title: 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.
  
  
  CONCLUSIONS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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).
authors.forename: Julian
authors.initials: J
authors.lastname: Macoveanu
authors.affiliation: 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).
authors.forename: Kamilla
authors.initials: K
authors.lastname: Miskowiak
authors.affiliation: 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).
authors.forename: Lars V
authors.initials: LV
authors.lastname: Kessing
authors.affiliation: 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).
authors.forename: Maj
authors.initials: M
authors.lastname: Vinberg
authors.affiliation: 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).
authors.forename: Hartwig R
authors.initials: HR
authors.lastname: Siebner
mesh_terms: D001008:Anxiety Disorders / Q000503:physiopathology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology*; D002755:Choice Behavior / Q000502:physiology; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D003863:Depression / Q000503:physiopathology; D005260:Female; D005715:Gambling / Q000503:physiopathology* / Q000523:psychology*; D005717:Games, Experimental; D020022:Genetic Predisposition to Disease; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000503:physiopathology* / Q000523:psychology*; D000075384:Neuroticism; D011569:Psychiatric Status Rating Scales; D012306:Risk; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D066328:Ventral Striatum / Q000503:physiopathology; D014796:Visual Perception / Q000502:physiology