- Email: [email protected]
Depression in the aged: Relation to folate and vitamins C and B12
210
BIOL PSYCHIATRY 1989;26:209-220
Correspondence
Peter Briiunig’ Johannes Bleistein* Marie Luke Rao’
Universitiitsnervenklinik Psychiatric’ und Neurologie* Sigmund-Freud-?%. 2.5 5300 Bonn 1 Federal Republic of Germany
References Angelucci L, PatacchioliPR, Bohus B, de Kloet ER (1982): Serotonergic innervation and glucocorticoid binding in the hippocampus, relevance to depression. In Costa E, Racagni G (eds), Typical and Atypical A&depressants: Molecular Mechanisms. New York: Raven Press, pp 365-370. .&berg M, T&&man L, Thoren P (1976): 5-HIAA in the cere.brospinal fluid: A biochemical suicide predictor? Arch Gen Psychiatry 38:1193-l 197.
Banki CM, Arato M (1983): Amine metabolites and neuroendocrine responses related to depression and suicide. J Affect Disord 5:223-226.
Bdunig P, Bleistein J (1988a): Kortisoninduzierte Psychosen. Nervenarzr 591596-602. Br%mig P, Bleistein J (1988b): Kortisonpsychosen:Eine Analyse von 150 Flillen der Literatur. ZBI Neurol 250:195-211.
Depression in the Aged: Relation to Folate and Vitamins C and B12 To the Editor: The literature on the relationships among vi. tamin C, vltamm B12, and folate status and psychiatric disorders is sparse and controversial (Camey and Sheffield 1978; Ghadirian et al. 1980; Zucker et al. 1981). We have explored relationships among plasma vitamin C, serum vitamin B12, and erythrocyte folate and depression in the elderly using a controlled transversal design. The population consisted of 40 depressed persons (DSM-III criteria) (Kivell et al. 1986, 1988) and a sex- and agematched control group of 40 nondepressives. The study was conducted in January and February 1988. Plasma vitamin C levels were determined by highperformance liquid chromatography (normal values
Bunney W, Fawcett J (1965): Possibility of a biochemical test for suicide potential. Arch Gen Psychiatry 13:232237.
Crawley JN, Sutton ME, Pickar D (1985): Animal models of self-destructive behavior and suicide. Psychiutr Clin North Am 8:299-310.
Curzon G, Green AR (1968): Effect of hydrocortisone on rat brain 5-hydroxytryptamine. Life Sci 7:657-661. Foote WE, Lieb JP, Martz RL, Gordon MW (1972): Effect of hydmcortisone on single unit activity in midbrain raphe. Brain Res 41:242-244. Fuxe K, H&&and A, Agnati LF, Yu Z-Y, Cintra A, Wikstriim A-C, Okret S, Cantoni E, Gustafsson J-A (1985): Immunocytochemical studies on the localization of glucocorticoid receptor immunoreactive nerve cells in the lower brain stem and spinal cord of the male rat using a monoclonal antibody against rat liver glucocorticoid receptor. Neurosci Len 60:1-6. Krieger G (1974): The plasma level of cortisol as a predictor of suicide. Dis Nerv Syst 35:237-240. Ling MHM, Perry DJ, Trumans MI (1981): Side effects of corticosteroid therapy. Psychiatric aspects. Arch Gen Psychiatry 381471-477.
Murphy GE (1986): Suicide and attempted suicide. In Winokur G, Clayton P (eds), The Medical Basis of Psy chiarry. Philadelphia: Saunders. van Praag HM (1986): Biological suicide research: Outcome and limitations. Biol Psychiatry 21: 1305-1323. WhitJock FA (1982): Symptomatic affective disorders. Sydney: Academic Press, pp 85-98.
