Structural and functional cerebral changes in patients with schizophrenia and genetic risk-allele carriers

Kambeitz, Joseph (2014): Structural and functional cerebral changes in patients with schizophrenia and genetic risk-allele carriers. Dissertation, LMU München: Medizinische Fakultät

Abstract

Schizophrenia is one of the most frequent psychiatric disorders and is associated with a substantial part of worldwide disease burdon1. The clinical symptoms of patients with schizophrenia can be separated into positive symptoms such as halluciations and delusions as well as negative symptoms such as cognitive impairments, apathy, blunted affect and social withdrawal2. It has been suggested that understanding the underlying pathophysiological processes that give rise to these symptoms is a crucial step for the development of efficient treatment for schizophrenia3. In the presented work two aspects of the clinical symptomatology of schizophrenia are analyzed with respect to their potential neurobiological correlate. Following the dopamine-hypothesis, patients with schizophrenia exhibit an increase in dopaminergic neurotransmission in the striatum which might be related to the experience of positive symptoms4,5. In the first publication evidence for this dopamine-hypothesis from in-vivo neuroimaging studies was investigated in a comprehensive meta-analysis. Results are in the line with the dopamine-hypothesis and point to an increase of striatal presynaptic dopamine synthesis in schizophrenia: - Howes OD*, Kambeitz J*, Kim E, Stahl D, Slifstein M, Abi-Dargham A*, Kapur S* (2012): The nature of dopamine dysfunction in schizophrenia and what this means for treatment. Arch Gen Psychiatry 69: 776–786. * these authors contributed equally ISI Web of Knowledge: Archives of General Psychiatry (now: JAMA Psychiatry) impact factor 2012: 13.77 5-year impact factor 2012: 14.47 Ranked 3rd of all psychiatry journals The negative symptoms of schizophrenia such as cognitive impairments have frequently been associated with changes of cerebral gray matter in numerous brain regions including the hippocampus6–9. In the second publication, effects of a potential risk-gene on the hippocampus are analyzed. Results indicate reduced hippocampal structure and function in carriers of the met-allele of the BDNF polymorphism val(66)met: - Kambeitz JP*, Bhattacharyya S*, Kambeitz-Ilankovic LM, Valli I, Collier DA, McGuire P (2012): Effect of BDNF val(66)met polymorphism on declarative memory and its neural substrate: a meta-analysis. Neurosci Biobehav Rev 36: 2165–2177. * these authors contributed equally ISI Web of Knowledge: Neuroscience and Biobehavioral Reviews impact factor 2012: 9.44 5-year impact factor 2012: 9.92 Ranked 12th of all neurosciences journals

• Dokumententyp: Dissertationen (Dissertation, LMU München)
• Keywords: schizophrenia, psychosis, dopamine, striatum, bdnf, val66met, genetic risk, risk allele, memory, hippocampus
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften ; 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Fakultäten: Medizinische Fakultät
• Sprache der Hochschulschrift: Englisch
• Datum der mündlichen Prüfung: 26. Juni 2014
• 1. Bericht­erstatter:in: Meisenzahl-Lechner, Eva Maria