Familial liability and schizophrenia phenotypes: a polydiagnostic approach

Area of Science:

• Psychiatry
• Genetics
• Clinical Psychology

Background:

• Conflicting evidence exists regarding the link between schizophrenia diagnostic phenotypes and genetic factors.
• A polydiagnostic approach is needed to clarify the relationship between familial liability and schizophrenia phenotypes.

Purpose of the Study:

• To investigate the relationship between familial liability and various schizophrenia phenotypes using a polydiagnostic approach.
• To assess the predictive validity of familial liability for different diagnostic systems and phenotypic criteria of schizophrenia.

Main Methods:

• Utilized a sample of 660 psychotic probands and 2987 first-degree relatives.
• Assessed probands using 23 schizophrenia diagnostic systems, broadness criteria, subtyping criteria, and clinical features.
• Analyzed familial morbid risk of schizophrenia in relatives using receiver operator characteristic curve analysis and logistic regression.

Main Results:

• Familial liability showed poor predictive performance for most diagnostic criteria of schizophrenia (AUC .55–.61).
• Broader phenotypic criteria demonstrated better prediction than restrictive ones.
• The strongest predictive ability (AUC=.71) was observed for empirically-derived criteria including early onset, absence of mood syndrome, and specific affective/delusional symptoms.

Conclusions:

• Familial liability has limited predictive validity for current diagnostic systems of schizophrenia.
• Broader and empirically-derived phenotypes of schizophrenia are more strongly associated with familial liability than restrictive or subtype-based definitions.