Is aberrant functional connectivity a psychosis endophenotype? A resting state functional magnetic resonance imaging study

Sabin Khadka, Shashwath A. Meda, Michael C. Stevens, David C. Glahn, Vince D. Calhoun, John A. Sweeney, Carol A. Tamminga, Matcheri S. Keshavan, Kasey O'Neil, David Schretlen, Godfrey D. Pearlson

Research output: Contribution to journalArticle

125 Citations (Scopus)

Abstract

Background Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives. Methods We investigated resting state functional magnetic resonance imaging in 70 schizophrenia and 64 psychotic bipolar probands, their respective first-degree relatives (n = 70 and 52), and 118 healthy subjects. We used independent component analysis to identify components representing various resting state networks and assessed spatial aspects of functional connectivity within all networks. We first investigated group differences using five-level, one-way analysis of covariance (ANCOVA), followed by post hoc t tests within regions displaying ANCOVA group differences and correlation of such functional connectivity measures with symptom ratings to examine clinical relationships. Results Seven networks revealed abnormalities (five-level one-way ANCOVA, family-wise error correction p <.05): A) fronto-occipital, B) midbrain/cerebellum, C) frontal/thalamic/basal ganglia, D) meso/paralimbic, E) posterior default mode network, F) fronto-temporal/ paralimbic and G) sensorimotor networks. Abnormalities in networks B and F were unique to schizophrenia probands. Furthermore, abnormalities in networks D and E were common to both patient groups. Finally, networks A, C, and G showed abnormalities shared by probands and their relative groups. Negative correlation with Positive and Negative Syndrome Scale negative and positive scores were found in regions within network C and F respectively, and positive correlation with Positive and Negative Syndrome Scale negative scores was found in regions in network D among schizophrenia probands only. Conclusions Schizophrenia, psychotic bipolar probands, and their relatives share both unique and overlapping within-network brain connectivity abnormalities, revealing potential psychosis endophenotypes.

Original languageEnglish (US)
Pages (from-to)458-466
Number of pages9
JournalBiological Psychiatry
Volume74
Issue number6
DOIs
StatePublished - Sep 15 2013

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Endophenotypes
Psychotic Disorders
Schizophrenia
Magnetic Resonance Imaging
Mesencephalon
Basal Ganglia
Bipolar Disorder
Cerebellum
Healthy Volunteers
Brain
Genes

Keywords

  • Bipolar
  • endophenotype
  • relatives
  • resting state
  • schizophrenia
  • within-network connectivity

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Is aberrant functional connectivity a psychosis endophenotype? A resting state functional magnetic resonance imaging study. / Khadka, Sabin; Meda, Shashwath A.; Stevens, Michael C.; Glahn, David C.; Calhoun, Vince D.; Sweeney, John A.; Tamminga, Carol A.; Keshavan, Matcheri S.; O'Neil, Kasey; Schretlen, David; Pearlson, Godfrey D.

In: Biological Psychiatry, Vol. 74, No. 6, 15.09.2013, p. 458-466.

Research output: Contribution to journalArticle

Khadka, S, Meda, SA, Stevens, MC, Glahn, DC, Calhoun, VD, Sweeney, JA, Tamminga, CA, Keshavan, MS, O'Neil, K, Schretlen, D & Pearlson, GD 2013, 'Is aberrant functional connectivity a psychosis endophenotype? A resting state functional magnetic resonance imaging study', Biological Psychiatry, vol. 74, no. 6, pp. 458-466. https://doi.org/10.1016/j.biopsych.2013.04.024
Khadka, Sabin ; Meda, Shashwath A. ; Stevens, Michael C. ; Glahn, David C. ; Calhoun, Vince D. ; Sweeney, John A. ; Tamminga, Carol A. ; Keshavan, Matcheri S. ; O'Neil, Kasey ; Schretlen, David ; Pearlson, Godfrey D. / Is aberrant functional connectivity a psychosis endophenotype? A resting state functional magnetic resonance imaging study. In: Biological Psychiatry. 2013 ; Vol. 74, No. 6. pp. 458-466.
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abstract = "Background Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives. Methods We investigated resting state functional magnetic resonance imaging in 70 schizophrenia and 64 psychotic bipolar probands, their respective first-degree relatives (n = 70 and 52), and 118 healthy subjects. We used independent component analysis to identify components representing various resting state networks and assessed spatial aspects of functional connectivity within all networks. We first investigated group differences using five-level, one-way analysis of covariance (ANCOVA), followed by post hoc t tests within regions displaying ANCOVA group differences and correlation of such functional connectivity measures with symptom ratings to examine clinical relationships. Results Seven networks revealed abnormalities (five-level one-way ANCOVA, family-wise error correction p <.05): A) fronto-occipital, B) midbrain/cerebellum, C) frontal/thalamic/basal ganglia, D) meso/paralimbic, E) posterior default mode network, F) fronto-temporal/ paralimbic and G) sensorimotor networks. Abnormalities in networks B and F were unique to schizophrenia probands. Furthermore, abnormalities in networks D and E were common to both patient groups. Finally, networks A, C, and G showed abnormalities shared by probands and their relative groups. Negative correlation with Positive and Negative Syndrome Scale negative and positive scores were found in regions within network C and F respectively, and positive correlation with Positive and Negative Syndrome Scale negative scores was found in regions in network D among schizophrenia probands only. Conclusions Schizophrenia, psychotic bipolar probands, and their relatives share both unique and overlapping within-network brain connectivity abnormalities, revealing potential psychosis endophenotypes.",
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T1 - Is aberrant functional connectivity a psychosis endophenotype? A resting state functional magnetic resonance imaging study

