The role of 5-HTTLPR polymorphism in antidepressant-associated mania in bipolar disorder

Ferreira, Alexandre de Aguiar; Neves, Fernando Silva; Rocha, Felipe Filardi da; Silva, Gustavo Silveira e; Romano-Silva, Marco Aurélio; Miranda, Débora Marques de; Marco, Luiz; Corrêa, Humberto

doi:10.1016/j.jad.2008.04.012

Cited by 37 publications

(28 citation statements)

References 27 publications

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“…The mechanisms to explain rapid-cycling in BD are not understood, but may include genetic pathways related to stress and plasticity (Muller et al, 2006; Serretti et al, 2006). The serotonin transporter polymorphism (5-HTTLPR, locus SLC6A4 ) has been associated with rapid-cycling and antidepressant induced mania in BD (Cusin et al, 2001; Ferreira Ade et al, 2009; Mundo et al, 2001; Rousseva et al, 2003), as well as altered hippocampus volume in major depressive disorder (Frodl et al, 2004; Taylor et al, 2005). Whereas homozygosity for the val allele of the Val66Met brain derived neurotrophic growth factor gene is associated with susceptibility to BD and rapid-cycling, the met allele is associated with decreases in hippocampus volume (Chepenik et al, 2009; Geller et al, 2004; Matsuo et al, 2009; Muller et al, 2006; Sklar et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Structure–function associations in hippocampus in bipolar disorder

Chepenik

Wang

Spencer

et al. 2012

Biological Psychology

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Hippocampus volume decreases and verbal memory deficits have been reported in bipolar disorder (BD) as independent observations. We investigated potential associations between these deficits in subjects with BD. Hippocampus volumes were measured on magnetic resonance images of 31 subjects with BD and 32 healthy comparison (HC) subjects. The California Verbal Learning Test-Second Edition (CVLT) assessed verbal memory function in these subjects. Compared to the HC group, the BD group showed both significantly smaller hippocampus volumes and impaired performance on CVLT tests of immediate, short delay and long delay cued and free recall. Further, smaller hippocampus volume correlated with impaired performance in BD. Post-hoc analyses revealed a trend towards improved memory in BD subjects taking antidepressant medications. These results support associations between morphological changes in hippocampus structure in BD and verbal memory impairment. They provide preliminary evidence pharmacotherapy may reverse hippocampus-related memory deficits.

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Section: Discussionmentioning

confidence: 99%

Structure–function associations in hippocampus in bipolar disorder

Chepenik

Wang

Spencer

et al. 2012

Biological Psychology

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“…Adolescents who have not manifested the manic component of a bipolar disorder may be particularly vulnerable to SSRI antidepressant-induced mania or hypomania (Frye et al, 2009). Although preliminary studies showed conflicting results regarding the association between 5-HTTLPR polymorphism and antidepressant-induced mania (Mundo et al, 2001; Rousseva et al, 2003; Serretti et al, 2004; Baumer et al, 2006; Masoliver et al, 2006; Ferreira Ade et al, 2009), a recent meta-analysis indicated a higher incidence of antidepressant-induced mania in patients with the “s” variant of 5-HTTLPR (Daray et al, 2010). Likelihood of SSRI monotherapy response is deemed low once failure of the “SSRI challenge” test has been observed in this category.…”

Section: Untoward Effects Of “Ssri Challenge”mentioning

confidence: 99%

A Neurobiological Hypothesis of Treatment-Resistant Depression â€“ Mechanisms for Selective Serotonin Reuptake Inhibitor Non-Efficacy

Coplan

Gopinath

Abdallah

et al. 2014

Front. Behav. Neurosci.

