Brain Imaging Study in Menopausal Women With and Without Major Depressive Disorder
Condition: Menopause; Depression
MeSH terms: Depression; Depressive Disorder
Intervention: MDD diagnosis and Estrogen treatment; MDD diagnosis and Fluoxetine treatment; MDD diagnosis with both Estrogen and Fluoxetine treatment; No depression and estrogen treatment
Intervention description: Treatment for major depressive disorder occurring in the context of the menopause while participating in brain imaging sessions pre and post treatment. Women receiving treatment for depression will be compared to normal controls receiving estrogen only for physical symptoms of menopause.; Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with fluoxetine alone.; Menopausal women between the ages of 40-70 diagnosed with Major Depressive Disorder receiving treatment with estrogen and fluoxetine combined.; Control participants with no MDD diagnosis received estrogen only for the treatment of physical symptoms of menopause.
Intervention MeSH terms: Fluoxetine; Estrogens
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: Female
Minimum age: 40 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: menopause; women; major depressive disorder; Magnetic Resonance Spectroscopy

Summary:

      The purpose this study is to measure cortical gama-aminobutyric acid levels (GABA) levels in
      menopausal women with major depressive disorder and healthy subjects using nuclear magnetic
      resonance spectroscopy (MRS). Measurements will be compared in 1) menopausal healthy subjects
      before and after estrogen replacement, and after fourteen days of medroxyprogesterone
      administration; and 2) in depressed menopausal subjects before and after treatment of their
      depression with antidepressant alone, estrogen alone or antidepressant plus estrogen.
      Cortical GABA levels will be correlated with plasma GABA and neurosteroid levels.
      Neurosteroids to be measured include progesterone, allopregnanolone, pregnenolone, and
      pregnenolone sulfate.
    

Eligibility criteria:

        Inclusion criteria for Depressed Patients:

          -  Aged 40-70 years and able to give voluntary written informed consent.

          -  Meet DSM-IV criteria for major depression based on a structured clinical interview
             (SCID).

          -  Have no medical contraindication to estrogen. (This will include written documentation
             of a recent normal gynecological evaluation and mammogram).

          -  A minimum score of 25 on the 25-item Hamilton Depression Rating Scale on initial
             baseline rating which does not show improvement during the one-week observation
             period.

          -  Perimenopausal subjects will be those who have had irregular menses of either <21 days
             or >35 days for the previous six months to one year. Postmenopausal subjects will be
             those with no menstrual cycles and no hormone therapy for at least one year and serum
             FSH >45.

        Exclusion criteria:

          -  Meeting DSM-IV for any other Axis I disorder.

          -  A history of serious medical or neurological illness, including (but not limited to)
             major cardiovascular disease, severe hypertension, intracranial mass lesions, seizure
             disorder, severe hepatic or renal disease, unstable endocrine or metabolic disease,
             and unstable hematologic disease.

          -  A history of moderate to severe endometriosis; milder cases will require subject's
             Gynecologists permission to participate.

          -  Use of anticonvulsants or benzodiazepines within the last month.

          -  Use of psychotropic medication in last week (except as stated above).

          -  Use of alcohol within last month.

          -  Current pregnancy (for the perimenopausal subjects).

          -  Positive urine drug screen.

          -  Metallic implants.

        Inclusion Criteria for Healthy Subjects:

          -  No DSM-IV psychiatric or substance abuse diagnosis by structured diagnostic interview
             (SCID).

          -  No medical contraindication to estrogen (this will include written documentation of a
             recent normal gynecological exam with mammogram).

          -  Matched to depressed patients by age and menopausal status.

          -  Have no menstrual cycles or hormone therapy for at least one year or irregular menses
             of either <21 days or 35 days for the previous six months to one year.

        Exclusion Criteria for Healthy Subjects:

          -  Medical, neurologic or cerebrovascular disorder (CVA, seizure disorder, etc.).

          -  Evidence of substance use on urine toxicology screen done upon recruitment.

          -  Current treatment with psychoactive medication.

          -  Diabetes controlled by means other than diet.

          -  Use of alcohol within last month.

          -  Implanted metallic devices.

          -  Positive urine drug screen.