tDCS, Stress and Risk for Schizophrenia

Overview

An exacerbated response to stress mediated by activation of the Hypothalamo-Pituitary-Adrenocortical (HPA) axis is thought to play an important role in the onset, worsening and relapse of schizophrenia. Subjects at risk for schizophrenia (unaffected siblings of patients) displayed an intermediate hyperreactivity to stress as compared with patients and healthy controls. Symptoms of schizophrenia can be reduced with noninvasive brain stimulation (NIBS) applied over the dorsolateral prefrontal cortex (DLPFC). Importantly, this same DLPFC NIBS protocol can modulate decision making processes and modulate biological reactivity to stress by decreasing salivary cortisol concentration in acute stress condition.

The objective of this project is to evaluate how the modulation of DLPFC activity in acute stress condition influences decision-making in unaffected siblings of patients with schizophrenia. Methods: 30 unaffected siblings of patients with schizophrenia will be enrolled and randomized into 2 groups. 15 subjects will receive active tDCS (2mA, 30 min, anode left DLPFC, cathode right DLPFC) and 15 will receive sham tDCS. tDCS procedure: There is a total of 30 minutes of stimulation at the intensity of 2mA (ramp up and ramp down: 30 sec). Sham stimulation consists in delivering 1 minute of real stimulation. The stimulation site (DLPFC) will be anatomically determined according to 10/20 EEG system (F3 \& F4). This procedure is in accordance with international guidelines for safety. Safety and blinding will be assessed using specific tools at the end of the protocol. Stress paradigm: In order to induce moderate stress in humans in laboratory condition, the investigators will use the Maastricht Acute Stress Test (MAST). This test is a combination between physical (hand immersion in cold water) and cognitive (arithmetic calculation) stress. Test will start 5 minutes after the beginning of stimulation session. Decision-making paradigm: The decision-making task will be performed before and after the MAST (during the stimulation) in order to compare changes induce by stress and/or stimulation. The choose test is the Delay Discounting Task (DDT) permitting a measure of decision-making, reward seeking and impulsivity. Stress measure: Saliva samples will be collected using a Salivette®, samples will be stored frozen (- 20°C). Saliva cortisol levels will be measured by ELISA. The investigators also will measure heart rate, systolic and diastolic blood pressures at each time of saliva extraction (each 15 minutes, 1st sample at 9:00 am, please see figure 1). Anxiety will be assessed using the State-Trait Anxiety Inventory (STAI) before and after stimulation