REtinal and VIsual Cortical Response in Early PSYchosis (REVIPSY)

The purpose of the REVIPSY study is to measure retinal and the visual cortical electrophysiological responses in situations at risk of psychosis in patients who have experienced a first psychotic episode. A perspective of this project will be to create new electrophysiological biomarkers predictive of the risk of conversion to psychosis

Study Overview

• Status: Terminated
• Conditions: Prodromal Schizophrenia; Prodromal Symptoms; Healthy Controls; Psychotic Episode
• Intervention / Treatment: Device: Retinaute (BioSerenity); Device: EEG Headset 64 electrodes (BioSemi); Device: MonPackOne (Metrovision)

Detailed Description

The severity of psychotic disorders and their disabling potential in young patients represent a major public health problem. These populations are affected by high-level cognitive disorders associated with highly integrative functions. However, there is increasing evidence of lower-level impairments, including vision. Indeed, the literature reports electrophysiological abnormalities at the retinal level, reflected by an alteration of the signal transmission in the retinal ganglion cells (RGC), photoreceptors and bipolar cells. At the cortical level, numerous studies report electrophysiological abnormalities associated with the activity of the primary visual areas. These both electrophysiological measurements have the advantage of being objective, reliable and reproducible, thus leading to new research perspectives concerning the link between retinal and cortical measures in psychosis. These measures could also be interesting for the detection of the risk of conversion to psychosis, before it develops.

The transition to a state of psychosis is in fact marked by the appearance of symptoms, which can occur several years before the diagnosis and impact the duration of the untreated psychosis. Thus, the notion of a clinical state at high risk of psychosis (CHRP) defines a population of patients said to be at risk of psychosis. These symptoms precede the occurrence of the first psychotic episode (FEP), indicating the clear transition to psychotic illness. The questions that arise at the present time concerned the early detection and intervention of psychosis during this prodromal phase. This detection could be done via electrophysiological measures associated to the visual processing, but also via measures of neuropsychological evaluations and behavioral measures.

That is why, a study on retinal and visual cortical alterations coupled with neuropsychological assessments and behavioral measures in populations at risk of populations at risk of CHRP psychosis and in FEP would potentially reveal predictive biomarkers of the pathology. Such a project could lead to the development of retino-cortical biomarkers in mental health and will eventually lead to to create ultra-portable, reliable and routinely usable measurement devices for the early detection of psychosis in clinic.

Main objective: To measure retinal and visual cortical electrophysiological responses in clinical subjects at high risk of psychosis (CHRP) in comparison with first-episode psychotic patients (FEP) and healthy controls (CS)

Secondary objective(s) :

Compare ERG traces obtained from the "Retinaute" portable ERG device produced by the company BioSerenity with ERG traces obtained from a standard device ERG measurement device "MyPackOne" produced by the company Metrovision among healthy controls

To measure performance on neuropsychological tests in clinical subjects at high risk of psychosis (CHRP) compared to patients with a first episode of psychosis (FEP)

Measuring temporal prediction in tactile modality (unimodal) with a motor task, in clinical subjects at high risk of psychosis (CHRP) in comparison with first-episode patients (FEP) and healthy controls (CS)

Measuring temporal prediction in visual and tactile (multimodal) modalities/Measuring temporal prediction in visual modality (unimodal) with a classical perceptual task in clinical subjects at high risk of psychosis (CHRP) in comparison with patients with a first psychotic episode with a first episode of psychosis (FEP) and healthy controls (CS)

To compare the sensitivity of behavioural and EEG measures to the prediction of tactile vs. visual stimuli, and multimodal vs. unimodal

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Laxou, France, 54520
    • Centre Psychothérapeutique de Nancy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

1. Inclusion Criteria:

   1. All groups

      Age and gender matching

      Age between 18 and 40

      Enrolled in a social security plan

      Normal or corrected-to-normal visual acuity verified by Monoyer test

      In women of childbearing age: negative urine pregnancy test at the inclusion visit

      Person who has received and understood prior information about the study

      Person who has given free and informed written consent prior to any participation in the study

