Richter-Levin G, Müller I, Tripathi K, Stork O. Active resilience in response to traumatic stress. In: Chen A, (ed). Stress Resilience: Molecular and Behavioral Aspects. San Diego: Elsevier Inc./Academic Press, 2020: 95-106. Link
The mechanisms behind individual variability which leads only some individuals to develop stress-related psychopathologies is one of the key questions in stress research today. Here we explore the contribution of one target molecule, the GABA synthetic enzyme glutamic acid decarboxylase (GAD)65, to mechanisms of vulnerability and resilience. GAD65 is critically involved in the activity-dependent regulation of GABAergic inhibition in the central nervous system. It is also required for the maturation of the GABAergic system during adolescence, a phase that is critical for the development of several neuropsychiatric diseases. Mice bearing null mutation of the GAD65 gene develop hyperexcitability of the amygdala and hippocampus, and a phenotype of increased anxiety and pathological fear memory reminiscent of post-traumatic stress disorder. However, GAD65 haplodeficiency, which results in delayed postnatal increase of GABA levels, provides resilience to juvenile-stress induced anxiety to GAD65(+/-) mice.
Results obtained so far clearly indicate that GAD65 functioning is relevant to both stress vulnerability and stress resilience. The variable results regarding stress-related alterations in the expression of GAD65, together with the differences between effects of homozygous GAD65(-/-) knockout and GAD65 haplodeficiency, suggest that the role of GAD65 in stress vulnerability and resilience may differ in different brain regions and between different developmental stages. More temporal- and spatial- specific manipulations of expression are required in order to more accurately describe the role played by this enzyme in coping with stress.
Gad65 is brought here only as an example. Similar caution is required when examining the role of other target molecules in individual difference related to stress vulnerability and stress resilience.