Psychosis and Affective Research Domains and Intermediate Phenotypes (PARDIP)

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.

Study Overview

• Status: Completed
• Conditions: Bipolar I Disorder, Unspecified, With Psychotic Features; Bipolar I Disorder, Unspecified, Without Psychotic Features

Detailed Description

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 (Actual): 113

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

The study population will be comprised of individuals between the ages of 18-60 years old who meet DSM-IV criteria for Bipolar I disorder, read/speak/understand the English language, and are deemed capable of completing the study procedures by the research investigators.

Description

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)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Bipolar I disorder, with psychosis; Individuals diagnosed with Bipolar I disorder, with psychotic features
Bipolar I disorder, without psychosis; Individuals diagnosed with Bipolar I disorder, without psychotic features
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Differences in those with Bipolar disorder with psychosis, without psychosis, and healthy controls on functional and structural brain imaging, neurocognitive assessments, and neurophysiological tests	One day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	One day

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in those with Bipolar disorder with psychosis, without psychosis, and healthy controls in DNA and dermal biopsy sampling	The investigators will collect DNA from all proband and relative subjects and collaboratively sequence the genetic material to associate genes with specific biomarkers and composite Biotype definitions. We will also collect plasma and cellular specimens to bank for analysis of additional molecular biomarkers unique to each Biotype.	One day

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Institute of Mental Health (NIMH); Beth Israel Deaconess Medical Center; University of Georgia; Hartford Hospital
• Investigators: Principal Investigator: Carol A Tamminga, M.D., UT Southwestern Medical Center

Publications and helpful links

Helpful Links

• Tamminga Lab and Clinic Website

Study record dates

Study Major Dates

• Study Start: April 1, 2014
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: August 11, 2014
• First Submitted That Met QC Criteria: August 14, 2014
• First Posted (Estimate): August 18, 2014

Study Record Updates

• Last Update Posted (Actual): September 19, 2019
• Last Update Submitted That Met QC Criteria: September 18, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Schizophrenia; Psychosis; Bipolar disorder
• Additional Relevant MeSH Terms: Pathologic Processes; Schizophrenia Spectrum and Other Psychotic Disorders; Disease; Psychotic Disorders; Mental Disorders
• Other Study ID Numbers: MH077851; 1R01MH096913-01A1 (U.S. NIH Grant/Contract)