Psychosis and Affective Research Domains and Intermediate Phenotypes

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.

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)