Evaluating gene × psychological risk factor effects in the pathogenesis of anxiety: A new model approach.

Schmidt, Norman B.; Storey, Julie; Greenberg, Benjamin D.; Santiago, Helen T.; Li, Qian; Murphy, Dennis L.

doi:10.1037/0021-843x.109.2.308

Cited by 59 publications

(30 citation statements)

References 71 publications

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“…11,18,24,31 In one study 21 there was insufficient data to test for departure from HW equilibrium. In two studies data were not reported in a format that enabled their inclusion in the subsequent meta-analysis 28,31 and attempts to contact the authors of these studies to request data in an appropriate format were unsuccessful. A total of 24 studies therefore contributed to the meta-analysis, of which three reported genotype frequencies that deviated from HW equilibrium.…”

Section: Resultsmentioning

confidence: 99%

Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis

2004

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We attempted to replicate the findings of two recent meta-analyses that personality inventory moderates the association between the serotonin transporter gene and anxiety-related traits. A total of 24 studies contributed to the meta-analysis, of which three reported genotype frequencies that deviated from Hardy-Weinberg (HW) equilibrium. We found some support for the view that results depend on the type of questionnaire used, although in a direction opposite to that previously reported. Contrasts between the S/S and L/L groups were significant for TCI/TPQ harm avoidance studies (P ¼ 0.0024) but not NEO neuroticism (P ¼ 0.9757). When studies not in HW equilibrium were excluded the TCI/TPQ result for the S/S genotype still exceeded our 5% threshold, although with reduced significance (P ¼ 0.0082), and the NEO result remained nonsignificant (P ¼ 0.9109). While we cannot rule out an association between the 5HTT gene and anxiety-related traits, particularly for TCI/TPQ harm avoidance, our findings do indicate that the effect, if present, is small. Our results emphasise the importance of complete ascertainment of studies and the identification of relevant sources of heterogeneity. Molecular Psychiatry ( It is now accepted that a substantial proportion of variability in human personality is attributable to genetic variation. 1 As theories of personality propose that individual differences in specific traits are associated with individual differences in specific neurotransmitters, a number of candidate genes with known functional effects on neurotransmitter pathways have been investigated. 2 One pathway that has received considerable attention is the serotonin system, which is known to play an important role in emotional behaviour. 3 However, attempts to demonstrate an association between variation in genes involved in serotonin function and neuroticism or harm avoidance, a personality trait believed to reflect inherited differences in emotional response, have yielded inconsistent results.Even three independent meta-analyses of the large number of relevant publications do not come to a consensus: while Munafò et al 4 found little evidence for an association, both Schinka et al 5 and Sen et al 6 reported that 5HTT-LPR was significantly associated with neuroticism as measured using the class of personality questionnaires derived from Costa and McCrae's 7 five-factor model of personality (NEO-PI, NEO-PI-R, NEO-FFI), but was not associated with harm avoidance as measured using the class of questionnaires derived from Cloninger's 8 tridimensional theory of personality (TCI, TPQ).The findings of the Schinka and Sen meta-analyses are an important methodological and conceptual challenge to personality genetics. NEO neuroticism demonstrates substantial psychometric form equivalence with TCI/TPQ harm avoidance 9 and, assuming that questionnaire equivalence reflects the measurement of the same underlying biological substrate, each assessment of neuroticism should be associated with the same genetic variants. Failure to provide com...

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Section: Resultsmentioning

confidence: 99%

Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis

2004

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“…Pertinently, another study found that healthy females with the LL genotype were more sensitive to CCK-4-induced panic attacks than those who are carriers of S allele (Maron et al, 2004b). Also Schmidt et al (2000) reported that subjects homozygous for the long variant were at greater risk for behavioral hyper-reactivity to 35% CO 2 challenge than those with short-allele genotypes. On the contrary, in patients with PD, CO 2 reactivity was not influenced by 5-HTTLPR genetic variants (Perna et al, 2004).…”

Section: -Htt Genementioning

confidence: 99%

Serotonin Function in Panic Disorder: Important, But Why?