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First-line treatment of major depression includes administration of a selective serotonin reuptake inhibitor (SSRI), yet studies suggest that remission rates following two trials of an SSRI are <50%. The authors examine the putative biological substrates underlying “treatment resistant depression (TRD)” with the goal of elucidating novel rationales to treat TRD. We look at relevant articles from the preclinical and clinical literature combined with clinical exposure to TRD patients. A major focus was to outline pathophysiological mechanisms whereby the serotonin system becomes impervious to the desired enhancement of serotonin neurotransmission by SSRIs. A complementary focus was to dissect neurotransmitter systems, which serve to inhibit the dorsal raphe. We propose, based on a body of translational studies, TRD may not represent a simple serotonin deficit state but rather an excess of midbrain peri-raphe serotonin and subsequent deficit at key fronto-limbic projection sites, with ultimate compromise in serotonin-mediated neuroplasticity. Glutamate, serotonin, noradrenaline, and histamine are activated by stress and exert an inhibitory effect on serotonin outflow, in part by “flooding” 5-HT1A autoreceptors by serotonin itself. Certain factors putatively exacerbate this scenario – presence of the short arm of the serotonin transporter gene, early-life adversity and comorbid bipolar disorder – each of which has been associated with SSRI-treatment resistance. By utilizing an incremental approach, we provide a system for treating the TRD patient based on a strategy of rescuing serotonin neurotransmission from a state of SSRI-induced dorsal raphe stasis. This calls for “stacked” interventions, with an SSRI base, targeting, if necessary, the glutamatergic, serotonergic, noradrenergic, and histaminergic systems, thereby successively eliminating the inhibitory effects each are capable of exerting on serotonin neurons. Future studies are recommended to test this biologically based approach for treatment of TRD.

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“…Many genes associated with BPD risk were detected using a candidate gene approach. Examples of these genes include those coding for monoamine oxidase (MAOA), dopamine transporter (DAT), serotonin transporter (5-HTT), 5-HT2A receptors, catechol-O-methyltransferase, brain-derived neurotrophic factor, Neuregulin 1, and disrupted-in-schizophrenia 1 (Neves et al, 2008;Perlis et al, 2008;Serretti and Mandelli, 2008;Barnett and Smoller, 2009;Ferreira et al, 2009). This necessitates a multiple gene blasting approach for more in-depth research into BPD.…”

Section: Discussionmentioning

confidence: 99%

Associations of serotonin receptor gene HTR3A, HTR3B, and HTR3A haplotypes with bipolar disorder in Chinese patients

et al. 2016

Genet. Mol. Res.

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ABSTRACT. Single nucleotide polymorphisms (SNPs) in HTR3A and HTR3B have been reported to be associated with bipolar disorder in European and Japanese populations. We explored the roles of 21 tag SNPs in HTR3A and HTR3B in susceptibility to bipolar disorder in a Chinese cohort. Twenty-one Tag SNPs were genotyped in a study consisting of 130 patients with bipolar disorder, who visited Shandong Mental Health Center between June 2013 and May 2014, and 109 healthy individuals as controls. All of the tag SNPs were genotyped using Sequenom MassArray matrix-assisted laser desorption/ionization time of flight spectrometry. Plink 1.07, Haploview 4.2, and SPSS 20.0 were used for the analysis of the genotypes and the associations of the haplotypes with bipolar disorder. Association analyses of tag SNPs detected significant associations with the A allele in HTR3A rs1176719 (P = 0.030) and the C allele in HTR3A rs1176713 (P = 0.048). Haplotype-based association analyses indicated a statistically significant (P = 0.035) five-SNP haplotype (rs1062613:C, rs11604247:C, rs1176722:G, rs2276302:A, rs1176719:G) of linkage disequilibrium in block 3. Analysis of our small Chinese sample revealed a significant association of HTR3A with bipolar disorder, but yielded no evidence of an association between HTR3B and bipolar disorder. Furthermore, evidence for an association was found for a haplotype of HTR3A. Studies with larger Chinese samples are needed to verify our findings.

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The role of 5-HTTLPR polymorphism in antidepressant-associated mania in bipolar disorder

Cited by 37 publications

References 27 publications

Structure–function associations in hippocampus in bipolar disorder

Structure–function associations in hippocampus in bipolar disorder

A Neurobiological Hypothesis of Treatment-Resistant Depression â€“ Mechanisms for Selective Serotonin Reuptake Inhibitor Non-Efficacy

Associations of serotonin receptor gene HTR3A, HTR3B, and HTR3A haplotypes with bipolar disorder in Chinese patients

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