Is Aberrant Functional Connectivity A Psychosis Endophenotype? A Resting State Functional Magnetic Resonance Imaging Study
Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives. We investigated resting state functional magnetic resonance imaging in 70 schizophrenia and 64 psychotic bipolar probands, their r...
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| Published in | Biological psychiatry (1969) Vol. 74; no. 6; pp. 458 - 466 |
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| Main Authors | , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
15.09.2013
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| Subjects | |
| Online Access | Get full text |
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| Abstract | Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives.
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.
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.
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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| AbstractList | Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives.
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.
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.
Schizophrenia, psychotic bipolar probands, and their relatives share both unique and overlapping within-network brain connectivity abnormalities, revealing potential psychosis endophenotypes. Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives.BACKGROUNDSchizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in relatives.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.METHODSWe 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.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.RESULTSSeven 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.Schizophrenia, psychotic bipolar probands, and their relatives share both unique and overlapping within-network brain connectivity abnormalities, revealing potential psychosis endophenotypes.CONCLUSIONSSchizophrenia, psychotic bipolar probands, and their relatives share both unique and overlapping within-network brain connectivity abnormalities, revealing potential psychosis endophenotypes. 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. |
| Author | Khadka, Sabin Glahn, David C. O’Neil, Kasey Schretlen, David Meda, Shashwath A. Keshavan, Matcheri S. Tamminga, Carol A. Pearlson, Godfrey D. Stevens, Michael C. Sweeney, John A. Calhoun, Vince D. |
| AuthorAffiliation | 3 Mind Research Network, Albuquerque, NM 87131 4 Department of Electrical and Computer Engineering, University of New Mexico, NM 87131 5 Department of Psychiatry, Johns Hopkins Hospital, Baltimore, MD 02138 7 Department of Psychiatry, Harvard Medical School, Boston, MA 02138 6 Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX 75390 8 Department of Neurobiology, Yale university, New Haven 06511 1 Olin Neuropsychiatry Research Center, Hartford Hospital/IOL, CT 06106 2 Department of Psychiatry, Yale University, New Haven, CT 06511 |
| AuthorAffiliation_xml | – name: 3 Mind Research Network, Albuquerque, NM 87131 – name: 8 Department of Neurobiology, Yale university, New Haven 06511 – name: 6 Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX 75390 – name: 5 Department of Psychiatry, Johns Hopkins Hospital, Baltimore, MD 02138 – name: 1 Olin Neuropsychiatry Research Center, Hartford Hospital/IOL, CT 06106 – name: 2 Department of Psychiatry, Yale University, New Haven, CT 06511 – name: 4 Department of Electrical and Computer Engineering, University of New Mexico, NM 87131 – name: 7 Department of Psychiatry, Harvard Medical School, Boston, MA 02138 |
| Author_xml | – sequence: 1 givenname: Sabin surname: Khadka fullname: Khadka, Sabin email: skhadka@harthosp.org organization: Olin Neuropsychiatry Research Center, Hartford Hospital/Institute of Living, Hartford – sequence: 2 givenname: Shashwath A. surname: Meda fullname: Meda, Shashwath A. organization: Olin Neuropsychiatry Research Center, Hartford Hospital/Institute of Living, Hartford – sequence: 3 givenname: Michael C. surname: Stevens fullname: Stevens, Michael C. organization: Olin Neuropsychiatry Research Center, Hartford Hospital/Institute of Living, Hartford – sequence: 4 givenname: David C. surname: Glahn fullname: Glahn, David C. organization: Olin Neuropsychiatry Research Center, Hartford Hospital/Institute of Living, Hartford – sequence: 5 givenname: Vince D. surname: Calhoun fullname: Calhoun, Vince D. organization: Olin Neuropsychiatry Research Center, Hartford Hospital/Institute of Living, Hartford – sequence: 6 givenname: John A. surname: Sweeney fullname: Sweeney, John A. organization: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas – sequence: 7 givenname: Carol A. surname: Tamminga fullname: Tamminga, Carol A. organization: Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas – sequence: 8 givenname: Matcheri S. surname: Keshavan fullname: Keshavan, Matcheri S. organization: Department of Psychiatry, Harvard Medical School, Boston, Massachusetts – sequence: 9 givenname: Kasey surname: O’Neil fullname: O’Neil, Kasey organization: Olin Neuropsychiatry Research Center, Hartford Hospital/Institute of Living, Hartford – sequence: 10 givenname: David surname: Schretlen fullname: Schretlen, David organization: Johns Hopkins Hospital, Baltimore, Maryland – sequence: 11 givenname: Godfrey D. surname: Pearlson fullname: Pearlson, Godfrey D. organization: Olin Neuropsychiatry Research Center, Hartford Hospital/Institute of Living, Hartford |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/23746539$$D View this record in MEDLINE/PubMed |
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| Keywords | endophenotype Bipolar resting state schizophrenia relatives within-network connectivity |
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| Snippet | Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both disorders and in... Background Schizophrenia and bipolar disorder share overlapping symptoms and risk genes. Shared aberrant functional connectivity is hypothesized in both... |
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| SubjectTerms | Adult Bipolar Bipolar Disorder - physiopathology Brain - physiopathology Brain Mapping endophenotype Endophenotypes Female Humans Magnetic Resonance Imaging Male Nerve Net - physiopathology Psychiatry relatives Rest - physiology resting state schizophrenia Schizophrenia - physiopathology within-network connectivity |
| Title | Is Aberrant Functional Connectivity A Psychosis Endophenotype? A Resting State Functional Magnetic Resonance Imaging Study |
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