مشارکت سیستم سروتونین برای صفات اضطراب و افسردگی که ممکن است تا حدی مسئول برای تنوع نمونه بولیمیا باشد
|کد مقاله||سال انتشار||مقاله انگلیسی||ترجمه فارسی||تعداد کلمات|
|32520||2008||8 صفحه PDF||سفارش دهید||5608 کلمه|
Publisher : Elsevier - Science Direct (الزویر - ساینس دایرکت)
Journal : Journal of Psychiatric Research, Volume 42, Issue 1, January 2008, Pages 50–57
Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric phenotypes influenced by both genetic and environmental factors. We investigated the genetic contribution of four single nucleotide polymorphisms (SNPs) within the serotonin receptor 5HT2C and two sequence variants within the serotonin transporter SLC6A4 to different ED-related psychopathological symptoms in a total sample of 82 ED patients. All patients were diagnosed according to DSM-IV criteria and underwent diagnostic and psychopathological assessments by means of structured clinical interviews and rating scales. We detected significant evidence of association between the −995A/−759T/−697C/Cys23 haplotype of the 5HT2C gene and different anxious and depressive subscales of the SCL90-R instrument, that included Somatization (p = 0.029), Obsessive-Compulsiveness (p = 0.021), Depression (p = 0.032), Anxiety (p = 0.004), Hostility (p = 0.028), Phobic Anxiety (p = 0.029) and Paranoid Ideation (p = 0.008), in BN patients. We also observed a strong association between the 5HTTLPR polymorphism of the SLC6A4 gene and Anxiety in the same group of BN patients (p = 0.004). However, no epistatic effects between the 5HT2C and SLC6A4 genes on the different anxious and depressive subscales were observed. Our preliminary data suggest that the serotoninergic system contributes to the different psychopathological symptoms that may be partially responsible for the phenotypical variability within the bulimic phenotype.
Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric phenotypes influenced by both genetic and environmental factors (Fairburn and Harrison, 2003). It has been reported a high comorbidity between ED and Axis I or Axis II disorders, such as affective disorders, personality disorders, anxiety disorders, impulse control disorders and substances abuse (Bulik et al., 2004, Fernández-Aranda et al., in press-a, Godart et al., 2000, Grilo et al., 2003, Kaye et al., 2004, Milos et al., 2004, Solano et al., 2005 and Steiger et al., 2005). Different lines of investigation show that certain ED-related personality and psychopathological traits persist after normalization of body weight. These traits are known to be heritable and may be partially responsible for the genetically driven phenotypical variability within the different ED categories and could influence susceptibility to AN and BN (Augestad et al., 1999, Bean et al., 2005, Blonigen et al., 2005, Cassin and von Ranson, 2005, Fassino et al., 2002, Lilenfeld et al., 2005 and Reba et al., 2005). Genes involved in the serotoninergic system, such as the serotonin receptor 5HT2C and the serotonin transporter SLC6A4, are good candidates for their involvement in some of the phenotypical traits postulated to underlie ED, such as anxiety, hostility, depression, aggressiveness and impulsivity ( Fernández-Aranda et al., in press-b, Frankle et al., 2005, Lesch et al., 1996, Nonogaki et al., 1998, Tsai et al., 2002 and Willis-Owen et al., 2005). The 5HT2C gene maps to human chromosome Xq24, is widely expressed throughout the central nervous system, including the hypothalamus nuclei that control body weight, and its disruption causes obesity and hyperphagia in the 5ht2c (−/−) knock-out mice ( Milatovich et al., 1992, Nonogaki et al., 1998 and Tecott et al., 1995). Together with the 5HT2C receptor, the serotonin transporter 5HTT, which is encoded by a single gene (SLC6A4) on human chromosome 17q12, is essential for the serotoninergic activity by regulating the magnitude and duration of serotoninergic responses ( Blakely et al., 1991). Different studies have shown a strong association between 5HT2C and SLC6A4 and different anxiety-related personality traits using different inventories ( Ebstein et al., 1997, Kuhn et al., 1999, Lesch et al., 1996, Melke et al., 2001 and Munafo et al., 2005). Based on these investigations we hypothesized that psychopathological traits associated to ED are substantially influenced by alterations in the serotonin pathways. To test this hypothesis, we have examined the involvement of the 5HT2C and SLC6A4 genes in the psychopathological symptomatology measured by the SCL90-revised questionnaire (SCL90-R) in a total sample of 82 patients with ED.