Healthy co-twins of patients with affective disorders show reduced risk-related activation of the insula during a monetary gambling task

Healthy co-twins of patients with affective disorders show reduced risk-related activation of the insula during a monetary gambling task

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J Psychiatry Neurosci 2016;41(1):38-47

Julian Macoveanu, PhD; Kamilla Miskowiak, PhD; Lars Vedel Kessing, MD, DMSc; Maj Vinberg, MD, PhD;* Hartwig Roman Siebner, MD, DMSc*

Abstract

Background: Healthy first-degree relatives of patients with affective disorders are at increased risk for affective disorders and express discrete structural and functional abnormalities in the brain reward system. However, value-based decision making is not well understood in these at-risk individuals.

Methods: We investigated healthy monozygotic and dizygotic twins with or without a co-twin history of affective disorders (high-risk and low-risk groups, respectively) using functional MRI during a gambling task. We assessed group differences in activity related to gambling risk over the entire brain.

Results: We included 30 monozygotic and 37 dizygotic twins in our analysis. Neural activity in the anterior insula and ventral striatum increased linearly with the amount of gambling risk in the entire cohort. Individual neuroticism scores were positively correlated with the neural response in the ventral striatum to increasing gambling risk and negatively correlated with individual risk-taking behaviour. Compared with low-risk twins, the high-risk twins showed a bilateral reduction of risk-related activity in the middle insula extending into the temporal cortex with increasing gambling risk. Post hoc analyses revealed that this effect was strongest in dizygotic twins.

Limitations: The relatively old average age of the mono- and dizygotic twin cohort (49.2 yr) may indicate an increased resilience to affective disorders. The size of the monozygotic high-risk group was relatively small (n = 13).

Conclusion: The reduced processing of risk magnitude in the middle insula may indicate a deficient integration of exteroceptive information related to risk-related cues with interoceptive states in individuals at familial risk for affective disorders. Impaired risk processing might contribute to increased vulnerability to affective disorders.


*These authors contributed equally to this work.

Submitted Aug. 11, 2014; Revised Jan. 13, 2015; Accepted Apr. 15, 2015; Early-released Sept. 22, 2015

Acknowledgements: The study was supported by the Danish Council for Independent Research, Lundbeck Foundation and the Foundation of Einar Geert-Joergensen and wife Ellen Geert-Joergensen. J. Macoveanu is funded through a centre grant of the Lundbeck Foundation for the Center for Integrated Molecular Brain Imaging. H.R. Siebner is supported by a Grant of Excellence on the control of actions ‘‘ContAct’’ from Lundbeck Foundation (R59 A5399). The authors acknowledge the Simon Spies Foundation for their donation of the Siemens Trio Scanner.

Affiliations: From the Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital, Hvidovre, Denmark ( Macoveanu, Siebner); the Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Macoveanu); the Psychiatric Centre Copenhagen, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark (Macoveanu, Miskowiak, Kessing, Vinberg); and the Department of Neurology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark (Siebner).

Competing interests: None declared for J. Macoveanu. K. Miskowiak has received consultancy fees from Lundbeck. L.V. Kessing has within the last 3 years been a consultant for Lundbeck and AstraZeneca. M. Vinberg has been a consultant for Eli Lilly, Lundbeck, Servier and Astra Zeneca. H.R. Siebner over the past 4 years has received honoraria as a reviewing editor for NeuroImage, as a speaker for Biogen Idec Denmark A/S, and as a scientific advisor for Lundbeck A/S, Valby, Denmark.

Contributors: All authors designed the study, wrote and reviewed the article and aproved the final version for publication. K. Miskowiak and M. Vinberg acquired the data, which J. Macoveanu and H.R. Siebner analyzed.

DOI: 10.1503/jpn.140220

Correspondence to: J. Macoveanu, Danish Research Centre for Magnetic Resonance, Copenhagen University Hospital Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark; julianm@drcmr.dk