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Altered zinc metabolism in mood disorder patients
646
Brief Reports
EIOL PSYCHIATRY 198~26:646-648
ease and aging changes in brain. In Katzman R, Teny RD, Bick KL (eds), Alzhei~r’s Disease: Senile Dementia andRelated Disorders. New York: Raven Press, 515. Eysenck HJ, Eysenck SBG (f964): bandy of the Eysenck Personality Inventory. London: University of London Press. Folstein MF, Folstein SE, McHugh PR (197.5): Minimental state: A practical method for grading the cognitive state of patients for the clinician. I Psychiutr Res 12:189-198. Hamilton MA (1960): A rating scale for depression. I Nertroi, Neurosurg, Psychiatry 2356-62. Kalayam B, A~exo~ulos GS (1989): Late onset depression and hearing toss. Abstracts, Annual Meeting, American Association of Geriatric Psychiatry . Titley W (1936): Prepsychotic personatity of patients
with involutianal ~l~cholia.
Arch ~~~~o~ Psy-
chiut~ 36: 19-33.
von Zerssen D (1982): Personality and affective disorders. In Paykel ES (ed), ~a~ook of A~ective Disorders. New York: The Guilford Press. Winer BJ (1971): Statistical Principles in Experimental Design. New York: McGraw Hill.
Young RC, Abrarns RC, Alexopoulos GS (1986): Sensation seeking in treated geriatric depressives compared to controls. Abstracts, Cotlegium Intemation~ Ne~opsychoph~acologicum. Zuckerman M, Buchsbaum MS, Murphy DL ( 1980): Sensation seeking and its biotogicai correlates. Psycho1 Bull 88:187-214.
ZuckerrnanM, Eysenck S, Eysenck HJ (1978): Sensation seeking in England and America: Cross cultural, age and sex comparisons. J Consult Clin Psycho1 46: 139.
Altered Zinc Metabolism in Mood Disorder Patients Karley Y. Little, Xavier Castellanos, Laurie L. Hu~p~es,
and
Joan Austin
Int~ductiQn
chronically hospitalized, mood-disordered patients compared to controls, but he also noted lower levels in acute psychia~~ patients with mixed diagnoses, confirming the findings of others . The current study explored zinc metabolism (including urinary excretion) in an acute mooddisordered population.
Zinc deficiency has been associated with anorexia, foss of libido, and fatigue, all of which have responded to zinc replacement (TasmanJones, 1980). These symptoms partially define the major depressive syndromes, suggesting that zinc deficiency could conceivably cause or aggravate primary mood disorders. Hullin (1983) reported equivalent serum zinc levels in 29
Methods
Fromthe Department af Psych&y,University of Kentucky Medical Center. Lexington, Kentucky Address reprint reqtwts to l&&y Y. Little, M.D., Department of Psychiatzy, Annex II, Room 206, Unive~ity of Kentucky, Lexington, KY 40536. Received December 28, 1987; revised February 6, 1989.
Thirty consecutive patients with mood disorders, diagnosed by DSM-III-R criteria, were enrolled over a 19”week period. Recent weight loss and alcohol intake were estimated on a fourpoint scale. Percentage of meals eaten was documented as a measure of anorexia. Previously
0 1989 Society of Biological Psychiatry
Brief Reports
prescribed psychiatric drugs were sometimes continued during the initial evaluation phase. Carcinoma of the lung and diabetes mellitus, known to affect zinc metabolism, were each detected in 1 case. Fasting serum specimens were collected on the first or second morning in metal-free plastic tubes, centrifuged, and frozen. Twenty-four-hour urine specimens were collected, beginning either day 2, 3, or 4, in metal-free plastic containers kept refrigerated during the collection day. Samples underwent standard dilution and were quantitated using direct flame atomic absorption. Hospital reference values for 24-hr zinc urinary excretion were 150-750 mcg/day in women and 250-900 mcg/day in men. Serum values were 70-l 50 mcgid. Mean serum zinc, urinary zinc, age, weight loss, anorexia, alcohol intake, and thyroid indices for zinc-deficient versus nondeficient patients were compared using the r-test. Nonparametric testing was not done as none of those comparisons approached significance. Chi-square was calculated to compare sex, thyroid status, diagnosis, and previous treatment versus zinc status. Correlations between both serum zinc and 24-hr urinary zinc excretion versus age, anorexia, weight loss, alcohol intake, and thyroid indices were calculated using Pearson Product Moments in all patients, diuretic-free patients, and diuretic-free women. One-way analysis of variance and Kruskal-Wallis one-way analysis were done for effects of treatments (diuretics, antidepressants, antipsychotics, and anxiolytits) and hypothyroidism on zinc measures. Logarithmic transformation of urinary zinc was done when nonconstant variance was found by Bartlett’s test.
