Recent advances in understanding schizophrenia

Abstract

Schizophrenia is a highly disabling disorder whose causes remain to be better understood, and treatments have to be improved. However, several recent advances have been made in diagnosis, etiopathology, and treatment. Whereas reliability of diagnosis has improved with operational criteria, including Diagnostic and Statistical Manual of Mental Disorders, (DSM) Fifth Edition, validity of the disease boundaries remains unclear because of substantive overlaps with other psychotic disorders. Recent emphasis on dimensional approaches and translational bio-behavioral research domain criteria may eventually help move toward a neuroscience-based definition of schizophrenia. The etiology of schizophrenia is now thought to be multifactorial, with multiple small-effect and fewer large-effect susceptibility genes interacting with several environmental factors. These factors may lead to developmentally mediated alterations in neuroplasticity, manifesting in a cascade of neurotransmitter and circuit dysfunctions and impaired connectivity with an onset around early adolescence. Such etiopathological understanding has motivated a renewed search for novel pharmacological as well as psychotherapeutic targets. Addressing the core features of the illness, such as cognitive deficits and negative symptoms, and developing hypothesis-driven early interventions and preventive strategies are high-priority goals for the field. Schizophrenia is a severe, chronic mental disorder and is among the most disabling disorders in all of medicine. It is estimated by the National Institute of Mental Health (NIMH) that 2.4 million people over the age of 18 in the US suffer from schizophrenia. This illness typically begins in adolescence and derails the formative goals of school, family, and work, leading to considerable suffering and disability and reduced life expectancy by about 20 years. Treatment outcomes are variable, and some people are successfully treated and reintegrated (i.e. go back to work). Despite the effort of many experts in the field, however, schizophrenia remains a chronic relapsing and remitting disorder associated with significant impairments in social and vocational functioning and a shortened lifespan. Comprehensive treatment entails a multi-modal approach, including psychopharmacology, psychosocial interventions, and assistance with housing and financial sustenance. Research to date suggests a network of genetic, neural, behavioral, and environmental factors to be responsible for its development and course. This article aims to summarize and explain recent advancements in research on schizophrenia, to suggest how these recent discoveries may lead to a better understanding and possible further development of effective therapies, and to highlight the paradigm shifts that have taken place in our understanding of the diagnosis, etiopathology, and treatment.

Figure 1.. Etiology of schizophrenia

The multifactorial etiology of schizophrenia including a) rare genes that have a large effect, b) common genes that have a small effect, and c) the environmental factors and gene-environmental interactions that confer risk for schizophrenia.