The purpose of this study is to determine the impact of inflammation on central nervous system (CNS) glutamate, white matter pathology and alterations in behavior and cognition in middle-aged patients with major depression. Depression is associated with significant alterations in glutamate concentrations and white matter integrity, which has been associated with decreased antidepressant response, poor functional outcome, and cognitive impairment.

This study involves behavioral assessments, neurocognitive testing, blood sampling and magnetic resonance imaging (MRI) scanning. Goals of this study are to determine the impact of inflammation on glutamate concentrations in the basal ganglia and on the integrity of white matter tracts in the basal ganglia and other subcortical regions of middle-aged depressed versus non-depressed individuals and to associated the impact of glutamate and white matter changes on behavioral symptoms among the same group of patients.

Inclusion Criteria for Participants with Depression:

• Willing and able to give written informed consent

• Meet criteria for Major Depression per DSM-V criteria using Structured Clinical Interview for DSM-V (SCID-V) and a score ≧18 on the 17-item Hamilton Rating Scale for Depression (HAMD).

• Absence of significant suicidal ideation, determined by the Columbia Suicide Severity Rating Scale - Screen Version (CSSRS)

• Meets MRI scanning safety requirements:

  • Absence of embedded MR-unsafe metallic objects
  • Location and quantity of MR-safe metallic objects will minimally impact rigor/reproducibility standards of the MR data (as determined by the PI in consultation with the neuroimaging team)

Specific Inclusion Criteria for Controls:

• Criteria for major depression not met per the SCID-V
• HAMD scores ≦7
• Absence of any Axis I pathology

Exclusion Criteria:

• Unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease as evidenced by any of the following:

  • Clinically significant abnormalities in lab values, medical history and physical exam as determined by PI or their designee
  • Changes in medications prescribed for chronic medical illnesses within past 4 weeks,
  • Hospitalization or drastic medical changes within past 4 weeks

• Cognitive impairment as defined by:

  • Score of < 28 on Mini-mental exam (MMSE)
  • Below 8th grade reading ability as defined by Wide Range Achievement Test-3 (WRAT3) score

• Presence of psychosis (lifetime) / mania (current) as defined by:

  • Lifetime diagnosis of psychotic disorders SCID-V
  • SCID-V criteria for current mania/hypomania within the current episode

• Clinically significant substance abuse within the past 6 months as defined by meeting the SCID-V threshold of severity for > 4/11 criteria for substance abuse disorder

• Presence of active symptoms of an eating disorder as defined by:

  • SCID-V diagnosis of Anorexia or bulimia nervosa.
  • Binge eating and/or purging behavior in the absence of mood alterations or precipitating stress (bingeing within the current episode of mood symptoms will not be exclusionary)

• Presence of significant psychiatric comorbidities during current episode:

  • Primary diagnosis of anxiety-spectrum disorders (panic, generalized anxiety, social phobia etc.), PTSD, OCD based on SCID-V criteria
  • Severity of above diagnoses exceeds that of major depression based on assessments by the PI and the Study Team members

• Severe Axis II personality pathology as determined by a clinician

• Use of immune-active medications:

  • Continuous use of prescribed, standard dose non-steroidal anti-inflammatory (NSAIDs) excluding 81 mg of aspirin within past 1 week and PRN use of NSAIDs within past 72 hours
  • Intake of antibiotics within the past 2 weeks
  • Immunization (including seasonal flu) within the past 2 weeks
  • Use of topical or inhaled steroids within 72 hours unless otherwise approved by PI
  • Use of systemic steroids (oral or parenteral) within past 6 months
  • Patients taking herbal supplements with currently known effects on immune system including omega-3 supplements within 2 weeks or probiotics prior to research blood draws and scan unless approved by PI.

• Use of psychotropics:

  • Daily intake of standard doses of antidepressants, mood stabilizers, antipsychotics, psychostimulants within 2 weeks (8 weeks for fluoxetine) prior to initiation of study procedures (scan and research blood sampling)
  • Daily/clinically significant use of sedative-hypnotics and tranquilizers and opiates as determined by PI
  • PRN use of sedative/hypnotics, benzodiazepines exceeding equivalent of clonazepam 1mg within 48 hours of study visit.

• Cancer and autoimmunity:

  • Life time history of diagnosis and/or treatment of cancers other than basal cell carcinoma
  • Life time history of diagnosis and/or treatment of autoimmune disorders including but not restricted to multiple sclerosis, inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, and Hashimoto's thyroiditis

Male and female patients who have a diagnosis of depression or bipolar depression and men and women without a diagnosis of depression or bipolar depression in the control group