Dissertation (PhD)--Stellenbosch University, 2001. / ENGLISH ABSTRACT: Obsessive-compulsive disorder (OCD) is characterized by intrusive
thoughts (obsessions) and repetiti ve mental acts or behaviours
(compulsions) . For many years, it was considered a rather
uncommon condition, caused by unconscious conflict, and somewhat
resistant to treatment. In recent decades, however, it has
emerged that OCD is a highly prevalent disorder, mediated by
particular neuroanatomical circuits (e.g. striatal pathways) and
neurochemical systems (e.g. the serotonin system), and responsive
to treatment with serotonin reuptake inhibitors (SRIs) .
Nevertheless, many questions remain; about the specificity of
neuroanatomical findings to OCD, about the role of the multiple
serotonin (5-HT) receptor subtypes (e.g. 5-HT10)' and about the
appropriate pharmacotherapy for patients resistent to SRI
treatment? In a series of studies, 1) the neuroanatomy of OCD was
assessed by means of magnetic resonance imaging and
neuropsychological testing, 2) the neurochemistry of OCD was
assessed by means of functional brain imaging after administration
of a 5-HT10 agonist, and 3) the pharmacotherapy of OCD was
explored in a series of treatment-refractory OCD and OCD spectrum
disorder patients using SRI augmentation with a dopamine blocker.
Although no significant difference was found in the volume of the
caudate in women with OCD and controls, there was a significant
correlation between caudate volume and neuropsychological
dysfunction in patients, consistent with evidence of striatal
involvement in OCD. Functional imaging demonstrated behavioural
heterogeneity, but brain-behaviour correlations were positive,
consistent with preclinical evidence of a role for the 5-HTlD
receptor in the mediation of OCD. Finally, preliminary treatment
findings with dopamine blocker augmentation of a SRI were
promising, consistent with preclinical understandings of the
interactions between the dopamine and serotonin systems. Although oeD is a complex disorder, a number of future research avenues
hold promise for providing a thorough delineation of its
pathogenesis. / AFRIKAANSE OPSOMMING: Obsessief-kompulsiewe steuring (OKS) word gekenmerk deur
indringende gedagtes (obsessies) en herhalende gedagtes of gedrag
(kompulsies). Vir baie jare is dit beskou as 'n redelik seldsame
toestand wat veroorsaak word deur onbewustelike konflik, en wat
in 'n mate teen behandeling weerstandig is. Meer onlangs het dit
egter na vore getree as 'n toestand wat baie dikwels voorkom, wat
deur spesifieke neuroanatomiese siklusse (bv. striatale bane) en
neurochemiese sisteme (bv. die serotonien-sisteem) teweeg gebring
word, en wat op behandeling met serotonien heropname inhibeerders
(SHIs) reageer. Nogtans is daar steeds baie vrae; oor die
spesifisiteit van neuroanatomiese bevindinge vir OKS, oor die rol
van die veelvuldige serotonien (5-HT) reseptor subtipes (bv. 5-
HT1D), en oor die toepaslike farmakoterapie vir pasiënte wat
weerstandig is vir SHI behandeling. In' n reeks van
navorsingstudies, is 1.) die neuroanatomie van OKS deur middel
van magnetiese resonans beelding en neurosielkundige toetse
ondersoek, 2. ) die neurochemie van OKS deur middel van
funksionele breinbeelding na toediening van 'n 5-HT1D agonis
bepaal, en 3.) die farmakoterapie van OKS in 'n reeks van
behandelingsweerstandige OKS en OKS-spektrum steuring pasiënte -
waar gebruik gemaak is van SHI aanvulling met 'n dopamien-blokker
- ondersoek. Alhoewel daar geen beduidende verskil in die volume
van die caudata in vroue met OKS en kontroles gevind is nie, was
daar 'n beduidende korrelasie tussen die caudata volume en
neurosielkundige wanfunksionering in pasiënte, in ooreenstemming
met striatale betrokkenheid in OKS. Funksionele beelding het
positief, in
demonstreer, maar
ooreenstemming met
brein-gedrag
pre-kliniese
heterogeneïteit
korrelasies was
in gedrag
bewyse vir 'n rol vir die 5-HT1D reseptor in die bemiddeling van
OKS. Ten laaste, voorlopige behandelingsbevindinge oor dopamienblokker
aanvulling van 'n SHI is belowend, in ooreenstemming met v
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/52550 |
| Date | 12 1900 |
| Creators | Stein, Dan J |
| Contributors | Emsley, R. A., Stellenbosch University. Faculty of Medicine & Health Sciences . Dept. of Psychiatry. |
| Publisher | Stellenbosch : Stellenbosch University |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | English |
| Type | Thesis |
| Format | 111 p. : ill. |
| Rights | Stellenbosch University |
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