The Schizophrenia Construct After 100 Years of Challenges

Abstract

The concept of schizophrenia (SZ) (nee dementia praecox) has been widely used in medicine for the last 100 years. However, major controversies concerning the construct have yet to be resolved. The traditional categorical nosology of functional psychoses is challenged by observations that SZ, schizoaffective disorder (SAD), major depression (MDD) and bipolar disorder (BPD) share clinical presentations, endophenotypes and several genes. The present overview presents various theoretical frameworks for categorical and dimensional models, and specifically their applicability to the fields of epidemiology, genetic epidemiology, genetics and endophenotype studies. It should be noted that clinical dimensions, candidate genes and endophenotypes have not been found to be specific to any one type of functional psychosis. Clinical syndromes, including depression, anxiety, and substance use disorders, co-occur with SZ, SAD, MDD and BPD at appreciable rates. Genetic linkage studies have primarily focused on the phenotype of functional psychoses (SZ, SAD, MDD, and BPD) susceptibility. To date, however, relatively limited work has been conducted to identify the genetic variants associated with symptom dimensions. While the potential advantages of an endophenotype based approach are widely appreciated in the investigation of the genetics of functional psychoses, there is no consensus for achieving this goal. Overlapping endophenotype processes include physiological or electrophysiological anomalies, psychological or neurocognitive deficits and biochemical alterations. Specific challenges need to be addressed in the future if we hope to move forward in our goal to reach meaningful and applicable clinical results. We conclude that we need: (a) a new concept for functional psychoses in order to develop a new classification for research purposes, (b) new and improved clinical assessment tools, (c) to target persons with functional psychoses; and (d) to conduct molecular genetic studies using a number of candidate genes and endophenotypes with measured symptom dimensions and patterns.