Article

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.

Download full-text

Full-text

Available from: Charles B Nemeroff, Jul 01, 2015
0 Followers
 · 
79 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Psychiatric disorders are often considered as simple imbalances between a limited number of cerebral neurotransmitters. In fact, it is more complicated than this “simple approach” and each psychiatric disorder constitutes network dysfunction within which several agents and factors are implicated. Thus, the therapeutical perspectives and implications are as vast and as numerous as the diversity of those network dysfunctions. Furthermore, the description of factors influencing diseases prognoses and treatment efficacy indicates new elements to consider both in therapies and drug researches.
    Saudi Pharmaceutical Journal 04/2014; 22(2):95–100. DOI:10.1016/j.jsps.2013.01.008 · 1.00 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The existence of a high co-morbidity between Alzheimer's disease (AD) and depression has been known for a long time. More interesting though are recent studies indicating that depression and number of depressive episodes earlier in life is associated with increased risk of AD development. This suggests the existence of common neuropathological mechanisms behind depression and AD. Here we propose that the brain changes associated with depressive episodes that compromise the brain's ability to cope with stress may constitute risk factors for development of AD. Furthermore, in individuals with a genetic linkage to depression, there may be an increased vulnerability towards the initiation of a detrimental neurodegenerative cascade. The following review will deal with the various observations reported within the different neurobiological systems known to be involved and affected in depression, like serotonergic and cholinergic system, hypothalamic-pituitary-adrenal axis and brain derived neurotrophic factor, and discussed in relation to AD.
    Journal of Alzheimer's disease: JAD 01/2011; 23(2):177-93. DOI:10.3233/JAD-2010-100390 · 3.61 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Serotonin (5-hydroxytryptamine, 5-HT) has long been implicated in regulation of mood. Medications that block the neuronal 5-HT transporter (SERT) are used as major pharmacological treatment for mood disorders. Conversely, stimuli that enhance SERT activity might be predicted to diminish synaptic 5-HT availability and increase the risk for 5-HT-related CNS disorders. We have shown that the inflammatory cytokines enhance brain SERT activity in cultured serotonergic cells and nerve terminal preparations in vitro. In this study, we establish that intraperitoneal injection of the cytokine-inducer lipopolysaccharide (LPS) stimulates brain SERT activity, acting at doses below those required to induce overt motor suppression. SERT stimulation by LPS is paralleled by increased immobility in both the tail suspension test (TST) and the forced swim test (FST); antidepressant-sensitive alterations are thought to model aspects of behavioral despair. Both the stimulation of SERT activity and induced immobility are absent when LPS is administered to interleukin-1 receptor (IL-1R)-deficient mice and in the presence of SB203580, an inhibitor of IL-1R-stimulated p38 MAPK. Moreover, the ability of LPS to enhance immobility in TST is lost in SERT knockout mice. These findings reveal an ability of peripheral inflammatory stimuli to enhance brain SERT activity through IL-1R and p38 MAPK pathways in vivo and identify a requirement for SERT expression in immune-system-modulated despair behaviors. Our studies identify IL-1R- and p38 MAPK-dependent regulation of SERT as one of the mechanisms by which environmentally driven immune system activation can trigger despair-like behavior in an animal model, encouraging future analysis of the pathway for risk factors in neuropsychiatric disorders.
    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 12/2010; 35(13):2510-20. DOI:10.1038/npp.2010.116 · 7.83 Impact Factor