Food and Behaviour Research

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Zinc deficiency induces depression-like symptoms in adult rats.

Tassabehji NM, Corniola RS, Alshingiti A, Levenson CW. (2008) Physiol Behav.  95(3) 365-9. Epub 2008 Jul 3 

Web URL: View this and related abstracts via PubMed here


There is mounting evidence suggesting a link between serum zinc levels and clinical depression. Not only is serum zinc negatively correlated with the severity of symptoms, but zinc levels appear to be lowest in patients who do not respond to antidepressant drug therapy.

It is not known if reduced zinc levels are contributing to depression, or the result of dietary or other factors associated with major depression.
Thus, we designed this study to test the hypothesis that dietary zinc deficiency would induce depression-like behaviors in rats.

Two-month-old male rats were fed zinc adequate (ZA, 30 ppm), deficient (ZD, 1 ppm), or supplemented (ZS, 180 ppm) diets for 3 weeks. Consistent with the development of depression, ZD rats displayed anorexia (p<0.001), anhedonia (reduced saccharin:water intake, p< 0.001), and increased anxiety-like behaviors in a light-dark box test (p<0.05).

Furthermore, the antidepressant drug fluoxetine (10 mg/kg body wt) reduced behavioral despair, as measured by the forced swim test, in rats fed the ZA and ZS rats (p<0.05), but was ineffective in ZD rats.

Together these studies suggest that zinc deficiency leads to the development of depression-like behaviors that may be refractory to antidepressant treatment.


Zinc is needed as a co-factor for the normal functioning for as many as 300 different enzymes in the brain and body, and plays key roles in immune function, cell division and replication, DNA and protein synthesis, and energy metabolism, as well as skin health, and the senses of taste and smell. 

In addition to these roles, zinc also affects brain function directly as a neurotransmitter - with particular involvement in emotional regulation, cognition, and links between the two.  Zinc deficiency has long been linked with many developmental and mental health conditions, including ADHD, anxiety, depression, and anorexia, although good evidence for causality from clinical trials is still limited. 

This animal study confirmed that a zinc deficient diet induced depression - as assessed by loss of appetite and anorexia, anhedonia (insensitivity to pain or reward), and behavioural anxiety.

Importantly, this research also showed that the zinc deficient diet effectively blocked the actions of a standard antidepressant medication (fluoxetine, or Prozac) in reducing behavioural despair, compared to a diet with average or high zinc levels.

These findings have potentially important implications for the management of depression in humans. They provide a clear rationale for the assessment of zinc status in this condition, and for clinical trials of zinc supplementation - particularly for patients who fail to respond to standard medications.

For more information on zinc and mental health, see: