Assessment of glutamate in striatal subregions in obsessive-compulsive disorder with proton magnetic resonance spectroscopy

Abstract

Glutamatergic signaling abnormalities in cortico-striatal circuits are hypothesized to lead to the repetitive thoughts and behaviors of obsessive-compulsive disorder (OCD). To test this hypothesis, studies have used proton magnetic resonance spectroscopy (1H MRS) to measure glutamatergic compounds in the striatum of individuals with OCD. However, none has used methods that could measure glutamate minimally contaminated by glutamine and γ-aminobutyric acid (GABA) in striatal subregions. Therefore, in this study, a proton MRS imaging (1H MRSI) technique with relatively high spatial resolution at 3.0 T was used to measure minimally contaminated glutamate levels in three striatal subregions (i.e., dorsal caudate, dorsal putamen, and ventral striatum) in 15 unmedicated adults with OCD and 16 matched healthy control subjects. No significant group differences in glutamate levels were found in any of the three striatal subregions. In contrast, a study in unmedicated pediatric OCD patients that measured glutamatergic compounds in the dorsal caudate by MRS at 1.5T found significant elevations. Further studies are warranted to assess whether these discrepant MRS findings are due to differences in subject age or MRS methodology, or potentially are associated with glutamatergic gene variants implicated in OCD.

Striatal Magnetic Resonance Spectroscopy Abnormalities in Young Adult Sapap3 Knockout Mice

“…This apparent discrepancy could be related to species, methodological, genetics, or other differences. However, our null finding in SAPAP3 KO mice is consistent with a recent report in medication-free adults with OCD using optimized striatal glutamate detection methods (61). As noted above, striatal glutamate abnormalities may become apparent in older SAPAP3 KO mice, especially after the onset of severe compulsive grooming.…”

“…While a number of striatal MRS studies in people with OCRD have been published (see 34 for review; and 61, 88–92), none reported on lactate or GSH levels. This is due in part to the fact that MRS scan sequences used previously in humans were not optimal for quantifying these metabolites in striatum.…”

Toward identifying reproducible brain signatures of obsessive-compulsive profiles: rationale and methods for a new global initiative

“…Specifically, patients differ from one another both in the specific content of their OCD symptoms and in many other clinical features, including symptom severity, age of onset, course of illness, degree of insight, comorbidity, family history, and degree of functional impairment [61][62][63][64]. Some have reported that this variation in clinical presentation is reflected in different brain abnormalities [10,27,62,[65][66][67][68]. However, other differences in disease expression may be better explained by specific environmental and cultural factors.…”

Role of Glutamatergic System in Obsessive-Compulsive Disorder with Possible Therapeutic Implications

“…The authors interpret this finding as a demonstration of the interaction between serotonin and glutamate pathways in OCD pathology. Conversely, Simpson et al [37] reported no significant differences in glutamate levels in any of the 3 striatal regions (dorsal caudate, dorsal putamen, and ventral striatum) between OCD patients and matched healthy control subjects. It is noteworthy that the authors found negative results using a 1H-MRS imaging technique with a relatively high spatial resolution at 3.0 T, while MRS at 1.5 T in another study revealed significant elevations in glutamatergic compounds.…”

“…It is noteworthy that the authors found negative results using a 1H-MRS imaging technique with a relatively high spatial resolution at 3.0 T, while MRS at 1.5 T in another study revealed significant elevations in glutamatergic compounds. Therefore, at least some of these contradicting findings might be caused by differences in methodology [37].…”