Results Nine patients met our criteria for definite (N = 7) or probable (N = 2) zinc deficiency by demonstrating either serum zinc less than or equal to 70 mcg/dl or daily zinc excretion below 150 mcg (women) or 250 mcg (men). (Two patients with serum zincs of 70 mcg/dl and relatively
BIOL PSYCHIATRY 1989:26:64f&48
641
low urine excretion were included as probables.) Women had a greater tendency to be zinc deficient (9 of 21 versus 1 of 9 men, chi-square = 2.18, p = 0.13) Age, alcohol use, weight loss, and anorexia were not significantly different between groups and were not correlated with serum or urinary zinc. Six of 9 zinc-deficient patients were either endogenously or psychotically depressed. A smaller number of normal zinc patients (5 of 2 1) had these diagnoses (chisquare = 4.98, p = 0.03). The 5 patients on diuretics had significantly elevated urinary zinc (mean 873 ? 285 versus 385 + 317; Kruskal-Wallis Statistic = 7.45, sig. level = 0.006). Urinary zinc correlated with serum zinc even after deleting those on diuretics (r = 0.44, p = 0.04). Patients on admission taking anxiolytics excreted significantly more zinc, 779 * 475 versus 347 t 221 (after log transform; Kruskal-Wallis Statistic = 4.56, sig. level = 0.03). Groups with and without antidepressant or antipsychotic use, or hypothyroidism had similar zinc indices. The patient with previously undiagnosed lung carcinoma was zinc deficient, but not the patient with diabetes. Twelve patients (9 women, 3 men) had thyroid abnormalities, including 6 with frank hypothyroidism (2 with coincidental hyperparathyroidism), 5 with newly discovered elevated basal thyrotropin stimulating hormone (TSH), and 1 with excessive TSH response to thyrotropin releasing hormone (TRH). These patients were significantly older (mean 57 ? 15 years versus 43 t 17, t = 2.37, p = 0.02), and more likely to be women (1 l/21 women, l/9 men, chi-square = 4.47, p = 0.03). Thyroid clinical classification did not predict zinc classification (5/10 hypothyroid patients with complete labs were zinc deficient versus 4/18 euthyroid patients, chi-square = 2.27, p = 0.13). Excluding patients on diuretics made slight difference. However, among women not on diuretics, urinary zinc was correlated with thyroxine (T4) (r = 0.50, p = 0.05). There were no other categorical or correlational relationships between thyroid and zinc measures.
