Decrease in Caudate Glutamatergic Concentrations in Pediatric Obsessive-Compulsive Disorder Patients Taking Paroxetine

Rosenberg, David; MacMaster, Frank P.; Keshavan, Matcheri S.; Fitzgerald, Kate D.; Stewart, Carol M.; Moore, Gregory J.

doi:10.1097/00004583-200009000-00008

Cited by 347 publications

(241 citation statements)

References 27 publications

Supporting

Mentioning

222

Contrasting

Unclassified

Order By: Relevance

“…The findings of our study that glutamatergic dysfunction is related to the pathophysiology of OCD has been supported also by findings from animal studies, in addition to the MRS-imaging studies in pediatric OCD (Moore et al, 1998;Rosenberg et al, 2000;Bolton et al, 2001). McGrath et al (2000) have shown that MK-801, a noncompetitive NMDA receptor antagonist that indirectly stimulates cortical-limbic glutamate output, aggravated a transgenedependent abnormal behavior (repetitive climbing and leaping) in a transgenic mouse model of comorbid Tourette's syndrome and OCD, at doses insufficient to induce stereotypies, and more readily induced stereotypies and limbic seizure behaviours at higher doses.…”

Section: Discussionsupporting

confidence: 83%

“…In one of the first reports implicating glutamatergic dysfunction in OCD, Moore et al (1998) reported striking changes in caudate glutamate resonance on proton magnetic resonance spectroscopy (1H-MRS) in a 9-year-old boy with OCD following 12 weeks of paroxetine treatment. Subsequently, Rosenberg et al (2000) studied 11 psychotropic drug-naïve children (8-17 years) with OCD, with single-voxel 1H-MRS examinations and demonstrated that caudate glutamate concentrations were significantly greater in the patients compared to healthy controls. They also found that the caudate glutamate levels in patients decreased significantly following 12-weeks treatment with paroxetine to levels comparable to that of controls and the decrease was associated with decrease in symptom severity of the OCD patients.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glutamatergic Dysfunction in OCD

Chakrabarty

Bhattacharyya

Christopher

et al. 2005

Neuropsychopharmacol

311

191

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Glutamatergic Dysfunction in OCD

Chakrabarty

Bhattacharyya

Christopher

et al. 2005

Neuropsychopharmacol

311

191

View full text Add to dashboard Cite

show abstract

“…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].…”

Section: Discussionmentioning

confidence: 99%

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

Bienvenu

Wang

Shugart

et al. 2009

American J of Med Genetics Pt B

192

130

View full text Add to dashboard Cite

SAP90/PSD95-associated protein (SAPAP) family proteins are post-synaptic density (PSD) components that interact with other proteins to form a key scaffolding complex at excitatory (glutamatergic) synapses. A recent study found that mice with a deletion of the Sapap3 gene groomed themselves excessively, exhibited increased anxiety-like behaviors, and had corticostriatal synaptic defects, all of which were preventable with lentiviral-mediated expression of Sapap3 in the striatum; the behavioral abnormalities were also reversible with fluoxetine. In the current study, we sought to determine whether variation within the human Sapap3 gene was associated with grooming disorders (GDs: pathologic nail biting, pathologic skin picking, and/or trichotillomania) and/or obsessive-compulsive disorder (OCD) in 383 families thoroughly phenotyped for OCD genetic studies. We conducted family-based association analyses using the FBAT and GenAssoc statistical packages. Thirty-two percent of the 1,618 participants met criteria for a GD, and 65% met criteria for OCD. Four of six SNPs were nominally associated (P < 0.05) with at least one GD (genotypic relative risks: 1.6-3.3), and all three haplotypes were nominally associated with at least one GD (permuted P < 0.05). None of the SNPs or haplotypes were significantly associated with OCD itself. We conclude that Sapap3 is a promising functional candidate gene for human GDs, though further work is necessary to confirm this preliminary evidence of association.

show abstract

“…Interestingly, this elevation in Glx has been shown to normalize in OCD subjects who respond to treatment with SRI medications. 88,89 In contrast, the same group recently found decreased Glx levels in the anterior cingulated in subjects with OCD. 90 As these authors point out, the combined finding of reduced anterior cingulate Glx concentrations and increased caudate Glx parallels prior studies demonstrating an inverse relationship between anterior cingulate and basal ganglia volume in patients with OCD.…”

Section: Magnetic Resonance Spectroscopy (Mrs) Measurements Of Glutammentioning

confidence: 92%

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

Pittenger

Krystal

Coric

2006

NeuroRX

195

128

View full text Add to dashboard Cite

Summary:Obsessive-compulsive disorder (OCD) is a common psychiatric disorder that produces significant morbidity. The introduction of serotonin reuptake inhibitors in the 1980s represented an important advance in the treatment of OCD. However, few patients show complete remission of their symptoms, and some patients show minimal improvement with existing treatments. We review current treatment strategies and initial data supporting the efficacy of glutamate modulating agents as a novel class of pharmaceuticals for the treatment of OCD. Functional neuroimaging studies repeatedly reported metabolic hyperactivity in the cortico-striato-thalamo-cortical circuitry in patients with OCD. Recent magnetic resonance spectroscopy studies provide evidence of elevated glutamate levels in several brain regions in patients suffering from OCD.These findings raised the possibility that agents that reduce glutamate hyperactivity or its consequences in the CNS might be efficacious as novel therapeutic interventions. Indeed, initial evidence from our group suggests that the antiglutamatergic agent riluzole (Rilutek), which was developed for the treatment of amyotrophic lateral sclerosis, is effective in treatment-resistant OCD. Case reports suggest that other agents that modulate glutamatergic activity may likewise be effective. This new application of glutamate modulating agents holds promise for the treatment of this disabling and often inadequately treated disease.

show abstract

Decrease in Caudate Glutamatergic Concentrations in Pediatric Obsessive-Compulsive Disorder Patients Taking Paroxetine

Cited by 347 publications

References 27 publications

Glutamatergic Dysfunction in OCD

Glutamatergic Dysfunction in OCD

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

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

Contact Info

Product

Resources

About