Functional and Biochemical Alterations of the Medial Frontal Cortex in Obsessive-Compulsive Disorder (original) (raw)
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Journal of Neural Transmission, 2008
1H magnetic resonance spectroscopy (1H MRS) studies exploring brain metabolites, especially glutamine + glutamate (Glx), in obsessive compulsive disorder (OCD) are of vital interest for trying to understand more about the pathophysiology of OCD. Therefore, we conducted the present 1H MRS study with the aims of (1) comparing MRS metabolites in a group of adult patients with OCD and a group of healthy controls, and (2) examining the relationship between MRS metabolite concentrations and symptom severity in the patient group. Three brain regions were studied, the right caudate nucleus, the anterior gyrus cinguli and the occipital cortex bilaterally. Since multivariate analysis is a highly useful tool for extraction of 1H MRS data, we applied principal component analysis (PCA) and partial least square projection to latent structures (PLS) to the MRS data. PLS disclosed a strong relationship between several of the metabolites and OCD symptom severity, as measured with Yale-Brown obsessive-compulsive scale (YBOCS): the YBOCS score was found to be positively correlated to caudate creatine, Glx, glutamate, and choline compounds as well as occipital cortex myoinositol, and negatively correlated to occipital cortex Glx. The negative correlation between occipital cortex Glx and YBOCS was the most impressive. PCA did not reveal any tendency for a separation between the patients with OCD and controls with respect to MRS metabolites. The results are discussed in relation to corticostriatothalamocortical feedback and previous observations of poor visuospatial ability in OCD.
Neuropsychopharmacology, 2015
The anterior cingulate cortex is implicated in the neurobiology of obsessive-compulsive disorder (OCD). However, few studies have examined functional and neurochemical abnormalities specifically in the rostral subdivision of the ACC (rACC) in OCD patients. We used functional magnetic resonance imaging (fMRI) during an emotional counting Stroop task and single-voxel J-resolved proton magnetic resonance spectroscopy (1 H-MRS) in the rACC to examine the function and neurochemistry of the rACC in individuals with OCD and comparison individuals without OCD. Between-group differences in rACC activation and glutamine/glutamate ratio (Gln/Glu), Glu, and Gln levels, as well as associations between rACC activation, Gln/Glu, Glu, Gln, behavioral, and clinical measures were examined using linear regression. In a sample of 30 participants with OCD and 29 age-and sex-matched participants without OCD, participants with OCD displayed significantly reduced rACC deactivation compared with those without OCD in response to OCD-specific words versus neutral words on the emotional counting Stroop task. However, Gln/Glu, Glu, and Gln in the rACC did not differ between groups nor was there an association between reduced rACC deactivation and Gln/Glu, Glu, or Gln in the OCD group. Taken together, these findings strengthen the evidence for rACC dysfunction in OCD, but weigh against an underlying association with abnormal rACC glutamatergic neurotransmission.
Volumetric MRI study of key brain regions implicated in obsessive–compulsive disorder
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2007
Neuroanatomic abnormalities have been implicated in the pathophysiology of obsessive-compulsive disorder (OCD). To date, no study has measured the orbito-frontal cortex (OFC), anterior cingulate, caudate nucleus, and thalamus concurrently in first-episode patients. Thus, we performed a volumetric MRI study in patients who were treatment-naive and healthy controls focusing on the in vivo neuroanatomy of the whole brain, total gray and white matter volume, thalamus, caudate nucleus, anterior cingulate cortex, and OFC concurrently. The volumes of thalamus, caudate nucleus, anterior cingulate cortex, and OFC were measured in 12 OCD patients who were treatment-naive and 12 healthy control subjects. Anterior cingulate and OFC volumes included both white and gray matters. Volumetric measurements were made with T1-weighted coronal MRI images, with 1.5-mm-thick slices, at 1.5 T. The patients had increased white matter volume than healthy controls. The patient group had significantly smaller left and right OFC volumes and significantly greater left and right thalamus volumes compared with healthy controls. Anterior cingulate exhibited a near-significant difference between the patients and healthy controls on left side. Significant correlations were found between Y-BOCS scores and left OFC, and right OFC, and between Y-BOCS and left thalamus volumes in the patient group. In conclusion, our findings suggest that abnormalities in these areas may play an important role in the pathophysiology of OCD.
