Towards a natural history of schizophrenia.

Abstract

All scientific knowledge relies on observation, but with complex phenomena there is often an awful lot to observe. Schizophrenia is a neuropsychiatric disorder characterised by a wide range of symptoms such as delusions, hallucinations, lack of motivation, cognitive difficulties, impaired speech and aberrant motor functioning. Beyond the behavioural level of symptoms, however, additional hallmarks of the disorder have been discovered across every level of neuroscientific investigation. Epidemiological studies have shown, for example, strong heritability, late-adolescent onset, and increased incidence in men. Neuroimaging studies have found characteristic alterations in both structural and functional brain connectivity. Pharmacological studies have uncovered disruptions in dopamine function. Histological studies have implicated parvalbumin-containing GABAergic neurons. Transcriptomic studies of post-mortem brain tissue have highlighted hundreds of differentially expressed genes, while GWAS studies have identified scores of risk loci in the genome. However, this rich, multi-scale description of what the disorder is makes it ever more challenging to advance mechanistic hypotheses for how these complex phenotypes come about. In this issue of Brain [1], van den Heuvel and colleagues cannily propose that we may get closer to understanding how schizophrenia emerges by focusing first on the apparently harder question of why it exists at all.