Resting-state brain function in schizophrenia and psychotic bipolar probands and their first-degree relatives

S. Lui, L. Yao, Y. Xiao, S. K. Keedy, J. L. Reilly, R. S. Keefe, C. A. Tamminga, M. S. Keshavan, G. D. Pearlson, Q. Gong, J. A. Sweeney

Research output: Contribution to journalArticle

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Abstract

Background. Schizophrenia (SCZ) and psychotic bipolar disorder (PBD) share considerable overlap in clinical features, genetic risk factors and co-occurrence among relatives. The common and unique functional cerebral deficits in these disorders, and in unaffected relatives, remain to be identified. Method. A total of 59 healthy controls, 37 SCZ and 57 PBD probands and their unaffected first-degree relatives (38 and 28, respectively) were studied using resting-state functional magnetic resonance imaging (rfMRI). Regional cerebral function was evaluated by measuring the amplitude of low-frequency fluctuations (ALFF). Areas with ALFF alterations were used as seeds in whole-brain functional connectivity analysis. We then tested whether abnormalities identified in probands were present in unaffected relatives. Results. SCZ and PBD probands both demonstrated regional hypoactivity in the orbital frontal cortex and cingulate gyrus, as well as abnormal connectivity within striatal-thalamo-cortical networks. SCZ probands showed greater and more widely distributed ALFF alterations including the thalamus and bilateral parahippocampal gyri. Increased parahippocampal ALFF was related to positive symptoms and cognitive deficit. PBD patients showed uniquely increased functional connectivity between the thalamus and bilateral insula. Only PBD relatives showed abnormal connectivity within striatal-thalamo-cortical networks seen in both proband groups. Conclusions. The present findings reveal a common pattern of deficits in frontostriatal circuitry across SCZ and PBD, and unique regional and functional connectivity abnormalities that distinguish them. The abnormal network connectivity in PBD relatives that was present in both proband groups may reflect genetic susceptibility associated with risk for psychosis, but within-family associations of this measure were not high.

Original languageEnglish (US)
Pages (from-to)97-108
Number of pages12
JournalPsychological Medicine
Volume45
Issue number1
DOIs
StatePublished - Jan 12 2015

Fingerprint

Psychotic Disorders
Bipolar Disorder
Schizophrenia
Brain
Corpus Striatum
Thalamus
Parahippocampal Gyrus
Neurobehavioral Manifestations
Gyrus Cinguli
Frontal Lobe
Genetic Predisposition to Disease
Prefrontal Cortex
Seeds
Magnetic Resonance Imaging

Keywords

  • Bipolar disorder
  • brain function
  • magnetic resonance imaging
  • relatives
  • resting state
  • schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Applied Psychology

Cite this

Lui, S., Yao, L., Xiao, Y., Keedy, S. K., Reilly, J. L., Keefe, R. S., ... Sweeney, J. A. (2015). Resting-state brain function in schizophrenia and psychotic bipolar probands and their first-degree relatives. Psychological Medicine, 45(1), 97-108. https://doi.org/10.1017/S003329171400110X

Resting-state brain function in schizophrenia and psychotic bipolar probands and their first-degree relatives. / Lui, S.; Yao, L.; Xiao, Y.; Keedy, S. K.; Reilly, J. L.; Keefe, R. S.; Tamminga, C. A.; Keshavan, M. S.; Pearlson, G. D.; Gong, Q.; Sweeney, J. A.

In: Psychological Medicine, Vol. 45, No. 1, 12.01.2015, p. 97-108.

Research output: Contribution to journalArticle

Lui, S, Yao, L, Xiao, Y, Keedy, SK, Reilly, JL, Keefe, RS, Tamminga, CA, Keshavan, MS, Pearlson, GD, Gong, Q & Sweeney, JA 2015, 'Resting-state brain function in schizophrenia and psychotic bipolar probands and their first-degree relatives', Psychological Medicine, vol. 45, no. 1, pp. 97-108. https://doi.org/10.1017/S003329171400110X
Lui, S. ; Yao, L. ; Xiao, Y. ; Keedy, S. K. ; Reilly, J. L. ; Keefe, R. S. ; Tamminga, C. A. ; Keshavan, M. S. ; Pearlson, G. D. ; Gong, Q. ; Sweeney, J. A. / Resting-state brain function in schizophrenia and psychotic bipolar probands and their first-degree relatives. In: Psychological Medicine. 2015 ; Vol. 45, No. 1. pp. 97-108.
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abstract = "Background. Schizophrenia (SCZ) and psychotic bipolar disorder (PBD) share considerable overlap in clinical features, genetic risk factors and co-occurrence among relatives. The common and unique functional cerebral deficits in these disorders, and in unaffected relatives, remain to be identified. Method. A total of 59 healthy controls, 37 SCZ and 57 PBD probands and their unaffected first-degree relatives (38 and 28, respectively) were studied using resting-state functional magnetic resonance imaging (rfMRI). Regional cerebral function was evaluated by measuring the amplitude of low-frequency fluctuations (ALFF). Areas with ALFF alterations were used as seeds in whole-brain functional connectivity analysis. We then tested whether abnormalities identified in probands were present in unaffected relatives. Results. SCZ and PBD probands both demonstrated regional hypoactivity in the orbital frontal cortex and cingulate gyrus, as well as abnormal connectivity within striatal-thalamo-cortical networks. SCZ probands showed greater and more widely distributed ALFF alterations including the thalamus and bilateral parahippocampal gyri. Increased parahippocampal ALFF was related to positive symptoms and cognitive deficit. PBD patients showed uniquely increased functional connectivity between the thalamus and bilateral insula. Only PBD relatives showed abnormal connectivity within striatal-thalamo-cortical networks seen in both proband groups. Conclusions. The present findings reveal a common pattern of deficits in frontostriatal circuitry across SCZ and PBD, and unique regional and functional connectivity abnormalities that distinguish them. The abnormal network connectivity in PBD relatives that was present in both proband groups may reflect genetic susceptibility associated with risk for psychosis, but within-family associations of this measure were not high.",
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AU - Lui, S.

