Association study between the dopamine receptor D 4 gene and obsessive-compulsive disorder Beatriz Camarena a , Cristina Loyzaga a , Alejandro Aguilar a , Karen Weissbecker b , Humberto Nicolini c,d, ⁎ a Department of Psychiatric Genetics, National Institute of Psychiatry Ramón de la Fuente, Mexico D.F., 14370, Mexico b Tulane University Health Science Center, New Orleans, LA 70115, United States c Carracci Medical Group, Mexico, D.F., 13740, Mexico d Universidad Autónoma de la Ciudad de México, Mexico, D.F., 13740, Mexico Received 23 June 2005; received in revised form 18 April 2006; accepted 8 August 2006 Abstract Pharmacological and neuroanatomical evidence suggest the involvement of the dopaminergic system in obsessive–compulsive disorder (OCD). Analysis of the 48-bp dopamine receptor D 4 (DRD4) gene polymorphism in a sample of 210 OCD patients and 202 healthy control subjects showed a significant association (χ 2 = 27.5, df =6, p =0.0003). This difference was attributable to a lower frequency of allele 4R in OCD patients compared with the control group (χ 2 = 9.33, p =0.0027). However, we did not replicate previous findings of an association between the 7R allele and OCD patients with tics. Finally, we analyzed a sub-sample of 86 OCD families. E-TDT analysis in 70 informative parents did not confirm the association observed in our case–control analysis. In conclusion, the current study cannot exclude an association between DRD4 gene and OCD in the largest sample analyzed. However, further studies will be required to confirm if the DRD4 gene is involved in the pathogenesis of this disorder. © 2006 Elsevier B.V. and ECNP. All rights reserved. KEYWORDS OCD; Dopamine D 4 receptor gene; Gender; Tics 1. Introduction Obsessive–compulsive disorder (OCD) is an anxiety disorder with a lifetime prevalence of 2% to 3%. Pharmacological studies have reported that a dopaminergic antagonist in combination with selective serotonin reuptake inhibitors has proved effective treatment for resistant OCD patients, suggesting that serotoninergic and dopaminergic systems are involved in the pathophysiology of this disorder (Denys et al., 2004b). Also, a modulation has been reported between both systems in regions of the fronto-thalamo- basal ganglia circuitry areas implicated in OCD (Di Giovanni et al., 2000; Smith et al., 1997). Additional evidence for the role of the dopamine system in OCD comes from clinical data. In particular, an association between the presence of OCD symptoms and basal ganglia neuropathology has been reported (Stahl, 1988). In addition, a down-regulated dopamine D 2 receptor binding was observed in the left caudate nucleus of patients with OCD compared with healthy subjects (Denys et al., 2004a). Animal studies have demonstrated that the use of dopaminergic agents induces stereotypic behaviors that are reminiscent of some OCD symptoms (Szechtman et al., 1998; ⁎ Corresponding author. Carracci Medical Group, Carracci 107, Insurgentes Extremadura, México D.F.,13740, Mexico. Tel./fax: +52 55 5611 3028. E-mail address: nicolini _ humberto@yahoo.com (H. Nicolini). 0924-977X/$ - see front matter © 2006 Elsevier B.V. and ECNP. All rights reserved. doi:10.1016/j.euroneuro.2006.08.001 www.elsevier.com/locate/euroneuro European Neuropsychopharmacology (2007) 17, 406–409