Acta psychiat. scand. (1979) 59, 145-152 Department of Psychiatry (Head V.Lunn, 0. J . Rajaelsen and T. Vanggaard), Rigshospitalet, Copenhagen, Denmark
Vitamin BIZ concentrations in psychiatric patients L. ELSBORG, T. HANSEN AND 0. J. RAFAELSEN In an attempt to evaluate the possible relationship between vitamin B,, deficiency and mental disease, the blood content of vitamin B,, was investigated in 835 consecutive psychiatric patients. Low serum vitamin B,, values were found in approximately 10 % of these patients, due to latent pernicious anaemia in one case, post-gastrectomy in seven cases and small intestinal resection in one case. In the remaining 72 cases vitamin B,, deficiency was probably caused
by nutritional insufficiency. After correction of the dietary defect there was a spontaneous increase in serum vitamin B,, in 75 % of these patients. No specific psychiatric syndrome was connected with hypovitaminosis BIZ, but a preponderance of arteriosclerotic dementia suggests that low serum vitamin B,, values are secondary to mental illness leading to apathy and loss of appetite. Most cases will recover without further vitamin B,, supplements. But some patients may need treatment because of severe mental and physical disabilities. Key words: Hypovitaminosis B,, - nutritional insufficiency chiatric patients - serum vitamin B12.
- psy-
It is an old observation that psychiatric disturbance may be present in pernicious anaemia (Warburg & J#rgensen (1928, 1929), Holmes (1956)). Even in the absence of frank anaemia mental disturbances and EEG abnormalities may be found in untreated pernicious anaemia (Wallace & Westmoreland (1976)). Earlier investigators have found a relatively high frequency of hypovitaminosis B,, among psychiatric patients (Droller & Dossett (1959), Edwin et al. (1965), Shulman (1967), Zsaksson et al. (1971), Carney & Shefield (1978)), suggesting a relationship between vitamin B,, deficiency and mental illness. This study was performed in an attempt to elucidate to what extent hypovitaminosis B,, may contribute to mental illness in a psychiatric ward with special regard to its possible causality. MATERIAL AND METHODS During a period extending over 10 months (November-August) a venepuncture for assay of vitamin B,, was performed on admission to the Department of Psychiatry, Rigshospitalet, Copenhagen, in 835 consecutive patients. There were 438 men and 397 women aged 17-98 years. The serum vitamin BIZ concentra10
0001-690X/79/020145-08$02.50/0 @ 1979 Munksgaard, Copenhagen
146 tion was determined by the lactobacillus Leichmanni method (performed by the Research Laboratories of Dumex Ltd., Copenhagen; Hansen & Hauschildt (1974)). Patients treated with antibiotics at the time of admission were primarily excluded from the study. Patients with normal serum vitamin BIZ levels, i.e. above 200 pg/ml, were subjected to no further study. In patients with low concentrations of vitamin BIZ an investigation program was instituted, comprising blood examinations, serum iron, total iron binding capacity, marrow examination, Schilling-test and examinations of EEG recordings. Finally, after a delay of 4-6 weeks, the serum % PROBIT SCALE
t
99
-
-
80
50-
10-
52-
I
1
100
I
I
200 300
I
LOO
I
I
500 600
I
*
700 800 pg/ml
SERUM VITAMIN 812
Fig. 1. Cumulative frequency of serum vitamin B , , in 88 normal persons. No.
t
Serum vitamin BI,
pglml
Fig. 2. Distribution of 835 psychiatric patients related to serum vitamin B I E .
