Advances in Psychiatry

Researchers from the Institute of Geriatric Psychiatry at NewYork-Presbyterian/Weill Cornell Medicine recently published findings in the Journal of Affective Disorders from a pilot study looking at the response of the brain’s positive valence systems (PVS) to two forms of reward-focused psychotherapy for treating late-life depression. The study, which is one of the first to look at the neural mechanisms of reward-focused interventions for major depression in older adults, found that emotional engagement with rewarding stimuli may be a dynamic marker of depressive state, whereas an absent initial response to rewards may constitute a vulnerability factor for late-life depression.

Dr. Jennifer Bress

“Positive valence systems are the systems in the brain that are responsible for either anticipating or responding to or learning from stimuli that are rewarding in some way,” says Jennifer Bress, Ph.D., the study’s lead author and a clinical psychologist at NewYork-Presbyterian/Weill Cornell Medicine. “Rewarding can mean a lot of different things to different people and these systems can respond broadly, but it can be things like winning money or seeing a pleasant picture or getting positive social feedback.”

Like many other changes that occur as someone ages, PVS also decline. “There are changes in the behavioral responses that people have to things that are rewarding,” says Dr. Bress. “The volume of certain areas of the brain that are involved in reward processing get smaller and don’t respond as strongly to certain reward cues, which leads to people responding less efficiently to things that are rewarding.”

Dr. Bress and the other study authors – including Faith Gunning, Ph.D., a clinical neuropsychologist, vice chair of research in the Department of Psychiatry, and director of the Institute of Geriatric Psychiatry at NewYork-Presbyterian/Weill Cornell Medicine, and George Alexopoulos, MD, professor emeritus of psychiatry at NewYork-Presbyterian/Weill Cornell Medicine – investigated changes in event-related potential (ERP) measures of PVS function during psychotherapy designed to treat depression by increasing rewarding experiences. Specifically, the researchers examined two ERPs, the late positive potential (LPP) and the reward positivity (RewP), which become attenuated in those with depression. The LPP is elicited by exposure to rewarding images and is associated with sustained attention to emotional content. The RewP is elicited by feedback indicating rewarding outcomes and remains blunted after depression remits.

Use of reward-focused psychotherapy

The study included 18 adults ≥ 60 with major depressive disorder (with a Montgomery-Åsberg Depression Rating Scale score ≥ 20) who were either off anti-depressants or on a stable dose for >12 weeks. Criteria for study exclusion included psychosis, a Mini Mental Health State Exam score <24, suicidal ideations, psychiatric comorbidity other than generalized anxiety disorder, and use of additional psychotropic medications or cholinesterase inhibitors, other than a low dose of a benzodiazepine. The Hamilton Rating Scale for Depression (HAM-D) was used to assess depression severity.

The study’s participants were randomized to receive nine weeks of a reward-focused psychotherapy – either Problem-Solving Therapy (PST) or Engage therapy – with a master’s level mental health clinician. Both PST and Engage therapy increase the likelihood of a reward, or something positive, happening. “The idea behind this study was that, even though we had two different therapies, they were both likely to change or activate these reward systems by presenting positive experiences,” says Dr. Bress.

Engage therapy, which was originally developed by Dr. Alexopoulos and his colleagues, is a type of psychotherapy for late-life depression that is informed by neurobiological constructs and principles of behavioral activation. It helps patients identify meaningful or rewarding activities and structure a personalized plan to complete them. Engage also involves motivational strategies if needed to help encourage individuals to engage in the rewarding activities. PST is designed to help people identify a problem they would like to solve and figure out, step-by-step, different possible solutions, rate the different possible solutions, figure out which one will be the best solution to the problem at hand, and develop a plan to solve it. For this study, data from patients receiving Engage and PST were analyzed together.

The study, which is one of the first to look at the neural mechanisms of reward-focused interventions for major depression in older adults, found that emotional engagement with rewarding stimuli may be a dynamic marker of depressive state, whereas an absent initial response to rewards may constitute a vulnerability factor for late-life depression.

Eliciting and measuring LPP and RewP

Passive picture-viewing was used to elicit the LPP. Thirty neutral and 30 positive images were presented randomly over two blocks; neutral images included natural and man-made objects, outdoor scenes, and mundane tasks. Positive images included babies, baby animals, and people interacting with each other or with animals happily.

The RewP was elicited with the Doors task. Participants viewed an image of two doors and had to select one. The door selected then showed a feedback image – either an upward green arrow indicating a gain of $0.50 or a downward red arrow indicating a loss of $0.25. Thirty gains and 30 losses were presented randomly over three blocks. Participants received $7.50 in winnings from the Doors task.

LPP and RewP measures were derived from an electroencephalogram (EEG) recorded at baseline and at week six of treatment. The study findings showed that:

• The LPP was larger for positive images, and it increased from baseline to week six.
• Change in HAM-D from baseline to week six did not correlate with any LPP measure.
• LPP for positive images was larger at week six than baseline.
• LPP for neutral images did not differ between baseline and week six.
• The absent RewP effect observed at baseline did not change

The findings confirmed Dr. Bress’ hypothesis and previous research. “What I expected, based on prior research, was that the late positive potential to rewarding stimuli would increase so that we would see greater attentional engagement with rewarding stimuli over the course of treatment, and that the reward positivity might not change,” she says. “We know, for instance, that [reward positivity] is blunted in people who have remitted depression where they used to be depressed, but they’re not anymore. I was hypothesizing that the reward positivity might just always be blunted in people with a predisposition for depression, whereas the LPP might be more of a movable target for these treatments.”

Looking toward the future

Dr. Bress says the next steps are to conduct a similar study in a larger group and to use a comparison condition that is not believed to act on the PVS, which she is currently doing through a K23 study funded by the National Institute of Mental Health. “I’m comparing Engage therapy specifically to supportive therapy,” she says. “This will be a more robust test of whether we can actually target these Positive Valence System markers using a reward-focused therapy.”

If the results are similar in the larger sample, the results could improve existing psychological interventions and inform personalized approaches to treating late-life depression.