Functional Neuroimaging and the Neuroanatomy of Obsessive-Compulsive Disorder

Saxena, Sanjaya; Rauch, Scott L.

doi:10.1016/s0193-953x(05)70181-7

Cited by 721 publications

(500 citation statements)

References 75 publications

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“…In our patients with OCD, the LD of the right primary auditory cortex (tangential dipole) was associated with both serotonin and dopamine transporter availabilities. Brain functional abnormalities in patients with OCD have repeatedly been shown in imaging and neurophysiological studies, and many of these investigations revealed more pronounced right-sided alterations (Baxter et al, 1992;Saxena et al, 1999;Saxena and Rauch, 2000). This could explain that in our study only the right LD, representing the right primary auditory cortex, revealed significant correlations with the imaging data.…”

Section: Discussionsupporting

confidence: 62%

Serotonin and Dopamine Transporter Availabilities Correlate with the Loudness Dependence of Auditory Evoked Potentials in Patients with Obsessive-Compulsive Disorder

Pogarell

Tatsch

Juckel

et al. 2004

Neuropsychopharmacol

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Brain monoaminergic function is involved in the pathophysiology of psychiatric disorders. The loudness dependence (LD) of the N1/P2 component of auditory evoked potentials has been proposed as a noninvasive indicator of central serotonergic function, whereas single photon emission computed tomography (SPECT) and [ 123 I]b-CIT can be used to visualize both serotonin (SERT) and dopamine transporters (DAT). The aim of the study was to correlate LD and SPECT measures in patients with obsessive-compulsive disorder, a condition with evidence for a serotonergic dysfunction. A total of 10 subjects received both neurophysiological and imaging investigations. Evoked potentials were recorded following the application of acoustic stimuli with increasing intensities. The LD of the relevant subcomponents (tangential dipoles) was investigated using dipole source analysis. SPECT was performed 20-24 h after injection of a mean 140 MBq [ 123 I]b-CIT. As a measure of brain SERT and DAT availabilities, a ratio of specific to nonspecific [ 123 I]b-CIT binding for the midbrain . pons region (SERT) and the striatum (DAT) was used. The LD of the right tangential dipole correlated significantly with both SERT and DAT availabilities (Pearson's correlations: r ¼ 0.69, po0.05, and r ¼ 0.80, po0.01, respectively). The correlations remained significant after controlling for the effects of age, gender, and severity of clinical symptoms. Associations between LD and both SERT and DAT availabilities further validate the use of neurophysiological approaches as noninvasive indirect measures of neurochemical brain function and point at a hypothesized interconnection of central monoaminergic systems.

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Section: Discussionsupporting

confidence: 62%

Serotonin and Dopamine Transporter Availabilities Correlate with the Loudness Dependence of Auditory Evoked Potentials in Patients with Obsessive-Compulsive Disorder

Pogarell

Tatsch

Juckel

et al. 2004

Neuropsychopharmacol

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“…On the basis of functional, structural, and spectroscopic brain imaging studies, it has been postulated that OCD involves dysfunction in one of the several hypothesized parallel corticostriato-pallido-thalamo-cortical loops (Alexander et al, 1986;Saxena and Rauch, 2000). The OCD circuit is hypothesized to have two loops: (1) the direct pathway, projecting from the cerebral cortex to striatum to the internal segment of the globus pallidus-substantia nigrapars reticulata complex (Gpi/SNr) and then to thalamus and back to cortex; and (2) the indirect pathway, projecting from the cortex to striatum and then to the external segment of the globus pallidus followed by subthalamic nucleus before returning to the Gpi/SNr, where it rejoins the common pathway to the thalamus before returning to the cortex (Saxena and Rauch, 2000). Although there are various neurotransmitters that modulate the activity of afferents and efferents in these loops, it is significant that excitatory inputs in these pathways are predominantly glutamatergic, whereas inhibitory ones are predominantly GABAergic (Parent and Hazrati, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Although functional, structural, and spectroscopic brain imaging studies have implicated dysfunction in either the 'direct' or 'indirect' loops of the cortico-striato-pallido-thalamo-cortical OCD circuit (Saxena and Rauch, 2000), where the predominant excitatory neurotransmitter is glutamate, there have been few hypothesis-driven studies investigating glutamatergic dysfunction in OCD. In one of the first reports implicating glutamatergic dysfunction in OCD, Moore et al (1998) reported striking changes in caudate glutamate resonance on proton magnetic resonance spectroscopy (1H-MRS) in a 9-year-old boy with OCD following 12 weeks of paroxetine treatment.…”

Section: Introductionmentioning

confidence: 99%

Glutamatergic Dysfunction in OCD

Chakrabarty

Bhattacharyya

Christopher

et al. 2005

Neuropsychopharmacol

310

191

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The role of glutamatergic dysfunction in the pathophysiology of OCD has hardly been explored despite recent reports implicating glutamatergic dysfunction in OCD. We decided to investigate CSF glutamate levels in adult OCD probands compared to psychiatrically normal controls. In total, 21 consenting psychotropic drug-naïve adult OCD patients, diagnosed using SCID-IV-CV, and 18 consenting psychiatrically normal controls with age within 10 years of age of the patients, who did not have any history of head injury or neurological illness, were included into the study. Aseptically collected and stored CSF samples obtained from the patients and control subjects were used for glutamate estimation, which was carried out by a modification of the procedure described by Lund (1986). CSF glutamate (mmol/l) level was found to be significantly higher [F(1,31) ¼ 6.846, p ¼ 0.014] in OCD patients (47.1274.25) compared to control subjects (41.3673.63) on analysis of covariance. There was no effect of gender, age, duration of illness, Y-BOCS score, or CGI-S score on CSF glutamate levels. Our study provides preliminary evidence implicating glutamatergic excess in the pathophysiology of OCD, which needs to be further explored by studies from other centers involving larger sample sets from different age groups.

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“…A functional MRI study of gambling urges in male pathologic gamblers suggests that PG has neural features (relatively decreased activation within cortical, basal ganglionic, and thalamic brain regions in subjects who have PG as compared with controls) distinct from the brain activation pattern observed in cue-provocation studies of OCD (relatively increased cortico-basal-ganglionic-thalamic activity) [24,25]. Whereas research on the neurobiology of PG is increasing, the neurobiologic relationship of PG to OCD remains to be qualified.…”

Section: Impaired Control Over Motor Activities Which Measures Urges mentioning

confidence: 99%