Journal
PSYCHOLOGICAL MEDICINE
Volume 45, Issue 1, Pages 97-108Publisher
CAMBRIDGE UNIV PRESS
DOI: 10.1017/S003329171400110X
Keywords
Bipolar disorder; brain function; magnetic resonance imaging; relatives; resting state; schizophrenia
Categories
Funding
- National Institute of Mental Health [MH078113, MH077945, MH077852, MH077851, MH077862, MH072767, MH083888]
- National Natural Science Foundation (China) [81222018, 81371527, 81030027, 81227002, 81220108013]
- Intracellular Therapies (ITI, Inc.)
- PureTech Ventures
- Eli Lilly
- Sunovion
- Astellas
- Merck
- International Congress on Schizophrenia Research
- National Alliance on Mental Illness
- American Psychiatric Association
- Finnegan Henderson Farabow Garrett Dunner, LLP.
- GlaxoSmithKline
- Takeda
- Pfizer
- BMS
- Janssen
- Allon
- AstraZeneca
- Department of Veterans' Affairs
- Feinstein Institute for Medical Research
- National Institute of Mental Health, Novartis, Psychogenics
- Research Foundation for Mental Hygiene, Inc.
- Singapore National Medical Research Council
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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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