Major depressive disorder (MDD) is a serious public health problem with modest treatment response,
which may, in part, be due to its heterogeneous clinical presentation. One way to improve these clinical
outcomes is to investigate the role of particular features of MDD that are tied to specific pathogenic
mechanisms - work that would help identify novel and focal treatment targets. Psychomotor disturbance (e.g.,
agitation [PmA] and retardation [PmR]) is a particularly significant feature of MDD as it relates to more severe
depression and worse treatment response. However, traditional assessment approaches of psychomotor
disturbance (e.g., self- and observer-reports) are limited as they (a) miss less overt, but relevant abnormalities,
and (b) are susceptible to bias. A more promising approach is using motoric features of the voice extracted
from standardized speech tasks. These vocal motor features are promising indicators of psychomotor
disturbances in MDD as they are objective, non-intrusive, mediated by neural circuits involved in coordinated
motor control, computed automatically, and easily assessed in the “real-world” (and thus able to be used in
real-time mobile assessments and treatments).
Aim 1 of this proposal is therefore to test whether vocal indicators of PmR (speech rate) and PmA
(variability in speech rate) (a) are abnormal in MDD and (b) can be measured naturalistically by participants
talking into their smartphones “outside of the lab.” Aim 2 will test the validity of vocal motor measures as
indicators of psychomotor disturbance by evaluating their association with mechanistically relevant measures
of PmA and PmR (i.e., laboratory instrumental measures, actigraphy, EEG/ERPs). Aim 3 will follow-up
subjects two times over 12 months to evaluate whether motor symptoms (as assessed by the voice) change in
tandem with overall depressive symptoms and social and role functioning over time; and/or whether baseline
PmR/PmA predicts course of depression and functioning. Finding that motor and overall depression severity
co-vary over time, or that the motor variables predict subsequent change in overall depression severity is
particularly clinically significant as it would support the potential clinical utility of the proposed novel, reliable,
and easily administered motor assessments.
To test these aims, the proposed project will recruit individuals (age 18-45) with current MDD (n = 100),
remitted MDD (n = 100) and controls (n = 50). Including a remitted MDD group is particularly significant as it
will provide evidence that psychomotor disturbance is independent of acute depressive symptoms, and allows
us to explore whether vocal indicators of PmR and/or PmA predict relapse (in the remitted MDD group) and/or
remission (in the current MDD group). In sum, the present proposal has the potential to identify novel, easily
assessed, cheap, and scalable treatment markers of psychomotor disturbance – work that will ultimately
improve the monitoring and treatment of a devastating and prevalent psychiatric condition.
