A Multivariate Prediction Model of Schizophrenia

Abstract

Univariate prediction models of schizophrenia may be adequate for hypothesis testing but are narrowly focused and limited in predictive efficacy. Therefore, we used a multivariate design to maximize the prediction of schizophrenia from premorbid measures and to evaluate the relative importance of various predictors. Two hundred twelve Danish subjects with at least one parent diagnosed in the schizophrenia spectrum (high risk) and 99 matched subjects with no such parent (low risk) were assessed on 25 premorbid variables in seven domains (genetic risk, birth factors, autonomic responsiveness, cognitive functioning, rearing environment, personality, and school behavior) when the subjects averaged 15 years of age. Twenty-five years later, 33 subjects had received lifetime diagnoses of schizophrenia. Discriminant function analyses were used to discriminate schizophrenia outcomes from no mental illness and nonschizophrenia outcomes on the basis of premorbid measures. Regardless of the comparison group used, schizophrenia was predicted by the interaction of genetic risk with rearing environment, and disruptive school behavior. Within the high-risk group, two-thirds of schizophrenia outcomes were correctly predicted by these premorbid measures; three-quarters of those with no mental illness were also correctly predicted. Prediction was enhanced among those with two schizophrenia spectrum parents, lending support to a multiplicative gene x environment model. Implications for early identification/primary prevention efforts are discussed.

Generalized and Specific Cognitive Performance in Clinical High-Risk Cohorts: A Review Highlighting Potential Vulnerability Markers for Psychosis

“…Apart from findings on generalized batteries of tests (eg, Wechsler Intelligence Scale for Children [WISC], 36 Rivermead Behavioral Memory Test 37 ), 29,[38][39][40] relatively more specific domains of vulnerability include visuo-motor development, 41,42 perceptual problems, conceptual sorting, language processing, and possibly mental tracking, sustained attention, short-term memory, working memory, and verbal recognition and recall. 38,[43][44][45][46][47][48] These deficits are moderate, 49 and in cross-sectional studies they have been reported to be greater in relatives with a higher genetic loading.…”

Maternal Care and DNA Methylation of a Glutamic Acid Decarboxylase 1 Promoter in Rat Hippocampus

“…Parenting influences endophenotypes that associate with a wide range of psychopathologies (Rapee, 1997;Carter et al, 2002). The challenge is that of establishing a direct relationship between parental care and the development of the neural systems that mediate the relevant cognitive and emotional endophenotypes, as well as identifying candidate mechanisms.…”

Single-subject classification of schizophrenia by event-related potentials during selective attention

“…Much effort has been made to optimize the diagnostic process reflected in the evolution of diagnostic criteria from Bleuler's descriptive psychopathology to current elaborated diagnostic concepts of DSM-IV (American Psychiatric Association, 1994) and ICD-10 (World Health Organization, 1993). It has been suggested repeatedly that the inclusion of laboratory tests might improve diagnostic homogeneity of schizophrenia (Sponheim et al, 2001;Carter et al, 2002). However, reliable and objective biomarkers are missing and clinicians still depend on formal diagnostic criteria and their clinical impression, consequently running the risk to bias objective criteria towards subjective experience.…”