[markog]

Basically it looks like the best options revolve around behavioral treatments still one up on any chemical treatments.

What also looked interesting to me was that there was increased DAT activity in the Basal ganglia (pre-treatment) and there was decreased D1 and D2 receptor binding. These seems pretty obvious at first, but points out to me that serotonin doesn't look like it has any direct effects in OCD rather its the indirect effects on dopamine, decreasing the release and upregulating the receptors.

It also looks like from this that Nardil seems like it would be a fantastic drug for OCD, but it doesn't do particularly well in trials. I think this because of its ability to increase levels of GABA in the caudate-putamen and NAC. And increasing levels of all NT's in the frontal lobes, thus decreasing glucose metabolism. On paper it looks good anyway....

Nakatani E, Nakgawa A, Ohara Y, Goto S, Uozumi N, Iwakiri M, Yamamoto Y, Motomura K, Iikura Y, Yamagami T.
Effects of behavior therapy on regional cerebral blood flow in obsessive-compulsive disorder.
Psychiatry Res. 2003 Oct 30;124(2):113-20.
"Very few functional neuroimaging studies have been performed on patients with obsessive-compulsive disorder (OCD) undergoing behavior therapy, even though it is recognized to be an effective treatment for this disorder. We measured the regional cerebral blood flow (rCBF) using the Xenon inhalation method in 31 treatment-refractory patients with OCD and the same number of age-matched normal controls. We also studied changes in rCBF in 22 OCD patients who had demonstrated a significant improvement after the behavior therapy. The OCD patients showed a significant bilateral elevation in the rCBF in the basal ganglia compared with the normal controls. After successful treatment, a significant decrease was found in the rCBF in the right head of the caudate nucleus that tended to correlate with clinical improvement." [Abstract]

Benazon NR, Moore GJ, Rosenberg DR.
Neurochemical analyses in pediatric obsessive-compulsive disorder in patients treated with cognitive-behavioral therapy.
J Am Acad Child Adolesc Psychiatry. 2003 Nov;42(11):1279-85.
"OBJECTIVE: To investigate neurochemical changes in the caudate nucleus of pediatric obsessive-compulsive disorder (OCD) patients before and after cognitive-behavioral therapy (CBT), and to examine corresponding changes in symptom severity. METHOD: Single-voxel proton magnetic resonance spectroscopic (1H-MRS) examination of the left caudate was conducted in 21 treatment-naive children, aged 6 to 16 years, before and after 12 weeks of CBT. Subjects were measured at baseline and posttreatment by the Yale-Brown Obsessive Compulsive Scale for Children, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale. RESULTS: No significant changes in caudate neurochemistry were observed in OCD patients before and after CBT despite unambiguous improvement in OCD symptoms, depression, and anxiety. CONCLUSIONS: Findings suggest that reduction in caudate Glx may be specific to SSRI treatment and not due to a more generalized treatment response or spontaneous improvement of symptoms. Differential sets of pathophysiologic and treatment response markers may moderate/mediate the effects of particular treatments on outcome." [Abstract]

Kang DH, Kwon JS, Kim JJ, Youn T, Park HJ, Kim MS, Lee DS, Lee MC.
Brain glucose metabolic changes associated with neuropsychological improvements after 4 months of treatment in patients with obsessive-compulsive disorder.
Acta Psychiatr Scand. 2003 Apr;107(4):291-7.
"OBJECTIVE: The study was designed to elucidate regional brain metabolic changes according to a treatment and their relationship with neuropsychological performance changes in obsessive-compulsive disorder (OCD). METHOD: Cerebral glucose metabolic rates were repeatedly measured before and after treatment in 10 patients with OCD using [18F]-2-fluoro-deoxyglucose positron emission tomography (PET). They were compared on a voxel-basis, and the correlations were counted between the regional metabolic changes and the degree to improvement on the neuropsychological assessments. RESULTS: After treatment, the patients showed significant (P < 0.005, two-tailed) regional metabolic changes in multiple brain areas involving frontal-subcortical circuits and parietal-cerebellar networks. Especially, the metabolic changes of the putamen, the cerebellum, and the hippocampus were significantly correlated with the improvement of the immediate- and delayed-recall scores of the Rey-Osterrieth Complex Figure Test (RCFT). CONCLUSION: These results suggest a possibility that metabolic changes of frontal-subcortical and parietal-cerebellar circuit changes may underlie cognitive improvements in patients with OCD." [Abstract]

Szeszko PR, MacMillan S, McMeniman M, Lorch E, Madden R, Ivey J, Banerjee SP, Moore GJ, Rosenberg DR.
Amygdala volume reductions in pediatric patients with obsessive-compulsive disorder treated with paroxetine: preliminary findings.
Neuropsychopharmacology. 2004 Apr;29(4):826-32.
"The amygdala is believed to be highly relevant to the pathophysiology of obsessive-compulsive disorder (OCD) given its prominent role in fear conditioning and because it is an important target of the serotonin reuptake inhibitors (SRIs), the pharmacotherapy of choice for OCD. In the present study, we measured in vivo volumetric changes in the amygdala in pediatric patients with OCD following 16 weeks of monotherapy with the selective SRI, paroxetine hydrochloride. Amygdala volumes were computed from contiguous 1.5 mm magnetic resonance (MR) images in 11 psychotropic drug-naive patients with OCD prior to and then following treatment. Eleven healthy pediatric comparison subjects also had baseline and follow-up scans, but none of these subjects received medication. Patients demonstrated significant asymmetry of the amygdala (L>R) prior to pharmacologic intervention in contrast to healthy comparison subjects who showed no asymmetry at the time of their baseline scan. Mixed model analyses using age and total brain volume as time varying covariates indicated that left amygdala volume decreased significantly in patients following treatment. The reduction in left amygdala volume in patients correlated significantly with higher paroxetine dosage at the time of the follow-up scan and total cumulative paroxetine exposure between the scans. No significant changes in either right or left amygdala volume were evident among healthy comparison subjects from the baseline to the follow-up scan. These preliminary findings suggest that abnormal asymmetry of the amygdala may play a role in the pathogenesis of OCD and that paroxetine treatment may be associated with a reduction in amygdala volume." [Abstract]

Saxena, Sanjaya, Brody, Arthur L., Ho, Matthew L., Zohrabi, Narineh, Maidment, Karron M., Baxter, Lewis R., Jr.
Differential Brain Metabolic Predictors of Response to Paroxetine in Obsessive-Compulsive Disorder Versus Major Depression
Am J Psychiatry 2003 160: 522-532
"OBJECTIVE: Serotonin reuptake inhibitor (SRI) medications are effective in the treatment of both major depressive disorder and obsessive-compulsive disorder (OCD), but it is unknown whether the neural substrates of treatment response for the two disorders are the same or different. The authors sought to identify pretreatment cerebral glucose metabolic markers of responsiveness to SRI treatment in patients with OCD versus major depressive disorder and to determine whether the pretreatment patterns associated with improvement of OCD symptoms were the same as or different from those associated with improvement of major depressive disorder symptoms. METHOD: [18F]Fluorodeoxyglucose positron emission tomography was used to measure cerebral glucose metabolism in 27 patients with OCD alone, 27 with major depressive disorder alone, and 17 with concurrent OCD and major depressive disorder, who were all then treated with 30–60 mg/day of paroxetine for 8–12 weeks. Correlations were calculated between pretreatment regional metabolism and pre- to posttreatment changes in the severity of OCD symptoms, depressive symptoms, and overall functioning. RESULTS: While improvement of OCD symptoms was significantly correlated with higher pretreatment glucose metabolism in the right caudate nucleus (partial r=–0.53), improvement of major depressive disorder symptoms was significantly correlated with lower pretreatment metabolism in the amygdala (partial r=0.71) and thalamus (partial r=0.34) and with higher pretreatment metabolism in the medial prefrontal cortex and rostral anterior cingulate gyrus (Talairach coordinates: x=0, y=62, z=10) (z=2.91). CONCLUSIONS: These findings suggest that, although both OCD and major depressive disorder respond to SRIs, the two syndromes have different neurobiological substrates for response. Elevated activity in the right caudate may be a marker of responsiveness to antiobsessional treatment, while lower right amygdala activity and higher midline prefrontal activity may be required for response of depressive symptoms to treatment." [Abstract]


Hansen ES, Hasselbalch S, Law I, Bolwig TG.
The caudate nucleus in obsessive-compulsive disorder. Reduced metabolism following treatment with paroxetine: a PET study.
Int J Neuropsychopharmacol. 2002 Mar;5(1):1-10.
"Several neuroimaging studies of patients with OCD have pointed to basal ganglia and the frontal cortical regions being relevant for an understanding of the pathophysiology and therapy of OCD. In a search for the neural substrate underlying the therapeutic action of paroxetine in the therapy of OCD we measured regional glucose metabolism in a PET study of 20 OCD patients before and after at least 3 months of treatment. We used 18-fluoro-deoxyglucose PET-scanning to measure regional cerebral glucose metabolic rate (rCMRglc) in 20 non-depressed patients fulfilling DSM-IV criteria for OCD. Patients were studied before and after 12-20 wk of treatment with the serotonin re-uptake inhibitor paroxetine. Clinical assessment rating with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) was performed before the first and after the second study. The PET data was analysed regionally using statistical parametric mapping (SPM-96). A clinical improvement was indicated by a mean decrease of 55% in the Y-BOCS score. There was no difference in global cerebral metabolism before and after treatment whereas a post-treatment reduction in normalized rCMRglc was found in the right caudate nucleus. This finding also showed a significant positive correlation with symptom severity. Our results support hypotheses regarding a malfunction of the cortico-striato-thalamic system in the pathophysiology of OCD and particularly point to the caudate nucleus playing an important role for the therapeutic action of paroxetine in the treatment of OCD." [Abstract]

Rosenberg DR, MacMaster FP, Keshavan MS, Fitzgerald KD, Stewart CM, Moore GJ.
Decrease in caudate glutamatergic concentrations in pediatric obsessive-compulsive disorder patients taking paroxetine.
J Am Acad Child Adolesc Psychiatry. 2000 Sep;39(9):1096-103.
"OBJECTIVE: To measure in vivo neurochemical changes in the caudate nucleus in pediatric obsessive-compulsive disorder (OCD) before and after treatment. METHOD: Single-voxel proton magnetic resonance spectroscopic (1H-MRS) examinations of the left caudate were conducted in 11 psychotropic drug-naive children, aged 8 to 17 years, with OCD before and after 12 weeks of monotherapy with the selective serotonin reuptake inhibitor paroxetine (10-60 mg/day) and 11 healthy children aged 8 to 17 years. A different sample of 8 pediatric OCD patients and 8 healthy children had a 1H-MRS examination of occipital cortex. RESULTS: Caudate glutamatergic concentrations (Glx) were significantly greater in treatment-naive OCD patients than in controls but declined significantly after paroxetine treatment to levels comparable with those of controls. Decrease in caudate Glx was associated with decrease in OCD symptom severity. Occipital Glx did not differ between OCD patients and controls. CONCLUSIONS: These preliminary findings provide new evidence of Glx abnormalities in the caudate nucleus in pediatric OCD and suggest that paroxetine treatment may be mediated by a serotonergically modulated reduction in caudate Glx." [Abstract]

Bolton J, Moore GJ, MacMillan S, Stewart CM, Rosenberg DR.
Case study: caudate glutamatergic changes with paroxetine persist after medication discontinuation in pediatric OCD.
J Am Acad Child Adolesc Psychiatry. 2001 Aug;40(8):903-6.
"Proton magnetic resonance spectroscopy (1H-MRS) was used to examine glutamatergic (Glx) abnormalities in the caudate nucleus in pediatric obsessive-compulsive disorder (OCD), associated with severity of illness and response to acute (12 weeks) treatment with paroxetine. In this report, OCD symptoms improved markedly in an 8-year-old girl treated for 14 months with the selective serotonin reuptake inhibitor paroxetine (titrated from 10 to 40 mg/day). Paroxetine dose was then decreased in 10-mg decrements and discontinued without symptom recurrence. Serial 1H-MRS examinations were acquired before and after 12 weeks of paroxetine treatment (40 mg/day) and 3 months after medication discontinuation. A striking decrease in caudate Glx was observed after 12 weeks of treatment which persisted after medication discontinuation. These data provide further support for a reversible glutamatergically mediated dysfunction of the caudate nucleus in OCD that may serve as a pathophysiological and treatment response marker." [Abstract]

Diler RS, Kibar M, Avci A.
Pharmacotherapy and regional cerebral blood flow in children with obsessive compulsive disorder.
Yonsei Med J. 2004 Feb 29;45(1):90-9.
"While regional cerebral blood flow (rCBF) studies on adults involving the caudate, prefrontal, orbitofrontal, and cingulated areas have been reported, no such published data on children exist. In this study, we aimed to determine the significance of pre- and post-treatment regional cerebral blood flow (rCBF) differences in children with obsessive compulsive disorder (OCD) and compared them with healthy controls. Eighteen drug-free obsessive compulsive children, aged 11 to 15, without comorbid states except for anxiety disorders--participated in this study. The control group consisted of 12 children, aged 11 to 15, with no medical or psychiatric illnesses. Using SPECT (Single Photon Emission Computerized Tomography) scans with Technetium-99m-HMPAO-hexamethly propyleneamine oxime (Tc99mHMPAO), the rCBF was calculated in 15 regions of the control group according to a standard protocol, while in the study group, it was measured at baseline and after 12 weeks of treatment with a fixed dose of paroxetine (20 mg qd). We compared the resulting pre- and post-treatment CBF values for the control group and study group. The right and left caudates, right and left dorsolateral prefrontals, and cingulate had significantly higher rCBF in children with obsessive compulsive disorder than in the control group. These areas, in addition to the right anteromedial temporal, showed significant rCBF reduction after treatment with paroxetine. The mean percentage of change in obsession scores during the treatment correlated significantly with the baseline and post- treatment rCBF level of the right caudate, post-treatment left caudate, and baseline left caudate. Our findings on children are consistent with adult studies and support the theory of a cortical-striatal-thalamic-cortical loop disturbance in OCD." [Abstract]


Rauch SL, Shin LM, Dougherty DD, Alpert NM, Fischman AJ, Jenike MA.
Predictors of fluvoxamine response in contamination-related obsessive compulsive disorder: a PET symptom provocation study.
Neuropsychopharmacology. 2002 Nov;27(5):782-91.
"The purpose of this study was to identify neuroimaging predictors of medication response in contamination-related obsessive compulsive disorder (OCD). Prior studies of OCD had indicated that glucose metabolic rates within orbitofrontal cortex (OFC) were inversely correlated with subsequent response to serotonergic reuptake inhibitors (SRIs) and that glucose metabolic rates within posterior cingulate cortex (PCC) were positively correlated with subsequent response to cingulotomy. Nine subjects with contamination-related OCD underwent a 12-week open trial of treatment with the SRI fluvoxamine. Percent change in Yale-Brown Obsessive Compulsive Scale score, from pre- to post-treatment, served as the index of treatment response. Positron emission tomography (PET) measurements of regional cerebral blood flow (rCBF) were obtained prior to treatment, in the context of a symptom provocation paradigm. Statistical parametric mapping was used to identify brain loci where pre-treatment rCBF was significantly correlated with subsequent treatment response. Consistent with a priori hypotheses, lower rCBF values in OFC and higher rCBF values in PCC predicted better treatment response. This same pattern of associations was present regardless of whether the imaging data were acquired during a provoked or neutral state. These findings are consistent with prior studies of OCD, indicating that PET indices of brain activity within OFC are inversely correlated with subsequent response to SRIs. In addition, similar to findings regarding cingulotomy for OCD, indices of activity within PCC appear to be positively correlated with response to fluvoxamine as well. Finally, this pattern is sufficiently robust as to be relatively independent of symptomatic state at the time of tracer uptake." [Abstract]