648
BIOL PSYCHIATRY 1989:26:fX-648
Discussion Although zinc abnormalities may exist in some mood disorder patients, it is unclear to what extent this phenomenon is contributor. Poor diet, nonspecific stress, or drug treatment, all secondary to a depressive syndrome. might explain zinc deficiency among this population. Our study does not provide direct evidence that zinc i~eguI~ities cause or worsen any symptoms. However, patients who are found zinc deficient tended to be diagnosed as having endogenous or psychotic major depression, not receiving psychopharmacological treatment, and not suffering greater weight loss or anorexia. Other factors common in this population affect zinc metabolism. Diuretic use in 5 patients led to significantly elevated zinc excretion, as previously described (Reyes et al. 1982). (These patients may be subject to eventual total body zinc depletion.) High urinary zinc in patients on anxiolytics has not been previously reported. However, as these patients required hospitalization, their higher zinc levels wouId not appear to have been diminishing depressive symptoms. Also, in our series, there was a 40% prevalence rate of thyroid abnormalities, Previous work has noted low urinary zinc in hy~~~oid patients, and we found a statistical relationship between T4 and urinary zinc in women (Aihara et al. 1984). Although unlikely, diuretics, anxiolytics, or hypothyroidism could conceivably have psychoactive effects attributabIe to intermedia~ zinc changes.
Brief Reports
Limitations of the current study include (1) possibility of erroneous sampling techniques, (2) lack of internal control group, (3) high prevalence of coincidental physical problems, and (4) lack of drug washout. Obviously, an unequivocal improvement in depressive symptoms after zinc replenishment (versus controls) would best establish the relevance of zinc deficiency. Nevertheless, considering the high incidence of zinc abno~~ities we detected and the role of zinc in neural function, further exploration seems indicated, particularly in treatment-resistant and medically ill patients. The authors would like to thank the nursing staff of 3-South for their clinical contribution, and Virginia Lynn Gift and Debbie Howard for their typographical services.
References Aihara K, Nishi Y, Hatano S, et al. (1984): Zinc, copper, manganese, and selenium metabolism in thyroid disease. Am J Clin Nutr 40:26-35. Hullin RP (1983): Serum zinc in psychiatric patients. In Prasad AS, Cavdar AO, Brewer GJ, Aggett PJ (eds), Progress in Clinical and ~iologicai Research, VoI 129. New York: Liss. Reyes AJ, Leary WP, Lockett CJ, Alcocer L (1982): Diuretics and zinc. SA h4ed J 62(4):373-375. ‘Tasman-Jones C (1980): Zinc deficiency states. Adv Intern Med :97-l 14.
Brief Reports
EIOL PSYCHIATRY 198~26:646-648
ease and aging changes in brain. In Katzman R, Teny RD, Bick KL (eds), Alzhei~r’s Disease: Senile Dementia andRelated Disorders. New York: Raven Press, 515. Eysenck HJ, Eysenck SBG (f964): bandy of the Eysenck Personality Inventory. London: University of London Press. Folstein MF, Folstein SE, McHugh PR (197.5): Minimental state: A practical method for grading the cognitive state of patients for the clinician. I Psychiutr Res 12:189-198. Hamilton MA (1960): A rating scale for depression. I Nertroi, Neurosurg, Psychiatry 2356-62. Kalayam B, A~exo~ulos GS (1989): Late onset depression and hearing toss. Abstracts, Annual Meeting, American Association of Geriatric Psychiatry . Titley W (1936): Prepsychotic personatity of patients
with involutianal ~l~cholia.
Arch ~~~~o~ Psy-
chiut~ 36: 19-33.
von Zerssen D (1982): Personality and affective disorders. In Paykel ES (ed), ~a~ook of A~ective Disorders. New York: The Guilford Press. Winer BJ (1971): Statistical Principles in Experimental Design. New York: McGraw Hill.
Young RC, Abrarns RC, Alexopoulos GS (1986): Sensation seeking in treated geriatric depressives compared to controls. Abstracts, Cotlegium Intemation~ Ne~opsychoph~acologicum. Zuckerman M, Buchsbaum MS, Murphy DL ( 1980): Sensation seeking and its biotogicai correlates. Psycho1 Bull 88:187-214.
ZuckerrnanM, Eysenck S, Eysenck HJ (1978): Sensation seeking in England and America: Cross cultural, age and sex comparisons. J Consult Clin Psycho1 46: 139.
