Going up in Smoke? A Review of nAChRs-based Treatment Strategies for Improving Cognition in Schizophrenia

Abstract

Cognitive impairment is known to be a core deficit in schizophrenia. Existing treatments for schizophrenia have limited efficacy against cognitive impairment. The ubiquitous use of nicotine in this population is thought to reflect an attempt by patients to self-medicate certain symptoms associated with the illness. Concurrently there is evidence that nicotinic receptors that have lower affinity for nicotine are more important in cognition. Therefore, a number of medications that target nicotinic acetylcholine receptors (nAChRs) have been tested or are in development. In this article we summarize the clinical evidence of nAChRs dysfunction in schizophrenia and review clinical studies testing either nicotine or nicotinic medications for the treatment of cognitive impairment in schizophrenia. Some evidence suggests beneficial effects of nAChRs based treatments for the attentional deficits associated with schizophrenia. Standardized cognitive test batteries have failed to capture consistent improvements from drugs acting at nAChRs. However, more proximal measures of brain function, such as ERPs relevant to information processing impairments in schizophrenia, have shown some benefit. Further work is necessary to conclude that nAChRs based treatments are of clinical utility in the treatment of cognitive deficits of schizophrenia.

Multiple Kinases Involved in the Nicotinic Modulation of Gamma Oscillations in the Rat Hippocampal CA3 Area

“…Nicotine use is increased in schizophrenia patients, where it has cognitive benefits (Boggs et al, 2014). Also nicotine increases visual attention and working memory in healthy volunteers (Ernst et al, 2001).…”

Neuroimmune Interactions in Schizophrenia: Focus on Vagus Nerve Stimulation and Activation of the Alpha-7 Nicotinic Acetylcholine Receptor

“…A recent review stated that α7nAChR-agonists induce beneficial effects in patients with psychiatric disorders (139) ameliorating cognitive deficits, negative symptoms, and sensory gating disturbances in both preclinical and clinical trials of schizophrenia (139, 157–161). Advantageous effects for the negative symptoms have been reported repeatedly, while improvements in the cognitive domain remain controversial, deserving further exploration (175, 176). Together, these studies indicate that the vagus nerve and the α7nAChR may be involved in the inflammatory hypothesis of schizophrenia (Figure 1).…”

May Non-antipsychotic Drugs Improve Cognition of Schizophrenia Patients?

“…In addition to being an acetylcholinesterase inhibitor, galantamine is an allosteric acetylcholine receptor (nAChR) modulator and a number of data have shown that treatments increasing nAChr activity may improve schizophrenia cognitive symptoms [60]. Two schizophrenia patients treated with galantamine (8-10 mg/day) showed improvement in attention and speech after 12-20 days [61].…”