Saxena S, Brody AL, Maidment KM, Dunkin JJ, Colgan M, Alborzian S, Phelps ME, Baxter LR Jr.
Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder.
Neuropsychopharmacology. 1999 Dec;21(6):683-93.
"Previous positron emission tomography (PET) studies of patients with obsessive-compulsive disorder (OCD) have found elevated glucose metabolic rates in the orbitofrontal cortex (OFC) and caudate nuclei that normalize with response to treatment. Furthermore, OCD symptom provocation differentially activates specific subregions of the OFC, which have distinct patterns of connectivity and serve different functions. Therefore, we sought to determine the role of specific subregions of the OFC and associated subcortical structures in mediating OCD symptoms, by determining how glucose metabolism in these structures changed with paroxetine treatment of OCD patients. We also sought to determine whether pretreatment OFC metabolism would predict response to paroxetine, as it has for other OCD treatments. Twenty subjects with OCD received [18F]-fluorodeoxyglucose (FDG)-PET scans before and after 8 to 12 weeks of treatment with paroxetine, 40 mg/day. In patients who responded to paroxetine, glucose metabolism decreased significantly in right anterolateral OFC and right caudate nucleus. Lower pretreatment metabolism in both left and right OFC predicted greater improvement in OCD severity with treatment. These results add to evidence indicating that orbitofrontal-subcortical circuit function mediates the symptomatic expression of OCD. Specific subregions of the OFC may be differentially involved in the pathophysiology of OCD and/or its response to pharmacotherapy." [Abstract]

Swedo SE, Pietrini P, Leonard HL, Schapiro MB, Rettew DC, Goldberger EL, Rapoport SI, Rapoport JL, Grady CL.
Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder. Revisualization during pharmacotherapy.
Arch Gen Psychiatry. 1992 Sep;49(9):690-4.
"To investigate the effects of drug treatment in childhood-onset obsessive-compulsive disorder (OCD), we repeated positron emission tomographic scans in 13 adults with OCD (eight taking clomipramine, two taking fluoxetine, and three taking no drug) after at least 1 year of pharmacotherapy. As a group, the patients had a significant improvement on all OCD and anxiety ratings. Positron emission tomography revealed a significant decrease in normalized orbitofrontal regional cerebral glucose metabolism (relative to global metabolism) bilaterally. Among the treated patients, the decrease in right orbitofrontal metabolism was directly correlated with two measures of OCD improvement. These results extend previous positron emission tomographic findings of regional dysfunction in OCD and suggest involvement of the orbitofrontal regions in the pathophysiology of OCD." [Abstract]

Rubin RT, Ananth J, Villanueva-Meyer J, Trajmar PG, Mena I.
Regional 133xenon cerebral blood flow and cerebral 99mTc-HMPAO uptake in patients with obsessive-compulsive disorder before and during treatment.
Biol Psychiatry. 1995 Oct 1;38(7):429-37.
"We previously reported increased regional cerebral cortical uptake and decreased caudate nucleus uptake of 99mTc-HMPAO in patients with obsessive-compulsive disorder(OCD) before treatment compared to matched normal controls. In the present study, we determined whether or not these changes persisted during treatment. Single-photon emission computed tomography was used to measure regional cerebral blood flow (rCBF) by 133Xe inhalation and cerebral uptake of 99mTc-HMPAO in eight adult male OCD patients before and during treatment with chlomipramine, and in eight age-matched normal male controls. With 133Xe, there were no significant differences in rCBF between patients with OCD and their matched controls, and no significant differences in rCBF in the patients before and during treatment. Significantly increased HMPAO uptake in the orbital frontal cortex, posterofrontal cortex, and high dorsal parietal cortex bilaterally occurred in the OCD patients before treatment compared to their matched controls, and there were significant reductions of HMPAO uptake, into the normal range, in all these areas in the patients during treatment. Significantly reduced HMPAO uptake in the caudate nucleus bilaterally occurred in the patients before treatment compared to their matched controls, and these reductions persisted during treatment. This study provides additional support for the involvement of both the orbital frontal cortex and the caudate nuclei in the pathophysiology of OCD." [Abstract]

Saxena S, Brody AL, Ho ML, Alborzian S, Maidment KM, Zohrabi N, Ho MK, Huang SC, Wu HM, Baxter LR Jr.
Differential cerebral metabolic changes with paroxetine treatment of obsessive-compulsive disorder vs major depression.
Arch Gen Psychiatry. 2002 Mar;59(3):250-61.
"BACKGROUND: Serotonin reuptake inhibitors (SRIs) effectively treat both major depressive disorder (MDD) and obsessive-compulsive disorder (OCD). We compared and contrasted the functional neuroanatomical effects of SRIs in OCD and MDD as these 2 disorders occurred separately and concurrently by measuring pretreatment to posttreatment cerebral glucose metabolic changes in OCD vs MDD vs concurrent OCD + MDD. METHODS: We obtained [(18)F]fluorodeoxyglucose positron emission tomography (PET) brain scans on 25 subjects with OCD, 25 with MDD, and 16 with concurrent OCD + MDD before and after 8 to 12 weeks of treatment with paroxetine hydrochloride. Controls (n = 16) were scanned 10 to 12 weeks apart without treatment. Treatment response was defined as a more than 25% decline in OCD symptom severity, a more than 50% decline in MDD severity, and "much improved" clinical global impression. RESULTS: Although all patient groups received the same paroxetine dose for the same duration, regional metabolic changes differed significantly among diagnostic groups. Subjects with OCD alone showed significant metabolic decreases in the right caudate nucleus, right ventrolateral prefrontal cortex (VLPFC), bilateral orbitofrontal cortex, and thalamus that were not seen in any other group. Both the MDD and concurrent OCD + MDD groups showed metabolic decreases in the left VLPFC and increases in the right striatum. Treatment response was associated with a decrease in striatal metabolism in nondepressed OCD patients but with an increase in striatal activity in patients with OCD + MDD. CONCLUSIONS: Brain metabolic responses to SRIs are both disorder-specific and response-specific. They vary according to the underlying pathophysiology of the patient and the degree of symptomatic improvement." [Abstract]

Hoehn-Saric R, Schlaepfer TE, Greenberg BD, McLeod DR, Pearlson GD, Wong SH.
Cerebral blood flow in obsessive-compulsive patients with major depression: effect of treatment with sertraline or desipramine on treatment responders and non-responders.
Psychiatry Res. 2001 Nov 30;108(2):89-100.
"We examined the effects of sertraline and of desipramine on patients with OCD and comorbid major depressive episodes at study entry. Sixteen patients, 9 receiving sertraline and 7 desipramine, received HMPAO SPECT scans while free of medication and after 12 weeks of treatment. Patients on sertraline showed significantly reduced regional cerebral blood flow (rCBF) in the right prefrontal and temporal regions. Patients on desipramine showed more diffuse rCBF reductions in frontal and temporal regions, more so in the left side. In a second analysis, patients who had a symptom reduction on the Yale-Brown Obsessive Compulsive Scale (YBOCS), irrespective of the type of medication, were retrospectively classified as 'responders' to treatment. Eleven patients were 'responders' and 5 'non-responders'. Before being medicated, responders differed from non-responders through higher rCBF in prefrontal regions, mostly on the left, and higher rCBF in the cingulate and basal ganglia bilaterally. After 12 weeks of treatment, responders showed a diffuse reduction of rCBF in prefrontal regions while non-responders showed only a few scattered low-frequency responses. Thus, higher prefrontal and subcortical activity was associated with better response to drug treatment. In addition, clinical change, but not the administration of medication as such, was associated with a decrease of prefrontal rCBF." [Abstract]

Saxena S, Brody AL, Ho ML, Alborzian S, Ho MK, Maidment KM, Huang SC, Wu HM, Au SC, Baxter LR Jr.
Cerebral metabolism in major depression and obsessive-compulsive disorder occurring separately and concurrently.
Biol Psychiatry. 2001 Aug 1;50(3):159-70.
"BACKGROUND: The frequent comorbidity of major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) suggests a fundamental relationship between them. We sought to determine whether MDD and OCD have unique cerebral metabolic patterns that remain the same when they coexist as when they occur independently. METHODS: [18F]-fluorodeoxyglucose positron emission tomography (PET) brain scans were obtained on 27 subjects with OCD alone, 27 with MDD alone, 17 with concurrent OCD+MDD, and 17 normal control subjects, all in the untreated state. Regional cerebral glucose metabolism was compared between groups. RESULTS: Left hippocampal metabolism was significantly lower in subjects with MDD alone and in subjects with concurrent OCD+MDD than in control subjects or subjects with OCD alone. Hippocampal metabolism was negatively correlated with depression severity across all subjects. Thalamic metabolism was significantly elevated in OCD alone and in MDD alone. Subjects with concurrent OCD+MDD had significantly lower metabolism in thalamus, caudate, and hippocampus than subjects with OCD alone. CONCLUSIONS: Left hippocampal dysfunction was associated with major depressive episodes, regardless of primary diagnosis. Other cerebral metabolic abnormalities found in OCD and MDD occurring separately were not seen when the disorders coexisted. Depressive episodes occurring in OCD patients may be mediated by different basal ganglia-thalamic abnormalities than in primary MDD patients." [Abstract]

Lucey JV, Costa DC, Busatto G, Pilowsky LS, Marks IM, Ell PJ, Kerwin RW.
Caudate regional cerebral blood flow in obsessive-compulsive disorder, panic disorder and healthy controls on single photon emission computerised tomography.
Psychiatry Res. 1997 Mar 14;74(1):25-33.
"We compared regional cerebral blood flow (rCBF) in 15 patients with DSM IIIR obsessive-compulsive disorder (OCD), 15 patients with DSM IIIR panic disorder and 15 healthy controls matched for age, sex and hand preference, using uptake of technetium-99m-D,L-hexamethyl-propylene amine oxime (99mTc HMPAO), on single photon emission computerised tomography (SPECT). Caudate rCBF was significantly reduced in OCD patients compared to healthy subjects and panic disorder patients. When four patients were excluded from each group, right caudate rCBF remained significantly lower in OCD patients than in panic disorder patients or healthy subjects. The data suggest functional involvement of the right caudate nucleus is present in OCD." [Abstract]

Kim JJ, Lee MC, Kim J, Kim IY, Kim SI, Han MH, Chang KH, Kwon JS.
Grey matter abnormalities in obsessive-compulsive disorder: statistical parametric mapping of segmented magnetic resonance images.
Br J Psychiatry. 2001 Oct;179:330-4.
"BACKGROUND: Although a number of functional imaging studies are in agreement in suggesting orbitofrontal and subcortical hyperfunction in the pathophysiology of obsessive-compulsive disorder (OCD), the structural findings have been contradictory. AIMS: To investigate grey matter abnormalities in patients with OCD by employing a novel voxel-based analysis of magnetic resonance images. METHOD: Statistical parametric mapping was utilised to compare segmented grey matter images from 25 patients with OCD with those from 25 matched controls. RESULTS: Increased regional grey matter density was found in multiple cortical areas, including the left orbitofrontal cortex, and in subcortical areas, including the thalamus. On the other hand, regions of reduction were confined to posterior parts of the brain, such as the left cuneus and the left cerebellum. CONCLUSIONS: Increased grey matter density of frontal-subcortical circuits, consonant with the hypermetabolic findings from functional imaging studies, seems to exist in patients with OCD, and cerebellar dysfunction may be involved in the pathophysiology of OCD." [Abstract]

Choi JS, Kang DH, Kim JJ, Ha TH, Lee JM, Youn T, Kim IY, Kim SI, Kwon JS.
Left anterior subregion of orbitofrontal cortex volume reduction and impaired organizational strategies in obsessive-compulsive disorder.
J Psychiatr Res. 2004 Mar-Apr;38(2):193-9.
"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." [Abstract]


Alptekin K, Degirmenci B, Kivircik B, Durak H, Yemez B, Derebek E, Tunca Z.
Tc-99m HMPAO brain perfusion SPECT in drug-free obsessive-compulsive patients without depression.
Psychiatry Res. 2001 Jul 1;107(1):51-6.
"The aim of this study was to confirm prior results of brain-imaging studies on obsessive-compulsive disorder (OCD) in a sample of Turkish patients, as a cross-cultural study. Tc-99m HMPAO brain perfusion SPECT imaging was performed in nine drug-free OCD patients without depression and six controls. The patients' Hamilton Depression Rating Scale scores were <16. The severity of obsessive-compulsive symptoms was rated with the Yale-Brown Obsessive-Compulsive Rating Scale (YBOCS). Quantitative evaluation of regional cerebral blood flow revealed that right thalamus, left frontotemporal cortex and bilateral orbitofrontal cortex showed significant hyperperfusion in patients with OCD compared with controls. YBOCS scores did not show any correlation with hyperperfusion in regional cerebral blood flow in these areas. Results of this cross-cultural study may support orbitofrontal and thalamic dysfunction in OCD in a sample of Turkish patients." [Abstract]

Berthier ML, Kulisevsky JJ, Gironell A, Lopez OL.
Obsessivecompulsive disorder and traumatic brain injury: behavioral, cognitive, and neuroimaging findings.
Neuropsychiatry Neuropsychol Behav Neurol. 2001 Jan;14(1):23-31.
"OBJECTIVE: The goal of this study was to evaluate behavior and cognition in a consecutive series of patients who developed obsessive-compulsive disorder (OCD) after suffering a traumatic brain injury (TBI). BACKGROUND: Because OCD is a rare sequelae of TBI, the phenomenology of obsessions and compulsions, the comorbid psychiatric disorders, the performance on cognitive tests, and the neural correlates have not been well characterized. METHODS: Ten adult patients who met DSM-IV diagnostic criteria for OCD after suffering either mild (6 cases), moderate (2 cases), or severe (2 cases) TBI were studied using structured psychiatric rating scales (i.e., Yale-Brown Obsessive Compulsive Scale), cognitive tests, and magnetic resonance imaging (MRI). RESULTS: Global severity of OCD ranged from moderate to severe, and all patients had multiple obsessions and compulsions. There was a high frequency of aggressive, contamination, need for symmetry/exactness, somatic, and sexual obsessions as well as cleaning/washing, checking, and repeating compulsions. Unusual features such as obsessional slowness (3 cases) and compulsive exercising (3 cases) were also documented. Comorbid psychiatric diagnoses were common and included posttraumatic stress disorder, anxiety with panic attacks, depression, and intermittent explosive disorder. Compared with 10 age-matched normal controls, the OCD group had poor performance on tests of general intelligence, attention, learning, memory, word-retrieval, and executive functions; these cognitive deficits were more pervasive among patients displaying obsessional slowness. All OCD patients with mild TBI had normal MRI scans, whereas focal contusions in the frontotemporal cortices, subcortical structures (caudate nucleus), or both were found in OCD patients with moderate and severe TBI. CONCLUSIONS: Posttraumatic OCD has a relatively specific pattern of symptoms even in patients with mild TBI and is associated with a variety of other psychiatric disorders, particularly non-OCD anxiety. The patterns of cognitive deficits and MRI findings suggest dysfunction of frontal-subcortical circuits." [Abstract]

