Inverse relationship between thalamic and orbitofrontal volumes in obsessive–compulsive disorder

Volumetric magnetic resonance imaging (MRI) studies in obsessive–compulsive disorder (OCD) have reported a smaller volume of the orbitofrontal cortex (OFC) and a larger volume of the thalamus compared with healthy controls. Both of these brain regions are strongly connected; therefore, it may be hypothesized that cortical and thalamic alterations are related. Here, we investigated the relationship between thalamic and orbitofrontal volumes in OCD patients relative to healthy controls. MRI volumetric measurements of the thalamus and the OFC were obtained in 16 OCD patients without comorbidity and 16 comparison subjects matched for age, sex and educational level. Partial correlation analyses that controlled for intracranial volume (ICV) were performed to explore relationships between thalamic and OFC volumes in each group. In order to assess the specificity of this relationship, we conducted similar analyses of the anterior cingulate cortex (ACC) as a non-OFC cortical volume. Finally, by using data from previously published volumetric MRI studies, we conducted a meta-regression to explore the relationships between volume changes in these regions of interest. Results showed that thalamic volumes were significantly negatively correlated with OFC volumes in OCD patients (r = − 0.83, p < 0.001), but not in healthy subjects (r = − 0.15, p = 0.59). A significant relationship between thalamic and ACC volumes was found neither in the OCD patients (r = 0.03, p = 0.91) nor in the comparison subjects (r = − 0.23, p = 0.40). Furthermore, meta-regression analyses showed that previously reported volume changes in the thalamus were significantly correlated with OFC volume changes (r = − 0.71, p < 0.05), but not with ACC volume changes (r = 0.07, p = 0.86). Although our results do not allow for any causal relationship to be established, they suggest that structural alterations of both the thalamus and the OFC are inversely and specifically related in OCD.     

Orbitofrontal cortex and impulsivity in borderline personality disorder: an MRI study of baseline brain perfusion

Behavioral and neuroimaging studies in patients with borderline personality disorder (BPD) have associated orbitofrontal cortex (OFC) dysfunction with distinct symptom clusters such as impulsivity. It is unclear, however, whether abnormal patterns of OFC activity are also present during resting-state conditions and whether OFC dysfunction is specifically associated with impulsivity in BPD. This study tested the hypothesis that BPD patients would exhibit changes of OFC baseline perfusion and explored the relationship between regional cerebral blood flow and distinct BPD symptom clusters, such as impulsivity, dissociation tension and depressive symptoms. Using continuous arterial spin labeling magnetic resonance imaging at 3 Tesla, we investigated 16 women with BPD according to DSM-IV criteria and 16 healthy female control participants during resting-state conditions. Between-group comparisons were conducted using an analysis of variance (p?<?0.05 cluster corrected). Compared to controls, BPD patients exhibited decreased blood flow in the medial OFC, whereas increased blood flow was found in the left and right lateral OFC. Correlation analyses revealed a positive relationship between medial and lateral orbitofrontal blood flow and impulsivity scores, whereas measures of dissociation tension and depression did not exhibit a significant correlation with OFC perfusion. These data suggest that dysfunction of medial and lateral regions of the OFC could specifically mediate symptoms of impulsivity in BPD.     

Predictors of treatment response to fluvoxamine in obsessive-compulsive disorder: An fMRI study

Recent neuroimaging studies suggest that the pathophysiology of obsessive-compulsive disorder (OCD) may involve more widely distributed large-scale brain systems, including the parietal, occipital, and cerebellar areas, rather than the conventional orbitofronto-striatal model. We hypothesized that not only orbitofrontal cortex and caudate nucleus activities but also posterior brain regions might be associated with subsequent treatment response to serotonin reuptake inhibitors in OCD. The participants were 17 patients with OCD. Each patient was required to undergo fluvoxamine pharmacotherapy for 12 weeks. Before treatment, fMRI images of the subjects were obtained in the context of a symptom-provocation paradigm. The percentage changes in total Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores, from pre- to post-treatment, served as the index of treatment response. Statistical Parametric Mapping was used to identify brain loci where pre-treatment brain activation significantly correlated with the subsequent treatment response. Fifteen of 17 patients completed the 12-week treatment. During the symptom provocation task, patients showed brain activation in the left superior temporal gyrus (STG), left precuneus, left frontal cortices, right cerebellum, and right frontal cortices. We found that pre-treatment activation in the right cerebellum (Z-score = 5.10, x,y,z=22,-84,-18) and the left STG (Z-score = 4.95, x,y,z=-62,-22,0) was positively correlated with the improvement in the Y-BOCS score. Our results suggest that pre-treatment activation in the right cerebellum and in the left STG predict subsequent reduction in OCD symptom severity. There is every possibility that fMRI can be used as a tool to predict treatment response.     

