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.  Recent and 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-associated 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, based upon clinical evidence, 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 manipulations (psychotherapy) that dampen these behaviors will facilitate social support that will further help to mitigate these behaviors.   Thus, FOSS is proposed as a dual-acting mechanism for therapeutic gain 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 2.  These processes are reciprocal, self-sustaining, and should be additive or synergistic such that manipulations that directly impact social support would reduce target symptoms, an effect that would further facilitate social support.
SN  - 2638-1311
UR  - https://doi.org/10.21926/obm.geriatr.1903073
DO  - 10.21926/obm.geriatr.1903073
ID  - Witkin2019
ER  -