The relationship between genetic risk variants with brain structure and function in bipolar disorder: A systematic review of genetic-neuroimaging studies

Licia P Pereira; Cristiano A Köhler; Rafael T de Sousa; Marco Solmi; Bárbara P de Freitas; Michele Fornaro; Rodrigo Machado-Vieira; Kamilla W Miskowiak; Eduard Vieta; Nicola Veronese; Brendon Stubbs; André F Carvalho

doi:10.1016/j.neubiorev.2017.05.002

The relationship between genetic risk variants with brain structure and function in bipolar disorder: A systematic review of genetic-neuroimaging studies

Neurosci Biobehav Rev. 2017 Aug:79:87-109. doi: 10.1016/j.neubiorev.2017.05.002. Epub 2017 May 4.

Affiliations

¹ Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil.
² Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, NIH, Bethesda, MD, USA.
³ Department of Neuroscience, University of Padova, Padova, Italy; Institute for Clinical Research and Education in Medicine (IREM), Padova, Italy.
⁴ New York State Psychiatric Institute (NYSPI), Columbia University, New York, NY, USA.
⁵ Copenhagen Psychiatric Centre, Copenhagen University Hospital, Rigshospitalet, Denmark.
⁶ Bipolar Unit, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain.
⁷ Institute for Clinical Research and Education in Medicine (IREM), Padova, Italy; National Research Council, Neuroscience Institute, Aging Branch, Padova, Italy.
⁸ Institute for Clinical Research and Education in Medicine (IREM), Padova, Italy; Physiotherapy Department, South London and Maudsley NHS Foundation Trust, Denmark Hill, London SE5 8AZ, United Kingdom; Health Service and Population Research Department, Institute of Psychiatry, Psychology and Neuroscience, King's College London, De Crespigny Park, London, SE5 8AF, United Kingdom; Faculty of Health, Social Care and Education, Anglia Ruskin University, Bishop Hall Lane, Chelmsford CM1 1SQ, United Kingdom.
⁹ Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil; Institute for Clinical Research and Education in Medicine (IREM), Padova, Italy. Electronic address: andrefc7@terra.com.br.

PMID: 28479278
DOI: 10.1016/j.neubiorev.2017.05.002

Abstract

Genetic-neuroimaging paradigms could provide insights regarding the pathophysiology of bipolar disorder (BD). Nevertheless, findings have been inconsistent across studies. A systematic review of gene-imaging studies involving individuals with BD was conducted across electronic major databases from inception until January 9th, 2017. Forty-four studies met eligibility criteria (N=2122 BD participants). Twenty-six gene variants were investigated across candidate gene studies and 4 studies used a genome-wide association approach. Replicated evidence (i.e. in >2 studies) suggests that individuals with BD carrying the BDNF Val66Met risk allele could have reduced hippocampal volumes compared to non-carriers. This review underscores the potential of gene-neuroimaging paradigms to provide mechanistic insights for BD. However, this systematic review found a single replicated finding. Suggestions to improve the reproducibility of this emerging field are provided, including the adoption of a trans-diagnostic approach.

Keywords: Bipolar disorder; Diffusion tensor imagingvoxel based morphometry; Functional MRI; Genetic polymorphisms; Magnetic resonance imaging; Neuroimaging.

Publication types

Review
Systematic Review

MeSH terms

Bipolar Disorder / genetics*
Brain
Genome-Wide Association Study
Humans
Magnetic Resonance Imaging
Neuroimaging
Reproducibility of Results