The dementia of dementia praecox

Acta psychiat. scand. (1978) 57, 305-324

Divisions of Psychiatry and Radiology (Heads: T. 1. Crow, Ph.D., L. Kreel, M.D.), Clinical Research Centre, Harrow, Middlesex, England

The dementia of dementia praecox

E. C. JOHNSTONE, T. J. CROW, C. D. F m , M. STEVENS, L. KREEL AND J. HUSBAND

A group of 18 long-stay patients with a diagnosis of schizophrenia were compared with a group of 10 age-matched subjects who had been institutionalized by reason of physical disease, on performance on tests of intellectual function; and with a group of age- matched healthy subjects, both on tests of intellectual function, and radiographically, using the technique of computerized axial torno; graphy (EM1 scan) of the brain. By comparison with the normal controls the patients with schizophrenia had increased cerebral vea- tricular size (assessed as cross-sectional area) and, by comparison with both control groups, showed substantial impairments on intellectual testing. The differences in ventricular area between patients and controls remained significant (P < 0.01) after four patients who had been leucotomized had been excluded. Within the non-leucotomized patient group ventricular area was unrelated to previous neuroleptic medication, ECT or insulin coma therapy, but there was a significant relationship between ventricular area and intellectual impairment (P < 0.01). Intellectual impairment, as assessed by the Withers & Hinton test battery, the Inglis paired associate learning test, and the digits-backward test, was greater (P < 0.05) in patients with negative features (affective flattening, retardation, poverty of speech) than in those without such features. Premorbid occupational histories suggested that nearly all of these patients had at one time functioned at an adequate intellectual level. The findings suggest that within the group of patients with schizophrenia there is a subgroup whose illnesses have hitherto been considered typically schizophrenic, who have severe intellectual impairment associated with evidence of structural brain disease. The size of this subgroup and the significance of the cerebral changes remain to be determined.

Key words: Schizophrenia - cognitive impairment - increased ventricular size.

In developing the concept of dementia praecox Kraepelin expressed in 1919 the opinion that intellectual functions (e.g. orientation, consciousness and memory: see Kraepelin (1971) p. 17) were unimpaired. Bleuler (1950) referring to “the group of schizophrenias” expressed similar views: “In contrast to the organic psychoses, we find in schizophrenia ... that sensation, memory, consciousness and motility are not directly disturbed” (p. 55), and “memory as such does not suffer in this disease” (p. 59). Concerning the chronic states of schizophrenia there is a discrepancy between the views of these two authors. Whereas Bleuler

306

states unequivocally that “consciousness ... is not altered in the chronic conditions of schizophrenia. In this respect the schizophrenics behave as do the healthy” (Bleuler (1950), p. 62), Kraepelin qualified his comment that consciousness is clear with the reservation “if we leave out of account the terminal condition of dementia”. In his chapter on terminal states he describes “drivelling dementia” in which there is a “general decay of mental efficiency” and patients “are often nut clear about their position and surroundings” (Kraepelin (1971) pp. 197-1981, and “simple weak-mindedness” in which patients are clear “about time, place and person” (p. 189) but they “lose a great part of their knowledge; they become impoverished in thought, monotonous in their mental activities” (p. 190).

In the years since Kraepelin wrote it has always been recognized that a proportion of patients proceed to a state characterized by lack of productive ac- tivity, social withdrawal and occasionally mutism (the “defect state”). However, the psychological nature of the defect in these cases has been relatively little studied. It seems generally to have been assumed that intellectual deterioration, the hallmark of organic cerebral disease, is the characteristic which distinguishes the organic from the functional psychoses, and that structural changes do not occur in the latter case. However, patients with chronic schizophrenia often perform poorly on tests of intellectual impairment (Payne (1973)), and although this poor performance has been attributed to lack of volition or preoccupation with psychotic phenomena, no satisfactory method for separating such supposed secondary impairments from a primary defect of intellectual function has been established. The view that these impairments are secondary has been encouraged by observations that performance can be improved if the conditions of institutional life are made more interesting (Hamilton (1963)). More recent work (Lilli- ston (1973), Depue et al. (1975)) suggests that intellectual function in schizophrenia is closely related to social withdrawal, apathy and poverty of speech. The generally accepted view that the intellectual defects, if they exist, are entirely explicable in terms of the volitional state, rests largely upon the difficulty of accurately assessing intellectual function in the presence of poverty of speech and lack of motivation. Tests of intellectual capacity rely upon a co-operative and motivated subject, and this view is therefore difficult, if not impossible, to refute on the basis of the results of psychological testing alone. The alternative possibility that the intellectual deficit may, in some cases, be substantial and primary, while apathy and poverty of speech are secondary has seldom been considered in view of the difficulty of eliminating the former, less strihing, hypothesis. Nevertheless Jaspers (1963) has written:

“If with the organic dementias we find it difficult to separate personality from the intelligence, the schizophrenic deterioration or dulling of the kind from which the majority of chronic mental hospital patients suffer presents us with an even greater problem. Perhaps the intelligence remains quite intact in these cases and the changes are due to alterations in personality alone. It would be of fundamental importance for our understanding of these illnesses if it were possible to separate this latter type of case - which forms of the majority - from those cases where a true disturbance of the intelligence could be demonstrated’’ @. 218).

