PubMed · 2017 · 27 citations · 48 references
Life SciencesGeneticsNeuroscienceMolecular NeuroscienceNeurogeneticsNeuropsychiatryGlutamatergic SignalingNeuropsychiatric GeneticsNeurotransmissionObsessive-compulsive DisordersPsychiatric GeneticsSynaptic TransmissionGlutamate NeurotransmissionGlutamate Signaling PathwaysGlutamatergic DysfunctionGlutamatergic NeurotransmissionGlutamatergic Synaptic DysfunctionNeurotransmission DisruptionObsessive-compulsive Disorder GeneticsThalamocortical Glutamatergic Signaling
OBJECTIVE: Obsessive-compulsive disorder (OCD) is common and debilitating with patients exhibiting persistent intrusive thoughts (obsessions), repetitive ritualistic behaviours (compulsions) and anxiety. While it is known that OCD is highly heritable, the specific genetic risk factors for OCD are still largely unknown. The etiology of OCD has also not been fully elucidated but there is growing evidence that glutamate signaling dysfunction in the cortico-striatal-thalamo-cortical (CSTC) circuitry plays a role in its pathogenesis. METHODS: We conducted a focused review of recent literature on the role of glutamate genes in OCD. RESULTS: There have been several recent discoveries in the SAPAP (DLGAP) family, SLC1A1, and GRIN/GRIK families of proteins related to OCD. CONCLUSION: There is growing evidence supporting a role for genetic variation leading to dysfunctional glutamate signaling in OCD. Based on this new evidence we hypothesize that sustained glutamatergic neurotransmission in key areas of the brain may be contributing to the etiology of OCD.
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Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice
Jeffrey M. Welch, Jing Lü, Ramona M. Rodriguiz et al. · Nature · 2007 · 856 citations · Full text