Major depressive disorder

The chance that one of us will suffer from a major depressive episode during our life is approximately 10% [1]. Depression has a dramatic effect on quality of life because it results in a persistent low mood that is accompanied by a low self-esteem and a loss of interest in things that give pleasure [2]. Reason enough to carry out research on the background of major depression.

Current versus new medicines

Traditional medicines to treat a major depression increase the activity of monoamine neurotransmitters like serotonine or dopamine. However, it may take four to six weeks before these medicines have any effect and for a large percentage of people, they do not work at all. More recently, focus has shifted towards N-methyl-D-aspartate receptors (NMDAR), which allow transfer of electrical signals between neurons in the brain and the spine. Treatment with ketamine, which is an NMDAR inhibitor, had an antidepressant effect on patients that are resistant to monoamine-based medicines. Furthermore, this effect is immediate, in contrast to monoamine-based medicines.

Does zinc deficiency cause depression?

Ursula Doboszewska and colleagues [4] investigated the effect of zinc, an NMDAR inhibitor, in rats on behaviors associated with depression. In addition to this, the authors assessed the effect of zinc deficiency on several chemicals that are associated with NMDAR. The authors kept rats on either a zinc deficient diet or a normal diet for four or six weeks. Then they assessed depression in a Porsolt Forced Swim test, in which the rats are placed in a water cylinder. In this test the duration of immobility, during which the rats do not try to escape or swim, is a measure of depression. The authors also determined locomotor ability, the motivation to consume sucrose, and social interaction with another rat. To score social interaction, behavior was annotated and analyzed in The Observer XT annotation software. In addition to this, the concentration of several compounds associated to NMDAR was measured in the rats’ hippocampus and prefrontal cortex.

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Zinc deficient rats are depressed

The rats that were on a zinc deficient diet had longer periods during which they were immobile and did not struggle or try to escape in the Porsolt Forced Swim test. This is a measure for depression-like behavior. In addition to this, the zinc deficient rats were less motivated to consume sucrose. This is a measure for anhedonia, which is the inability to gain pleasure from enjoyable experiences. In the behavioral observations, the zinc deficient rats showed less social behaviors, like sniffing the other rat or licking the other rat’s fur. There was no effect of zinc deficiency on locomotion. These results together indicate that zinc deficiency induces depression.

Zinc deficiency alters NMDAR

The chemical analysis of the rats’ hippocampus and prefrontal cortex showed that several chemical compounds associated with NMDAR were affected. It looks like zinc deficiency alters the way NMDAR functions in the brain and thereby alters the transfer of electrical signals through the nerves. The effect on the compounds associated with NMDAR was larger in the hippocampus than in the prefrontal cortex and took longer to become apparent in the prefrontal cortex. Interestingly, the hippocampus is the brain area with the highest zinc concentration. Therefore, NMDAR in the hippocampus may be more susceptible to zinc restriction.

Concluding

The authors conclude that zinc deficiency causes behavioral changes in rats that resemble depression. Furthermore alterations in NMDAR may be involved in the pathology of depression. Zinc deficient rats are a valuable model to study depressive behavior and its chemical background.

References

1. http://en.wikipedia.org/wiki/Epidemiology_of_depression
2. http://en.wikipedia.org/wiki/Major_depressive_disorder
3. http://en.wikipedia.org/wiki/NMDA_receptor_antagonist
4. Doboszewska U, et al, Zinc deficiency in rats is associated with up-regulation of hippocampal NMDA receptor, Prog Neuro-Psychopharmacol Biol Psychiatry (2014), http://dx.doi.org/10.1016/j.pnpbp.2014.09.013