Original Article

The Pharmacogenomics Journal (2005) 5, 135–141. doi:10.1038/sj.tpj.6500301 Published online 25 January 2005

Depression in Parkinson's disease is related to a genetic polymorphism of the cannabinoid receptor gene (CNR1)

F J Barrero1, I Ampuero2, B Morales1, F Vives3, J de Dios Luna del Castillo4, J Hoenicka2 and J García Yébenes2,5

  1. 1Movement Diseases Unit, University Hospital of San Cecilio, Granada, Spain
  2. 2Banco de Tejidos para Investigaciones Neurológicas, Facultad de Medicina, Universidad Complutense de Madrid, Spain
  3. 3Department of Physiology, Faculty of Medicine, University of Granada, Spain
  4. 4Department of Biostatistics, Faculty of Medicine, University of Granada, Spain
  5. 5Department of Neurology, Foundation Jiménez Díaz, Madrid, Spain

Correspondence: Dr B Morales, Movement Diseases Unit, University Hospital of San Cecilio. Avda. Madrid s/n, Granada 18012, Spain. Fax: +34 958023356; E-mail: blasmorales@saludalia.com

Received 29 April 2004; Revised 22 September 2004; Accepted 19 October 2004; Published online 25 January 2005.



Depression is a common symptom in Parkinson's disease (PD) and it is present in up to 40% of the patients. The cause of depression in PD is thought to be related to disturbance of monoamine neurotransmission. The endogenous cannabinoid system mediates different brain processes that play a role in the control of behaviour and emotions. Cannabinoid function may be altered in neuropsychiatry diseases, directly or through interactions with monoamine, GABA and glutamate systems. For this reason, we have investigated whether there is a genetic risk factor for depression in PD linked to the polymorphisms of CB1 receptor gene. Depression was more frequent in patients with PD than in controls with osteoarthritis. The presence of depression did not correlate with the stage of the disease but it was more frequent in patients with pure akinetic syndrome than in those with tremoric or mixed type PD. The CB1 receptor gene polymorphism (AAT)n is considered to modify the transcription of the gene and, therefore, it may have functional relevance. We analysed the length of the polymorphic triplet (AAT)n of the gene that encodes CB1 (CNR1) receptor in 89 subjects (48 PD patients and 41 controls). In patients with PD, the presence of two long alleles, with more than 16 repeated AAT trinucleotides in the CNR1 gene, was associated with a reduced prevalence of depression (Fisher's exact test: P=0.003). This association did not reach significant differences in the control group, but the number of control individuals with depression was too small to allow for statistical analysis. Since the alleles with long expansions may have functional impact in cannabinoid neurotransmission, our data suggest that the pharmacological manipulation of cannabinoid neurotransmission could open a new therapeutic approach for the treatment of depression in PD and possibly in other conditions.


CNR1, depression, Parkinson's disease, polymorphisms, cannabinoid system