Rauch SL, Kim H, Makris N, Cosgrove GR, Cassem EH, Savage CR, Price BH, Nierenberg AA, Shera D, Baer L, Buchbinder B, Caviness VS Jr, Jenike MA, Kennedy DN.
Volume reduction in the caudate nucleus following stereotactic placement of lesions in the anterior cingulate cortex in humans: a morphometric magnetic resonance imaging study.
J Neurosurg. 2000 Dec;93(6):1019-25.
"OBJECT: The goal of this study was to test hypotheses regarding changes in volume in subcortical structures following anterior cingulotomy. METHODS: Morphometric magnetic resonance (MR) imaging methods were used to assess volume reductions in subcortical regions following anterior cingulate lesioning in nine patients. Magnetic resonance imaging data obtained before and 9 +/- 6 months following anterior cingulotomy were subjected to segmentation and subcortical parcellation. Significant volume reductions were predicted and found bilaterally within the caudate nucleus, but not in the amygdala, thalamus, lenticular nuclei, or hippocampus. Subcortical parcellation revealed that the volume reduction in the caudate nucleus was principally referrable to the body, rather than the head. Furthermore, the magnitude of volume reduction in the caudate body was significantly correlated with total lesion volume. CONCLUSIONS: Taken together, these findings implicate significant connectivity between a region of anterior cingulate cortex (ACC) lesioned during cingulotomy and the caudate body. This unique data set complements published findings in nonhuman primates, and advances our knowledge regarding patterns of cortical-subcortical connectivity involving the ACC in humans. Moreover, these findings indicate changes distant from the site of anterior cingulotomy lesions that may play a role in the clinical response to this neurosurgical procedure." [Abstract]

Szeszko PR, Robinson D, Alvir JM, Bilder RM, Lencz T, Ashtari M, Wu H, Bogerts B.
Orbital frontal and amygdala volume reductions in obsessive-compulsive disorder.
Arch Gen Psychiatry. 1999 Oct;56(10):913-9.
"BACKGROUND: Functional neuroimaging studies have implicated the frontal lobes and the hippocampus-amygdala complex in the pathophysiology of obsessive-compulsive disorder (OCD). These brain regions have not been well investigated in patients with OCD, however, using magnetic resonance imaging. METHODS: Volumes of the superior frontal gyrus, anterior cingulate gyrus, orbital frontal region, hippocampus, and amygdala were computed from contiguous magnetic resonance images in a sample of 26 patients with OCD and 26 healthy comparison subjects. RESULTS: Patients with OCD had significantly reduced bilateral orbital frontal and amygdala volumes compared with healthy comparison subjects and lacked the normal hemispheric asymmetry of the hippocampus-amygdala complex. Neither brain structure volumes nor asymmetry indices were significantly correlated with total illness duration or length of current OCD episode. CONCLUSIONS: Findings of reduced orbital frontal and amygdala volumes in patients implicate a structural abnormality of these brain regions in the pathophysiology of OCD. Absence of the normal hemispheric asymmetry of the hippocampus-amygdala complex in patients is consistent with an anomalous neurodevelopmental process." [Abstract]

Santosh, Paramala Janardhanan
Current topic: Neuroimaging in child and adolescent psychiatric disorders
Arch. Dis. Child. 2000 82: 412-419 [Full Text]


Fitzgerald KD, Moore GJ, Paulson LA, Stewart CM, Rosenberg DR.
Proton spectroscopic imaging of the thalamus in treatment-naive pediatric obsessive-compulsive disorder.
Biol Psychiatry. 2000 Feb 1;47(3):174-82.
"BACKGROUND: Neurobiological abnormalities in the thalamus, particularly the dorsomedial nucleus of the thalamus, are believed to be involved in the pathophysiology of obsessive-compulsive disorder. Although obsessive-compulsive disorder commonly arises in childhood and adolescence, no prior study has examined the thalamus in pediatric obsessive-compulsive disorder patients. METHODS: In this study, N-acetyl-aspartate, a putative marker of neuronal viability, creatine/phosphocreatine, and choline levels were measured in the lateral and medical subregions of the left and right thalami using a multislice proton magnetic resonance spectroscopic imaging sequence in 11 treatment-naive, nondepressed obsessive-compulsive disorder outpatients, 8-15 years old, and 11 case-matched control subjects. RESULTS: A significant reduction in N-acetyl-aspartate/choline and N-acetyl-aspartate/(creatine/phosphocreatine + choline) was observed in both the right and left medial thalami in obsessive-compulsive disorder patients compared with control subjects. The N-acetyl-aspartate/choline and N-acetyl-aspartate/(creatine/phosphocreatine + choline) levels did not differ significantly between case-control pairs in either the left or the right lateral thalamus. Reduction in N-acetyl-aspartate levels in the left medial thalamus was inversely correlated with increased obsessive-compulsive disorder symptom severity. CONCLUSIONS: These findings provide new evidence of localized functional neurochemical marker abnormalities in the thalamus in pediatric obsessive-compulsive disorder. Our results must be considered preliminary, however, given the small sample size." [Abstract]

Crespo-Facorro B, Cabranes JA, Lopez-Ibor Alcocer MI, Paya B, Fernandez Perez C, Encinas M, Ayuso Mateos JL, Lopez-Ibor JJ Jr.
Regional cerebral blood flow in obsessive-compulsive patients with and without a chronic tic disorder. A SPECT study.
Eur Arch Psychiatry Clin Neurosci. 1999;249(3):156-61.
"The main goal of the present study was to explore whether regional cerebral blood flow (rCBF) differs between obsessive-compulsive disorder (OCD) patients without chronic motor tic disorder and those OCD patients with a comorbid chronic tic disorder. Twenty-seven patients suffering from OCD (DSM-IV criteria), including 7 OCD patients who met DSM-IV criteria for simple chronic motor dic disorder, and 16 healthy volunteers were examined at rest using a high resolution SPECT. Seven regions of interest (ROIs) were manually traced and quantified as a percentage of the mean cerebellar uptake. Severity of obsessive-compulsive symptoms (OCS), anxiety and depressive symptoms and presence of motor tics were assessed with the Y-BOCS, HRS-A, HRS-D, MADRS, and Yale Global Tics Severity Scale, respectively. We found a significant relative decrease in rCBF in OCD patients without motor tics compared to healthy volunteers in the right orbitofrontal cortex (OCD without tics = 0.87; healthy volunteers = 0.94; p = 0.02). No significant differences in rCBF were seen when OCD patients with and without chronic tics were directly compared. A lower severity of OCS in OCD patients with chronic tics was found. These results are consistent with previous functional neuroimaging studies at rest that have widely involved the orbitofrontal cortex in the pathophysiology of the OCD. However, our results do not support the idea that OCD patients with chronic tics may constitute a biological subgroup within the OCD." [Abstract]

Bartha R, Stein MB, Williamson PC, Drost DJ, Neufeld RW, Carr TJ, Canaran G, Densmore M, Anderson G, Siddiqui AR.
A short echo 1H spectroscopy and volumetric MRI study of the corpus striatum in patients with obsessive-compulsive disorder and comparison subjects.
Am J Psychiatry. 1998 Nov;155(11):1584-91.
"OBJECTIVE: It is likely that the corpus striatum is involved in obsessive-compulsive disorder (OCD). Prior studies have inconsistently found alterations in caudate volumes in patients with OCD. This study was undertaken in the hope that N-acetylaspartate and volumetric measures together would elucidate the presence and nature of corpus striatum volumetric abnormalities in OCD. METHOD: Thirteen patients meeting the DSM-IV criteria for OCD, who had been medication free for a minimum of 6 weeks, and 13 psychiatrically normal matched comparison subjects participated in the study. Short echo 1H magnetic resonance spectroscopy (1H-MRS) was used to measure levels of N-acetylaspartate and several other cerebral metabolites from a 4.5-cm3 volume in the left corpus striatum of all 26 subjects. Metabolite levels were estimated by fitting the time domain spectroscopy data with a noninteractive computer program. Volumes of the left and right head of the caudate nucleus in each subject were determined by semiautomatic segmentation of the volumetric images. RESULTS: N-Acetylaspartate levels from the left corpus striatum were significantly lower in the patients with OCD than in the comparison subjects. There were no differences in either left or right caudate volume between the two groups. CONCLUSIONS: Despite the lack of differences in caudate volumes between the OCD patients and the comparison subjects, the lower level of N-acetylaspartate in the left corpus striatum of the patients suggests reduced neuronal density in this region. Inconsistent volumetric findings among prior studies may reflect a poorer sensitivity of magnetic resonance imaging morphometry for detecting neuronal loss compared with 1H-MRS measurement of N-acetylaspartate." [Abstract]


Rauch SL, Savage CR, Alpert NM, Dougherty D, Kendrick A, Curran T, Brown HD, Manzo P, Fischman AJ, Jenike MA.
Probing striatal function in obsessive-compulsive disorder: a PET study of implicit sequence learning.
J Neuropsychiatry Clin Neurosci. 1997 Fall;9(4):568-73.
"Positron emission tomography was employed to contrast the brain activation pattern in patients with obsessive-compulsive disorder (OCD) to that of matched control subjects while they performed an implicit learning task. Although patients and control subjects evidenced comparable learning, imaging data from control subjects indicated bilateral inferior striatal activation, whereas OCD patients did not activate right or left inferior striatum and instead showed bilateral medial temporal activation. The findings further implicate corticostriatal dysfunction in obsessive-compulsive disorder. Furthermore, when OCD patients are confronted with stimuli that call for recruitment of corticostriatal systems, they instead appear to access brain regions normally associated with explicit (conscious) information processing." [Abstract]

Lucey JV, Burness CE, Costa DC, Gacinovic S, Pilowsky LS, Ell PJ, Marks IM, Kerwin RW.
Wisconsin Card Sorting Task (WCST) errors and cerebral blood flow in obsessive-compulsive disorder (OCD).
Br J Med Psychol. 1997 Dec;70 ( Pt 4):403-11.
"We compared Wisconsin Card Sorting Task (WCST) performance in 19 obsessive-compulsive disorder (OCD) patients and 19 individually matched healthy controls. Measures of intelligence and mood were taken into account for all participants. Within the patient group, factors such as duration and severity of symptoms (as assessed using the Yale-Brown Obsessive-Compulsive Scale, Y-BOCS) were considered. We explored the relationship between OCD WCST errors and regional cerebral blood flow (rCBF) on brain dedicated, high resolution, single photon emission tomography (SPET). We used uptake of 99mTc-hexamethylpropylamine oxime (HMPAO) on SPET to estimate rCBF, and regional values were quantified as ratios of cerebellar blood flow. WCST results confirmed OCD patients were significantly impared when compared with age- and sex-matched healthy volunteers. Patients made significantly more trials, more preseverative errors, and more null-sorts. OCD patients Y-BOCS 'obsessive' subtotal significantly correlated with many WCST errors. Furthermore OCD WCST null-sorts correlated significantly with SPET OCD left inferior frontal cortical rCBF (r(18) = .47, p = .05) and left caudate rCBF (r(18) = .72, p = .01). The implications of these findings are discussed in the context of other studies which examine functional imaging and neuropsychology in OCD." [Abstract]

Breiter HC, Rauch SL, Kwong KK, Baker JR, Weisskoff RM, Kennedy DN, Kendrick AD, Davis TL, Jiang A, Cohen MS, Stern CE, Belliveau JW, Baer L, O'Sullivan RL, Savage CR, Jenike MA, Rosen BR.
Functional magnetic resonance imaging of symptom provocation in obsessive-compulsive disorder.
Arch Gen Psychiatry. 1996 Jul;53(7):595-606.
"BACKGROUND: The new technique of functional magnetic resonance imaging was used to investigate the mediating neuroanatomy of obsessive-compulsive disorder symptoms. METHODS: Ten patients with obsessive-compulsive disorder and 5 normal subjects were studied via functional magnetic resonance imaging during control and provoked conditions. Data analysis entailed parametric and nonparametric statistical mapping. RESULTS: Statistical maps (nonparametric; P < 10(-3)) showed activation for 70% or more of patients with obsessive-compulsive disorder in medial orbitofrontal, lateral frontal, anterior temporal, anterior cingulate, and insular cortex, as well as caudate, lenticulate, and amygdala. No normal subjects exhibited activation in any brain region. CONCLUSIONS: Results of functional magnetic resonance imaging were consistent with past studies of obsessive-compulsive disorder that used other functional neuroimaging modalities. However, paralimbic and limbic activations were more prominent in the present study." [Abstract]

Aylward EH, Harris GJ, Hoehn-Saric R, Barta PE, Machlin SR, Pearlson GD.
Normal caudate nucleus in obsessive-compulsive disorder assessed by quantitative neuroimaging.
Arch Gen Psychiatry. 1996 Jul;53(7):577-84.
"BACKGROUND: Prior neuroimaging studies have not consistently demonstrated a structural or functional abnormality of the caudate nucleus in patients with obsessive-compulsive disorder (OCD). However, there is theoretical support for some associated dysfunction of the caudate nucleus. METHODS: We examined volumes of the caudate nucleus and putamen with magnetic resonance imaging in 24 patients with adult-onset OCD and 21 control subjects, group-matched on age, race, education, and sex. Patients were relatively free from tics. To evaluate function (metabolism or blood flow) of the caudate nucleus, we performed a quantitative review, including a meta-analysis, of normalized data from functional neuroimaging studies that compared patients who had OCD with normal control subjects. RESULTS: All structural basal ganglia measures failed to exhibit differences between patients with OCD and matched normal control subjects. Patients did not demonstrate evidence of ventricular enlargement. Quantitative meta-analysis of the functional neuroimaging literature did not demonstrate a consistent abnormality of the caudate nucleus. CONCLUSIONS: We did not observe evidence of a structural abnormality of the caudate nucleus in patients with OCD. Prior reports of a structural aberration of the caudate nucleus were mixed. We also did not find strong support for relative caudate metabolic or perfusion dysfunction in the literature, although increased function in the frontal cerebral cortex was identified. The heterogeneous nature of this disorder may account for inconsistencies between studies. For example, ventricular enlargement or reduced caudate volume or blood flow might be evident in patients with soft neurological signs (eg, tics), while patients in the current study were relatively free from tics. Although theories of OCD suggest a dysfunction of the caudate nucleus, the structural and functional neuroimaging literature has not consistently verified this." [Abstract]

