Heritability estimates for psychotic symptom dimensions in twins with psychotic disorders

Abstract

Factor analysis of psychotic symptoms frequently results in positive, negative, and disorganized dimensions, but heritability estimates have not yet been reported. Symptom dimensions are usually only measured in individuals with psychotic disorders. Here, it is valuable to assess influences acting via liability to psychosis and independent modifying effects. We estimated heritability for psychotic symptom dimensions, taking account of these issues. Two-hundred-and-twenty-four probandwise twin pairs (106 monozygotic, 118 same-sex dizygotic), where probands had psychoses, were ascertained from the Maudsley Twin Register in London (1948-1993). Lifetime history of DSM-III-R psychotic disorder and psychotic symptom dimensions was assessed from clinical records and research interviews and rated using the Operational Criteria Checklist. Estimates of heritability and environmental components of variance in liability were made with structural equation modeling using a causal-contingent common pathway model adapted for ascertainment from a clinical register. Significant heritability was found for DSM-III-R psychotic disorder (h² = 90%, 95%CI 68-94%) and the disorganized symptom dimension (h² = 84%, 95%CI 18-93%). The heritability for the disorganized dimension remained significant when influences acting through liability to psychosis were set to zero, suggesting that some influences on disorganization are modifying factors independent of psychosis liability. However, the relative extent of modifying factors versus influences acting through psychosis liability could not be clearly determined. To our knowledge, this study provides the first formal evidence of substantive heritability for the disorganized symptom dimension, and suggests that genetic loci influencing disorganization in individuals with psychoses are in some cases different from loci that influence risk of psychotic disorders themselves.

Is disorganization a feature of schizophrenia or a modifying influence: Evidence of covariation of perceptual and cognitive organization in a non-patient sample

“…Our interpretations complement those of recent studies demonstrating that clinical disorganization is highly heritable (Loftus et al, 1998; Rietkerk et al, 2008; McGrath et al, 2009), but independent of psychosis (Paulus et al, 2001; Rijsdijk et al, 2011). Furthermore, work by Debanné and colleagues (2013) suggests that schizotypic disorganization, though largely independent of positive schizotypy, directly influences the expression of positive schizotypic symptoms.…”

“…For example: 1) cognitive disorganization is related to perceptual impairments in people without schizophrenia who have high levels of schizotypy (Cappe et al, 2012); 2) while both highly heritable, disorganization and psychosis have been shown to sort independently, suggesting different genetic origins (Rijsdijk et al, 2011); 3) disorganization traits are persistent across illness duration regardless of state (Paulus et al, 2001); and 4) trait-related allusive thinking, a mild form of thought disorder, occurs in the general population and is associated with reduced auditory mismatch negativity amplitude, suggesting that disorganized thinking is related to poorer pre-attentive processing, of which reduced PO is also a manifestation (Ward et al, 1992; McConaghy et al, 1993). …”

The Impact of Copy Number Deletions on General Cognitive Ability and Ventricle Size in Patients with Schizophrenia and Healthy Control Subjects

“…This was the only symptom scale significantly related to either deletion burden or ventricle size. A recent report based on the Maudsley Twin Register found that “the heritability for the disorganized dimension remained significant when influences acting through liability to psychosis were set to zero, suggesting that some influences on disorganization are modifying factors independent of psychosis liability” (p.89) [47]. Deletion burden may function as just this kind of modifying factor.…”

Genetics of Schizophrenia and other Psychotic Disorders

“…Among the psychotic symptom dimensions, the evidence is currently strongest for the disorganized dimension as having a substantial genetic contribution. It consistently shows significant familial aggregation in pairs of affected siblings or other relatives [72] and has an estimated heritability of 84% (95% CI 18-93%) [73].…”