Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

Meda, Shashwath A.; Ruaño, Gualberto; Windemuth, Andreas; O’Neil, Kasey; Berwise, Clifton; Dunn, Sabra M.; Boccaccio, Leah E.; Narayanan, Balaji; Kocherla, Mohan; Sprooten, Emma; Keshavan, Matcheri S.; Tamminga, Carol A.; Sweeney, John A.; Clementz, Brett A.; Calhoun, Vince D.; Pearlson, Godfrey D.

doi:10.1073/pnas.1313093111

Cited by 242Functional Brain Connectivity StudiesSchizophrenia research and treatmentGenetic Associations and Epidemiology

Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

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Meda, Shashwath A., Ruaño, Gualberto, Windemuth, Andreas, O’Neil, Kasey, Berwise, Clifton, Dunn, Sabra M., Boccaccio, Leah E., Narayanan, Balaji +8 more·2014·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1313093111PMC PMC4024891

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Abstract

Significance: Connectivity within the brain’s resting-state default mode network (DMN) has been shown to be compromised in multiple genetically complex/heritable neuropsychiatric disorders. Uncovering the source of such alterations will help in developing targeted treatments for these disorders. To our knowledge, this study is the first attempt to do so by using a multivariate data-driven fusion approach. We report five major DMN subnodes, all of which were found to be hypo-connected in probands with psychotic illnesses. Further, we found an overrepresentation of genes in major relevant pathways such as NMDA potentiation, PKA/immune response signalling, synaptogenesis, and axon guidance that influenced altered DMN connectivity in psychoses. The study thus identifies several putative genes and pathways related to an important biological marker known to be compromised in psychosis.

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Schizophrenia, ADHD, Autism, and potentially other DSM-defined disorders each constitute a highly heterogeneous set of etiologies.
“The first challenge is the ever-expanding evidence that Schizophrenia (Meda et al., 2014; Satterthwaite and Baker, 2015), ADHD (Costa Dias et al., 2015; Fair et al., 2012a; Gates et al., 2014; Karalunas et al., 2014), Autism (Jeste and Geschwind, 2014; Rudie et al., 2012), and potentially other DSM defined disorders, each constitutes a highly heterogeneous set of etiologies.”
From Development of large-scale functional networks from birth to adulthood: A guide to the neuroimaging literature (2017) · cites this paper as Meda et al., 2014

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Authors: Meda, S. A., Ruaño, G., Windemuth, A., O’Neil, K., Berwise, C., Dunn, S. M., Boccaccio, L. E., Narayanan, B., Kocherla, M., Sprooten, E., Keshavan, M. S., Tamminga, C. A., Sweeney, J. A., Clementz, B. A., Calhoun, V. D., & Pearlson, G. D.
Affiliations: Hartford Hospital (US)
Genomas (United States) (US)
Olin Neuropsychiatry Research Center, Institute of Living at Hartford Hospital, Hartford, CT 06102;
Beth Israel Deaconess Medical Center (US)
The University of Texas Southwestern Medical Center (US)
University of Georgia (US)
Mind Research Network (US)
ORCID: Meda, Shashwath A.
Ruaño, Gualberto
Windemuth, Andreas
Narayanan, Balaji
Sprooten, Emma
Keshavan, Matcheri S.
Tamminga, Carol A.
Sweeney, John A.
Clementz, Brett A.
Calhoun, Vince D.
Pearlson, Godfrey D.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2014-04-28
Volume: 111
Issue: 19
Pages: E2066-75
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1313093111
PMC: PMC4024891
OpenAlex: W1986094520
Cited by: 242
References: 92
Citations by year: 2026: 3 · 2025: 15 · 2024: 18 · 2023: 13 · 2022: 16 · 2021: 23 · 2020: 21 · 2019: 28 · 2018: 20 · 2017: 25 · 2016: 26 · 2015: 29 · 2014: 5
FWCI: 15.80
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Mental Health (R01MH077852, MH‐077945, MH 077852, R01MH077851, MH-078113, MH077851, R01MH096913, R44MH075481, MH‐077862, R01MH078113, R01MH077862, R01MH077945)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: default mode network, psychotic bipolar disorder, schizophrenia, genetic association, resting-state functional connectivity, first-degree relatives, endophenotypes, long-term potentiation, PKA signaling, axon guidance, synaptogenesis, brain development, mood disorders, psychosis
MeSH terms: Adult, Bipolar Disorder, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net, Rest, Risk Factors, Schizophrenia, Multivariate Analysis, Genetic Predisposition to Disease, Young Adult

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Multivariate analysis reveals genetic associations of the resting default mode network in psychotic bipolar disorder and schizophrenia

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