Microbiome of Depression & Treatment Response to Citalopram

The study will be conducted at Mayo Clinic Jacksonville Department of Psychiatry (recruit up
to 10 patients and 10 controls with paired data) and Mayo Clinic Depression Center in
Rochester (recruit up to 30 patients and 30 controls with paired data). Patients with major
depression, Bipolar Disorder I or Bipolar Disorder II confirmed by structured diagnostic
interview (SCID) and moderate symptom severity (Quick Inventory of Depressive Symptomatology
or S-C16) will be enrolled in the 12 week study. We will explore the gut microbiome (and its
genetic material) and gut-brain markers of inflammation (cortisol, cytokines) from stool
specimens and serum samples, respectively. Collections will be at baseline, week 2, and week
12 of the study. Healthy controls matched for age, sex (including menopausal status of female
subjects), and body-mass index (BMI) will have only baseline stool and serum collections.
Statistical t-tests will be used to assess baseline differences between patient and controls
in microbiome and inflammatory markers. Treatment response (50% reduction in QIDS), treatment
remission (QIDS-C16 < 6) will be analyzed with change in microbiome and inflammation markers.
Correlational analysis with multiple testing corrections will be conducted between depression
symptom severity and measures of cortisol, cytokines, and gut microbiome composition.

This study will focus on early translation of Dr. Fryer and Dr. Chia's research and will
bring the gut-brain interface to the field of individualizing treatment to patients who
struggle with depression. This project will provide insight into how gut microbiota may be
implicated in depression, how antidepressant treatments alter microbiota composition, and how
these factors impact key physiologic mediators of depression (i.e. cortisol and cytokine
levels). The public health implications of more focused drug development and treatment for
depression are substantial.

Inclusion Criteria:

- Outpatients or inpatients with nonpsychotic major depressive disorder (MDD) or Bipolar
I or II Disorder.

- A score of >16 on the QIDS

- Outpatients or inpatients for whom antidepressant treatment is deemed appropriate by
the treating clinician

- Subjects who are between 18-55 years of age

Exclusion Criteria:

- Contraindications to citalopram treatment

- Axis I or II disorder other than depression that is the primary reason for seeking
treatment intervention and/or psychiatric care

- Subjects diagnosed with Borderline Personality Disorder (BPD) as their primary
diagnosis.

- For healthy controls, a first degree relative who has been diagnosed with an Axis I
disorder

- Patients with schizophrenia, schizoaffective disorder, or bipolar I disorder

- Antidepressant treatment within 4 days of study (1 week if fluoxetine). Subjects
currently on antidepressant medication with subtherapeutic results in terms of
depression management after providing informed consent, will undergo a medication
taper and discontinuation prior to initiation of citalopram treatment. The subject
must be off of previous antidepressants for at least 4 days week prior to starting
citalopram (1 week if fluoxetine). The subject will be closely monitored by the
research study psychiatrist (with or without additional monitoring from primary
clinical psychiatric providers). The medication taper is left up to the research study
psychiatrist in consultation with patient's primary care or psychiatric provider.
Study subjects who cannot be safely tapered from their medication or experience
adverse effects during the taper will be excluded from the study

- Study subjects using their antidepressant medication for management of nicotine
dependence, chronic pain, migraine prophylaxis, or other diagnoses will not be
eligible for the study unless they remain on a stable dose of the medication for the
12 weeks of the study.

- Trazodone, melatonin, and diphenhydramine may be used as rescue medications for
insomnia. Benzodiazepines may be used for treatment of anxiety, not to exceed 4 mg/24
hour of lorazepam

- Subjects who are currently on an antibiotic or an antibiotic within 2 weeks. (Topical
antibiotics are OK)

- Daily use of aspirin, NSAID's or Warfarin (low dose of baby aspirin OK)

- Subjects unable to give informed consent are excluded

- Pregnant subjects will be excluded

- Subjects who are currently breastfeeding and who plan to continue breastfeeding will
be excluded

- Postmenopausal women are not eligible for this study