Reactivity of the Vestibular System to Caloric Vestibular Stimulation in Schizophrenia

Study Overview
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Brief Summary
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This study aims to determine if individuals with schizophrenia have greater reactivity to vestibular stimulation than healthy controls. The physiological response of vestibular stimulation will be assessed with electronystagmography, which provides a measure of the intensity of the nystagmus via PSPV. Positive results would suggest greater vestibular system reactivity to vestibular stimulation may be a biomarker of schizophrenia. Pathophysiologically, increased vestibular reactivity to vestibular stimulation may reflect abnormal vestibular function or impaired central suppression of the vestibular ocular reflex.

Detailed Description
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In schizophrenia, there is no conclusive link between psychopathology and vestibular dysfunction and we are not aware of any data that exists on the range of responses to caloric vestibular stimulation (CVS) in persons with schizophrenia. Initial data from another CVS study from our group suggests individuals with schizophrenia have greater reactivity to body temperature (37°C) CVS, as measured by the peak slow phase velocity of the resulting nystagmus (PSPV), than would be expected from individuals without schizophrenia versus healthy participants. Intriguingly, CVS at 37°C should not theoretically produce a significant vestibulocular reflex response due to the stimulus' approximation to body temperature. Hence, the primary aim of this study is to determine if individuals with schizophrenia will have greater vestibular reactivity, as measured by nystagmus PSPV, to CVS in comparison with healthy participants. The secondary aim is to assess illness awareness pre and post CVS administration in attempts to replicate our previous observation. A total of 20 patients with schizophrenia and 20 healthy control participants will be recruited. All participants will receive three conditions bilaterally: (1) body temperature (37°C) vestibular stimulation; (2) warm CVS (44°C), and (3) cold CVS (30°C).

Official Title
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Reactivity of the Vestibular System to Caloric Vestibular Stimulation in Schizophrenia

Conditions
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Schizophrenia, Healthy

Intervention / Treatment
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* Procedure: Left body temperature VS
* Procedure: Right body temperature VS
* Procedure: Left warm CVS
* Procedure: Right warm CVS
* Procedure: Left cold CVS
* Procedure: Right cold CVS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for Schizophrenia group: Male or female inpatients or outpatients age ≥18 Having a DSM-5 diagnosis of schizophrenia or schizoaffective disorder Voluntary and capable of consenting to participation in the research study Fluent in English Inclusion Criteria for Healthy Controls group: Male or female and age ≥18 Voluntary and capable of consenting to participation in the research study Fluent in English Absence of history of psychiatric illness using the Mini-International Neuropsychiatric Interview (MINI) Exclusion Criteria for all participants: Serious unstable medical illness or any concomitant major medical or neurological illness Acute suicidal and/or homicidal ideation Formal thought disorder rating of over 2 on the Scale for Assessment of Positive Symptoms (SAPS) [patients only] DSM-IV substance dependence (except caffeine and nicotine) within one month prior to entering the study Pregnant women Positive urine drug screen History of external or middle ear pathology History or signs of middle ear surgery (e.g. Tympanoplasty, mastoidectomy) Signs of active ear disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Each participant will successively receive 6 vestibular stimulation conditions. Side of stimulation will be randomized.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Left body temperature VS<br>Left body temperature (37°C) vestibular stimulation | Procedure: Left body temperature VS<br>* Caloric vestibular stimulation (CVS), which involves the irrigation of cold or warm water into the external ear canal, induces a temperature gradient across the semicircular canals of the vestibular apparatus stimulating the vestibular nerve. It is commonly used in both otolaryngology to assess vestibular function and neurology to test brain stem function<br>|
| Experimental: Right body temperature VS<br>Right body temperature (37°C) vestibular stimulation | Procedure: Right body temperature VS<br>* Caloric vestibular stimulation (CVS), which involves the irrigation of cold or warm water into the external ear canal, induces a temperature gradient across the semicircular canals of the vestibular apparatus stimulating the vestibular nerve. It is commonly used in both otolaryngology to assess vestibular function and neurology to test brain stem function<br>|
| Experimental: Left warm CVS<br>Left warm (44°C) caloric vestibular stimulation | Procedure: Left warm CVS<br>* Caloric vestibular stimulation (CVS), which involves the irrigation of cold or warm water into the external ear canal, induces a temperature gradient across the semicircular canals of the vestibular apparatus stimulating the vestibular nerve. It is commonly used in both otolaryngology to assess vestibular function and neurology to test brain stem function<br>|
| Experimental: Right warm CVS<br>Right warm (44°C) caloric vestibular stimulation | Procedure: Right warm CVS<br>* Caloric vestibular stimulation (CVS), which involves the irrigation of cold or warm water into the external ear canal, induces a temperature gradient across the semicircular canals of the vestibular apparatus stimulating the vestibular nerve. It is commonly used in both otolaryngology to assess vestibular function and neurology to test brain stem function<br>|
| Experimental: Left cold CVS<br>Left cold (30°C) caloric vestibular stimulation | Procedure: Left cold CVS<br>* Caloric vestibular stimulation (CVS), which involves the irrigation of cold or warm water into the external ear canal, induces a temperature gradient across the semicircular canals of the vestibular apparatus stimulating the vestibular nerve. It is commonly used in both otolaryngology to assess vestibular function and neurology to test brain stem function<br>|
| Experimental: Right cold CVS<br>Right cold (30°C) caloric vestibular stimulation | Procedure: Right cold CVS<br>* Caloric vestibular stimulation (CVS), which involves the irrigation of cold or warm water into the external ear canal, induces a temperature gradient across the semicircular canals of the vestibular apparatus stimulating the vestibular nerve. It is commonly used in both otolaryngology to assess vestibular function and neurology to test brain stem function<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nystagmus response (peak slow phase velocity) | Nystagmus response will be measured at between thirty and 60 seconds post irrigations, looking for the highest velocities. | Between 30 and 60 sec after each CVS condition | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Illness awareness | Changes in illness awareness will be assessed using a questionnaire. | Before CVS session and10 min after CVS session |