Processes and Circuitry Underlying Threat Sensitivity as a Treatment Target for Co-morbid Anxiety and Depression

Who can take part

• All subjects:
• Female or male sex assigned at birth
• Age 18-65
• Normal or corrected to normal vision/hearing, as protocol elements may not be valid otherwise
• Fluent English speaker, capable of providing written informed consent; MDD and AD-MDD subjects:
• Current major depressive episode assessed by clinician with guidance from the MINI
• Minimum score of 55 on PROMIS Depression scale; AD and AD-MDD subjects:
• Current anxiety disorder (generalized anxiety disorder, panic disorder, agoraphobia and social phobia) assessed by clinician with guidance from the MINI
• Minimum score of 55 on PROMIS Anxiety Scale

Who cannot take part

• Current use of medications with major effects on brain function or the fMRI hemodynamic response (e.g., methylphenidate, acetazolamide, excessive caffeine intake > 1000 mg/day) following an initial list compiled by LIBR but also assessed on a case-by-case basis. Individuals who are currently on medication (antidepressants such as SSRIs, TCAs, SNRIs, and Bupropion) and who have not undergone dose or medication changes over the past 6 weeks will be allowed to participate
• Drug or alcohol intoxication (based on positive UTOX or breathalyzer test at screening or study session) or reported alcohol/drug withdrawal, last cannabis use must be >48 hours prior to study session
• Has a risk of suicide according to the Investigator's clinical judgement or per Columbia-Suicide Severity Rating Scale (C-SSRS) or equivalent PhenX instrument, the subject scores "yes" on items 4 or 5 in the Suicidal Ideation section with referent to a 30-day period prior to Screening/Baseline or the subject has had one or more suicidal attempts with reference to a 2-year period prior to Screening
• Has uncontrolled, clinically significant neurologic (including seizure disorders): cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, immunologic, endocrine disease, or psychiatric disorder, or other abnormality, which may impact the ability of the subject to participate or potentially confound the study results
• History of moderate or severe traumatic brain injury, as assessed by a TBI questionnaire
• History of eating disorder or obsessive-compulsive disorder, schizophrenia, schizo-affective disorder, bipolar disorder or any sign of psychosis
• Current post-traumatic stress disorder (PTSD) diagnosis (although history of trauma is allowed)
• Moderate to severe current substance use disorder, defined as 5 or more symptoms of the criteria for Substance Use Disorder according to DSM 5
• Current (assessed by clinician with guidance from the MINI) anxiety disorder
• All subjects:
• Reported body mass index (BMI) > 40
• Current benzodiazepine or opiate use
• MRI contraindications
• Is pregnant or lactating or intending to become pregnant before, during, or within 12 weeks after participating in this study; or intending to donate ova during this time-period
• Any subject judged by the Investigator to be inappropriate for the study; MDD subjects:
• Score of > 60 on PROMIS Anxiety Scale; AD subjects:
• Current or past recurrent major depressive episodes assessed by clinician with guidance from the MINI
• Score of > 60 on PROMIS Depression scale

Other criteria

• An individual must meet the following criteria to be considered eligible to participate in the study: