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Am J Geriatr Psychiatry. 2019 Oct;27(10):1046-1056. doi: 10.1016/j.jagp.2019.04.009. Epub 2019 Apr 29.

Neurodegenerative Disease Caregivers' 5-HTTLPR Genotype Moderates the Effect of Patients' Empathic Accuracy Deficits on Caregivers' Well-Being.

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Department of Psychology (JLW, CLB, AYH, PDS, K-HC, RWL), University of California, Berkeley, CA.
Department of Neurology (DRD, GC), University of California, Los Angeles.
Department of Psychology (CMH), Northwestern University, Evanston, IL.
Department of Psychology (JLW, CLB, AYH, PDS, K-HC, RWL), University of California, Berkeley, CA. Electronic address:



To test the hypothesis that a functional polymorphism of the serotonin transporter gene (serotonin-transporter-linked polymorphic region [5-HTTLPR]), which is thought to be associated with differential environmental sensitivity, moderates the association between low levels of empathic accuracy (i.e., ability to recognize emotions in others) in patients with neurodegenerative disease and caregivers' well-being.


Participants were 54 patients with neurodegenerative disease and their caregivers. Patients' empathic accuracy was measured using a dynamic tracking task in which they continuously rated the emotions of a character in a film; accuracy was determined by comparing patient ratings with those made by an expert panel. Caregivers provided a saliva sample for genotyping. Caregivers' well-being was measured as a latent construct indicated by validated measures of depression, anxiety, and negative affect.


Lower levels of patients' empathic accuracy were associated with lower levels of caregivers' well-being. Importantly, caregivers' 5-HTTLPR genotype moderated this association such that lower empathic accuracy in patients predicted lower well-being for caregivers with the short/short genotype (standardized β = 0.66), but not for caregivers with the short/long (standardized β = 0.05) or long/long genotypes (standardized β = -0.21).


Consistent with previous findings that the short/short variant of 5-HTTLPR is associated with greater sensitivity to environmental influences, caregivers with the short/short variant manifest lower well-being when caring for a patient with low levels of empathic accuracy than caregivers with the other variants. This finding contributes to the authors' understanding of biological factors associated with individual differences in caregiver vulnerability and resilience.


5-HTTLPR; Caregiver; anxiety; depression; empathic accuracy; gene-environment interaction

[Available on 2019-10-01]

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