Effect of a Triallelic Functional Polymorphism of the Serotonin-Transporter-Linked Promoter Region on Expression of Serotonin Transporter in the Human Brain

Parsey, Ramin V.; Hastings, Ramin; Oquendo, María A.; Hu, Xian‐Zhang; Goldman, David; Huang, Yung‐yu; Simpson, Norman R.; Arcement, Julie; Huang, Yiyun; Ogden, R. Todd; Heertum, Ronald L. Van; Arango, Victoria; Mann, J. John

doi:10.1176/appi.ajp.163.1.48

Cited by 245 publications

(191 citation statements)

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“…A functional promotor polymorphism in the 5-HTT gene (5-HTTLPR) (Lesch et al, 1996) has previously been associated with antidepressant response (Serretti, Benedetti, Zanardi, & Smeraldi, 2005), and 5-HTTLPR genotype may be independent of 5-HTT binding (Parsey et al, 2006a;Shioe et al, 2003;Van Dyck et al, 2004). While the sample size of the current study was not sufficient for a genetic association study, we include genetic data obtained from this sample in the discussion, which should be considered exploratory.…”

Section: Discussionmentioning

confidence: 99%

“…Remitters had a higher frequency of the biallelic L allele than controls (85.7% vs. 51.3%; Fisher's, p=0.02), but did not differ from non-remitters (non-remitters: 58.3%; Fisher's, p=0.15). It is not clear that 5-HTTLPR genotype is predictive of adult human brain 5-HTT binding (Parsey et al, 2006a;Shioe et al, 2003;Van Dyck et al, 2004), so these trends may be due to an independent effect of genotype on clinical outcome. Incorporating 5-HTTLPR genotype with 5-HTT binding into the logistic regression model did not improve its predictive power.…”

Section: Discussionmentioning

confidence: 99%

“…PET and magnetic resonance imaging (MRI) data acquisition, analysis, and measurement of metabolite corrected arterial input functions were performed as previously described (Parsey et al, 2006a;Parsey et al, 2006b;Parsey et al, 2000). After a ten-minute transmission scan, [ 11 C]McN5652 was injected intravenously and emission data acquired for 130 minutes.…”

Section: Image Analysis and Modelingmentioning

confidence: 99%

“…The log transform was necessary because of two features of our BP P data: skewness, and unequal standard deviation (SD) of measurements across groups with different binding levels (with SD roughly proportional to the binding level). We and others have used this or related statistical approaches to allow for valid statistical analysis of PET data with these characteristics (Meltzer et al, 2004;Oquendo et al, 2006;Parsey et al, 2006a;Parsey et al, 2006b;Parsey et al, 2006c;Parsey et al, 2006d;Rabiner et al, 2002;Sullivan et al, 2005). Graph of binding potential (Figures 1 and 2) uses actual (not log-transformed) BP P values.…”

Section: Statisticsmentioning

confidence: 99%

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Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder

Miller

Oquendo

Ogden

et al. 2008

Journal of Psychiatric Research

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Objective-Lower serotonin transporter (5-HTT) binding (BP P = = f P B avail /K D ) is reported during a major depressive episode (MDE) compared to healthy controls. Higher 5-HTT binding in the diencephalon has previously been associated with acute response to antidepressant treatment. We assessed baseline 5-HTT binding as a predictor of one-year remission from a MDE, examining binding in brain regions implicated in the pathophysiology of major depressive disorder (MDD). Results-Significant differences in 5-HTT binding among the three groups (healthy controls, remitters, and non-remitters) were observed in a linear mixed-effects model. Post-hoc, non-remitters had lower 5-HTT binding than controls in midbrain, amygdala, and anterior cingulate. Remitters did not differ significantly from controls or non-remitters in 5-HTT binding. Remitters did not differ from non-remitters in clinical characteristics apart from greater family history of depression among non-remitters. A logistic regression model fit to determine the capacity of baseline 5-HTT binding to predict remission status at one year yielded a coefficient that was suggestive but not significant (p=0.057). Methods-5-HTTLimitations-The small sample size and heterogeneous treatments received reduced statistical power to detect differences in binding based on clinical outcome.Conclusions-Lower pretreatment 5-HTT binding may be predictive of non-remission from major depression following one year of naturalistic antidepressant treatment. Future studies using standardized treatment are warranted.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Image Analysis and Modelingmentioning