307

The approach to this problem which we have attempted is to relate assessments of intellectual function and clinical state to independent indices of cerebral capacity based upon a recent radiological innovation, computerized axial tomography (the EM1 scan). Some relationships between cerebral ventricular size and sulcal width assessed from EM1 scan data have already been described in relation to the organic dementias (Huckman et al. (1975)). In this study we have attempted to determine whether changes in these parameters are associated with intellectual impairments, and other features of the “defect state”, in hospitalized patients who have suffered from schizophrenia-like illnesses. We compared a group of these patients with a group of age-matched normal individuals who also under- went EM1 scan of the brain. In view of the evidence that many aspects of the “defect state” are associated with particular features of long-stay institutions (Wing & Brown (1961)) we also included a second control group who had received long-term institutional care for non-psychiatric illness. These subjects were assessed on psychological tests but did not undergo the EM1 scan procedure.

A preliminary report of the radiological findings has already appeared (John- stone et al. (1976)).

METHOD Selection of patients and controls Schizophrenics. Male patients only were considered for the study. Twenty-four patients who persistently estimated their own age as within 5 years of that at which they were admitted (a psychological feature which may be a marker of impaired learning capacity in chronic patients; Crow & Mitchell (1975)) and who conformed to the criteria for the diagnosis of schizophrenia devised by Feighner et af. (1972) were identified from an earlier survey of a long-stay mental hospital population. Nine of these were selected, principally on the basis of their willingness to participate in the study. In the same base population there were 36 patients who conformed to the diagnostic criteria for schizophrenia, who were not agedisordered by the above criterion and who resembled the index group in age, duration of inpatient care, and previous treatment. Nine patients were selected from this group on the basis of willingness to participate and closeness of matching on these various factors. To further define the diagnosis the inventory of the Present State Examination (Wing et at. (1974)) was applied to the casenotes of these 18 patients and as much detail as possible was collected concerning their health and functioning before the onset of the psychosis.

Controls. A suitable control group from the point of view of institutionalization was not easy to find. In view of the duration of inpatient treatment in the schizophrenic group (Table 1) no suitable population of psychiatric patients could be found. We therefore studied patients who had been in hospital for many years with long-standing and severe physical disease. In the hospital we visited there were 33 patients who had illnesses of which cerebral involvement was not a feature and who were prepared to participate in the study. None of them had a disordered concept of their own age. Ten patients were matched as closely

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tain

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1 2 3 4 5 6 7 8 9 10

11

12

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14

15

16

17

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as

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310

as possible for age and duration of hospitalization with the schizophrenic group. The normal control group was selected from volunteers from the male ancillary staff of the Clinical Research Centre and Northwick Park Hospital. Eight subjects who closely resembled the index group in age and occupational status, were obtained.

Assessments The mental states of the schizophrenic patients and both groups of controls were assessed in terms of the rating scale for chronic schizophrenia devised by Kra- wiecka et al. (1977). This rating assesses on a 0-4 point scale each of the eight variables, anxiety, depression, psychomotor retardation, flatteninghcongruity of affect, delusions, hallucinations, thought disorder and mutenesdpoverty of speech.

1. The “tests of the sensorium” designed by Withers & Hinton (1971). 2. The Znglis Paired Associate Learning Test (1959). 3. The “memory for faces” test in which the subject is required to recognize 10

faces. This is a shortened and modified version of the test designed by War- rington (1974).

The following psychological tests were carried out:

4. The “face sorting” test (Frith (1977)).

Physical investigations The following investigations were planned: physical examination; full blood count with white cell count, blood film and erythrocyte sedimentation rate; urea and electrolytes; liver function tests; serum BI2 and folate; thyroid function tests; specific serology; chest and skull X-ray; EEG; cerebral blood flow assessed by xenon inhalation; computerized axial tomography of the brain.

The mental state assessments were carried out on all patients and controls. Because of their serious incapacity the physical investigations were not attempted in the institutionalized controls. Physical investigations were first carried out upon the age-disordered schizophrenics. Assessment of cerebral blood flow by xenon inhalation proved impracticable because of leakage of xenon between the mask and the somewhat sunken faces of these edentulous patients. This investigation was therefore not attempted in the remaining patients and controls. The EEGs, skull and chest X-rays in the age-disordered schizophrenic patients showed no significant abnormalities and these tests aIso were omitted in the remaining cases. The other investigations listed were carried out on all the participants in the study except the physically ill patients. EM1 scans of the brain were obtained in 17 of 18 schizophrenics and from eight controls (adequate co-operation with the EM1 scan procedure could not be obtained from one schizophrenic patient). This investigation was carried out with a view of assessing the presence of structural cerebral changes.