Rubin RT, Villanueva-Meyer J, Ananth J, Trajmar PG, Mena I.
Regional xenon 133 cerebral blood flow and cerebral technetium 99m HMPAO uptake in unmedicated patients with obsessive-compulsive disorder and matched normal control subjects. Determination by high-resolution single-photon emission computed tomography.
Arch Gen Psychiatry. 1992 Sep;49(9):695-702.
"We measured regional cerebral blood flow (rCBF) with the xenon 133 (133Xe) inhalation method and with regional cerebral uptake of technetium 99m d,l-hexamethyl propyleneamine oxime (99mTc-HMPAO) by single-photon emission computed tomography in 10 adult male patients with obsessive-compulsive disorder (OCD) and in 10 age-matched adult male normal controls. With the 133Xe method, there were no significant differences in cortical or basal ganglia blood flow between the patients with OCD and their matched controls. In the patients, there was a positive relationship between rCBF and the severity of both obsessive and compulsive symptoms (average r = .48). These rCBF findings were consistent with those of earlier reports of increased rCBF in patients with OCD who were undergoing imaginal flooding and who had exacerbation of symptoms following m-CPP administration. 99mTc-HMPAO is a lipophilic molecule that crosses the blood-brain barrier and is converted to a hydrophilic form that is trapped in the brain. The amount that is trapped is determined primarily by blood flow, but also by membrane permeability and kinetics of conversion of the 99mTc-HMPAO to the hydrophilic form. Compared with their matched controls, the patients with OCD had significantly increased 99mTc-HMPAO uptake in the high dorsal parietal cortex bilaterally, in the left posterofrontal cortex, and in the orbital frontal cortex bilaterally. Possible explanations include (1) increased rCBF that was not detected with 133Xe, (2) increased permeability of the blood-brain barrier and/or cell membranes, and (3) increased conversion and trapping of the lipophilic, injected form of 99mTc-HMPAO in these regions." [Abstract]

Robinson D, Wu H, Munne RA, Ashtari M, Alvir JM, Lerner G, Koreen A, Cole K, Bogerts B.
Reduced caudate nucleus volume in obsessive-compulsive disorder.
Arch Gen Psychiatry. 1995 May;52(5):393-8.
"BACKGROUND: Current hypotheses about the neuroanatomical structures involved in obsessive-compulsive disorder (OCD) suggest abnormalities in cortical-striatal-thalamic-cortical circuits. This study examined selected brain regions within or adjacent to these circuits. METHODS: Magnetic resonance imaging scans from 26 patients with OCD and 26 healthy controls were analyzed to determine the volumes of the following structures: prefrontal cortex (cortex anterior to the genu of the corpus callosum), caudate nucleus, lateral and third ventricles, and whole brain. RESULTS: Patients with OCD had significantly smaller caudate nucleus volumes than controls (F[1,48] = 9.4, P = .004) but did not differ in prefrontal cortex size or in volumes of the lateral or third ventricles. Structural volumes were not significantly correlated with the duration or severity of OCD symptoms. CONCLUSION: Our findings provide additional evidence for pathological involvement of the caudate in OCD." [Abstract]

Scarone S, Colombo C, Livian S, Abbruzzese M, Ronchi P, Locatelli M, Scotti G, Smeraldi E.
Increased right caudate nucleus size in obsessive-compulsive disorder: detection with magnetic resonance imaging.
Psychiatry Res. 1992 Aug;45(2):115-21.
"Magnetic resonance images were used to measure the volume of the head of the caudate nucleus in 20 patients with obsessive-compulsive disorder and 16 normal control subjects. The obsessive-compulsive patients showed a significant increase in the volume of the right side of the head of the caudate nucleus compared with that of control subjects. This finding was not correlated with demographic, psychopathological, or clinical characteristics." [Abstract]

Calabrese G, Colombo C, Bonfanti A, Scotti G, Scarone S.
Caudate nucleus abnormalities in obsessive-compulsive disorder: measurements of MRI signal intensity.
Psychiatry Res. 1993 Jun;50(2):89-92.
"A previous magnetic resonance imaging (MRI) study from our group reported increased size of the right caudate nucleus in obsessive-compulsive patients compared with control subjects. To test the hypothesis of a structural abnormality underlying such volume alteration, MRI signal intensity (SI), as an index of T1 relaxation values, was measured in the caudate nucleus of the same sampling data. Results showed higher SI values in the left caudate nucleus compared with the right in the patient group, whereas no asymmetry was found in the control group." [Abstract]

Perani D, Colombo C, Bressi S, Bonfanti A, Grassi F, Scarone S, Bellodi L, Smeraldi E, Fazio F.
[18F]FDG PET study in obsessive-compulsive disorder. A clinical/metabolic correlation study after treatment.
Br J Psychiatry. 1995 Feb;166(2):244-50.
"BACKGROUND. We used [18F]FDG and PET in patients with obsessive-compulsive disorder (OCD) to evaluate cerebral metabolic involvement before and after treatment with serotonin-specific reuptake inhibitors. METHOD. In 11 untreated, drug-free adults, regional cerebral metabolic rate for glucose (rCMRglu) was compared with that of 15 age-matched normal controls. RESULTS. rCMRglu values were significantly increased in the cingulate cortex, thalamus and pallidum/putamen complex. After treatment a significant improvement in obsessive-compulsive symptoms on the Y-BOC scale (t = 3.59, P < 0.01) was associated with a significant bilateral decrease of metabolism in the whole cingulate cortex (P < 0.001). Clinical and metabolic data were significantly intercorrelated (Kendall's tau = 0.65; P < 0.01). CONCLUSIONS. These findings indicate that OCD is associated with functional hyperactivity of a selected neuronal network and that treatment to reduce symptoms may have a selective neuromodulatory effect on cingulate cortex." [Abstract]

Rauch SL, Jenike MA, Alpert NM, Baer L, Breiter HC, Savage CR, Fischman AJ.
Regional cerebral blood flow measured during symptom provocation in obsessive-compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography.
Arch Gen Psychiatry. 1994 Jan;51(1):62-70.
"BACKGROUND: The study was designed to determine the mediating neuroanatomy of obsessive-compulsive disorder (OCD). METHODS: The short half-life tracer oxygen 15-labeled carbon dioxide was used to allow for repeated positron emission tomographic determinations of regional cerebral blood flow on each of eight patients with OCD during a resting and a provoked (symptomatic) state. RESULTS: Individually tailored provocative stimuli were successful in provoking OCD symptoms, in comparison with paired innocuous stimuli, as measured by self-report on OCD analogue scales (P = .002). Omnibus subtraction images demonstrated a statistically significant increase in relative regional cerebral blood flow during the OCD symptomatic state vs the resting state in right caudate nucleus (P < .006), left anterior cingulate cortex (P < .045), and bilateral orbitofrontal cortex (P < .008); increases in the left thalamus approached but did not reach statistical significance (P = .07). CONCLUSIONS: These findings are consistent with results of previous functional neuroimaging studies and contemporary neurocircuitry models of OCD. The data further implicate orbitofrontal cortex, caudate nucleus, and anterior cingulate cortex in the pathophysiology of OCD and in mediating OCD symptoms." [Abstract]

Baxter LR Jr, Phelps ME, Mazziotta JC, Guze BH, Schwartz JM, Selin CE.
Local cerebral glucose metabolic rates in obsessive-compulsive disorder. A comparison with rates in unipolar depression and in normal controls.
Arch Gen Psychiatry. 1987 Mar;44(3):211-8.
"We studied 14 patients with obsessive-compulsive disorder (OCD) by positron emission tomography and the fluorodeoxyglucose method, looking for abnormalities in local cerebral metabolic rates for glucose in brain structures that have been hypothesized to function abnormally in OCD. These patients were compared with 14 normal controls and 14 patients with unipolar depression. The patients with unipolar depression and OCD did not differ in levels of anxiety, tension, or depression. In OCD, metabolic rates were significantly increased in the left orbital gyrus and bilaterally in the caudate nuclei. This was apparent on all statistical comparisons with both controls and unipolar depression. The right orbital gyrus showed at least a trend to an increased metabolic rate in all comparisons. The metabolic rate in the left orbital gyrus, relative to that in the ipsilateral hemisphere (orbital gyrus/hemisphere ratio), was significantly elevated compared to controls and subjects with unipolar depression, and stayed high even with successful drug treatment. Though it was in the normal range in the morbid state, with improvement in OCD symptoms after drug treatment, the caudate/hemisphere metabolic ratio increased uniformly and significantly bilaterally. This ratio did not increase in patients who did not respond to treatment. Thus, OCD showed cerebral glucose metabolic patterns that differed from controls in both the symptomatic and recovered states." [Abstract]

Amo C, Quesney LF, Ortiz T, Maestu F, Fernandez A, Lopez-Ibor MI, Lopez-Ibor JJ.
Limbic paroxysmal magnetoencephalographic activity in 12 obsessive-compulsive disorder patients: a new diagnostic finding.
J Clin Psychiatry. 2004 Feb;65(2):156-62.
"BACKGROUND: We describe frontotemporal paroxysmal rhythmic activity recorded by magnetoencephalography (MEG) in patients with obsessive-compulsive disorder (OCD). METHOD: Twelve patients with OCD (per ICD-10 and DSM-IV criteria), aged 18 to 65 years, were assessed using MEG. Patients' classification according to the Yale Brown OCD Scale was as follows: severe = 8, moderate = 3, and mild = 1. MEG findings were compared with those of 12 age- and sex-matched healthy subjects (control group) with no previous history of psychiatric or neurologic disorders. All study participants underwent neurologic and basic medical examinations, including magnetic resonance imaging, electrocardiograms (EEGs), and electrooculograms. The study was conducted between January 2001 and January 2002. RESULTS: Two types of MEG activity were observed in patients with OCD: (1) frontotemporal paroxysmal rhythmic activity with low-amplitude spikes (< 1 picoTesla) in 92% (11/12) of patients and (2) intermittent isolated spikes and sharp waves in all patients (12/12). The OCD group had paroxysmal rhythmic MEG activity in the cingulate cortex (12/12), insula (10/12), hippocampus (9/12), temporal superior gyrus and angular and supramarginal gyri (9/12), precentral and post-central gyri (8/12), orbitofrontal cortex (5/12), and parietal lobes (5/12). MEG recordings were normal in the control group, and EEG findings were normal in both the OCD and control groups. CONCLUSIONS: Frontotemporal paroxysmal rhythmic activity with a preferential limbic distribution is a sensitive MEG finding in patients with OCD. Although the pathophysiology of this abnormality remains unknown, a corticostriatal network dysfunction was hypothesized." [Abstract]

Kwon JS, Shin YW, Kim CW, Kim YI, Youn T, Han MH, Chang KH, Kim JJ.
Similarity and disparity of obsessive-compulsive disorder and schizophrenia in MR volumetric abnormalities of the hippocampus-amygdala complex.
J Neurol Neurosurg Psychiatry. 2003 Jul;74(7):962-4.
"OBJECTIVES: Given that obsessive-compulsive disorder (OCD) and schizophrenia may share clinical symptoms as well as functional brain abnormalities, this study was designed to clarify common and different morphological abnormalities in OCD and schizophrenia. METHODS: Volumes of the hippocampus, the amygdala, and the thalamus were measured in three age and sex matched groups of 22 patients with OCD, 22 patients with schizophrenia, and 22 normal subjects using three dimensional magnetic resonance imaging. Volume tracing was performed manually on serial coronal slices with the references of sagittal or axial planes using internal landmarks. RESULTS: Hippocampal volume was bilaterally reduced in both OCD and schizophrenic patients versus the normal controls. Left amygdala volume was significantly enlarged in patients with OCD but not in patients with schizophrenia versus the normal controls. The thalamus did not show any volumetric group differences. CONCLUSIONS: Non-specific hippocampal reduction in both the OCD and schizophrenic groups is likely to link to a clinical overlap between the two illnesses, whereas the left amygdala enlargement observed only in the OCD patients seems to be suggestive of a unique role for the amygdala in the pathophysiology of OCD." [Abstract]

Gamazo-Garran P, Soutullo CA, Ortuno F.
Obsessive-compulsive disorder secondary to brain dysgerminoma in an adolescent boy: a positron emission tomography case report.
J Child Adolesc Psychopharmacol. 2002 Fall;12(3):259-63.
"The neuroanatomical model involved in the pathophysiology of obsessive-compulsive disorder (OCD) postulates a hyperactivation of orbitofrontal, limbic, and basal ganglia circuits. We report a case of OCD secondary to brain dysgerminoma affecting this circuit in an adolescent who responded to citalopram. The patient is a 16-year-old-boy with a midline germinal tumor (dysgerminoma) affecting the caudate nuclei; left lenticular, right internal capsule's genu; and bilateral involvement of the interventricular septum close to the interventricular foramina. He had OCD symptoms and elevated tumor markers when he had a tumor relapse, and fluorodeoxyglucose positron emission tomography showed caudate nuclei involvement. He responded to citalopram that had to be titrated gradually to 80 mg/day." [Abstract]

Mac Master FP, Keshavan MS, Dick EL, Rosenberg DR.
Corpus callosal signal intensity in treatment-naive pediatric obsessive compulsive disorders.
Prog Neuropsychopharmacol Biol Psychiatry. 1999 May;23(4):601-12.
"1. Obsessive compulsive disorder (OCD) is increasingly recognized as a severe, highly prevalent and chronically disabling disorder, emerging during childhood in as many as 80% of cases. The authors previously found significant abnormalities in the region of the corpus callosum (CC) connecting ventral prefrontal cortex and striatum in pediatric OCD patients compared to controls that correlated significantly with OCD symptom severity. We speculated that this abnormality might reflect aberrant myelinization in OCD patients. 2. In order to better characterize the abnormality, the authors examined CC signal intensity (SI), believed to be a reliable index of myelinization of the CC. Lower numbers would indicate a greater concentration of white matter, while higher numbers indicate higher concentrations of gray matter. We compared the SI from midsagittal magnetic resonance images of 21 treatment-naive OCD patients, 7.2-17.7 years, and 21 case-matched healthy controls to examine regional CC signal intensity of the anterior, middle and posterior genu, body, isthmus, and the anterior, middle and the posterior splenii. 3. Mean total genu SI for the patient group (.993 + .006) was significantly less than the total genu SI of controls (.994 + .006) at F(1,37) = 4.73; p = .036. This abnormality in SI was localized to the CC region connecting ventral PFC and striatum, the anterior genu for the OCD group (.991 + .007) which was also less than control (.995 + .007) at F(1,37) = 5.47; p = .025., with no abnormality observed in middle or posterior genu regions. Genu SI was also inversely correlated with OCD symptom severity (r = -.55, p = .013) but not illness duration. Genu SI also correlated positively with genu area (r = .52, p = .020) in OCD patients but not controls. 4. Developmental abnormalities in genu size may arise from abnormalities in myelination in early onset OCD patients. The increased genu myelination observed in OCD patients may alter signal transduction and function of VPFC-striatal association circuits." [Abstract]

