TY - JOUR

T1 - Reward Processing as an Indicator of Vulnerability or Compensatory Resilience in Psychoses? Results From a Twin Study

AU - Nielsen, Mette Ødegaard

AU - Rostrup, Egill

AU - Hilker, Rikke

AU - Legind, Christian

AU - Anhøj, Simon

AU - Robbins, Trevor William

AU - Sahakian, Barbara J.

AU - Fagerlund, Birgitte

AU - Glenthøj, Birte

N1 - Publisher Copyright: © 2022 The Authors

PY - 2023

Y1 - 2023

N2 - Background: Findings of reward disturbances in unaffected relatives of patients with schizophrenia suggest reward disturbances as an endophenotype for schizophrenia. Twin studies, where 1 twin has been diagnosed with a schizophrenia spectrum disorder, can further explore this. Methods: We used Danish registries to identify twin pairs with at least 1 twin having a schizophrenia spectrum disorder diagnosis and control twin pairs matched on age, sex, and zygosity. The analyses included data from 34 unaffected co-twins (16 females), 42 probands with schizophrenia spectrum disorder (17 females), and 83 control twins (42 females). Participants performed a modified incentive delay task during functional magnetic resonance imaging. Whole-brain group differences were analyzed by performing comparisons between co-twins and control twins. Correlations with cognitive flexibility were tested. Results: Compared with control twins, co-twins showed no differences in striatal regions, but increased signal in the dorsolateral prefrontal cortex (DLPFC) during missed target contrast was observed. In co-twins, increased DLPFC signal was associated with lower intra-extra dimensional set-shifting scores indicative of higher cognitive flexibility. Conclusions: Unaffected co-twins did not have decreased striatal activity during anticipation as previously reported for patients with schizophrenia. Instead, they showed increased activity in the DLPFC during evaluation of missed target contrast, which correlated with their level of cognitive flexibility. Unaffected co-twins had no diagnosis at a mean age of 40 years. This could indicate that greater cognitive flexibility and increased activity in the right DLPFC during processing of unexpected negative outcome represents a compensatory resilience mechanism in predisposed twins.

AB - Background: Findings of reward disturbances in unaffected relatives of patients with schizophrenia suggest reward disturbances as an endophenotype for schizophrenia. Twin studies, where 1 twin has been diagnosed with a schizophrenia spectrum disorder, can further explore this. Methods: We used Danish registries to identify twin pairs with at least 1 twin having a schizophrenia spectrum disorder diagnosis and control twin pairs matched on age, sex, and zygosity. The analyses included data from 34 unaffected co-twins (16 females), 42 probands with schizophrenia spectrum disorder (17 females), and 83 control twins (42 females). Participants performed a modified incentive delay task during functional magnetic resonance imaging. Whole-brain group differences were analyzed by performing comparisons between co-twins and control twins. Correlations with cognitive flexibility were tested. Results: Compared with control twins, co-twins showed no differences in striatal regions, but increased signal in the dorsolateral prefrontal cortex (DLPFC) during missed target contrast was observed. In co-twins, increased DLPFC signal was associated with lower intra-extra dimensional set-shifting scores indicative of higher cognitive flexibility. Conclusions: Unaffected co-twins did not have decreased striatal activity during anticipation as previously reported for patients with schizophrenia. Instead, they showed increased activity in the DLPFC during evaluation of missed target contrast, which correlated with their level of cognitive flexibility. Unaffected co-twins had no diagnosis at a mean age of 40 years. This could indicate that greater cognitive flexibility and increased activity in the right DLPFC during processing of unexpected negative outcome represents a compensatory resilience mechanism in predisposed twins.

KW - Functional magnetic resonance imaging

KW - Prediction error

KW - Reward

KW - Schizophrenia

KW - Twins

KW - Vulnerability indicator

U2 - 10.1016/j.bpsgos.2022.01.002

DO - 10.1016/j.bpsgos.2022.01.002

M3 - Journal article

C2 - 36712565

AN - SCOPUS:85148563094

VL - 3

SP - 47

EP - 55

JO - Biological Psychiatry Global Open Science

JF - Biological Psychiatry Global Open Science

SN - 2667-1743

IS - 1

ER -