Clinical Risk Factors and Serotonin Transporter Gene Variants Associated With Antidepressant-Induced Mania

Frye, Mark A.; McElroy, Susan L.; Prieto, Miguel L.; Harper, Kelly L.; Walker, Denise L.; Kung, Simon; Chauhan, Monika; Crow, Scott J.; Sutor, Bruce; Galardy, Christine; Veldić, Marin; Palmer, Brian A.; Geske, Jennifer R.; Fuentes, Manuel; Cuellar-Barboza, Alfredo B.; Seymour, Lisa R.; Mori, Nicole; Biernacka, Joanna M.

doi:10.4088/jcp.14m09127

Cited by 28 publications

(37 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The AIM literature is complicated by differences in study populations and use of mood stabilizers, and most studies did not genotype rs25531. Despite these issues, a meta‐analysis of existing studies in patients on antidepressants (not exclusively SSRIs) shows a suggestive association of the S allele with AIM (p=0.059) . The observed association between gastrointestinal adverse effects and the S allele is not statistically significant in many individual studies but is fairly consistent in both Asian and white populations.…”

Section: Resultsmentioning

confidence: 97%

“…Of seven studies investigating 5‐HTTLPR in relation to AIM, three found significant evidence associating the S allele with increased odds of AIM, one showed a nonsignificant trend in that direction, and three showed little signal of association . Studies examining STin2 are consistent in that all three studies failed to show an association between STin2 and AIM . One group performed a haplotype analysis of 5‐HTTLPR, rs25531, and STin2 and concluded that the L A ‐10 haplotype is associated with a reduced risk of AIM – a finding that is physiologically confusing given the increased expression owed to the 5‐HTTLPR and rs25531 genotypes and decreased expression related to STin2 10 repeat allele.…”

Section: Resultsmentioning

confidence: 99%

“…Some of the earliest studies in this domain examined a potential genetic association of SLC6A4 with antidepressant-induced mania (AIM). Of seven studies investigating 5-HTTLPR in relation to AIM, three found significant evidence associating the S allele with increased odds of AIM, [25][26][27] one showed a nonsignificant trend in that direction, 28 and three showed little signal of association. [29][30][31] Studies examining STin2 are consistent in that all three studies failed to show an association between STin2 and AIM.…”

Section: Neuropsychiatric Adverse Eventsmentioning

confidence: 99%

“…[29][30][31] Studies examining STin2 are consistent in that all three studies failed to show an association between STin2 and AIM. 25,26,28 One group performed a haplotype analysis of 5-HTTLPR, rs25531, and STin2 and concluded that the L A -10 haplotype is associated with a reduced risk of AIM 28 a finding that is physiologically confusing given the increased expression owed to the 5-HTTLPR and rs25531 genotypes and decreased expression related to STin2 10 repeat allele. Studies examining combined effects of these loci are rare, and the proper methodology for such studies is still debated.…”

Section: Neuropsychiatric Adverse Eventsmentioning

confidence: 99%

See 3 more Smart Citations

Serotonin Transporter Gene Polymorphisms and Selective Serotonin Reuptake Inhibitor Tolerability: Review of Pharmacogenetic Evidence

2017

View full text Add to dashboard Cite

Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacotherapy for mood and anxiety disorders. The common mechanism of drugs in this class is antagonism of the serotonin transporter. Within the serotonin transporter gene SLC6A4, two polymorphic sites termed 5-HTTLPR and STin2 are proposed to have functional consequences and thus have been attractive candidates for pharmacogenetic studies of SSRI efficacy and tolerability. This review summarizes approximately 15 years of study of these polymorphisms as they relate to SSRI tolerability phenotypes. Four online databases (PubMed, Cochrane CENTRAL, PsycINFO, and PharmGKB) were searched for articles on polymorphisms of SLC6A4 including 5-HTTLPR and STin2 by using a systematic approach. Specific and general psychopharmacology terms, along with adverse effect and tolerability concepts, added to the search strategy. The Human Gene Mutation Database was checked for additional references. Forty studies met the inclusion criteria. While null and occasionally opposite associations are reported, the low expression 5-HTTLPR S allele is generally associated with greater adverse drug reaction burden during SSRI therapy. The most convincing evidence is in studies of antidepressant-induced mania and gastrointestinal adverse events. Studies of STin2 are sparse and have conflicting findings. In conclusion, the S allele of 5-HTTLPR may be predictive of increased adverse event burden, and this effect appears specific to certain classes of adverse events. Limitations and challenges in interpreting this body of evidence include assay errors, dissimilar grouping of genotypes, the role of ethnicity in associations, and study methodological differences. The clinical utility of serotonin transporter genotypes is not yet delineated but will ultimately depend on genotypic effects on both tolerability and efficacy of SSRIs.

