Lifetime history of Bipolar Disorder, Dementia, Autism Spectrum Disorder, Schizophrenia, or any other Psychotic Disorder.
Psychotic symptoms occurring at any time during the current major depressive episode.
Current (past 12 months) diagnosis of Panic disorder, Obsessive Compulsive Disorder, Posttraumatic Stress Disorder, Anorexia Nervosa, or Bulimia Nervosa.
Alcohol or Drug Dependence within 12 months or Abuse within 3 months (excluding nicotine and caffeine) of baseline visit, as assessed by history and urine drug screen.
Clinical evidence of a severe Personality Disorder, as assessed by the study psychiatrist, which would impede participation or completion of the trial.
Known neurological disorders or documented serious head injury.
Serious and unstable medical illnesses including cardiovascular disease and cancer.
Active medical conditions with known mood changes (endocrine, autoimmune disorders).
Current diabetes mellitus.
For women, pregnancy, lactation, or unwillingness to comply with birth control requirements.
Use of any of the following treatments or any other alternative therapy within 2 weeks of the pre-treatment PET scan that may have beneficial effects on mood, including St John's Wort, S-adenosyl methionine (SAMe), n-3 fatty acids, or light therapy.
Use of antidepressant medication within 1 month of the pre-treatment PET scan (within 5 weeks for fluoxetine and protryptyline).
Failure to achieve a much improved status (i.e. equivalent to >50% symptom reduction) with any lifetime treatment course of CBT (defined as a minimum of 4 sessions of a specified manual-driven therapy by a CBT-trained therapist) or escitalopram (defined as a minimum of 6 weeks of at least 10 mg/day).
Clinically significant active suicidal ideation or self-injurious behavior necessitating immediate treatment, as determined by the investigator.
Received electroconvulsive therapy in the past 6 months or during the current depressive episode.
Currently responding to medication treatment, without clinical reasons to change.
Current treatment with weekly individual or group psychotherapy of any type targeted at depressive symptoms.
QTc >500 milliseconds on EKG at screening.
Contraindications for MRI, including, but not limited to pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, intra-uterine devices for birth control.
Maintenance or prophylactic therapy for stable medical conditions.
Hypnotic medication prescribed or approved by the study physician, (up to a three doses per week) for insomnia, as long if not the night before a PET/MRI or clinic ratings visit. Antipsychotic medications, whether prescribed for sleep or other indications, are prohibited.

NCT02137369_exc_T1
Condition
Bipolar Disorder
NCT02137369_exc_T2
Condition
Dementia
NCT02137369_exc_T3
Condition
Autism Spectrum Disorder
NCT02137369_exc_T4
Condition
Schizophrenia
NCT02137369_exc_T5
Condition
Psychotic Disorder
NCT02137369_exc_T6
Condition
Psychotic symptoms
NCT02137369_exc_T7
Condition
major depressive episode
NCT02137369_exc_T8
Condition
Panic disorder
NCT02137369_exc_T9
Condition
Obsessive Compulsive Disorder
NCT02137369_exc_T10
Condition
Posttraumatic Stress Disorder
NCT02137369_exc_T11
Condition
Anorexia Nervosa
NCT02137369_exc_T12
Condition
Bulimia Nervosa
NCT02137369_exc_T13
Condition
Drug Dependence
NCT02137369_exc_T14
Condition
ohol or endence wi
NCT02137369_exc_T15
Temporal
past 12 months
NCT02137369_exc_T16
Scope
Panic disorder, Obsessive Compulsive Disorder, Posttraumatic Stress Disorder, Anorexia Nervosa, or Bulimia Nervosa
NCT02137369_exc_T17
Temporal
within 12 months
NCT02137369_exc_T18
Condition
ohol or se wi
NCT02137369_exc_T19
Condition
g De se wi
NCT02137369_exc_T20
Temporal
within 3 months
NCT02137369_exc_T21
Drug
nicotine
NCT02137369_exc_T22
Drug
caffeine
NCT02137369_exc_T23
Measurement
urine drug screen
NCT02137369_exc_T24
Scope
nicotine and caffeine
NCT02137369_exc_T25
Qualifier
severe
NCT02137369_exc_T26
Condition
Personality Disorder
NCT02137369_exc_T27
Condition
head injury
NCT02137369_exc_T28
Qualifier
serious
NCT02137369_exc_T29
Condition
neurological disorders
NCT02137369_exc_T30
Condition
medical illnesses
NCT02137369_exc_T31
Qualifier
Serious
NCT02137369_exc_T32
Qualifier
unstable
NCT02137369_exc_T33
Scope
Serious and unstable
NCT02137369_exc_T34
Condition
cardiovascular disease
NCT02137369_exc_T35
Condition
cancer
NCT02137369_exc_T36
Scope
cardiovascular disease and cancer
NCT02137369_exc_T38
Condition
ne, autoi rs).