Relevance of orbitofrontal neurochemistry for the outcome of cognitive-behavioural therapy in patients with obsessive–compulsive disorder

Since the advent of non-invasive methods such as proton magnetic resonance spectroscopy ((1)H-MRS), obsessive-compulsive disorder (OCD) has been increasingly associated with an altered composition of neurometabolites and neurotransmitters in several brain areas. Particularly, Inositol has not only been implicated in OCD pathophysiology, but also shown effective in pilot studies in therapy-refractory OCD patients. However, the relevance of regional brain neurochemistry for therapy outcome has not yet been investigated. Whereas numerous neuroimaging findings support a dysfunction of the orbitofrontal cortex (OFC) in OCD, MR-spectroscopic investigations of this region are missing. (1)H-MRS and psychometric measurements were obtained from twenty unmedicated patients with OCD, subsequently enrolled in a 3-month structured inpatient cognitive-behavioural therapy programme, and from eleven matched control subjects. Multiple regression of symptom score changes (Y-BOCS) on (myo-)inositol concentrations in three areas (right orbitofrontal cortex (OFC), right striatum and anterior cingulate cortex) was performed. The concentration of (myo-)inositol in the OFC only predicted the outcome of subsequent CBT regarding Y-BOCS score reduction (Spearman's r ( s )?=?.81, P?相似文献   

Comprehensive evaluation of cortical structure abnormalities in drug-naïve, adult patients with obsessive-compulsive disorder: A surface-based morphometry study

The study objective was to comprehensively evaluate drug-naïve, adult patients with Obsessive Compulsive Disorder (OCD) for cortical structure abnormalities in comparison with healthy controls. In this cross-sectional study of case–control design, Magnetic Resonance Imaging (1-mm) was performed in drug-naïve OCD patients (N = 50) &; age- sex-, education- and handedness-matched healthy controls (N = 40). We examined cortical volume, thickness, surface area &; local Gyrification Index (LGI) through a completely automated surface-based morphometric analysis using FreeSurfer software. OCD symptoms and insight were assessed using Yale-Brown Obsessive Compulsive Symptom (Y-BOCS) check-list and severity scale. Illness severity was assessed using Clinical Global Impression Severity (CGI-S) Scale. OCD patients had significantly deficient volume, thickness and surface area of right anterior cingulate gyrus (ACG). Right lingual gyrus surface area was found to be significantly decreased in patients. Y-BOCS obsession score had significant negative correlation with left frontal pole volume. Y-BOCS compulsion score had significant negative correlations with right ACG volume and surface area and right lateral orbitofrontal cortex LGI. CGI-Severity score had significant negative correlations with right lingual gyrus volume, thickness and surface area as well as right lateral orbitofrontal area. Y-BOCS insight score showed a significant negative correlation with LGI of left medial OFC and left rostral ACG. Identification of novel deficits involving occipital brain regions and first-time observations of relevant correlations between various illness characteristics and cortical measures in OCD patients supports a network involving anterior cingulate, orbitofrontal and occipital brain regions in the pathogenesis of OCD.     

Left anterior subregion of orbitofrontal cortex volume reduction and impaired organizational strategies in obsessive-compulsive disorder

The orbitofrontal cortex (OFC) may be involved in the clinical and cognitive expressions of obsessive-compulsive disorder (OCD) and is a heterogenous region with respect to its cytoarchitecture, function and connectivity. This study was designed to examine the morphological abnormality of the anterior subregion of OFC and its relationship to clinical symptoms and cognitive performance in patients with OCD. We divided the OFC into anterior and posterior subregions using an external landmark and measured the gray matter volumes of each by three-dimensional magnetic resonance imaging in age- and sex-matched groups, which consisted of 34 OCD and 34 normal volunteers. Clinical and cognitive evaluations were completed using Yale-Brown Obsessive Compulsive Scale (YBOCS) and four sets of neuropsychological tests that assessed executive functions and visual memory. Volume reduction of the left anterior OFC was observed in patients with OCD versus normal controls. Also, a significant positive correlation was found between left anterior OFC gray matter volume and the copy score of the Rey-Osterrieth Complex Figure Test in patients with OCD. These results suggest that left anterior subregion volume reduction of the OFC may be related to impaired organizational strategies in patients with OCD.     