147 vitamin B,, determination was repeated. In all patients a complete medical, psychiatric and neurological examination was carried out. The reference material consisted of 88 persons, 54 men and 34 women, aged 18-64 years (mean 33 k 11 years). Statistical calculation was performed by a modified chi-square test (Sokal & Rohlf (1969)), Kolmorgorov-Smirnow test, analyses of co-variations and correlations. RESULTS From the frequency distribution diagram the reference material appears to follow a normal distribution (Fig. l), the mean value 436 k 118 pg/ml. Thus the normal range is calculated as 200-700 pg/ml. The correlation between age and serum vitamin B12 concentration was non-significant (r = -0.07, P > 0.10). The distribution of psychiatric patients related to serum vitamin Blz (Fig. 2) was skew and did not fit a normal distribution. The mean value was 399 pg/ml (range 50-1,050 pg/ml. The majority of patients (61 %) had serum vitamin Blz values below 400 pg/ml and in 81 patients (9.7 %) the serum vitamin BIZ was under 200 pg/ml, the lower limit of normal range. Five patients (0.6 %) had extremely low values (< 100 pg/ml). The age distribution in patients with low serum vitamin B12 values was compared with the age distribution in patients with normal serum vitamin B12 (Fig. 3). Generally patients with low serum vitamin B12 were older than patients with normal serum vitamin BIZ (P< 0.001). Based on the levels of serum vitamin BlZ the patients were divided into three groups (Table 1). In the first group (serum vitamin B12 < 100 pg/ml) of five patients, one patient, a 72-year old woman, had genuine pernicious anaemia based on diagnostic criteria as previously described (Elsborg et al. (1976)). Another patient, a 71-year old woman, appeared to be a fanatic vegetarian with most peculiar dietary habits. Neither this patient nor the remaining three patients in this group fulfilled the criteria of pernicious anaemia. The second group (serum vitamin B12 100-150 pg/ml) consisted of 23 patients. None of these suffered from pernicious anaemia, but mild megaloblastic transformation in the bone marrow was found in two patients. One of these patients had a pathologically low Schilling-test, which, however, normalized in a repeated study. In the third group (serum vitamin B,, 150-200 pg/ml) of 53 patients no cases of pernicious anaemia were disclosed. EEG abnormalities (Table 1) were relatively frequent findings, occurring in 100 % (five out of five) of the low vitamin Blz group, 40 % (six out of 15) of the medium vitamin B12 group and 52 % (11 out of 21) of the high vitamin BlZ group. Neurological disturbances were found in 11 %, in most cases secondary to other disorders (epilepsy, hemiparesis, syphilis), which were fairly common findings in patients with hypovitaminosis B12 (Table 2). A history of drug addiction (11 %) and alcoholism (16 %) was often revealed. The Schilling-test was per10.
148 Table 1. Serum vitamin Bla concentration related to various haematological and clinical studies in 81 psychiatric patients
Serum vitamin B12 @g/ml) 50-100 100-150 150-200
No. patients Hgb < 12 g/lOO ml MCV > 100 fl Sideropenia Megaloblastic marrow Schilling test < 10 % Neurological abnormalities EEG abnormalities
5 1 1
23 1 1
1 2 1 5
53
Total no. of patients 81 81 73
1
6 1 2
65
2 1 2 6
1 6 11
15 13 78 41
formed in four gastrectomized patients and gave a normal result in all. Comparison of psychiatric syndromes (Fig. 4) in patients with low and with normal serum vitamin B,, showed that arteriosclerotic brain disease was the only syndrome occurring predominantly in patients with low serum vitamin BI2 values ( P < 0.001). %
25
251
Normal serum vitamin BlZ
I1
mean = 42 n = 754
20 15
10 5
zl$
Low serum vitamin B12
Fig. 3. Histogram showing the distribution of psychiatric patients with normal and low serum vitamin B,, values as compared with their ages.
