Neurological soft signs as candidate endophenotypes for schizophrenia: A shooting star or a Northern star?

Raymond C.K. Chan, Irving I. Gottesman

Research output: Contribution to journalReview articlepeer-review

167 Scopus citations


The crucial role of neurological indicators in schizophrenia has been recognized as among the "target features" that encompass the idea that genetic and non-genetic processes lead to neurointegrative defects later manifested in neurocognitive systems. In addition, aberrant neurological indicators have also been suggested as potential endophenotypes in schizophrenia. In the current paper, we review evidence for the utility of quantifiable neurological soft signs as potential endophenotypes for schizophrenia spectrum disorders. We start by defining endophenotypes and justifying their utility. We highlight the key criteria that must be met for an endophenotype to be useful and assess the extent to which the manifestations of neurological soft signs meet these criteria. Finally, we recommend areas in which additional research should be done to further elucidate the potential use of neurological soft signs for schizophrenia research.

Original languageEnglish (US)
Pages (from-to)957-971
Number of pages15
JournalNeuroscience and Biobehavioral Reviews
Issue number5
StatePublished - Jul 2008

Bibliographical note

Funding Information:
The authors would like to thank R. Walter Heinrichs for his constructive comments on the previous versions of this paper and Todd Gould for his help in finalizing the figure illustrating neurological soft signs as another candidate endophenotype for schizophrenia. The preparation of the paper was supported partially by the Research Initiation Fund of the 100-scholar Plan (O7CX031003), a grant from Institute of Psychology, Chinese Academy of Sciences (KSCX2-YW-R-131) and a grant from the National Science Fund China (30770723) to Raymond Chan, and a National Basic Research Programme of China (973 Program) (2007CB512305); and, the Drs. Irving and Dorothy Bernstein Professorship in Adult Psychiatry at the University of Minnesota Medical School to I.I.G.


  • Endophenotype
  • Neurological soft signs
  • Schizophrenia


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