Efficiency of a Composite Personalised Care on Functional Outcome in Early Psychosis

Chronic psychosis, including schizophrenia is now viewed as a progressive disorder where cognitive deficits predate the clinical onset. Early intervention programs improve the general outcome with staged care strategies, supporting the view that the period before and around the first episode of psychosis is a window of opportunity for improving its functional recovery. Pioneering epigenetic analyses indicate that psychosis onset involves oxidative stress and inflammation suggesting that neuroprotective strategies could limit or even prevent the onset of or the transition into a chronic disorder. Several biological factors associated with the emergence of psychosis can all be rectified by using safe and easily accepted supplements including alterations folate deficiency/hyperhomocysteinemia; redox imbalance and deficit in polyunsaturated fatty acids (PUFA). The prevalence of these anomalies (20-30%) justifies a systematic detection and could guide personalised add-on strategy. Cognitive remediation improves quality of life (QoL) and functional outcome in patients with chronic psychosis. It would even be more efficacious in the early phase of psychosis by tackling the negative impact of psychosis on education achievement and employment. However, cognitive dysfunctions are often overlooked in patients at ultra-high risk (UHR) for psychosis and patient with a first episode of psychosis (FEP) and cognitive remediation is not always accessible. New technologies can provide us with youth-friendly, non-stigmatising tools, such as applications with cognitive strategies, motivational tools and functioning guidance personalised according to the need of each individual. Patients can have access to it, wherever they live. Early psychosis can be associated with inflammation, metabolic deficiency, as well as early structural brain anomalies that reflect brain plasticity abilities and could influence the prognosis and response to cognitive training. The study hypothesis is that promoting neuroplasticity by cognitive training and personalised virtual psychoeducation guidance could attenuate or reverse early cognitive deficits and improve the overall functional outcome in young patients UHR or FEP and that this effect is modulated by individual brain plasticity abilities. The overall objective of PsyCARE\_trial is to improve early intervention in psychosis by providing a composite personalised care (CPC) that will enable personalised cognitive training and psychoeducation guidance, adapted to individuals' needs, cognitive abilities and biological background.

Inclusion Criteria: * Adolescent and young adults, both sexes, aged 15 to 30 years, * Persons characterised according to the CAARMS criteria \[8\] as UHR or FEP in the first year after having received diagnosis and care, if any * Informed and written signed consent, * Participant with regular health insurance Exclusion Criteria: * Severe and unstabilised medical conditions, * Insufficient level in reading and/or French language, * Current participation in another intervention trial or in a full cognitive remediation programme, * Enforced hospitalization , * Intellectual Deficiency (i.e. Intelligence Quotient\<70), and / or sensorimotor deficits incompatible with the cognitive reinforcement, * Former treated episode of psychosis, chronic schizophrenia, schizoaffective, or Bipolar disorder (preceeding the 12 months established in the inclusion criteria), * Current severe depression (in case of doubt, MADRS \> 34), * Receiving therapeutic levels of antipsychotics for more than 12 months, * Current medication with benzodiazepine \>30 mg per day equivalent diazepam * Current daily use of substance of abuse other than nicotine and alcohol and higher than an average equivalent of 5 cannabis cigarettes AND/OR severe substance use disorder (DSMV criteria/dependence DSMIV criteria) other than nicotine during the last 6 months or for more than 5 years. * Pregnant women, parturients, and lactating women, * Individuals deprived of their liberty by a judicial or administrative decision, persons under psychiatric care under articles L3212-1 and 3213-1 (Public Health Code), * Individuals of legal age who are the subject of a legal protection measure or unable to express their consent