title: A Cys 23-Ser 23 substitution in the 5-HT(2C) receptor gene influences body weight regulation in females with seasonal affective disorder: an Austrian-Canadian collaborative study.
abstract: Most females with seasonal affective disorder (SAD) exhibit atypical vegetative symptoms such as overeating, and weight gain when depressed. The serotonin 2C receptor (5-HT(2C)) plays a key role in control of appetite and satiety. A 5-HT(2C) Cys 23 Ser substitution, coded for by a single nucleotide polymorphism (Cys 23 Ser) within the 5-HT(2C) gene, has been shown to influence 5-HT(2C) function. We hypothesized that Cys 23 Ser influences weight regulation in females with SAD. Two independent samples from Austria (162 females with SAD, 119 controls), and Canada (90 females with SAD, 42 controls) were genotyped for Cys 23 Ser. Influence on weight regulation was analyzed within patients with atypical features. In Austrians, genotype distribution differed between patients and controls (p=0.044) and Cys 23 Ser was associated with weight (p=0.039), body mass index (BMI; p=0.038), and seasonal appetite change (p=0.031). All values were highest in Cys/Cys, intermediate in Cys/Ser, and lowest in Ser/Ser carriers. In Canadian patients, Cys 23 Ser was associated with minimum lifetime BMI (p=0.046), with lowest values in Ser/Ser carriers. Our data provide evidence that Cys 23 Ser mediates severity of weight regulation disturbances in females with SAD, and the gene-dose effect-like differences suggest a direct functional role of Cys 23 Ser in the behavioral regulation of body weight.
authors.affiliation: Department of General Psychiatry, Medical University of Vienna, Austria. nicole.praschak-reider@meduniwien.ac.at
authors.forename: Nicole
authors.initials: N
authors.lastname: Praschak-Rieder
authors.forename: Matthäus
authors.initials: M
authors.lastname: Willeit
authors.forename: Peter
authors.initials: P
authors.lastname: Zill
authors.forename: Dietmar
authors.initials: D
authors.lastname: Winkler
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Thierry
authors.forename: Anastasios
authors.initials: A
authors.lastname: Konstantinidis
authors.forename: Mario
authors.initials: M
authors.lastname: Masellis
authors.forename: Vincenzo S
authors.initials: VS
authors.lastname: Basile
authors.forename: Brigitta
authors.initials: B
authors.lastname: Bondy
authors.forename: Manfred
authors.initials: M
authors.lastname: Ackenheil
authors.forename: Alexander
authors.initials: A
authors.lastname: Neumeister
authors.forename: Allan S
authors.initials: AS
authors.lastname: Kaplan
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kasper
authors.forename: Robert
authors.initials: R
authors.lastname: Levitan
mesh_terms: D000328:Adult; D001066:Appetite; D015992:Body Mass Index; D001835:Body Weight; D016022:Case-Control Studies; D005260:Female; D018628:Gene Dosage; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D012527:Satiation; D016574:Seasonal Affective Disorder / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D015430:Weight Gain
chemical_list: D044405:Receptor, Serotonin, 5-HT2C