The associative and limbic thalamus in the pathophysiology of obsessive-compulsive disorder: An experimental study in the monkey
Transl Psychiatry. 2012-09-01; 2(9): e161-e161
DOI: 10.1038/tp.2012.88
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1. Transl Psychiatry. 2012 Sep 25;2:e161. doi: 10.1038/tp.2012.88.
The associative and limbic thalamus in the pathophysiology of
obsessive-compulsive disorder: an experimental study in the monkey.
Rotge JY(1), Aouizerate B, Amestoy V, Lambrecq V, Langbour N, Nguyen TH, Dovero
S, Cardoit L, Tignol J, Bioulac B, Burbaud P, Guehl D.
Author information:
(1)Univ Bordeaux, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux,
France.
Obsessive-compulsive disorder (OCD) is a frequent psychiatric disorder
characterized by repetitive intrusive thoughts and severe anxiety, leading to
compulsive behaviors. Although medical treatment is effective in most cases,
resistance is observed in about 30% of patients. In this context, deep brain
stimulation (DBS) of the caudate or subthalamic nuclei has been recently proposed
with encouraging results. However, some patients were unimproved or exhibited
awkward side effects. Therefore, exploration of new targets for DBS remains
critical in OCD. In the latter, functional imaging studies revealed overactivity
in the limbic and associative cortico-subcortical loops encompassing the
thalamus. However, the role of the thalamus in the genesis of repetitive
behaviors and related anxiety is unknown. Here, we tested the hypothesis that
pharmacological-induced overactivity of the medial thalamus could give rise to
abnormal behaviors close to that observed in OCD. We modulated the ventral
anterior (VA) and medial dorsal (MD) nuclei activity by in situ bicuculline
(GABA(A) antagonist) microinjections in subhuman primates and assessed their
pharmacological-induced behavior. Bicuculline injections within the VA caused
significant repetitive and time-consuming motor acts whereas those performed
within the MD induced symptoms of dysautonomic dysregulation along with abnormal
vocalizations and marked motor hypoactivity. These findings suggest that
overactivation of the VA and MD nuclei of the thalamus provokes compulsive-like
behaviors and neurovegetative manifestations usually associated with the feeling
of anxiety in OCD patients. In further research, this translational approach
should allow us to test the effectiveness and side effects of these thalamic
nuclei DBS in monkey and perhaps, in a second step, to propose a transfer of this
technique to severely disabled OCD patients.
DOI: 10.1038/tp.2012.88
PMCID: PMC3565210
PMID: 23010765 [Indexed for MEDLINE]