confidence: 99%

Section: Statisticsmentioning

confidence: 99%

See 2 more Smart Citations

Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder

Miller

Oquendo

Ogden

et al. 2008

Journal of Psychiatric Research

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“…68,[70][71][72][73] However, the translation of in vitro findings into in vivo functioning does not appear straightforward. Human neuroimaging studies of 5-HTT availability [74][75][76][77][78][79] and post-mortem studies of 5-HTT bindings and rRNA expression [80][81][82] have not detected any consistent effect of 5-HTTLPR. No reliable association was found between 5-HTLPR and the level of serotonin metabolite in the cerebrospinal fluid.…”

Section: The Functionality Of 5-httlprmentioning

confidence: 99%

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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Acute and Posttraumatic Stress Symptoms in a Prospective Gene × Environment Study of a University Campus Shooting

Mercer

Orcutt²,

Quinn³

et al. 2012

Arch Gen Psychiatry

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Context The serotonin transporter (SLC6A4) has been associated with several stress-related syndromes including posttraumatic stress disorder (PTSD). The ability to detect meaningful associations is largely dependent on reliable measures of preexisting trauma. Objective To study the association of genetic variants within SLC6A4 with acute and posttraumatic stress symptoms in a civilian cohort with known levels of preexisting trauma and PTSD symptoms collected prior to a shared index traumatic event. Design Ongoing longitudinal study. Setting On February 14, 2008, a lone gunman shot multiple people on the campus of Northern Illinois University in DeKalb, Illinois, killing 5 and wounding 21. As part of an ongoing longitudinal study on that campus, a cohort of female undergraduate students, interviewed prior to the shooting, completed follow-up trauma-related measures including PTSD symptom severity (follow-up survey was launched 17 days postshooting; n=691). To obtain DNA, salivary samples were collected from a subset of the original study population based on willingness to participate (n=276). Participants Two hundred four undergraduate women. Main Outcome Measures SLC6A4 polymorphisms STin2, 5-HTTLPR, and rs25531 were genotyped in 235 individuals. Results We found that although the STin2 variant and 5-HTTLPR alone did not associate with increased PTSD symptoms, rs25531 and the 5-HTTLPRmultimarker genotype (combined 5-HTTLPR and rs25531) were associated with significantly increased acute stress disorder symptoms at 2 to 4 weeks postshooting (n = 161; P<.05). This association remained significant when controlling for race and for level of shooting exposure (n = 123; P<.007). The association was most robust with the 5-HTTLPR multimarker genotype and avoidance symptoms (P=.003). Conclusion These data suggest that differential function of the serotonin transporter may mediate differential response to a severe trauma. When examined in a relatively homogenous sample with shared trauma and known prior levels of child and adult trauma, the 5-HTTLPR multimarker genotype may serve as a useful predictor of risk for PTSD-related symptoms in the weeks and months following the trauma.

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Effect of a Triallelic Functional Polymorphism of the Serotonin-Transporter-Linked Promoter Region on Expression of Serotonin Transporter in the Human Brain

Abstract: Associations of the 5-HTTLPR polymorphism to clinical phenotypes appear to be due to developmental effects of 5-HTTLPR on expression and not due to its direct effect on serotonin transporter binding in adulthood.

Cited by 245 publications

References 14 publications

Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder

Serotonin transporter binding as a possible predictor of one-year remission in major depressive disorder

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

Acute and Posttraumatic Stress Symptoms in a Prospective Gene × Environment Study of a University Campus Shooting

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