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The genetics of schizophrenia : sex, drugs, and cognition

Koch, Elise, 1980- (författare)
Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB)
Kauppi, Karolina, PhD (preses)
Umeå universitet,Institutionen för integrativ medicinsk biologi (IMB),Umeå centrum för funktionell hjärnavbildning (UFBI),Institutionen för strålningsvetenskaper
Nyberg, Lars, Professor, 1966- (preses)
Umeå universitet,Umeå centrum för funktionell hjärnavbildning (UFBI),Institutionen för psykologi,Fysiologi,Diagnostisk radiologi
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Lundquist, Anders, PhD, 1978- (preses)
Umeå universitet,Umeå centrum för funktionell hjärnavbildning (UFBI),Statistik,Immunologi/immunkemi,Institutionen för integrativ medicinsk biologi (IMB)
Serretti, Alessandro, Associate Professor (opponent)
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy
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 (creator_code:org_t)
ISBN 9789178557554
Umeå : Umeå universitet, 2022
Engelska 65 s.
Serie: Umeå University medical dissertations, 0346-6612 ; 2185
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
Abstract Ämnesord
Stäng  
  • Cognitive impairment constitutes an important predictor of general functional outcomes in schizophrenia. Polygenic risk for schizophrenia has been linked to cognitive ability as well as brain activation during cognitive processing. Although sex differences have long been observed in schizophrenia patients, it is not known if genetic effects on cognitive phenotypes differ between males and females. Despite attempts to develop drugs that address the cognitive symptoms in schizophrenia or to investigate existing drugs with potential procognitive effects, there are currently no available medications that efficiently treat these symptoms in schizophrenia. The aim of this PhD project was to explore the genetic underpinnings of cognitive symptoms in schizophrenia, and to identify existing drugs that potentially could be used for repurposing to address these symptoms. We identified male-specific effects of polygenic risk for schizophrenia on lifespan cognitive functioning as well as brain activation during cognitive processing. Within gene networks, we identified a significant overlap between schizophrenia risk genes and genes associated with cognitive performance, and identified novel schizophrenia risk genes that are related to cognitive functioning. Utilizing gene networks incorporating gene expression data, we identified eight existing drugs that could potentially be used for repurposing to address the cognitive symptoms in schizophrenia, most of which have anti-inflammatory and neuroprotective effects. Using sex-specific gene expression data, we identified different repurposing candidates for male and female schizophrenia patients. In conclusion, the findings of this PhD project indicate that the effects of schizophrenia genetics on cognitive functioning are dependent on biological processes that differ between the sexes, and suggest that the cognitive symptoms in schizophrenia should be addressed by sex-specific pharmacological treatments.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

schizophrenia
genetics
cognition
sex differences
polygenic risk
fMRI
network medicine
drug repurposing
precision medicine

Publikations- och innehållstyp

vet (ämneskategori)
dok (ämneskategori)

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