Controlled studies concerning the evaluation of cerebral atrophy are few. The effects of age are uncertain and the effects of leucotomy on the total pic- ture are not known. It seemed essential to make this examination as objective as possible and the following method was therefore adopted:

Tomographic sections through the brain were taken beginning at a line at an

311

angle of 25’ to Reid’s base line (New & Scott (1975)), and continuing parallel to it, at 1-cm intervals, to the vertex. Three images were selected for each patient. Cut l showed the anterior and posterior horns of the lateral ventricles together with the third ventricle; the second (cut 2) showed the body of the lateral ventricles, and the third (cut 3) showed the upper portions of the cerebral hemispheres. The positions of these tomographic sections are illustrated in Fig. 1. The images were photographed. In each photograph the internal area of the skull and the area of the brain was measured with a planimeter, an instrument which measures the area contained within a circumference. These measurements were made blindly. In the photographs of images of cuts 1 and 2 the total area of the ventricles was assessed with the planimeter. These measurements were made blindly on two separate occasions by two independent investigators to give four measurements of ventricular area on each patient. The measurements of the sulci were made using the photograph of the image of cut 3. The sulci were too narrow in parts for the planimeter to be used and tracings of the sulci were made onto mm square tracing paper and the area of the sulci estimated by counting squares. This was done blindly on two separate occasions by two independent investigators.

RESULTS Subject characteristics Details of the ages, occupations, past treatment, PSE classification and duration of hospitalization of the schizophrenic patients are shown in Table 1, together with additional relevant information. Details of the ages, occupations, duration of hospitalization, and illnesses of the physically ill controls are shown in Table 2, and the ages and occupations of the normal controls in Table 3. (It was not possible to obtain an all male group of physically disabled controls and this sample consisted of six men and four women.) Although there was a tendency for the physically disabled patients to have been in hospital for a somewhat shorter time than the schizophrenics, many of them had been invalids at home for years before being admitted to hospital and the duration of their inability to participate in society tended to be greater than that of the schizophrenics (Table 4).

11 Porlerior horn of lateral ventricle Atrium of lateral ventricle Middle of iaterai ventricle

Anterior horn of lateral ventrzle 4$1

”/ Fig. 1. Siting of tomographic cuts.

312

Table 2. Physically disabled patients ~

Duration

Sex hospitaliza- Previous invalidiza- Age tion occupation tion before

(in years) hospitaliza-

Duration of of total Disease suffered

tion

Poliomyelitis 74 F 43 None 22

Spina bifida 54 F 54 None - Poliomyelitis 73 F 36 None 26

Syringomy elia 45 F 13% Clerk 13 Muscular Semi-skilled fac-

dystrophy 66 M 18 toryworker 12 Flexion Sales

contractures 55 M 3 assistant 2 Peripheral

vascular disease 70 M 8 Clerk - Poliomyelitis 41 M 1 None 40 Poliomyelitis 73 M 39 None 20 Juvenile rheu-

matoid arthritis 80 M 21 Fireman 40

Psychological tests The results of the cognitive function tests are shown in Table 5 and illustrated in Fig. 2A and B. The performances of the normal control group and the physically ill patients were closely similar. No significant ditferences were established between these two groups. The schizophrenic groups in general performed much less well than the control groups. Both schizophrenic groups did, however, achieve results comparable to those of the non-psychotic groups in the digit span forward test, and in the face sorting test the age-orientated schizophrenics performed slightly, but not significantly, better than the normal controls.

UJ

10

60 M D

M M 10

0 I PA LT 0 Age disordered

Hlnton (L Withers Physically ill patients

Age orlenlatd 0 Normals

" hlem0i-y Memory Digits Digils 9uallly of lor laces lor laces toward backward lac@ sorting (1 minl I10 min)

Age disordered Ageorientated 0 Normals

Pbysiratty ill patients

A B

Fig. 2. Results of psychological tests in both groups of schizophrenics, physically disabled patients and normal controls.

313

Table 3. Normal controls

Age, Y-S Sex Occupation

58 61 67 62 56 50 40 42

M M M M M M M M

Technical supervisor Porter Messenger Porter Maintenance engineer Porter Engineer Maintenance engineer

Mental state ratings Examination of the mental states of the physically disabled and normal control groups revealed no psychotic features, and no morbid ratings of depression or anxiety, except in the case of one physically ill patient who was found to be mildly anxious. No marked ratings of depression or anxiety (2 2 on Krawiecka scale) were obtained in the schizophrenic patients. The positive (hallucinations, delusions and thought disorder) and negative features (flatteninglincongruity of affect, psychomotor retardation and poverty of speechlmuteness) of schizophrenia in the patients with that disease are seen in Table 1. There were eight patients with, and 10 patients without, positive symptoms. There were 11 patients with, and seven patients without, negative symptoms. The relationship between the clinical features and the results of the cognitive tests is shown in Table 6. There is a weak association between the presence of positive features of schizophrenia and a relatively good performance on cognitive tests, and a strong association between the presence of negative features of schizophrenia and a relatively poor performance on cognitive tests.

Physical investigations No significant abnormalities were found on physical examination. FBC/WBC/

0-

..- ..