   2. Healthy control group (HC; n=30)

      Met "all groups" criteria

      No current disorders as assessed by the MINI global assessment

      No lifetime (hypo)manic episodes or psychotic disorders and current

      No current or past disorders by CAARMS assessment

      No current disorders according to ICD-10 criteria

      No positive family history (parents/first degree) for affective affective, non-affective psychoses or major affective disorders

      No regular use (more than 3 psychotropic medications: benzodiazepines, hypnotics,antidepressants, antipsychotics or mood regulators or psychostimulants) during the past last 12 months

   3. High clinical risk group for psychosis (CHRP; n=30)

      Met "all groups" criteria, Assessment at CAARMS:

      • Attenuated positive symptoms (APS)
      • OR Brief Intermittent Psychotic Symptoms (BIPS)
      • OR Attenuated psychosis of sub-laminar frequency
      • OR sub-laminar attenuated psychosis

      Antipsychotic treatment with a cumulative dose of equivalent chlorpromazine <2500mg lifetime (1)

   4. First Episode Psychosis (FEP; n=30)

   All-group criteria met CAARMS assessment: Psychosis/antipsychotic treatment threshold treatment threshold achieved at CAARMS

   Antipsychotic treatment with a cumulative dose of equivalent chlorpromazine <2500mg lifetime (1)

2. Exclusion Criteria (all groups):

Impairment of the subject that makes it difficult or impossible to participate in the or comprehension of the information provided to him/her

Dyslexia

Substance use disorder according to CIM-10

Neurological history including progressive neurological pathology

Progressive retinal disease

Chronic glaucoma

Ophthalmologic pathology affecting visual acuity

Current ocular infection

Major under guardianship, curatorship or safeguard of justice

Pregnant or breastfeeding women

Persons in a life-threatening emergency situation

Result of the preliminary medical examination incompatible with the research

Patient presenting a suicidal risk.

Criteria incompatible with the use of the Retinaute:

• Allergy to silver
• Known or suspected allergy to any of the following components:

polyamide, polyester, elastane, latex, rubber, silicone, or any synthetic material as well as to cotton in case the device is used without the device is used without a protective head covering

• Sensory disorders making the patient insensitive to pain on the skin.
• Behavioral problems making the patient extremely agitation or aggression.
• Mental disorders incompatible with the use of the device.
• Seizure disorder.
• Open wound in an area covered or wrapped by the device.
• User at high risk of contagion.
• Wearing an implantable medical device (e.g. pacemaker)
• Pregnant women, women in labor or nursing mothers.
• Allergy or skin sensitivity to one of the components of the cream Elefix or equivalent on the market: coconut oil, egg oil, propylene glycol egg oil, propylene glycol, glycerin, lanolin...
• Allergy or skin sensitivity to one of the components of the cream NuPrep or market equivalent

Participation in another interventional study (exclusion period included)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy Controls (HC); n=90	Device: Retinaute (BioSerenity); Wearable device in the form of a virtual reality headset for the recording of electrophysiological measurements such as electroretinogram (ERG) and electrocenphalogram (EEG), ISCEV standards; Device: EEG Headset 64 electrodes (BioSemi); EEG headset with 64 electrodes for the recording of visual cortical electrophysiological signals; Device: MonPackOne (Metrovision); Standard device for the recording of electroretinography (ERG) measurements, ISCEV standards WARNING : Device used only in 3 healthy controls to address the secondary objective
Experimental: Clinical High Risk of Psychosis (CHRP); n=30	Device: Retinaute (BioSerenity); Wearable device in the form of a virtual reality headset for the recording of electrophysiological measurements such as electroretinogram (ERG) and electrocenphalogram (EEG), ISCEV standards; Device: EEG Headset 64 electrodes (BioSemi); EEG headset with 64 electrodes for the recording of visual cortical electrophysiological signals
Experimental: First Episode Psychosis (FEP); n=30	Device: Retinaute (BioSerenity); Wearable device in the form of a virtual reality headset for the recording of electrophysiological measurements such as electroretinogram (ERG) and electrocenphalogram (EEG), ISCEV standards; Device: EEG Headset 64 electrodes (BioSemi); EEG headset with 64 electrodes for the recording of visual cortical electrophysiological signals