show abstract

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

Section: Neuropsychiatric Adverse Eventsmentioning

confidence: 99%

Section: Neuropsychiatric Adverse Eventsmentioning

confidence: 99%

See 2 more Smart Citations

Serotonin Transporter Gene Polymorphisms and Selective Serotonin Reuptake Inhibitor Tolerability: Review of Pharmacogenetic Evidence

2017

View full text Add to dashboard Cite

show abstract

“…Our regression analyses showed that low‐expressing genotypes, those with an S allele, predicted child fear, but none of the genotypes predicted child AL. Historically, the 5‐HTTLPR gene and the rs‐25531 polymorphism have been associated with depression, obsessive compulsive disorder, and many psychiatric diagnoses, although many of these conflict in the nature of how the SNP regulates or affects these outcomes (Frye et al., ; Klauke et al., ; Voyiaziakis et al., ). Therefore, due to the inconsistent nature of both the literature and our findings, there is a need for further research examining child temperament and the 5‐HTTLPR polymorphism.…”

Section: Discussionmentioning

confidence: 99%

An exploratory genetic analysis: Associations between parent depression symptoms, child temperament, and the serotonin transporter gene polymorphism (5HTTLPR)

Gazor

Fang

Gagne

2017

J Appl Biobehavioral Res

View full text Add to dashboard Cite

Child temperament has been shown to be biologically based and heritable; however, genetic association studies of temperament have been fairly inconclusive, and the role that parental depressive symptoms play is largely unexplored in this context. The relationship between parent depressive symptoms and the child temperament dimensions of fear and activity level (AL) were examined in 100 sibling pairs 2.5–5.5 years of age and their mothers. Parent reports of child temperament and parent self‐reports of depressive symptoms were obtained from families, as well as DNA samples from each child during their lab visit. Associations between the serotonin transporter gene (SLC6A4) polymorphism 5‐HTTLPR/rs25531 and the phenotypic variables were also explored. Parent depressive symptoms were significantly related to higher child AL, but minimally associated with fear outcomes. More powerful regression analyses revealed that parent depressive symptoms, child gender, and child age predicted child AL, but only child gender and age predicted child fear. In our exploratory candidate gene analyses, the low‐expressing genotypes of the 5‐HTTLPR/rs25531 polymorphism predicted child fearfulness, but not child AL. Our phenotypic findings indicate that a child with at least one parent with depressive symptoms is more likely to have higher AL, and results of the initial genetic analyses show that the 5‐HTTLPR/rs25531 polymorphism is associated with child fearfulness. Future research employing larger samples, observational assessments, and related child behavioral maladjustment measures will further clarify these findings.

show abstract

Effects of somatic treatments on suicidal ideation and completed suicides

et al. 2021

View full text Add to dashboard Cite

Objective: This work was undertaken to define and characterize the role of currently available somatic treatments in psychiatry in either increasing or reducing the risk for suicide.Methods: Members of the Suicide Prevention Task Group of the National Network of Depression Centers performed a literature review of somatic treatments known to increase or reduce the risk for suicide. The reviews ventured to include all relevant information about the risk for both suicide ideation and completed suicides.Results: Lithium and clozapine are the only two somatic treatments that have highquality data documenting their antisuicide effects in mood disorders and schizophrenia, respectively. Lithium discontinuation is also associated with increased suicide risk.Ketamine and esketamine may have a small, but immediate, antisuicide effect. Despite the recent Food and Drug Administration approval of esketamine use in depressed suicidal patients, the small disproportional overrepresentation of suicide in subjects who had received esketamine versus placebo (3 vs. 0 among > 3500 subjects) requires ongoing evaluation. The purported antisuicide effect of electroconvulsive therapy is based on low-quality data. The effect of antidepressants is not at all clear. There appears to be direct evidence for antidepressants increasing suicidal ideation and the risk for suicide over the short-term in young people, but indirect (low quality) evidence that antidepressants reduce suicide risk over the long term. Conclusions:Clinicians have an expanding pharmacopeia to address suicide potential in their patients. Some of the agents with documented antisuicide effects may also increase suicidality under specific circumstances.

show abstract

Clinical Risk Factors and Serotonin Transporter Gene Variants Associated With Antidepressant-Induced Mania

Abstract: Narrowly defined, AIM appears to be at greatest risk for bipolar I patients. Our haplotype analysis of SLC6A4 suggests that future pharmacogenetic studies should not only focus on the SLC6A4 promotor variation but also investigate the role of other variants in the gene.

Cited by 28 publications

References 0 publications

Serotonin Transporter Gene Polymorphisms and Selective Serotonin Reuptake Inhibitor Tolerability: Review of Pharmacogenetic Evidence

Serotonin Transporter Gene Polymorphisms and Selective Serotonin Reuptake Inhibitor Tolerability: Review of Pharmacogenetic Evidence

An exploratory genetic analysis: Associations between parent depression symptoms, child temperament, and the serotonin transporter gene polymorphism (5HTTLPR)

Effects of somatic treatments on suicidal ideation and completed suicides

Contact Info

Product

Resources

About