The 5HTTLPR polymorphism of the serotonin transporter gene is associated with affective temperaments as measured by TEMPS-A

Gonda, Xénia; Rihmer, Zoltán; Zsombók, Terézia; Bagdy, György; Akiskal, Kareen K.; Akiskal, Hagop S.

doi:10.1016/j.jad.2005.12.048

Cited by 132 publications

(67 citation statements)

References 42 publications

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“…In a recent study [39] , a significant association was found between the S allele of the serotonin transporter gene and the four affective temperaments, containing more or less of a depressive component (depressive, cyclothymic, irritable and anxious). Earlier studies already reported a strong association between this allele and 'subthreshold' as well as 'threshold' unipolar and bipolar major depression [40] .…”

Section: Discussionmentioning

confidence: 93%

Psychopathological Correlates of Lifetime Anxiety Comorbidity in Bipolar I Patients: Findings from a French National Cohort

et al. 2009

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Background: Despite numerous studies on the comorbidity of bipolar and anxiety disorders, there is no satisfactory psychopathological model for their overlap. Method: 1,090 hospitalized patients meeting DSM-IV criteria for a manic episode of bipolar I disorder were subtyped according to the presence or not of lifetime anxiety comorbidity and assessed for demographic, illness course, clinical, associated condition, temperament, and treatment characteristics. Results: Lifetime anxiety comorbidity, defined as presence of at least one anxiety disorder in lifetime, was found in 27.2% (n = 297) of the sample. Compared to patients without such a comorbidity (n = 793), those who had it experienced a higher number of mood episodes and suicide attempts in the previous year, more stressors, organic disorders and less free intervals; furthermore, they showed more temperaments with depressive features and complex treatment. At study entry, they also experienced manic episodes with higher levels of depression, psychosis and hostility. The following independent variables were associated with lifetime anxiety comorbidity: higher scores on the Montgomery-Åsberg Depression Rating Scale, depressive temperament, irritable temperament, higher scores on the Scale for the Assessment of Positive Symptoms, episodes without free intervals and at least one stressor before the index episode. Conclusions: Factors associated with lifetime anxiety comorbidity in bipolar I patients may be integrated into a comprehensive diathesis-stress model emphasizing the role of irritable temperament as a source of mood instability and stress, and interacting with other temperamental characteristics to trigger the outbreak of both anxiety and bipolar symptoms.

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Section: Discussionmentioning

confidence: 93%

Psychopathological Correlates of Lifetime Anxiety Comorbidity in Bipolar I Patients: Findings from a French National Cohort

et al. 2009

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“…Although several researchers reported no significant association of the 5HTTLPR polymorphism with hyperthymic temperament (Gonda et al 2006(Gonda et al , 2009Kang et al 2008), to our knowledge, there have been no studies investigating hyperthymic temperament by using the serotonergic neuroendocrine challenge test which can estimate central serotonergic function. Thus, the second aim of the present study is to examine whether the central serotonergic function is associated with hyperthymic temperament.…”

Section: Introductionmentioning

confidence: 83%

Biological aspect of hyperthymic temperament: light, sleep, and serotonin

et al. 2010

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“…5-HTTLPR is a well-known functional length-polymorphism located in the promoter of SLC6A4. The ''S'' allele, resulting reduced 5-HTT expression [Lesch et al, 1996], was previously associated with certain psychiatric disorders [Sen et al, 2004;Gonda et al, 2005;Gonda et al, 2006;Serretti et al, 2006;D'Souza and Craig, 2008;Lazary et al, 2008;Murphy et al, 2008] however, data regarding anxiety are contradictory [Lesch et al, 1996;Ball et al, 1997;Ebstein et al, 1997;Gelernter et al, 1998;Jorm et al, 1998;Ricketts et al, 1998;Deary et al, 1999;Seretti et al, 1999;Sen et al, 2004;Gonda et al, 2007].…”

Section: Discussionmentioning

confidence: 99%

Promoter variants of the cannabinoid receptor 1 gene (CNR1) in interaction with 5‐HTTLPR affect the anxious phenotype

Lazáry

Gonda

et al. 2009

American J of Med Genetics Pt B

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Anxiety is a polygenic condition, and the recently discovered Endocannabinoid System (ECS) is one plausible candidate. Experimental data suggest that the ECS can modulate several neurotransmitter systems, including the serotonergic system, which itself plays a significant role in anxiety. However, to date there is no evidence of gene-gene interactions; indeed genetic studies focusing separately on the two systems provide conflicting data. Thus, the aim of our study was to analyze the interaction of the promoter regions of the serotonin transporter (SLC6A4) and cannabinoid receptor 1 (CNR1) genes on anxiety. We genotyped 706 individuals for the 5-HTTLPR in the SLC6A4 promoter and 4 SNPs located in the CNR1 promoter region. Anxiety was measured by the State-Trait Anxiety Inventory (STAI-S, STAI-T), the anxiety subscale of TEMPS-A (TEMPS-Anx), and the Brief Symptom Inventory (BSI-Anx). Significant 5-HTTLPR x CNR1 promoter-promoter interaction was observed using STAI-T (P = 0.0006) and TEMPS-Anx (P = 0.0013). The risk of high anxiety scores on BSI-Anx was 4.6-fold greater in homozygous 'GG' rs2180619 in combination with homozygous 'SS' 5-HTTLPR (P = 0.0005) compared to other genotypes. The effect of previously described "TGC" haplotype in the alternative promoter of CNR1 depended both on the conventional promoter polymorphism and the 5-HTTLPR. Our haplotype and putative transcription binding profile analyses strongly suggest that certain constellations of CB1-receptor and 5-HTT promoters yield extremely high or low synaptic 5-HT concentrations, and these are associated with an anxious phenotype. In conclusion, genetically determined serotonergic and endocannabinoid dysfunctions could lead to a vulnerability causing anxiety disorders and possibly depression.

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The 5HTTLPR polymorphism of the serotonin transporter gene is associated with affective temperaments as measured by TEMPS-A

Cited by 132 publications

References 42 publications

Psychopathological Correlates of Lifetime Anxiety Comorbidity in Bipolar I Patients: Findings from a French National Cohort

Psychopathological Correlates of Lifetime Anxiety Comorbidity in Bipolar I Patients: Findings from a French National Cohort

Biological aspect of hyperthymic temperament: light, sleep, and serotonin

Promoter variants of the cannabinoid receptor 1 gene (CNR1) in interaction with 5‐HTTLPR affect the anxious phenotype

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