20-80 FmoVliter) Parviainen et al. 1986), serum vitamin B12 levels by the radioimmunoassay method (Amersham kit) (normal values 170-640 pm0Hite.r) (Lin and Sullivan 1972), and serum folate levels by a radioimmunoassay method (Amersham kit), after which erythrocyte folate levels were calculated by dividing serum folate by hematocrit (normal values over 350 nmolfliter) (DUM and Foster 1973). Blood hemoglobin and blood cell counts were analyzed by an automated analyzer. One depressed patient refused to participate. The statistical tests used were the t-test and the Kolmogorov-Smimov test (for differences between two means), the one-way analysis of Variance (for differences between three means), and the chi-square test [for categorical variables). Both the depressed and the nondepressed group consisted of 10 men and 29 women (Table 1). The
BIOL PSYCHIATRY 1989;26:209-220
Correspondence
211
Table 1. Description of the Study Population Not depressed
Depressed
Gender Male Female Total Place of residence Home Institution Functional capacity Independent Not independent Educational level Less than basic Basic or more Mean f SDage (yea@
n
p-Value r-Test
Chi-square test
n
(96)
10 29 39
(26) (74) (100)
10 29 39
(26) (74) (100)
32 7
(82) (18)
36 3
(92) (8)
27 12
(69) (31)
8 31
(20) (80)
0.437
11 28
(28) (72)
11 28
(28) (72)
1.000
(8)
1.000 0.310
75.5 + 7.4
75.9 k 7.9
0.814
“Needs help in more difficult self-care and daily activities, but not in walking.
age range was 65-99 years for the depressed and 6593 years for the nondepressed population. The depressed group consisted of 3 (8%) major depressives, 35 (90%) dysthymic patients, and 1 (2%) with atypical depression. Plasma vitamin C varied from 6 to 103 pmoUliter in the depressed group and from 6 to 87 pmoVliter in the nondepressed group (Table 2). Eleven (28%) depressed and 11 (28%) nondepressed persons showed values lower than 20 pmol/liter. Serum vitamin B I2variedfrom 124 to 83 1 pmol/liter in the depressed group and from 80 to 462 pmol/liter
in nondepressed persons. Two (5%) depressed and 5 (13%) nondepressed persons showed values lower than 170 pmol/liter. Erythrocyte folate varied from 232 to 900 mnoYliter in depressed persons and from 21 to 988 nmoVliter in nondepressed persons. Thirteen (33%) depressed and 14 (36%) nondepressed persons showed values lower than 350 nmohliter. The mean values and the distributions of plasma vitamin C, serum vitamin B,z, or erythrocyte folate did not differ between depressives and nondepressives. Neither did they differ among major depres-
Table 2. Distribution of Plasma Vitamin C (pmol/liter) Serum Vitamin Blz (pmol/liter), and Erythrocyte Folate (nmol/liter) Levels by Depression Depressed (n = 39) Mean Plasma Vitamin C Serum vitamin Biz Whrocyte folate ‘Kolmogorov-Smimov test
Not depressed (n = 39) SD
Mean
SD
p-Value r-Test
K-S test
41.2
25.8
39.6
22.9
0.771
0.202
360.3
152.6
316.3
107.2
0.146
0.410
471.7
174.7
422.6
184.1
0.231
0.377
212
BIOL PSYCHIATRY
Correspondence
1989;26:20!%220
Table 3. Distribution
of Blood Hemoglobulin and Cell Counts by Depression Depressed (n = 39) Mean
Hemoglobulin Hematocrit White blood cell count ( x E9/liter) Red blood cell count (X ElZ/liter) Mean corpuscular volume (8) Mean corpuscular hemoglobin (pg) Mean coxpusc~~lar hemoglobin concentration (g/liter)
SD
143.1 14.7 0.42 0.04 6.7 1.8
Not depressed (n = 39) Mean
SD
p-Value
r-Test K-S test’
144.2 0.43 6.6
11.2 0.03 2.2
0.698 0.697 0.960
0.609 0.109 0.239
4.8
0.4
4.8
0.4
0.915
0.273
89.4
4.3
89.6
5.1
0.791
0.244
29.3
1.8
29.8
1.6
0.175
0.009
333.6
8.6
335.3
6.9
0.346
0.763
“Kolmogorov-Smimov test
