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Acetylcholinergic Nicotinic Receptors as Pharmacological Targets for Cognitive Enhancement: Emerging Evidence from Psychosis Populations

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Abstract

Cognitive deficits have been recognised since the first conceptualisation of psychosis; indeed it was initially labelled ‘dementia praecox’, or presenile dementia, in recognition of the primacy of these problems. However, these were largely ignored – in part due to a lack of effective interventions – in the sixty or so years since the discovery of dopaminergic antagonist antipsychotic medications. In recent times there has been a renewed growth of interest in putative cognitive enhancers in this condition, with much work looking at agents that modulate the acetylcholinergic (ACh) system that is intimately linked with cognition and memory. Unlike memory sparing medications in dementia, which prevent the enzymatic degradation of synaptic ACh, in psychosis the emphasis has been on direct agonists. To date, several compounds have been tested in humans, and interesting early results support a pro-cognitive effect in some, but not all. A challenge, however, is understanding why only some appear to derive benefit, and whether any such factors can be used for predictive prescribing, so that more efficacious future agents can be developed.

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Abbreviations

ACh:

Acetylcholine

BPRS:

Brief psychiatric rating scale

CANTAB:

Cambridge neuropsychological test automated battery

CPT:

Continuous performance test

CPT-IP:

Continuous performance test – identical pairs version

DSST:

Digital symbol substitution test

GAF:

Global assessment of functioning

HRT-SD:

Hit reaction time variability

KMMSE:

Korean Mini-Mental State Examination

LOF:

Level of functioning

LTD:

Long-term depression

LTP:

Long-term potentiation

MAPK:

Mitogen-activated protein kinase

MATRICS:

Measurement and treatment research to improve cognition in schizophrenia

MCCB:

MATRICS consensus cognitive battery

nAChR:

Nicotinic acetylcholine receptor

NMDA:

N-methyl-D-aspartate

PANSS:

Positive and negative syndrome scale

PCP:

Phencyclidine

RBANS:

Repeatable battery for the assessment of neuropsychological status

RCT:

Randomised controlled trial

SANS:

Scale for the assessment of negative symptoms

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  1. Crisis, Inpatient, and Rehabilitation Services, Oxleas NHS Foundation Trust, London, UK

    Derek K. Tracy & Valentina Casetti

  2. Cognition Schizophrenia and Imaging Laboratory, Department of Psychosis Studies, The Institute of Psychiatry, King’s College, London, UK

    Derek K. Tracy, Valentina Casetti, Arann R. Rowe, Louise Mercer & Sukhwinder S. Shergill

  3. The National Psychosis Unit, South London and Maudsley NHS Foundation Trust, London, UK

    Sukhwinder S. Shergill

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    Takahiro A. Kato

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Tracy, D.K., Casetti, V., Rowe, A.R., Mercer, L., Shergill, S.S. (2016). Acetylcholinergic Nicotinic Receptors as Pharmacological Targets for Cognitive Enhancement: Emerging Evidence from Psychosis Populations. In: López-Muñoz, F., Srinivasan, V., de Berardis, D., Álamo, C., Kato, T. (eds) Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2803-5_42

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  • DOI: https://doi.org/10.1007/978-81-322-2803-5_42

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