Transcranial Direct Current Stimulation for Hallucinations in First-Episode Schizophrenia

This study looks to investigate whether patients with recent onset psychosis may benefit from
tDCS treatment. The main hypothesis to be tested in this study is that treatment with
risperidone supplemented with tDCS will yield a decrease in auditory hallucinations and
negative symptoms; and improve working memory and attention.

To test this hypothesis the investigators will enroll 30 patients with recent-onset psychosis
into a 16-week long randomized double blind controlled study of risperidone treatment
supplemented with tDCS versus risperidone plus sham tDCS. Patients who present for treatment
of a first psychotic episode with a schizophrenia spectrum diagnosis and who are eligible to
undergo or are already on treatment with risperidone, will be randomized to either tDCS or
sham tDCS twice a day for five consecutive days. Neuropsychological testing, Magnetic
Resonance Imaging (MRI) and electroencephalogram (EEG) will be conducted at baseline, week 1
(after completion of tDCS or sham tDCS intervention) and week 16. Clinical interviews to
assess symptoms and medical assessments for side effects will be done at baseline, weekly for
the first four weeks and then every two weeks until study completion. The primary outcome
measure will be the Auditory Hallucinations Rating Scale (AHRS) score.

Specific aims are:

To determine the efficacy of tDCS for auditory hallucinations in patients with first episode
schizophrenia. The investigators hypothesize that risperidone plus tDCS is associated with a
faster and more robust decrease in auditory hallucinations compared to risperidone plus sham
tDCS.

To test the efficacy of tDCS in cognitive and negative symptoms in patients with first
episode schizophrenia. The investigators hypothesize that tDCS improves working memory,
attention/vigilance and decreases negative symptoms.

To examine the neuronal basis of tDCS effects in ameliorating auditory hallucinations in
schizophrenia by conducting event-related potential (ERP) and resting state EEG. The
investigators hypothesize that the Delta N-100 amplitude is associated with improvement of
auditory hallucinations after tDCS treatment.

To determine the effects of tDCS on brain structure and function by conducting structural
MRI, diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI).

Inclusion Criteria:

1. current Diagnostic and Statistical Manual-IV (DSM-IV) -defined diagnosis of
schizophrenia, schizophreniform, schizoaffective disorder, psychosis NOS as assessed
using the Structured Clinical Interview for Axis I DSM-IV Disorders (SCID-I/P) (First
et al, 1994).

2. does not meet DSM-IV criteria for a current substance-induced psychotic disorder, a
psychotic disorder due to a general medical condition, delusional disorder, brief
psychotic disorder, shared psychotic disorder, or a mood disorder with psychotic
features.

3. current positive symptoms rated ≥4 (moderate) on one or more of these BPRS (Woerner et
al., 1988) items: conceptual disorganization, grandiosity, hallucinatory behavior,
unusual thought content

4. current positive symptoms rated ≥4 (moderate) on one or more of these BPRS (Woerner et
al., 1988) items: conceptual disorganization, grandiosity or unusual thought content
and is in the first episode of the illness as defined by having taken antipsychotic
medications for a cumulative lifetime period of 4 weeks or less,

5. age 15 to 40.

6. competent and willing to sign informed consent.

7. for women, negative pregnancy test and agreement to use a medically accepted birth
control method.

Exclusion Criteria:

1. serious neurological or endocrine disorder or any medical condition or treatment known
to affect the brain.

2. any medical condition which requires treatment with a medication with psychotropic
effects.

3. significant risk of suicidal or homicidal behavior;

4. cognitive or language limitations, or any other factor that would preclude subjects
providing informed consent.

5. medical contraindications to treatment with risperidone (e.g. neuroleptic malignant
syndrome with prior risperidone exposure).

6. lack of response to a prior adequate trial of risperidone.

7. requires treatment with an antidepressant or mood stabilizing medication.

8. presence of an electrically, magnetically or mechanically activated implant (including
cardiac pacemaker), an intracerebral vascular clip, or any other electrically
sensitive support system.

9. damaged skin at the site of stimulation (i.e. skin with ingrown hairs, acne, razor
nicks, wounds that have not healed, recent scar tissue, broken skin, etc.).