The power of sample size and homogenous sampling: association between the 5-HTTLPR serotonin transporter polymorphism and major depressive disorder. Biol Psychiatry

Department of Psychiatry, University of Bonn, Germany.
Biological Psychiatry (Impact Factor: 10.25). 03/2005; 57(3):247-51. DOI: 10.1016/j.biopsych.2004.11.027
Source: PubMed

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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    • "In our study, we only included cases that followed all the inclusion requirements, and cases with any deviation from our criteria were excluded. The excluded papers included 13 studies that were not for geriatric depression [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19], 3 brief reports or reviews [20] [21] [22] and 1 that is on Alzheimer's disease related depression [23]. We also excluded 3 studies that contained cases of unclear diagnosis of depression [24] [25] [26]. "
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    ABSTRACT: Serotonin-transporter-linked promoter region (5-HTTLPR) polymorphism is the genetic variant coding for the serotonin transporter and may play an important role in the etiology of depression. However, genetic studies examining the relationship between 5-HTTLPR polymorphism and geriatric depression have produced inconsistent results. We conducted a meta-analysis to compare the frequency of 5-HTTLPR variants in geriatric depression cases and non-depressed controls in the elderly. A total of 5 studies involving 579 geriatric cases and 1372 non-depressed controls met the inclusion criteria. With strong statistical power, pooled odds ratios (ORs) and 95% confidence intervals (CIs) for genotypic analyses (S carrier versus L/L, S/S versus L/L) were provided. The results of our analysis indicate statistically significant association between S allele and the risk of geriatric depression (OR ScarriervsS/S=1.29, 95% CI 1.01-1.66; OR S/SvsL/L=1.68, 95% CI 1.20-2.35). Our findings suggest that 5-HTTLPR polymorphism is of importance in the development of geriatric depression.
    Neuroscience Letters 07/2014; 578. DOI:10.1016/j.neulet.2014.06.046 · 2.06 Impact Factor
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    • "(s), The s allele is associated with decreased transcriptional efficiency leading to reduced reuptake of serotonin in the pre-synaptic neuron (Lesch et al., 1996; Canli and Lesch, 2007). One or two copies of the s allele have been associated with a BPD diagnosis in adults (Ni et al., 2006; Lis et al., 2007) as well as BPD features among adults, such as emotional lability (Frankle et al., 2005; Hoefgen et al., 2005) and greater sensitivity to emotional stimuli (Beevers et al., 2009a,b; Caspi et al., 2010). For example, 5-HTTLPR is associated with amygdala activation in response to emotional faces (Hariri et al., 2005), and BPD adults exhibit dysregulated amygdala activity (Donegan et al., 2003; Ebner-Priemer et al., 2005). "
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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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    • "Genetic polymorphisms may also potentially identify individuals who are especially likely to benefit from socially supportive interactions during quitting compared with others. One possibility is a variant of the 5-HTTLPR genotype that is associated with both smoking cessation (Munafo, Clark, Johnstone, Murphy, & Walton, 2004) and vulnerability to depression in response to stressors (Hoefgen et al., 2005; Jacobs et al., 2006; Otte, McCaffery, Ali, & Whooley, 2007; Zalsman et al., 2006). There is also evidence, however, that social support for these individuals is particularly beneficial (Kaufman et al., 2004). "
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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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