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Neurocognition in individuals at high familial risk of mood disorders with or without subsequent onset of depression

  • M. Papmeyer (a1), J. E. Sussmann (a1), J. Hall (a2), J. McKirdy (a1), A. Peel (a1), A. Macdonald (a1), S. M. Lawrie (a1), H. C. Whalley (a1) and A. M. McIntosh (a1)...



Neurocognitive performance deficits have been observed in mood disorder patients and their unaffected relatives and may therefore qualify as endophenotypes. However, the precise time course of neurocognitive deficits has not been studied so that it is unknown whether neurocognitive abnormalities reflect the early effects of familial vulnerability to mood disorders or if they emerge at illness onset.


A neuropsychological test battery was administered at baseline and after a 2-year follow-up interval in 111 initially unaffected young adults at high familial risk of mood disorders and 93 healthy controls (HC). During the follow-up period, 20 high-risk subjects developed major depressive disorder (HR-MDD), with the remainder remaining well (HR-well). Linear mixed-effects models were used to investigate differences and longitudinal changes in the domains of attentional processing, working memory, verbal learning and memory, and cognitive flexibility.


Reduced long delay verbal memory and extradimensional set-shifting performance across both time points were found in the HR-well group relative to controls. The HR-MDD group displayed decreased extradimensional set-shifting abilities across both time points as compared with the HC group only. There were no significant performance differences between the two high-risk groups.


Reduced verbal memory and cognitive flexibility are familial trait markers for vulnerability to mood disorders in individuals with a close family history of bipolar disorder. Both neurocognitive performance deficits appear to be relatively stable over a 2-year time period and do not appear to be linked to the onset of MDD. These findings support their use as stable quantitative endophenotypes for mood disorders.


Corresponding author

* Address for correspondence: M. Papmeyer, Ph.D., University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK. (Email:


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