Narmair

I .

Schizophrenics o Leucotomired

palient

Fig. 3. Ventricular size in patients and controls.

2w

2 120

40

Normals Schizophrenics 0 Leucotomised

patient

Fig. 4. Sulcal size in patients and controls.

20 ACTA PSYCH 57:4

314

Table 4. Comparison between schizophrenics and physically ill with respect to duration of institutionalization

Mean and standard Mean and standard deviation in deviation in Significance

schizophrenics physically ill

Age 57.8, s.d. 8.9 63.1, s.d. 13.4 NS

Duration of hospitalization, years 31.9, s.d. 7.5 23.7, s.d. 18.3 NS

Duration of illness, years 31.9, s.d. 7.5 41.3, s.d. 22.8 NS

film, urea and electrolytes, liver function tests, thyroid function tests, specific serology, serum B1, and folate showed no abnormality.

Computerized axial tomography In the EM1 scan assessments there was a high correlation between the measurements of ventricular size obtained by the two separate observers (cut 1, r = 0.96 (P << 0.001), cut 2, r = 0.94 (P << 0.001)) and it would appear that this is a reliable method of measuring ventricular size. The correlation between the measurements at the two levels in the same patient was high (cut 1 v. cut 2; r = 0.68 (P < 0.001)) and this suggests that minor variation in the exact site of the tomographic sections is unlikely to exert a significant effect upon the assessment of ventricular size. The means of the four measurements of ventricular size in each case are illustrated in Fig. 3. Leucotomy is associated with increased ventricular size (Table 9) and in some cases with distortion of the ventricles. For this reason leucotomized patients were omitted from all calculations concerning ventricular size except those concerning the effects of leucotomy. Ven- tricular size in the schizophrenic group with leucotomized patients excluded is significantly greater than that in the control group (P < 0.01).

The correlations between the measurements of sulcal size obtained by the two separate observers was high (r = 0.99, P << 0.001). The means of the two measurements of sulcal size are illustrated in Fig. 4. Sulcal size was significantly greater in the leucotomized than in the non-leucotomized patients, but there was no significant difference between the schizophrenics and the normals (Table 7). Mean values of the area of the brain at the three levels were calculated. Omitting the leucotomized cases, values in schizophrenic patients were slightly less than those in the normal controls (schizophrenics mean 52.74, s.d. 4.30, normal mean 55.63, s.d. 3.20, P < 0.10). Mean values of the internal area of the skull at the three levels were calculated and there were no significant differences between the non-leucotomized schizophrenics and the normal controls (schizophrenics mean 77.17, s.d. 4.65; normal mean 78.06, s.d. 4.72, NS). The ratios between ventricular or sulcal area and the area of the brain at the same level were calculated and the results are shown in Table 7.

The significant correlations between ventricular size and cognitive function

5 T

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ory

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317

Table 7. Sulcal, ventricular, brain and skull measurements

Sulcal area Ventricular Brain area Sulcal area

skull area brain area area as % of as % of as % of brain area (mm?

(mean) (mean)

Schizophrenic 77.00, 18.69, 66.54, 0.296, s.d. 43.46 s.d. 4.22 s.d. 4.91 s.d. 0.19

Leucotomized 246.25, 23.13, 65.25, 0.79, s.d. 116.23 s.d. 2.39 s.d. 6.90 s.d. 0.18

Normal controls 90.81, 10.51, 70.62, 0.37, s.d. 53.59 s.d. 1.96 s.d. 4.44 s.d. 0.19

Non-leucotomized schizophrenics NS t = 5.12 t = 1.92 NS v. controls P < 0.001 P < 0.1

Non-leucotomized t = 1.98 NS t = 4.58 schizophrenics t = 4.56

v. leucotmized P < 0.001 P < 0.10 P < 0.001

tests and between brain areas and cognitive function tests are shown in Table 8. All other comparisons between measures of cerebral size and assessments of cognitive function or mental state were not significant, and there was no relationship between age and any measure of cerebral size. Apart from the association with leucotomy there was no relationship between sulcal size and any form of treatment. The relationships between ventricular size and previous physical treat- ments are shown in Table 9.

DISCUSSION Intellectual impairment in schizophrenia On six of the seven tests of intellectual function the group of chronic schizophrenic patients performed less well than normal controls and physically ill institutionalized patients. On two well-established tests, the Withers & Hinton tests of the sensorium, and the Inglis Paired Associate Learning Test, the differences between the schizophrenics and each of the two control groups sepa- rately were substantial and significant at the 0.01 level or less (Table 5). Only on the “digits forward” test was the performance of the schizophrenic group comparable to that of the two control groups.

