressive illness, Lancet, ii ( I98 I) 470. Penn, R.D., Belanger, M.G. and Yasnoff, W.A., Ventricular volume in man computed from CAT scans, Ann. Neurol., 3 (1978) 216-223. Pope, H.G. and Lipinski, J.F., Diagnosis in schizophrenia and manic-depressive illness-A reassessment of the specificity of ‘schizophrenic’ symptoms in the light of current research, Arch. Gen. Psychiat., 35 (1978) 81 l-828. Rieder, R.O., Donnelly, E.F., Herdt, J.R. and Waldman, IN., Sulcal prominence in young chronic schizophrenic patients-CT scan findings associated with impairment on neuropsychological tests, Psychiat. Res., I (1979) 1-8. Weinberger, D.R., Torrey, E.F., Neophytides, A.N. et al.. Lateral cerebral ventricular enlargement in chronic schizophrenia, Arch. Gen. Psychiat., 36 (1979a) 735-739. Weinberger, D.R., Torrey, E.F., Neophytides, A.N. and Wyatt, R.J., Structural abnormalities of the cerebral cortex in chronic schizophrenia, Arch. Gen. Psychiat., 36 (1979b) 935-939. Weinberger, D.R., Torrey, E.F. and Wyatt, R.J., Cerebellar atrophy in chronic schizophrenia, Lancet, i (1979~) 718-719.