umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Revisiting Antipsychotic Drug Actions Through Gene Networks Associated With Schizophrenia
Umeå University, Faculty of Medicine, Department of Radiation Sciences.
Show others and affiliations
2018 (English)In: American Journal of Psychiatry, ISSN 0002-953X, E-ISSN 1535-7228, Vol. 175, no 7, p. 674-682Article in journal (Refereed) Published
Abstract [en]

Objective: Antipsychotic drugs were incidentally discovered in the 1950s, but their mechanisms of action are still not understood. Better understanding of schizophrenia pathogenesis could shed light on actions of current drugs and reveal novel "druggable" pathways for unmet therapeutic needs. Recent genome-wide association studies offer unprecedented opportunities to characterize disease gene networks and uncover drug-disease relationships. Polygenic overlap between schizophrenia risk genes and antipsychotic drug targets has been demonstrated, but specific genes and pathways constituting this overlap are undetermined. Risk genes of polygenic disorders do not operate in isolation but in combination with other genes through protein-protein interactions among gene product.

Method: The protein interactome was used to map antipsychotic drug targets (N=88) to networks of schizophrenia risk genes (N=328).

Results: Schizophrenia risk genes were significantly localized in the interactome, forming a distinct disease module. Core genes of the module were enriched for genes involved in developmental biology and cognition, which may have a central role in schizophrenia etiology. Antipsychotic drug targets overlapped with the core disease module and comprised multiple pathways beyond dopamine. Some important risk genes like CHRN, PCDH, and HCN families were not connected to existing antipsychotics but may be suitable targets for novel drugs or drug repurposing opportunities to treat other aspects of schizophrenia, such as cognitive or negative symptoms.

Conclusions: The network medicine approach provides a platform to collate information of disease genetics and drug-gene interactions to shift focus from development of antipsychotics to multitarget antischizophrenia drugs. This approach is transferable to other diseases.

Place, publisher, year, edition, pages
AMER PSYCHIATRIC PUBLISHING, INC , 2018. Vol. 175, no 7, p. 674-682
National Category
Psychiatry
Identifiers
URN: urn:nbn:se:umu:diva-150746DOI: 10.1176/appi.ajp.2017.17040410ISI: 000437319200013PubMedID: 29495895Scopus ID: 2-s2.0-85049391454OAI: oai:DiVA.org:umu-150746DiVA, id: diva2:1240130
Available from: 2018-08-20 Created: 2018-08-20 Last updated: 2019-01-11Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMedScopus

Authority records BETA

Kauppi, Karolina

Search in DiVA

By author/editor
Kauppi, KarolinaBrin Rosenthal, Sara
By organisation
Department of Radiation Sciences
In the same journal
American Journal of Psychiatry
Psychiatry

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 38 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf