Brain activation during a working memory task in schizophrenia and major depression

Hintergrund: Einschränkungen des Arbeitsgedächtnisses (WM) gehören zu den Hauptsymptomen der Schizophrenie (SZ) und sind in allen Krankheitsphasen präsent. Betroffen sind unterschiedliche Hirnareale, die mit Aufgaben des WM in Verbindung stehen. Dabei liegt ein besonderer Fokus auf dem dorsolaterale...

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Bibliographic Details
Main Author: Hölldorfer, Julian
Contributors: Krug, Axel (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2022
Online Access:PDF Full Text
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Background: Working memory (WM) impairment is a core symptom in all phases of schizophrenia (SZ). It affects different brain areas which are connected to working memory tasks. Special attention is given to the dorsolateral prefrontal cortex (DLPFC). There are different reports of hyper- and hypo-activation during a WM task. A model where the activation follows an inverted u-shaped curve has been proposed. For patients with SZ the activation is shifted to an earlier stage. On the other hand, WM dysfunction is also a core symptom in the acute phase of a major depressive disorder (MDD), but is reported to regress in remission. Comparisons between the disorders show that there are differences in performance and activation. Those studies, however investigated a similar range of activation. The goal of the current study is to examine differences and similarities between both disorders in a very difficult WM task. The focus is also on the activation of the brain areas underlying WM. As the DLPFC plays a major role, special attention is given to this area and the intergroup differences. Methods: A total number of 124 subjects were selected for the present study including 42 patients with SZ, 40 with a MDD and 42 healthy control (HC) subjects. No subject was in a highly acute state of the respective disorder. All subjects underwent four behavioral tests. To investigate WM, a visual WM task was used with a baseline condition and two levels of difficulty. The task was performed in a 3-Tesla MRI scanner where the brain activation was measured. To analyze the data SPSS 21 and SPM 8 was used. Results: In two of the four behavioral tests there were no significant differences between the three groups. In one test, SZ performed significantly worse than the two other groups and in one test MDD and SZ performed both significantly worse than the HC group. During scanning, in the 2-back task SZ performed significantly worse than both other groups, while there were no differences between the groups in the 0-, and 3-back condition. The fMRI data showed hyperactivation especially during the 2-back task in SZ in comparison to both other groups in areas typically implied in WM. In the DLPFC hyperactivation was found in SZ and MDD compared to the HC in the 2-back task. Discussion: The results of the study confirm the assumption that patients with SZ have a more severe WM deficiency than MDD. It appears to be a global WM dysfunction affecting various WM-related areas of the brain that only occur in SZ. However, there is a dysfunction in the DLPFC in both disorders. If we go along with the assumptions of the proposed model, we can underline a shift of the activation curve for each group. The results of the current study contribute to the ongoing debate if there is a connection between SZ and MDD. Further investigations should have a look at MDD with psychotic symptoms and bipolar disorder and whether those disorders have similarities WM deficiencies. In the long run it could reveal a new understanding of the disorders and consequently lead to new ways in the treatment of patients.