Fusar-Poli et al's paper1 provides a comprehensive synthesis of the best practices for optimal and integrative care to individuals with psychosis in settings with variable levels of resources. While the recommendations are stratified according to the different disease stages, from clinical at-risk states to non-remitting schizophrenia, some cross-cutting issues can be further underlined. It is now well demonstrated that early developmental disruptions linked to genetics and/or environmental insults are at the core of vulnerability to schizophrenia spectrum disorders. Considering neurodevelopmental burden is also an important dimension to personalize care across the different stages of these disorders. Indeed, this burden is not only a risk factor, but also predicts response to treatment in established psychosis2. While in high-income countries a comprehensive exploration may include genetic testing and brain imaging, neurodevelopmental burden can also be assessed by simple questions regarding developmental trajectories and disease history, possibly with the help of digital tools, and by a physical examination accessible everywhere. The identification of rare genetic variants with major impact and the recent large genome-wide association studies open new avenues for therapeutic approaches, departing from dopaminergic dysregulation, taking into account that many patients are resistant to anti-dopaminergic medications. Indeed, glutamatergic systems and synaptic functioning are identified as key players in neurodevelopmental disorders, including schizophrenia, underlining the role of neuroplasticity in disease processes. For instance, there is compelling evidence that omega 3 depletion or abnormalities in one-carbon metabolism (particularly involving folate3) are frequent in persons with schizophrenia spectrum disorders, even at early stages. These deficits impact many critical processes, including neurotransmitter synthesis and release, redox regulation, epigenetic mechanisms, and resilience to inflammation4. Interestingly, boosting the biological processes underlying neuroplasticity and resilience is attainable also without complex interventions. Supplementation and nutritional approaches are safe and cost-effective, and directly accessible across all stages of the schizophrenia spectrum5. Psychosocial and psychotherapeutic interventions also promote brain plasticity and resilience. Stress is a recognized precipitating factor for psychosis, impacting the amygdala-hippocampus-prefrontal circuits6. Cognitive behavioral therapy has a documented efficacy in stress-related disorders as well as acting on brain connectivity7. Similarly, cognitive remediation has shown its efficacy and its positive impact on brain connectivity8. Thus, evidence-based effective psychological interventions in schizophrenia seem to act at the core of the pathophysiology of the disorder and should be deployed worldwide as disease-modifying strategies, with cultural and contextual adaptations. The distribution and organization of mental health care resources have a major influence on the modalities and quality of care for patients with schizophrenia. The organization based on catchment areas/sectors implemented in some high-income countries has similarities with the picture described for several middle-income countries, where the community has a central role in delivering support and psychosocial interventions. The initiatives developed to cope with scarce resources provide inspiring perspectives to offer and sustain integrative care at the different stages of psychosis. The development of the task-sharing model not only partly responds to the lack of specialized clinicians, but is also a natural way to involve users, caregivers, parents, peers, and non-specialized first-line professionals (e.g., counselors, job coaches) into integrative personalized care programs. The condition to ensure that appropriate care is delivered is nevertheless to extensively provide reliable training to all actors and sensibilization to the community, with relevant materials to be adapted to the cultural context. In addition, a critical issue in this type of organization is to maintain the access to physical care and emergency medical services, a critical need for severe forms of the illness and for those with somatic comorbidities. As underlined in Fusar-Poli et al's paper, reducing the delay to care has a major impact on the outcome and the economic burden of schizophrenia. It is thus crucial to deploy sensibilization campaigns and ensure that first-line actors can appropriately decide what to do, since not all young people with emerging mental health difficulties require highly specialized care. Questionnaires, including self-rated questionnaires, can optimize the referral of persons with early symptoms of psychosis with no delay. This is also a way to destigmatize psychotic disorders, since it familiarizes non-professionals with the early symptoms experienced by patients, and helps patients to put words on their inner unusual perceptions9. Several of these interventions can rely on digital tools, which provide a true opportunity to reduce inequalities across countries or regions. Adapted to the cultural context, they enable remote dissemination of psychosocial care to patients and families, including cognitive remediation, psychoeducation and cognitive behavioral therapy, as well as sensibilization and training of professional and non-professional actors. Furthermore, questionnaires accessible online and/or on smartphones are valuable and transposable tools to facilitate access to care and optimize the use of specialized resources, especially useful in conditions of economic constraints. Fusar-Poli et al's review brings solid bricks to build an integrative and personalized approach to schizophrenia spectrum disorders across stages and countries, worldwide. It opens an inspiring crosstalk between the different fields and settings, from the more clinical to the more community-based. This will improve the dissemination of new insights in the dynamics of the pathophysiology of these disorders and hopefully lead to better global care for all patients with these eventually disabling conditions.
Marie‐Odile Krebs (Fri,) studied this question.