This study evaluates the efficacy of sleep deprivation treatment in accelerating antidepressant responses when administered during the first week of medications and augmenting a sustained response with chronobiological interventions. Sleep deprivation and chronobiological augmentation may offer a rapid and sustained antidepressant response in mood disorder patients treated with medication, sleep deprivation, bright light therapy and sleep phase advance compared with medication only. The chronobiological treatment is rapid, non-invasive and has few side effects and could be of significant clinical benefit.

Inclusion Criteria:

Inclusion criteria include:

1. Subjects must be English speaking
2. Subjects must have either bipolar or unipolar depression diagnosis or be a normal control.
3. Subjects must be between : 18 to 75

Non-English speaking subjects will be excluded since scales for measuring depression have not been validated in languages other than English.

Exclusion Criteria:

Exclusion criteria include:

1. Suicidality, or psychosis
2. Unstable medical conditions
3. Epilepsy, serious head injury, or other significant neurological disorders
4. Dementia, mental retardation (moderate or severe), coma
5. Prior exposure to radiation which might cause the subject to exceed standard guidelines
6. Substance abuse or alcoholism in the past six months
7. Unreliability or inability to adhere to the requirements of the study
8. Irregular sleep-wake schedules (nightshift, jet lag)
9. Use of CNS medications which may affect sleep or functional brain imaging (i.e., use of sleeping pills, antidepressants or other mood stabilizers or other medications which may affect the sleep EEG)
10. Sleep apnea, periodic limb movements of sleep, narcolepsy, circadian sleep phase disorders
11. Donation or loss of blood (>400 ml) within the past month
12. Current or very recent intercurrent illnesses, painful conditions or other disorders, which in the judgement of the investigators, might invalidate the scientific goals of the study or pose undesirable difficulties or risks for the subject.
13. Hamilton Rating Scale of Depression (HRSD-17 items)<17 unless subject is a normal control subject.
14. Pregnancy or breast feeding
15. Individuals who would be unable to undergo a magnetic resonance imaging (MRI) scan, for example, individuals who suffer from claustrophobia, or who have metal clips in their body.
16. Unable to cease taking psychoactive medications which are not part of this protocol (2-5 weeks) prior to PET scans.
17. Patients with previous history of significant adverse reactions to sertraline or sertraline-like drugs or other SSRI's such as Paxil or Prozac
18. Subjects with diagnosis of eating disorder/bulimia