149 Table 2. Concomitant disabilities in 81 psychiatric patients with vitamin B I , deficiency
Drug addiction Loneliness Gastrectomy Dietary insufliciency Epilepsy Physical disorder Neurosyphilis Intellectual disability Pernicious anaemia Crohn's disease Septicaemia Total
Males
Females
Total
3 1 5 1
6 6 2 5 3
9 7 7 6 4
1 1
3 2
1 2 1 1
1
1 1 1 1
26
42
1 1
16
The serum vitamin BI2 concentration was re-examined in 41 patients with initial low values. In Fig. 5 the changes in serum vitamin B,, are plotted against observed changes in the patient's body weight. It seems that in the majority of cases (75 %) there was a concomitant increase in serum vitamin BI2 and body weight, while others showed a concomitant fall in both of these parametres. Two of these patients, a 77-year-old and an 89-year-old woman, both died later on from pneumonia. First main axis is described as y = -69.45 7 3 . 7 4 ~(my = 0.47, P < 0.01), showing that a co-variation exists between changes in serum vitamin B,, concentrations and in the body weight.
+
Fig. 4. Distribution of patients with low and normal serum vitamin B,, based on clinical diagnoses.
150 DISCUSSION Since assay of serum vitamin B,, is one of the most commonly used screening analyses for vitamin B12 deficiency it is important to realize that normally the blood content of cobalamin does not decrease with advancing age. This is in agreement with results previously reported from our group (Elsborg et al. (1976)). When the serum vitamin Blz in psychiatric patients showed a tendency to lower values, i.e. 10 % of patients had values beneath the lower normal range, this can not simply be due to a higher age among psychiatric patients. Genuine pernicious anaemia was found in one patient. This is in agreement with an expected and observed incidence of approximately 0.1 % in the general population of the same age range (Pedersen & Mosbech (1969)). Gastrectomy might have contributed to low serum vitamin B12 values in another seven cases, even though vitamin BIZ absorption as assessed by the Schilling-test proved to be normal. Small intestinal resection (Crohn’s disease) could be the cause of vitamin B,, deficiency in one case. Finally, vitamin B,, deficiency might be due to peculiar dietary habits in one patient. In the majority of cases (90 %) no specific cause of low vitamin B,, values was found. It is impressive, however, that many patients gave a history of alcoholism, drug addiction, poverty, loneliness, apathy and severe physical disabilities, which may lead to dietary insufficiency and nutritional deficiency of vitamin B,, (Elsborg et al. (1976), Hessov & Elsborg
CHANGES IN SERUM VITAMIN 61, pglml
*500 OI
Fig. 5 . Co-variation of serum vitamin B,, and body weight in 41 psychiatric patients during hospital stay.
151 (1976)). That bad dietary habits may be of major importance in these patients is shown by the fact that concomitant with gain in weight during hospitalization there was a clear-cut increase in the serum vitamin B12 levels. The question arises of a causality of vitamin B12 deficiency and psychiatric illness. With regard to psychiatric classification no special trend could be found among the patients with low levels of serum vitamin B,,. The preponderance of patients with arteriosclerotic dementia in the group with low and subnormal values does not prove that the condition was caused by vitamin B,, deficiency. This syndrome has little resemblance to the syndrome described by Warburg & Jgrgensen (1929) and by Smith (1960). Furthermore, neurological disturbances and EEG abnormalities (Wallace & Westmoreland (1976)), often found in organic syndromes of vitamin B,, deficiency, occurred at a rather low rate in our material. In our opinion it is most likely that these patients first developed a psychiatric disorder, e.g. a dementia, and secondarily a dietary insufficiency as their food intake quantitatively and qualitatively deteriorated. It should not be overlooked, however, that shortage of vitamin B,, and probably of other vitamins, e.g. folic acid, may lead to an aggravation of the already impaired functioning of the brain. In a controlled clinical trial Hughes et al. (1970)found improvement in psychiatric disorders of the elderly whether vitamin BIZ or placebo was given, but there was no evidence suggesting that vitamin B12 was superior to placebo. Shulman (1972) noted that in many patients with hypovitaminosis B,, there was a remission in mood even before treatment with vitamin Blz was started. In this context it is of interest that in 75 % of the patients in our study a spontaneous enhancement of serum vitamin B,, and body weight was observed shortly after admission, suggesting that proper feeding with a wellbalanced hospital diet may be a contributory factor in treatment of mental illness. Evidence is accumulating that dietary cobalamin deficiency is not so rare in our community as previously thought (Nielsen (1965), Elsborg et al. (1976), Hessov & Elsborg (1976), Hippe et al. (1978)). Most cases are mild and will recover after correction of the nutritional defect without further vitamin B,, supplements. If it proves difficult for the patients to change their dietary habits because of old age, dementia, intellectual reduction or complicating factors as gastrectomy and small intestinal resection a deficiency state should be treated with vitamin B12 in order to avoid further damage to nervous tissue.