Curr
NCT02137369_exc_T39
Condition
autoimmune disorders
NCT02137369_exc_T40
Condition
diabetes mellitus
NCT02137369_exc_T42
Procedure
treatments
NCT02137369_exc_T43
Procedure
alternative therapy
NCT02137369_exc_T44
Temporal
within 2 weeks of the pre-treatment PET scan
NCT02137369_exc_T45
Reference_point
pre-treatment PET scan
NCT02137369_exc_T46
Scope
treatments or any other alternative therapy
NCT02137369_exc_T47
Condition
mood
NCT02137369_exc_T48
Drug
St John's Wort
NCT02137369_exc_T49
Drug
S-adenosyl methionine
NCT02137369_exc_T50
Drug
SAMe
NCT02137369_exc_T51
Drug
n-3 fatty acids
NCT02137369_exc_T52
Procedure
light therapy
NCT02137369_exc_T53
Scope
St John's Wort, S-adenosyl methionine (SAMe), n-3 fatty acids, or light therapy
NCT02137369_exc_T54
Drug
antidepressant medication
NCT02137369_exc_T55
Temporal
within 1 month of the pre-treatment PET scan
NCT02137369_exc_T56
Reference_point
pre-treatment PET scan
NCT02137369_exc_T57
Temporal
within 5 weeks for fluoxetine and protryptyline
NCT02137369_exc_T58
Reference_point
fluoxetine and protryptyline
NCT02137369_exc_T60
Condition
suicidal ideation
NCT02137369_exc_T61
Condition
self-injurious behavior
NCT02137369_exc_T62
Procedure
treatment
NCT02137369_exc_T63
Qualifier
immediate
NCT02137369_exc_T64
Scope
active suicidal ideation or self-injurious behavior
NCT02137369_exc_T66
Procedure
psychotherapy
NCT02137369_exc_T67
Qualifier
group
NCT02137369_exc_T68
Qualifier
individual
NCT02137369_exc_T69
Scope
individual or group
NCT02137369_exc_T70
Multiplier
weekly
NCT02137369_exc_T71
Condition
depressive symptoms
NCT02137369_exc_T72
Measurement
QTc
NCT02137369_exc_T73
Value
>500 milliseconds
NCT02137369_exc_T74
Temporal
at screening
NCT02137369_exc_T75
Reference_point
screening
NCT02137369_exc_T76
Procedure
EKG
NCT02137369_exc_T77
Condition
Contraindications
NCT02137369_exc_T78
Procedure
MRI
NCT02137369_exc_T79
Negation
not
NCT02137369_exc_T80
Device
pacemaker
NCT02137369_exc_T81
Device
aneurysm clips
NCT02137369_exc_T82
Device
neurostimulators
NCT02137369_exc_T83
Device
cochlear implants
NCT02137369_exc_T84
Device
metal
NCT02137369_exc_T85
Qualifier
eyes
NCT02137369_exc_T86
Device
steel worker
NCT02137369_exc_T87
Device
intra-uterine devices
NCT02137369_exc_T88
Scope
pacemaker, aneurysm clips, neurostimulators, cochlear implants, metal in eyes, steel worker, intra-uterine devices
NCT02137369_exc_T90
Drug
Hypnotic medication
NCT02137369_exc_T91
Condition
insomnia
NCT02137369_exc_T92
Temporal
the night before a PET/MRI or clinic ratings visit.
NCT02137369_exc_T93
Reference_point
PET/MRI
NCT02137369_exc_T94
Reference_point
clinic ratings visit.
NCT02137369_exc_T95
Scope
PET/MRI or clinic ratings visit.
NCT02137369_exc_T96
Negation
not
NCT02137369_exc_T97
Drug
Antipsychotic medications
NCT02137369_exc_T98
Temporal
at any time during the current major depressive episode
NCT02137369_exc_T99
Reference_point
the current major depressive episode
NCT02137369_exc_T100
Temporal
current
NCT02137369_exc_T101
Procedure
electroconvulsive therapy
NCT02137369_exc_T102
Temporal
in the past 6 months
NCT02137369_exc_T103
Temporal
during the current depressive episode
NCT02137369_exc_T104
Reference_point
the current depressive episode
NCT02137369_exc_T105
Temporal
current
NCT02137369_exc_T106
Condition
depressive episode
NCT02137369_exc_T107
Procedure
PET scan
NCT02137369_exc_T108
Drug
fluoxetine
NCT02137369_exc_T109
Drug
protryptyline
NCT02137369_exc_T110
Temporal
pre-treatment
NCT02137369_exc_T111
Scope
in the past 6 months or during the current depressive episode
NCT02137369_exc_T112
Qualifier
active