Effects of Treatment on Decision-making in Major Depression
Effects of Treatment on Decision-making in Major Depression
In this trial, fifty participants with current major depressive disorder who are not
 receiving an antidepressant medication and fifty healthy controls will complete
 questionnaires and computerized tasks to assess their decision-making styles. There will be
 three visits for depressed patients and two for healthy controls (the first and third
 visits). The first visit will involve interviews and questionnaires to assess the
 participant's level of depression, medical history and quality of life. Participants will
 then complete the decision-making tasks, and will earn between $5-40 based on their choices,
 in order to make the decisions on the computer tasks financially meaningful. At the
 completion of this visit, depressed patients will be prescribed an FDA-approved
 antidepressant, chosen in consultation with the treating psychiatrist. Patients will be
 responsible for paying for the prescription themselves. After two weeks on the medication,
 the patient will be seen for a follow-up visit to ensure tolerability of the medicine. After
 six weeks on the medicine, patients and healthy controls will return to repeat the
 questionnaires and the computer based decision-making tasks, and will again earn between
 $5-40 based on their performance.
During episodes of depression patients with major depressive disorder (MDD) may make
 sub-optimal decisions based on exaggerated negative beliefs about themselves, the future, or
 the world around them. These disruptions in decision-making contribute adversely to quality
 of life, in both work and personal realms. Although effective treatments for depression are
 available, very little work has explored the effects of treatment on how people make
 decisions. The specific aspects of decision-making that differ between depressed and health
 control individuals are unknown, and whether any changes in these decision-making features
 occur as a result of improvement from depression, or whether medication treatment itself can
 lead to changes in decision-making, even in the absence of clinical improvement.

 In this trial, fifty participants with current major depressive disorder who are not
 receiving an antidepressant medication and fifty healthy controls will complete
 questionnaires and computerized tasks to assess their decision-making styles. There will be
 three visits for depressed patients and two for healthy controls (the first and third
 visits). The first visit will involve interviews and questionnaires to assess the
 participant's level of depression, medical history and quality of life. Participants will
 then complete the decision-making tasks, and will earn between $5-40 based on their choices,
 in order to make the decisions on the computer tasks financially meaningful. At the
 completion of this visit, depressed patients will be prescribed an FDA-approved
 antidepressant, chosen in consultation with the treating psychiatrist. Patients will be
 responsible for paying for the prescription themselves. After two weeks on the medication,
 the patient will be seen for a follow-up visit to ensure tolerability of the medicine. After
 six weeks on the medicine, patients and healthy controls will return to repeat the
 questionnaires and the computer based decision-making tasks, and will again earn between
 $5-40 based on their performance.

 The overall goal of this study will be to identify whether decision-making characteristics in
 people with major depression is affected by treatment, and whether depressed patients make
 decisions differently from healthy controls. A total of 4 decision-making tasks and one
 control task will be administered via computer to eligible subjects. The specific tasks are:

 1. Risk Task - This task assesses tolerance of risk by having participants decide whether
 they wish to accept a specific dollar payout, or to play a lottery with an uncertain
 payout.

 2. Balloon Analogue Risk Task - The participant is presented with a balloon and offered the
 chance to earn money by pumping the balloon up by clicking a button. Each click causes
 the balloon to incrementally inflate and money to be added to a counter up until some
 threshold, at which point the balloon is over inflated and explodes. Thus, each pump
 confers greater risk but also greater potential reward. If the participant chooses to
 cash-out prior to the balloon exploding then they collect the money earned for that
 trial, but if balloon explodes earnings for that trial are lost. Participants are not
 informed about the balloons breakpoints; the absence of this information allows for
 testing both participants' initial responses to the task and changes in responding as
 they gain experience with the task contingencies.

 3. Temporal Discounting Task - Participants are initially asked to choose between taking an
 immediate reward now or a larger reward at some time in the future. Decisions for seven
 time points over a 10-year time frame are proposed. The task is then repeated using
 choices between immediate and delayed losses, based on the same seven time points. This
 task assesses the manner in which subjects value immediate outcomes compared to
 long-term consequences.

 4. Ultimatum Game - The ultimatum game (UG) is a well-established game-theoretical paradigm
 commonly employed in behavioral economics to measure emotional reactions to unfair
 offers. In the UG, two subjects sequentially exchange real monetary amounts.
 Specifically, a proposer is provided with a sum of money by the experimenter ($10), and
 asked to share this amount of money with another player, the responder. The responder
 then decides whether to accept or reject the offer made by the proposer. If the
 responder accepts the offer, both players receive the respective amounts from the
 proposer's offer. If she rejects the offer made by the proposer, both players receive
 nothing ($0). This is best illustrated via the following two potential scenarios: 1. the
 proposer offers a fair split of $5 for himself and $5 for the responder. This is an
 offer that is typically accepted by a great majority of responders. 2. The proposer
 offers a split of $9 for himself and $1 for the responder. Such offers are commonly
 rejected by the majority of responders, despite incurring a financial loss of $1.

 5. Continuous Performance Task - This task involves identifying patterns of numbers briefly
 displayed on a computer screen. This task will serve as a control variable for attention
 in analyzing the results of the decision-making tasks.
Inclusion Criteria for MDD Subjects:

 1. Male or female, age 18-65

 2. Primary Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text
 Revision (DSM-IV TR) Diagnosis of Major Depressive Disorder.

 3. Has a 17-item Hamilton depression rating scale (HDRS-17) score >=16.

 4. Ability to visually read and understand English language

 5. Not currently taking an antidepressant.

 6. Women of reproductive potential must be willing to take a medically approved form of
 birth control throughout the duration of the study.

 Inclusion Criteria for Healthy Control Subjects:

 1. Male or female, age 18-65

 2. No current DSM-IV TR diagnosis of a mental illness.

 3. No lifetime history of Major Depressive Disorder or Dysthymia.

 4. Has a 17-item Hamilton depression rating scale (HDRS-17) score ≤7.

 5. Ability to visually read and understand English language

 6. Not currently taking any psychoactive medication

 Exclusion Criteria for all subjects:

 1. Has met criteria at any time during their life for bipolar disorder, a primary
 psychotic disorder (e.g. schizophrenia), or dementia.

 2. Meet criteria for substance abuse or dependence within three months of the screening
 visit.

 3. Presents with a clinically significant suicide risk, as assessed by a study physician.

 4. Presence of any unstable or central nervous system-related medical illness that would
 interfere with cognition or participation.

 5. Women who are currently pregnant or lactating, or plan to become pregnant during the
 study.