Novel allelic variants in the human serotonin transporter gene linked polymorphism (5-HTTLPR) among depressed patients with suicide attempt

Segal, Jair; Schenkel, Laila C.; Oliveira, Marcela Herbstrith de; Salum, Giovanni Abrahão; Bau, Claiton H.D.; Manfro, Gisele Gus; Leistner-Segal, Sandra

doi:10.1016/j.neulet.2008.12.015

Cited by 16 publications

(8 citation statements)

References 12 publications

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“…This conclusion agreed with several studies that found no significant relationship between the 5-HTTLPR polymorphism and the development of mood disorders, such as major depression [37], depression and attempted suicide [38], depression and stressful life events [39], and bipolar disorders [40]. In a meta-analysis, Risch et al [18] observed no association between the 5-HTTLPR genotype, either alone or in conjunction with stressful events, and risk for depression in either gender.…”

Section: Discussionsupporting

confidence: 89%

Evaluation of the 5-HTTLPR and 5-HTTVNTR Polymorphisms in the Serotonin Transporter Gene in Women with Postpartum Depression

Zimmermann-Peruzatto¹,

Almeida²,

Lucion³

et al. 2012

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Objective: The purpose of the present study was to evaluate the association between the 5-HTTLPR and 5-HTTVNTR polymorphisms in the serotonin transporter gene (SLC6A4) in Brazilian women with diagnosed postpartum depression (PPD) and the presence of depressive symptoms. Method: The cohort consisted of 128 white women who were characterized based on skin color and morphological characteristics. The Beck Depression Inventory was used to diagnose PPD and to score the depressive symptoms. The 5-HTTLPR and 5-HTTVNTR polymorphisms were analyzed by PCR-based methods. Results: No association was observed between the PPD diagnosis and either the 5-HTTLPR (p = 0.48) or the 5-HTTVNTR (p = 0.77) polymorphism. When the polymorphisms were analyzed together with haplotype data, the analyses demonstrated that women carriers of the L-12/L-12 diplotype have lower Beck Depression Inventory scores than women carrying other diplotypes (p = 0.04). Discussion: Few studies have investigated the association of SLC6A4 polymorphisms with PPD, and the role of 5-HTTLPR and 5-HTTVNTR polymorphisms in PPD susceptibility has not been established to date. Therefore, our findings link the haplotypes of these two variants with depression symptoms, thereby contributing to our understanding of PPD susceptibility.

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Section: Discussionsupporting

confidence: 89%

Evaluation of the 5-HTTLPR and 5-HTTVNTR Polymorphisms in the Serotonin Transporter Gene in Women with Postpartum Depression

Zimmermann-Peruzatto¹,

Almeida²,

Lucion³

et al. 2012

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“…Numerous gene variants have been identified, which have a significant impact on its functioning. The most studied of these SERT gene variants is the SERT gene-linked polymorphic region (5-HTTLPR), which results in a short or long form (Nakamura et al, 2000; Segal et al, 2009): the short form is characterized by a reduction in SERT mRNA, SERT binding, and 5-HT when compared with the long form.…”

Section: The Role Of 5-ht In Working Spatial and Episodic Memorymentioning

confidence: 99%

Neurobiology of Anorexia Nervosa: Serotonin Dysfunctions Link Self-Starvation with Body Image Disturbances through an Impaired Body Memory

Riva

2016

Front. Hum. Neurosci.

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The etiology of anorexia nervosa (AN) is still unclear, despite that it is a critical and potentially mortal illness. A recent neurobiological model considers AN as the outcome of dysfunctions in the neuronal processes related to appetite and emotionality (Kaye et al., 2009, 2013). However, this model still is not able to answer a critical question: What is behind body image disturbances (BIDs) in AN? The article starts its analysis from reviewing some of the studies exploring the effects of the serotonin systems in memory (episodic, working, and spatial) and its dysfunctions. The review suggests that serotonin disturbances may: (a) facilitate the encoding of third person (allocentric) episodic memories; (b) facilitate the consolidation of emotional episodic memories (e.g., teasing), if preceded by repeated stress; (c) reduce voluntary inhibition of mnestic contents; (d) impair allocentric spatial memory. If we discuss these results within the interpretative frame suggested by the “Allocentric Lock Hypothesis” (Riva, 2012, 2014), we can hypothesize that altered serotoninergic activity in AN patients: (i) improves their ability to store and consolidate negative autobiographical memories, including those of their body, in allocentric perspective; (ii) impairs their ability to trigger voluntary inhibition of the previously stored negative memory of the body; (iii) impairs their capacity to retrieve/update allocentric information. Taken together, these points suggest a possible link between serotonin dysfunctions, memory impairments and BIDs: the impossibility of updating a disturbed body memory using real time experiential data—I'm locked to a wrong body stored in long term memory—pushes AN patients to control body weight and shape even when underweight.

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“…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). Inhibitors of SERT, the serotonin-selective reuptake inhibitors (SSRIs), represent a frontline pharmacological therapy for a number of these prevalent psychiatric conditions, including anxiety, depression, and OCD (Vaswani et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Interleukin-1 Receptor Activation by Systemic Lipopolysaccharide Induces Behavioral Despair Linked to MAPK Regulation of CNS Serotonin Transporters

Zhu

Lindler

Owens

et al. 2010

Neuropsychopharmacol

261

226

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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.

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Novel allelic variants in the human serotonin transporter gene linked polymorphism (5-HTTLPR) among depressed patients with suicide attempt

Cited by 16 publications

References 12 publications

Evaluation of the 5-<i>HTTLPR</i> and 5-<i>HTTVNTR</i> Polymorphisms in the Serotonin Transporter Gene in Women with Postpartum Depression

Evaluation of the 5-<i>HTTLPR</i> and 5-<i>HTTVNTR</i> Polymorphisms in the Serotonin Transporter Gene in Women with Postpartum Depression

Neurobiology of Anorexia Nervosa: Serotonin Dysfunctions Link Self-Starvation with Body Image Disturbances through an Impaired Body Memory

Interleukin-1 Receptor Activation by Systemic Lipopolysaccharide Induces Behavioral Despair Linked to MAPK Regulation of CNS Serotonin Transporters

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Novel allelic variants in the human serotonin transporter gene linked polymorphism (5-HTTLPR) among depressed patients with suicide attempt

Cited by 16 publications

References 12 publications

Evaluation of the 5-&lt;i&gt;HTTLPR&lt;/i&gt; and 5-&lt;i&gt;HTTVNTR&lt;/i&gt; Polymorphisms in the Serotonin Transporter Gene in Women with Postpartum Depression

Evaluation of the 5-&lt;i&gt;HTTLPR&lt;/i&gt; and 5-&lt;i&gt;HTTVNTR&lt;/i&gt; Polymorphisms in the Serotonin Transporter Gene in Women with Postpartum Depression

Neurobiology of Anorexia Nervosa: Serotonin Dysfunctions Link Self-Starvation with Body Image Disturbances through an Impaired Body Memory

Interleukin-1 Receptor Activation by Systemic Lipopolysaccharide Induces Behavioral Despair Linked to MAPK Regulation of CNS Serotonin Transporters

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Product

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Evaluation of the 5-<i>HTTLPR</i> and 5-<i>HTTVNTR</i> Polymorphisms in the Serotonin Transporter Gene in Women with Postpartum Depression

Evaluation of the 5-<i>HTTLPR</i> and 5-<i>HTTVNTR</i> Polymorphisms in the Serotonin Transporter Gene in Women with Postpartum Depression