Is negative self-referent bias an endophenotype for depression? An fMRI study of emotional self-referent words in twins at high vs. low risk of depression

J Affect Disord. 2018 Jan 15;226:267-273. doi: 10.1016/j.jad.2017.10.013. Epub 2017 Oct 3.


Background: Negative cognitive bias and aberrant neural processing of self-referent emotional words seem to be trait-marks of depression. However, it is unclear whether these neurocognitive changes are present in unaffected first-degree relatives and constitute an illness endophenotype.

Methods: Fifty-three healthy, never-depressed monozygotic or dizygotic twins with a co-twin history of depression (high-risk group: n = 26) or no first-degree family history of depression (low-risk group: n = 27) underwent neurocognitive testing and functional magnetic imaging (fMRI) as part of a follow-up cohort study. Participants performed a self-referent emotional word categorisation task and free word recall task followed by a recognition task during fMRI. Participants also completed questionnaires assessing mood, personality traits and coping strategies.

Results: High-risk and low-risk twins (age, mean ± SD: 40 ± 11) were well-balanced for demographic variables, mood, coping and neuroticism. High-risk twins showed lower accuracy during self-referent categorisation of emotional words independent of valence and more false recollections of negative words than low-risk twins during free recall. Functional MRI yielded no differences between high-risk and low-risk twins in retrieval-specific neural activity for positive or negative words or during the recognition of negative versus positive words within the hippocampus or prefrontal cortex.

Conclusions: The subtle display of negative recall bias is consistent with the hypothesis that self-referent negative memory bias is an endophenotype for depression. High-risk twins' lower categorisation accuracy adds to the evidence for valence-independent cognitive deficits in individuals at familial risk for depression.

Keywords: Cognition; Depression; Endophenotype; FMRI; Familial risk.

Publication types

  • Twin Study

MeSH terms

  • Adult
  • Brain Mapping
  • Cognition Disorders
  • Cohort Studies
  • Depressive Disorder / physiopathology*
  • Emotions / physiology*
  • Endophenotypes*
  • Female
  • Hippocampus / physiology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mental Recall
  • Prefrontal Cortex / physiology*
  • Twins, Dizygotic
  • Verbal Behavior / physiology*