The only index of premorbid intellectual function available for the psychiatri- cally and physically ill institutionalized patients is the record of their occupation when well. A comparison of the premorbid occupations of these two groups (Table 1, column 2; Table 2) with the current occupations of the normal controls (Table 3) reveals no obvious differences, except that five of the physically disabled had never been in regular employment. This suggests that the intellectual abilities of the three groups were roughly comparable at one time and that the

318

Table 8. Correlations between cognitive function and measures of brain size within the group of patients with schizophrenia

Comparison Significance Correlation No. of coefficient patients

Withers & Hinton v. ventricular area

Withers & Hinton v. ventricular area as % of brain area

R = -0.70 13 P < 0.01

R = -0.64 13 P < 0.05 Withers & Hinton

v. brain area as % of skull area R = -0.51 13 P < 0.10

(P < 0.05 1-tailed)

ability of the schizophrenic patients to perform tests of intellectual function has declined. The fact that the physically ill patients have retained their ability to perform these tests suggests that institutionalization alone is an inadequate explanation of impaired function in the schizophrenic group. It appears that the poor intellectual function of these patients results, at least in part, from the disease from which they suffer, and is unlikely to be due to the conditions under which they live.

There are significant relationships between the clinical features of schizophrenia and intellectual performance. Patients with positive features of schizophrenia (hallucinations, delusions, thought disorder) perform somewhat better than those without such features (Inglis Paired Associate Learning Test, P < 0.05, Table 6). Patients with negative features (poverty of speech, retardation, flattening and incongruity of affect) perform much less well than those without them (P < 0.01, digits backwards; P < 0.05, Withers & Hinton test battery, Inglis Paired Associate Learning Test). Since patients with positive symptoms generally have low scores on negative symptoms these relationships reflect the single observation that impaired intellectual function is strongly correlated with the negative features of schizophrenia. This observation itself suggests that preoccupation with florid psychotic phenomena is not an explanation of the poor cognitive test performance of chronic schizophrenics as a whole. Our findings do, however, confirm the conclusions of some recent workers (Lilliston (1973), Depue et al. (1975)) that poor intellectual performance is associated with the features (poverty of speech, retardation and flattening of afTect) of the defect state.

Within the schizophrenic group patients selected as showing the age disorientation phenomenon (Crow & Mitchell (1975)) showed greater intellectual impairment than the group without age disorientation on each of the tests other than “digits forward” (Fig. 2A and B); but these differences were significant (P < 0.05) only in the case of the Inglis Paired Associate and the face sorting tests. These findings are consistent with the conjecture that “age disorientation” may identify a group of chronic schizophrenic patients with particularly severe

319

Table 9. Relationship between previous treatment and ventricular size in schizophrenics, leucotomized cases omitted

Mean ventricular size, No. of cases t P Form of

treatment With Without With Without treatment treatment treatment treatment

Leucotomy 12.3, s.d. 0.70

ECT 9.9, s.d. 2.96

Phenothiazines 9.3, s.d. 1.76

Insulin comas 8.5, s.d. 1.45

9.9, 4 13 < 0.10 s.d. 2.20 2.06 (< 0.05

1-tailed)

9.97, s.d. 1.57 6 7 0.04 NS

11.3, s.d.2.76 9 4 1.57 NS

11.2, s.d. 2.0 6 7 2.71 < 0.05

cognitive deficits, but it is worthy of note that on the Withers & Hinton test battery and the Inglis Paired Associate Learning Test the differences between the age-disorientated and age-orientated schizophrenic groups were less than those between the latter and the two non-schizophrenic control groups. On their own the psychological test results do not clarify the question of

whether the poor performance of schizophrenic patients on cognitive tests is due to lack of ability or failure of co-operation.

Cerebral structure in chronic schizophrenia The EM1 scan investigations establish (Table 7, Fig. 3) that there are significant differences in cerebral ventricular area between the group of schizophrenic patients and the normal controls. Expressed as a percentage of brain area these differences are still highly significant (P < 0.001; Table 7) even when the four leucotomized patients, whose ventricular structure is very abnormal, are excluded.

Increased ventricular size on computerized axial tomography has already been demonstrated in dementia (Huckman et al. (1975)). With the earlier technique of pneumoencephalography there have been a number of claims that ventricular size may be increased in some cases of schizophrenia. Pneumoencephalography was introduced by Dandy in 1919. Jacobi & Winkler in 1927 were the first to claim that abnormal encephalographic appearances were to be found in schizophrenia, and a number of subsequent authors have made similar claims, often on quite large patient samples. For example, Moore et al. (1933) reported a series of 60 patients in which they felt there was a “tendency to selective atrophy involving the parietal lobes and the h u l a of Reil area”, and in 25 cases they thought there was evidence of increased sue of the ventricles and cisternae. Huber (1964) claimed that of 212 institutionalized schizophrenics under 50 years old, 81.6 76 showed atrophic changes in the ventricles, most commonly the third.

Substantial objections to these conclusions are the lack of objective criteria for defining structural abnormality and the lack of a normal control group.

