Neural subgroups in unaffected first-degree relatives of patients with bipolar disorder during emotion regulation

Hanne Lie Kjærstad*, Florien Ritsma, Klara Coello, Sharleny Stanislaus, Klaus Munkholm, Maria Faurholt-Jepsen, Julian MacOveanu, Anne Juul Bjertrup, Maj Vinberg, Lars Vedel Kessing, Kamilla Woznica Miskowiak

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

Background
Impaired emotion regulation has been proposed as a putative endophenotype in bipolar disorder (BD). Functional magnetic resonance imaging (fMRI) studies investigating this in unaffected first-degree relatives (UR) have thus far yielded incongruent findings. Hence, the current paper examines neural subgroups among UR during emotion regulation.

Methods
71 UR of patients with BD and 66 healthy controls (HC) underwent fMRI scanning while performing an emotion regulation task. Hierarchical cluster analysis was performed on extracted signal change during emotion down-regulation in pre-defined regions of interest (ROIs). Identified subgroups were compared on neural activation, demographic, clinical, and cognitive variables.

Results
Two subgroups of UR were identified: subgroup 1 (39 UR; 55%) was characterized by hypo-activity in the dorsolateral, dorsomedial, and ventrolateral prefrontal cortex and the bilateral amygdalae, but comparable activation to HC in the other ROIs; subgroup 2 (32 UR; 45%) was characterized by hyperactivity in all ROIs. Subgroup 1 had lower success in emotion regulation compared to HC and reported more childhood trauma compared to subgroup 2 and HC. Subgroup 2 reported more anxiety, lower functioning, and greater attentional vigilance toward fearful faces compared to HC. Relatives from both subgroups were poorer in recognizing positive faces compared to HC.

Conclusions
These findings may explain the discrepancy in earlier fMRI studies on emotion regulation in UR, showing two different subgroups of UR that both exhibited aberrant neural activity during emotion regulation, but in opposite directions. Furthermore, the results suggest that impaired recognition of positive facial expressions is a broad endophenotype of BD.
OriginalsprogEngelsk
Artikelnummere45
TidsskriftPsychological Medicine
Vol/bind55
Antal sider11
ISSN0033-2917
DOI
StatusUdgivet - 2025

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Publisher Copyright:
© The Author(s), 2025.

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