engleski

Apoptosis – the potential pathophysiological mechanism in mood disorders modifable by lithium salts

In recent years, our knowledge about the pathophysiological and pathoanatomical changes in the central nervous system (CNS) of patients suffering from a broad spectrum of clinical pictures of mood disorder has seen considerable progress. In this context, mention should be made of the studies that tend to characterize mood disorders as neurodegenerative diseases underlain to a significant extent by glial cell destruction. The studies that describe apoptotic destruction of glial cells and other CNS cells have provided strong evidence for the mechanism of apoptosis to be crucial in the etiology of mood disorder at the molecular level. These concepts have not only changed previous opinions on mood disorders to be caused by impairment in the monoaminergic system of neurotransmitters but have also modified current considerations about glial cells. Until recently, glial cells were believed to act exclusively as a CNS supportive tissue, a sort of "connective tissue". Now, however, glial cells can be with certainty described as a functional part of the CNS. In other words, glial cells are the main store of the excitatory neurotransmitter, glutamate, and CNS excitability depends on the glutamate metabolism and release by glial cells. In this way, glial cells with the neuron constitute a functional unity. Furthermore, other neurotransmitter receptors, e.g., dopaminergic and serotonergic receptors have also been demonstrated on glial cells. On the other hand, psychopharmacotherapy as the main treatment in the management of mood disorders includes the use of various psychop-harmaceuticals, from antidepressants through mood stabilizers. Of the latter, lithium salts have a prominent place in the treatment of mood disorders, either as a drug to suppress the symptoms of manic mood disorders or as a mood stabilizer, for enhancement of antidepressant action along with anti-depressants, or as a drug to prevent the occurrence of new episodes of mood disorder. The latter indication for lithium administration appears to be quite interesting, conferring a special place for lithium in psychopharmacotherapy as well as in pharmacotherapy in general, since it is also used for prevention, whereas other drugs mostly have curative action. The action of lithium as well as of antidepressants is known to only occur after a period, days or even weeks, of administration. Thus, had the therapeutic effect of lithium been strictly limited to the action on neurotransmitters, as believed to date, change in the clinical picture would occur immediately. Therefore, lithium should be postulated to act via a more subtle mechanism through CNS cell adjustment to the new conditions. The more so, there is ever more evidence for lithium to be able to modify neuronal plasticity by its action on apoptotic mechanisms.

lithium ; apoptosis ; mood disorders

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