Novel gene-brain structure relationships in psychotic disorder revealed using parallel independent component analyses

Neeraj Tandon, Pranav Nanda, Jaya L. Padmanabhan, Ian T. Mathew, Shaun M. Eack, Balaji Narayanan, Shashwath A. Meda, Sarah E. Bergen, Gualbert Ruaño, Andreas Windemuth, Mohan Kocherla, Tracey L. Petryshen, Brett Clementz, John Sweeney, Carol Tamminga, Godfrey Pearlson, Matcheri S. Keshavan

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background Schizophrenia, schizoaffective disorder, and psychotic bipolar disorder overlap with regard to symptoms, structural and functional brain abnormalities, and genetic risk factors. Neurobiological pathways connecting genes to clinical phenotypes across the spectrum from schizophrenia to psychotic bipolar disorder remain largely unknown. Methods We examined the relationship between structural brain changes and risk alleles across the psychosis spectrum in the multi-site Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) cohort. Regional MRI brain volumes were examined in 389 subjects with a psychotic disorder (139 schizophrenia, 90 schizoaffective disorder, and 160 psychotic bipolar disorder) and 123 healthy controls. 451,701 single-nucleotide polymorphisms were screened and processed using parallel independent component analysis (para-ICA) to assess associations between genes and structural brain abnormalities in probands. Results 482 subjects were included after quality control (364 individuals with psychotic disorder and 118 healthy controls). Para-ICA identified four genetic components including several risk genes already known to contribute to schizophrenia and bipolar disorder and revealed three structural components that showed overlapping relationships with the disease risk genes across the three psychotic disorders. Functional ontologies representing these gene clusters included physiological pathways involved in brain development, synaptic transmission, and ion channel activity. Conclusions Heritable brain structural findings such as reduced cortical thickness and surface area in probands across the psychosis spectrum were associated with somewhat distinct genes related to putative disease pathways implicated in psychotic disorders. This suggests that brain structural alterations might represent discrete psychosis intermediate phenotypes along common neurobiological pathways underlying disease expression across the psychosis spectrum.

Original languageEnglish (US)
Pages (from-to)74-83
Number of pages10
JournalSchizophrenia Research
Volume182
DOIs
StatePublished - Apr 1 2017

Keywords

  • Bipolar disorder
  • Brain structure
  • Endophenotype
  • Genes
  • Intermediate phenotype
  • MRI
  • Nosology
  • Schizoaffective disorder
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Biological Psychiatry

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    Tandon, N., Nanda, P., Padmanabhan, J. L., Mathew, I. T., Eack, S. M., Narayanan, B., Meda, S. A., Bergen, S. E., Ruaño, G., Windemuth, A., Kocherla, M., Petryshen, T. L., Clementz, B., Sweeney, J., Tamminga, C., Pearlson, G., & Keshavan, M. S. (2017). Novel gene-brain structure relationships in psychotic disorder revealed using parallel independent component analyses. Schizophrenia Research, 182, 74-83. https://doi.org/10.1016/j.schres.2016.10.026