320

Storey (1966) attempted to resolve these difficulties by comparing measurements of ventricular width in the pneumoencephalograms of 18 schizophrenics with those in pneumoencephalograms carried out for various reasons which had been reported as normal. No significant differences between the two groups were found. Haug (1962) used carefully defined indices of cerebral ventricular size in a pneumoencephalographic study of 278 psychiatric patients divided into groups with (1) non-organic mental disorders, (2) schizophrenia and (3) organic mental disorders: he found that the mean ventricular size of the 101 patients with schizophrenia was significantly greater (P < 0.05) than that of the group with non-organic mental disorders and that within the schizophrenic group there was a highly significant correlation between mental deterioration assessed clinically and ventricular enlargement (P < 0.001). Asano (1967) applied well-defined criteria of ventricular size in a study of 53 schizophrenic patients of mean age 28.9 years, patients being divided into nuclear and peripheral groups. Pneumo- encephalographic abnormalities consisting mainly of ventricular enlargement were found in 94.4 % of the nuclear group, particularly in those with personality deterioration, and in 42.9 % of the peripheral group.

Thus there are already several studies in the literature which suggest that there is ventricular enlargement in some patients with schizophrenia and two studies based on standardized quantitative measurements, which suggest that schizophrenic patients with deterioration can be distinguished, at least from other psychiatric patients and from schizophrenic patients without deterioration, in terms of their cerebral ventricular size assessed pneumoencephalographically. These findings stand in contrast to the general failure of post-mortem studies to reveal unequivocal changes in patients who had suffered from schizophrenic illnesses in life. However, measurements of ventricular size in pneumoencephalography and axiaI tomography correlate well together and with measurements derived from ventricular casts (Gyldensted & Kosteljunetz (1976)). A careful study of ventricular size and brain weight at necropsy with reference to the presence or absence in life of the features of the defect state would appear to be of particular interest.

In the present study no differences in sulcal area, measured as described in the methods, were observed between non-leucotomized schizophrenics and controls, although leucotomized patients showed a substantial increase in this par- ameter (Table 7). Asuno (1967) noted that abnormalities of the cerebra1 surface were observed much less frequently than ventricular changes in his schizophrenic patients, and the differences between his groups in this respect were small. Huber (1964) also reported fewer cerebral cortical abnormalities than changes in the ventricles. It has been suggested that the dimensions of the body of the lateral ventricle are a better indicator of prognosis in patients with evidence of “generalized cortical atrophy” than the appearance of the cortical surface (Mann (1973)). However, Nielsen et al. (1966) found that in patients with organic brain disease there was a closer relationship between cortical atrophy and intellectual impairment than between ventricular dilatation and impairment, and Brewer & Perrett (1971) reported similar findings in a group of alcoholics, of whom a large proportion had psychometric evidence of brain

321

damage. Whether or not the apparent selectivity of the changes for the cerebral ventricles observed by Huber (1964) and Asano (1967), and in the present study is specific for schizophrenia, or is a reflection of a general rule that changes in ventricular size are more reliable than cortical changes as indicators of brain damage, remains to be established.

The findings of the present study demonstrate a significant relationship between impaired cognitive function and increased ventricular size (Table 8). Since increased ventricular size is known to be associated with intellectual defect in the case of the organic dementias (Huckman et al. (1975)) the findings suggest that the poor performance on tests of intellectual function observed in these patients is more likely to be due to organic brain disease than to be secondary to the other features of the disease.

General discussion The conclusion that the type of intellectual impairment commonly associated with organic brain disease may be a feature of the defect state in schizophrenia is at variance with most current views of this condition. Moreover, the claim that there are structural cerebral changes in the brain in some patients with schizophrenia is difficult to reconcile with the paucity of definite post-mortem findings. Alternative explanations of the present findings must therefore be considered. The fist issue to be considered is the question of diagnosis. Is it possible that some of our patients suffered from a disease other than schizophrenia? For years research has been bedevilled by controversy over what does or does not constitute schizophrenia, and these disputes may not yet be settled. How- ever, the patients in this study conformed to both of two sets of criteria (the Feighner criteria, and the casenote inventory of the Present State Examination), which are amongst the most restrictive available. Both sets of criteria refer to clinical features of the condition at a much earlier stage, and do not make an explicit attempt to exclude “organic” factors. “Schizophrenia-like” psychoses occur in association with many forms of organic brain disease (Davison & Bagley (1969); although whether the association is above chance expectation in these cases remains to be established), but the question of whether a diagnosis of schizophrenia should not be made in the presence of known brain disease is controversial. In theory such a strategy will lead, with increasing knowledge, to a diminishing group of patients eligible for a diagnosis of schizophrenia, but as McClelland et al. (1968) have pointed out, including such patients in the category of schizophrenia may lead to a better understanding of the schizophrenic process.

It is possible that in some of the present cases organic brain disease (for example encephalitis) may have preceded the development of schizophrenic symptoms, but there is no evidence that this was the case. Indeed in only six of the schizophrenic patients is there a history of febrile illness of any kind at any time before the onset of the psychosis (Table 1). From the information available on their previous occupations (Table 1) it appears that all of these patients functioned well before they became ill. The problem therefore is to identify a pathological process severe enough to produce total occupational incapacity, yet

322

of a non-life threatening nature, and which did not at the time arouse suspicions of an infective, toxic or other organic process. In 30 % of patients on whom information was available, a family history of schizophrenia was found (Table 1) and this appears close to the proportion to be expected in a group of patients with chronic schizophrenia (Stater & Cowie (1971)). It cannot be excluded that there exists a fairly common form of organic brain disease, e.g. viral encephalitis, which presents with an acute schizophrenia-like illness and progresses to an end- state of cognitive impairment and increased ventricular size. However, if this is the case it appears that the causal agent has not been identified, and the question of whether or not such an illness is a “true” schizophrenia is a terminological one rather than a practical research problem.

