The Efficacy of Neural Stimulation in Individuals With Schizophrenia

Study Overview
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Brief Summary
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The purpose of this study is to understand the relationship between psychotic symptoms and social functioning in individuals with schizophrenia spectrum disorders. Our goal is to determine whether stimulating the brain using transcranial Direct Current Stimulation (tDCS) can improve symptoms and daily functioning.

Detailed Description
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Paranoid ideation is a common delusion experienced by individuals with schizophrenia spectrum disorders (SSD) that negatively impacts social interactions and quality of life. Therefore, efforts to reduce paranoid thinking via neuromodulation techniques [e.g., transcranial direct current stimulation (tDCS)] are in development, with amygdala-prefrontal cortex (PFC) circuits targeted as critical components of the neural mechanisms underlying paranoia. This project aims to alleviate paranoia and improve social functioning in individuals with SSD by implementing tDCS to ventrolateral PFC. A double-blind, within-subjects, crossover design will be used to compare the effects of active vs. sham tDCS. Ecological Momentary Assessments (EMA) will also be utilized to quantify any delayed stimulation effects in daily social interactions.

Official Title
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The Efficacy of Neural Stimulation in Individuals With Schizophrenia

Conditions
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Schizophrenia, Schizo Affective Disorder

Intervention / Treatment
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* Device: tDCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age = 18-60 Diagnosed with schizophrenia or schizoaffective disorder Having current (in the past week) or recent (in the past month) paranoia Exclusion Criteria: Presence or history of a pervasive developmental disorder or mental retardation as defined by IQ < 70 Presence or history of neurological or medical disorders that contraindicate neural stimulation (e.g. presence or history of epilepsy, seizures, etc.) Demonstrating sensory limitations, including uncorrectable visual or hearing impairments that interfere with assessment History of electroconvulsive therapy Lack of proficiency in English Substance use disorder not in remission in the past 6 months Any implanted devices such as pace maker, neurostimulator Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Participants will complete active and sham simulation sessions in a randomized, counterbalanced order about one week apart.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active anodal tDCS first, then Sham tDCS<br>Active anodal tDCS (40 minutes; divided into two 20-minutes sessions) followed by behavioral testing; Washout (about 1 week); sham stimulation (40 minutes; divided into two 20-minutes sessions) followed by behavioral testing. | Device: tDCS<br>* active anodal tDCS and sham tDCS<br>|
| Sham Comparator: Sham tDCS first, then Active anodal tDCS<br>Sham tDCS (40 minutes; divided into two 20-minutes sessions) followed by behavioral testing; Washout (about 1 week); Active anodal tDCS (40 minutes; divided into two 20-minutes sessions) followed by behavioral testing Intervention. | Device: tDCS<br>* active anodal tDCS and sham tDCS<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Paranoid Ideation for Active vs. Sham Stimulation | Paranoid ideation will be measured by the State Social Paranoia Scale (SSPS). Participants will indicate how much they agree with each of 20 statements (e.g., Someone was hostile towards me, Someone was trying to isolate me) using a 5-point Likert scale (1 = do not agree, 5 = totally agree). Scores range from 20-100, and higher scores represent higher state paranoid ideation. | The assessment will be completed 30 minutes after completion of the active/sham stimulation | 
| Paranoid Ideation for Active vs. Sham Stimulation | Paranoid ideation will be measured by the Hostility Scale of the Personality Inventory for DSM-5 (PID-5-HS). PID-5-HS contains 10 self-report items (e.g., I snap at people when they do little things that irritate me) assessing pathological hostility on a 4-point scale (0 = very false or often false, 3 = very true or often true), with higher total scores indicating more hostility (range = 0-30). | The assessment will be completed 30 minutes after completion of the active/sham stimulation | 
| Paranoid Ideation for Active vs. Sham Stimulation | Paranoid ideation will be measured by the Ambiguous Intentions Hostility Questionnaire (AIHQ). Five ambiguous scenarios will be presented to participants, and they will be asked to give reasons why each situation happened, indicate how much they think that people did this to them on purpose, how angry they are, how much they will blame others, and what they will do about it. Responses will be recorded verbatim or based on 6-point (if the behavior is on purpose) and 5-point (how angry they are, how much they will blame others) Likert scales. For the open-ended questions, hostility and aggression biases will be rated by three independent, trained raters using a 5-point Likert scale (1 = not hostile/aggressive at all, 5 = very hostile/aggressive). Inter-rater reliability will be computed by ICC among all the raters, with ICC > .80 being acceptable. | The assessment will be completed 30 minutes after completion of the active/sham stimulation | 
| Paranoid Ideation for Active vs. Sham Stimulation | Paranoid ideation will be measured by the Scrambled-sentences task (SST) | The assessment will be completed 30 minutes after completion of the active/sham stimulation | 
| Paranoid Ideation for Active vs. Sham Stimulation | Paranoid ideation will be measured by the Trustworthiness Task | The assessment will be completed 30 minutes after completion of the active/sham stimulation | 
| Paranoid Ideation for Active vs. Sham Stimulation | Paranoid ideation will be measured by EMA (i.e., questions about feelings of paranoia in daily life). | Change in daily paranoia feelings will be assessed from the pre-stimulation EMA period (7 days before the stimulation visit) to the post-stimulation EMA period (7 days after the stimulation visit) | 
| Social functioning for Active vs. Sham Stimulation | Social functioning will be measured by the Birchwood Social Functioning Scale (SFS). This scale measures social adjustment based on self-reports (4- or 5-point scales), with higher total scores indicating better social functioning (range = 0-223). | The assessment will be completed 30 minutes after completion of the active/sham stimulation | 
| Social functioning for Active vs. Sham Stimulation | Social functioning will be measured by EMA (i.e., questions about daily interactions with others) | Change in daily interactions will be assessed from the pre-stimulation EMA period (7 days before the stimulation visit) to the post-stimulation EMA period (7 days after the stimulation visit) | 
| Social functioning for Active vs. Sham Stimulation | Social functioning will be measured by EMA (i.e., questions about daily experience in social interactions). | Change in daily experience in social interactions will be assessed from the pre-stimulation EMA period (7 days before the stimulation visit) to the post-stimulation EMA period (7 days after the stimulation visit) | 
| Social functioning for Active vs. Sham Stimulation | Social functioning will be measured by EMA (i.e., questions about daily expectations of social interactions). | Change in daily expectations of social interactions will be assessed from the pre-stimulation EMA period (7 days before the stimulation visit) to the post-stimulation EMA period (7 days after the stimulation visit) |