Purpose: Investigating the effects of non-invasive transcranial alternating current stimulation (tACS) on healthy participants and participants with mood disorders.

Participants: 40 males and females, ages 18-65, with depressed mood; 40 healthy males and females, ages 18-65, free of neurological or psychiatric conditions.

Procedures: This is a single visit study with two stimulation conditions (tACS and sham tACS). The session will begin with clinical assessments (including confirmation of diagnosis), followed by an interactive EEG task, then a 7 minute resting state EEG (2 minutes eyes closed, 5 minutes eyes open), followed by the stimulation session (40 minutes of tACS or sham tACS), followed by an additional 5 minute resting state EEG. The stimulation will involved 40 minutes of transcranial alternating current stimulation, 2 mA in amplitude and at individualized alpha frequency (determined by the 2 minutes eyes closed EEG recording; between 8 and 12Hz).

Participants will report for a study visit and will review and sign a consent form.

Participants will complete several clinical assessments and also take a urine drug test and urine pregnancy test (if applicable). Eligibility will be re-assessed by the investigators before the participant moves on to the next phase.

If the participant still qualifies, the participant will first be fitted with two 5x5cm electrodes placed over F3/F4 (10-20 measurement system) and one 5x7cm electrode placed over Cz. In addition, the participant will have a 128-channel EEG net placed on their head. Participants will provide a saliva sample to assess for brain-derived neurotrophic factor (BDNF), which may affect how the participant's brain responds to stimulation. Once the participant is fitted with this equipment, the participant will complete two interactive EEG tasks, then 2-minute resting state EEG with the participant's eyes closed, then a 5-minute resting state EEG with the participant's eyes open.

Following these recordings, participants will respond to additional questionnaires. Immediately following this, the participant will receive 40 minutes of stimulation (tACS or sham tACS). During this stimulation, participants will sit comfortably upright and awake.

After stimulation has completed, participants will respond to additional questionnaires. Once completed, participants will then complete an additional 5-minute resting state EEG with the participant's eyes open, as well as complete one of the additional interactive EEG tasks.

Finally, participants will respond to a blinding questionnaire to assess if the participant thought that the participant received stimulation. Once complete, the participant will leave. This session is estimated to last about 4 hours.

Inclusion Criteria for individuals with depressed mood:

• Ages 18-65 years
• Hamilton Depression Rating Scale score >8
• Capacity to understand all relevant risks and potential benefits of the study (informed consent)
• Low suicide risk which will be determined through the use of both the Structured Clinical Interview for the DSM-5 and by scoring less than 3 (0,1, or 2) in the Hamilton rating depression scale.
• Negative pregnancy test for female participants

Exclusion Criteria for individuals with depressed mood:

• DSM-5 diagnosis of alcohol of substance abuse (other than nicotine) within the 12 months
• DSM-5 diagnosis of alcohol or substance dependence (other than nicotine) within the last 12 months
• DSM-5 diagnosis of personality disorder
• Eating disorder (current or within the past 3 months)
• Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study
• Neurological disorders, including but not limited to history of seizures (except childhood febrile seizures and electro-convulsive therapy (ECT) induced seizures), dementia, history of stroke, Parkinson's disease, multiple sclerosis, cerebral aneurysm.
• Medical or neurological illness (unstable cardiac disease, AIDS, malignancy, liver or renal impairment) or treatment for a medical disorder that could interfere with study participation
• History of traumatic brain injury, reoccurring seizures or later cognitive rehabilitation or causing cognitive sequelae
• History of childhood trauma (determined by the Childhood Trauma Questionnaire)
• Prior brain surgery
• Any brain devices/implants, including cochlear implants and aneurysm clips
• Co-morbid neurological condition (i.e. seizure disorder, brain tumor)
• Use of illicit drugs, confirmed by a drug test
• Non English speakers
• Pregnant or nursing females
• Current use of benzodiazepines or anti-epileptic drugs

Inclusion Criteria for healthy controls:

• Ages 18-65 years
• Hamilton Depression Rating Scale score ≤8
• Capacity to understand all relevant risks and potential benefits of the study (informed consent)
• Negative pregnancy test for female participants

Exclusion Criteria for healthy controls:

• History of major neurological or psychiatric illness, including epilepsy
• Medication use associated with neurological or psychiatric illnesses
• Currently undergoing counseling or psychotherapy treatment for depression, anxiety, eating disorders, PTSD or other behavioral conditions
• DSM-5 diagnosis of personality disorder
• First degree relative (parent, sibling, child) with major neurological or psychiatric illness
• Prior brain surgery
• Major head injury
• Any brain devices/implants (including cochlear implants and aneurysm clips)
• History of childhood trauma (determined by the Childhood Trauma Questionnaire)
• Use of illicit drugs, confirmed by a drug test
• Braids or other hair styling that prevents direct access to the scalp (if removal not possible)
• Skin allergies or very sensitive skin
• Non English speakers
• Pregnant or nursing females

One healthy control participant that received sham stimulation was excluded from analysis as we were unable to find an age and sex matched participant. One healthy control participant that received sham stimulation did not complete the study due to technical difficulties.

Adverse events were collected over the 5 hours of the single session experiment

This is a double-blind study, meaning that neither the participant nor the experimenter knows what kind of stimulation the participant is receiving. An unblinded monitor (separate from the staff that interacts with the participant) is responsible for creating the stimulation codes that run each session and for ensuring that these codes worked correctly.