REFERENCES Carney,M . W . P., & B. F. Shefield (1978): Serum folic acid and B,, in 272 psychiatric in-patients. Physiol. Med. 8, 139-144. Droller, H., & J . A . Dossett (1959): Vitamin B,, levels in senile dementia and confusional states. Geront. Clin. 1, 96-106. Edwin, E., K . Holten, K . R. Norum, A . Schrumph & 0.E. Skaug (1965): Vitamin B,, hypovitaminosis in mental diseases. Acta med. scand. 117, 689-699. Elsborg, L., V.Lund & P . Basrrup-Madsen (1976):Serum vitamin B,, levels in the aged. Acta med. scand. ZOO, 309-314.
152
Hansen, T., & E. Hauschildt (1974): Microbiological assay of vitamin B,, in biological fluids. The lactobacillus leichmannii method. Scand. J. Gastroent., Suppl. 29, 27-31. Hessov, I., & L. Elsborg (1976): Nutritional studies on long-term surgical patients with special reference to the intakes of vitamin B,, and folic acid. Int. J. Vitamin. Nutr. Res. 46, 427-432. Hippe, E., O . P . Hansen, L. Lauridsen & S. Gjlrup (1978): Vitamin B og folinsyrekoncentration i blodet hos patienter p i en langtidsmedicinsk afdeling i KZbenhavn. Ugeskr. Leg. 140, 2034-2037. Holmes, J . M . (1956): Cerebral manifestations of vitamin B,, deficiency. Brit. med. J. 2, 1394-1398. Hughes, D., P. C. Elwood, N . K . Shinton & R. J . Wrighton (1970): Clinical trial of the effects of vitamin B,, in elderly subjects with low serum B,, levels. Brit. med. J. 2, 458460. Zsaksson, A., A . Nyrstener & J . - 0 . Ottosson (1971): Screening for vitamin B,, deficiency in psychiatric patients. Acta psychiat. scand., Suppl. 221, 133-142. Nielsen, B . (1965): The blood vitamin B,, concentration of older patients admitted to a neurological department. Acta neurol. scand. 41, 513-526. Pedersen, A . B., & J . Mosbech (1969): Morbidity of pernicious anaemia. Acta. med. scand. 185, 449-452. Shulman, R . (1967): A survey of vitamin B,, deficiency in an elderly psychiatric population. Brit. J. Psychiat. 113, 241-251. Shulman, R . (1972): The present status of vitamin B,, and folic acid deficiency in psychiatric illness. Canad. psychiat. Ass. J. 17, 205-216. Smith, A . D. M . (1960): Megaloblastic madness. Brit. med. J. 3, 1840-1843. Sokal, R . R., & F. J . Rohlf (1969): Biometry. The principles and practice of statistics in biological research. W. H. Freeman & Co., San Francisco. Wallace, P. W., & B . F. Westmoreland (1976): The electroencephalogram in pernicious anaemia. Mayo Clin. Proc. 51, 281-285. Warburg, E. J., & S. Jlrgensen (1928): Psychoses and neurasthenia associated with achylia gastrica and megalocytosis and the relation between this syndrome and pernicious anaemia. Acta med. scand. 69, 537-592. Warburg, E. S., & S. @rgensen (1929): Psychoses and neurasthenia associated with achylia gastrica and megalocytosis and the relation between this syndrome and pernicious anaemia. Acta med. scand. 70, 193-215.