Maron

Shlik

2005

Neuropsychopharmacol

106

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The essential role of serotonin (5-hydroxytryptamine (5-HT)) system in the neurobiology and pharmacotherapy of panic disorder (PD) continues to be a topic of intensive interdisciplinary research. Interest in the involvement of 5-HT in PD has been fuelled by clinical studies demonstrating that medications increasing the synaptic availability of 5-HT, such as selective 5-HT re-uptake inhibitors, are effective in the treatment of PD. Rival theories of 5-HT deficiency vs excess have attempted to explain the impact of 5-HT function in PD. In the past decade, knowledge of the role of 5-HT in the neurobiology of PD has expanded dramatically due to much new research including experimental, treatment, brain-imaging, and genetic studies. The current review attempts to summarize the new data and their implications. The challenge and treatment studies generally confirm the specific inhibitory influence of 5-HT on panicogenesis. The brainimaging studies in PD patients demonstrate functional and clinically relevant alterations in various elements of 5-HT system affecting the neurocircuitry of panic. The findings of genetic association studies suggest that certain 5-HT-related genes may contribute to the susceptibility to PD; however, these data are rather limited and inconsistent. It appears that, even if not the primary etiological factor in PD, the 5-HT function conveys important vulnerability, as well as adaptive factors. A better understanding of these processes may be critical in achieving progress in the treatment of patients suffering from PD.

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“…It consists of a 44-base pair (bp) insertion/deletion and, in vitro, the basal activity of the long (l) variant was more than twice that of the short (s) one, suggesting that serotonin transporter gene transcription is modulated by such variants Lesch et al, 1996]. Schmidt et al [2000] recently reported a significant difference in subjective reactivity to CO 2 inhalation between 5-HTTLPR genotype groups in healthy subjects. In their sample, subjects homozygous for the long variant (l) appear to be at risk for behavioral hyperreactivity to the 35% CO 2 inhalation test.…”

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Lack of relationship between CO₂ reactivity and serotonin transporter gene regulatory region polymorphism in panic disorder

Perna

Bella

Favaron

et al. 2004

American J of Med Genetics Pt B

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Changes in the function of the serotonergic system influence both panic phobic symptoms and carbon dioxide (CO2) reactivity in patients with panic disorder. Schmidt et al. [2000: J Abnorm Psychol 109(2):308-320] recently reported a predictive role of the genetic variants of the 5-HTTLPR on the fearful response to CO2 in healthy controls. We tested the hypothesis that the heterogeneity of CO2 reactivity in patients with panic disorder could be related to the allelic variation of the 5-HTT promoter. Ninety-five patients with panic disorder were challenged with 35% CO2. 5-HTTLPR allelic variation in each subject was determined using a PCR-based method. There were no differences for all the measures of CO2 reactivity among the genotype groups. CO2 reactivity of patients with panic disorder seems not to be influenced by the genetic variants of the 5-HTTLPR; this finding does not support a role for the serotonin transporter in the etiopathogenesis of CO2 reactivity in panic disorder.

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Evaluating gene × psychological risk factor effects in the pathogenesis of anxiety: A new model approach.

Cited by 59 publications

References 71 publications

Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis

Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis

Serotonin Function in Panic Disorder: Important, But Why?

Lack of relationship between CO₂ reactivity and serotonin transporter gene regulatory region polymorphism in panic disorder

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Evaluating gene × psychological risk factor effects in the pathogenesis of anxiety: A new model approach.

Cited by 59 publications

References 71 publications

Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis

Does measurement instrument moderate the association between the serotonin transporter gene and anxiety-related personality traits? A meta-analysis

Serotonin Function in Panic Disorder: Important, But Why?

Lack of relationship between CO2 reactivity and serotonin transporter gene regulatory region polymorphism in panic disorder

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Lack of relationship between CO₂ reactivity and serotonin transporter gene regulatory region polymorphism in panic disorder