The interaction of serotonin transporter gene polymorphisms and early adverse life events on vulnerability for major depression

Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Suite 4000 WMRB, 101 Woodruff Circle, Atlanta, GA 30322, USA.
Current Psychiatry Reports (Impact Factor: 3.05). 01/2007; 8(6):452-7. DOI: 10.1007/s11920-006-0050-y
Source: PubMed

ABSTRACT Considerable literature supports the hypothesis of dysfunction in central nervous system serotonergic circuits in the pathophysiology of mood disorders, specifically major depression. Since the development of the selective serotonin (5-HT) reuptake inhibitors, a putative role for the 5-HT transporter (SERT) in the etiology of depression has been explored. The discovery of a functional SERT polymorphism has provided a novel tool to further scrutinize the role of serotonergic neurons in depression. This article reviews the burgeoning evidence of an interaction between early life stress and an SERT polymorphism on vulnerability to depression.

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Available from: Charles B Nemeroff, Aug 25, 2015
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    • "Whereas glutamatergic and GABAergic systems are implicated in anxiety, learning and memory processes (Roozendaal et al., 2009), serotonin (5-HT), due to the important functions it play mainly -but not only-within the amygdala , 5-HT has a regulatory role in the anxiety behaviors and among the fifteen serotonin receptors, 5-HT1A and 5-HT2C receptors are relatively abundant in the amygdala (Li et al., 2012). Moreover, polymorphisms of the gene coding for the serotonin transporter have been linked to stress induced depression (Caspi et al., 2003; Vergne and Nemeroff, 2006). In pharmacology, 5-HT1A receptor agonists, such as buspirone due to its anxiolytic effects, have constituted an anxiolytic drug (De Vry, 1995; Li et al., 2012). "
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    • "These are the gene encoding the rate-limiting enzyme in the biosynthesis of serotonin, tryptophan hydroxylase [59] [60] [61], the serotonin transporter [62, 63], and the 5-HT 1A [64, 65] and 5-HT 2A [66] receptors. Genetically determined dysfunction of the serotonergic system increases the risk of developing depression and in particular, the genetic makeup seems to interact with environmental life-stressors [67] [68]. "
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    • "An expansive literature has proposed an important role of altered serotonergic neurotransmission in the origin, manifestations, and treatment of mood disorders, as well as other psychiatric illnesses (Lesch, 2001; Gaspar et al, 2003; Firk and Markus, 2007). The plasma membrane serotonin (5-hydroxytryptamine, 5-HT) transporter (SERT, SLC6A4) has received special attention as a genetic risk determinant in these disorders due to its central role in synaptic 5-HT inactivation (Caspi et al, 2003; Blakely et al, 2005; Vergne and Nemeroff, 2006). Genetic and functional variation in SERT is associated with psychiatric disorders, including alcoholism (Ait-Daoud et al, 2009), autism (Prasad et al, 2009), anxiety (Laucht et al, 2009), obsessive–compulsive disorder (OCD) (Ozaki et al, 2003), depression, and suicide (Segal et al, 2009). "
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