Differences in resting-state functional magnetic resonance imaging functional network connectivity between schizophrenia and psychotic bipolar probands and their unaffected first-degree relatives

Shashwath A. Meda, Adrienne Gill, Michael C. Stevens, Raymond P. Lorenzoni, David C. Glahn, Vince D. Calhoun, John A. Sweeney, Carol A. Tamminga, Matcheri S. Keshavan, Gunvant Thaker, Godfrey D. Pearlson

Research output: Contribution to journalArticle

169 Citations (Scopus)

Abstract

Background: Schizophrenia and bipolar disorder share overlapping symptoms and genetic etiology. Functional brain dysconnectivity is seen in both disorders. Methods: We compared 70 schizophrenia and 64 psychotic bipolar probands, their respective unaffected first-degree relatives (n = 70, and n = 52), and 118 healthy subjects, all group age-, gender-, and ethnicity-matched. We used functional network connectivity analysis to measure differential connectivity among 16 functional magnetic resonance imaging resting state networks. First, we examined connectivity differences between probands and control subjects. Next, we probed these dysfunctional connections in relatives for potential endophenotypes. Network connectivity was then correlated with Positive and Negative Syndrome Scale (PANSS) scores to reveal clinical relationships. Results: Three different network pairs were differentially connected in probands (false-discovery rate corrected q <.05) involving five individual resting-state networks: (A) fronto/occipital, (B) anterior default mode/prefrontal, (C) meso/paralimbic, (D) fronto-temporal/paralimbic, and (E) sensory-motor. One abnormal pair was unique to schizophrenia, (C-E), one unique to bipolar, (C-D), and one (A-B) was shared. Two of these three combinations (A-B, C-E) were also abnormal in bipolar relatives but none was normal in schizophrenia relatives (nonsignificant trend for C-E). The paralimbic circuit (C-D), which uniquely distinguished bipolar probands, contained multiple mood-relevant regions. Network relationship C-D correlated significantly with PANSS negative scores in bipolar probands, and A-B with PANSS positive and general scores in schizophrenia. Conclusions: Schizophrenia and psychotic bipolar probands share several abnormal resting state network connections, but there are also unique neural network underpinnings between disorders. We identified specific connections that might also be candidate psychosis endophenotypes.

Original languageEnglish (US)
Pages (from-to)881-889
Number of pages9
JournalBiological Psychiatry
Volume71
Issue number10
DOIs
StatePublished - May 15 2012

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Schizophrenia
Magnetic Resonance Imaging
Endophenotypes
Tocopherols
Bipolar Disorder
Psychotic Disorders
Healthy Volunteers
Age Groups
Brain

Keywords

  • Bipolar
  • default mode
  • functional connectivity
  • gene
  • relatives
  • resting state
  • schizophrenia

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Differences in resting-state functional magnetic resonance imaging functional network connectivity between schizophrenia and psychotic bipolar probands and their unaffected first-degree relatives. / Meda, Shashwath A.; Gill, Adrienne; Stevens, Michael C.; Lorenzoni, Raymond P.; Glahn, David C.; Calhoun, Vince D.; Sweeney, John A.; Tamminga, Carol A.; Keshavan, Matcheri S.; Thaker, Gunvant; Pearlson, Godfrey D.

In: Biological Psychiatry, Vol. 71, No. 10, 15.05.2012, p. 881-889.

Research output: Contribution to journalArticle

Meda, Shashwath A. ; Gill, Adrienne ; Stevens, Michael C. ; Lorenzoni, Raymond P. ; Glahn, David C. ; Calhoun, Vince D. ; Sweeney, John A. ; Tamminga, Carol A. ; Keshavan, Matcheri S. ; Thaker, Gunvant ; Pearlson, Godfrey D. / Differences in resting-state functional magnetic resonance imaging functional network connectivity between schizophrenia and psychotic bipolar probands and their unaffected first-degree relatives. In: Biological Psychiatry. 2012 ; Vol. 71, No. 10. pp. 881-889.
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AU - Meda, Shashwath A.

