Testing a Transdiagnostic TMS Treatment Target

Eligibility Criteria

• * Age 18-65
• * English proficiency sufficient for informed consent, questionnaires/tasks, and treatment
• * Diagnosis of MDD per DSM-5 criteria (Quick Structured Clinical Interview for DSM-5 Disorders) and currently experiencing a moderate to severe episode:
• * \>20 on Beck Depression Inventory (BDI)
• * \>20 on the Montgomery-Åsberg Depression Rating Scale (MADRS) 14, 15
• * Moderate to severe level of treatment resistance (Maudsley Staging Method)16, 17
• * Diagnosis of at least one or more of the following psychiatric conditions per DSM-5 criteria (Quick Structured Clinical Interview for DSM-5 Disorders):
• * Generalized anxiety disorder (GAD), panic disorder (PD), or social anxiety disorder (SAD)
• * Obsessive compulsive disorder (OCD)
• * Post-traumatic stress disorder (PTSD)
• * Physician referral for individuals with either schizophrenia or schizoaffective disorder
• * Stable psychiatric medication regimen, or remain medication free, for 4 weeks prior to treatment and to remain on this regimen throughout the study until the two-week post-treatment visit
• * Primary clinician (e.g. psychiatrist, therapist, psychologist, APRN, PA, etc.) responsible for psychiatric care before, during, and after the trial
• * Agreement to lifestyle considerations
• * Abstain from becoming pregnant from time of screening to two weeks after treatment (post-treatment MRI visit)
• * Continue usual intake patterns of caffeine- or xanthine-containing products (e.g. coffee, tea, soft drinks, chocolate) throughout treatment
• * Abstain from alcohol, tobacco, and recreational drugs for at least 24 hours before the start of each MRI and each TMS session
• * Active pregnancy as determined by a urine pregnancy test
• * Positive urine drug screen for illicit substances (not including THC)
• * Depressive symptoms refractory to 8 sessions of electroconvulsive therapy (ECT)
• * Recent (within 4 weeks) or concurrent use of rapid acting antidepressant agent (ketamine/esketamine/ECT)
• * Receiving or planning to receive other TMS treatments during course of participation
• * History of
• * Autism spectrum disorder
• * Neurosurgical intervention for depression
• * Intellectual disability
• * Severe cognitive impairment
• * Significant neurological illness (e.g., dementia, Parkinson's, Huntington's, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, brain lesion)
• * Untreated or insufficiently treated endocrine disorder
• * Treatment with investigational drug or intervention during the study period
• * Depth-adjusted TMS treatment dose \> 65% maximum stimulator output
• * Existing tinnitus (ringing in the ears)
• * Current evidence of:
• * Mania or hypomania
• * Active suicidal ideation or a suicide attempt (defined by C-SSRS) within the past year
• * Neurological lesion
• * Contraindications to either TMS or MRI (e.g., metallic implants, severe insomnia \> 4 hours per night with hypnotic, etc.).
• * Moderate or severe substance use disorder or demonstrating signs of acute substance withdrawal (not including cannabis or nicotine use disorders)
• * Bipolar I disorder
• * For participants with schizophrenia or schizoaffective disorder referred by a physician:
• * Total PANSS score \>90
• * Score \>4 (moderate-severe) on any positive PANSS item
• * Active substance use disorder (other than nicotine)
• * Hospitalization for psychosis in the past 6 months
• * Severe borderline personality disorder
• * Any other condition deemed by the PI to interfere with the study or increase risk to the participant