Evidence from epidemiological, clinical, and biological research resulted in the immune hypothesis: the hypothesis that immune system dysfunction is involved in the pathophysiology of schizophrenia spectrum disorders (SSD). The promising implication of this hypothesis is the potential to use existing immunomodulatory treatment for innovative interventions for SSD. Here, we provide a selective historical review of important discoveries that have shaped our understanding of immune dysfunction in SSD. We first explain the basic principles of immune dysfunction, after which we travel more than a century back in time. Starting our journey with neurosyphilis-associated psychosis in the nineteenth century, we continue by evaluating the role of infections and autoimmunity in SSD and findings from assessment of immune function using new techniques, such as cytokine levels, microglia density, neuroimaging, and gene expression. Drawing from these findings, we discuss anti-inflammatory interventions for SSD, and we conclude with a look into the future.
Depression is an eminently treatable disorder that responds to psychotherapy or medications; the efficacy of each has been established in hundreds of controlled trials. Nonetheless, the prevalence of depression has increased in recent years despite the existence of efficacious treatments-a phenomenon known as the treatment-prevalence paradox. We consider several possible explanations for this paradox, which range from a misunderstanding of the very nature of depression, inflated efficacy of the established treatments, and a lack of access to efficacious delivery of treatments. We find support for each of these possible explanations but especially the notion that large segments of the population lack access to efficacious treatments that are implemented as intended. We conclude by describing the potential of using lay therapists and digital technologies to overcome this lack of access and to reach historically underserved populations and simultaneously guarantee the quality of the interventions delivered.