Anticholinergic Activity and Schizophrenia

Abstract

In this article, we review the downregulation of acetylcholinergic activity in schizophrenia and discuss the similarity and difference between Alzheimer's disease (AD) and schizophrenia in terms of acetylcholine (ACh) and anticholinergic activity (AA); then, we propose the use of cognition-enhancing therapy for schizophrenia. As ACh regulates an inflammatory system, when the cholinergic system is downregulated to a critical level, the inflammatory system is activated. We consider the possibility that AA appears endogenously in AD and accelerates AD pathology. This hypothesis can also be applied to schizophrenia. In fact, even before the onset of the disorder, in the prodromal phase of schizophrenia, cognitive dysfunction exists, and antibodies against astrocyte muscarinic-1 and muscarinic-2 receptors are present in the serum of patients with the paranoid type of schizophrenia. Then we noted that the prodromal phase in schizophrenia might correspond to the mild stage in AD and the acute phase to moderate stage concerning AA. We also think that we should enhance cognition in schizophrenia even in the prodromal phase because as mentioned above, downregulation of ACh is prominent in schizophrenia even in the prodromal phase.

Cognitive burden of anticholinergic medications in psychotic disorders

“…Antipsychotic medication use or dose does not appear related to decreased muscarinic receptor density (Crook et al, 2001, 2000, 1999; Dean et al, 2002; Deng and Huang, 2005; Gibbons et al, 2013, 2009; Zavitsanou et al, 2004). Given the already decreased central cholinergic activity through fewer muscarinic receptors in schizophrenia patients, even a small amount of anticholinergic load may cause a significant adverse impact on cognition due to M1 receptor saturation, which may in turn make them more vulnerable to cognitive impairing effects of anticholinergic medication burden compared to those with mood-related psychotic disorders or healthy controls who have greater M1 availability (Tani et al, 2015). …”

Reduced Short-Latency Afferent Inhibition in Prefrontal but not Motor Cortex and Its Association With Executive Function in Schizophrenia: A Combined TMS-EEG Study

“…[37][38][39][40] Recent evidence suggests that patients with schizophrenia show reductions in cholinergic receptor signaling such as in the α7 nicotinic receptor 41 and cholinergic muscarinic 1 and muscarinic 4 receptors in the cortex. [42][43][44] Furthermore, it is known that GABA A ergic dysfunction is also strongly implicated in the pathophysiology of schizophrenia [37][38][39][40] and indeed GABA A receptor mediated inhibition is partially associated with the mechanism of SAI. [10][11][12][13] Therefore, our finding of a selective impairment of SAI in the DLPFC in patients with schizophrenia may also be related to the pathophysiology of GABA A ergic function that has been demonstrated in previous studies.…”

TMS-EEG Research to Elucidate the Pathophysiological Neural Bases in Patients with Schizophrenia: A Systematic Review

“…In addition, the decrease in SAI in the DLPFC of SCZ reported by Noda et al indicates that the cholinergic function of the region may be reduced in SCZ [ 41 ], supporting the cholinergic hypothesis [ 76 ]. However, in the TMS-EEG experiments of Noda et al at that time, noise masking methods such as white noise were not used to suppress the auditory evoked potential (AEP) to TMS clicks.…”