Validating non-linguistic laboratory biomarkers of depression in persons with aphasia

Aphasia is a multi-modality disturbance of language that is more common than disorders such as Parkinson’s
disease and has a greater negative impact on quality of life than Alzheimer’s disease and many cancers. Persons
with Aphasia (PWAs) are thought to be at a higher risk for depression than other stroke survivors. Depression is
also thought to worsen language and cognitive performance in PWAs and decrease their quality of life. However,
identifying depression in PWAs is challenging as their language disturbances make it difficult to assess
depressive symptoms using traditional methods such as questionnaires and interviews as these methods require
PWAs to report on their inner experiences (e.g., their sadness, experience of pleasure, etc.). An alternative
approach to diagnostic interviews or questionnaires is to utilize laboratory-assessed biomarkers that require
minimal language abilities and have shown to robustly identify depression in neurologically healthy individuals.
A goal of this study is thus to assess the ability of three laboratory tests to detect depression in PWAs (N=46):
(a) heart-rate variability at rest, (b) pupil dilation, and (c) gaze duration (a measure of biased attention) to
negatively and positively valenced images. A challenge of this study is that without a gold-standard way to assess
depression in PWAs, it is difficult to truly know whether the three biomarkers are validly assessing depression in
people who have difficulty verbally reporting on their inner experiences. Aim 1 of the study will therefore apply a
novel convergent validity approach and use as its validator a composite reference standard based on multiple
indicators or proxies of depression - specifically, informant (e.g., family member, caregiver) report of PWAs (a)
depression symptoms, (b) pre-morbid history of PWAs depression (a robust predictor of future depression in
non-neurological and neurological patients), and (c) a self-report depression scale adapted for PWAs. Composite
reference standards are routinely employed to evaluate new tests when gold-standard and imperfect diagnostic
tests exist, but this approach has not been used to assess depression in PWA. Aim 2 will test whether laboratory-
assessed biomarkers predict PWAs day-to-day experiences of affect and social interaction (a critical factor for
successful rehabilitation), using experience sampling methodology (ESM). ESM is an approach that requires
brief, frequent (multiple per day), at-home assessments (in this case, from caregivers). ESM minimizes recall
bias and increases ecological validity of assessments. Lastly, aim 3 will establish the retest reliability of
laboratory-assessed biomarkers of depression by re-administering all measures to PWAs 7 days later. The
proposed project has the potential for high impact for PWAs since accurate diagnosis of depression in PWAs
can lead to better management of depression, which can positively impact linguistic and cognitive functioning
and improve PWA’s quality of life. The project will lay the foundation for a future research platform for the early-
stage PI that examines whether the laboratory-assessed biomarkers predict different depression treatment
responses and language and functional improvements related to the treatments longitudnally.

Grant Number: 1R03HD111008-01A1
NIH Institute/Center: NIH
Principal Investigator: Sameer Ashaie