• INCLUSION CRITERIA:

The presence of inclusion and exclusion criteria will be established using both unstructured psychiatric interview with a psychiatrist and the Structured Clinical Interview for DSM-IV (SCID; (Williams et al., 1992). Family history of mental illness will be obtained using the Family Interview of Genetic Studies (Maxwell, 1982).

MDD Depressed Sample: Forty-six subjects (ages 18-55) male and female will be selected, with primary MDD currently depressed as defined by DSM-IV criteria for recurrent MDD.

Bipolar Depressed Sample: Forty subjects (ages 18-55) male and female will be selected who meet DSM-IV criteria for bipolar I or II disorder and are currently depressed, with HDRS score in the moderately-to-severely depressed range (greater than 18). Subjects may be inpatients or outpatients. Because effective treatment will not be discontinued for the purposes of this protocol, subjects will be identified who have never been treated or who have discontinued medication due to lack of efficacy, noncompliance, physician order or other reasons prior to study entry.

Healthy, Control Sample: Forty-six subjects (ages 18-55) male and female who have not met criteria for any major psychiatric disorder will be selected. From this large sample a control subject will be matched to each depressed subject for age, gender, handedness and stage of menstrual cycle. The control subjects will have no known first degree relatives with mood disorders.

EXCLUSION CRITERIA:

Subjects must not have taken antidepressant or other medications likely to alter monoamine neurochemistry or cerebrovascular function for at least 3 weeks (8 weeks for fluoxetine and for any drug with known anticholinergic effects) prior to scanning. Because effective medications will not be discontinued for the purposes of this study, subjects will be identified who have never been treated or who have discontinued medication due to lack of efficacy, noncompliance, physician order or other reasons prior to study entry. Subjects will be excluded if they: a) have had serious suicidal ideation or behavior in the previous two months, or b) psychosis, or c) medical or neurological illnesses (i.e. seizure disorder, a coma in past) likely to affect physiology or anatomy, d) a history of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria), e) are HIV positive or have AIDS, f)current pregnancy (documented by history and pregnancy testing prior to scanning), g) current breast feeding, h) general MRI exclusion criteria which include the subject having a pacemaker or significant claustrophobia.