Effects of clonidine on MMN and P3a amplitude in schizophrenia patients on stable medication
- 23 February 2019
- journal article
- research article
- Published by Springer Science and Business Media LLC in Neuropsychopharmacology
- Vol. 44 (6), 1062-1067
- https://doi.org/10.1038/s41386-019-0351-6
Abstract
Schizophrenia is a complex brain disease involving several neurotransmitter systems, including aberrant noradrenergic activity, which might underlie cognitive deficits. Clonidine is an α2A-agonist and previous research has demonstrated that single dosages of clonidine normalize sensori(motor) gating in schizophrenia. Currently, we investigated whether clonidine is able to normalize mismatch negativity (MMN) and P3a amplitude deficits in this same group of patients. This is important, since reports have shown that MMN amplitude is associated with cognitive functioning and daily life functions in schizophrenia. Twenty chronically ill, male schizophrenia patients were tested with the MMN paradigm from the Copenhagen Psychophysiological Test Battery (CPTB) on 5 occasions, separated by a week. Patients received randomized, yet balanced, either a placebo or a single dose (25, 50, 75 or 150 μg) of clonidine (each dose only once) on top of their usual medication on each occasion. Patients were matched on age and gender with 20 healthy controls (HC) who did not receive any treatment. We found decreased MMN and P3a amplitudes in our patients compared to HC. Although clonidine did neither significantly increase MMN nor P3a amplitude in our patients, it did increase certain levels of MMN and P3a amplitude such that these were not significantly different anymore from the healthy controls. Together with our previous reports indicating normalized sensori(motor) gating in the same patients following administration of clonidine, our results could be of potential high clinical relevance in treating schizophrenia. Future studies should focus on longer trial periods to investigate if clonidine also improves cognitive functioning in schizophrenia.Funding Information
- Sundhed og Sygdom, Det Frie Forskningsråd (271-06-0308, 271-06-0308)
- Lundbeckfonden (R25-A2701, R25-A2701)
This publication has 44 references indexed in Scilit:
- Noradrenergic Modulation of Cognition in Health and DiseaseNeural Plasticity, 2017
- Differential cognitive actions of norepinephrine a2 and a1 receptor signaling in the prefrontal cortexBrain Research, 2016
- Determinants of different aspects of everyday outcome in schizophrenia: The roles of negative symptoms, cognition, and functional capacitySchizophrenia Research, 2015
- Validation of mismatch negativity and P3a for use in multi-site studies of schizophrenia: Characterization of demographic, clinical, cognitive, and functional correlates in COGS-2Schizophrenia Research, 2014
- Schizophrenia Is a Cognitive IllnessJAMA Psychiatry, 2013
- Prefrontal cortical network connections: key site of vulnerability in stress and schizophreniaInternational Journal of Developmental Neuroscience, 2011
- Catecholamine and Second Messenger Influences on Prefrontal Cortical Networks of "Representational Knowledge": A Rational Bridge between Genetics and the Symptoms of Mental IllnessCerebral Cortex, 2007
- Adrenergic targets for the treatment of cognitive deficits in schizophreniaPsychopharmacology, 2003
- The role of norepinephrine in the pathophysiology of cognitive disorders: potential applications to the treatment of cognitive dysfunction in schizophrenia and Alzheimer's diseaseBiological Psychiatry, 1999
- Clonidine improves memory function in schizophrenia independently from change in psychosis: Preliminary findingsSchizophrenia Research, 1988