Altered Zinc Metabolism in Mood Disorder Patients Karley Y. Little, Xavier Castellanos, Laurie L. Hu~p~es,
and
Joan Austin
Int~ductiQn
chronically hospitalized, mood-disordered patients compared to controls, but he also noted lower levels in acute psychia~~ patients with mixed diagnoses, confirming the findings of others . The current study explored zinc metabolism (including urinary excretion) in an acute mooddisordered population.
Zinc deficiency has been associated with anorexia, foss of libido, and fatigue, all of which have responded to zinc replacement (TasmanJones, 1980). These symptoms partially define the major depressive syndromes, suggesting that zinc deficiency could conceivably cause or aggravate primary mood disorders. Hullin (1983) reported equivalent serum zinc levels in 29
Methods
Fromthe Department af Psych&y,University of Kentucky Medical Center. Lexington, Kentucky Address reprint reqtwts to l&&y Y. Little, M.D., Department of Psychiatzy, Annex II, Room 206, Unive~ity of Kentucky, Lexington, KY 40536. Received December 28, 1987; revised February 6, 1989.
Thirty consecutive patients with mood disorders, diagnosed by DSM-III-R criteria, were enrolled over a 19”week period. Recent weight loss and alcohol intake were estimated on a fourpoint scale. Percentage of meals eaten was documented as a measure of anorexia. Previously
0 1989 Society of Biological Psychiatry
Brief Reports
prescribed psychiatric drugs were sometimes continued during the initial evaluation phase. Carcinoma of the lung and diabetes mellitus, known to affect zinc metabolism, were each detected in 1 case. Fasting serum specimens were collected on the first or second morning in metal-free plastic tubes, centrifuged, and frozen. Twenty-four-hour urine specimens were collected, beginning either day 2, 3, or 4, in metal-free plastic containers kept refrigerated during the collection day. Samples underwent standard dilution and were quantitated using direct flame atomic absorption. Hospital reference values for 24-hr zinc urinary excretion were 150-750 mcg/day in women and 250-900 mcg/day in men. Serum values were 70-l 50 mcgid. Mean serum zinc, urinary zinc, age, weight loss, anorexia, alcohol intake, and thyroid indices for zinc-deficient versus nondeficient patients were compared using the r-test. Nonparametric testing was not done as none of those comparisons approached significance. Chi-square was calculated to compare sex, thyroid status, diagnosis, and previous treatment versus zinc status. Correlations between both serum zinc and 24-hr urinary zinc excretion versus age, anorexia, weight loss, alcohol intake, and thyroid indices were calculated using Pearson Product Moments in all patients, diuretic-free patients, and diuretic-free women. One-way analysis of variance and Kruskal-Wallis one-way analysis were done for effects of treatments (diuretics, antidepressants, antipsychotics, and anxiolytits) and hypothyroidism on zinc measures. Logarithmic transformation of urinary zinc was done when nonconstant variance was found by Bartlett’s test.
