STIMULATING THE PREFRONTAL CORTEX TO REDUCE HYPERREACTIVITY TO STRESS IN PEOPLE AT RISK OF SCHIZOPHRENIA

Abstract Background According to the vulnerability stress model of schizophrenia, an abnormal hyperreactivity to stress is incriminated in the transition from at risk stages to full-blown psychotic episodes. Aims & Objectives We proposed that stimulating the dorsolateral prefrontal cortex (DLPFC) with transcranial direct current stimulation (tDCS) during acute stress exposure would lead to modulation of hypothalamo-pituitary-adrenal (HPA) axis responsiveness in people at risk for schizophrenia. Method In a randomized sham-controlled 2-arm study (http://clinicaltrials.gov, NCT03217357, 05/07/2017), 30 unaffected siblings of patients with schizophrenia were randomly allocated to receive either active (n=15) or sham tDCS (n=15) while exposed to an acute stress situation combining physical and psychological stress (the Maastricht Acute Stress Test). The stress exposure started 5 minutes after the start of the tDCS session and lasted 10 minutes. Active stimulation consisted of delivering 2 mA of DC current for 30 min with the anode placed over the left DLPFC and the cathode over the right DLPFC. Sham stimulation consisted of 30 s of ramp up/down and 1 min of active stimulation followed by no stimulation for the remaining 30 min of the stimulation period. Our primary outcome was the concentration of salivary cortisol. A saliva sample was taken every 10 min (every 5 min during stress exposure) for a total of 10 samples. A general linear model with group (active, sham) and time (10 saliva samples) followed by FDR corrected contrasts was performed to examine the effect of tDCS on HPA axis reactivity. Results The two groups did not differ at baseline in any sociodemographic characteristics, nor in baseline cortisol concentration (4.69 nmol/L (± 2.53) in the sham group versus 3.54 nmol/L (± SD 1.99) in the active group; W = 78.00; p = 0.25). The GLM revealed a significant association between the group and the time (X2 = 41.16; p <0.001), with the difference between groups being significant at 5 and 10 minutes after the end of the stress exposure. In the sham group, the mean increase in cortisol release was +291% from baseline, whereas the cortisol increase in the active group was +259%. Discussion & Conclusion Bifrontal tDCS can prevent stress-induced cortisol release in people at genetic risk of schizophrenia. These results are consistent with our previous studies in healthy participants and suggest that tDCS, which shows promise in treating patients with treatment-resistant symptoms of schizophrenia, may also be of interest in the early stages of the disease to reduce biological hyperreactivity to stress.