Glutamatergic Dysfunction in OCD

Abstract

The role of glutamatergic dysfunction in the pathophysiology of OCD has hardly been explored despite recent reports implicating glutamatergic dysfunction in OCD. We decided to investigate CSF glutamate levels in adult OCD probands compared to psychiatrically normal controls. In total, 21 consenting psychotropic drug-naïve adult OCD patients, diagnosed using SCID-IV-CV, and 18 consenting psychiatrically normal controls with age within 10 years of age of the patients, who did not have any history of head injury or neurological illness, were included into the study. Aseptically collected and stored CSF samples obtained from the patients and control subjects were used for glutamate estimation, which was carried out by a modification of the procedure described by Lund (1986). CSF glutamate (mmol/l) level was found to be significantly higher [F(1,31) ¼ 6.846, p ¼ 0.014] in OCD patients (47.1274.25) compared to control subjects (41.3673.63) on analysis of covariance. There was no effect of gender, age, duration of illness, Y-BOCS score, or CGI-S score on CSF glutamate levels. Our study provides preliminary evidence implicating glutamatergic excess in the pathophysiology of OCD, which needs to be further explored by studies from other centers involving larger sample sets from different age groups.

Sapap3 and pathological grooming in humans: Results from the OCD collaborative genetics study

“…Given the prominence of glutamatergic neurotransmission in the ''OCD circuit'' [Graybiel and Rauch, 2000;Saxena and Rauch, 2000;Aouizerate et al, 2004;Swedo and Snider, 2004], glutamate has been receiving increasing attention in the OCD literature [Rosenberg et al, 2000;Chakrabarty et al, 2005;Coric et al, 2005;Pittenger et al, 2006]. At least two other genes affecting glutamatergic neurotransmission appear associated with OCD, SLC1A1 [Arnold et al, 2006;Dickel et al, 2006;Stewart et al, 2007] and, more preliminarily, GRIN2B [Arnold et al, 2004].…”

Glutamate-modulating drugs as novel pharmacotherapeutic agents in the treatment of obsessive-compulsive disorder

“…Chakrabarty et al 97 examined the CSF of 21 drug-naive OCD patients and 18 control subjects, and found CSF glutamate levels to be significantly elevated in those subjects with OCD. This study requires replication with a larger number of patients, but it supports the MRS data in suggesting glutamatergic dysfunction as an important component of the pathophysiology of OCD.…”

“…127 Because cortico-striatal projections are predominantly glutamatergic, excess striatal glutamate in OCD may simply be a byproduct of increased firing of coritco-striatal projection neurons. If this is the case, then increased Glx measurement in MRS studies 87 and increased glutamate in the CSF of OCD patients 97 may simply be a surrogate marker for excessive firing of these projection neurons; and the observed normalization of Glx levels by MRS with treatment 87 may similarly be equivalent to the normalization of hyperactive brain regions when OCD symptoms are treated. 127 Few data exist to evaluate this possibility.…”

Estudos de associação genética no transtorno obsessivo-compulsivo

“…Abnormal levels of glutamate have been reported in OCD patients, predominantly in prefrontal regions such as the orbitofrontal cortex and its projection areas in the striatum [59][60][61] . Glutamate levels in the CSF were also significantly higher in patients with OCD compared to controls (p = 0.014) 62 . Drugs that modulate glutamate have been recently used as boosters of pharmacological treatment of OCD in adults 63,64 , adolescents and children 65 .…”