Brain structural and white matter changes in first-episode schizophrenia and their demographic, clinical and cognitive correlates
| dc.contributor.advisor | Emsley, Robin | en_ZA |
| dc.contributor.advisor | Dazzan, Paola | en_ZA |
| dc.contributor.author | Asmal, Laila | en_ZA |
| dc.contributor.other | Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry. | en_ZA |
| dc.date.accessioned | 2018-02-26T19:23:06Z | |
| dc.date.accessioned | 2018-04-09T06:51:50Z | |
| dc.date.available | 2018-02-26T19:23:06Z | |
| dc.date.available | 2018-04-09T06:51:50Z | |
| dc.date.issued | 2018-03 | |
| dc.description | Thesis (PhD)--Stellenbosch University, 2018. | en_ZA |
| dc.description.abstract | ENGLISH SUMMARY : In schizophrenia, decreased brain volume and altered cortical thinning (especially in the frontal and temporal areas), as well as white matter deficits are described at the first-episode. The relationship between these brain measures and clinical symptoms, whether there is progression, and the extent to which antipsychotic medication contribute to or mitigate those changes remains unclear. The aim of this PhD was to examine cortical thickness, brain volume (cortical, subcortical, white matter) and diffusion tensor imaging data, looking at the relationship between these brain measures and clinical variables in the first year of schizophrenia treatment. This PhD focused on the MRI subcomponent of a larger prospective longitudinal study in first-episode schizophrenia (FES) patients treated with flupenthixol decanoate medication. The thesis integrates the findings of five journal manuscripts that each focused on a clinically relevant neuroimaging question that emerged as we assessed patients in the parent study, namely insight, childhood trauma, neuroimaging predictors of symptom expression, and antipsychotic related brain changes. In our first manuscript, baseline fractional anisotropy (FA) in a number of white matter tracts predicted poorer total insight in 89 FES patients, with a predilection for tracts associated with cortical midline structures. In our second manuscript, the ‘symptom misattribution’ domain of clinical insight was associated with significantly thinner left anterior cingulate and left rostral middle frontal cortices. Our studies address a need for research in larger samples in FES to better understand the neurobiology of insight in schizophrenia. In our third manuscript, baseline FA deficits in cortico-limbic circuitry was associated with childhood trauma in 53 FES patients compared to 51 controls, and there were differential effects of childhood emotional neglect (increased FA) and sexual abuse (decreased FA) on white matter in patients. To our knowledge, at the time of manuscript submission for publication, this was the first study examining the relationship between childhood trauma, FA and FES. For our fourth manuscript, baseline brain measures in 54 FES patients were differentially associated with state and trait symptom expression over 12 months, with global gray matter significantly associated with sensory integration and verbal learning trait scores, cortical volume with verbal learning trait scores, cortical thickness with social and occupational functioning trait scores, and white matter volume with motor coordination state scores. Of potential relevance to patient care is that these neuroimaging deficits at initial presentation in FES may predict enduring trait deficits in cognition, functioning and neurological soft signs. For our final manuscript, total antipsychotic dose was a predictor of substantial cortical brain volume reductions over twelve months of treatment in 23 antipsychotic naïve patients compared to 53 matched controls. Our finding of a significant relationship between antipsychotic dose and cortical volume reduction in this study strongly suggests causality. Future research directions stemming from this PhD include further exploration of our longitudinal data, strengthening our clinical assessments of insight and childhood trauma, connectomic analyses, a multi-modality neuroimaging approach, hippocampal subfield segmentation, and broadening our international collaborations. | en_ZA |
