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

Macoveanu J, Miskowiak KW, Kessing LV, Siebner HR, Vinberg M

J Psychiatry Neuroscience (in press)


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

Methods: We investigated healthy monozygotic (n = 30) and dizygotic (n = 37) twins with or without a co-twin history of affective disorders (high-risk and low-risk groups, respectively) using functional MRI while performing a gambling task. We assessed group differences in activity related to gambling risk over the entire brain.

Results: Neural activity in 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 ventral striatum to increasing gambling risk and negatively correlated with individual risk-taking behavior. Compared with low-risk twins, the high-risk twins showed a bilateral reduction of risk-related activity in the middle insula extending into temporal cortex with increasing gambling risk. Post-hoc analyses revealed that this effect was strongest in dizygotic twins.

Limitations: The higher average age of the twin cohort (49.2 years) 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.