Iselin Meluken, MD; Ninja Ottesen, MD; Catherine Harmer, PhD, MA; Julian Macoveanu, MSc, PhD; Hartwig Siebner, MD, DMSc; Lars Kessing, MD, DMSc; Maj Vinberg, MD, DMSc, PhD; Kamilla Miskowiak, DPhil, DMSc
Background: Aberrant neural and cognitive response to emotional faces has been observed in people at familial risk of an affective disorder. In this functional MRI (fMRI) study of monozygotic twins, we explored neural correlates of the attentional avoidance of emotional faces that we had previously observed in high-risk versus affected twins, and whether an abnormal neural response to emotional faces represents a risk endophenotype.
Methods: We recruited unaffected monozygotic twins with a co-twin history of mood episodes (highrisk), monozygotic twins with previous mood episodes (affected) and monozygotic twins with no personal or first-degree history of mood episodes (low-risk) between December 2014 and January 2017 based on a nationwide register linkage. Participants viewed fearful and happy faces while performing a gender discrimination task during fMRI and performed emotional faces dot-probe and facial expression recognition tasks outside the scanner.
Results: A total of 129 monozygotic twins underwent whole-brain fMRI. High-risk twins (n = 38) displayed greater medial and superior prefrontal response to emotional faces than affected twins (n = 62). This greater activity correlated with stronger attentional avoidance of emotional faces in high-risk twins. In contrast, high-risk and affected twins showed no aberrant neural activity to emotional faces compared with low-risk twins (n = 29).
Limitations: A limitation of this study was its cross-sectional design.
Conclusion: Greater recruitment of the medial and superior prefrontal cortex during implicit emotion processing in high-risk versus affected twins may represent a compensatory or resilience mechanism. In contrast, aberrant neural response to emotional faces does not seem to be a risk endophenotype for affective disorders.
Submitted Dec. 22, 2017; Revised May 24, 2018; Revised Nov. 20, 2018; Accepted Nov. 24, 2018; Published online Apr. 3, 2019
Affiliations: From the Copenhagen Affective Disorder Research Centre (CADIC), Psychiatric Centre Copenhagen, University Hospital of Copenhagen, Rigshospitalet, and University of Copenhagen, Denmark (Meluken, Ottesen, Macoveanu, Kessing, Vinberg, Miskowiak); the Department of Psychology, University of Copenhagen, Copenhagen, Denmark (Miskowiak); the Department of Psychiatry, University of Oxford, Oxford, United Kingdom (Harmer); the Danish Research Centre of Magnetic Resonance, Copenhagen University Hospital Hvidovre, Denmark (Meluken, Siebner, Miskowiak); and the Department of Neurology, Copenhagen University Hospital, Bispebjerg, University of Copenhagen, Denmark (Siebner).
Funding: I. Meluken’s PhD salary was funded by the Lundbeck Foundation (grant number R108-A10015), and the Hørslev Foundation is acknowledged for their financial contribution to running costs. The Lundbeck Foundation and Weimann Foundation are acknowledged for their contributions to K. Miskowiak’s salary to increase her time for research between 2012 and 2021.
Competing interests: C. Harmer has received consultancy fees from P1vital Ltd, Lundbeck, Servier and Eli-Lilly, and is a company director of Oxford Psychologists Ltd. She has also received grant income from GSK, UCB, Janssen Inc, Lundbeck, Servier and AstraZeneca. H. Siebner discloses honoraria as journal editor from Elsevier Publishers and book editor from Springer Publishing, as well as honoraria as speaker from Genzyme and MerckSerono, and grant support from Biogen-idec within the last 3 years. M. Vinberg discloses consultancy fees from Lundbeck within the last 3 years. L. Kessing has been a consultant for Sunovion within the last 3 years. K. Miskowiak reports having received consultancy fees from Lundbeck and Allergan in the past 3 years. No other competing interests declared.
Contributors: I. Meluken, N. Ottesen, L. Kessing, M. Vinberg and K. Miskowiak designed the study. I. Meluken, N. Ottesen, J. Macoveanu, H. Siebner, M. Vinberg and K. Miskowiak acquired the data, which I. Meluken, C. Harmer, J. Macoveanu, H. Siebner, L. Kessing, M. Vinberg and K. Miskowiak analyzed. I. Meluken, M. Vinberg and K. Miskowiak wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Correspondence to: K.W. Miskowiak, Psychiatric Centre Copenhagen, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark; email@example.com