AU - Khadka, Sabin

AU - Meda, Shashwath A.

AU - Stevens, Michael C.

AU - Glahn, David C.

AU - Calhoun, Vince D.

AU - Sweeney, John A.

AU - Tamminga, Carol A.

AU - Keshavan, Matcheri S.

AU - O'Neil, Kasey

AU - Schretlen, David

AU - Pearlson, Godfrey D.

PY - 2013/9/15

Y1 - 2013/9/15

N2 - Background Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives. Methods We investigated resting state functional magnetic resonance imaging in 70 schizophrenia and 64 psychotic bipolar probands, their respective first-degree relatives (n = 70 and 52), and 118 healthy subjects. We used independent component analysis to identify components representing various resting state networks and assessed spatial aspects of functional connectivity within all networks. We first investigated group differences using five-level, one-way analysis of covariance (ANCOVA), followed by post hoc t tests within regions displaying ANCOVA group differences and correlation of such functional connectivity measures with symptom ratings to examine clinical relationships. Results Seven networks revealed abnormalities (five-level one-way ANCOVA, family-wise error correction p <.05): A) fronto-occipital, B) midbrain/cerebellum, C) frontal/thalamic/basal ganglia, D) meso/paralimbic, E) posterior default mode network, F) fronto-temporal/ paralimbic and G) sensorimotor networks. Abnormalities in networks B and F were unique to schizophrenia probands. Furthermore, abnormalities in networks D and E were common to both patient groups. Finally, networks A, C, and G showed abnormalities shared by probands and their relative groups. Negative correlation with Positive and Negative Syndrome Scale negative and positive scores were found in regions within network C and F respectively, and positive correlation with Positive and Negative Syndrome Scale negative scores was found in regions in network D among schizophrenia probands only. Conclusions Schizophrenia, psychotic bipolar probands, and their relatives share both unique and overlapping within-network brain connectivity abnormalities, revealing potential psychosis endophenotypes.

AB - Background Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives. Methods We investigated resting state functional magnetic resonance imaging in 70 schizophrenia and 64 psychotic bipolar probands, their respective first-degree relatives (n = 70 and 52), and 118 healthy subjects. We used independent component analysis to identify components representing various resting state networks and assessed spatial aspects of functional connectivity within all networks. We first investigated group differences using five-level, one-way analysis of covariance (ANCOVA), followed by post hoc t tests within regions displaying ANCOVA group differences and correlation of such functional connectivity measures with symptom ratings to examine clinical relationships. Results Seven networks revealed abnormalities (five-level one-way ANCOVA, family-wise error correction p <.05): A) fronto-occipital, B) midbrain/cerebellum, C) frontal/thalamic/basal ganglia, D) meso/paralimbic, E) posterior default mode network, F) fronto-temporal/ paralimbic and G) sensorimotor networks. Abnormalities in networks B and F were unique to schizophrenia probands. Furthermore, abnormalities in networks D and E were common to both patient groups. Finally, networks A, C, and G showed abnormalities shared by probands and their relative groups. Negative correlation with Positive and Negative Syndrome Scale negative and positive scores were found in regions within network C and F respectively, and positive correlation with Positive and Negative Syndrome Scale negative scores was found in regions in network D among schizophrenia probands only. Conclusions Schizophrenia, psychotic bipolar probands, and their relatives share both unique and overlapping within-network brain connectivity abnormalities, revealing potential psychosis endophenotypes.

KW - Bipolar

KW - endophenotype

KW - relatives

KW - resting state

KW - schizophrenia

KW - within-network connectivity

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U2 - 10.1016/j.biopsych.2013.04.024

DO - 10.1016/j.biopsych.2013.04.024

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