Psychosis and Affective Research Domains and Intermediate Phenotypes

Study ID

Cancer Related

Healthy Volunteers

Study Sites

  • UT Southwestern-Other
  • Dallas Veteran's Affairs Medical Center

Asha Philip

Principal Investigator
Carol Tamminga, M.D.

Official Title

Psychosis and Affective Research Domains and Intermediate Phenotypes

Brief 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.

Participant Eligibility

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

- 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)