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

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

This is a cross-sectional, open, monocentric, non-randomized study applied in psychiatry and neuroscience. This study will include three groups of adults subject (>18 years) Patients with clinical high risk of psychosis (CHRP ; n=30) Patients having experienced a first psychotic episode (FEP ; n=30) Healthy Controls (HC ; n=30)

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

Standard device for the recording of electroretinography (ERG) measurements, ISCEV standards WARNING : Device used only in 3 healthy controls to address the secondary objective

Amplitude reaction time between a warning and a go signal as measured by electroencephalography (EEG)

Inclusion Criteria: 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 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 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) 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) 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)

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