title: No association of endocannabinoid genes with bipolar disorder or lithium response in a Sardinian sample.
abstract: Bipolar disorder (BD) is a chronic and severe psychiatric condition with an underlying component of genetic susceptibility. Mounting evidence suggests a potential role of the endogenous cannabinoid (eCB) system in the pathogenesis of BD. Here we investigated the role of genes encoding for key eCB elements on the risk of developing BD in a sample of 357BD patients and 422 healthy controls of Sardinian ancestry. Using the HapMap CEU population SNP database, we selected 25 tag Single Nucleotide Polymorphisms (tSNPs) in N-acyl phosphatidylethanolamine phospholipase D (NAPE-PLD), cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes. No significant association was reported for FAAH or CNR1. SNPs rs11487077 and rs6465903 in NAPE-PLD showed nominal association (p=0.033 and p=0.026, respectively) with BD, not significant after permutation testing. These SNPs were also tested for association with lithium response in 204 BD patients characterized for response to long-term lithium treatment, reporting no significant findings. As a whole, our results do not support a clear role of FAAH, CNR1 and NAPE-PLD in BD and lithium response. Additional studies on independent, larger samples are warranted to further explore the involvement of the eCB system in BD.
authors.affiliation: Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Pisanu
authors.forename: Donatella
authors.initials: D
authors.lastname: Congiu
authors.forename: Marta
authors.initials: M
authors.lastname: Costa
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Sestu
authors.forename: Caterina
authors.initials: C
authors.lastname: Chillotti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Ardau
authors.forename: Valeria
authors.initials: V
authors.lastname: Deiana
authors.forename: Mirko
authors.initials: M
authors.lastname: Manchia
authors.forename: Alessio
authors.initials: A
authors.lastname: Squassina
authors.forename: Maria
authors.initials: M
authors.lastname: Del Zompo
mesh_terms: D000328:Adult; D000581:Amidohydrolases / Q000235:genetics*; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000523:psychology; D063388:Endocannabinoids / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008094:Lithium / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010739:Phospholipase D / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics*; D016896:Treatment Outcome; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D014150:Antipsychotic Agents; D063388:Endocannabinoids; D008094:Lithium; D010739:Phospholipase D; D043884:Receptor, Cannabinoid, CB1; D000099252:Fatty Acid Amide Hydrolases; C571130:CNR1 protein, human; C581518:NAPEPLD protein, human
keywords: Association study; Bipolar; Lithium treatment; NAPE-PLD, FAAH, CNR1; Pharmacogenetics