Predictors of Antidepressant Response

% BOLD signal changes in the nucleus accumbens from the Inactive to the Active Placebo condition.

Time frame: (90 minute fMRI scans) assessed at Weeks 1 and 2

Population: Data was missing in 11 subjects due to movement artifacts, or incidental findings that made the data not usable.

Binding Potential = Bmax/Kd (receptor concentration/affinity). This is the most common measure of in vivo receptor binding with positron emission tomography. Whole brain changes in mu-opioid receptors binding potential during PET from the Inactive to the Active placebo condition. Positive numbers presented here represent reductions in binding potential from the inactive to the active condition.

Time frame: (90 minute PET scans) assessed at Weeks 1 and 2

Population: Data in four subjects was missing due to failure in the synthesis of the radio tracer for at least one of the two scans.

The Patient Health Questionnaire-9, is a multipurpose instrument for screening, diagnosing, monitoring and measuring the severity of depression, based on participant answers. PHQ-9 scores of 5, 10, 15, and 20 represents mild, moderate, moderately severe and severe depression, respectively. The minimum possible score is 0 and the maximum possible score is 27. The PHQ-9 and QIDS were used to assess changes in mood during the placebo intervention (first 2 weeks), and therefore results are described as changes from the inactive to the active condition.

Time frame: From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)

Population: Changes in PHQ-9 score from the beginning of the active/inactive placebo and the end of active/inactive PET scan.~Approximately 1-2 weeks between the two conditions.

This scale is a self-report measure of depression with 16 items. Questions in the QIDS - SR-116 correlate with the nine DSM-IV symptom criterion domains, Including: Sleep disturbance (initial, middle, and late insomnia or hypersomnia) (Q 1 - 4), Sad mood (Q 5), Decrease/increase in appetite/weight (Q 6 - 9), Concentration (Q 10), Self-criticism (Q 11), Suicidal ideation (Q 12), Interest (Q 13), Energy/fatigue (Q 14), Psychomotor agitation/retardation (Q 15 - 16). Severity of depression can be judged based on the total score: 1-5= No depression; 6-10= Mild depression; 11-15= Moderate depression; 16-20= Severe depression; 21-27= Very severe depression. The PHQ-9 and QIDS were used to assess changes in mood during the placebo intervention (first 2 weeks), and therefore results are described as changes from the inactive to the active condition.

Time frame: From Pre to post- active placebo, and from pre to post- inactive placebo (1 week intervention)

Population: Changes in QIDS-16SR from screening active/inactive placebo condition to the post scan active/inactive placebo condition.~Approximately 1-2 weeks between the two conditions.

Binding Potential= Bmax/Kd (receptor concentration/affinity). This is the most common measure of in vivo receptor binding with PET. Striatal changes in D2/3 receptor binding potential during PET from the Inactive to the Active condition. Positive numbers presented here represented reductions in binding potential from the inactive to the active condition.

Time frame: (90 minute PET scan) assessed at Weeks 1 and 2

Population: Data was only collected in 26 subjects as proposed.

The total score is obtained by summing the score of each item, 0-4 (symptom is absent, mild, moderate, or severe) or 0-2 (absent, slight or trivial, clearly present). For the 17-item version, scores can range from 0 to 54, with 0 meaning no depression, and 54, severe depression. The Hamilton Depression Rating Scale was used to assess symptoms during the open label antidepressant treatment phase, so results are described as mean scores at each bi-weekly visit.

Time frame: Screening, week 0, week 2, week 4, week 8 and week 10

Designed in 1979 by researchers as an adjunct to the Hamilton Rating Scale for Depression (HAMD) which would be more sensitive to the changes brought on by antidepressants and other forms of treatment than the Hamilton Scale. MADRS was used to assess symptoms during the open label antidepressant treatment phase, so results are described as mean scores at each bi-weekly visit. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 where 0 is no depression and 60 is most extreme depression. The questionnaire includes questions on the following symptoms 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts Usual cutoff points are: 0 to 6 - normal\[5\] /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression \>34 - severe depression

Time frame: Screening, week 0, week 2, week 4, week 8 and week 10