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The Experimental Therapeutics and Pathophysiology Branch (ETPB)

The overarching goals of the current (ETPB) are: (1) to provide administrative support for our Section (SNMD); (2) to maintain a common screening program for the Division of Intramural Research Program (DIRP) studies on mood and anxiety disorders; and (3) to support clinical and research training. The Screening Program (01-M-0254) provides oversight, training, and quality control of administration of a range of structured diagnostic and dimensional measures of psychopathology. Aside from extensive clinical measures, the major data components that are centralized in the program include: (1) CTDB-Clinical trials database; (2) BioBNK that contains a diverse set of biologic measures; and (3) MAP-R (Mood and Anxiety Disorders Repository protocol) of neuroimaging data. The clinical measures collected include comprehensive diagnostic interviews including history of suicide attempts and ideation, stress/trauma, sleep problems, temperament, psychosis, medical conditions, as well as dimensional measures of the core features of mood and related disorders including positive and negative affect, arousal/regulatory systems and cognitive function.

Section on the Neurobiology and Treatment of Mood Disorders (SNMD)

The major goal of the SNMD is to conduct therapeutic studies on treatment-resistant depression, with a more recent extension to patients with suicidal ideation and behavior. The major focus of our clinical research is treatment-resistant depression.

SNMD is housed in the Mood Disorders Research Unit, 7SE north of the NIH Clinical Center, a state-of-the art facility which currently has 12 inpatient beds designated for patients with mood disorders of which Dr. Zarate is the Unit Chief. Clinical staffing includes a 24 hour, 365 day on-call psychiatrist, experienced nurse clinicians, etc. Our ability to study patients for long periods of time, over nights and weekends in both the drug free as well as post-treatment states provides a unique opportunity for comprehensive evaluation that would not be possible in the extramural world.

The program attempts to identify reasons for and ameliorate the high failure rate in recent pharmacologic trials of mood disorders including patient heterogeneity, inadequate diagnostic and response biomarkers, incorrect dose range, high placebo response rates, inadequate trial designs, patient and investigator expectation biases, lack of target engagement, and a host of operational issues. By avoiding many of these situations, we can improve the feasibility and acceptability by advancing early proof-of-concept clinical trials designs that can be subsequently translated to our extramural partners for larger effectiveness and efficacy studies.

In addition to collaborative efforts designed to cover the full range of biologic pathways underlying mood disorders, we have focused our research on treatment-resistant depression in two major research areas: (1) neuroimaging; and (2) biomarkers of mood disorders and treatment response. The NIMH DIRP Cores have also provided an ideal source of expertise in our neuroimaging studies. Our research has also benefited enormously from both the NIH Clinical Center facilities and the DIRP CORE facilities (e.g., sMRI, fMRI, PET, PSG, MEG, MRS, etc).