A SPECT study of apathy in Alzheimer's disease

BACKGROUND/AIMS: To assess the association between regional cerebral blood flow (rCBF) and apathy in Alzheimer's Disease (AD). METHODS: SPECT and MRI scans were obtained from 51 nondepressed outpatients meeting criteria for probable AD (age 77.6 +/- 6.6 years; MMSE 22.3 +/- 5.1; 23 apathetic, 28 nonapathetic) and 23 healthy elderly (75.6 +/- 3.8 years) controls. The following regions of interest (ROIs) were compared between apathetic and nonapathetic AD patients and then referenced against aged controls: anterior cingulate, orbitofrontal cortex, middle medial temporal cortex, hippocampus, medial superior temporal cortex, thalamus/hypothalamus and pons. RESULTS: Apathetic and nonapathetic patients had significant differences in rCBF. Relative to nonapathetic AD patients, apathetic AD patients had lower perfusion in 2 ROIs (right orbitofrontal cortex and left anterior cingulate) and higher perfusion in 5 ROIs (right and left hippocampi, left medial superior temporal gyrus, and right and left middle medial temporal cortex). Comparison of rCBF in these 7 ROIs to healthy elderly controls confirmed hypoperfusion in the left anterior cingulate and right orbitofrontal cortex and suggested a relative sparing of perfusion among apathetic AD patients in the remaining 5 ROIs. CONCLUSIONS: In this group of nondepressed patients with AD, apathetic subjects displayed significant perfusion differences compared to nonapathetic subjects.     

fMRI of neuronal activation with symptom provocation in unmedicated patients with obsessive compulsive disorder

BACKGROUND: Previous studies suggest that a neural circuit involving over-activation of cortical, paralimbic, limbic, and striatal structures may underlie OCD symptomatology, but results may have been limited by medication use in those studies. To address this, we examined the effects of symptom induction on fMRI neural activation in medication-free patients with OCD. METHODS: Seven outpatients with OCD were exposed to individually tailored provocative and innocuous stimuli during fMRI scans. Self-ratings of OCD symptoms were performed prior to each scan and after exposure to stimuli. Images were analyzed as composite data sets and individually. RESULTS: Stimulus presentation was associated with significant increases in OCD self-ratings. Significant activation was demonstrated in several regions of the frontal cortex (orbitofrontal, superior frontal, and the dorsolateral prefrontal); the anterior, medial and lateral temporal cortex; and the right anterior cingulate. Right superior frontal activation inversely correlated with baseline compulsion symptomatology and left orbitofrontal cortical activation was inversely associated with changes in OCD self-ratings following provocative stimuli. CONCLUSIONS: These results in unmedicated patients are consistent with those from previous studies with medicated patients and suggest that OCD symptomatology is mediated by multiple brain regions including the anterior cingulate as well as frontal and temporal brain regions.     

Anatomic evaluation of the orbitofrontal cortex in major depressive disorder.

BACKGROUND: The orbitofrontal cortex (OFC) plays a major role in neuropsychologic functioning including exteroceptive and interoceptive information coding, reward-guided behavior, impulse control, and mood regulation. This study examined the OFC and its subdivisions in patients with MDD and matched healthy control subjects. METHODS: Magnetic resonance imaging (MRI) was performed on 31 unmedicated MDD and 34 control subjects matched for age, gender, and race. Gray matter volumes of the OFC and its lateral and medial subdivisions were measured blindly. RESULTS: The MDD patients had smaller gray matter volumes in right medial [two-way analysis of covariance F(1,60) = 4.285; p =.043] and left lateral OFC [F(1,60) = 4.252; p =.044]. Left lateral OFC volume correlated negatively with age in patients but not in control subjects. Male, but not female patients exhibited smaller left and right medial OFC volumes compared with healthy control subjects of the same gender. CONCLUSIONS: These findings suggest that patients with MDD have reduced OFC gray matter volumes. Although this reduction might be important in understanding the pathophysiology of MDD, its functional and psychopathologic consequences are as yet unclear. Future studies examining the relationship between specific symptomatic dimensions of MDD and OFC volumes could be especially informative.     