sive, dysthymic, and atypical depressive patients. No differences were found among major depressive, dysthymic, or atypical depressive patients and their individual controls. Mean corpuscular hemoglobin was lower in depressed persons, which was the only significant difference in blood cell counts (Table 3). Though it would have been interesting to see which clinical changes could be observed if deficiencies were corrected, we had no opportunity to follow the population. Our results, however, do not support the idea that poor vitamin C, vitamin B,*, or folate status is related to depression in old age. Our sample was heterogeneous, consisting of three subtypes of depression, but the results obtained by subdividing the population suggest that the negative findings hold true for all subtypes. Differences between earlier findings and our results can be explained by differences in population and methods: a nondepressed control group was included here, whereas earlier studies did not usually compare depressed persons with nondepressed persons. Dysthymic disorder was common in our group, whereas the subjects of earlier studies had been major depressive hospital patients. Sirkka-Liisa Kivelii, ’ Kimmo Pahkala2 Ari Eronen’
’ University of Oulu Department of Public Health Science (Aapistie 3 SF-90220 Oulu, Finland * Ahtiirinj;irvi Health Centre ;ihttii, Finland ’ University of Tampere Department of Public Health Tampere , Finland This study has been supported by a grant from Roche Phar-
maceutical Company.
References Camey MWP, Sheffield BP (1978): Serum folic acid and Bf2 in 272 psychiatric inpatients. Psycho1 Med 8:139-144.
Dunn RT, Foster LB (1973): Radioassay of serum folate. Clin Chem 19:1101-l 105. Ghadirian AM, Ananth J, Engelsmann F (1980): Folic acid deficiency and depression. Psychosomatics 21:926-929.
Kivell S-L, Pahkala K, Tervo R-R (1986): Prevalence of depressive symptoms among an elderly Finnish population. Nord Psykiatr Tidsskr 40:4550.
Kivelii S-L, Pahkala K, Laippala P (1988): Prevalence of depression in an elderly Finnish population. Acta Psychiatr Scami 78:401-413.
Correspondence
Lin YK, Sullivan LW (1972): An improved radioisotope dilution assay for serum vitamin Bir using haemoglobm-coated charcoal. Blood 39:426-432. Parviainen M, Nyyssbnen K, Penttilli I, Sepptien K, Rauramaa R, Salonen J, Gref CG (1986): A method for routine assay of plasma ascorbic acid using
Melanocyte-Stimulating Hormone in Tardive Dyskinesia To The Editor: There is evidence to suggest that the development of tardive dyskinesia (TD) may be related to preexisting brain damage (Youssef and Waddington 1988). Recently, Sorokin et al. (1988) investigated specific types of memory functions in 40 schizophrenic patients with and without TD and observed that TD patients scored significantly lower than non-TD patients on parameters of visual learning, although no differences were found in parameters of verbal memory. Although these findings may suggest that the integrity of the right hemisphere is more compromised in TD compared to non-TD patients, they also suggest that the emergence of TD may be associated with abnormalities in the activity of the melanocytestimulating hormone (MSH) peptides. Animal studies have suggested that MSH peptides are involved in memory and learning processes, particularly those related to visual-motor learning, as distinguished from verbal memory (O’Donohue and Dorsa 1982). Human studies have supported these findings, specifically implicating MSH peptides in visual memory processes (O’Donohue and Dorsa 1982). Various studies have reported that administration of alpha-MSH to humans enhanced visual memory exclusively, where as auditory memory processing was unaffected (O’Donohue and Dorsa 1982). Abnormal MSH functions (Rainero et al. 1988) may also be associated with visuospatial deficits observed in patients with Parkinson’s disease (PD) (Stem et al. 1984). In addition to their role in visual memory processing, MSH peptides have also been implicated in the patho-
BIOL PSYCHIATRY 1989;26:209-220
213
high-performance liquid chromatography. J Liq Chromatogr 9-10:2185-2197.
