Magnetic Resonance Spectroscopy (MRS) in Midlife Depression

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-Research Version (SCID-V-RV) and at least one of the following:

- Greater than 6/9 SCID-V-RV criteria at threshold level for current major
depressive episode

- 17-item Hamilton Rating Scale for Depression (HAMD) score ≧18

- 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)

Specifice Inclusion Criteria for Controls:

- Criteria for major depression not met per the SCID-V-RV

- HAMD scores ≦7

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-RV

- SCID-V-RV 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-RV threshold of severity for > 4/11 criteria for substance abuse disorder

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

- SCID-V-RV 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-RV 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

- S/p 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