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2016, Number 1

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Salud Mental 2016; 39 (1)

Neurobiología de la depresión mayor y de su tratamiento farmacológico

Cruzblanca HH, Lupercio CP, Collas AJ, Castro RE

Language: Spanish
References: 116
Page: 47-58
PDF size: 725.12 Kb.


ABSTRACT

Introduction The major depressive disorder (MDD) arises from the interaction of environmental, genetic and epigenetic factors, producing a deficit in monoaminergic transmission within the brain. However, our understanding of its pathophysiology is quite limited.
Objective To reach an integrative view of the MDD pathophysiology, as well as the mechanisms of action of antidepressant drugs.
Method We used the PubMed database to search for the documents by using the appropriate key words. Most of them are experimental research and molecular genetics and brain imaging studies in humans.
Results The pathophysiology of MDD is characterized by: i) shrinkage of the cingulate anterior cortex; ii) hyper-metabolism of the Cg25 area; iii) lower expression of the 5-HT1A receptor; iv) enhanced expression of monoamine oxidase A. Besides, certain gene polymorphisms are strongly linked to the pathophysiology, and there is evidence that 5-HT1A receptor expression is reduced by psychological stress. Antidepressants reverse the hyper-metabolic state of Cg25, stimulate neurogenesis and the cAMP pathway. We found that imipramine increases and reduces the expression of Gαs and Gαs, respectively (data no published).
Discussion and conclusion The disruption in monoaminergic transmission could be mediated by: i) the G1463A hTPH2 polymorphism that reduces the serotonin synthesis; ii) the C(-1019)G 5-HT1A polymorphism that increases the receptor expression in the dorsal rafe, and reduces serotonin release; iii) an increase in monoamine degradation. The reduced 5-HT1A expression is discussed considering its inhibitory properties in the prefrontal cortex. The effects of imipramine on Gαs and Gαs are in agreement with the antidepressant-induced stimulation of the cAMP pathway.


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