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
N95 wave	Amplitude	Day1
a wave	Amplitude	Day1
b wave	Amplitude	Day1
P100 wave	Amplitude	Day1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Visual Object and Space Perception (VOSP)	Score	Day1
Verbal Fluency	Score	Day1
Working Memory	Score	Day1
Betarythm (EEG oscillatory responses)	Amplitude	Day1
Contingent Negative Variation (CNV)	Amplitude reaction time between a warning and a go signal as measured by electroencephalography (EEG)	Day1
CPT-AX (Continuous Performance Task version AX)	Score	Day1
fNART (French adaptation of National Adult Reading Test)	Score	Day1
TAP (Test of Attentional Performance)	Score	Day1

Collaborators and Investigators

• Sponsor: Centre Psychothérapique de Nancy
• Collaborators: Institut National de la Santé Et de la Recherche Médicale, France; BioSerenity
• Investigators: Principal Investigator: Vincent LAPRÉVOTE, Pr. MD PhD, Centre Psychothérapique de Nancy

Publications and helpful links

General Publications

• Laprevote V, Heitz U, Di Patrizio P, Studerus E, Ligier F, Schwitzer T, Schwan R, Riecher-Rossler A. [Why and how to treat psychosis earlier?]. Presse Med. 2016 Nov;45(11):992-1000. doi: 10.1016/j.lpm.2016.07.011. Epub 2016 Aug 21. French.
• Demmin DL, Davis Q, Roche M, Silverstein SM. Electroretinographic anomalies in schizophrenia. J Abnorm Psychol. 2018 May;127(4):417-428. doi: 10.1037/abn0000347.
• Moghimi P, Torres Jimenez N, McLoon LK, Netoff TI, Lee MS, MacDonald A 3rd, Miller RF. Electoretinographic evidence of retinal ganglion cell-dependent function in schizophrenia. Schizophr Res. 2020 May;219:34-46. doi: 10.1016/j.schres.2019.09.005. Epub 2019 Oct 12.
• Tan A, Schwitzer T, Conart JB, Angioi-Duprez K. [Retinal investigations in patients with major depressive disorder, bipolar disorder or schizophrenia: A review of the literature]. J Fr Ophtalmol. 2020 Sep;43(7):586-597. doi: 10.1016/j.jfo.2019.10.029. Epub 2020 Jul 4. French.
• Butler PD, Martinez A, Foxe JJ, Kim D, Zemon V, Silipo G, Mahoney J, Shpaner M, Jalbrzikowski M, Javitt DC. Subcortical visual dysfunction in schizophrenia drives secondary cortical impairments. Brain. 2007 Feb;130(Pt 2):417-30. doi: 10.1093/brain/awl233. Epub 2006 Sep 19.
• Knebel JF, Javitt DC, Murray MM. Impaired early visual response modulations to spatial information in chronic schizophrenia. Psychiatry Res. 2011 Sep 30;193(3):168-76. doi: 10.1016/j.pscychresns.2011.02.006. Epub 2011 Jul 20.
• Kim DW, Shim M, Song MJ, Im CH, Lee SH. Early visual processing deficits in patients with schizophrenia during spatial frequency-dependent facial affect processing. Schizophr Res. 2015 Feb;161(2-3):314-21. doi: 10.1016/j.schres.2014.12.020. Epub 2014 Dec 29.

Study record dates

Study Major Dates

• Study Start (Actual): January 26, 2022
• Primary Completion (Actual): July 20, 2023
• Study Completion (Actual): July 20, 2023

Study Registration Dates

• First Submitted: October 4, 2021
• First Submitted That Met QC Criteria: December 9, 2021
• First Posted (Actual): December 22, 2021

Study Record Updates

• Last Update Posted (Actual): August 22, 2024
• Last Update Submitted That Met QC Criteria: August 20, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Retina; EEG; Vision; Early psychosis; Visual Cortex; Electrophysiology; ERG
• Additional Relevant MeSH Terms: Schizophrenia Spectrum and Other Psychotic Disorders; Schizophrenia; Psychotic Disorders; Mental Disorders; Prodromal Symptoms
• Other Study ID Numbers: RIPH 2021-04; n° IDRCB 2021-A01700-41 (Other Identifier: ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No