A second possible explanation of the present findings is that these patients were admitted to hospital with a primary schizophrenic illness but later devel- oped some form of organic brain disease and the signs of dementia. The means of selection of the subjects was highly dependent upon their willingness to co- operate in transfer to another and unfamiliar hospital environment, and to sub- mit to a variety of complex procedures. It might be argued that such docility would correlate with dementia. However, the 18 patients were selected from a population of 60 and this would imply a prevalence of dementia of at least 15 % in this population by comparison with an expectation of 3-5 % in the general population over 60 (Gunner-Svensson & Jensen (1976)). Therefore, it appears that this explanation in tenable only on the basis of the presence of some other factor predisposing the long-stay mental hospital population to dementia. We think it unlikely, although perhaps it cannot be dismissed altogether, that the conditions of our mental hospitals are such, of themselves, as to induce organic brain disease and dementia (as suggested, for example, by Jellinek (1976)). It is also relevant that in his pneumoencephalographic study Asuno (1967) found that the excess of abnormalities in his group of patients with “severe nuclear” schizophrenia was as great in patients aged less than 40 years as in the older age group.

The patients in this study were by no means a random sample of patients with schizophrenia. They were selected from a group of patients who had had an illness of such severity that they had required continuous inpatient care for at least 20 years. Hospital statistics concerning patients with a diagnosis of schizophrenia admitted in the same decade as most of this group suggest that in only about 40 % of cases did the illness run this deteriorating course (Harris & Norris (1955)). In this respect our findings may be related to the earlier pneumoencephalographic studies. Huber (1964), Haug (1962) and Asuno (1967) are in agreement that pneumoencephalographic abnormalities, defined by these authors in somewhat different ways, are found more frequently in severe and unremitting illnesses and with personality deterioration. The results of the present and the earlier studies suggest that among patients with schizophrenia in whom the illness runs an unremitting and progressive course there is a group in whom the disease is associated with increased ventricular sue and impaired intellectual capacity. Whether the increase in ventricular size is a factor which predisposes towards a deteriorating course or whether it is a direct result of the

323

disease process is a question which cannot be answered on the basis of the data at present available.

ACKNOWLEDGEMENTS We are grateful to the patients and controls for their ccroperation with the often tedious procedures involved in this study. We should also like to thank the medical and nursing staff of the Royal Home and Hospital for Incurables, Shenley Hospitzl and Northwick Park Hospitals. We are grateful to Dr. Maureen Tudor, Dr. M . W . P. Carney and Dr. H . I. Hershon for their kindness in allowing us to study patients under their care. Lastly we thank Mr. J . Twydle who managed the EM1 scanner and Mrs. P. Wright and Mrs. M . Conunt for secretarial assistance. This study was conducted under the auspices of the ethical committees of Northwick Park Hospital and Shenley Hospital and was camed out according to the rules of these committees.

REFERENCES Asano, N . (1967): Pneumoencephalographic study of schizophrenia. In Mitsuda, H., &

0. Takusuki (eds.): Clinical genetics in psychiatry. Problems in nosological classification. Igaku-Shoin, Tokyo, pp. 209-219.

Bleuler, E. (1950): Dementia praecox or the group of schizophrenias (translated by Zinkin, J.). International Universities Press, New York.

Brewer, C., & L.Perrett (1971): Brain damage due to alcohol consumption: an air- encephalographic, psychometric and electroencephalographic study. Brit. J. Addict. 66, 170-182.

Crow, T . J. , & W . S. Mitchell (1975): Subjective age in chronic schizophrenia: evidence for a subgroup of patients with defective learning capacity. Brit. J. Psychiat. 126, 360-363.

Dandy, W . E. (1919): Roentgenography of the brain after the injection of air into the cerebral ventricles. Amer. J. Roentgenol. 6, 26.

Davison, K., & C. R . Bugley (1969): Schizophrenia-like psychoses associated with organic disorders of the central nervous system - a review of the literature. In Herringtun, R . N . (ed.): Brit. J. Psychiat., Special publ. no. 4, 113-184.

Depue, R . A., M . D . Dubicki & T . McCurthy (1975): DifEerential recovery of intellectual, associational, and psychophysiological functioning in withdrawn and active schizophrenics. J. abnorm. Psychol. 84, 325-330.

Feighner, J . P., E. Robins, S . B. Guze, R . A . Woodruff, G . Winokur & R . Munoz (1972): Diagnostic criteria for use in psychiatric research. Arch. gen. Psychiat. 26, 57-63.

Frith, C. D. (1977): Two kinds of cognitive deficit associated with chronic schizophrenia. Psychol. Med. 7, 171-173.

