Molecular Psychiatry (2012) 17, 1174–1179; doi:10.1038/mp.2012.105; published online 7 August 2012

Why has it taken so long for biological psychiatry to develop clinical tests and what to do about it?

S Kapur1, A G Phillips2 and T R Insel3

  1. 1King's College London, Institute of Psychiatry, London, UK
  2. 2University of British Columbia, Department of Psychiatry and The CIHR Institute of Neurosciences, Mental Health and Addiction, Vancouver, BC, Canada
  3. 3National Institute of Mental Health, Bethesda, MD, USA

Correspondence: Professor S Kapur, King's College London, Institute of Psychiatry, DeCrespigny Park, London SE5 8AF, UK. E-mail:

Received 2 December 2011; Revised 21 May 2012; Accepted 29 May 2012
Advance online publication 7 August 2012



Patients with mental disorders show many biological abnormalities which distinguish them from normal volunteers; however, few of these have led to tests with clinical utility. Several reasons contribute to this delay: lack of a biological ‘gold standard’ definition of psychiatric illnesses; a profusion of statistically significant, but minimally differentiating, biological findings; ‘approximate replications’ of these findings in a way that neither confirms nor refutes them; and a focus on comparing prototypical patients to healthy controls which generates differentiations with limited clinical applicability. Overcoming these hurdles will require a new approach. Rather than seek biomedical tests that can ‘diagnose’ DSM-defined disorders, the field should focus on identifying biologically homogenous subtypes that cut across phenotypic diagnosis—thereby sidestepping the issue of a gold standard. To ensure clinical relevance and applicability, the field needs to focus on clinically meaningful differences between relevant clinical populations, rather than hypothesis-rejection versus normal controls. Validating these new biomarker-defined subtypes will require longitudinal studies with standardized measures which can be shared and compared across studies—thereby overcoming the problem of significance chasing and approximate replications. Such biological tests, and the subtypes they define, will provide a natural basis for a ‘stratified psychiatry’ that will improve clinical outcomes across conventional diagnostic boundaries.


clinical tests; diagnosis; stratified medicine; stratified psychiatry