Exogenous depression

One model of an ionic mechanism of action of Li+ in affective disorders has been proposed, in which the receptors for Li+ are ion channels and cation coenzyme receptor sites, and in which the presence of intracellular Li+ in excitable cells results in the displacement of exogenous Na+ and/or other intracellular cations [13]. It has been suggested that this could lead to a decrease in the release of neurotransmitters alternatively it may be that this intracellular Li+ is altering a preexisting, disease-related electrolyte imbalance [14]. A number of observations of such imbalances in affective disorders have been made depression is associated with elevated levels of intracellular Na+ [15] retention of Li+ is observed in manic-depressive patients prior to an episode of mania [ 16] and Na+/K+ activity is defective during both mania and depression [17]. 

Cowley, J. J., Harvey, F., Johnson, A. T. and Brooksbank, B. W. L. (1980) Irritability and depression during the menstrual cycle - possible role for an exogenous pheromone Irish J. Psychol. 3, 143-156. 

MAO inhibitors are used in treating severe endogenous, exogenous, and reactive depressions that do not react to treatment with tricyclic antidepressants, as well as for controlling depressive phases in manic-depressive psychoses. 

Depression In general, the MAOIs appear to be indicated in patients with atypical (exogenous) depression, and in some patients unresponsive to other antidepressive therapy. They are rarely a drug of first choice. 

Depression Do not use methylphenidate to treat severe depression of exogenous or endogenous origin. 

A number of clinical circumstances have been identified which are characterized by an often profoundly depressed rate of erythropoiesis (Table 6.7). Many, if not all, such conditions could be/are responsive to administration of exogenous EPO. The prevalence of anaemia, and the medical complications which ensue, prompts tremendous therapeutic interest in this haemopoietic growth factor. EPO has been approved for use to treat various forms of anaemia (Table 6.8). It was the first therapeutic protein produced by genetic engineering, whose annual sales value topped 1 billion. Its current annual sales value is now close to 2 billion. EPO used therapeutically is produced by recombinant means in CHO cells. 

Infusion of exogenous CRF increases ACTH levels and provides a test of pituitary sensitivity. In several studies of major depression, the ACTH response to CRF was shown to be blunted, reflecting a reduced sensitivity of the pituitary to CRF (e.g., Krishnan 1993). This finding has been widely interpreted as reflecting a downregulation of pituitary CRF receptors secondary to CRF hypersecretion, but may also reflect increased cortisol inhibition of ACTH secondary to hypercortisolism (Krishnan 1993 Yehuda and Nemeroff 1994). 

Precursor therapy as a means of increasing dopaminergic transmissions is limited to L-tyrosine and L-dopa. Although under basal conditions the exogenous administration of tyrosine leads to specific enhancement of noradrenergic transmission, it can enhance dopaminergic transmission in conditions of DA deficiency [Kapur and Mann 1992). Only one adequately controlled clinical trial has been reported, in which 65 patients with major depression were randomly selected to treatment for 4 weeks with oral L-tyrosine 100 mg/kg/day, imipramine 2.5 mg/kg/day, or placebo [Gelenberg et al. 1990). Tyrosine increased and imipramine decreased excretion of the main metabolite of NA, but no evidence was found that tyrosine had antidepressant activity in contrast with imipramine. 

Depressive disorders are the most prevalent of psychiatric illnesses, occurring more often among women (16%) than among men (8%). Depression, a recurrent but self-limiting disorder, is classified as (1) exogenous or reactive depression or as (2) endogenous depression. Depression is further... 

Endogenous opioids and exogenously administered delta opioid receptor agonists have been demonstrated to have antidepressant-like effects in animal models used to evaluate novel antidepressant compounds. This chapter reviews some of the previous research investigating the role of the opioid system, and more specifically the delta opioid receptor system, in clinical depression and in animal models used to study human depression and antidepressant treatments. In addition, this chapter discusses the interpretation of animal models of depression and their uses in the evaluation of new potential therapeutics. 

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