A magnetic resonance spectroscopy investigation of obsessive–compulsive disorder and anxiety
Psychiatry Research: Neuroimaging, 2006
The aim of the current study was to use proton magnetic resonance spectroscopy (MRS) to investigate potential irregularities in neurochemical compounds in obsessive-compulsive disorder (OCD) and the extent to which these irregularities are related to state anxiety. Single voxel MRS was used to image the head of the caudate nucleus (HOC) and orbitofrontal white matter (OFWM) bilaterally in adult patients with OCD and a control group. The results indicated that patients with OCD had increased levels of a combined measure of glutamate and glutamine (Glx/Cr) and N-acetyl-l-aspartic acid (NAA/Cr) relative to creatine in the right OFWM and reduced levels of myo-inositol relative to creatine (mI/Cr) in the HOC bilaterally. Correlational analyses indicated that Glx/Cr in the OFWM was related to OCD symptoms, while mI/Cr in the HOC was related to trait and/or state anxiety. Reanalysis of the significant group differences controlling for state anxiety symptoms erased three of the four group differences. These results are discussed in context of the methodological difficulties facing this area of research.
Psychiatry research, 2007
Proton magnetic resonance spectroscopic imaging was performed to compare brain metabolism in patients with obsessivecompulsive OCD. Evaluation was done on responders and non-responders to pharmacotherapy and on healthy controls. The results showed significantly lower NAA/Cr ratios in the right basal ganglia in non-responders than in responders or in controls and higher Cho/Cr ratios in the right thalamus in non-responders than responders. Abnormal neuronal metabolism in the right basal ganglia and right thalamus may be indicating lack of response to treatment to selective serotonin reuptake inhibitor.
BMC Psychiatry
Background While considerable progress has been made in exploring the psychological, the neural, and the neurochemical dimensions of OCD separately, their interplay is still an open question, especially their changes during psychotherapy. Methods Seventeen patients were assessed at these three levels by psychological questionnaires, fMRI, and venipuncture before and after inpatient psychotherapy. Seventeen controls were scanned at comparable time intervals. First, pre/post treatment changes were investigated for all three levels separately: symptom severity, whole-brain and regional activity, and the concentrations of cortisol, serotonin, dopamine, brain-derived neurotrophic factor (BDNF), and immunological parameters (IL-6, IL-10, TNFα). Second, stepwise linear modeling was used to find relations between the variables of the levels. Results The obsessive-compulsive, depressive, and overall symptom severity was significantly reduced after psychotherapy. At the neural level, the acti...
Neuropsychopharmacology, 2012
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.
Journal of affective disorders, 2012
BACKGROUND: Abnormality of orbitofronto-striatal circuits was postulated in obsessive-compulsive disorder (OCD). The aim of this study is to test the abnormality hypothesis of orbitofronto-striatal circuits and explore whether there are any other dysfunctional brain regions in OCD using a resting-state functional magnetic resonance imaging (fMRI), and further investigate the relationship between the whole-brain voxel-based spontaneous neuronal activity of patients with OCD and clinical characteristics. METHODS: 23 patients with OCD and 23 age- and gender-matched normal controls were examined using resting-state fMRI, and amplitude of low-frequency fluctuation (ALFF) approach was used to analyze fMRI data. RESULTS: Compared with normal controls, patients with OCD presented increased ALFF in the bilateral orbitofrontal cortex (OFC), anterior cingulate cortex (ACC) as well as decreased ALFF in the bilateral cerebellum and parietal cortex (P<0.01, corrected). Additionally, the ALFF v...
There has been relatively little analysis of possible neurochemical correlates of compulsive behavior to illuminate its underlying neural mechanisms. We utilised 7-Tesla proton magnetic resonance spectroscopy (1H-MRS) to assess the balance of excitatory and inhibitory neurotransmission by measuring glutamate and GABA levels in anterior cingulate cortex and supplementary motor area (SMA) of healthy volunteers and patients with Obsessive-Compulsive Disorder (OCD). Within the SMA, trait and clinical measures of compulsive behavior were related to glutamate levels, whereas a behavioral index of habitual control correlated with the glutamate:GABA ratio. OCD patients additionally exhibited elevated glutamate levels and glutamate:GABA ratios in anterior cingulate cortex which also correlated with habitual control. This study highlights important underlying relationships between SMA mechanisms of habitual control relevant to compulsive behavior, common to the healthy sub-clinical and OCD po...