Rosenberg DR, Keshavan MS, Dick EL, Bagwell WW, MacMaster FP, Birmaher B.
Corpus callosal morphology in treatment-naive pediatric obsessive compulsive disorder.
Prog Neuropsychopharmacol Biol Psychiatry. 1997 Nov;21(8):1269-83.
"1. Abnormalities in association circuits have been described in Obsessive Compulsive Disorder (OCD) and may reflect neurodevelopmental abnormalities. Primary and association cortices are topographically mapped in the corpus callosum (CC). The authors hypothesized alterations in CC subdivisions that connect association, but not primary cortices in pediatric OCD. The authors predicted that normal age-related increases in CC area would be absent in OCD. 2. The authors compared the midsagittal magnetic resonance images of 21 psychotropic-naive, nondepressed OCD patients, 7.2-17.7 years, and 21 case-matched healthy controls. Total CC area as well as that of the anterior, middle and posterior genu, anterior and posterior bodies, isthmus, and the anterior, middle and the posterior splenii were measured. 3. All of the CC regions except the isthmus were significantly larger in OCD patients than in controls. CC area correlated significantly with OCD symptom severity but not illness duration. The age-related increase in CC size seen in normal subjects was absent in OCD patients. 4. These findings support theories of abnormal association cortex development in OCD but also suggest possible abnormalities of other primary cortical regions as well." [Abstract]

Farchione TR, Lorch E, Rosenberg DR.
Hypoplasia of the corpus callosum and obsessive-compulsive symptoms.
J Child Neurol. 2002 Jul;17(7):535-7.
"Abnormalities in the corpus callosum, which connects the cerebral hemispheres, have been implicated in the pathogenesis of obsessive-compulsive disorder. This is a report of two cases of obsessive-compulsive disorder associated with hypoplasia of the corpus callosum. These data provide further support for corpus callosum-mediated dysfunction in obsessive-compulsive disorder." [Abstract]
Denys D, van der Wee N, Janssen J, De Geus F, Westenberg HG.
Low level of dopaminergic D2 receptor binding in obsessive-compulsive disorder.
Biol Psychiatry. 2004 May 15;55(10):1041-5.
"BACKGROUND: Despite growing evidence for involvement of the dopaminergic system in obsessive-compulsive disorder (OCD), the functional anatomy of the dopaminergic system in the basal ganglia has been investigated sparsely. METHODS: Dopamine D(2) receptor binding was assessed in 10 medication-free OCD patients and 10 healthy control subjects, matched for age, gender, and handedness. The binding potential was measured with single photon emission computerized tomography (SPECT) and infusion of the D(2) receptor radiotracer [(123)I] iodobenzamide. With magnetic resonance imaging as reference, regions of interest (caudate and putamen) were delineated for each hemisphere and coregistered with the corresponding SPECT scans. RESULTS: Dopamine D(2) receptor binding in the left caudate nucleus was significantly lower in the patients with OCD than in healthy control subjects [F(1,18) = 7.0, p =.016]. In addition, an interhemispheric difference was observed in the patient sample. Both the D(2) receptor binding potential (df = 9, p =.012), and the volume (df = 9, p =.029) of the left caudate nucleus were statistically significantly reduced relative to the right caudate nucleus. CONCLUSIONS: This study provides in vivo evidence for abnormalities in the binding potential of the dopamine D(2) receptor, which suggest the direct involvement of the dopaminergic system in the pathophysiology of OCD." [Abstract]

Kim CH, Koo MS, Cheon KA, Ryu YH, Lee JD, Lee HS.
Dopamine transporter density of basal ganglia assessed with [123I]IPT SPET in obsessive-compulsive disorder.
Eur J Nucl Med Mol Imaging. 2003 Dec;30(12):1637-43. Epub 2003 Sep 25.
"It has been suggested that dopamine, as well as serotonin, is associated with the pathophysiology of obsessive-compulsive disorder (OCD). Thus, many studies have been performed on brain regions associated with dopamine in patients with OCD. In the present study, we investigated the DAT density of the basal ganglia using iodine-123 labelled N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane ([123I]IPT) single-photon emission tomography (SPET) and evaluated the activity of the presynaptic dopamine function in patients with OCD. Fifteen patients with OCD and 19 normal control adults were included in the study. We performed brain SPET 2 h after the intravenous administration of [123I]IPT and carried out both quantitative and qualitative analyses using the obtained SPET data, which were reconstructed for the assessment of the specific/non-specific dopamine transporter (DAT) binding ratio in the basal ganglia. We then investigated the correlation between the severity scores of OCD symptoms assessed with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and the specific/non-specific DAT binding ratio of the basal ganglia. Compared with normal control adults, patients with OCD showed a significantly increased specific/non-specific DAT binding ratio in the right basal ganglia and a tendency towards an increased specific/non-specific DAT binding ratio in the left basal ganglia. No significant correlation was found between the total scores on the Y-BOCS and the specific/non-specific DAT binding ratio of the basal ganglia. These findings suggest that the dopaminergic neurotransmitter system of the basal ganglia in patients with OCD could be involved in the pathophysiology of OCD." [Abstract]

Pogarell O, Hamann C, Popperl G, Juckel G, Chouker M, Zaudig M, Riedel M, Moller HJ, Hegerl U, Tatsch K.
Elevated brain serotonin transporter availability in patients with obsessive-compulsive disorder.
Biol Psychiatry. 2003 Dec 15;54(12):1406-13.
"BACKGROUND: A central serotonergic dysfunction is considered to be involved in the pathophysiology of obsessive-compulsive disorder (OCD). The aim of this study was to investigate the serotonin transporter availability in patients with OCD as an in vivo marker of the central serotonergic system. METHODS: Nine unmedicated (7 drug-naive) patients with OCD and 10 healthy control subjects were included and received single photon emission computed tomography (SPECT) 20.75 +/- 1.51 hours after injection of a mean 147.20 +/- 6.74 MBq [(123)I]-2beta-carbomethoxy-3beta-(4-iodophenyl)tropane ([(123)I]beta-CIT). As a measure of brain serotonin transporter availability, a ratio of specific-to-nonspecific [(123)I]beta-CIT binding for the midbrain-pons (V(3)" = [midbrain/pons-occipital]/occipital) was used. RESULTS: Mean specific-to-nonspecific ratios showed a 25% higher midbrain-pons [(123)I]beta-CIT binding in the patients as compared with healthy controls (2.26 +/-.37 vs. 1.81 +/-.23, p <.01). The difference remained significant after adjustment for clinical variables and controlling for age and gender. Stratification of the patients according to onset of the disorder revealed significant differences between controls and patients with early (childhood, adolescence) but not late (adult) onset of OCD. CONCLUSIONS: The study provides evidence of a serotonergic dysfunction in patients with OCD and suggests a serotonergic component in the pathophysiology of the disorder." [Abstract]

Simpson HB, Lombardo I, Slifstein M, Huang HY, Hwang DR, Abi-Dargham A, Liebowitz MR, Laruelle M.
Serotonin transporters in obsessive-compulsive disorder: a positron emission tomography study with [(11)C]McN 5652.
Biol Psychiatry. 2003 Dec 15;54(12):1414-21.
"BACKGROUND: Serotonergic abnormalities have been hypothesized to contribute to obsessive-compulsive disorder (OCD). This study examined whether brain serotonin transporter (SERT) availability is altered in OCD using positron emission tomography (PET) and the SERT PET radiotracer [(11)C]McN 5652. METHODS: Eleven OCD subjects, free of psychiatric medications and comorbid depression, and 11 matched healthy control subjects underwent PET scans following injection of [(11)C]McN 5652 and magnetic resonance imaging (MRI) scans. Total distribution volumes (V(T)) were derived by kinetic analysis (one tissue compartment model) using the arterial input function. Two measures of SERT availability were computed: binding potential (BP) and specific to nonspecific partition coefficient (V(3)"). Groups were compared using region of interest (ROI) analysis and voxelwise analysis of spatially normalized parametric maps; ROIs were selected based on their relatively high SERT density and included subcortical (dorsal caudate, dorsal putamen, ventral striatum, midbrain, thalamus) and limbic (hippocampus, amygdala, anterior cingulate cortex) regions. RESULTS: No significant group differences were observed in [(11)C]McN 5652 BP or V(3)" in the ROIs. No significant group differences were detected in the voxelwise analysis of BP or V(3)" maps. CONCLUSIONS: OCD without comorbid depression, may not be associated with major changes in SERT availability in subcortical and limbic regions." [Abstract]

Lacerda AL, Dalgalarrondo P, Caetano D, Haas GL, Camargo EE, Keshavan MS.
Neuropsychological performance and regional cerebral blood flow in obsessive-compulsive disorder.
Prog Neuropsychopharmacol Biol Psychiatry. 2003 Jun;27(4):657-65.
"Convergent findings from neuropsychological and neuroimaging studies have suggested that neural dysfunction in frontal-subcortical circuits may play a central role in the pathophysiology of obsessive-compulsive disorder (OCD). To further examine the relationship between these two sets of findings we investigated both neuropsychological functions and regional cerebral blood flow (rCBF) in a combined study. Fourteen unmedicated patients fulfilling DSM-IV criteria for OCD and 14 healthy controls matched for age, gender, handedness, and education were assessed on neuropsychological tests that included Trail Making Test (TMT), Rey Complex Figure Test (RCF) (copy and 5-min recall), Verbal Fluency Test (VFT), and Wisconsin Card Sorting Test (WCST). rCBF was studied with 99 mTc-hexamethyl-propyleneamine-oxime (HMPAO) single photon emission computed tomography (SPECT). Patients performed more poorly than controls (P<.05) on RCF (copy), VFT, and WCST (perseverative errors). Spearman's correlations indicated that severity of OCD correlated inversely with performance on the RCF (copy and recall scores) and positively with rCBF in the right thalamus. Positive correlations were observed between nonperseverative errors (WCST) and rCBF in frontal areas and anterior cingulate. Perseverative errors (WCST) correlated negatively with rCBF in the right thalamus. These findings are consistent with most previously published studies and suggest neural dysfunctions in the frontal-subcortical circuits probably more pronounced in the right hemisphere. They also extend the existing research, showing associations between deficits in cortical-subcortical circuitry and performance on neuropsychological tests of controlled attention and visuospatial functions." [Abstract]

Kwon JS, Kim JJ, Lee DW, Lee JS, Lee DS, Kim MS, Lyoo IK, Cho MJ, Lee MC.
Neural correlates of clinical symptoms and cognitive dysfunctions in obsessive-compulsive disorder.
Psychiatry Res. 2003 Jan 20;122(1):37-47.
"Although results from neuropsychological and neuroimaging studies have postulated the involvement of the frontal lobe and the subcortical brain regions in the pathophysiology of obsessive-compulsive disorder (OCD), neuroimaging studies have provided little evidence that cognitive abnormalities in patients with OCD are related to dysfunctions in these areas. This study was designed to determine whether the clinical features and cognitive deficits of OCD might be taken to reflect frontal-subcortical dysfunction. Fourteen patients with OCD and 14 case-matched normal subjects completed clinical and cognitive evaluation, including four sets of neuropsychological tests that assessed the executive functions and visual memory. Cerebral glucose metabolic rates were measured by using positron emission tomography (PET) with 18F-fluorodeoxyglucose. Behavioral and PET data were analyzed using statistical parametric mapping for group differences and behavioral-metabolic correlates. The right orbitofrontal cortex showed increased metabolic activity and the left parieto-occipital junction showed decreased metabolic activity in patients. Metabolism in the right hippocampus, the left putamen and the right parietal region was associated with the severity of obsessive-compulsive symptoms. Correlations between metabolic rates and neuropsychological test scores in the prefrontal cortex and the putamen occurred only in the patient group. These results suggest that patients with OCD have distinct features of brain metabolic activities for performing cognitive tasks as well as presenting obsessive-compulsive symptoms. In particular, the frontal-subcortical circuits might mediate not only symptomatic expression but also cognitive expression in patients with OCD." [Abstract]

[markog]

Ursu S, Stenger VA, Shear MK, Jones MR, Carter CS.
Overactive action monitoring in obsessive-compulsive disorder: evidence from functional magnetic resonance imaging.
Psychol Sci. 2003 Jul;14(4):347-53.
"The anterior cingulate cortex (ACC) in patients with obsessive-compulsive disorder (OCD) has been found to be hyperactive at rest, during symptom provocation, and after commission of errors in cognitive tasks. This hyperactivity might reflect an abnormality in conflict detection, a hypothesized basic mechanism for the action-monitoring function of the ACC. This hypothesis was tested using functional magnetic resonance imaging, by scanning 11 OCD patients and 13 matched control subjects while they performed a version of the continuous-performance task with four trial types that induced graded levels of response conflict. Although a behavioral index of conflict (i.e., accuracy) was similar for patients and control subjects, the ACC activation was increased in patients during high-conflict trials. The error-related activity in the same brain region was also higher in patients, consistent with previous electrophysiological findings. Both conflict- and error-related activity showed trends for positive correlations with severity of OCD symptoms, but not with anxiety. These findings suggest that as part of an overactive action-monitoring system, the ACC is more directly involved in the pathophysiology of OCD than previously thought." [Abstract]

van der Wee NJ, Ramsey NF, Jansma JM, Denys DA, van Megen HJ, Westenberg HM, Kahn RS.
Spatial working memory deficits in obsessive compulsive disorder are associated with excessive engagement of the medial frontal cortex.
Neuroimage. 2003 Dec;20(4):2271-80.
"Recent studies have shown that obsessive compulsive disorder (OCD) is associated with a specific deficit in spatial working memory, especially when task difficulty (i.e., working memory load) is high. It is not clear whether this deficit is associated with dysfunction of the brain system that subserves spatial working memory, or whether it is associated with a more generalized effect on executive functions. In contrast to studies in healthy volunteers and schizophrenia, spatial working memory in OCD has not been investigated before using functional neuroimaging techniques. We conducted a functional MRI study in 11 treatment-free female patients with OCD and 11 for sex-, age-, education-, and handedness pairwise-matched healthy controls in order to assess performance on a parametric spatial n-back task as well as the underlying neuronal substrate and its dynamics. Patients with OCD performed poorly at the highest level of task difficulty and engaged the same set of brain regions as the matched healthy controls. In this set, the effect of difficulty on magnitude of brain activity was the same in patients and in controls except for a region covering the anterior cingulate cortex. In this region activity was significantly elevated in patients with OCD at all levels of the parametric task. These findings do not provide evidence for a deficit of the spatial working memory system proper, but suggest that the abnormal performance pattern may be secondary to another aspect of executive dysfunctioning in OCD." [Abstract]

van Veen V, Carter CS.
The anterior cingulate as a conflict monitor: fMRI and ERP studies.
Physiol Behav. 2002 Dec;77(4-5):477-82.
"We propose that the anterior cingulate cortex (ACC) contributes to cognition by detecting the presence of conflict during information processing, and to alert systems involved in top-down control to resolve this conflict. Here, we review several functional magnetic resonance imaging (fMRI) and event-related potential (ERP) studies that have used simple response interference tasks, and propose that ACC activity is activated prior to the response during correct conflict trials and reflected in the frontocentral N2, and immediately following error trials and reflected in the error-related negativity (ERN). Furthermore, we suggest that certain disturbances in cognition and behavior in common mental disorders such as schizophrenia and obsessive-compulsive disorder (OCD) can be understood as resulting from alteration in performance monitoring functions associated with this region of the brain." [Abstract]

