Translational assessment of butyrylcholinesterase activity as a diagnostic biomarker for depression using a chemiluminescent probe

Depressive episode is a globally prevalent psychiatric condition with a complex, multifactorial etiology involving genetic and environmental factors and despite advances in biomarker research, clinical applications remain limited due to methodological inconsistencies and population variability. Butyrylcholinesterase (BChE), an enzyme involved in cholinergic transmission, has been less studied in the context of depression compared to acetylcholinesterase. Utilizing a BChE-responsive chemiluminescent probe (BCC), BChE activity was measured in a translational approach: human serum, rat plasma, and a cell culture model. First, BChE activity was assessed in patients with depression (32 unipolar depression (UD), 21 bipolar disorder with depressive episode (BD-D)) compared to controls, then changes with respect to remission were reassessed (n = 15). Second, a chronic unpredictable mild stress (CUMS) model in rats was used to assess BChE activity in response to fluoxetine treatment. Lastly, BChE activity in response to corticosterone, norepinephrine and fluoxetine was measured in a cell culture model. Results demonstrated significantly lower BChE activity in UD and BD-D patients compared to healthy controls, with restoration following remission. In rats, BChE activity correlated with stress-induced anhedonia, and fluoxetine increased BChE levels although not reaching significance. In vitro, corticosterone exposure reduced BChE activity while fluoxetine reversed this effect and norepinephrine increased BChE activity in solely exposure and subsequent fluoxetine. These findings suggest that BChE activity may serve as a diagnostic biomarker for depression and a potential indicator of treatment response.