The Impact of Working Memory and Reward Markers on DLPFC Activity in Treatment-resistant Depression

Prior treatment

• Drug abuse or dependence within the last 6 months, excluding caffeine and nicotine.
• Contraindication to receiving the rTMS (e.g. history of seizure, cochlear implants, benzodiazepine use (lorazepam or equivalent daily dose \>2mg daily), cardiac pacemaker, implanted neurostimulator, significant head trauma with loss of consciousness for greater than or equal to 5 minutes).
• Electroconvulsive therapy (ECT) within the current depressive episode.
• Presence of contraindications for MRI, including metallic implants.

Other illness

• A MINI-confirmed diagnosis of bipolar disorder, or another comorbidity (e.g., obsessive-compulsive disorder, post-traumatic stress disorder) that is primary in severity and disability relative to their MDD.
• Other major medical comorbidities requiring immediate investigation or treatment, cardiac pacemaker, or implanted medication pump.
• Lifetime history of psychosis, including schizophrenia, schizoaffective disorder, delusional disorder, or current psychotic symptoms.
• Have any significant neurological disorder or insult including, but not limited to: any condition likely to be associated with increased intracranial pressure, space occupying brain lesion, any history of seizure except those therapeutically induced by ECT, cerebral aneurysm, Parkinson's disease, Huntington's chorea, multiple sclerosis, dementia, significant head trauma with loss of consciousness for greater than or equal to 5 minutes.

Other

• All Participants:
• Are pregnant/lactating.
• Acute suicidality, defined as a score \>3 on the 17-item Hamilton Depression Rating Scale, Item #3.

• Depressed Participants:
• Between the ages of 18 and 65 years old.
• Capable of giving voluntary and informed consent.
• Fluent in English.
• Meet Diagnostic and Statistical Manual criteria for single or recurrent Major Depressive Disorder (current major depressive episode), confirmed via the Mini-International Neuropsychiatric Interview (MINI).
• Moderate to severe depression severity, defined as a 17-item Hamilton Depression Rating Scale260 score ≥ 18.
• Have failed to achieve a clinical response to an adequate dose of an antidepressant based in an Antidepressant Treatment History Form (ATHF) score ≥ 3 in the current episode, or have been unable to tolerate at least 2 separate trials of antidepressants of inadequate dose and duration (AHTF = 1 or 2)
• Have had no initiation or dose change in any psychotropic medication in the four weeks prior to screening.
• If participating in psychotherapy, must have been in stable treatment for at least 3 months prior to entry into the study, with no anticipation of change in the frequency of therapeutic sessions, or the therapeutic focus over the duration of the study.
• Can adhere to the study schedule.
  • Nondepressed Participants:
• Between the ages of 18 and 65 years old.
• Capable of giving voluntary and informed consent.
• Fluent in English.
• No current or previous history of psychiatric diagnoses.
• Absent/non-clinical depression severity, defined as a 17-item Hamilton Depression Rating Scale260 \< 8.
• No history of antidepressant use, as measured by the ATHF.