Schizophrenia and psychosis in children and adolescents: An inspiring journey of scientific progress and the rich influences of history and religion.

The human brain begins in utero through neurulation, during which the neural plate develops into the neural tube. Through a complex journey of remarkable neurological intricacy, the central nervous system (CNS) forms with billions of neurons and trillions of connections. This extraordinary process is filled with dangers, including genetic abnormalities (from both maternal and paternal sources), maternal injuries such as infections, substance use, immunological conditions, and other factors. It is somewhere during this development of cerebral functions that a vulnerability to schizophrenia arises. The evolutionary origins still remain elusive to this day. Clinically recognized about 130 years ago, the history of schizophrenia spans thousands of years, with conceptualization evolving from linking the condition to supernatural invasions to understanding it as a complex brain disorder, as defined by the American Psychiatric Association's 2013 DSM-5 criteria. The typical age range for presentation and diagnosis is usually between 15 and 30 years of age; presentations in older and younger age groups are also identified. Diagnostic definitions can vary; in this discussion, presentation of schizophrenia prior to 18 years of age is called pediatric schizophrenia (or EOS: early-onset schizophrenia) and COS: childhood-onset schizophrenia (very early-onset schizophrenia or VEOS) with onset prior to 13 years of age. Concepts of pediatric schizophrenia are considered that include historical perspectives, epidemiology, diagnosis, etiology, co-morbid conditions, differential diagnoses, evaluation principles, and concepts of management (i.e., psychopharmacology, psychotherapy, ECT and psychosocial support). Clinicians evaluating a child or adolescent with features suggestive of psychosis must keep in mind the numerous medical and psychological conditions that can serve as differential diagnoses and co-morbid conditions. These disorders are discussed in this treatise. The younger the child, the more likely there is another disorder simulating schizophrenia, such as epilepsy, infection, inborn errors of metabolism, porphyria, immunologic conditions, genetic (epigenetic) aberrations, and numerous others. Before treating this young person for schizophrenia, one must have the back-up or support of a comprehensive testing protocol (i.e., laboratory studies, neuroimaging results, genetic analyses, etc.). Always screen for suicidality as suicide is a persistent peril for individuals with psychosis. As one provides psychopharmacologic products (i.e., mostly dopamine receptor antagonists) for this psychiatric problem, the medical and psychiatric health of the child or adolescent must be known in detail. The potential side effects (i.e., neurologic, extrapyramidal, metabolic, cardiac, others) of these current agents are disturbing to these young individuals and are reviewed along with management principles. Clozapine remains the gold standard for drug-resistant schizophrenia and violence-linked psychosis, despite its potentially menacing side effect profile (i.e., agranulocytosis, seizures, sialorrhea, others). Comprehensive care for co-morbid conditions is critical in the overall picture of optimal management. Principles of psychosocial support for the primary care clinician are provided to help the young person who has schizophrenia and the family with the goal of transforming what may be labeled as a sinister situation into a chronic, yet manageable, as well as non-stigmatizing disorder.