The power of sample size and homogenous sampling: association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder.
ABSTRACT Several lines of evidence indicate that abnormalities in the functioning of the central serotonergic system are involved in the pathogenesis of affective illness. A 44-base-pair insertion/deletion polymorphism in the 5' regulatory region of the serotonin transporter gene (5-HTTLPR), which influences expression of the serotonin transporter, has been the focus of intensive research since an initial report on an association between 5-HTTLPR and depression-related personality traits. Consistently replicated evidence for an involvement of this polymorphism in the etiology of mood disorders, particularly in major depressive disorder (MDD), remains scant.
We assessed a potential association between 5-HTTLPR and MDD, using the largest reported sample to date (466 patients, 836 control subjects). Individuals were all of German descent. Patients were systematically recruited from consecutive inpatient admissions. Control subjects were drawn from random lists of the local Census Bureau and screened for psychiatric disorders.
The short allele of 5-HTTLPR was significantly more frequent in patients than in control subjects (45.5% vs. 39.9%; p = .006; odds ratio = 1.26).
These results support an involvement of 5-HTTLPR in the etiology of MDD. They also demonstrate that the detection of small genetic effects requires very large and homogenous samples.
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ABSTRACT: This study provides the first genetic association examination of borderline personality disorder (BPD) traits in children and adolescents (ages 9-15) using two independent samples of youth recruited from the general community. We tested the a priori hypothesis that the serotonin transporter promoter gene (5-HTTLPR) would relate specifically to BPD traits in youth. This association was hypothesized based on prior genetic association research with BPD adults and theory positing that emotion dysregulation may be a core risk process contributing to BPD. Youth provided DNA via buccal cells. Both youth and a parent completed self-report measures assessing youth's BPD traits and depressive symptoms. Results from both Study 1 (N = 242) and an independent replication sample of Study 2 (N = 144) showed that carriers of the short allele of 5-HTTLPR exhibited the highest levels of BPD traits. This relation was observed even after controlling for the substantial co-occurrence between BPD traits and depressive symptoms. This specific association between 5-HTTLPR and BPD traits among youth supports previous genetic associations with adults diagnosed with BPD and provides preliminary support for a developmental extension of etiological risk for BPD among youth.Frontiers in Psychiatry 03/2011; 2:6. DOI:10.3389/fpsyt.2011.00006
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ABSTRACT: INTRODUCTION: The majority of smokers attempt to quit smoking on their own, but in any given year, only 5% or less are successful. To improve cessation rates, tapping social networks for social support during quitting has been recommended or tested in some interventions. Prior reviews of this research, however, have concluded that there is little to no evidence that partner support interventions are effective. DISCUSSION: Given the theoretical importance of the concept of social support, its demonstrated value in treatments that are implicitly supportive (e.g., telephone counseling), and the general lack of a guiding conceptual framework for research on the effects of peer or partner support for cessation, we describe theoretical models that explicitly incorporate social support constructs in predicting motivation for and success in quitting. Conclusion: Better differentiation of support concepts and elucidating causal pathways will lead to studies that demonstrate the value of social relationships in improving smokers' likelihood of cessation.Nicotine & Tobacco Research 07/2010; 12(7):695-707. DOI:10.1093/ntr/ntq077 · 2.81 Impact Factor
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ABSTRACT: Dysbindin (DTNBP1) is a widely studied candidate gene for schizophrenia (SCZ); however, inconsistent results across studies triggered skepticism towards the validity of the findings. In this HapMap-based study, we reappraised the association between Dysbindin and SCZ in a large sample of German ethnicity. Six hundred thirty-four cases with DSM-IV SCZ, 776 controls, and 180 parent-offspring trios were genotyped for 38 Dysbindin SNPs. We also studied two phenotypically-defined subsamples: 147 patients with a positive family history of SCZ (FH-SCZ+) and SCZ patients characterized for cognitive performance with Trail-Making Tests A and B (TMT-A: n=219; TMT-B: n=247). Given previous evidence of gene-gene interactions in SCZ involving the COMT gene, we also assessed epistatic interactions between Dysbindin markers and 14 SNPs in COMT. No association was detected between Dysbindin markers and SCZ, or in the FH-SCZ+ subgroup. Only one marker (rs1047631, previously reported to be part of a risk haplotype), showed a nominally significant association with performance on TMT-A and TMT-B; these findings did not remain significant after correction for multiple comparisons. Similarly, no pair-wise epistatic interactions between Dysbindin and COMT markers remained significant after correction for 504 pair-wise comparisons. Our results, based on one of the largest samples of European Caucasians and using narrowly-defined criteria for SCZ, do not support the etiological involvement of Dysbindin markers in SCZ. Larger samples may be needed in order to unravel Dysbindin's possible role in the genetic basis of proposed intermediate phenotypes of SCZ or to detect epistatic interactions.Schizophrenia Research 05/2010; 118(1-3):98-105. DOI:10.1016/j.schres.2009.12.025 · 4.43 Impact Factor