ABSTRACT
BACKGROUND: In schizophrenia research, 'high risk' traditionally referred to studies of the offspring of schizophrenic parents at genetically enhanced risk of illness development. Sixteen major high-risk studies have been undertaken although only six followed through to formal illness so data on prediction remain weak. Recently, 'high risk' has widened to encompass individuals considered 'at risk' by having 'high risk mental states', regardless of family history, in whom initiation of early treatment is postulated to improve outcome. METHOD: The major familial high-risk studies are reviewed from the perspective of the Edinburgh High Risk Study of Schizophrenia (EHRS), with emphasis on prediction. RESULTS: Familial high-risk studies have established multiple biological markers, the most reproducible of which relate to neuromotor development and cognition, especially aspects of memory/learning. Although most are probably not specific, they support a neurodevelopmental hypothesis. Family and environmental variables point largely to secondary or indirect associations. Pre-illness, non-specific affective symptomatology may be of greater predictive power than most psychotic phenomena. CONCLUSIONS: Traditional high-risk designs embody many problems but are able to distinguish non-specific markers from illness predictors, and are ideally suited to exploring the evolution of schizophrenia both clinically and biologically (especially with imaging techniques). The EHRS supports the view that greater specificity may accrue to cognitive domains as precursors of predictive utility.
Subject(s)
Cognition Disorders/genetics , Schizophrenia/epidemiology , Schizophrenia/genetics , Schizophrenic Psychology , Schizotypal Personality Disorder/epidemiology , Schizotypal Personality Disorder/genetics , Adolescent , Adult , Brain Damage, Chronic/diagnosis , Brain Damage, Chronic/epidemiology , Brain Damage, Chronic/genetics , Brain Damage, Chronic/psychology , Child , Child, Preschool , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Cognition Disorders/psychology , Cross-Sectional Studies , Developmental Disabilities/diagnosis , Developmental Disabilities/epidemiology , Developmental Disabilities/genetics , Developmental Disabilities/psychology , Early Diagnosis , Genetic Predisposition to Disease/genetics , Humans , Infant , Middle Aged , Risk Factors , Schizophrenia/diagnosis , Schizotypal Personality Disorder/diagnosis , Schizotypal Personality Disorder/psychology , Scotland , Social EnvironmentABSTRACT
BACKGROUND: Despite interest in early treatment of schizophrenia, premorbid and prodromal symptomatology remain poorly delineated. AIMS: To compare pre-illness symptomatology in patients at high risk of schizophrenia who progress to illness with that of high-risk subjects who remain well and with normal controls. METHOD: Using Present State Examination (PSE) data, symptomatic scales were devised from participants of the Northwick Park Study of first-episode schizophrenia and scores were compared on the first and last PSEs of participants of the Edinburgh High Risk Study. RESULTS: At entry, when still well, high-risk individuals who subsequently became ill (mean time to diagnosis 929 days; s.e.=138 days) scored significantly higher on'situational anxiety', 'nervous tension', 'depression', 'changed perception'and 'hallucinations'than those remaining well and normal controls, who did not differ. With illness onset, affective symptomatology remained high but essentially stable. CONCLUSIONS: In genetically predisposed individuals, affective and perceptual disorders are prominent before any behavioural or subjective change that usually characterises the shift to schizophrenic prodrome or active illness.