Gunner-Svensson, F., & K . Jensen (1976): Frequency of mental disorders in old age. Acta psychiat. scand. 53, 283-297.

Gyldensted, C., & M . Kusteljanetz (1976): Measurements of the normal ventricular system with computer tomography of the brain: a preliminary study on 44 adults. Neuroradiology 10, 205-213.

Hamilton, V. (1963): I.Q. changes in chronic schizophrenia. Brit. J. Psychiat. 109, 642- 648.

Harris, A., & V. Norris (1955): Expectation of life and liberty in patients suffering from functional psychoses. Psychiat. Quart. 29, 33-47.

Haug, J . 0. (1962): Pneumoencephalographic studies in mental disease. Acta psychiat. scand., Suppl. 165, 1-104.

Huber, G . (1964): Neuroradiologie und Psychiatrie. In Gruhle, H . W., R . lung, W . Muyer-Gross & M . Muller (eds.): Psychiatrie der Gegenwart, Forschung und Praxis, Vol. l U B , Grundlagenforschung zur Psychiatrie, Part B. Springer-Verlag, Berlin.

Huckman, M . S., J . Fox & J . Tope1 (1975): The validity of criteria for the evaluation of cerebral atrophy by computed tomography. Radiology 116, 85-92.

324

Znglis, J . (1959): A paired associate learning test for use with psychiatric patients. J. ment. Sci. 105, 44W43.

lacobi, W., & H. Winkler (1927): Encephalographische Studien an chronisch Schizophre nen. Arch. Psychiat. Nervenkr. 81, 299-332.

Jaspers, K. (1963): General psychopathology (translated by Hoenig, J., & M . W . Hamil- ton). Manchester University Press, London.

Jellinek, E. H . (1976): Cerebral atrophy and cognitive impairment in chronic schizophrenia. Lancet ii, 1202-1203.

Johnstone, E. C., T . I . Crow, C. D . Frith, J . Husband & L. Kreel (1976): Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet ii, 924- 926.

Kraepelin, E. (1971): Dementia praecox and paraphrenia (translated by Barclay, R . M., & G. M . Robertson). R. E. Krieger, New York.

Krawiecka, M., D . Goldberg & M . Vaughan (1977): A standardized psychiatric assessment scale for rating chronic psychotic patients. Acta psychiat. scand. 55, 299- 308.

Lilliston, L. (1973): Schizophrenic symptomatology as a function of probability of cerebral damage. J. abnorm. Psychol. 82, 377-381.

Mann, A. H. (1973): Cortical atrophy and air encephalography: a clinical and radiological study. Psychol. Med. 3, 374-378.

McClelland, H . A., M . Roth, H . Neubauer & R . F. Garside (1968): Some observations on case material based on patients with certain common schizophrenic symptoms. Proceedings of IVth World Congress in Psychiatry, Madrid, 1966. Excerpta Medica Foundation, Amsterdam, p. 2955.

Moore, M . T., D . Nathan, A . R . Elliott & C. Laubach (1933): Encephalographic studies in schizophrenia (dementia praecox), report of sixty cases. Amer. I. Psychiat. 12,

New,P. F. J . , & W . R . D . Scott (1975): Computed tomography of the brain and orbit (EM1 scanning). Williams & Wilkins, Baltimore, pp. 23-34.

Nielsen, R., 0. Petersen, P. Thygesen & R . Willanger (1966): Encephalographic ventricular atrophy: relationships between size of ventricular system and intellectual impairment. Acta radiol. (Stwkh.) 4, 240-256.

Payne, R . W . (1973): Cognitive abnormalities. In Eysenck, H . J . (ed.): Handbook of abnormal psychology. Pitman, London, pp. 424-433.

Sluter, E., & V . Cowie (1971): The genetics of mental disorders. Oxford University Press, London.

Storey, P. B. (1966): Lumbar air encephalography in chronic schizophrenia: a controlled experiment. Brit. J. Psychiat. 112, 135-144.

Warrington, E. K . (1974): Deficient recognition memory in organic amnesia. Cortex 10, 289-291.

Wing, J . K., & G. W . Brown (1961): Social treatment of chronic schizophrenia - a com- parative survey of three mental hospitals. J. ment. Sci. 107, 847-861.

Wing, 1. K., J . E. Cooper & N . Sartorius (1974): The measurement and classification of psychiatric symptoms: an instruction manual for the PSE and Catego Program. Cambridge University Press, London.

Withers, E., & J . Hinton (1971): Three forms of the clinical tests of the sensurium and their reliability. Brit. J. Psychiat. 119, 1-8.

801-810.

Received June 30, 1977

Eve C. Johnstone, M.D. T . J . Crow, Ph.D. C. D . Frith, Ph.D. Marilyn Stevens, B.A. Division of Psychiatry Clinical Research Centre

L. Kreel, M.D. Janet Husband, M.B. Division of Radiology Clinical Research Centre Northwick Park Hospital Watford Road Harrow HA1 3UJ, Middlesex England

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