Zucker DK, Livingstone RL, Nakra R, Clayton PJ (1981): Br2 deficiency and psychiatric disorders: Case report and literature review. Viol Psychiatry 16:197-205.
physiology of human movement disorders, as administration of ACTH(l-24) and alpha-MSH into the vicinity of the locus coeruleus of rats produced postural asymmetry resembling human dystonia (Jacquet and Abrams 1982). Moreover, pinealectomy results in increased pituitary MSH levels (Kastin et al. 1967), and pinealectomized rats have increased incidence of spontaneous abnormal perioral movements (Sandyk et al. 1988). Abnormal MSH functions in schizophrenic patients with TD may be related to both the disease process and the effects of neuroleptic drugs. Increased plasma alpha-MSH levels have been reported in several human disorders associated with delayed brain maturation, including anencephaly (Honnebier and Swaab 1973), Tourette’s syndrome (Sandyk 1988), and in infants of diabetic mothers (Hassan et al. 1986). Neuroleptics may affect pituitary MSH release by blocking the inhibitory effects of the tuberoinfundibular dopaminergic system on MSH release (O’Donohue and Dorsa 1982) or by stimulating hypothalamic messenger-RNA Proopiomelanocortin (POMC) biosynthesis (Tilders et al. 1985). In addition, neuroleptic drugs may alter MSH bioactivity by influencing the processing of MSH from the POMC precursor (Tilders et al. 1985). To further investigate the role of MSH in TD, we examined the relationship between the severity of TD and seborrheic dermatitis in three neuroleptic-treated male schizophrenic patients ages 28-34 years. As elevated plasma beta-MSH levels have been associated with seborrheic dermatitis (Shuster et al. 1973), the latter was used as a clinical marker of plasma beta-MSH activity. In all patients, low TD scores (on the Rockland Scale) were associated
BIOL PSYCHIATRY 1989;26:209-220
Correspondence
Peter Briiunig’ Johannes Bleistein* Marie Luke Rao’
Universitiitsnervenklinik Psychiatric’ und Neurologie* Sigmund-Freud-?%. 2.5 5300 Bonn 1 Federal Republic of Germany
References Angelucci L, PatacchioliPR, Bohus B, de Kloet ER (1982): Serotonergic innervation and glucocorticoid binding in the hippocampus, relevance to depression. In Costa E, Racagni G (eds), Typical and Atypical A&depressants: Molecular Mechanisms. New York: Raven Press, pp 365-370. .&berg M, T&&man L, Thoren P (1976): 5-HIAA in the cere.brospinal fluid: A biochemical suicide predictor? Arch Gen Psychiatry 38:1193-l 197.
Banki CM, Arato M (1983): Amine metabolites and neuroendocrine responses related to depression and suicide. J Affect Disord 5:223-226.
Bdunig P, Bleistein J (1988a): Kortisoninduzierte Psychosen. Nervenarzr 591596-602. Br%mig P, Bleistein J (1988b): Kortisonpsychosen:Eine Analyse von 150 Flillen der Literatur. ZBI Neurol 250:195-211.
Depression in the Aged: Relation to Folate and Vitamins C and B12 To the Editor: The literature on the relationships among vi. tamin C, vltamm B12, and folate status and psychiatric disorders is sparse and controversial (Camey and Sheffield 1978; Ghadirian et al. 1980; Zucker et al. 1981). We have explored relationships among plasma vitamin C, serum vitamin B12, and erythrocyte folate and depression in the elderly using a controlled transversal design. The population consisted of 40 depressed persons (DSM-III criteria) (Kivell et al. 1986, 1988) and a sex- and agematched control group of 40 nondepressives. The study was conducted in January and February 1988. Plasma vitamin C levels were determined by highperformance liquid chromatography (normal values
Bunney W, Fawcett J (1965): Possibility of a biochemical test for suicide potential. Arch Gen Psychiatry 13:232237.
