Year: 2017
Type: conference-abstract
Abstract: Background: Conventional diagnoses arguably have not been successful at organizing psychiatric conditions into disease constructs with clear pathophysiology and etiology. Moreover, research has shown that conventional diagnoses are poorly characterized, if at all, by discrete functional brain biomarkers or biomarker composites. Methods: The Bipolar and Schizophrenia Network for Intermediate Phenotypes (BSNIP) recruited a large group of probands with psychotic conditions, their family members, and healthy controls (N > 2300) to carry out deep phenotyping across 5 sites in the United States. Results: In the BSNIP1 study, none of the biomarkers sampled (>50 distinct endophenotypes) fell discretely onto any of the phenomenologically defined conventional diagnoses. Alternatively, using the endophenotypes to create homogeneous, neurobiologically distinct proband groups resulted in units we called Biotypes, each with distinctive neurobiological characteristics, which tempted further biological formulations. The analyses of additional biomarkers garnered support for biomarker-based classification (potentially the Biotype formulation) for psychosis research. The probands show nearly the same levels of psychosis across the three Biotypes (1–3), while profoundly high negative symptoms are clustered in Biotype 1. Biotypes 1 and 2 differ in basal EEG power, with B-1 showing low and B-2 showing high basal EEG characteristics. The lifetime rates of Axis I and II psychosis in relatives distinguishes the Biotype groups (highest in B-I, lowest in B-3) as does the frequency of adolescent cannabis use (highest in B-3). Biotype was a significant predictor of gray matter change in the psychosis group, while conventional diagnosis was not based on step-wise regression analysis. Relatives of the Biotypes show the same, but less extreme, pattern of deviations on each of the biomarkers and on the biomarker composites as do the probands, indicating familiality. Conclusion: These early analyses of disease group characteristics based on endophenotypes lead us to suggest “proof-of-principal” demonstration of the value of neurobiologically based endophenotype groups, groups with indicate Irv Gottesman’s generativity in psychosis research. Whether or not these endophenotype-defined groups lead to genes, to distinct molecular markers and onto distinct treatments, will be a definitive test of their usefulness.
Source: Schizophrenia Bulletin
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2603956126