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Transdiagnostic and Illness-Specific Functional Dysconnectivity Across Schizophrenia, Bipolar Disorder and Major Depression and Relationships with Working Memory

33 Pages Posted: 23 Mar 2019

See all articles by Chu-Chung Huang

Chu-Chung Huang

National Yang-Ming University - Aging and Health Research Center

Qiang Luo

Fudan University - Institute of Science and Technology for Brain-Inspired Intelligence and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence

Lena Palaniyappan

University of Western Ontario - Department of Psychiatry

Albert C. Yang

Harvard University - Beth Israel Deaconess Medical Center

Chia-Chun Hung

National Yang-Ming University

Kun-Hsien Chou

National Yang-Ming University

Chun-Yi Zac Lo

Fudan University - Institute of Science and Technology for Brain-Inspired Intelligence and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence

Mu-N Liu

National Yang-Ming University

Shih-Jen Tsai

National Yang-Ming University

Deanna M. Barch

Washington University in St. Louis - Department of Psychological and Brain Sciences; Washington University in St. Louis - Mallinckrodt Institute of Radiology; Washington University in St. Louis - Department of Psychiatry

Trevor W. Robbins

University of Cambridge - Department of Psychology

Jianfeng Feng

Fudan University - Institute of Science and Technology for Brain-Inspired Intelligence and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence; University of Warwick - Department of Computer Science

Ching-Po Lin

National Yang-Ming University - Aging and Health Research Center; Fudan University - Institute of Science and Technology for Brain-Inspired Intelligence and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence; National Yang-Ming University - Institute of Neuroscience

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Abstract

Background:  Mental disorders are typically defined as distinct diagnostic entities but similar patterns of clinical impairments are frequently found in practice across the diagnostic groups. We investigate whether the transdiagnostic deficits result from a common neurocognitive mechanism across disorders, or various illness-specific mechanisms, or a combination of both.    

Methods:  Functional MRI data were collected from the clinically stable patients with major depressive disorder (MDD; n=53), bipolar disorder (BIP; n=78), or schizophrenia (SCZ; n=100), and the matched healthy control subjects (n=109) using a single scanner. Group comparisons were conducted to identify both the transdiagnostic and the illness-specific features. A multivariate approach with cross-validation was used to assess the association between the brain functional dysconnectivity and the cognitive deficits. The confounding effect of medication on the findings was also tested.    

Findings: Compared with the healthy controls, the patients displayed shared working memory deficits [Cohen's d (d) in MDD/BIP/SCZ=0·73/0·65/0·89], and functional dysconnectivity within brain networks [somatomotor (d:0·50- 0·58) and salience (d:0·52-0·58)] and between brain networks [subcortical-limbic (d:0·55-0·69) and subcortical-dorsal attention (d:0·56-0·61)]. The illness-specific dysconnectivity were found between the executive control and default-mode networks in SCZ (d:0·46-0·56), between the salience and subcortical networks in BIP (d:0·47-0·48), and between the salience and default-mode networks in MDD (d:0·53-0·55). Working memory deficits were associated with a linear combination of 10 transdiagnostic and 4 illness-specific dysconnectivity patterns (r = 0·368, p = 2·45e-12, n = 340). The associations between the dysconnectivity patterns and the medication dosage did not reach statistical significance.    

Interpretation  This study emphasizes that transdiagnostic deficits in cognition may be mediated by multiple interactions between many brain networks, and including diagnostic-specific patterns of functional dysconnectivity in different psychiatric disorders.    

Funding Statement:  Ministry of Science and Technology, National Health Research Institutes (Taiwan). National Natural Science Foundation, National Key Research and Development Program, Shanghai Municipal Science and Technology Major Project, Shanghai Science and Technology Innovation Plan, Shanghai AI Platform for Diagnosis and Treatment of Brain Diseases, the Project of Zhangjiang Hi-Tech District Management, and Zhangjiang Lab (China). Academic Medical Organsiation of Southwest Ontario and the Bucke Family Funds.

