Bipolar Proteomic Assay Validation Study
Bipolar Proteomic Assay Validation Study
The purpose of this study is to validate a set of signatures, based on a panel of proteomic
 markers, that discriminate BDI, BDII, and MDD in people seeking treatment for a depressive
 episode.
This is a hypothesis-driven confirmatory study to validate the diagnostic signature (model)
 for distinguishing BDI from MDD that also aims to optimize the models to discriminate BDII
 from MDD and BDI. A binary classification model, using linear discriminant analysis and based
 on 13 a priori-defined proteomic markers will aim to distinguish BDI from MDD. An alternative
 binary classification model based on multiple logistic regression and using 10 a priori
 -defined proteomic markers will aim for the same result. To improve the predictive
 performance of the signatures, items from self-report mood rating scales and
 treatment-emergent changes in proteomic markers will be analyzed. In addition, the study will
 examine if baseline or early treatment-emergent changes in proteomic markers predict
 treatment response.
Inclusion Criteria:

 -  Diagnosed with BDI, BDII, or MDD, confirmed with the Structured Clinical Interview for
 DSM-5 (SCID).

 -  Currently depressed for ≥4 weeks and ≤104 weeks, without psychotic features,

 -  MADRS score ≥ 20 (consistent with at least moderately-severe depression)

 -  YMRS score ≤ 8 (consistent with the absence of hypomanic symptoms)

 Exclusion Criteria:

 -  At high risk for suicide, defined as a score ≥4 on item 10 of the MADRS

 -  Current depression has psychotic features, diagnosed with the SCID

 -  Meeting criteria for severe alcohol, cannabis, or THC use disorders, as defined by
 DSM-5 and confirmed by the SCID, in the past 3 months, or meeting criteria for other
 substance use disorders of any severity (eg. cocaine use disorder). For substances
 other than alcohol, cannabis, and opioids, a positive drug screen at both the
 screening and baseline visits is also exclusionary. Caffeine and nicotine use
 disorders of any severity will not be exclusionary.

 -  Diagnosis of borderline personality disorder, diagnosed with the Zanarini Rating Scale
 for Borderline Personality Disorder.

 -  Medical conditions with neurological sequelae (eg. stroke, brain cancer, multiple
 sclerosis, loss of consciousness > 30 min, HIV)

 -  Severe chronic pain, at the discretion of the investigator

 -  Receiving treatment with high-potency immune-modulating medications, such as
 corticosteroids, chemotherapy, monoclonal antibodies, or disease-modifying agents for
 arthritis, multiple sclerosis

 -  Any acute unstable medical illness (at the discretion of the site investigator)

 -  In MDD patients: strong risk factors for bipolarity, including 1) short (1-3 day) mood
 elevations not meeting DSM-5 time criteria for hypomania; 2) a family history of BDI
 or BDII in a first-degree relative; and 3) a history of antidepressant-induced
 symptoms suggestive of bipolarity, particularly antidepressant-induced hypo/mania.