AU - Gill, Adrienne

AU - Stevens, Michael C.

AU - Lorenzoni, Raymond P.

AU - Glahn, David C.

AU - Calhoun, Vince D.

AU - Sweeney, John A.

AU - Tamminga, Carol A.

AU - Keshavan, Matcheri S.

AU - Thaker, Gunvant

AU - Pearlson, Godfrey D.

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N2 - Background: Schizophrenia and bipolar disorder share overlapping symptoms and genetic etiology. Functional brain dysconnectivity is seen in both disorders. Methods: We compared 70 schizophrenia and 64 psychotic bipolar probands, their respective unaffected first-degree relatives (n = 70, and n = 52), and 118 healthy subjects, all group age-, gender-, and ethnicity-matched. We used functional network connectivity analysis to measure differential connectivity among 16 functional magnetic resonance imaging resting state networks. First, we examined connectivity differences between probands and control subjects. Next, we probed these dysfunctional connections in relatives for potential endophenotypes. Network connectivity was then correlated with Positive and Negative Syndrome Scale (PANSS) scores to reveal clinical relationships. Results: Three different network pairs were differentially connected in probands (false-discovery rate corrected q <.05) involving five individual resting-state networks: (A) fronto/occipital, (B) anterior default mode/prefrontal, (C) meso/paralimbic, (D) fronto-temporal/paralimbic, and (E) sensory-motor. One abnormal pair was unique to schizophrenia, (C-E), one unique to bipolar, (C-D), and one (A-B) was shared. Two of these three combinations (A-B, C-E) were also abnormal in bipolar relatives but none was normal in schizophrenia relatives (nonsignificant trend for C-E). The paralimbic circuit (C-D), which uniquely distinguished bipolar probands, contained multiple mood-relevant regions. Network relationship C-D correlated significantly with PANSS negative scores in bipolar probands, and A-B with PANSS positive and general scores in schizophrenia. Conclusions: Schizophrenia and psychotic bipolar probands share several abnormal resting state network connections, but there are also unique neural network underpinnings between disorders. We identified specific connections that might also be candidate psychosis endophenotypes.

AB - Background: Schizophrenia and bipolar disorder share overlapping symptoms and genetic etiology. Functional brain dysconnectivity is seen in both disorders. Methods: We compared 70 schizophrenia and 64 psychotic bipolar probands, their respective unaffected first-degree relatives (n = 70, and n = 52), and 118 healthy subjects, all group age-, gender-, and ethnicity-matched. We used functional network connectivity analysis to measure differential connectivity among 16 functional magnetic resonance imaging resting state networks. First, we examined connectivity differences between probands and control subjects. Next, we probed these dysfunctional connections in relatives for potential endophenotypes. Network connectivity was then correlated with Positive and Negative Syndrome Scale (PANSS) scores to reveal clinical relationships. Results: Three different network pairs were differentially connected in probands (false-discovery rate corrected q <.05) involving five individual resting-state networks: (A) fronto/occipital, (B) anterior default mode/prefrontal, (C) meso/paralimbic, (D) fronto-temporal/paralimbic, and (E) sensory-motor. One abnormal pair was unique to schizophrenia, (C-E), one unique to bipolar, (C-D), and one (A-B) was shared. Two of these three combinations (A-B, C-E) were also abnormal in bipolar relatives but none was normal in schizophrenia relatives (nonsignificant trend for C-E). The paralimbic circuit (C-D), which uniquely distinguished bipolar probands, contained multiple mood-relevant regions. Network relationship C-D correlated significantly with PANSS negative scores in bipolar probands, and A-B with PANSS positive and general scores in schizophrenia. Conclusions: Schizophrenia and psychotic bipolar probands share several abnormal resting state network connections, but there are also unique neural network underpinnings between disorders. We identified specific connections that might also be candidate psychosis endophenotypes.

KW - Bipolar

KW - default mode

KW - functional connectivity

KW - gene

KW - relatives

KW - resting state

KW - schizophrenia

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