Declaration of Interests: Dr Palaniyappan reports educational grants and personal fees from Otsuka Canada and Janssen Canada, educational grants from Sunovion, personal fees from SPMM Course (UK) and Canadian Psychiatric Association, and royalties from Oxford University Press outside the submitted work. Dr. Robbins reports personal fees from Cambridge Cognition, Unilever, Mundipharma, Greenfiled Inc, grants from Shionogi, Lundbeck, Small Pharma, personal fees from Elsevier, Springer Verlag, outside the submitted work. No other disclosures were reported

Ethics Approval Statement: The study was approved by the Institutional Review Board of Taipei Veterans General Hospital. Written informed consent was obtained from all participants before commencement of the study.

Keywords: Transdiagnosis, Depression, Bipolar Disorder, Schizophrenia, Working Memory, Dysconnectivity

Suggested Citation

Huang, Chu-Chung and Luo, Qiang and Palaniyappan, Lena and Yang, Albert C. and Hung, Chia-Chun and Chou, Kun-Hsien and Lo, Chun-Yi Zac and Liu, Mu-N and Tsai, Shih-Jen and Barch, Deanna M. and Robbins, Trevor W. and Feng, Jianfeng and Lin, Ching-Po, Transdiagnostic and Illness-Specific Functional Dysconnectivity Across Schizophrenia, Bipolar Disorder and Major Depression and Relationships with Working Memory (March 20, 2019). Available at SSRN: https://ssrn.com/abstract=3356860

Chu-Chung Huang

National Yang-Ming University - Aging and Health Research Center

Taipei
Taiwan

Qiang Luo

Fudan University - Institute of Science and Technology for Brain-Inspired Intelligence and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence

Shanghai
China

Lena Palaniyappan

University of Western Ontario - Department of Psychiatry

London, Ontario N6A 5W9
Canada

Albert C. Yang

Harvard University - Beth Israel Deaconess Medical Center

330 Brookline Avenue
Boston, MA 02115
United States

Chia-Chun Hung

National Yang-Ming University

(112) 155 Li-Nong Street
Sec. 2 Pei-Tou
Taipei
Taiwan

Kun-Hsien Chou

National Yang-Ming University

(112) 155 Li-Nong Street
Sec. 2 Pei-Tou
Taipei
Taiwan

Chun-Yi Zac Lo

Fudan University - Institute of Science and Technology for Brain-Inspired Intelligence and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence

Shanghai
China

Mu-N Liu

National Yang-Ming University

(112) 155 Li-Nong Street
Sec. 2 Pei-Tou
Taipei
Taiwan

Shih-Jen Tsai

National Yang-Ming University

(112) 155 Li-Nong Street
Sec. 2 Pei-Tou
Taipei
Taiwan

Deanna M. Barch

Washington University in St. Louis - Department of Psychological and Brain Sciences

1 Brookings Drive
St. Louis, MO 63130
United States

Washington University in St. Louis - Mallinckrodt Institute of Radiology

St. Louis, MO
United States

Washington University in St. Louis - Department of Psychiatry

660 S. Euclid Avenue
St. Louis, MO 63110
United States

Trevor W. Robbins

University of Cambridge - Department of Psychology ( email )

Downing St.
Cambridge, CB2 3EB
United Kingdom

Jianfeng Feng

Fudan University - Institute of Science and Technology for Brain-Inspired Intelligence and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence ( email )

Shanghai
China

University of Warwick - Department of Computer Science ( email )

Dept of Computer Science
Coventry CV4 7AL, CV4 7AL
United Kingdom

Ching-Po Lin (Contact Author)

National Yang-Ming University - Aging and Health Research Center ( email )

Taipei
Taiwan

Fudan University - Institute of Science and Technology for Brain-Inspired Intelligence and Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence ( email )

Shanghai
China

National Yang-Ming University - Institute of Neuroscience ( email )

Taipei
Taiwan

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