Multivariate genetic determinants of EEG oscillations in schizophrenia and psychotic bipolar disorder from the BSNIP study

B. Narayanan, P. Soh, V. D. Calhoun, G. Ruaño, M. Kocherla, A. Windemuth, B. A. Clementz, C. A. Tamminga, J. A. Sweeney, M. S. Keshavan, G. D. Pearlson

Research output: Contribution to journalArticle

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Abstract

Schizophrenia (SZ) and psychotic bipolar disorder (PBP) are disabling psychiatric illnesses with complex and unclear etiologies. Electroencephalogram (EEG) oscillatory abnormalities in SZ and PBP probands are heritable and expressed in their relatives, but the neurobiology and genetic factors mediating these abnormalities in the psychosis dimension of either disorder are less explored. We examined the polygenic architecture of eyes-open resting state EEG frequency activity (intrinsic frequency) from 64 channels in 105 SZ, 145 PBP probands and 56 healthy controls (HCs) from the multisite BSNIP (Bipolar-Schizophrenia Network on Intermediate Phenotypes) study. One million single-nucleotide polymorphisms (SNPs) were derived from DNA. We assessed eight data-driven EEG frequency activity derived from group-independent component analysis (ICA) in conjunction with a reduced subset of 10 422 SNPs through novel multivariate association using parallel ICA (para-ICA). Genes contributing to the association were examined collectively using pathway analysis tools. Para-ICA extracted five frequency and nine SNP components, of which theta and delta activities were significantly correlated with two different gene components, comprising genes participating extensively in brain development, neurogenesis and synaptogenesis. Delta and theta abnormality was present in both SZ and PBP, while theta differed between the two disorders. Theta abnormalities were also mediated by gene clusters involved in glutamic acid pathways, cadherin and synaptic contact-based cell adhesion processes. Our data suggest plausible multifactorial genetic networks, including novel and several previously identified (DISC1) candidate risk genes, mediating low frequency delta and theta abnormalities in psychoses. The gene clusters were enriched for biological properties affecting neural circuitry and involved in brain function and/or development.

Original languageEnglish (US)
Article numbere588
JournalTranslational Psychiatry
Volume5
Issue number6
DOIs
StatePublished - Jun 30 2015

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Bipolar Disorder
Psychotic Disorders
Electroencephalography
Schizophrenia
Phenotype
Single Nucleotide Polymorphism
Multigene Family
Genes
Gene Components
Neurobiology
Neurogenesis
Brain
Cadherins
Cell Adhesion
Psychiatry
Glutamic Acid
DNA

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Narayanan, B., Soh, P., Calhoun, V. D., Ruaño, G., Kocherla, M., Windemuth, A., ... Pearlson, G. D. (2015). Multivariate genetic determinants of EEG oscillations in schizophrenia and psychotic bipolar disorder from the BSNIP study. Translational Psychiatry, 5(6), [e588]. https://doi.org/10.1038/tp.2015.76

Multivariate genetic determinants of EEG oscillations in schizophrenia and psychotic bipolar disorder from the BSNIP study. / Narayanan, B.; Soh, P.; Calhoun, V. D.; Ruaño, G.; Kocherla, M.; Windemuth, A.; Clementz, B. A.; Tamminga, C. A.; Sweeney, J. A.; Keshavan, M. S.; Pearlson, G. D.

In: Translational Psychiatry, Vol. 5, No. 6, e588, 30.06.2015.

Research output: Contribution to journalArticle

Narayanan, B, Soh, P, Calhoun, VD, Ruaño, G, Kocherla, M, Windemuth, A, Clementz, BA, Tamminga, CA, Sweeney, JA, Keshavan, MS & Pearlson, GD 2015, 'Multivariate genetic determinants of EEG oscillations in schizophrenia and psychotic bipolar disorder from the BSNIP study', Translational Psychiatry, vol. 5, no. 6, e588. https://doi.org/10.1038/tp.2015.76
Narayanan, B. ; Soh, P. ; Calhoun, V. D. ; Ruaño, G. ; Kocherla, M. ; Windemuth, A. ; Clementz, B. A. ; Tamminga, C. A. ; Sweeney, J. A. ; Keshavan, M. S. ; Pearlson, G. D. / Multivariate genetic determinants of EEG oscillations in schizophrenia and psychotic bipolar disorder from the BSNIP study. In: Translational Psychiatry. 2015 ; Vol. 5, No. 6.
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