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: 10.26). 03/2005; 57(3):247-51. DOI: 10.1016/j.biopsych.2004.11.027
Source: PubMed


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 · 2.03 Impact Factor
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    • "The genotype frequency of 5-HTTLPR differs significantly between Caucasians and Asians. Studies in Caucasian populations have shown that the short allele is the risk allele for mood-related disorders (Caspi et al., 2003; Hoefgen et al., 2005; Kiyohara and Yoshimasu, 2010; Osher et al., 2000; Smeraldi et al., 1998), but it trends to have the opposite association in Asian populations (Kim et al., 2000, 2006; Yoshida et al., 2002; Zhang et al., 2009). In a behavioral and multimodal neuroimaging study of a large group (n = 233) of healthy Han Chinese participants , Long et al. found that long-allele carriers have higher anxiety scores, and reduced functional and anatomical connectivity in the prefrontal-amygdala circuit, which correlated with anxiety or depression scores (Long et al., 2013). "
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    Neuroscience & Biobehavioral Reviews 10/2013; 37(10). DOI:10.1016/j.neubiorev.2013.10.004 · 8.80 Impact Factor
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    • "Clear evidence indicates a mutual predisposition; for example, biologically based MDD is predicted nearly equally by the presence of familial MDD or FM. This mutual predisposition is likely due to a combination of genetic and environmental factors [12, 19, 78–82]. These predisposed individuals are particularly vulnerable to a precipitating event that triggers FM or MDD. "
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