Reduced Anterior Cingulate Glutamatergic Concentrations in Childhood OCD and Major Depression Versus Healthy Controls

Rosenberg, David; Mirza, Yousha; Russell, Aileen; Tang, Jennifer; Smith, Janet; Banerjee, Sube; Bhandari, Rashmi; Rose, Michelle; Ivey, Jennifer; Boyd, Courtney; Moore, Gregory J.

doi:10.1097/01.chi.0000132812.44664.2d

Cited by 216 publications

(206 citation statements)

References 50 publications

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“…To our knowledge, this is the first time that MPFC GABA abnormalities in OCD have been reported. Our finding that OCD adults (ages 20-52) did not differ from healthy controls in MPFC Glx levels is in contrast to the findings of Rosenberg et al (2004). They found significant decreases (B15%) in Glx levels (using a 1.5 T MR system) in pediatric OCD patients (ages 7-19) in an ACC voxel that our MPFC voxel encompassed.…”

Section: Discussioncontrasting

confidence: 56%

“…Using a 3.0T MR system, Yucel et al (2008) found no overall differences in Glx levels in 6.5-cm 3 dorsal or rostral ACC voxels in 20 adults with OCD (some on medication) compared with 26 healthy controls. On the other hand, post-hoc analyses revealed that female OCD patients had significantly reduced Glx levels in the rostral ACC that included the voxel studied by Rosenberg et al (2004), and these Glx levels were correlated with symptom severity. Using a 1.5T MR system, Starck et al (2008) found no significant differences in Glx levels in 3.6-cm 3 ACC voxels in 9 adults with OCD (some on medication) and 15 controls; their voxel was more dorsal and posterior.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, three MRS studies of the cortex in OCD focused on the ACC. Using a 1.5 T MR system, Rosenberg et al (2004) found decreased Glx levels in 3.0-cm 3 ACC voxels in 20 unmedicated pediatric OCD patients compared with 14 healthy controls. Using a 3.0T MR system, Yucel et al (2008) found no overall differences in Glx levels in 6.5-cm 3 dorsal or rostral ACC voxels in 20 adults with OCD (some on medication) compared with 26 healthy controls.…”

Section: Introductionmentioning

confidence: 99%

“…We used this method to measure cortical Glx and GABA in 24 unmedicated adults with OCD and 22 healthy control subjects. The region of interest was the medial prefrontal cortex (MPFC), which includes the pregenual (rostral) ACC, encompassing the voxel assessed by Rosenberg et al (2004) and overlapping that used by Yucel et al (2008). To assess regional specificity, we also measured Glx and GABA in the dorsolateral prefrontal cortex (DLPFC), a brain region not directly implicated in most OCD models.…”

Section: Introductionmentioning

confidence: 99%

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Investigation of Cortical Glutamate–Glutamine and γ-Aminobutyric Acid in Obsessive–Compulsive Disorder by Proton Magnetic Resonance Spectroscopy

Simpson

Shungu

Bender

et al. 2012

Neuropsychopharmacol

124

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Glutamatergic abnormalities in corticostriatal brain circuits are thought to underlie obsessive-compulsive disorder (OCD). Whether these abnormalities exist in adults with OCD is not clear. We used proton magnetic resonance spectroscopy ( 1 H MRS) to test our hypothesis that unmedicated adults with OCD have reduced glutamate plus glutamine (Glx) levels in the medial prefrontal cortex (MPFC) compared with healthy controls. Levels of g-aminobutyric acid (GABA) were also explored. Twenty-four unmedicated adults with OCD and 22 matched healthy control subjects underwent 1 H MRS scans at 3.0 T. Resonances of both Glx and GABA were obtained using the standard J-editing technique and assessed as ratios relative to voxel tissue water (W) in the MPFC (the region of interest) and the dorsolateral prefrontal cortex (DLPFC) to explore the regional specificity of any finding. In the MPFC, Glx/W did not differ by diagnostic group (p ¼ 0.98) or sex (p ¼ 0.57). However, GABA/W was decreased in OCD (2.16 ± 0.46 Â 10 À3 ) compared with healthy controls (2.43 ± 0.45 Â 10 À3 , p ¼ 0.045); moreover, age of OCD onset was inversely correlated with MPFC GABA/W (r ¼ À0.50, p ¼ 0.015). MPFC GABA/W was higher in females than in males. In the DLPFC, there were no main effects of diagnosis or gender on Glx/W or GABA/W. These data indicate that unmedicated adults with OCD do not have Glx abnormalities in a MPFC voxel that includes the pregenual anterior cingulate cortex. However, they may have decreased MPFC GABA levels. How GABA abnormalities might contribute to corticostriatal dysfunction in OCD deserves further study.

