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A negative association between brainstem pontine grey-matter volume, well-being and resilience in healthy twins

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J Psychiatry Neurosci 2018;43(6):386-395

Justine M. Gatt, PhD; Karen L.O. Burton, PhD; Kylie M. Routledge, PhD; Katrina L. Grasby, PhD; Mayuresh S. Korgaonkar, PhD; Stuart M. Grieve, DPhil (Oxon), MBBS; Peter R. Schofield, PhD, DSc; Anthony W.F. Harris, MBBS, PhD; C. Richard Clark, PhD; Leanne M. Williams, PhD


Background: Associations between well-being, resilience to trauma and the volume of grey-matter regions involved in affective processing (e.g., threat/reward circuits) are largely unexplored, as are the roles of shared genetic and environmental factors derived from multivariate twin modelling.

Methods: This study presents, to our knowledge, the first exploration of well-being and volumes of grey-matter regions involved in affective processing using a region-of-interest, voxel-based approach in 263 healthy adult twins (60% monozygotic pairs, 61% females, mean age 39.69 yr). To examine patterns for resilience (i.e., positive adaptation following adversity), we evaluated associations between the same brain regions and well-being in a trauma-exposed subgroup.

Results: We found a correlated effect between increased well-being and reduced grey-matter volume of the pontine nuclei. This association was strongest for individuals with higher resilience to trauma. Multivariate twin modelling suggested that the common variance between the pons volume and well-being scores was due to environmental factors.

Limitations: We used a cross-sectional sample; results need to be replicated longitudinally and in a larger sample.

Conclusion: Associations with altered grey matter of the pontine nuclei suggest that basic sensory processes, such as arousal, startle, memory consolidation and/or emotional conditioning, may have a role in well-being and resilience.

Submitted July 3, 2017; Revised Dec. 3, 2017; Accepted Feb. 22, 2018; Published online June 20, 2018

Acknowledgements: This project was supported by an Australian Research Council (ARC) Linkage grant (LP0883621), with Brain Resource Ltd as industry partner. J. Gatt and M. Korgaonkar are supported by National Health & Medical Research Council (NHMRC) Career Development Fellowships (1062495 awarded to JMG and 1090148 to MSK). K. Routledge was supported by a NHMRC Postgraduate Public Health Scholarship (1055839). K. Grasby was supported by NHMRC grants (1103603 and 1103623). P. Schofield is supported by a NHMRC Program Grant (1037196). This research was facilitated through the Australian Twin Registry, a national research resource in part supported by a Centre of Research Excellence Grant from the National Health & Medical Research Council (NHMRC ID 1079102). S. Grieve acknowledges the support of the Parker Hughes bequest and the Heart Research Institute. The authors gratefully acknowledge Sicong Tu for helping create the MRI images in Figure 1, and George Paxinos for advice on localization of the brain region.

Affiliations: From the Neuroscience Research Australia, Randwick, Australia (Gatt, Burton, Schofield); the School of Psychology, University of New South Wales, Sydney, Australia (Gatt, Burton); the Brain Dynamics Centre, Westmead Institute for Medical Research, University of Sydney, Westmead, New South Wales, Australia (Routledge, Korgaonkar, Harris); the Queensland Institute of Medical Research, Brisbane, Queensland, Australia (Grasby); the Discipline of Psychiatry, School of Medicine, University of Sydney, New South Wales, Australia (Korgaonkar, Harris, Williams); the Sydney Translational Imaging Laboratory, Heart Research Institute, Charles Perkins Centre, University of Sydney, Australia, and the Department of Radiology, Royal Prince Alfred Hospital, Camperdown, Sydney, New South Wales, Australia (Grieve); the School of Medical Sciences, University of New South Wales, Sydney, Australia (Schofield); the School of Psychology, Flinders University, Bedford Park, South Australia, Australia, and Brain Clinics Australia, Unley, South Australia (Clark); the Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Stanford University, Stanford, California, United States of America (Williams); and the MIRECC VISN21, VA Palo Alto Health Care System, California, United States of America (Williams).

Competing interests: J. Gatt has previously received consultancy fees from Brain Resource Ltd unrelated to this study and is a stockholder in MAP Corp. Pte Ltd. A. Harris has consulted for Lundbeck Australia and received fees for lectures from Janssen-Cilag and Lundbeck Australia. He has been an investigator on industry-sponsored trials by Janssen-Cilag and Brain Resource Ltd. C.R. Clark holds a small quantum of stock and has received fees from Brain Resource Ltd for consultancies unrelated to this study. L. Williams has received fees for consultancies unrelated to this study and previously held stock options from Brain Resource Ltd. No other authors declare competing interests.

Contributors: J. Gatt., P. Schofield, C.R. Clark and L. Williams designed the study. J. Gatt, K. Burton, P. Schofield, C.R. Clark and L. Williams acquired the data, which J. Gatt, K. Burton, K. Routledge, K. Grasby analyzed. J. Gatt wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

DOI: 10.1503/jpn.170125

Correspondence to: J.M. Gatt, Neuroscience Research Australia, Barker St, Randwick, Sydney, NSW 2031 Australia; j.gatt@neura.edu.au