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

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.

Fig. 1

The card gambling task. Figure adapted with permission from Macoveanu and colleagues. (A) All trials had 3 phases: information, choice and outcome. During the information phase, participants were informed about the sum of money they had accumulated and the bet size (3, 4 or 5 Danish kroner [DKK]), which could be lost. In the choice phase, 2 sets of cards were presented together with the associated monetary reward. Participants chose the set of cards in which they believed the ace of hearts would be hidden. In the outcome phase, the ace of hearts was revealed, providing the participants with feedback on whether they chose the right set and whether they won the associated reward or lost the bet. (B) The 6 possible choices with associated winning amounts in DKK. (C) Risk choice behaviour during the gambling task. The panel shows the distribution of the 6 risk choices across the high-risk twins and low-risk twins. Choices are paired according to the 3 trial types, with the dark shade representing choices with winning odds less than 50% and the light shade representing choices with winning odds greater than 50%.

Fig. 2

Correlation analyses. (A) Regions showing a positive linear association between risk-related increase in neural activity during the choice phase and individual neuroticism scores. (B) Regions showing a negative linear association between risk-related increase in neural activity during the choice phase and the individual risk taking ratio. A low risk-taking ratio indicates risk-averse choices, whereas a high risk taking ratio indicates risky choices during gambling. The colour bar indicates t scores; extent threshold p < 0.005, uncorrected.

Fig. 3

Group differences in brain response during the choice phase. The blue clusters comprise contiguous voxels where high-risk twins displayed an attenuated increase in choice-related activity with higher gambling risk relative to low-risk twins. Reduced risk-related activity was located in the middle part of the insula extending into the superior temporal cortex. The green clusters are regions in the insula showing an interaction effect between familial risk and zygosity. There was a reduced influence of risk on choice-related activity in dizygotic high-risk twins as opposed to dizygotic low-risk twins, but no such difference was present in the monozygotic group. The red clusters show a risk-related increase in the insula’s response during the choice phase across all participants. For all clusters, we applied an extent threshold of p < 0.005, uncorrected.