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

Abstract

IntroductionHeritable genetic traits and environmental components both contribute to the etiology of affective disorders. While the specific contribution of these 2 factors to disorder onset remains elusive, family and twin studies have consistently identified a family history of affective disorders as a major risk factor.1 First-degree relatives of patients with depression have a 2-fold to 4-fold increased risk for depression than individuals with no psychiatric history in first-degree relatives.2 Yet the specific neurobiological correlates mediating this vulnerability to affective disorders, which are transmitted in affected families, remain to be identified.Recent studies in high-risk individuals have revealed that healthy individuals at familial risk for affective disorders show a range of neurobiological abnormalities. Two studies from our group showed lower serotonin (5-HT) transporter binding in the prefrontal cortex 3 and decreased hippocampal volume. 4 We recently observed altered neural response in the hippocampus and orbitofrontal cortex to monetary gains and losses in healthy first-degree relatives of patients with depression.5 Accordingly, other groups have shown altered frontal and subcortical reward-related neural processes in healthy individuals at familial risk for affective disorders. [6][7][8] Prospective longitudinal studies may provide valuable insights into the association between risk factors and disorder onset. By following healthy high-risk individuals for 7 years before the onset of any affective disorder, we were able to show that discrete subclinical symptoms predict subsequent disorder onset. 9 The personality trait neuroticism, which refers to emotional instability, vulnerability to stress and anxiety disorders, 10 was also found to predict subsequent disorder 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 e...

Altered response to risky decisions and reward in patients with obsessive–compulsive disorder

“…In the present study, we found a significant effect of risk level during the decision phase upon activity in the anterior insula: higher-risk choice led to increased activity. It has been frequently suggested that the anterior insula is relevant for higherlevel processing 42 and risk level, 43 as a consequence of its involvement in learning the negative value of loss-prediction cues. 44,45 Activation of the posterior insula has also been associated with lower risk levels, suggesting that different divisions of the insula play opposing roles during risk processing.…”

Reduced frontostriatal response to expected value and reward prediction error in remitted monozygotic twins with mood disorders and their unaffected high-risk co-twins

“…Converging neurobiological and behavioral evidence has attributed these symptoms to deficits in discrete reward-related processes, including reduction of attentional bias toward positive stimuli (Joormann & Gotlib, 2007), of positive affect in response to pleasant stimuli (Berenbaum & Oltmanns, 1992), and of reward responsiveness (Pizzagalli, Iosifescu, Hallett, Ratner, & Fava, 2008). The available neuroimaging data have revealed numerous functional and structural changes in the neural system subserving these processes in both patients with UD and BD (Bracht, Linden, & Keedwell, 2015;Diener et al, 2012;Hamilton, Chen, & Gotlib, 2013;Houenou et al, 2011;Wise et al, 2017) and never-depressed first-degree relatives (Macoveanu et al, 2014(Macoveanu et al, , 2016a(Macoveanu et al, , 2016b(Macoveanu et al, , 2018Olino et al, 2014;Singh et al, 2014). However, it remains unclear how distinct components of reward processing are affected in UD and BD and whether or not some of these changes are also present in unaffected relatives who are at increased risk for mood disorders (Oquendo et al, 2013).…”

Effects of recombinant human erythropoietin on cognition and neural activity in remitted patients with mood disorders and first-degree relatives of patients with psychiatric disorders: a study protocol for a randomized controlled trial

“…In particular, two randomized placebo-controlled trials from our group revealed that eight weekly EPO infusions improved several cognitive domains in patients with BD and TRD [ 39 , 40 ]. This was accompanied by increased activity in dlPFC and dorsomedial PFC (dmPFC) during working memory and episodic encoding tasks [ 44 , 45 ]. Notably, a single dose of EPO enhances cognition-related dlPFC and dmPFC activity without producing any change in red blood cells [ 46 , 47 ].…”