Working memory dysfunction in obsessive-compulsive disorder: A neuropsychological and functional MRI study

Previous neuropsychological studies indicate that OCD subtypes such as checking rituals might be associated with a working memory deficit. On the other hand, functional neuroimaging studies found functional abnormalities of the frontal cortex and subcortical structures in OCD. Combined with functional imaging method, we applied neuropsychological batteries to demonstrate a working memory deficit in OCD by comparison with normal controls. In addition, working memory and brain activation were further examined with symptom-based analysis. Forty patients with OCD and 25 normal controls were examined using neuropsychological tests including the WAIS-R, WCST, WMS-R, and R-OCFT and functional MRI (fMRI) during the N-back task including 0- and 2-back task. On fMRI, the brain regions activated during the performance and the differences in the activation between patients and controls were identified. Additional analyses of severity and subtypes were conducted by using Y-BOCS severity score, symptom-checklist and Leckman’s four-factor model, respectively. On the neuropsychological tests, the OCD patients had significantly lower scores on the delayed recall section of the WMS-R and the immediate recall section of the R-OCFT compared to the controls. On fMRI, the patients showed greater activation in the right dorsolateral prefrontal cortex (DLPFC), left superior temporal gyrus (STG), left insula, and cuneus during two-back task compared to the controls. Right orbitofrontal cortex activity showed a significant positive correlation with Y-BOCS scores in OCD. Furthermore, patients with obsessions/checking rituals (n = 10) showed severer memory deficits and decreased activity in the postcentral gyrus than patients with cleanliness/washing rituals (n = 14). In conclusion, we found neuropsychological dysfunction and brain abnormalities in OCD. Furthermore, our results suggested that symptom severity and symptom subtype such as obsessions/checking might affect neuropsychological dysfunction and related brain activities.     

A voxel-based investigation of regional cerebral blood flow abnormalities in obsessive-compulsive disorder using single photon emission computed tomography (SPECT)

Several functional imaging studies have reported abnormalities of the orbitofrontal and anterior cingulate cortices, striatum and thalamus in obsessive-compulsive disorder (OCD). These studies have often been limited by small patient samples and image analysis methods that rely on region-of-interest (ROI) approaches. We have assessed resting regional cerebral blood flow with 99mTc-ECD SPECT in 26 unmedicated OCD patients and 22 healthy control subjects using the voxel-based Statistical Parametric Mapping method for data analysis. We found a significantly reduced ECD uptake in OCD patients relative to the control subjects in the right lateral orbitofrontal cortex, and in the left dorsal anterior cingulate cortex (P<0.001 two-tailed, uncorrected for multiple comparisons). There were significant positive correlations in the OCD group between the ECD uptake in the left lateral orbitofrontal cortex and ratings for obsessive-compulsive symptoms (OCS), and between the ECD uptake in the right medial orbitofrontal cortex and the ratings for both OCS and depressive symptoms. There were also unpredicted significant ECD uptake increases in the cerebellum in OCD patients, as well as a negative correlation between posterior cingulate ECD uptake and OCS severity (P<0.05, corrected for multiple testing). These results implicate specific subregions of the orbitofrontal and anterior cingulate cortices in the pathophysiology of OCD, as well as suggesting the involvement of other areas not usually included in ROI-based imaging studies. With the incorporation of voxel-based methods and the use of large patient samples, rCBF-SPECT studies may continue to provide valuable information about the functional anatomy of OCD.     

Single photon emission computed tomography (SPECT) of anxiety disorders before and after treatment with citalopram

Background  

Several studies have now examined the effects of selective serotonin reuptake inhibitor (SSRI) treatment on brain function in a variety of anxiety disorders including obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), and social anxiety disorder (social phobia) (SAD). Regional changes in cerebral perfusion following SSRI treatment have been shown for all three disorders. The orbitofrontal cortex (OFC) (OCD), caudate (OCD), medial pre-frontal/cingulate (OCD, SAD, PTSD), temporal (OCD, SAD, PTSD) and, thalamic regions (OCD, SAD) are some of those implicated. Some data also suggests that higher perfusion pre-treatment in the anterior cingulate (PTSD), OFC, caudate (OCD) and antero-lateral temporal region (SAD) predicts subsequent treatment response. This paper further examines the notion of overlap in the neurocircuitry of treatment and indeed treatment response across anxiety disorders with SSRI treatment.     