Saxena S, Brody AL, Maidment KM, Smith EC, Zohrabi N, Katz E, Baker SK, Baxter LR Jr.
Cerebral glucose metabolism in obsessive-compulsive hoarding.
Am J Psychiatry. 2004 Jun;161(6):1038-48.
"OBJECTIVE: Compulsive hoarding and saving symptoms, found in many patients with obsessive-compulsive disorder (OCD), are part of a discrete clinical syndrome that includes indecisiveness, disorganization, perfectionism, procrastination, and avoidance and has been associated with poor response to medications and cognitive behavior therapy. The authors sought to identify cerebral metabolic patterns specifically associated with the compulsive hoarding syndrome using positron emission tomography (PET). METHOD: [(18)F]Fluorodeoxyglucose PET scans were obtained for 45 adult subjects who met DSM-IV criteria for OCD (12 of whom had compulsive hoarding as their most prominent OCD symptom factor) and 17 normal comparison subjects. All subjects had been free of psychotropic medication for at least 4 weeks. Regional cerebral glucose metabolism was compared between the groups. RESULTS: In relation to the comparison subjects, the patients with compulsive hoarding syndrome had significantly lower glucose metabolism in the posterior cingulate gyrus and cuneus, whereas the nonhoarding OCD patients had significantly higher glucose metabolism in the bilateral thalamus and caudate. In relation to nonhoarding OCD patients, compulsive hoarders had significantly lower metabolism in the dorsal anterior cingulate gyrus. Across all OCD patients, hoarding severity was negatively correlated with glucose metabolism in the dorsal anterior cingulate gyrus. CONCLUSIONS: OCD patients with the compulsive hoarding syndrome had a different pattern of cerebral glucose metabolism than nonhoarding OCD patients and comparison subjects. Obsessive-compulsive hoarding may be a neurobiologically distinct subgroup or variant of OCD whose symptoms and poor response to anti-obsessional treatment are mediated by lower activity in the cingulate cortex." [Abstract]

Mataix-Cols D, Wooderson S, Lawrence N, Brammer MJ, Speckens A, Phillips ML.
Distinct neural correlates of washing, checking, and hoarding symptom dimensions in obsessive-compulsive disorder.
Arch Gen Psychiatry. 2004 Jun;61(6):564-76.
"CONTEXT: Obsessive-compulsive disorder (OCD) is clinically heterogeneous, yet most previous functional neuroimaging studies grouped together patients with mixed symptoms, thus potentially reducing the power and obscuring the findings of such studies. OBJECTIVE: To investigate the neural correlates of washing, checking, and hoarding symptom dimensions in OCD. DESIGN: Symptom provocation paradigm, functional magnetic resonance imaging, block design, and nonparametric brain mapping analyses. SETTING: University hospital. PARTICIPANTS: Sixteen patients with OCD (11 inpatients, 5 outpatients) with mixed symptoms and 17 healthy volunteers of both sexes.Intervention All subjects participated in 4 functional magnetic resonance imaging experiments. They were scanned while viewing alternating blocks of emotional (washing-related, checking-related, hoarding-related, or aversive, symptom-unrelated) and neutral pictures, and imagining scenarios related to the content of each picture type.Main Outcome Measure Blood oxygenation level-dependent response. RESULTS: Both patients and control subjects experienced increased subjective anxiety during symptom provocation (patients significantly more so) and activated neural regions previously linked to OCD. Analyses of covariance, controlling for depression, showed a distinct pattern of activation associated with each symptom dimension. Patients demonstrated significantly greater activation than controls in bilateral ventromedial prefrontal regions and right caudate nucleus (washing); putamen/globus pallidus, thalamus, and dorsal cortical areas (checking); left precentral gyrus and right orbitofrontal cortex (hoarding); and left occipitotemporal regions (aversive, symptom-unrelated). These results were further supported by correlation analyses within patients, which showed highly specific positive associations between subjective anxiety, questionnaire scores, and neural response in each experiment. There were no consistently significant differences between patients with (n = 9) and without (n = 7) comorbid diagnoses. CONCLUSIONS: The findings suggest that different obsessive-compulsive symptom dimensions are mediated by relatively distinct components of frontostriatothalamic circuits implicated in cognitive and emotion processing. Obsessive-compulsive disorder may be best conceptualized as a spectrum of multiple, potentially overlapping syndromes rather than a unitary nosologic entity." [Abstract]

Mataix-Cols D, Cullen S, Lange K, Zelaya F, Andrew C, Amaro E, Brammer MJ, Williams SC, Speckens A, Phillips ML.
Neural correlates of anxiety associated with obsessive-compulsive symptom dimensions in normal volunteers.
Biol Psychiatry. 2003 Mar 15;53(6):482-93.
"BACKGROUND: The neural correlates of anxiety associated with obsessive-compulsive symptomlike provocation in normal volunteers are unknown. METHODS: Ten healthy volunteers participated in four functional magnetic resonance experiments. Subjects were scanned while viewing alternating blocks of emotional (normally aversive, washing-relevant, checking-relevant, or hoarding-relevant pictures) and neutral pictures, and imagining scenarios related to the content of each picture type. Nonparametric brain mapping analyses were used. RESULTS: In response to the provocative pictures in all experiments, increases in subjective anxiety and activation in bilateral ventral prefrontal, limbic, dorsal prefrontal, and visual regions were demonstrated. Anxiety related to different symptom dimensions was associated with different patterns of activation: provocation of washing-relevant anxiety predominantly activated dorsal and ventral prefrontal regions; checking-relevant anxiety predominantly activated dorsal prefrontal regions; and hoarding-relevant anxiety predominantly activated ventral prefrontal regions and the left amygdala. CONCLUSIONS: Our findings support a dimensional model of obsessive-compulsive disorder (OCD) whereby 1) the brain systems implicated in the mediation of anxiety in response to symptom-related material in normal subjects are similar to those identified in OCD patients during symptom provocation, and 2) anxiety associated with different symptom dimensions is associated with differential patterns of activation of these neural systems. Further investigation of the neural basis of OCD symptom dimensions is required." [Abstract]

Phillips ML, Marks IM, Senior C, Lythgoe D, O'Dwyer AM, Meehan O, Williams SC, Brammer MJ, Bullmore ET, McGuire PK.
A differential neural response in obsessive-compulsive disorder patients with washing compared with checking symptoms to disgust.
Psychol Med. 2000 Sep;30(5):1037-50.
"BACKGROUND: Patients with obsessive-compulsive disorder (OCD) have symptoms that predominantly concern washing (washers) or checking (checkers), or both. Functional neuroimaging has been used to identify the neural correlates of the urge to ritualize but has not distinguished between washing and checking symptoms in OCD. We used functional magnetic resonance imaging to compare the neural response to emotive pictures in washers and checkers. METHODS: In one of two 5-minute experiments, washers (N = 7), checkers (N = 7) and age-matched normal controls (N = 14) were scanned while viewing alternating blocks of normally disgusting (rated as disgusting by all subjects) and neutral pictures. In the other experiment, all patients and a normal subgroup (N = 8) viewed alternating blocks of washer-relevant (rated as more disgusting by washers than normal controls or checkers) and neutral pictures. RESULTS: In all subjects, normally disgusting pictures activated visual regions implicated in perception of aversive stimuli and the insula, important in disgust perception. Only in washers were similar regions activated by washer-relevant pictures. In checkers, these pictures activated fronto-striatal regions associated with the urge to ritualize in OCD. Normal controls were more similar in neural response to checkers than washers to these pictures. Both normal controls and checkers had frontal regions activated significantly more by washer-relevant than normally disgusting pictures, and had these regions activated significantly more than washers by washer-relevant pictures. CONCLUSIONS: We demonstrate a differential neural response to washer-relevant disgust in washers and checkers: only washers demonstrate a neural response to washer-relevant disgust associated with emotion perception rather than attention to non-emotive visual detail." [Abstract]

Shapira NA, Liu Y, He AG, Bradley MM, Lessig MC, James GA, Stein DJ, Lang PJ, Goodman WK.
Brain activation by disgust-inducing pictures in obsessive-compulsive disorder.
Biol Psychiatry. 2003 Oct 1;54(7):751-6.
"BACKGROUND: There is growing interest in the role of disgust in the pathogenesis of obsessive-compulsive disorder (OCD). METHODS: Eight OCD subjects with contamination preoccupations and eight gender- and age-matched healthy volunteers viewed pictures from the International Affective Picture System during functional magnetic resonance imaging scans. RESULTS: A different distribution of brain activations was found during disgust-inducing visual stimulation in several areas, most notably the insula, compared with neutral stimulation in both OCD subjects and healthy volunteers. Furthermore, whereas activation during the threat-inducing task in OCD subjects showed a pattern similar to that in healthy volunteers, the pattern of activation during the disgust-inducing task was significantly different, including greater increases in the right insula, parahippocampal region, and inferior frontal sites. CONCLUSIONS: This pilot study supports the relevance of disgust in the neurocircuitry of OCD with contamination-preoccupation symptoms; future studies looking at non-OCD individuals with high disgust ratings, non-contamination-preoccupied OCD individuals, and individuals with other anxiety disorders are needed." [Abstract]

Lacerda AL, Dalgalarrondo P, Caetano D, Camargo EE, Etchebehere EC, Soares JC.
Elevated thalamic and prefrontal regional cerebral blood flow in obsessive-compulsive disorder: a SPECT study.
Psychiatry Res. 2003 Jun 30;123(2):125-34.
"Functional neuroimaging studies have pointed to a possible role of cerebral circuits involving the prefrontal and anterior cingulate cortices, the striatum, and thalamus in the pathophysiology of obsessive-compulsive disorder (OCD). Regional cerebral blood flow (rCBF) of 16 drug-free Brazilian patients with OCD and 17 healthy subjects matched for age, gender, handedness and level of education was measured with [99m-Tc] HMPAO single photon emission computed tomography. Analysis of covariance identified four regions of interest with significantly higher rCBF: the right superior and inferior frontal cortex and the right and left thalamus. Positive correlations between symptom severity measured by Clinical Global Impression scores and rCBF were found in the right and left inferior frontal lobes and in the right basal ganglia. Compulsive behavior was inversely correlated with rCBF in the right thalamus, and duration of illness correlated positively with rCBF in the right and left superior frontal lobes and with the right thalamus. The findings of this SPECT study conducted in Brazil are in agreement with prior studies and provide additional support for the involvement of prefrontal-subcortical circuits in the pathophysiology of OCD. Furthermore, the study suggests that similar brain mechanisms appear to be involved cross-culturally." [Abstract]

Rosenberg DR, Amponsah A, Sullivan A, MacMillan S, Moore GJ.
Increased medial thalamic choline in pediatric obsessive-compulsive disorder as detected by quantitative in vivo spectroscopic imaging.
J Child Neurol. 2001 Sep;16(9):636-41.
"The thalamus has been implicated in the pathophysiology of obsessive-compulsive disorder. Using a multislice spectroscopic imaging sequence, we reported reductions in right and left medial thalamic N-acetylaspartate/cytosolic choline + creatine/phosphocreatine and N-acetylaspartate/cytosolic choline levels in 11 pediatric patients with obsessive-compulsive disorder, 8 to 15 years, versus 11 case-matched healthy controls. These changes may reflect a change in N-acetylaspartate, cytosolic choline, or creatine concentrations. Therefore, using a validated phantom replacement methodology, we obtained absolute measures (mmol/L) of N-acetylaspartate, a putative marker of neuronal viability, cytosolic choline, and creatine in these subjects. A significant increase in cytosolic choline was observed in right and left medial but not lateral thalami in patients with obsessive-compulsive disorder versus controls. N-acetylaspartate and creatine did not differ significantly between case-control pairs in the medial or lateral thalamus. These findings provide new evidence of cytosolic choline abnormalities in the thalamus in pediatric obsessive-compulsive disorder." [Abstract]

Smith EA, Russell A, Lorch E, Banerjee SP, Rose M, Ivey J, Bhandari R, Moore GJ, Rosenberg DR.
Increased medial thalamic choline found in pediatric patients with obsessive-compulsive disorder versus major depression or healthy control subjects: a magnetic resonance spectroscopy study.
Biol Psychiatry. 2003 Dec 15;54(12):1399-405.
"BACKGROUND: Neurobiologic abnormalities in medial thalamus have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). We previously used multislice proton magnetic resonance spectroscopic imaging (1-H MRSI) to identify localized functional neurochemical marker alterations in choline (Cho) in medial but not lateral thalamus in treatment-naive pediatric patients with OCD compared with matched control subjects. Altered brain Cho levels have also been implicated in the pathogenesis of mood disorders. METHODS: We used 1-H MRSI to study absolute Cho concentrations in 18 psychotropic-naive pediatric patients with major depressive disorder (MDD) not suffering from OCD, 9-17 years of age, 18 case-matched healthy control subjects, and 27 nondepressed, psychotropic-naive pediatric patients with OCD, 7-16 years of age. RESULTS: Significantly increased left and right medial thalamic Cho concentrations were observed in OCD patients compared with both healthy control subjects and patients with MDD. Medial thalamic Cho concentrations did not differ significantly between patients with MDD and control subjects. CONCLUSIONS: These results suggest that localized functional neurochemical marker alterations in medial thalamic Cho differentiate patients with OCD from healthy control subjects and patients with MDD. Although these results must be considered preliminary, further study of the diagnostic specificity of Cho as a relevant biomarker in OCD is clearly warranted." [Abstract]

Busatto GF, Buchpiguel CA, Zamignani DR, Garrido GE, Glabus MF, Rosario-Campos MC, Castro CC, Maia A, Rocha ET, McGuire PK, Miguel EC.
Regional cerebral blood flow abnormalities in early-onset obsessive-compulsive disorder: an exploratory SPECT study.
J Am Acad Child Adolesc Psychiatry. 2001 Mar;40(3):347-54.
"OBJECTIVE: Recent epidemiological and clinical data suggest that obsessive-compulsive disorder (OCD) may be subtyped according the age of onset of obsessive-compulsive symptoms. The regional cerebral blood flow (rCBF) single photon emission computed tomography (SPECT) technique was used to investigate whether the pathophysiology of OCD differs between early- and late-onset OCD subjects. METHOD: Resting rCBF was measured in 13 early-onset (<10 years) and 13 late-onset (>12 years) adult OCD subjects and in 22 healthy controls. Voxel-based rCBF comparisons were performed with statistical parametric mapping. RESULTS: Early-onset OCD cases showed decreased rCBF in the right thalamus, left anterior cingulate cortex, and bilateral inferior prefrontal cortex relative to late-onset subjects (p < .0005, uncorrected for multiple comparisons). Relative to controls, early-onset cases had decreased left anterior cingulate and right orbitofrontal rCBF, and increased rCBF in the right cerebellum, whereas late-onset subjects showed reduced right orbitofrontal rCBF and increased rCBF in the left precuneus. In early-onset subjects only, severity of obsessive-compulsive symptoms correlated positively with left orbitofrontal rCBF. CONCLUSIONS: rCBF differences in frontal-subcortical circuits between early-onset and late-onset OCD subjects were found, both in location and direction of changes. These results provide preliminary evidence that brain mechanisms in OCD may differ depending on the age at which symptoms are first expressed." [Abstract]

