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.

Nicotine Smoking Prevents the Effects of Frontotemporal Transcranial Direct Current Stimulation (tDCS) in Hallucinating Patients With Schizophrenia

“…This effect cannot be explained by age, medication and illness duration. Studies on motor cortex excitability have reported that smoking may enhance the physiological effect of a single session of tDCS over motor cortex [8], we report here that smoking prevents the effect of repeated sessions of fronto-temporal tDCS in patients with treatment-resistant auditory hallucinations. The situation of nicotine-withdrawal during stimulation could explain the abolished neuroplasticity in the smoking group [6].…”

“…It was recently reported that smoking patients with schizophrenia did not display abnormal neural plasticity induced by excitability-diminishing cathodal tDCS as compared to non-smoking patients [8]. This effect may be associated with the duration of withdrawal and on the intensity of symptoms, especially of negative symptoms [8].Thus the effect of nicotine on tDCS-induced neural plasticity seems to be different in patients with schizophrenia as compared to healthy controls and in smokers as compared to non-smokers. Therefore, we investigated the effect of nicotine smoking on the clinical effect induced by repeated sessions of tDCS in patients with schizophrenia and treatment-resistant auditory verbal hallucinations included in an open-label study (ClinicalTrials.gov Identifier: NCT00870909).…”

“…In patients with schizophrenia, abnormal neuroplasticity has been revealed by a single session of tDCS applied over M1 [7]. It was recently reported that smoking patients with schizophrenia did not display abnormal neural plasticity induced by excitability-diminishing cathodal tDCS as compared to non-smoking patients [8]. This effect may be associated with the duration of withdrawal and on the intensity of symptoms, especially of negative symptoms [8].…”

Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model

“…It is possible that this excessive activation of the PFC may be due to an imbalance in the two common forms of plasticity in PFC, namely, long-term potentiation (LTP) and long-term depression (LTD). Indeed, recent clinical literature suggests that there are deficits in LTD in patients diagnosed with schizophrenia (Hasan et al, 2013;Strube et al, 2014). Furthermore, a common preclinical model of schizophrenia involving transient blockade of N-methyl-D-aspartate receptors (NMDARs) with repeated administration of NMDAR antagonists during a critical period of adolescent development induces profound and lasting deficits in LTD at synapses from the hippocampus to PFC (Ghoshal and Conn, 2015;Thomases et al, 2014).…”

Effects of transcranial direct current stimulation (tDCS) on cognition, symptoms, and smoking in schizophrenia: A randomized controlled study

“…Schizophrenic smokers may be more prone to the cognitive deficits associated with the disorder (Wing et al, 2011;Zhang et al, 2012) possibly because of a greater dysregulation in their neuronal nicotinic system, and the administration of cigarettes or nicotinic agonists have been used to improve some aspects of cognitive function in schizophrenia (Smith et al, 2002(Smith et al, , 2006Sacco et al, 2005). A recent study also provided evidence that smoking in SZ may partially restore neuronal long-term potentiation (LTD) neuroplasticity which is deficient in SZ (Strube et al, 2015). Studies of tDCS in non-psychotic smokers have shown that tDCS stimulation reduced cigarette craving and, in some studies, number of cigarettes smoked (Fregni et al, 2006;Boggio et al, 2009;Fraser and Rosen, 2012;Fecteau et al, 2014) but whether tDCS is effective for reducing smoking or smoking urges in smokers with SZ has not been assessed.…”