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Cited by 52Schizophrenia research and treatmentGenetic Associations and EpidemiologyMental Health and Psychiatry

Mixture Model Clustering of Phenotype Features Reveals Evidence for Association of DTNBP1 to a Specific Subtype of Schizophrenia

Wessman, Jaana, Paunio, Tiina, Tuulio-Henriksson, Annamari, Koivisto, Mikko, Partonen, Timo, Suvisaari, Jaana, Turunen, Joni A., Wedenoja, Juho +5 more·2009·Biological Psychiatry
DOI 10.1016/j.biopsych.2009.05.034
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Abstract

Background While DTNBP1, DISC1, and NRG1 have been extensively studied as candidate genes of schizophrenia, results remain inconclusive. Possible explanations for this are that the genes might be relevant only to certain subtypes of the disease and/or only in certain populations.Methods We performed unsupervised clustering of individuals from Finnish schizophrenia families, based on extensive clinical and neuropsychological data, including Structured Clinical Interview for DSM-IV (SCID) information. Families with at least one affected member with DSM-IV diagnosis of a schizophrenia spectrum psychosis were included in a register-based ascertainment. Final sample consisted of 904 individuals from 288 families. We then used the cluster phenotypes in a genetic association study of candidate genes.Results A robust three-class clustering of individuals emerged: 1) psychotic disorder with mood symptoms (n = 172), 2) core schizophrenia (n = 223), and 3) absence of psychotic disorder (n = 509). One third of the individuals diagnosed with schizophrenia were assigned to cluster 1. These individuals had fewer negative and positive psychotic symptoms and cognitive deficits but more depressive symptoms than individuals in cluster 2. There was a significant association of cluster 2 cases with the DTNBP1 gene, while the DISC1 gene indicated a significant association with schizophrenia spectrum disorders based on the DSM-IV criteria.Conclusions In the Finnish population, DTNBP1 gene is associated with a schizophrenia phenotype characterized by prominent negative symptoms, generalized cognitive impairment, and few mood symptoms. Identification of genes and pathways related to schizophrenia necessitates novel definitions of disease phenotypes associated more directly with underlying biology.

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Crossref · 10.1016/j.biopsych.2009.05.034

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  • Another possible interpretation of the present findings is that there is substantial heterogeneity within and between clinical groups that could dilute the true effects of intranasal oxytocin on social threat processing among clinical populations.

    “Another possible interpretation of the present findings is that there is substantial heterogeneity within and between clinical groups that could dilute the true effects of intranasal oxytocin on social threat processing among clinical populations (Lamers et al., 2010;Melartin et al., 2002;Wessman et al., 2009).”

    From Meta-analytic review of the effects of a single dose of intranasal oxytocin on threat processing in humans (2018) · cites this paper as Wessman et al., 2009

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Authors
Wessman, J., Paunio, T., Tuulio-Henriksson, A., Koivisto, M., Partonen, T., Suvisaari, J., Turunen, J. A., Wedenoja, J., Hennah, W., Pietiläinen, O. P. H., Lönnqvist, J., Mannila, H., & Peltonen, L.
Affiliations
  • University of Helsinki (FI)
  • Broad Institute (US)
Corresponding author
Wessman, Jaana
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2009-12
Volume
66
Issue
11
Pages
990-996
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2009.05.034
OpenAlex
W2019053982
Cited by
52
References
62
Citations by year
2025: 3 · 2024: 1 · 2023: 1 · 2021: 3 · 2020: 6 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 5 · 2014: 2 · 2013: 3 · 2012: 9
FWCI
3.71
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Social Sciences › Arts and Humanities › Philosophy › Mental Health and Psychiatry
Keywords
DTNBP1, schizophrenia subtypes, schizophrenia spectrum disorders, DISC1, neuregulin-1, candidate genes, negative symptoms, cognitive impairment, mood symptoms, psychosis, genetic association
MeSH terms
Dysbindin, Adult, Aged, Alleles, Carrier Proteins, Humans, Middle Aged, Nerve Tissue Proteins, Phenotype, Psychotic Disorders, Schizophrenia, Schizophrenic Psychology, Cluster Analysis, Polymorphism, Single Nucleotide, Neuregulin-1, Dystrophin-Associated Proteins, Genetic Association Studies

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