The frontal-anatomic specificity of design fluency repetitions and their diagnostic relevance for behavioral variant frontotemporal dementia

On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer's disease, semantic dementia, progressive supranuclear palsy, or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD. (JINS, 2012, 18, 1-11).     

Early orbitofrontal hyperactivation in obsessive-compulsive disorder

Dysfunctional activity in the orbitofrontal cortex (OFC) is one of the core features in the pathophysiology of obsessive-compulsive disorder (OCD). Neuroimaging studies indicate orbitofrontal hyperactivation during the resting state as well as during symptom provocation, whereas orbitofrontal hypoactivation has been reported during tasks designed to dissociate specific cognitive processes. Combined magnetoencephalic and functional magnetic resonance imaging studies show early involvement of the OFC in stimulus processing in healthy subjects. However, it is unclear whether OFC activation is dysfunctional at an early stage in patients with OCD. We investigated early electrical OFC activation evoked by reward and punishment feedback in a visual probabilistic object reversal task (pORT). Patients with OCD (n=23) and healthy controls (n=27), matched for gender, age and educational level, performed the pORT during a 29-channel electroencephalographic recording. Low resolution brain electromagnetic tomography was applied to localize orbitofrontal sources of neuronal activity at 80 to 200 ms post-stimulus. Group comparison showed significantly higher orbitofrontal activation in OCD patients at 100-120 ms after the reward stimulus. No group differences were found with respect to OFC activation in response to punishment stimuli and in task performance. Results substantiate dysfunctional OFC activity at a very early stage in the processing of reward stimuli in patients with OCD. Our results provide support for the assumption that the OFC plays a more active role in the processing of visual stimuli as previously supposed. As orbitofrontal hyperactivation following rewarding feedback occurred as early as 100 ms after receipt of the visual stimulus in patients with OCD, and as we did not find any OFC dysfunction following negative feedback, our findings may point towards a specific early disturbance of reward processing in OCD. This finding might have implications for cognitive behavioural therapy of this disorder.     

Structural changes in the gray matter of unmedicated patients with obsessive-compulsive disorder: a voxel-based morphometric study

The aim of the current study was to use whole brain voxel-based morphometry（VBM）to assess the gray matter（GM）changes in unmedicated patients with obsessive-compulsive disorder（OCD）compared with normal controls.We compared the GM volumes in28 patients with 22 matched healthy controls using a1.5T MRI.Three-dimensional T1-weighted magnetic resonance images were obtained from all participants.VBM was performed to detect GM volume differences between the two groups.We detected increased regional GM volumes in the bilateral middle temporal gyri,bilateral middle occipital gyri,bilateral globus pallidus,right inferior parietal gyrus,left superior parietal gyrus,right parahippocampus,right supramarginal gyrus,right medial superior frontal gyrus,and left inferior frontal opercular cortex in the OCD patients relative to controls（P〈0.001,uncorrected,cluster size〉100 voxels）.No decreased GM volume was found in the OCD group compared with normal controls.Our findings suggest that structural changes in the GM are not limited to fronto-striato-thalamic circuits in the pathogenesis of OCD.Temporo-parietal cortex may also play an important role.     

Corticostriatal functional connectivity in non-medicated patients with obsessive-compulsive disorder

The basal ganglia represents a key component of the pathophysiological model for obsessive-compulsive disorder (OCD). This brain region is part of several neural circuits, including the orbitofronto-striatal circuit and dorsolateral prefronto-striatal circuit. There are, however, no published studies investigating those circuits at a network level in non-medicated patients with OCD. Resting state functional magnetic resonance imaging scans were obtained from 20 non-medicated patients with OCD and 23 matched healthy volunteers. Voxelwise statistical parametric maps testing strength of functional connectivity of three striatal seed regions of interest (ROIs) with remaining brain regions were calculated and compared between groups. We performed additional correlation analyses between strength of connectivity and the severity scores for obsessive-compulsive symptoms, depression, and anxiety in the OCD group. Positive functional connectivity with the ventral striatum was significantly increased (P_corrected <.05) in the orbitofrontal cortex, ventral medial prefrontal cortex and dorsal lateral prefrontal cortex of subjects with OCD. There was no significant correlation between measures of symptom severity and the strength of connectivity (P_uncorrected <.001). This is the first study to investigate the corticostriatal connectivity in non-medicated patients with OCD. These findings provide the first direct evidence supporting a pathophysiological model involving basal ganglia circuitry in OCD.     

