Table 2 Exclusion criteria

 Consent

Unable to give informed consent.

 Safety

Contraindications to MRI, including refusal to be informed of an incidental finding during MRI examination.

 Pregnancy

Pregnant or breastfeeding.

  Lifetime

Any bipolar disorder or psychiatric disorder or psychotic features as determined by the MINI. Anxiety disorders are not strictly excluded unless they are a primary cause of depressive symptoms.

Neurological disorders or neurodegenerative conditions.

Autoimmune disorders or chronic pain.

Clinically significant medical conditions, e.g., seizure disorders, history of cancer.

  Current

Acute risk of suicide as determined by clinician interview, MINI, and MADRS.

Acute infectious pathology or chronic or acute inflammatory diseases.

Significant renal, hepatic, or cardiovascular conditions.

> Stage II antidepressant resistance as defined by Thase and Rush [38].

Not clinically stable for ≥ 4 weeks.

 Medication and drug status

Long-term anti-inflammatory or immunosuppressive therapy.

Use of prescription opioid analgesics, antipsychotics, psychostimulants, and dopamine agonists.

Substance use disorders within the last 12 months.

Current recreational use of opioid-based drugs.

Allergy or intolerance to naltrexone.

Female participants of child-bearing age and not on a medically acceptable form of contraception.

Healthy participants (n= 24)

Any physical or psychiatric illness including major depressive disorder.

Hs-CRP < 1 mg/L.

Females on hormone suppressants.

Current use of any medication except birth control.