Crawley JN, Sutton ME, Pickar D (1985): Animal models of self-destructive behavior and suicide. Psychiutr Clin North Am 8:299-310.
Curzon G, Green AR (1968): Effect of hydrocortisone on rat brain 5-hydroxytryptamine. Life Sci 7:657-661. Foote WE, Lieb JP, Martz RL, Gordon MW (1972): Effect of hydmcortisone on single unit activity in midbrain raphe. Brain Res 41:242-244. Fuxe K, H&&and A, Agnati LF, Yu Z-Y, Cintra A, Wikstriim A-C, Okret S, Cantoni E, Gustafsson J-A (1985): Immunocytochemical studies on the localization of glucocorticoid receptor immunoreactive nerve cells in the lower brain stem and spinal cord of the male rat using a monoclonal antibody against rat liver glucocorticoid receptor. Neurosci Len 60:1-6. Krieger G (1974): The plasma level of cortisol as a predictor of suicide. Dis Nerv Syst 35:237-240. Ling MHM, Perry DJ, Trumans MI (1981): Side effects of corticosteroid therapy. Psychiatric aspects. Arch Gen Psychiatry 381471-477.
Murphy GE (1986): Suicide and attempted suicide. In Winokur G, Clayton P (eds), The Medical Basis of Psy chiarry. Philadelphia: Saunders. van Praag HM (1986): Biological suicide research: Outcome and limitations. Biol Psychiatry 21: 1305-1323. WhitJock FA (1982): Symptomatic affective disorders. Sydney: Academic Press, pp 85-98.
20-80 FmoVliter) Parviainen et al. 1986), serum vitamin B12 levels by the radioimmunoassay method (Amersham kit) (normal values 170-640 pm0Hite.r) (Lin and Sullivan 1972), and serum folate levels by a radioimmunoassay method (Amersham kit), after which erythrocyte folate levels were calculated by dividing serum folate by hematocrit (normal values over 350 nmolfliter) (DUM and Foster 1973). Blood hemoglobin and blood cell counts were analyzed by an automated analyzer. One depressed patient refused to participate. The statistical tests used were the t-test and the Kolmogorov-Smimov test (for differences between two means), the one-way analysis of Variance (for differences between three means), and the chi-square test [for categorical variables). Both the depressed and the nondepressed group consisted of 10 men and 29 women (Table 1). The
BIOL PSYCHIATRY 1989;26:209-220
Correspondence
211
Table 1. Description of the Study Population Not depressed
Depressed
Gender Male Female Total Place of residence Home Institution Functional capacity Independent Not independent Educational level Less than basic Basic or more Mean f SDage (yea@
n
p-Value r-Test
Chi-square test
n
(96)
10 29 39
(26) (74) (100)
10 29 39
(26) (74) (100)
32 7
(82) (18)
36 3
(92) (8)
27 12
(69) (31)
8 31
(20) (80)
0.437
11 28
(28) (72)
11 28
(28) (72)
1.000
(8)
1.000 0.310
75.5 + 7.4
75.9 k 7.9
0.814
“Needs help in more difficult self-care and daily activities, but not in walking.