Glutamate system genes and brain volume alterations in pediatric obsessive-compulsive disorder: A preliminary study

Obsessive-compulsive disorder (OCD) has been associated with regional volumetric brain abnormalities, which provide promising intermediate phenotypes of the disorder. In this study, volumes of brain regions selected for a priori evidence of association with OCD (orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), thalamus, caudate, putamen, globus pallidus and pituitary) were measured using structural magnetic resonance imaging (MRI) in 20 psychotropic-naïve pediatric OCD patients. We examined the association between these regional brain volumes and a total of 519 single nucleotide polymorphisms (SNPs) from nine glutamatergic candidate genes (DLGAP1, DLGAP2, DLGAP3, GRIN2B, SLC1A1, GRIK2, GRIK3, SLITRK1 and SLITRK5). These genes were selected based on either previous reported association with OCD in humans or evidence from animal models of OCD. After correcting for multiple comparisons by permutation testing, no SNP remained significantly associated with volumetric changes. The strongest trend toward association was identified between two SNPs in DLGAP2 (rs6558484 and rs7014992) and OFC white matter volume. Our other top ranked association findings were with ACC, OFC and thalamus. These preliminary results suggest that sequence variants in glutamate candidate genes may be associated with structural neuroimaging phenotypes of OCD.     

Orbital frontal cortex in treatment-naïve pediatric obsessive–compulsive disorder

The orbital frontal cortex (OFC) has been implicated in obsessive–compulsive disorder (OCD). Participants comprised 28 treatment-naïve pediatric OCD patients and 21 controls, who were examined using magnetic resonance imaging. OCD patients had larger right but not left OFC white matter volume than controls. This is fresh evidence implicating white matter in OCD.     

Decreased thalamic blood flow in obsessive-compulsive disorder patients responding to fluvoxamine

Functional imaging studies have pointed to a role of the orbitofrontal cortex (OFC), striatum and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Effective treatment has been found to change brain activity within this circuitry. The aim of the present study was to explore possible differential effects of OCD responders and non-responders to drug treatment on the regional cerebral blood flow (rCBF). Measurements of rCBF were carried out in 15 out of 22 patients with OCD who completed an open-label trial with fluvoxamine. Patients were studied with 99mTc-HMPAO single photon emission computed tomography (SPECT) before and after 12 weeks of treatment. In addition, structural magnetic resonance imaging was obtained on all patients. Regions of interest comprised the OFC, caudate nucleus, putamen and thalamus. Seven patients responded to treatment. Levels of rCBF decreased significantly in the left caudate nucleus and the left and right putamen in both responders and non-responders to treatment. In responders, but not in non-responders, a significant decrease in rCBF was found in the right thalamus. Pre-treatment cerebellar and whole brain HMPAO uptake was significantly higher in responders to treatment compared with non-responders. We suggest that the thalamus plays a central role in the response to drug treatment.     

Glutamate System Genes Associated with Ventral Prefrontal and Thalamic Volume in Pediatric Obsessive-Compulsive Disorder

This pilot study was undertaken to determine if there was a significant association between specific glutamate system genes and regional volumes of interest implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Volumetric magnetic resonance imaging (MRI) and genotyping of seven polymorphisms in two genes, glutamate receptor, ionotropic, N-methyl-d-aspartate 2B (GRIN2B) and solute linked carrier, family 1, member 1 (SLC1A1) were conducted in 31 psychotropic-naïve pediatric OCD patients. The rs1805476 variant of GRIN2B was associated with left but not right orbital frontal cortex (OFC) (p?=?0.04) and right but not left anterior cingulate cortex (ACC) volume (p?=?0.02). The SLC1A1 rs3056 variant was associated with increased total (p?=?0.01), left (p?=?0.02) and right (p?=?0.02) thalamic volume. These results suggest that GRIN2B and SLC1A1 may be associated with regional volumetric alterations in OFC, ACC, and thalamus in children with OCD.