Adler CM, McDonough-Ryan P, Sax KW, Holland SK, Arndt S, Strakowski SM.
fMRI of neuronal activation with symptom provocation in unmedicated patients with obsessive compulsive disorder.
J Psychiatr Res. 2000 Jul-Oct;34(4-5):317-24.
"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." [Abstract]

Gilbert AR, Moore GJ, Keshavan MS, Paulson LA, Narula V, Mac Master FP, Stewart CM, Rosenberg DR.
Decrease in thalamic volumes of pediatric patients with obsessive-compulsive disorder who are taking paroxetine.
Arch Gen Psychiatry. 2000 May;57(5):449-56.
"BACKGROUND: Thalamic dysfunction has been implicated in obsessive-compulsive disorder (OCD). While OCD frequently has its onset during childhood, to our knowledge, no prior study has measured neuroanatomical changes in the thalamus of patients with OCD near the onset of illness, and before and after treatment. METHODS: Volumetric magnetic resonance imaging studies were conducted in 21 psychotropic drug-naive children, aged 8 to 17 years, with OCD and 21 case-matched healthy comparison subjects. Magnetic resonance imaging studies were also conducted in 10 of the 21 patients with OCD after 12 weeks of monotherapy with the selective serotonin reuptake inhibitor, paroxetine hydrochloride. RESULTS: Thalamic volumes were significantly greater in treatment-naive patients with OCD than in controls but declined significantly after paroxetine monotherapy to levels comparable with those of controls. Decrease in thalamic volume in patients with OCD was associated with reduction in OCD symptom severity. CONCLUSIONS: Our findings provide new evidence of thalamic abnormalities in pediatric OCD and further suggest that paroxetine treatment may be paralleled by a reduction in thalamic volume. These reductions may, however, not be specific to paroxetine treatment and could be due to a more general treatment response, and/or spontaneous improvement in symptoms. Our findings are preliminary given the small sample size and our inability to measure discrete thalamic nuclei." [Abstract]

Rosenberg DR, Benazon NR, Gilbert A, Sullivan A, Moore GJ.
Thalamic volume in pediatric obsessive-compulsive disorder patients before and after cognitive behavioral therapy.
Biol Psychiatry. 2000 Aug 15;48(4):294-300.
"BACKGROUND: Neurobiologic abnormalities in the thalamus have been implicated in the pathophysiology of obsessive-compulsive disorder. We recently reported increased thalamic volume in treatment-naive pediatric obsessive-compulsive disorder patients versus case-matched healthy comparison subjects that decreased to levels comparable to control subjects after effective paroxetine therapy. To our knowledge, no prior study has measured neuroanatomic changes in the thalamus of obsessive-compulsive disorder patients near illness onset before and after cognitive behavioral therapy. METHODS: Volumetric magnetic resonance imaging studies were conducted in 11 psychotropic drug-naive 8-17-year-old children with obsessive-compulsive disorder before and after 12 weeks of effective cognitive behavioral therapy monotherapy (> or =30% reduction in obsessive-compulsive disorder symptom severity). RESULTS: No significant change in thalamic volume was observed in obsessive-compulsive disorder patients before and after cognitive behavioral therapy. CONCLUSIONS: Our findings suggest that reduction in thalamic volume after paroxetine therapy may be specific to paroxetine treatment and not the result of a general treatment response or spontaneous improvement. These results are preliminary in view of the small sample studied." [Abstract]

Schwartz JM, Stoessel PW, Baxter LR Jr, Martin KM, Phelps ME.
Systematic changes in cerebral glucose metabolic rate after successful behavior modification treatment of obsessive-compulsive disorder.
Arch Gen Psychiatry. 1996 Feb;53(2):109-13.
"BACKGROUND: We sought to determine in a new patient sample whether symptomatic improvement in obsessive-compulsive disorder treated with behavior modification is accompanied by significant changes in glucose metabolic rates in the caudate nucleus, measured with positron emission tomography, as seen in a previous study. Second, by combining samples from this and the previous study, we also examined whether there were pathologic correlational relationships among brain activity in the orbital cortex, caudate nucleus, and thalamus that obtained before behavioral treatment of obsessive-compulsive disorder, but that decreased significantly with symptom improvement. METHODS: Nine patients with obsessive-compulsive disorder were studied with positron emission tomography before and after 10 weeks of structured exposure and response prevention behavioral and cognitive treatment. Results were analyzed both alone and combined with those from nine similar subjects from the previous study. RESULTS: Behavior therapy responders had significant (P < .05) bilateral decreases in caudate glucose metabolic rates that were greater than those seen in poor responders to treatment. Before treatment, there were significant correlations of brain activity between the orbital gyri and the head of the caudate nucleus and the orbital gyri and the thalamus on the right. These correlations decreased significantly after effective treatment. CONCLUSIONS: These results replicate and extend previous findings of changes in caudate nucleus function with behavior therapy for obsessive-compulsive disorder. A prefrontal cortico-striato-thalamic brain system is implicated in mediation of symptoms of obsessive-compulsive disorder." [Abstract]

Busatto GF, Zamignani DR, Buchpiguel CA, Garrido GE, Glabus MF, Rocha ET, Maia AF, Rosario-Campos MC, Campi Castro C, Furuie SS, Gutierrez MA, McGuire PK, Miguel EC.
A voxel-based investigation of regional cerebral blood flow abnormalities in obsessive-compulsive disorder using single photon emission computed tomography (SPECT).
Psychiatry Res. 2000 Jul 10;99(1):15-27.
"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." [Abstract]

Ohara K, Isoda H, Suzuki Y, Takehara Y, Ochiai M, Takeda H, Igarashi Y, Ohara K.
Proton magnetic resonance spectroscopy of lenticular nuclei in obsessive-compulsive disorder.
Psychiatry Res. 1999 Dec 20;92(2-3):83-91.
"Our results suggest the normal viability of neuronal cells, as indicated by the quantification of NAA, Cr and Cho in the lenticular nuclei of patients with OCD." [Abstract]

Giedd JN, Rapoport JL, Garvey MA, Perlmutter S, Swedo SE.
MRI assessment of children with obsessive-compulsive disorder or tics associated with streptococcal infection.
Am J Psychiatry. 2000 Feb;157(2):281-3.
"OBJECTIVE: The authors assessed selective basal ganglia involvement in a subgroup of children with obsessive-compulsive disorder (OCD) and/or tics believed to be associated with streptococcal infection. METHOD: Using computer-assisted morphometric techniques, they analyzed the cerebral magnetic resonance images of 34 children with presumed streptococcus-associated OCD and/or tics and 82 healthy comparison children who were matched for age and sex. RESULTS: The average sizes of the caudate, putamen, and globus pallidus, but not of the thalamus or total cerebrum, were significantly greater in the group of children with streptococcus-associated OCD and/or tics than in the healthy children. The differences were similar to those found previously for subjects with Sydenham's chorea compared with normal subjects. CONCLUSIONS: These results support the hypothesis that there is a distinct subgroup of subjects with OCD and/or tics who have enlarged basal ganglia. These findings are consistent with the hypothesis of an autoimmune response to streptococcal infection." [Abstract]

Stein DJ, Van Heerden B, Wessels CJ, Van Kradenburg J, Warwick J, Wasserman HJ.
Single photon emission computed tomography of the brain with Tc-99m HMPAO during sumatriptan challenge in obsessive-compulsive disorder: investigating the functional role of the serotonin auto-receptor.
Prog Neuropsychopharmacol Biol Psychiatry. 1999 Aug;23(6):1079-99.
"1. Symptoms of obsessive-compulsive disorder (OCD) may be acutely exacerbated by administration of certain serotonin agonists Exacerbation of OCD symptoms by sumatriptan, a 5HT1D agonist (Zohar, 1993), is consistent with pre-clinical data suggesting that the serotonin auto-receptor plays an important role in this disorder (El Mansari et al, 1995). 2. In order to investigate the functional role of the serotonin auto-receptor in OCD, the authors undertook single photon emission computed tomography in OCD patients after administration of sumatriptan and placebo. The authors hypothesized that, as in the case of m-chlorophenylpiperazine (mCPP) challenge (Hollander et al, 1995), exacerbation of OCD symptoms would be accompanied by increased cortical metabolism and thus blood flow, and more specifically by increased activity in the orbitofrontal-striatal circuit. They also expected, that as in the case of mCPP challenge (Hollander et al, 1993), exacerbation of OCD symptoms would be associated with a relatively poor response to subsequent treatment with serotonin specific reuptake inhibitors. 3. Sumatriptan (100 mg orally) and placebo were administered on separate days to 14 patients who met DSM-IV diagnostic criteria for OCD, using a randomized double-blind design. After 90 minutes, patients were injected with Tc-99m HMPAO and underwent single photon emission computed tomography (SPECT) of the brain. Activity in regions of interest was calculated, and compared using repeated measures analysis of variance. Patients were subsequently treated with a serotonin specific reuptake inhibitor (SSRI). 4. Behavioral response to sumatriptan was heterogenous, with 4 patients showing acute exacerbation, and 4 patients demonstrating a decrease in symptoms. On sumatriptan challenge, there was a significant association between symptom exacerbation and decreased activity in frontal areas. There was an association between decreased activity in an inferior frontal area with worse response to treatment, and also patients with symptom exacerbation after sumatriptan had poorer response to SSRI treatment. 5. Heterogeneity of behavioral response to sumatriptan in OCD is consistent with previous studies demonstrating conflicting and heterogenous behavioral responses to serotonergic challenges (Hollander et al, 1992), and with underlying heterogeneity in the neurobiology of this disorder. 6. It may be hypothesized that increased frontal activity in some patients with OCD is itself a compensatory mechanism. In patients with such compensatory hyperactivity, administration of a serotonin auto-receptor agonist results in decreased frontal activity and exacerbation of OCD symptoms. These patients may also be less likely to respond to treatment with a SSRI. 7. Further work combining pharmacological challenge paradigms and functional imaging techniques in OCD may be helpful in elucidating the neurobiology of this complex disorder." [Abstract]

Lucey JV, Costa DC, Blanes T, Busatto GF, Pilowsky LS, Takei N, Marks IM, Ell PJ, Kerwin RW.
Regional cerebral blood flow in obsessive-compulsive disordered patients at rest. Differential correlates with obsessive-compulsive and anxious-avoidant dimensions.
Br J Psychiatry. 1995 Nov;167(5):629-34.
"BACKGROUND. We tested whether cortical and subcortical regional cerebral blood flow (rCBF) differs between patients with obsessive-compulsive disorder (OCD) and healthy controls. We then explored the relationship between rCBF and OCD mental state. METHOD. Thirty out-patients from the Maudsley Hospital with OCD as defined in DSM-III-R were scanned at rest using brain-dedicated, high-resolution, single photon emission tomography. RCBF was measured as uptake of 99mTc-HMPAO in 15 regions of interest and compared with rCBF data in 30 healthy people matched for age, sex and handedness. Symptom ratings were obtained using standard measures on the scanning day. Principal components factor analysis identified two distinct clinical dimensions: obsessive-compulsive (OC) and anxious-avoidant (AA). These were correlated with patients' rCBF measurements, using Spearman's rank correlation coefficient, and multiple regression coefficients calculated. RESULTS. We found significant reductions in rCBF measurements of OCD patients compared with resting, healthy controls (F = 1.92, P = 0.04) in seven brain regions: the right and left superior frontal cortex, right inferior frontal cortex, left temporal cortex, left parietal cortex, right caudate nucleus and right thalamus. Regional differences were not secondary to generalised reduction in patients' brain perfusion. Reduced blood flow to the right inferior frontal cortex correlated significantly with illness severity (r = 0.37, P = 0.02). There was no relationship with age, age-of-onset, sex, handedness, depression or medication status. OC clinical dimension, concerning obsessions, compulsions and low mood, was significantly negatively correlated with left inferior frontal, medial frontal and right parietal rCBF. AA dimension, concerning anxiety and avoidance, was significantly positively associated with left and right superior frontal, right inferior frontal, medial frontal cortical, and right and left caudate and thalamic rCBF. CONCLUSIONS. rCBF differs significantly between resting OCD patients and healthy controls, and separate clinical dimensions are associated with functionally distinct rCBF patterns." [Abstract]


Brody AL, Saxena S, Schwartz JM, Stoessel PW, Maidment K, Phelps ME, Baxter LR Jr.
FDG-PET predictors of response to behavioral therapy and pharmacotherapy in obsessive compulsive disorder.
Psychiatry Res. 1998 Nov 9;84(1):1-6.
"In subjects with obsessive-compulsive disorder (OCD), lower pre-treatment metabolism in the right orbitofrontal cortex (OFC) and anterior cingulate gyrus (AC) has been associated with a better response to clomipramine. We sought to determine pre-treatment metabolic predictors of response to behavioral therapy (BT) vs. pharmacotherapy in subjects with OCD. To do this, [18F]fluorodeoxyglucose positron emission tomography scans of the brain were obtained in subjects with OCD before treatment with either BT or fluoxetine. A Step-Wise Variable Selection was applied to normalized pre-treatment glucose metabolic rates in the OFC, AC, and caudate by treatment response (change in Yale-Brown Obsessive-Compulsive Scale) in the larger BT group. Left OFC metabolism (normalized to the ipsilateral hemisphere) alone was selected as predicting treatment response in the BT-treated group (F = 6.07, d.f. = 1,17, P = 0.025). Correlations between normalized left OFC metabolism and treatment response revealed that higher normalized metabolism in this region was associated with greater improvement in the BT-treated group (tau = 0.35, P = 0.04), but worse outcome (tau = -0.57, P = 0.03) in the fluoxetine-treated group. These results suggest that subjects with differing patterns of metabolism preferentially respond to BT vs. medication." [Abstract]

Pujol J, Soriano-Mas C, Alonso P, Cardoner N, Menchon JM, Deus J, Vallejo J.
Mapping structural brain alterations in obsessive-compulsive disorder.
Arch Gen Psychiatry. 2004 Jul;61(7):720-30.
"BACKGROUND: Recent technical developments have made it feasible to comprehensively assess brain anatomy in psychiatric populations. OBJECTIVE: To describe the structural brain alterations detected in the magnetic resonance images of a large series of patients with obsessive-compulsive disorder (OCD) using imaging procedures that allow the evaluation of volume changes throughout the brain. DESIGN: Case-control study. SETTING: Referral OCD unit in a tertiary hospital. PARTICIPANTS: A consecutive sample of 72 outpatients with OCD and 72 age- and sex-matched control subjects. INTERVENTIONS: Three-dimensional sequences were obtained in all participants. A statistical parametric mapping approach was used to delineate possible anatomical alterations in the entire brain. To preserve volumetric information, voxel values were modulated by the Jacobian determinants (volume change measurement) derived from spatial normalization. MAIN OUTCOME MEASURES: Voxelwise brain volumes. RESULTS: The brains of patients with OCD showed reduced gray matter volume in the medial frontal gyrus, the medial orbitofrontal cortex, and the left insulo-opercular region. A relative increase in gray matter volume was observed bilaterally in the ventral part of the putamen and in the anterior cerebellum. All these brain alterations were abnormally correlated in patients with OCD, and age statistically significantly contributed to the relative enlargement observed in the striatal areas. Disease severity, the nature of symptoms, and comorbidities were not related to the changes described. Nevertheless, patients with prominent aggressive obsessions and checking compulsions showed reduced amygdala volume in the right hemisphere. CONCLUSIONS: The pattern of anatomical features depicted by this voxelwise approach is consistent with data from functional studies. The reported anatomical maps identified the specific parts of the frontostriatal system that were altered in patients with OCD and detected changes in anatomically connected distant regions. These data further define the structural brain alterations in OCD and may contribute to constraining the prevailing biological models of this psychiatric process." [Abstract]

