TY - JOUR
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.
N1 - Funding Information:
John Sweeney is a consultant to Pfizer and has a research grant from Janssen. Carol Tamminga has the following disclosures to make: Intracellular Therapies (ITI, Inc.)—Advisory Board, drug development >$10,000; PureTech Ventures—Ad Hoc Consultant $10,000. The other authors report no biomedical financial interests or potential conflicts of interest.
Funding Information:
This study was funded by National Institute of Mental Health (NIMH) Grant Nos. R37MH43375 and R01MH074797 (GDP), the von Humboldt Foundation and NIMH Grant No. MH077862 (JAS), National Institutes of Health/National Institute of Biomedical Imaging and Bioengineering Grant No. 2R01 EB000840 and NIH/National Center for Research Resources Grant No. 5P20RR021938 (VDC), NIMH Grant No. MH78113 (MSK), NIMH Grant No. MH077851 (CAT), NIMH 5R01 Grant No. MH077945-03 to Gunvant Thaker, CAT, GDP, MSK, and JAS.
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
UR - http://www.scopus.com/inward/record.url?scp=84882592076&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2013.04.024
DO - 10.1016/j.biopsych.2013.04.024
M3 - Article
AN - SCOPUS:84882592076
SN - 0006-3223
VL - 74
SP - 458
EP - 466
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 6
ER -