Wasserthal, Sven Christian: Psychosis, social cognition and glutamatergic transmission - characteristics of deficits and opportunities for treatment. - Bonn, 2024. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-78028
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5-78028
@phdthesis{handle:20.500.11811/11983,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-78028,
doi: https://doi.org/10.48565/bonndoc-360,
author = {{Sven Christian Wasserthal}},
title = {Psychosis, social cognition and glutamatergic transmission - characteristics of deficits and opportunities for treatment},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2024,
month = aug,
note = {People affected by psychotic disorders often experience severe impairments in social cognition (SC) that correlate highly with deficits in community functioning and are thus an important potential treatment target. Because deterioration of social cognitive capabilities often persists throughout treatment with dopamine-receptor affine antipsychotics, altered glutamatergic transmission, a second possible pathway in the pathophysiology of schizophrenia, might partly explain these deficits. To test this hypothesis, studies 1 + 2 of this thesis investigated whether SC deficits can be temporarily induced by altering glutamatergic transmission. To this end, healthy participants received placebo or ketamine, which non-competitively antagonizes the N-methyl-D-aspartate receptor, thus altering glutamatergic transmission. In study 1, participants completed a video-based mentalizing task during functional magnetic resonance imaging. Behavioral data showed more answers not pertaining to any mentalizing capacity in the ketamine group. Functional imaging data showed hyperactivity of a cluster in the right posterior superior temporal sulcus in these participants. This cluster showed increased functional task-based connectivity with precuneus, potentially indicating that a dysfunctional shift of attention might partly be responsible for SC deficits. In study 2, participants were asked to encode and retrieve words in an episodic memory task and to make metacognitive confidence judgments about their performance. While showing no changes in episodic memory, participants receiving ketamine tended to be overconfident about their performance during the task. In the brain, this was accompanied by higher activity in the right superior-posterior parietal cortex during metacognitive judgments. This suggests that metacognition of memory, a process relevant in SC, might also be affected by disturbances of the glutamatergic pathway. In study 3, an experimental therapy targeting the glutamate pathway was given to patients at high risk for psychosis to reduce transition to schizophrenia and improve SC. They received either N-Acetyl-Cysteine or a placebo for 26 weeks. Additionally, they received either a specialized psychological intervention or stress-management training. Even though this multicentric clinical trial ultimately failed to sufficiently recruit patients, a tendency towards less transitions and improved SC in the treatment groups was apparent. In conclusion, the presented results indicate an important relationship between glutamatergic transmission and SC and their role as potential treatment target in early schizophrenia or clinical high risk for psychosis.},
url = {https://hdl.handle.net/20.500.11811/11983}
}
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5-78028,
doi: https://doi.org/10.48565/bonndoc-360,
author = {{Sven Christian Wasserthal}},
title = {Psychosis, social cognition and glutamatergic transmission - characteristics of deficits and opportunities for treatment},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2024,
month = aug,
note = {People affected by psychotic disorders often experience severe impairments in social cognition (SC) that correlate highly with deficits in community functioning and are thus an important potential treatment target. Because deterioration of social cognitive capabilities often persists throughout treatment with dopamine-receptor affine antipsychotics, altered glutamatergic transmission, a second possible pathway in the pathophysiology of schizophrenia, might partly explain these deficits. To test this hypothesis, studies 1 + 2 of this thesis investigated whether SC deficits can be temporarily induced by altering glutamatergic transmission. To this end, healthy participants received placebo or ketamine, which non-competitively antagonizes the N-methyl-D-aspartate receptor, thus altering glutamatergic transmission. In study 1, participants completed a video-based mentalizing task during functional magnetic resonance imaging. Behavioral data showed more answers not pertaining to any mentalizing capacity in the ketamine group. Functional imaging data showed hyperactivity of a cluster in the right posterior superior temporal sulcus in these participants. This cluster showed increased functional task-based connectivity with precuneus, potentially indicating that a dysfunctional shift of attention might partly be responsible for SC deficits. In study 2, participants were asked to encode and retrieve words in an episodic memory task and to make metacognitive confidence judgments about their performance. While showing no changes in episodic memory, participants receiving ketamine tended to be overconfident about their performance during the task. In the brain, this was accompanied by higher activity in the right superior-posterior parietal cortex during metacognitive judgments. This suggests that metacognition of memory, a process relevant in SC, might also be affected by disturbances of the glutamatergic pathway. In study 3, an experimental therapy targeting the glutamate pathway was given to patients at high risk for psychosis to reduce transition to schizophrenia and improve SC. They received either N-Acetyl-Cysteine or a placebo for 26 weeks. Additionally, they received either a specialized psychological intervention or stress-management training. Even though this multicentric clinical trial ultimately failed to sufficiently recruit patients, a tendency towards less transitions and improved SC in the treatment groups was apparent. In conclusion, the presented results indicate an important relationship between glutamatergic transmission and SC and their role as potential treatment target in early schizophrenia or clinical high risk for psychosis.},
url = {https://hdl.handle.net/20.500.11811/11983}
}