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Section: Discussioncontrasting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Investigation of Cortical Glutamate–Glutamine and γ-Aminobutyric Acid in Obsessive–Compulsive Disorder by Proton Magnetic Resonance Spectroscopy

Simpson

Shungu

Bender

et al. 2012

Neuropsychopharmacol

124

View full text Add to dashboard Cite

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“…Functional neuroimaging studies showed metabolic hyperactivity in the corticostriatal-thalamic-cortical circuits. 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 .…”

Section: Glutamate Related Genesmentioning

confidence: 99%

Estudos de associação genética no transtorno obsessivo-compulsivo

Sampaio¹,

Lins²,

Daltro-Oliveira³

et al. 2013

Rev. psiquiatr. clín.

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Background: Obsessive-compulsive disorder (OCD) segregates in families. It follows a complex model of genetic transmission, which involves the influence of several small effect genes interacting with the environment. Methods: A systematic review of genetic association studies in OCD was performed. Articles published until 2012 were searched in the databases PubMed, Embase and ScieLO using the terms of MeSH and its associates or synonyms for "obsessivecompulsive disorder", "gene" and "genetic association studies". Results: We selected 105 papers and described their main results grouped as genes related to: serotonin, dopamine, glutamate, GABA, white matter, immune system, hormones and other genes. Discussion: There is high variability between findings of association studies among the several candidate genes studied in OCD. Glutamate-related genes are promising candidates for OCD, but there is no conclusive association between any of the candidate genes studied and OCD. Association studies with large sample size, evaluation of more homogeneous subgroups of phenotype and meta-analyses are still needed.

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Anterior Cingulate Cortexγ-Aminobutyric Acid in Depressed Adolescents

Gabbay

Mao

Klein

et al. 2012

Arch Gen Psychiatry

172

145

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Context Anhedonia, a core symptom of major depressive disorder (MDD) and highly variable among adolescents with MDD, may involve alterations in the major inhibitory amino acid neurotransmitter system of γ-aminobutyric acid (GABA). Objective To test whether anterior cingulate cortex (ACC) GABA levels, measured by proton magnetic resonance spectroscopy, are decreased in adolescents with MDD. The associations of GABA alterations with the presence and severity of anhedonia were explored. Design Case-control, cross-sectional study using single-voxel proton magnetic resonance spectroscopy at 3 T. Setting Two clinical research divisions at 2 teaching hospitals. Participants Twenty psychotropic medication-free adolescents with MDD (10 anhedonic, 12 female, aged 12–19 years) with episode duration of 8 weeks or more and 21 control subjects group matched for sex and age. Main Outcome Measures Anterior cingulate cortex GABA levels expressed as ratios relative to unsuppressed voxel tissue water (w) and anhedonia scores expressed as a continuous variable. Results Compared with control subjects, adolescents with MDD had significantly decreased ACC GABA/w (t= 3.2; P<.003). When subjects with MDD were categorized based on the presence of anhedonia, only anhedonic patients had decreased GABA/w levels compared with control subjects (t=4.08; P<.001; PTukey<.001). Anterior cingulate cortex GABA/w levels were negatively correlated with anhedonia scores for the whole MDD group (r = −0.50; P = .02), as well as for the entire participant sample including the control subjects (r=−0.54; P<.001). Anterior cingulate cortex white matter was also significantly decreased in adolescents with MDD compared with controls (P=.04). Conclusions These findings suggest that GABA, the major inhibitory neurotransmitter in the brain, may be implicated in adolescent MDD and, more specifically, in those with anhedonia. In addition, use of a continuous rather than categorical scale of anhedonia, as in the present study, may permit greater specificity in evaluating this important clinical feature.

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Reduced Anterior Cingulate Glutamatergic Concentrations in Childhood OCD and Major Depression Versus Healthy Controls

Cited by 216 publications

References 50 publications

Investigation of Cortical Glutamate–Glutamine and γ-Aminobutyric Acid in Obsessive–Compulsive Disorder by Proton Magnetic Resonance Spectroscopy

Investigation of Cortical Glutamate–Glutamine and γ-Aminobutyric Acid in Obsessive–Compulsive Disorder by Proton Magnetic Resonance Spectroscopy

Estudos de associação genética no transtorno obsessivo-compulsivo

Anterior Cingulate Cortexγ-Aminobutyric Acid in Depressed Adolescents

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