I can't get the full text of this article now [Jung et al., 2009: (http://www.springerlink.com/content/73r65221u5g14456/)], but the authors found that markers of depression and excessive stress (results on the usual tests or questionnaires, etc.) were higher in people whose serum calcium/magnesium (Ca/Mg) ratios were in the highest of three ranges of values. (The authors grouped the various serum Ca and Mg values into three ranges, or tertiles, and a higher score on one or more of the tests was taken as being an indication that the people had been experiencing more depression or anxiety, at the time they'd taken the tests.) Low serum Mg levels were also associated with more depression or anxiety.
That article looks interesting and is likely to have some validity to it, and one could interpret the results in a number of different contexts. I think elevations in serum Ca could produce depression by producing ATP depletion in neurons and astrocytes in parts of the brain or in cerebral vascular endothelial cells, and that ATP depletion could result from an excessive degree of activation of the coagulation cascade or from an excessive rate of calcium influx into neurons. An important effect of Mg (Mg2+) is to act as a mild Ca channel antagonist, either by acting extracellularly or intracellularly (). One thing that researchers hardly ever discuss in the literature is that the rate of Ca influx into cells does, in fact, tend to increase in response to increases in extracellular Ca [one example: Hennings et al., 1989: (http://www.ncbi.nlm.nih.gov/pubmed/2702726)]. That's just really important, and I can't emphasize enough the importance of that phenomenon. The way the authors of most articles describe the regulation of Ca influx, one would think Ca influx is so "strictly regulated" as to be more "inviolable" than "Fort Knox." The intracellular Ca concentrations are something like one 10,000th of the extracellular Ca concentration, normally, and the intracellular and intramitochondrial Ca concentrations are highly regulated. But they can, nonetheless, be increased or decreased to a meaningful extent, in my opinion, in response to increases or decreases in extracellular Ca. And Mg tends to block Ca channels to some extent, but it doesn't just behave like a pharmacological Ca channel antagonist. But the point is that an excessive rate of Ca influx into platelets can augment their thrombogenic effects, and excessive Ca influx into neurons, in the long term, tends to decrease dopaminergic transmission and worsen cognitive functioning and oppose all of the effects that occur in response to either an acute increase in Ca influx or that occur under conditions of tonic or phasic dopamine release, etc. Chronic stress can lead to excessive glutamatergic stimulation of noradrenergic neurons, in the locus ceruleus and other adrenergic cell groups, and dopaminergic neurons, such as in the ventral striatum, and thereby cause excessive Ca influx, and this tends to impair mitochondrial functioning and thereby cause ATP depletion [I shouldn't have to cite anything for this, given that it's so well-known, but here are some hastily-chosen articles that discuss that: Knochel, 2000: (http://www.ncbi.nlm.nih.gov/pubmed/10806294); Moghtader et al., 1997: (http://www.ncbi.nlm.nih.gov/pubmed/9434995)]. This can tend to decrease noradrenergic and dopaminergic transmission, and the mild NMDA-receptor antagonism of Mg or other weak NMDA-receptor antagonists can acutely and paradoxically sensitize dopaminergic neurons, for example, to D1 dopamine receptor activation [see here (http://hardcorephysiologyfun.blogspot.com/2009/03/adenosine-and-guanosine-in-animal.html) and, for example, Peeters et al., 2002: (http://www.ncbi.nlm.nih.gov/pubmed/12213297); Deep et al., 1999: (http://www.ncbi.nlm.nih.gov/pubmed/10529725); Arai et al., 2003: (http://www.ncbi.nlm.nih.gov/pubmed/12711097); Konradi et al., 1996: (http://www.jneurosci.org/cgi/reprint/16/13/4231)(http://www.ncbi.nlm.nih.gov/pubmed/8753884?dopt=Abstract); Tokuyama et al., 2001: (http://www.ncbi.nlm.nih.gov/pubmed/11408088); Boyce-Rustay et al., 2006: (http://www.ncbi.nlm.nih.gov/pubmed/16482087)].
The main point is that an excessive rate of Ca influx, in response to or in the presence of any of the countless stimuli that normally increase or regulate Ca influx, is just generally detrimental to all sorts of physiological processes and to energy metabolism in particular. Excessive Ca influx, in response to ischemia or other metabolic insults, activates Ca-dependent proteases that cause many more problems and worsen ATP depletion, ATP depletion impairs the capacity of cells and their mitochondria to buffer intracellular and intramitochondrial Ca concentrations, and so on (http://scholar.google.com/scholar?hl=en&q=calcium+dependent+protease+ischemia). Calcium influx is obviously essential, but the key point that is not obvious in the literature is that, in many or most cases, in my opinion, there is no shortage of Ca influx. And Ca influx and serum Ca are not in danger of being too low in most disease states. One would obviously want to discuss these things with one's doctor, however, and I'm just talking about these types of adjunctive approaches. Obviously, zinc and copper supplementation would be things to consider cutting out entirely, supposing one were interested in "addressing" a psychiatric condition, given the countless reports of neurotoxicity from excessive zinc supplementation and the known, endless problems associated with an excess of intracellular or extracellular copper and with copper supplementation in general. But these are just my opinions, and one's doctor is going to be the person to advise any given individual.
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