Data on Zinc and Mood

According to nutritionist Blake Graham all vitamins and minerals are involved in one or more biochemical pathways and/or physiological actions which influence the function of the human brain. Most vitamin and mineral deficiencies result in psychiatric symptoms in a significant number of people, and in people with psychiatric diagnoses these deficiencies are often associated with more severe symptoms and poorer outcome from conventional treatment. 

Vitamin and mineral deficiencies may act as an exacerbating factor secondary to malnutrition, alcoholism, etc. or may be a primary causative factor. Either way, optimisation of nutrient levels is in each patients best interest.

Zinc is a mineral that may have a significant impact on mental health.

The antidepressants Imipramine and citalopram; and electroconvulsive shock have each been shown to induce an elevation of zinc concentration in the hippocampus of rats, suggesting the possibility that zinc regulation plays a role in antidepressant effects (Nowak & Schlegel-Zawadzka, 1999). Maes et al. (1997) found significantly lower serum zinc levels in 31 patients with major depression in comparison to 15 volunteers with normal mental health. Serum zinc levels were even lower for the 23 depressed patients who were treatment resistant; however, antidepressant therapy did not affect serum zinc levels.

Analyses showed lower serum zinc levels to be both sensitive (79%) and specific (93%) as a marker for treatment resistant depression. Maes et al. pointed out that these results might not be surprising as it has long been known by nutrition researchers that depression and impaired cognitive function are early clinical manifestations of zinc deficiency.

Walsh, Isaacson, Rehman, and Hall (1997) compared plasma
zinc and serum copper levels in 135 aggressive male subjects and 18 male subjects with no history of verbal or physical aggressive behavior (age range  3-20 years). The mean copper-zinc ratio was significantly higher in the aggressive male subjects (1.40  0.54 vs. 1.02  0.18). An interesting finding is that there was a
linear relationship between the degree of zinc deficiency (as reflected in the copper-zinc ratio) and the seriousness of the behavior, ranging from verbal assault to aggravated and violent assault. (Walsh et al., 1997). Although attention-deficit/hyperactivity disorder has been excluded from the current review, we note in
passing that zinc, and zinc- copper ratios, as well as their relationship to essential fatty acids, have been a focus of several studies in this population (Arnold et al., 2005; Arnold, Pinkham, & Votolato, 2000; Stevens et al., 2003; Toren et al., 1996)
Psychiatric manifestations of zinc deficiency include behavioural disturbances, depression and mental confusion. (Mann. 2000) Within major depression populations, lower zinc levels correlate with higher depression severity. (Maes M. 1994)
According to Dr. Bonnie Kaplan’s Vitamins, Minerals and Mood, zinc plays a role in catalysing, and/or is an active constituent of, over 150 enzymes in humans. (Mann. 2000) Zinc is involved in such functions as antioxidant defence, gene expression, nerve impulse transmission, thyroid function, digestion and a large array of other functions. Zinc is found in high concentrations in hippocampal and cortical neurons. (Nowak G. 1998) Zinc is also an inducer of brain derived neurotrophic factor (Nowak G. 2005), is an antagonist of the NMDA-receptor (Nowak G. 2005 & 2001) and is required for GABA metabolism. (Nowak G. 1998) Zinc deficiency causes biological membranes to be more prone to oxidative damage and impaired function. (O’Dell BL. 2000) In one study of six young men, experimentally induced zinc deficiency was shown to reduce basal metabolic rate ~9% and also significantly reduced protein utilization. (Wada L. 1986)

Three consecutive studies by Maes and colleagues found serum zinc levels were significantly lower in depressed patients as compared to healthy matched controls. (Maes M. 1994, 1997 & 1999) Lower serum zinc was associated with higher past treatment resistance. (Maes M. 1997) In a group of 30 patients with mood disorders, 7/30 had a clear zinc deficiency. (Little KY. 1989) 14 patients with primary affective disorder were found on admission to hospital to have lower plasma zinc levels than 14 controls. (McLoughlin IJ. 1990) Another study reported slightly lower plasma zinc levels in depressed patients, although this did not reach statistical significance. (Narang RL. 1991)

Nowak and colleagues investigated zinc concentrations of 10 suicide victims compared to 10 age-matched controls. (Nowak G. 2003) Hippocampal or cortical tissue showed no differences in zinc content between groups although there was a 26% decrease in the inhibition by zinc of [(3)H]MK-801 binding to NMDA receptors in hippocampal tissue, but not in cortical tissue.

Blake Graham, BSc (Honours), AACNEM
Clinical Nutritionist
Perth, Western Australia
Phone/Email: See Contact page
*Non-Perth residents may enquire about phone consultations.

References:

Little KY, Castellanos X, Humphries LL, Austin J. Altered zinc metabolism in mood disorder patients. Biol Psychiatry. 1989 Oct;26(6):646-8.
Kaplan B, Vitamins, Minerals and Mood. Psychological Bulletin Copyright 2007 by the American Psychological Association 2007, Vol. 133, No. 5, 747-760
Maes M, De Vos N, Demedts P, Wauters A, Neels H. Lower serum zinc in major depression in relation to changes in serum acute phase proteins. J Affect Disord. 1999 Dec;56(2-3):189-94.
Maes M, D’Haese PC, Scharpe S, D’Hondt P, Cosyns P, De Broe ME. Hypozincemia in depression. J Affect Disord. 1994Jun;31(2):135-40.
Maes M, Vandoolaeghe E, Neels H, Demedts P, Wauters A, Meltzer HY, Altamura C, Desnyder R. Lower serum zinc in major depression is a sensitive marker of treatment resistance and of the immune/inflammatory response in that illness. Biol Psychiatry. 1997 Sep 1;42(5):349-58.
Nowak G, Szewczyk B, Pilc A. Zinc and depression. An update. Pharmacol Rep. 2005 Nov-Dec;57(6):713-8.
Nowak G, Szewczyk B, Sadlik K, Piekoszewski W, Trela F, Florek E, Pilc A. Reduced potency of zinc to interact with NMDA receptors in hippocampal tissue of suicide victims. Pol J Pharmacol. 2003 May-Jun;55(3):455-9.
Nowak G, Zieba A, Dudek D, Schlegel-Zawadzka M, Pilc A. Zinc homeostasis and glutamatergic system in the pathogenesis and treatment of depression. Psychiatr Pol. 2001 Mar-Apr;35(2):257-66.
Nowak G. Alterations in zinc homeostasis in depression and antidepressant therapy. Pol J Pharmacol. 1998 Jan-Feb;50(1):1-4.
O’Dell BL. Role of zinc in plasma membrane function. J Nutr. 2000;130(5S Suppl):1432S-1436S.
Wada L, King JC. Effect of low zinc intakes on basal metabolic rate, thyroid hormones and protein utilization in adult men. J Nutr. 1986 Jun;116(6):1045-53.
Walsh, W., Glab, L., & Haakenson, M. (2004). Reduced violent behavior following biochemical therapy. Physiology & Behavior, 82,835-839.
Walsh, W. J., Isaacson, H. R., Rehman, F., & Hall, A.(1997). Elevated blood copper/zinc ratios in assaultive young males. Physiology & Behavior, 62, 327-329.

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