Psychiatry Res 2001 Jul 1;107(1):51-6 Tc-99m HMPAO brain perfusion SPECT in drug-free obsessive-compulsive patients without depression
Alptekin K, Degirmenci B, Kivircik B, Durak H, Yemez B, Derebek E, Tunca Z.
Department of Psychiatry, School of Medicine, University of Dokuz Eylul, 35340, Balcova-Izmir, Turkey
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.
Semin Clin Neuropsychiatry 2001 Apr;6(2):82-101
Brain-behavior relationships in obsessive-compulsive disorder.
Saxena S, Bota RG, Brody AL.
UCLA Obsessive-Compulsive Disorder Research Program, Department of Psychiatry and Biobehavioral Sciences, UCLA School of Medicine, Los Angeles, CA, USA. ssaxena@mednet.ucla.edu
Advances in neuroimaging have led to a greater understanding of brain-behavior relationships in obsessive-compulsive disorder (OCD). This article provides an updated review and analysis of the structural and functional neuroimaging studies in OCD published to date and discusses how evidence from various types of neuroimaging studies has been synthesized to generate and test hypotheses regarding these relationships. We also review the basic science literature on the functional neuroanatomy of cortico-basal ganglia-thalamo-cortical circuits and integrate this information with neuroimaging data in OCD, to present a theoretical model of brain mediation of OCD symptoms and response to treatment. Taken together, neuroimaging studies indicate that OCD symptoms are mediated by hyperactivity in orbitofrontal-subcortical circuits, which may be attributable to an imbalance of tone between direct and indirect striato-pallidal pathways. Serotonergic drugs may ameliorate OCD symptoms by changing the relative balance of tone through the indirect versus direct orbitofrontal-subcortical pathways, thereby decreasing activity in the overall circuit that exists in the symptomatic state. Copyright 2001
: J Am Acad Child Adolesc Psychiatry 2001 Mar;40(3):347-54
Regional cerebral blood flow abnormalities in early-onset obsessive-compulsive disorder: an exploratory SPECT study.
Busatto GF, Buchpiguel CA, Zamignani DR, Garrido GE, Glabus MF, Rosario-Campos MC, Castro CC, Maia A, Rocha ET, McGuire PK, Miguel EC.
Department of Psychiatry, University of Sao Paulo Medical School, Brazil. gbusatto@mtecnetsp.com.br
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.
New advances in neuroimaging in the diagnosis of obsessive-compulsive disorder].
[Article in Spanish]
Lopez-Ibor Alcocer MI, Ortiz Alonso T, Encinas Mejias M, Fernandez A, Maestu F, Lopez-Ibor Alino JJ.
Departamento de Psiquiatria y Psicologia Medica, Facultad de Medicina, Universidad Complutense, Madrid.
Brain-imaging research provides evidence to suggest that the underlying disfunction in Obsessive-Compulsive Disorder (OCD) is likely to be in the prefrontal cortex-basal ganglia thalamic circuit rather then in any one single brain region. Early computerized tomography and magnetic resonance imaging studies have shown morphological changes in the basal ganglia. Now more sophisticated techniques are enhancing the information available, specially with regard to the caudate nucleus. The serotonergic hypothesis remains a necessary but not sufficient explanation for the pathogenesis of OCD. Most evidence remains focussed on the basal ganglia and on a 5-HT/dopamine inter-relationship. Given the basal ganglia receive such rich innervation from both 5-Th and dopamine neurones, it has been postulated that OCD is subserved by a neuronal dysfunction in the basal ganglia and orbitofrontal cortex circuit. Combining behavioural challenge with brain imaging may be a better approach to capturing brain function while patients with OCD and control subjects are actually observed. Using this techniques has made it possible to identified changes in response to treatment, whether the treatment is pharmacological or behavioural. However, there are not data enough that allow us to understand the anatomical, physiological and chemical mechanisms implicated in OCD
: Prog Neuropsychopharmacol Biol Psychiatry 1999 Aug;23(6):1079-99
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.
Stein DJ, Van Heerden B, Wessels CJ, Van Kradenburg J, Warwick J, Wasserman HJ.
Dept of Psychiatry, University of Stellenbosch, Tygerberg, South Africa. djs2maties.sun.ac.za
- 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).
- 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.
- 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).
- 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
- 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.
- 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.
- Further work combining pharmacological challenge paradigms and functional imaging techniques in OCD may be helpful in elucidating the neurobiology of this complex disorder.
Reprinted with Permission
