TY - JOUR AU - Witkin, Jeffrey M. AU - Golani, Lalit K. AU - Cerne, Rok AU - Rahman, Md. Toufiqur AU - Li, Guanguan AU - Poe, Michael M. AU - Cook, James M. AU - Smith, Jodi L. PY - 2019 DA - 2019/08/26 TI - Facilitation of Social Support through Negative Allosteric Modulation of α5-Associated GABA<sub>A</sub> Receptors: A Novel Mechanism for the Treatment of Depression, Agitation, and Aggression in the Elderly JO - OBM Geriatrics SP - 073 VL - 03 IS - 03 AB - Major depressive disorder is a highly-prevalent and debilitating disorder in the aged population. Accumulating clinical evidence suggests a key role for social support in helping to mitigate depression. Preclinical data are reviewed that indicate that selective negative allosteric modulation of α5-containing GABAA receptors, as with RY-080, might rapidly impact depression in patients. Further, preclinical data in transgenic mice modeling neurodegenerative diseases has suggested that this mechanism might also function to reduce agitation and aggression. These data are discussed in terms of the concept of Facilitation of Social Support (FOSS). The concept posits that the expression of depression, agitation, and aggression, alone or in concert, reduces social support and thereby weakens this social link as a positive therapeutic intervention. Drugs like RY-080 or other interventions (psychotherapy) that dampen these behaviors will facilitate social support and further help to mitigate these behaviors. Thus, FOSS is proposed as a dual-acting mechanism with one component being drug or therapy-induced suppression of symptoms or disease, and the facilitation of social support that derives from this suppression as component number two. These processes are reciprocal, self-sustaining, and should be additive or synergistic SN - 2638-1311 UR - https://doi.org/10.21926/obm.geriatr.1903073 DO - 10.21926/obm.geriatr.1903073 ID - Witkin2019 ER -