Background: Schizophrenia is a severe neuropsychiatric disorder characterized by positive, negative and disorganized symptoms along with marked disturbances in cognitive, social, and affective domains. It is associated with poor outcome and quality of life. A hallmark symptom of schizophrenia is auditory verbal hallucination (AVH), reported in about 74% of the clinical cases. Though this symptom subsides on treatment with antipsychotic medication, one out of four patients with schizophrenia continues to hear voices despite adequate treatment and are said to have drug-resistant auditory verbal hallucination. In this context, it is interesting to note that a series of recent observations have consistently demonstrated a strikingly immediate amelioration of persistent auditory verbal hallucinations in schizophrenia with transcranial Direct Current Stimulation (tDCS).  Application of tDCS for various psychiatric disorders including schizophrenia has been commented upon as an exciting area requiring further systematic exploration. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory brain stimulation technique that delivers low intensity, direct current to cortical areas facilitating or inhibiting spontaneous neuronal activity.

Need for Study: Recent studies suggest promising utility of add-on tDCS in chronic schizophrenia patients to facilitate rapid improvement of AVH that were resistant to treatment with antipsychotic treatment.  Preliminary evidence suggests potential similar benefit of add-on tDCS in acute phase as well.  While these studies offer robust support for this clinical utility of add-on tDCS in treatment of AVH, no published report has examined its possible mechanistic basis. Evaluation using the proposed neurophysiological & neuroimaging parameters relevant to the pathogenesis of AVH will facilitate a comprehensive and integrative understanding of the neurobiological basis of the effect of add-on tDCS. Assessing antipsychotic-naïve / antipsychotic-free patients will facilitate optimal evaluation of the proposed parameters with minimal confounds of long term antipsychotic treatment. Moreover, systematic examination of early course patients can potentially help in expanding the clinical application of this safe & relatively inexpensive therapeutic tool for effective treatment of schizophrenia.

Apart from schizophrenia patients, 25 healthy controls would also be recruited as non-interventional group for establishing baseline comparison.

OBJECTIVES & HYPOTHESES

The aim of the study is to examine the neurobiological correlates of add-on tDCS on auditory verbal hallucinations in antipsychotic-naïve / antipsychotic-free schizophrenia patients using a randomized double-blind parallel arm tDCS protocol. 

OBJECTIVES

Primary Objectives

      To investigate the effect of add-on tDCS on neurophysiological, neuroimaging, cognitive and clinical correlates of auditory verbal hallucinations among patients with schizophrenia.

      To investigate the comparative profile of auditory processing efficiency (as measured by P300, N100 and N200) as well as fronto-temporo-parietal network connectivity (as measured by resting state fMRI) between antipsychotic-naïve / free schizophrenia patients and matched healthy controls.

Secondary Objective

      To investigate the effect of add-on tDCS on executive function & processing speed in schizophrenia patients with clinically significant auditory verbal hallucinations.

HYPOTHESES

Primary Hypotheses

      In patients with add-on “true” tDCS, the magnitude of reduction in severity of auditory verbal hallucination will have significant positive correlation with improvement in auditory processing efficiency (as measured by P300 & N1 related parameters) as well as increased functional connectivity of fronto-temporo-parietal network (as measured by resting fMRI); such changes will not be seen in schizophrenia patients that receive add-on “sham” tDCS.

      Antipsychotic-naïve / free schizophrenia patients with severe AVH will show significant deficits in auditory processing efficiency (as measured by P300, N100 and N200) as well as fronto-temporo-parietal network connectivity (as measured by resting state fMRI) in comparison with matched healthy controls.

Secondary Hypothesis

      In patients, there will be a significant improvement in executive function & processing speed in schizophrenia patients that receive ’true’ tDCS in comparison to those that receive sham ’tDCS’.