,,
Received May 31, 1978
0.I . Rafaelsen Department of Psychiatry Rigshospitalet DK-2100 Copenhagen $3 Denmark
Vitamin BIZ concentrations in psychiatric patients L. ELSBORG, T. HANSEN AND 0. J. RAFAELSEN In an attempt to evaluate the possible relationship between vitamin B,, deficiency and mental disease, the blood content of vitamin B,, was investigated in 835 consecutive psychiatric patients. Low serum vitamin B,, values were found in approximately 10 % of these patients, due to latent pernicious anaemia in one case, post-gastrectomy in seven cases and small intestinal resection in one case. In the remaining 72 cases vitamin B,, deficiency was probably caused
by nutritional insufficiency. After correction of the dietary defect there was a spontaneous increase in serum vitamin B,, in 75 % of these patients. No specific psychiatric syndrome was connected with hypovitaminosis BIZ, but a preponderance of arteriosclerotic dementia suggests that low serum vitamin B,, values are secondary to mental illness leading to apathy and loss of appetite. Most cases will recover without further vitamin B,, supplements. But some patients may need treatment because of severe mental and physical disabilities. Key words: Hypovitaminosis B,, - nutritional insufficiency chiatric patients - serum vitamin B12.
- psy-
It is an old observation that psychiatric disturbance may be present in pernicious anaemia (Warburg & J#rgensen (1928, 1929), Holmes (1956)). Even in the absence of frank anaemia mental disturbances and EEG abnormalities may be found in untreated pernicious anaemia (Wallace & Westmoreland (1976)). Earlier investigators have found a relatively high frequency of hypovitaminosis B,, among psychiatric patients (Droller & Dossett (1959), Edwin et al. (1965), Shulman (1967), Zsaksson et al. (1971), Carney & Shefield (1978)), suggesting a relationship between vitamin B,, deficiency and mental illness. This study was performed in an attempt to elucidate to what extent hypovitaminosis B,, may contribute to mental illness in a psychiatric ward with special regard to its possible causality. MATERIAL AND METHODS During a period extending over 10 months (November-August) a venepuncture for assay of vitamin B,, was performed on admission to the Department of Psychiatry, Rigshospitalet, Copenhagen, in 835 consecutive patients. There were 438 men and 397 women aged 17-98 years. The serum vitamin BIZ concentra10
0001-690X/79/020145-08$02.50/0 @ 1979 Munksgaard, Copenhagen
146 tion was determined by the lactobacillus Leichmanni method (performed by the Research Laboratories of Dumex Ltd., Copenhagen; Hansen & Hauschildt (1974)). Patients treated with antibiotics at the time of admission were primarily excluded from the study. Patients with normal serum vitamin BIZ levels, i.e. above 200 pg/ml, were subjected to no further study. In patients with low concentrations of vitamin BIZ an investigation program was instituted, comprising blood examinations, serum iron, total iron binding capacity, marrow examination, Schilling-test and examinations of EEG recordings. Finally, after a delay of 4-6 weeks, the serum % PROBIT SCALE
t
99
-
-
80
50-
10-
52-
I
1
100
I
I
200 300
I
LOO
I
I
500 600
I
*
700 800 pg/ml
SERUM VITAMIN 812
Fig. 1. Cumulative frequency of serum vitamin B , , in 88 normal persons. No.
t
Serum vitamin BI,
pglml
Fig. 2. Distribution of 835 psychiatric patients related to serum vitamin B I E .
