Psychosis and Affective Research Domains and Intermediate Phenotypes

University of Texas Southwestern Medical Center113 enrolled

Overview

The objective of this multi-site research collaboration is to test the manifestation and distribution of biological markers for psychosis and affect dimensions across the schizophrenia/bipolar (SZ-BD) diagnostic boundary, and to examine heritability and genetic associations for these biological markers.

The B-SNIP research consortium previously obtained dense phenotypes across the psychosis spectrum in an effort to observe features both (i) distinctive to and (ii) shared between DSM-type categorical diagnoses. Despite the broad range of extra-clinical phenotypes, we had limited success finding clinical SZ-BD diagnosis-specific features; instead, most phenotypes were distributed continuously across DSM diagnoses. To describe more biologically homogeneous groups, therefore, we combined all psychosis probands and implemented a multi-stage analysis procedure, beginning with identification of psychosis biomarkers (variables with the largest effect sizes for differentiating psychosis and healthy groups) including cognitive, electrophysiological, and oculo-motor measures ('classical' endophenotypes). We then estimated the number of subgroups that efficiently optimized variance among the biomarkers (n=3) and differentiated the individual psychosis cases into these subgroups. Subsequently, the subgroups were tested for biological uniqueness using meaningful external validators (structural and functional brain imaging, social functioning, and familial data). Given the neurobiological distinctiveness of these subgroups, we called them psychosis Biotypes. DSM diagnoses were distributed across all Biotypes. Compared to DSM diagnoses, Biotype membership enhanced group separations on biomarkers. These results indicate that groups of psychosis cases can be generated with homogeneous phenotypic characteristics independent of DSM diagnoses. The proposed study aims to further develop Biotype definitions and demonstrate that psychosis Biotypes constructed from a dense biomarker panel (i) are replicable, (ii) neurobiologically distinctive, and (iii) have unique genetic characteristics.

Study Type

OBSERVATIONAL

Enrollment

113

Conditions

Bipolar I Disorder, Unspecified, With Psychotic Features Bipolar I Disorder, Unspecified, Without Psychotic Features

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Must provide consent to participate after being fully informed about the study procedures and the information to be collected * Males and females * Ages 18-60 years old * All races and ethnicities * Probands: Must meet DSM-IV criteria for bipolar I disorder with or without lifetime history of psychosis; Healthy Controls: Must have no personal history of any psychotic or mood disorder, or a family history of psychotic or recurrent mood disorder among their first-degree relatives * Must be judged to be capable of completing the study procedures by study investigators * Must be able to read, speak, and understand English Exclusion Criteria: * An estimated IQ\<70 * Major neurological or cognitive disorder (e.g., seizure disorder, traumatic brain injury, cerebrovascular disease, pervasive developmental disorder) * Serious medical, neuro-ophthalmological, or neurological illness that could affect CNS functioning (e.g., decompensated cardiovascular disease, decompensated chronic obstructive pulmonary disease, late stages of diabetes, AIDS) * DSM-IV diagnosis of alcohol or illicit substance abuse within 1 month, or alcohol or substance dependence within 3 months, or extensive history of past substance use * Women who are pregnant (due to unknown risks related to MRI exposure) * Presence of medical (e.g., artificial joints, brain aneurism clips, surgical pins, rods, wires, implants) or non-medical (e.g., metal piercing) irremovable metallic objects on/inside body (due to MRI-relevant risks)

Locations (1)

UT Southwestern Medical Center

Dallas, Texas, United States

Outcomes

Primary Outcomes

Differences in those with Bipolar disorder with psychosis, without psychosis, and healthy controls on functional and structural brain imaging, neurocognitive assessments, and neurophysiological tests

Time frame: One day

Secondary Outcomes

Differences in those with Bipolar disorder with psychosis, without psychosis, and healthy controls on clinical assessment questionnaires

The investigators will assess clustering of probands and relatives across composite biomarkers independent of diagnostic status using multivariate taxometric procedures.

Time frame: One day

Data from ClinicalTrials.gov

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