age range was 65-99 years for the depressed and 6593 years for the nondepressed population. The depressed group consisted of 3 (8%) major depressives, 35 (90%) dysthymic patients, and 1 (2%) with atypical depression. Plasma vitamin C varied from 6 to 103 pmoUliter in the depressed group and from 6 to 87 pmoVliter in the nondepressed group (Table 2). Eleven (28%) depressed and 11 (28%) nondepressed persons showed values lower than 20 pmol/liter. Serum vitamin B I2variedfrom 124 to 83 1 pmol/liter in the depressed group and from 80 to 462 pmol/liter
in nondepressed persons. Two (5%) depressed and 5 (13%) nondepressed persons showed values lower than 170 pmol/liter. Erythrocyte folate varied from 232 to 900 mnoYliter in depressed persons and from 21 to 988 nmoVliter in nondepressed persons. Thirteen (33%) depressed and 14 (36%) nondepressed persons showed values lower than 350 nmohliter. The mean values and the distributions of plasma vitamin C, serum vitamin B,z, or erythrocyte folate did not differ between depressives and nondepressives. Neither did they differ among major depres-
Table 2. Distribution of Plasma Vitamin C (pmol/liter) Serum Vitamin Blz (pmol/liter), and Erythrocyte Folate (nmol/liter) Levels by Depression Depressed (n = 39) Mean Plasma Vitamin C Serum vitamin Biz Whrocyte folate ‘Kolmogorov-Smimov test
Not depressed (n = 39) SD
Mean
SD
p-Value r-Test
K-S test
41.2
25.8
39.6
22.9
0.771
0.202
360.3
152.6
316.3
107.2
0.146
0.410
471.7
174.7
422.6
184.1
0.231
0.377
212
BIOL PSYCHIATRY
Correspondence
1989;26:20!%220
Table 3. Distribution
of Blood Hemoglobulin and Cell Counts by Depression Depressed (n = 39) Mean
Hemoglobulin Hematocrit White blood cell count ( x E9/liter) Red blood cell count (X ElZ/liter) Mean corpuscular volume (8) Mean corpuscular hemoglobin (pg) Mean coxpusc~~lar hemoglobin concentration (g/liter)
SD
143.1 14.7 0.42 0.04 6.7 1.8
Not depressed (n = 39) Mean
SD
p-Value
r-Test K-S test’
144.2 0.43 6.6
11.2 0.03 2.2
0.698 0.697 0.960
0.609 0.109 0.239
4.8
0.4
4.8
0.4
0.915
0.273
89.4
4.3
89.6
5.1
0.791
0.244
29.3
1.8
29.8
1.6
0.175
0.009
333.6
8.6
335.3
6.9
0.346
0.763
“Kolmogorov-Smimov test
sive, dysthymic, and atypical depressive patients. No differences were found among major depressive, dysthymic, or atypical depressive patients and their individual controls. Mean corpuscular hemoglobin was lower in depressed persons, which was the only significant difference in blood cell counts (Table 3). Though it would have been interesting to see which clinical changes could be observed if deficiencies were corrected, we had no opportunity to follow the population. Our results, however, do not support the idea that poor vitamin C, vitamin B,*, or folate status is related to depression in old age. Our sample was heterogeneous, consisting of three subtypes of depression, but the results obtained by subdividing the population suggest that the negative findings hold true for all subtypes. Differences between earlier findings and our results can be explained by differences in population and methods: a nondepressed control group was included here, whereas earlier studies did not usually compare depressed persons with nondepressed persons. Dysthymic disorder was common in our group, whereas the subjects of earlier studies had been major depressive hospital patients. Sirkka-Liisa Kivelii, ’ Kimmo Pahkala2 Ari Eronen’
’ University of Oulu Department of Public Health Science (Aapistie 3 SF-90220 Oulu, Finland * Ahtiirinj;irvi Health Centre ;ihttii, Finland ’ University of Tampere Department of Public Health Tampere , Finland This study has been supported by a grant from Roche Phar-
maceutical Company.
References Camey MWP, Sheffield BP (1978): Serum folic acid and Bf2 in 272 psychiatric inpatients. Psycho1 Med 8:139-144.
Dunn RT, Foster LB (1973): Radioassay of serum folate. Clin Chem 19:1101-l 105. Ghadirian AM, Ananth J, Engelsmann F (1980): Folic acid deficiency and depression. Psychosomatics 21:926-929.
Kivell S-L, Pahkala K, Tervo R-R (1986): Prevalence of depressive symptoms among an elderly Finnish population. Nord Psykiatr Tidsskr 40:4550.