147 vitamin B,, determination was repeated. In all patients a complete medical, psychiatric and neurological examination was carried out. The reference material consisted of 88 persons, 54 men and 34 women, aged 18-64 years (mean 33 k 11 years). Statistical calculation was performed by a modified chi-square test (Sokal & Rohlf (1969)), Kolmorgorov-Smirnow test, analyses of co-variations and correlations. RESULTS From the frequency distribution diagram the reference material appears to follow a normal distribution (Fig. l), the mean value 436 k 118 pg/ml. Thus the normal range is calculated as 200-700 pg/ml. The correlation between age and serum vitamin B12 concentration was non-significant (r = -0.07, P > 0.10). The distribution of psychiatric patients related to serum vitamin Blz (Fig. 2) was skew and did not fit a normal distribution. The mean value was 399 pg/ml (range 50-1,050 pg/ml. The majority of patients (61 %) had serum vitamin Blz values below 400 pg/ml and in 81 patients (9.7 %) the serum vitamin BIZ was under 200 pg/ml, the lower limit of normal range. Five patients (0.6 %) had extremely low values (< 100 pg/ml). The age distribution in patients with low serum vitamin B12 values was compared with the age distribution in patients with normal serum vitamin B12 (Fig. 3). Generally patients with low serum vitamin B12 were older than patients with normal serum vitamin BIZ (P< 0.001). Based on the levels of serum vitamin BlZ the patients were divided into three groups (Table 1). In the first group (serum vitamin B12 < 100 pg/ml) of five patients, one patient, a 72-year old woman, had genuine pernicious anaemia based on diagnostic criteria as previously described (Elsborg et al. (1976)). Another patient, a 71-year old woman, appeared to be a fanatic vegetarian with most peculiar dietary habits. Neither this patient nor the remaining three patients in this group fulfilled the criteria of pernicious anaemia. The second group (serum vitamin B12 100-150 pg/ml) consisted of 23 patients. None of these suffered from pernicious anaemia, but mild megaloblastic transformation in the bone marrow was found in two patients. One of these patients had a pathologically low Schilling-test, which, however, normalized in a repeated study. In the third group (serum vitamin B,, 150-200 pg/ml) of 53 patients no cases of pernicious anaemia were disclosed. EEG abnormalities (Table 1) were relatively frequent findings, occurring in 100 % (five out of five) of the low vitamin Blz group, 40 % (six out of 15) of the medium vitamin B12 group and 52 % (11 out of 21) of the high vitamin BlZ group. Neurological disturbances were found in 11 %, in most cases secondary to other disorders (epilepsy, hemiparesis, syphilis), which were fairly common findings in patients with hypovitaminosis B12 (Table 2). A history of drug addiction (11 %) and alcoholism (16 %) was often revealed. The Schilling-test was per10.
148 Table 1. Serum vitamin Bla concentration related to various haematological and clinical studies in 81 psychiatric patients
Serum vitamin B12 @g/ml) 50-100 100-150 150-200
No. patients Hgb < 12 g/lOO ml MCV > 100 fl Sideropenia Megaloblastic marrow Schilling test < 10 % Neurological abnormalities EEG abnormalities
5 1 1
23 1 1
1 2 1 5
53
Total no. of patients 81 81 73
1
6 1 2
65
2 1 2 6
1 6 11
15 13 78 41
formed in four gastrectomized patients and gave a normal result in all. Comparison of psychiatric syndromes (Fig. 4) in patients with low and with normal serum vitamin B,, showed that arteriosclerotic brain disease was the only syndrome occurring predominantly in patients with low serum vitamin BI2 values ( P < 0.001). %
25
251
Normal serum vitamin BlZ
I1
mean = 42 n = 754
20 15
10 5
zl$
Low serum vitamin B12
Fig. 3. Histogram showing the distribution of psychiatric patients with normal and low serum vitamin B,, values as compared with their ages.
149 Table 2. Concomitant disabilities in 81 psychiatric patients with vitamin B I , deficiency
Drug addiction Loneliness Gastrectomy Dietary insufliciency Epilepsy Physical disorder Neurosyphilis Intellectual disability Pernicious anaemia Crohn's disease Septicaemia Total
Males
Females
Total
3 1 5 1
6 6 2 5 3
9 7 7 6 4
1 1
3 2
1 2 1 1
1
1 1 1 1
26
42
1 1
16
The serum vitamin BI2 concentration was re-examined in 41 patients with initial low values. In Fig. 5 the changes in serum vitamin B,, are plotted against observed changes in the patient's body weight. It seems that in the majority of cases (75 %) there was a concomitant increase in serum vitamin BI2 and body weight, while others showed a concomitant fall in both of these parametres. Two of these patients, a 77-year-old and an 89-year-old woman, both died later on from pneumonia. First main axis is described as y = -69.45 7 3 . 7 4 ~(my = 0.47, P < 0.01), showing that a co-variation exists between changes in serum vitamin B,, concentrations and in the body weight.