| dc.description.abstract | AFRIKAANSE OPSOMMING : In skisofrenie word verminderde breinvolume en veranderde kortikale verdunning (veral in die frontale en temporale areas) sowel as witstof-tekorte reeds by eerste aanvang beskryf. Die verwantskap tussen hierdie brein afmetings en kliniese simptome, of daar voorsetting is en die mate waartoe antipsigotiese medikasie hierdie veranderinge vererger of versag is onduidelik. Die doelwit van hierdie PhD was om kortikale dikte, breinvolume (kortikaal subkortikaal, witstof) en “diffuse tensor” beeldingsdata te ondersoek deur te kyk na die verhouding tussen hierdie brein afmetings en kliniese veranderlikes gedurende die eerste jaar van skisofrenie behandeling. Hierdie PhD se fokus was die MRB sub-afdeling van ‘n omvattende prospektiewe longitudinale studie in eerste aanvangs skisofrenie (EAS) pasiënte behandel met flupenthixol dekanoaat medikasie. Die tesis integreer die bevindinge van vyf joernaal manuskripte wat elkeen gefokus het op ‘n klinies relevante neurobeeldingsvraagstuk soos na vore gekom tydens die assessering van pasiënte in die oorhoofse studie; naamlik insig, trauma tydens kinderjare, neurobeeldingsvoorspellers van simptoom uitdrukking, en antipsigotika-verwante breinveranderinge. In ons eerste manuskrip het basislyn fraksionele anisotropie (FA) in ‘n aantal witstoftrakte laer globale insig in 89 EAS pasiënte voorspel met ‘n voorkeur vir trakte geassosieer met midlyn kortikale strukture. In ons tweede manuskrip was die “symptom misattribution” domein van kliniese insig geassosieer met ‘n beduidend dunner linker singulaat en linker rostrale middel frontale kortises. Ons studies spreek tot die behoefte vir groter studiegroepe in EAP om sodoende die neurobiologie van insig in skisofrenie beter te verstaan. In ons derde manuskrip was basislyn FA tekorte in kortiko-limbiese bane geassosieer met trauma in die kinderjare in 53 EAS pasiënte in vergelyking met 51 kontroles. Daar was ook differensiele effekte op witstof vir verwaarlosing in die kinderjare (verhoogde FA) en seksuele misbruik (verminderde FA) in pasiënte. Toe die manuskrip vir publikasie voorgelê is, was dit, na die beste van ons wete, die eerste studie wat die verwantskap tussen trauma in die kinderjare, FA en EAP ondersoek het. Vir ons vierde manuskrip was basislyn brein afmetings in 54 pasiënte differensieël geassosieer met toestand en eienskap simptoom uitdrukking oor 12 maande, met globale grysstof beduidend geassosieer met sensoriese integrasie en verbale leer eienskap tellings, kortikale volume en verbale leer eienskap tellings; kortikale dikte met sosiale- en werksfunksionering eienskap tellings en witstof volume met motor koordinasie toestand tellings. Dat hierdie neurobeeldingsuitvalle wat teenwoordig is met die eerste episode dalk blywende eienskap uitvalle in kognisie, funksionering en neurologiese sagte tekens mag voorspel is potensieel van waarde vir pasiëntsorg. Vir ons laaste manuskrip het die totale antipsigotika dosis aansienlike kortikale breinvolume vermindering voorspel oor 12 maande van behandeling van 23 antipsigotika naïewe pasiënte in vergelyking met 53 ooreenstemmende kontroles.Our finding of a significant relationship between antipsychotic dose and cortical volume reduction in this study strongly suggests causality. Ons bevinding in hierdie studie van ‘n beduidende verhouding tussen antipsigotika dosis en kortikale volume vermindering suggereer sterk oorsaaklikheid. Toekomstige navorsingsgeleenthede wat voortspruit uit hierdie PhD sluit in: verdere ondersoek van ons longitudinale data, geleenthede om kliniese assessering van insig en trauma in kinderjare te versterk; “connectomic” analises, multi-modale neurobeeldingsbenaderinge, hippokampale subveld segmentasie en die uitbreiding van ons internasionale samewerkings-ooreenkomste. | af_ZA |
| dc.format.extent | vii, 98 pages | |
| dc.identifier.uri | http://hdl.handle.net/10019.1/103286 | |
| dc.language.iso | en_ZA | en_ZA |
| dc.publisher | Stellenbosch : Stellenbosch University | |
| dc.rights.holder | Stellenbosch University | |
| dc.subject | Schizophrenia -- Diagnostic imaging | en_ZA |
| dc.subject | Schizophrenia -- Neuroimaging | en_ZA |
| dc.subject | Brain -- Diagnostic imaging | en_ZA |
| dc.subject | Neurosciences | en_ZA |
| dc.subject | Diffusion tensor imaging | en_ZA |
| dc.subject | White matter | en_ZA |
| dc.subject | UCTD | |
| dc.title | Brain structural and white matter changes in first-episode schizophrenia and their demographic, clinical and cognitive correlates | en_ZA |
| dc.type | Thesis | en_ZA |