Beyond DSM Criteria: Neurobiological and Treatment Implications of Clinically-Identifiable Phenotypes of Late-Life Depression

Abstract

The diagnosis of Major Depressive Disorder in older adults follows the same DSM5 criteria as is used in younger populations. However, this conceptualization limits us to clinical phenomenology as seen in younger populations. It is informed neither by contributory and comorbid aging processes nor by modern behavioral concepts with a specific underlying neurobiology. Such processes vary across the population of older depressed adults yet can influence short- and long-term clinical outcomes and may have prognostic value. Examples of aging processes include changes in cognitive performance but also extend to motor function, sensory deprivation, and fatigue. Behavioral markers with distinct neurobiological profiles include alterations in reward processes such as the development of apathy, as well as comorbid rumination, anxiety, worry and sleep disturbances.This symposium will discuss how aging processes and deeper assessments of behavioral symptom markers may present in and contribute to negative outcomes for patients with late-life depression (LLD). Dr. Bret Rutherford will discuss the role of motor and gait slowing in older adults. He will discuss how this common finding may influence the development of and presentation of LLD. He will also present a scientific model of how this may reflect underlying dysfunction of dopamine neurotransmitter systems. Dr. Sarah Szymkowicz will discuss work examining profiles of cognitive performance in patients will LLD. She will present data on how different cognitive performance profiles are related to demographic differences, clinical presentation, and how they may be related to acute treatment outcomes. Dr. Lauren Oberlin will then discuss the occurrence of apathy in LLD. She will review the clinical implications of apathy in this population and then present data from a neuroimaging study detailing the discrete functional imaging findings associated with this behavioral marker. Finally, Dr. Warren Taylor will present data from a recently completed pharmacoimaging study that includes clinical deep symptom phenotyping of patients with LLD, including apathy, rumination, and fatigue. He will discuss how different behavioral measures are associated with demographic differences yet also are related to differences in cognitive performance and functional disability. He will also present how these symptoms change during treatment with a selective serotonin reuptake inhibitor and how they may influence the overall antidepressant effect. The session will conclude with an open discussion involving the audience about how to integrate these findings and how they can inform clinical practice.This symposium will highlight the scientific need to do what many clinicians are already doing – conceptualizing LLD beyond traditional depressive symptoms. New approaches that embrace clinical heterogeneity with a broader conceptualization of the presentation of LLD have the potential to provide better prognostic information and identify new targets for pharmacological and non-pharmacological interventions.