AU - Yao, L.

AU - Xiao, Y.

AU - Keedy, S. K.

AU - Reilly, J. L.

AU - Keefe, R. S.

AU - Tamminga, C. A.

AU - Keshavan, M. S.

AU - Pearlson, G. D.

AU - Gong, Q.

AU - Sweeney, J. A.

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N2 - Background. Schizophrenia (SCZ) and psychotic bipolar disorder (PBD) share considerable overlap in clinical features, genetic risk factors and co-occurrence among relatives. The common and unique functional cerebral deficits in these disorders, and in unaffected relatives, remain to be identified. Method. A total of 59 healthy controls, 37 SCZ and 57 PBD probands and their unaffected first-degree relatives (38 and 28, respectively) were studied using resting-state functional magnetic resonance imaging (rfMRI). Regional cerebral function was evaluated by measuring the amplitude of low-frequency fluctuations (ALFF). Areas with ALFF alterations were used as seeds in whole-brain functional connectivity analysis. We then tested whether abnormalities identified in probands were present in unaffected relatives. Results. SCZ and PBD probands both demonstrated regional hypoactivity in the orbital frontal cortex and cingulate gyrus, as well as abnormal connectivity within striatal-thalamo-cortical networks. SCZ probands showed greater and more widely distributed ALFF alterations including the thalamus and bilateral parahippocampal gyri. Increased parahippocampal ALFF was related to positive symptoms and cognitive deficit. PBD patients showed uniquely increased functional connectivity between the thalamus and bilateral insula. Only PBD relatives showed abnormal connectivity within striatal-thalamo-cortical networks seen in both proband groups. Conclusions. The present findings reveal a common pattern of deficits in frontostriatal circuitry across SCZ and PBD, and unique regional and functional connectivity abnormalities that distinguish them. The abnormal network connectivity in PBD relatives that was present in both proband groups may reflect genetic susceptibility associated with risk for psychosis, but within-family associations of this measure were not high.

AB - Background. Schizophrenia (SCZ) and psychotic bipolar disorder (PBD) share considerable overlap in clinical features, genetic risk factors and co-occurrence among relatives. The common and unique functional cerebral deficits in these disorders, and in unaffected relatives, remain to be identified. Method. A total of 59 healthy controls, 37 SCZ and 57 PBD probands and their unaffected first-degree relatives (38 and 28, respectively) were studied using resting-state functional magnetic resonance imaging (rfMRI). Regional cerebral function was evaluated by measuring the amplitude of low-frequency fluctuations (ALFF). Areas with ALFF alterations were used as seeds in whole-brain functional connectivity analysis. We then tested whether abnormalities identified in probands were present in unaffected relatives. Results. SCZ and PBD probands both demonstrated regional hypoactivity in the orbital frontal cortex and cingulate gyrus, as well as abnormal connectivity within striatal-thalamo-cortical networks. SCZ probands showed greater and more widely distributed ALFF alterations including the thalamus and bilateral parahippocampal gyri. Increased parahippocampal ALFF was related to positive symptoms and cognitive deficit. PBD patients showed uniquely increased functional connectivity between the thalamus and bilateral insula. Only PBD relatives showed abnormal connectivity within striatal-thalamo-cortical networks seen in both proband groups. Conclusions. The present findings reveal a common pattern of deficits in frontostriatal circuitry across SCZ and PBD, and unique regional and functional connectivity abnormalities that distinguish them. The abnormal network connectivity in PBD relatives that was present in both proband groups may reflect genetic susceptibility associated with risk for psychosis, but within-family associations of this measure were not high.

KW - Bipolar disorder

KW - brain function

KW - magnetic resonance imaging

KW - relatives

KW - resting state

KW - schizophrenia

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