Szeszko PR, MacMillan S, McMeniman M, Chen S, Baribault K, Lim KO, Ivey J, Rose M, Banerjee SP, Bhandari R, Moore GJ, Rosenberg DR.
Brain structural abnormalities in psychotropic drug-naive pediatric patients with obsessive-compulsive disorder.
Am J Psychiatry. 2004 Jun;161(6):1049-56.
"OBJECTIVE: The authors investigated structural abnormalities in brain regions comprising cortical-striatal-thalamic-cortical loops in pediatric patients with obsessive-compulsive disorder (OCD). METHOD: Volumes of the caudate nucleus, putamen, and globus pallidus and gray and white matter volumes of the anterior cingulate gyrus and superior frontal gyrus were computed from contiguous 1.5-mm magnetic resonance images from 23 psychotropic drug-naive pediatric patients with OCD (seven male patients and 16 female patients) and 27 healthy volunteers (12 male subjects and 15 female subjects). RESULTS: Patients had smaller globus pallidus volumes than healthy volunteers, but the two groups did not differ in volumes of the caudate nucleus, putamen, or frontal white matter regions. Compared to healthy volunteers, patients had more total gray matter in the anterior cingulate gyrus but not the superior frontal gyrus. Total anterior cingulate gyrus volume correlated significantly and positively with globus pallidus volume in the healthy volunteers but not in patients. CONCLUSIONS: These findings provide evidence of smaller globus pallidus volume in patients with OCD without the potentially confounding effects of prior psychotropic drug exposure. Volumetric abnormalities in the anterior cingulate gyrus appear specific to the gray matter in OCD, at least at the gross anatomic level, and are consistent with findings of functional neuroimaging studies that have reported anterior cingulate hypermetabolism in the disorder." [Abstract]

Jenike MA, Breiter HC, Baer L, Kennedy DN, Savage CR, Olivares MJ, O'Sullivan RL, Shera DM, Rauch SL, Keuthen N, Rosen BR, Caviness VS, Filipek PA.
Cerebral structural abnormalities in obsessive-compulsive disorder. A quantitative morphometric magnetic resonance imaging study.
Arch Gen Psychiatry. 1996 Jul;53(7):625-32.
"BACKGROUND: A previous pilot study of only posterior brain regions found lower white-matter volume in patients with obsessive-compulsive disorder than in normal control subjects. We used new cohorts of patients and matched normal control subjects to study whole-brain volume differences between these groups with magnetic resonance imaging-based morphometry. METHODS: Ten female patients with obsessive-compulsive disorder and 10 female control subjects, matched for handedness, age, weight, education, and verbal IQ, underwent magnetic resonance imaging with a 3-dimensional volumetric protocol. Scans were blindly normalized and segmented by means of well-characterized semiautomated intensity contour mapping and differential intensity contour algorithms. Brain structures investigated included the cerebral hemispheres, cerebral cortex, diencephalon, caudate, putamen, globus pallidus, hippocampus amygdala, third and fourth ventricles, corpus callosum, operculum, cerebellum, and brain stem. Anterior to posterior neocortical regions, including precallosum, anterior pericallosum, posterior pericallosum, and retrocallosum, with adjacent white matter were also measured. Volumes found different between groups were correlated with Yale-Brown Obsessive Compulsive Scale score and Rey-Osterieth Complex Figure Test measures. RESULTS: Confirming results of our earlier pilot study and expanding the findings to the whole brain, patients with obsessive-compulsive disorder had significantly less total white matter but, in addition, significantly greater total cortex and opercular volumes. Severity of obsessive-compulsive disorder and nonverbal immediate memory correlated with opercular volume. CONCLUSIONS: Replication of volumetric white-matter differences suggests a widely distributed structural brain abnormality in obsessive-compulsive disorder. Whereas determining the etiogenesis may require research at a microscopic level, understanding its functional significance can be further explored via functional neuroimaging and neuropsychological studies." [Abstract]

Cottraux J, Gerard D, Cinotti L, Froment JC, Deiber MP, Le Bars D, Galy G, Millet P, Labbe C, Lavenne F, Bouvard M, Mauguiere F.
A controlled positron emission tomography study of obsessive and neutral auditory stimulation in obsessive-compulsive disorder with checking rituals.
Psychiatry Res. 1996 Mar 29;60(2-3):101-12.
"Ten nondepressed patients with obsessive-compulsive disorder (OCD) who were characterized by predominant checking rituals were compared with 10 age- and sex-matched control subjects. Hemispheric and regional cerebral blood flow levels (rCBF) were measured with positron emission tomography (H2 15O) across four conditions: rest, auditory stimulation with idiosyncratic normal or abnormal obsession, auditory stimulation with neutral verbal stimuli, and rest. Order of neutral and obsessive stimulation was randomized. Higher subjective responses to obsessive than to neutral stimulation were found in both groups; subjective response was higher in OCD patients when obsessive stimulation was presented first. A four-way analysis of variance (group x stimulation order x hemisphere x condition [neutral or obsessive stimulation]) was performed on stimulation minus rest normalized rCBF values. Control subjects had significantly higher rCBF in the thalamus and putamen. A trend toward higher rCBF in OCD patients was found in the superior temporal regions. When neutral stimulation was presented first, rCBF was significantly higher in the caudate region of control subjects. Obsessive stimulation was associated with higher rCBF than neutral stimulation in orbitofrontal regions in both groups of subjects. Under obsessive stimulation, superior temporal and orbitofrontal activities were correlated in OCD patients but not in control subjects. Our study suggests specific abnormalities of information processing in the basal ganglia and temporal structures of compulsive checkers." [Abstract]

Rosenberg DR, Keshavan MS, O'Hearn KM, Dick EL, Bagwell WW, Seymour AB, Montrose DM, Pierri JN, Birmaher B.
Frontostriatal measurement in treatment-naive children with obsessive-compulsive disorder.
Arch Gen Psychiatry. 1997 Sep;54(9):824-30.
"BACKGROUND: Abnormalities in frontostriatal circuits have been implicated in obsessive-compulsive disorder (OCD). Although OCD commonly emerges during childhood or adolescence, few studies have examined frontostriatal anatomy in psychotropic-naive children with OCD near the onset of illness to determine the possible role of atypical developmental processes in this disorder. METHODS: Magnetic resonance imaging scans from 19 children with OCD who had not been exposed to psychotropic drugs, aged 7 to 18 years, and 19 case-matched healthy control subjects were analyzed to determine the volumes of the following structures: prefrontal cortex, striatum (caudate and putamen), lateral and third ventricles, and intracranial volume. RESULTS: Patients with OCD had significantly smaller striatal volumes and significantly larger third ventricle volumes than controls, but did not differ in prefrontal cortical, lateral ventricular, or intracranial volumes. Striatal volumes were inversely correlated with OCD symptom severity but not illness duration. CONCLUSIONS: Our findings provide new evidence of abnormalities of the striatum in pediatric OCD. These results are preliminary, given the small sample size." [Abstract]

Russell A, Cortese B, Lorch E, Ivey J, Banerjee SP, Moore GJ, Rosenberg DR.
Localized functional neurochemical marker abnormalities in dorsolateral prefrontal cortex in pediatric obsessive-compulsive disorder.
J Child Adolesc Psychopharmacol. 2003;13 Suppl 1:S31-8.
"BACKGROUND: Neurobiological abnormalities in the prefrontal cortex have been implicated in the pathogenesis of obsessive-compulsive disorder (OCD). Although OCD commonly arises during childhood and adolescence, to our knowledge, no prior study has examined prefrontal cortex neurochemistry in pediatric patients with OCD. METHODS: A multislice spectroscopic imaging sequence with validated phantom replacement methodology was used to measure N-acetyl-aspartate (NAA), a putative neuronal marker; choline compounds (Cho); and creatine/phosphocreatine (Cr) in right and left dorsolateral prefrontal cortex (DLPFC) of 15 treatment-naive OCD patients, 8-15 years of age, and 15 case-matched healthy comparison subjects. RESULTS: A significant increase (21% higher) in NAA was observed in left but not right DLPFC in OCD patients versus control subjects. No significant differences in Cho or Cr were observed between groups in left or right DLPFC. CONCLUSIONS: These results provide new evidence of localized functional neurochemical marker alterations in left DLPFC in pediatric OCD. Increased left DLPFC NAA may represent neuronal hypertrophy or hyperplasia, glial hypoplasia, and/or abnormal pruning of neural brain elements in DLPFC." [Abstract]

Edmonstone Y, Austin MP, Prentice N, Dougall N, Freeman CP, Ebmeier KP, Goodwin GM.
Uptake of 99mTc-exametazime shown by single photon emission computerized tomography in obsessive-compulsive disorder compared with major depression and normal controls.
Acta Psychiatr Scand. 1994 Oct;90(4):298-303.
"Twelve patients with obsessive-compulsive disorder (OCD) were investigated at rest using single photon emission computerized tomography with 99mTc-exametazime. The uptake of 99mTc-exametazime was expressed relative to calcarine/occipital cortex. Patients were matched for drug treatment with 12 patients with a major depressive episode and the patient groups were compared with a control group. Significant bilateral decreases in tracer uptake were confined to basal ganglia in the OCD group. There was a paradoxical positive correlation between anxiety ratings and tracer uptake to basal ganglia in the OCD group. The findings confirm that the functional topography of OCD implicates altered function in the basal ganglia." [Abstract]

Adams BL, Warneke LB, McEwan AJ, Fraser BA.
Single photon emission computerized tomography in obsessive compulsive disorder: a preliminary study.
J Psychiatry Neurosci. 1993 May;18(3):109-12.
"Patterns of cerebral perfusion in patients with obsessive compulsive disorder were evaluated using single photon emission computerized tomography. Eleven patients, who satisfied the DSM-III-R criteria and Research Diagnostic Criteria for the disorder, were evaluated using the distribution of 99m-Tc-HMPAO as a radiotracer. The Yale-Brown Obsessive Compulsive Scale was administered to each patient to assess the severity of their symptoms. The images obtained were evaluated qualitatively and semi-quantitatively by a physician in nuclear medicine who was blind to the patients' diagnoses. Eight of the 11 patients demonstrated asymmetric perfusion of the basal ganglia; the left side showed impaired perfusion in six patients." [Abstract]

Machlin SR, Harris GJ, Pearlson GD, Hoehn-Saric R, Jeffery P, Camargo EE.
Elevated medial-frontal cerebral blood flow in obsessive-compulsive patients: a SPECT study.
Am J Psychiatry. 1991 Sep;148(9):1240-2.
"Regional cerebral blood flow was measured with single photon emission computed tomography in 10 obsessive-compulsive patients and eight comparison subjects. The patients had a significantly higher ratio of medial-frontal to whole cortex blood flow; this was unrelated to symptom severity but was correlated negatively with anxiety. No differences in orbital-frontal blood flow were found." [Abstract]

Kellner CH, Jolley RR, Holgate RC, Austin L, Lydiard RB, Laraia M, Ballenger JC.
Brain MRI in obsessive-compulsive disorder.
Psychiatry Res. 1991 Jan;36(1):45-9.
"Magnetic resonance imaging (MRI) brain scans were performed on 12 patients with obsessive-compulsive disorder and 12 healthy controls. Measurements of the area of the head of the caudate nucleus, cingulate gyrus thickness, intracaudate/frontal horn ratio, and area of the corpus callosum did not differ between the two groups. These limited data do not support the presence of a consistent gross brain structural abnormality in obsessive-compulsive disorder. Further studies using other anatomic measurements and other brain structural imaging techniques are warranted." [Abstract]

Benkelfat C, Nordahl TE, Semple WE, King AC, Murphy DL, Cohen RM.
Local cerebral glucose metabolic rates in obsessive-compulsive disorder. Patients treated with clomipramine.
Arch Gen Psychiatry. 1990 Sep;47(9):840-8.
"In a recent study, we reported abnormal local cerebral glucose metabolic rates in the orbital frontal cortex of patients with obsessive-compulsive disorder. Eight patients with obsessive-compulsive disorder scanned previously were scanned again during treatment with the tricyclic antidepressant clomipramine hydrochloride. Comparisons of local cerebral glucose metabolic rates for both groups showed a relative decrease in regions of the orbital frontal cortex and the left caudate, and an increase in other areas of the basal ganglia, including the right anterior putamen. When comparing patients who responded well to clomipramine with those who were either poor or partial responders, we found significant decreases only in the left caudate of patients who responded well to the drug. The present study suggests that clomipramine-induced improvement in obsessive-compulsive symptoms is associated with a return of regional brain metabolism to a more normal level in regions of the orbital frontal cortex and the caudate nucleus." [Abstract]


Martinot JL, Allilaire JF, Mazoyer BM, Hantouche E, Huret JD, Legaut-Demare F, Deslauriers AG, Hardy P, Pappata S, Baron JC, et al.
Obsessive-compulsive disorder: a clinical, neuropsychological and positron emission tomography study.

[Sonic]

Hey Markog,

Is your face and/or body asymmetric? (you will have to take a photo of yourself as looking into a mirror does not yield an accurate result)

This is a serious question, BTW.

[ATB]

nice work Markog

Did you individually cut and paste those?

[markog]

Hey Markog,

Is your face and/or body asymmetric? (you will have to take a photo of yourself as looking into a mirror does not yield an accurate result)

This is a serious question, BTW.

Do you think OCD is some kind of joke, you asshole. People severely suffer from stuff like that. Unbelievable

[Sonic]

Do you think OCD is some kind of joke, you asshole. People severely suffer from stuff like that. Unbelievable

Hey Markkog,

Chillax, there is no need to insult.

I have an ongoing theory that body asymmetries are signs of mental disturbances as they are associated with lack of impulse control and neuroticism amongst others. I would not be surprised if OCD was to be associated too. There is a guy in here that displays OCD behaviour and is constantly checking for body asymmetries.

If you are still interested, let me know.

[rickf]

Hey Markkog,

Chillax, there is no need to insult.

I have an ongoing theory that body asymmetries are signs of mental disturbances as they are associated with lack of impulse control and neuroticism amongst others. I would not be surprised if OCD was to be associated too. There is a guy in here that displays OCD behaviour and is constantly checking for body asymmetries.

If you are still interested, let me know.

I am interested....i have had OCD since i was a kid and i also have an asymmetry where the entire left side of my body is bigger than the right- more muscular(mostly the torso and upper leg/hip). but i can see it in my face as well. my obsession with it is chronic, and its not so much that I am obsessed by the way it looks, although it is noticeable visually...but i feel it- 24/7, in everything i do. i even feel it when i am sleeping. I actually have more sensation on the left side of my face than the right.