+
Fig. 4. Distribution of patients with low and normal serum vitamin B,, based on clinical diagnoses.
150 DISCUSSION Since assay of serum vitamin B,, is one of the most commonly used screening analyses for vitamin B12 deficiency it is important to realize that normally the blood content of cobalamin does not decrease with advancing age. This is in agreement with results previously reported from our group (Elsborg et al. (1976)). When the serum vitamin Blz in psychiatric patients showed a tendency to lower values, i.e. 10 % of patients had values beneath the lower normal range, this can not simply be due to a higher age among psychiatric patients. Genuine pernicious anaemia was found in one patient. This is in agreement with an expected and observed incidence of approximately 0.1 % in the general population of the same age range (Pedersen & Mosbech (1969)). Gastrectomy might have contributed to low serum vitamin B12 values in another seven cases, even though vitamin BIZ absorption as assessed by the Schilling-test proved to be normal. Small intestinal resection (Crohn’s disease) could be the cause of vitamin B,, deficiency in one case. Finally, vitamin B,, deficiency might be due to peculiar dietary habits in one patient. In the majority of cases (90 %) no specific cause of low vitamin B,, values was found. It is impressive, however, that many patients gave a history of alcoholism, drug addiction, poverty, loneliness, apathy and severe physical disabilities, which may lead to dietary insufficiency and nutritional deficiency of vitamin B,, (Elsborg et al. (1976), Hessov & Elsborg
CHANGES IN SERUM VITAMIN 61, pglml
*500 OI
Fig. 5 . Co-variation of serum vitamin B,, and body weight in 41 psychiatric patients during hospital stay.
151 (1976)). That bad dietary habits may be of major importance in these patients is shown by the fact that concomitant with gain in weight during hospitalization there was a clear-cut increase in the serum vitamin B12 levels. The question arises of a causality of vitamin B12 deficiency and psychiatric illness. With regard to psychiatric classification no special trend could be found among the patients with low levels of serum vitamin B,,. The preponderance of patients with arteriosclerotic dementia in the group with low and subnormal values does not prove that the condition was caused by vitamin B,, deficiency. This syndrome has little resemblance to the syndrome described by Warburg & Jgrgensen (1929) and by Smith (1960). Furthermore, neurological disturbances and EEG abnormalities (Wallace & Westmoreland (1976)), often found in organic syndromes of vitamin B,, deficiency, occurred at a rather low rate in our material. In our opinion it is most likely that these patients first developed a psychiatric disorder, e.g. a dementia, and secondarily a dietary insufficiency as their food intake quantitatively and qualitatively deteriorated. It should not be overlooked, however, that shortage of vitamin B,, and probably of other vitamins, e.g. folic acid, may lead to an aggravation of the already impaired functioning of the brain. In a controlled clinical trial Hughes et al. (1970)found improvement in psychiatric disorders of the elderly whether vitamin BIZ or placebo was given, but there was no evidence suggesting that vitamin B12 was superior to placebo. Shulman (1972) noted that in many patients with hypovitaminosis B,, there was a remission in mood even before treatment with vitamin Blz was started. In this context it is of interest that in 75 % of the patients in our study a spontaneous enhancement of serum vitamin B,, and body weight was observed shortly after admission, suggesting that proper feeding with a wellbalanced hospital diet may be a contributory factor in treatment of mental illness. Evidence is accumulating that dietary cobalamin deficiency is not so rare in our community as previously thought (Nielsen (1965), Elsborg et al. (1976), Hessov & Elsborg (1976), Hippe et al. (1978)). Most cases are mild and will recover after correction of the nutritional defect without further vitamin B,, supplements. If it proves difficult for the patients to change their dietary habits because of old age, dementia, intellectual reduction or complicating factors as gastrectomy and small intestinal resection a deficiency state should be treated with vitamin B12 in order to avoid further damage to nervous tissue.
