Funktionell- hirnbildgebende Untersuchung zu endophänotypischen Markern bei erstgradigen Angehörigen bipolarer Patienten

Functional brain-imaging study for endo phenotypic markers in first-degree relatives of bipolar patients

by Kathrin Jakob
Doctoral thesis
Date of Examination:2013-11-19
Date of issue:2013-11-12
Advisor:Prof. Dr. Oliver Gruber
Referee:PD Dr. Peter Dechent
Referee:Prof. Dr. Martin Oppermann
Persistent Address: http://dx.doi.org/10.53846/goediss-4151

 

 

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Abstract

English

Background: Bipolar disorder is marked by multifactorial etiology. As there is no evidence for a uniform etiology the search for neurobiological correlates, so called endophenotypes, are an important part of the research approach. Endophenotypes, which seem to have a close relationship to the genome, are important to investigating pathogenetic factors of disease. The use of functional magnetic resonance imaging (fMRI) to explore neural activity, particularly impairments in working memory and reward system, in samples of bipolar disorder patients and their unaffected first-degree relatives may present potential neurobiological endophenotypes for this disorder. Aim: The aim of this study (with the help of functional-brain imaging investigations) was to find more endophenotypical markers in working memory and reward system with the assistance of healthy, unaffected, first degree relatives of people with bipolar disorder. Method: 18 unaffected first degree relatives and 18 healthy controls performed a modified “Sternberg-paradigm” to investigate human verbal and visospatial working memory. In addition to this, the reward system, selective attention and task switching (with oddballs and incongruence) were also tested. Results: Hyper activation of the left praecentral and right middle frontal gyrus was shown in the relatives during articulatory rehearsal. When testing the visospatial working memory, higher activations were shown in the area of the ventral striatum/anterior thalamus and bilateral superior parietal lobules. During the “Desire-reason-Dilemma”-paradigm, both groups (relatives and controls) presented activations in the same brain areas (mesolimbic dopamine system) found in preliminary studies. In relation to the system of background monitoring and attention control no consistent findings could be shown. Conclusion: Brain activations during working memory tasks and reward system processes differentiated unaffected first degree relatives from healthy controls and marked potential candidates of endophenotypes. In the relatives more activation was shown in the left praecentral and right middle frontal gyrus during verbal working memory processes. More activation was also found in the ventral striatum/anterior thalamus and bilateral superior parietal lobuli during visual-spatial working memory process. The investigation of the reward system showed a hypo activation of the relatives in the area of the right thalamus, another potential endophenotype candidate.
Keywords: bipolar disorder; endophenotypes; working memory; reward system; unaffected first-degree relatives; functional-brain imaging; fMRI; Sternberg; verbal and visospatial working memory; oddball and incongruence
Schlagwörter: Bipolare Störung; Endophänotypen; visuelles und verbales Arbeitsgedächtnis; Belohnungssystem; Angehörige ersten Grades; fMRT; Sternberg Paradigma; Oddball und Inkongruenz Paradigma
 
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