title: Smoking restores impaired LTD-like plasticity in schizophrenia: a transcranial direct current stimulation study.
abstract: Impaired neuroplastic responses following noninvasive brain stimulation have been reported repeatedly in schizophrenia patients. These findings have been associated with deficits in GABAergic, glutamatergic, and cholinergic neurotransmission. Although various neurophysiological studies have indicated a relationship between nicotine and neuroplasticity in healthy individuals, the present study is the first investigation into the impact of nicotine on LTD-like plasticity in patients with schizophrenia. Cortical excitability and cortical plasticity were explored in 30 schizophrenia patients (17 smoker, 13 nonsmoker) and 45 healthy controls (13 smoker, 32 nonsmoker) by using single-pulse transcranial magnetic stimulation (TMS) before and following cathodal transcranial direct current stimulation (tDCS) applied to the left primary motor cortex. Our analysis revealed abolished LTD-like plasticity in nonsmoking schizophrenia patients. However, these plasticity deficits were not present in smoking schizophrenia patients. In healthy controls, significant MEP reductions following cathodal tDCS were observed in nonsmoking individuals, but only trend-level reductions in smokers. In smoking schizophrenia patients, the severity of negative symptoms correlated positively with reduced neuroplasticity, whereas nonsmoking patients displayed the opposite effect. Taken together, the data of our study support the notion of an association between chronic smoking and the restitution of impaired LTD-like plasticity in schizophrenia patients. Although replication and further research are needed to better understand this relationship, our findings indicate that nicotine intake might stabilize the impaired inhibition-facilitation balance in the schizophrenic brain through a complex interaction between cortical plasticity, and GABAergic and cholinergic neurotransmission, and might explain the reduced prevalence of negative symptoms in this population.
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Strube
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Bunse
authors.affiliation: Department of Clinical Neurophysiology, University of Goettingen, Goettingen, Germany.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nitsche
authors.affiliation: 1] Centre of Mental Health, Darmstadt-Dieburg Clinics, Darmstadt, Germany [2] Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wobrock
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Aborowa
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany.
authors.forename: Kristina
authors.initials: K
authors.lastname: Misewitsch
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Goettingen, Goettingen, Germany.
authors.forename: Maximiliane
authors.initials: M
authors.lastname: Herrmann
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Falkai
authors.affiliation: Department of Psychiatry and Psychotherapy, Ludwig Maximilian University, Munich, Germany.
authors.forename: Alkomiet
authors.initials: A
authors.lastname: Hasan
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D002540:Cerebral Cortex / Q000503:physiopathology*; D016009:Chi-Square Distribution; D019054:Evoked Potentials, Motor / Q000502:physiology; D005260:Female; D006801:Humans; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D012189:Retrospective Studies; D012559:Schizophrenia / Q000150:complications* / Q000473:pathology / Q000628:therapy; D012907:Smoking / Q000503:physiopathology*; D013223:Statistics as Topic; D050781:Transcranial Magnetic Stimulation; D055815:Young Adult