Results Nine patients met our criteria for definite (N = 7) or probable (N = 2) zinc deficiency by demonstrating either serum zinc less than or equal to 70 mcg/dl or daily zinc excretion below 150 mcg (women) or 250 mcg (men). (Two patients with serum zincs of 70 mcg/dl and relatively
BIOL PSYCHIATRY 1989:26:64f&48
641
low urine excretion were included as probables.) Women had a greater tendency to be zinc deficient (9 of 21 versus 1 of 9 men, chi-square = 2.18, p = 0.13) Age, alcohol use, weight loss, and anorexia were not significantly different between groups and were not correlated with serum or urinary zinc. Six of 9 zinc-deficient patients were either endogenously or psychotically depressed. A smaller number of normal zinc patients (5 of 2 1) had these diagnoses (chisquare = 4.98, p = 0.03). The 5 patients on diuretics had significantly elevated urinary zinc (mean 873 ? 285 versus 385 + 317; Kruskal-Wallis Statistic = 7.45, sig. level = 0.006). Urinary zinc correlated with serum zinc even after deleting those on diuretics (r = 0.44, p = 0.04). Patients on admission taking anxiolytics excreted significantly more zinc, 779 * 475 versus 347 t 221 (after log transform; Kruskal-Wallis Statistic = 4.56, sig. level = 0.03). Groups with and without antidepressant or antipsychotic use, or hypothyroidism had similar zinc indices. The patient with previously undiagnosed lung carcinoma was zinc deficient, but not the patient with diabetes. Twelve patients (9 women, 3 men) had thyroid abnormalities, including 6 with frank hypothyroidism (2 with coincidental hyperparathyroidism), 5 with newly discovered elevated basal thyrotropin stimulating hormone (TSH), and 1 with excessive TSH response to thyrotropin releasing hormone (TRH). These patients were significantly older (mean 57 ? 15 years versus 43 t 17, t = 2.37, p = 0.02), and more likely to be women (1 l/21 women, l/9 men, chi-square = 4.47, p = 0.03). Thyroid clinical classification did not predict zinc classification (5/10 hypothyroid patients with complete labs were zinc deficient versus 4/18 euthyroid patients, chi-square = 2.27, p = 0.13). Excluding patients on diuretics made slight difference. However, among women not on diuretics, urinary zinc was correlated with thyroxine (T4) (r = 0.50, p = 0.05). There were no other categorical or correlational relationships between thyroid and zinc measures.
648
BIOL PSYCHIATRY 1989:26:fX-648
Discussion Although zinc abnormalities may exist in some mood disorder patients, it is unclear to what extent this phenomenon is contributor. Poor diet, nonspecific stress, or drug treatment, all secondary to a depressive syndrome. might explain zinc deficiency among this population. Our study does not provide direct evidence that zinc i~eguI~ities cause or worsen any symptoms. However, patients who are found zinc deficient tended to be diagnosed as having endogenous or psychotic major depression, not receiving psychopharmacological treatment, and not suffering greater weight loss or anorexia. Other factors common in this population affect zinc metabolism. Diuretic use in 5 patients led to significantly elevated zinc excretion, as previously described (Reyes et al. 1982). (These patients may be subject to eventual total body zinc depletion.) High urinary zinc in patients on anxiolytics has not been previously reported. However, as these patients required hospitalization, their higher zinc levels wouId not appear to have been diminishing depressive symptoms. Also, in our series, there was a 40% prevalence rate of thyroid abnormalities, Previous work has noted low urinary zinc in hy~~~oid patients, and we found a statistical relationship between T4 and urinary zinc in women (Aihara et al. 1984). Although unlikely, diuretics, anxiolytics, or hypothyroidism could conceivably have psychoactive effects attributabIe to intermedia~ zinc changes.
Brief Reports
Limitations of the current study include (1) possibility of erroneous sampling techniques, (2) lack of internal control group, (3) high prevalence of coincidental physical problems, and (4) lack of drug washout. Obviously, an unequivocal improvement in depressive symptoms after zinc replenishment (versus controls) would best establish the relevance of zinc deficiency. Nevertheless, considering the high incidence of zinc abno~~ities we detected and the role of zinc in neural function, further exploration seems indicated, particularly in treatment-resistant and medically ill patients. The authors would like to thank the nursing staff of 3-South for their clinical contribution, and Virginia Lynn Gift and Debbie Howard for their typographical services.
References Aihara K, Nishi Y, Hatano S, et al. (1984): Zinc, copper, manganese, and selenium metabolism in thyroid disease. Am J Clin Nutr 40:26-35. Hullin RP (1983): Serum zinc in psychiatric patients. In Prasad AS, Cavdar AO, Brewer GJ, Aggett PJ (eds), Progress in Clinical and ~iologicai Research, VoI 129. New York: Liss. Reyes AJ, Leary WP, Lockett CJ, Alcocer L (1982): Diuretics and zinc. SA h4ed J 62(4):373-375. ‘Tasman-Jones C (1980): Zinc deficiency states. Adv Intern Med :97-l 14.