Cholinergic connectivity: it's implications for psychiatric disorders

Abstract

Acetylcholine has been implicated in both the pathophysiology and treatment of a number of psychiatric disorders, with most of the data related to its role and therapeutic potential focusing on schizophrenia. However, there is little thought given to the consequences of the documented changes in the cholinergic system and how they may affect the functioning of the brain. This review looks at the cholinergic system and its interactions with the intrinsic neurotransmitters glutamate and gamma-amino butyric acid as well as those with the projection neurotransmitters most implicated in the pathophysiologies of psychiatric disorders; dopamine and serotonin. In addition, with the recent focus on the role of factors normally associated with inflammation in the pathophysiologies of psychiatric disorders, links between the cholinergic system and these factors will also be examined. These interfaces are put into context, primarily for schizophrenia, by looking at the changes in each of these systems in the disorder and exploring, theoretically, whether the changes are interconnected with those seen in the cholinergic system. Thus, this review will provide a comprehensive overview of the connectivity between the cholinergic system and some of the major areas of research into the pathophysiologies of psychiatric disorders, resulting in a critical appraisal of the potential outcomes of a dysregulated central cholinergic system.

Association Between Serum Anticholinergic Activity and Psychiatric Symptoms of Chronic Schizophrenia

“…Interactions between cholinergic and dopaminergic systems are critical for the regulation of motor control. An imbalance between striatal cholinergic muscarinic and dopaminergic functioning due to antipsychotic agents results in hypoactivity of the dopaminergic system and hyperactivity of the cholinergic system, and may contribute to extrapyramidal motor symptoms 30 .…”

Muscarinic M1 receptor modulation of synaptic plasticity in nucleus accumbens of wild-type and fragile X mice

“…Acetylcholine is a major neurotransmitter and modulator in the CNS, acting via ionotropic nicotinic and metabotropic muscarinic receptors it is involved in a plethora of cognitive and executive functions 1 .…”

Mapping the pathophysiology of schizophrenia: interactions between multiple cellular pathways

“…They also discuss evidence on altered NMDA receptor subunits in schizophrenia and how these alterations interact with multiple schizophrenia susceptibility genes that lead to NMDA receptor dysfunction during development (Snyder and Gao, 2013). Scarr et al (2013) present an in depth and very detailed coverage of cholinergic involvement in schizophrenia and how it interacts with other neurotransmitters including glutamate, dopamine, GABA and serotonin, as well as its links with the inflammatory/immune system. The review also provides a frame work for testable hypotheses of the potential outcomes of a dysregulated cholinergic system for research into the pathophysiologies of psychiatric disorders .…”