Understanding how the orbitofrontal cortex guides approach vs. avoidance in depression

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

Researchers will examine neural signals from depth electrodes implanted in the orbitofrontal cortex while participants perform an approach-avoidance decision task. The study compares individuals with major depressive disorder to non-depressed controls to see if medial OFC activity favors approach and lateral OFC activity favors avoidance, and whether depression shifts these signals. It leverages inpatient sEEG monitoring to directly measure brain activity during decision making related to potential rewards and losses. The findings aim to clarify brain mechanisms that contribute to reduced motivation in depression.

Why it matters

Who can join: the full rules

Inclusion Criteria:

All participants:

* 18 years of age or older
* Implanted with stereo-EEG (sEEG) depth electrodes, including at least one electrode in the orbitofrontal cortex (OFC)
* Able to read, write, and provide informed consent

Depressed cohort:

* Enrolled in the PRESIDIO trial (NCT04004169) of deep brain stimulation for treatment-resistant depression and undergoing inpatient sEEG monitoring as part of that trial
* Meets DSM-5 criteria for major depressive disorder (single episode of at least 2 years' duration, or recurrent), without psychotic features, confirmed by structured clinical interview (e.g., MINI)

Control (non-depressed) cohort:

* Undergoing inpatient sEEG monitoring for a clinical indication other than depression (e.g., seizure localization in refractory epilepsy)
* No current diagnosis of major depressive disorder, confirmed by clinical psychiatric evaluation (e.g., MINI and symptom scales)

Exclusion Criteria:

All participants:

* Current or past DSM-5 diagnosis of a psychotic disorder or major depressive disorder with psychotic features
* Current or past DSM-5 diagnosis of bipolar or related disorder
* Current obsessive-compulsive disorder
* Intellectual disability
* Autism spectrum disorder
* Borderline, antisocial, histrionic, or narcissistic personality disorder
* Impaired decision-making capacity or cognitive deficits that preclude informed consent or task completion
* Employee of the investigator or study site with direct involvement in the study, or family member of the investigator

Control (non-depressed) cohort only:

\* Epileptiform abnormalities involving the OFC, OFC dysplasia, or prior OFC resection, as determined by clinical evaluation and imaging

Where it's running

• UCSF
  San Francisco, California, United States Recruiting

Study contacts

• Principal investigator: Andrew Krystal, MD — University of California, San Francisco
• Study coordinator: Clara K Starkweather, MD, PhD
• Email: clara.starkweather@ucsf.edu
• Phone: 706-330-0885

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.