Kivelii S-L, Pahkala K, Laippala P (1988): Prevalence of depression in an elderly Finnish population. Acta Psychiatr Scami 78:401-413.
Correspondence
Lin YK, Sullivan LW (1972): An improved radioisotope dilution assay for serum vitamin Bir using haemoglobm-coated charcoal. Blood 39:426-432. Parviainen M, Nyyssbnen K, Penttilli I, Sepptien K, Rauramaa R, Salonen J, Gref CG (1986): A method for routine assay of plasma ascorbic acid using
Melanocyte-Stimulating Hormone in Tardive Dyskinesia To The Editor: There is evidence to suggest that the development of tardive dyskinesia (TD) may be related to preexisting brain damage (Youssef and Waddington 1988). Recently, Sorokin et al. (1988) investigated specific types of memory functions in 40 schizophrenic patients with and without TD and observed that TD patients scored significantly lower than non-TD patients on parameters of visual learning, although no differences were found in parameters of verbal memory. Although these findings may suggest that the integrity of the right hemisphere is more compromised in TD compared to non-TD patients, they also suggest that the emergence of TD may be associated with abnormalities in the activity of the melanocytestimulating hormone (MSH) peptides. Animal studies have suggested that MSH peptides are involved in memory and learning processes, particularly those related to visual-motor learning, as distinguished from verbal memory (O’Donohue and Dorsa 1982). Human studies have supported these findings, specifically implicating MSH peptides in visual memory processes (O’Donohue and Dorsa 1982). Various studies have reported that administration of alpha-MSH to humans enhanced visual memory exclusively, where as auditory memory processing was unaffected (O’Donohue and Dorsa 1982). Abnormal MSH functions (Rainero et al. 1988) may also be associated with visuospatial deficits observed in patients with Parkinson’s disease (PD) (Stem et al. 1984). In addition to their role in visual memory processing, MSH peptides have also been implicated in the patho-
BIOL PSYCHIATRY 1989;26:209-220
213
high-performance liquid chromatography. J Liq Chromatogr 9-10:2185-2197.
Zucker DK, Livingstone RL, Nakra R, Clayton PJ (1981): Br2 deficiency and psychiatric disorders: Case report and literature review. Viol Psychiatry 16:197-205.
physiology of human movement disorders, as administration of ACTH(l-24) and alpha-MSH into the vicinity of the locus coeruleus of rats produced postural asymmetry resembling human dystonia (Jacquet and Abrams 1982). Moreover, pinealectomy results in increased pituitary MSH levels (Kastin et al. 1967), and pinealectomized rats have increased incidence of spontaneous abnormal perioral movements (Sandyk et al. 1988). Abnormal MSH functions in schizophrenic patients with TD may be related to both the disease process and the effects of neuroleptic drugs. Increased plasma alpha-MSH levels have been reported in several human disorders associated with delayed brain maturation, including anencephaly (Honnebier and Swaab 1973), Tourette’s syndrome (Sandyk 1988), and in infants of diabetic mothers (Hassan et al. 1986). Neuroleptics may affect pituitary MSH release by blocking the inhibitory effects of the tuberoinfundibular dopaminergic system on MSH release (O’Donohue and Dorsa 1982) or by stimulating hypothalamic messenger-RNA Proopiomelanocortin (POMC) biosynthesis (Tilders et al. 1985). In addition, neuroleptic drugs may alter MSH bioactivity by influencing the processing of MSH from the POMC precursor (Tilders et al. 1985). To further investigate the role of MSH in TD, we examined the relationship between the severity of TD and seborrheic dermatitis in three neuroleptic-treated male schizophrenic patients ages 28-34 years. As elevated plasma beta-MSH levels have been associated with seborrheic dermatitis (Shuster et al. 1973), the latter was used as a clinical marker of plasma beta-MSH activity. In all patients, low TD scores (on the Rockland Scale) were associated