Demonstrating the Role of Anticholinergic Activity in a Mood Disorder

Abstract

We report a case of a 54-year-old woman presenting with amnesia, apathy, work-related difficulties and mental stress. At presentation, her Mini-Mental State Examination score was 27 and her serum anticholinergic activity (SAA) was positive without medication or recent physical illnesses. In addition, magnetic resonance imaging revealed mild atrophy of the frontal and temporal lobes, with a relatively intact hippocampus. Consequently, we diagnosed mild cognitive impairment due to Alzheimer's disease and prescribed a cholinesterase inhibitor (donepezil, 10 mg/day); her SAA fully disappeared and clinical symptoms partially resolved. Addition of duloxetine coupled with environmental adjustments caused her cognitive function to return to a normal level, so we diagnosed pseudodementia due to depression. In this case, we believe that the simultaneous cholinergic burden and mental stress led to positive SAA, which made it reasonable to prescribe a cholinesterase inhibitor to ameliorate the associated acetylcholine hypoactivity. We believe that it is essential to recognize the importance of prescribing a cholinesterase inhibitor for specific patients, even those with pseudodementia, to control their clinical symptoms. Moreover, SAA might be a useful biomarker for identifying this subgroup of patients. We propose that anticholinergic activity appears endogenously in mood disorders (depression and bipolar disorder) and set out our rationalization for this hypothesis.

Plasma sphingolipids and depressive symptoms in coronary artery disease

“…Some antidepressants, including many SSRIs and tricyclic antidepressants (TCAs), have been shown to inhibit acidic sphingomyelinase (aSMase), an enzyme responsible for catalyzing the breakdown of sphingomyelin to ceramide and phosphorylcholine, resulting in decreased ceramide concentrations (Kornhuber et al, 2010). Use of antipsychotics was also an exclusion criterion due to their effects on mood and cognitive outcomes, as well as their potential effects on sphingolipid concentrations (Alexander, Gallagher, Mascola, Moloney, & Stafford, 2011;Hori et al, 2015;Kornhuber, Tripal, Gulbins, & Muehlbacher, 2013;Kornhuber et al, 2008). Patients diagnosed with any dementia, Parkinson's disease, Huntington's chorea, an autoimmune disease (e.g., multiple sclerosis, rheumatoid arthritis, Crohn's disease), active cancer, impaired liver or kidney function, or history of cerebrovascular accident (CVA), transient ischemic attack (TIA), brain tumor, subdural hematoma, epilepsy, or any other conditions likely to significantly impact mood or cognition were excluded from this study.…”

Role of Cholinergic System in Neuropsychiatric Disorders

“…However, at the pathological state (depressive state), more upregulation of ACh is not impossible because the ChAT activity is already upregulate. Therefore, in depression there might be a possibility of endogenous appearance of AA [14]. In delirium, we also speculate there might be a possibility of the appearance of AA in delirium.…”

Kappa Opioid Receptor Agonist Administration in Olfactory Bulbectomized Mice Restores Cognitive Impairment through Cholinergic Neuron Activation

“…Consistent with our previous results, the present study confirmed that OBX mice exhibit long-term memory-related behavioral impairments in the passive avoidance test, 14 d after the surgery. 13,23) We demonstrated that the administration of Dyn A or trans-(−)-U-50488 improved the cognitive deficits of OBX mice, and this effect was significantly inhibited by pre-administration of the κ-opioid receptor antagonist nor-BNI. These results are consistent with the findings of a previous study that used a rat model of memory deficits, induced by the muscarinic acetylcholine receptor antagonist scopolamine.…”

“…Step-Through Passive Avoidance Task The passive avoidance test was performed as previously described. 13,23) In the training trial, before the OBX surgery, each mouse was placed in the illuminated compartment and the latency to enter the dark compartment was recorded. As soon as the mouse had completely moved from the lighted compartment into the dark compartment, an electric foot-shock (1 mA for 500 ms) was delivered through the floor grids.…”