Differentiating Unipolar and Bipolar Depression in Young Adults Using fMRI
Condition: Bipolar Disorder; Major Depression
MeSH terms: Depression; Depressive Disorder; Bipolar Disorder
Intervention: Selective Serotonin Reuptake Inhibitor (SSRI)
Intervention description: Subjects with depression will be treated with a Selective Serotonin Reuptake Inhibitor (SSRI) or a Serotonin-norepinephrine reuptake inhibitor (SNRI) for 24 months.
Intervention MeSH terms: Norepinephrine; Serotonin; Selective Serotonin Reuptake Inhibitors
Phase: Phase 4
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 192.0
Sex: All
Minimum age: 15 Years
Maximum age: 30 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bipolar; Depression; Mania; Hypomania; fMRI; antidepressant

Summary:

      The purpose of the study is to find out what parts of the brain have increased or decreased
      activity and connectivity in individuals who have bipolar disorder, major depression, or no
      history of mood disorder. Another purpose of this study is to use MRI images to determine
      which young adults with major depression may be at greater risk for developing mild or more
      severe symptoms of mania which suggests a diagnosis of bipolar disorder.
    

Eligibility criteria:

        INCLUSION CRITERIA FOR BIPOLAR DEPRESSED PATIENTS:

          1. Ages 15 - 30 years (inclusive) and able to give voluntary informed consent (parents
             must also sign consent for subjects under 18)

          2. Satisfy criteria for Diagnostic and Statistical Manual 4th edition (DSM-IV-TR) for
             Bipolar I or II disorder

          3. Satisfy criteria for DSM-IV depressive episode-current

          4. 17-item Hamilton Depression Rating Scale > 15 but < 25;

          5. Young Mania Rating Scale score < 10

          6. Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire.

          7. Able to be managed as outpatients during the study as ascertained by the following -
             i. Clinical Global Severity Scale < 5 i.e. moderately ill; ii. No significant suicidal
             or homicidal ideation or grossly disabled.

        INCLUSION CRITERIA FOR ALL UNIPOLAR DEPRESSED PATIENTS:

          1. Ages 15 - 30 years and able to give voluntary informed consent (Parental consent must
             also be obtained for those under 18 years old).

          2. Satisfy criteria for DSM-IV-TR Major Depressive Episode using a Structured Interview

          3. Never met criteria for mania or hypomania

          4. 17-item Hamilton Depression Rating Scale score (HDRS) > 15 and < 25.

          5. Young Mania Rating Scale (YMRS) score < 10

          6. Satisfy safety criteria to undergo an MRI scan

          7. Able to be managed as outpatients during the study as ascertained by the following -
             i. Clinical Global Severity Scale < 5 i.e. moderately ill; ii. No significant suicidal
             or homicidal ideation or grossly disabled

        ADDITIONAL INCLUSION CRITERIA FOR HIGH RISK UD (HRUD) PATIENTS BESIDE THE INCLUSION
        CRITERIA FOR UD:

        At least one of the following:

          1. Family history of bipolar disorder in at least one first degree relative

          2. History of any sub-threshold hypomania symptoms

          3. History of mood episode related psychotic symptoms

        ADDITIONAL INCLUSION CRITERIA FOR LOW RISK UD (HRUD) PATIENTS BESIDE THE INCLUSION CRITERIA
        FOR UD:

          1. No family history of BD in a first or a second degree relative

          2. No past history of any sub-threshold hypomania symptoms

          3. No history of psychotic symptoms

        EXCLUSION CRITERIA FOR DEPRESSION AND BIPOLAR SUBJECTS:

          1. Meeting DSM-IV criteria for schizophrenia, schizophreniform disorder, schizoaffective
             disorder, mental retardation, pervasive developmental disorder.

          2. History of receiving electroconvulsive therapy in the past 1 year

          3. Use of neuroleptics, mood stabilizers or benzodiazepines in the past 2 weeks.

          4. Use of antidepressants in the past 2 weeks.

          5. If on fluoxetine in the past, then should not have been on this medication for 5
             weeks.

          6. Acutely suicidal or homicidal or requiring inpatient treatment.

          7. Meeting DSM-IV criteria for other substance/alcohol dependence within the past 6
             months or abuse in the past 3 months, excluding caffeine or nicotine. The criteria
             will be evaluated by interview and urinary toxicology screening. The use of caffeine
             or nicotine will be recorded.

          8. Use of alcohol in the past 1 week before the MRI scan.

          9. No serious acute or chronic medical or neurological illness, including previously
             known HIV positive status (due to possible CNS involvement) as assessed by history,
             physical examination and laboratory examination including EKG, CBC and blood
             chemistry.

         10. Current pregnancy or breast feeding.

         11. Metallic implants or other contraindication to MRI.

        INCLUSION CRITERIA FOR HEALTHY CONTROLS: Healthy subjects matched for age, gender and
        ethnicity will be included

          1. Ages 15 - 30 years (inclusive) and able to give voluntary informed consent (Parental
             consent must also be obtained for those under 18 years old)

          2. No current or past history of psychiatric illness or substance abuse or dependence.

          3. No current or past history of psychiatric illness or substance abuse or dependence in
             a first degree relative.

        EXCLUSION CRITERIA FOR HEALTHY CONTROLS:

          1. Pregnant or breast feeding.

          2. Metallic implants or other contraindication to MRI.

          3. Significant family history of psychiatric or neurological illness.

          4. Currently taking any prescription or centrally acting medications.

          5. Serious acute or chronic medical or neurological illness as assessed by history,
             physical examination and laboratory examination including CBC and blood chemistry.

          6. Use of alcohol in the past 1 week and not being able to avoid alcohol use during the
             course of the study.