REFERENCES Carney,M . W . P., & B. F. Shefield (1978): Serum folic acid and B,, in 272 psychiatric in-patients. Physiol. Med. 8, 139-144. Droller, H., & J . A . Dossett (1959): Vitamin B,, levels in senile dementia and confusional states. Geront. Clin. 1, 96-106. Edwin, E., K . Holten, K . R. Norum, A . Schrumph & 0.E. Skaug (1965): Vitamin B,, hypovitaminosis in mental diseases. Acta med. scand. 117, 689-699. Elsborg, L., V.Lund & P . Basrrup-Madsen (1976):Serum vitamin B,, levels in the aged. Acta med. scand. ZOO, 309-314.
152
Hansen, T., & E. Hauschildt (1974): Microbiological assay of vitamin B,, in biological fluids. The lactobacillus leichmannii method. Scand. J. Gastroent., Suppl. 29, 27-31. Hessov, I., & L. Elsborg (1976): Nutritional studies on long-term surgical patients with special reference to the intakes of vitamin B,, and folic acid. Int. J. Vitamin. Nutr. Res. 46, 427-432. Hippe, E., O . P . Hansen, L. Lauridsen & S. Gjlrup (1978): Vitamin B og folinsyrekoncentration i blodet hos patienter p i en langtidsmedicinsk afdeling i KZbenhavn. Ugeskr. Leg. 140, 2034-2037. Holmes, J . M . (1956): Cerebral manifestations of vitamin B,, deficiency. Brit. med. J. 2, 1394-1398. Hughes, D., P. C. Elwood, N . K . Shinton & R. J . Wrighton (1970): Clinical trial of the effects of vitamin B,, in elderly subjects with low serum B,, levels. Brit. med. J. 2, 458460. Zsaksson, A., A . Nyrstener & J . - 0 . Ottosson (1971): Screening for vitamin B,, deficiency in psychiatric patients. Acta psychiat. scand., Suppl. 221, 133-142. Nielsen, B . (1965): The blood vitamin B,, concentration of older patients admitted to a neurological department. Acta neurol. scand. 41, 513-526. Pedersen, A . B., & J . Mosbech (1969): Morbidity of pernicious anaemia. Acta. med. scand. 185, 449-452. Shulman, R . (1967): A survey of vitamin B,, deficiency in an elderly psychiatric population. Brit. J. Psychiat. 113, 241-251. Shulman, R . (1972): The present status of vitamin B,, and folic acid deficiency in psychiatric illness. Canad. psychiat. Ass. J. 17, 205-216. Smith, A . D. M . (1960): Megaloblastic madness. Brit. med. J. 3, 1840-1843. Sokal, R . R., & F. J . Rohlf (1969): Biometry. The principles and practice of statistics in biological research. W. H. Freeman & Co., San Francisco. Wallace, P. W., & B . F. Westmoreland (1976): The electroencephalogram in pernicious anaemia. Mayo Clin. Proc. 51, 281-285. Warburg, E. J., & S. Jlrgensen (1928): Psychoses and neurasthenia associated with achylia gastrica and megalocytosis and the relation between this syndrome and pernicious anaemia. Acta med. scand. 69, 537-592. Warburg, E. S., & S. @rgensen (1929): Psychoses and neurasthenia associated with achylia gastrica and megalocytosis and the relation between this syndrome and pernicious anaemia. Acta med. scand. 70, 193-215.
,,
Received May 31, 1978
0.I . Rafaelsen Department of Psychiatry Rigshospitalet DK-2100 Copenhagen $3 Denmark
