New Therapy Reprograms The Brain To Restore Depressed Brain

A new therapy is attempting to do something that many depression treatments still fail to do: restore the ability to feel pleasure, motivation, and joy. In a clinical study, patients showed greater emotional improvement when therapy focused directly on the brain's reward systems. Scientists believe this could change how we treat depression and anxiety in the future.

Depression isn't just about sadness. Many people stop enjoying things they once loved, lose interest in life, motivation disappears, and even happy moments seem emotionally "muted."

This symptom, called anhedonia, is one of the most difficult aspects of depression to treat and also appears in anxiety disorders, post-traumatic stress, and other psychiatric problems. While many current treatments can reduce negative emotions, they often fail to restore positive emotions, joy, enthusiasm, and a sense of connection to life.

It was precisely this problem that motivated scientists to develop a new therapeutic approach called Positive Affect Therapy. Instead of focusing solely on reducing negative thoughts, the therapy was designed to "reactivate" the brain systems linked to reward, pleasure, motivation, and hope.

The central idea was to teach the brain to respond emotionally to positive everyday experiences. Researchers wanted to discover if directly stimulating reward mechanisms could generate better results than traditional therapies focused primarily on suffering, fear, and negative emotions.

To investigate this, scientists conducted a clinical trial with nearly one hundred adults who presented with depression, anxiety, and extremely low levels of positive emotions. Participants were randomly divided into two groups. One received the new therapy focused on positive emotions, while the other received a therapy focused on negative emotions, used as a comparison.

Both treatments had the same number of sessions, similar duration, and professional follow-up. In this way, the researchers were able to directly compare which approach produced greater emotional improvement.

The new therapy was designed to work on three fundamental aspects of the brain's reward system. The first was the anticipation of reward, helping people to regain feelings of expectation, curiosity, and motivation in the face of future experiences.

The second was the ability to enjoy positive moments in the present, something often reduced in depressed patients. The third involved teaching the brain to relearn from pleasant experiences, strengthening positive emotional memories instead of just registering frustrations and threats.

Professors and student researchers from the SMU Center for Anxiety and Depression Research who participated in the study. First row (from left to right): Doga Certinkaya, Thomas Ritz, Alicia E. Meuret, Windsor Hall, David Rosenfield. Second row (from left to right): Sarah Corner, Sofia Uribe, Claire Anderson, Savannah Springfield, Mikaela Lopez, Emily Wang. Credit: Southern Methodist University

The scientists didn't just assess emotional symptoms. They tried to understand exactly how the brain and behavior changed throughout the treatment. To do this, they used detailed questionnaires about pleasure, motivation, anxiety, and quality of life, as well as behavioral tasks and physiological measures, such as changes in heart rate associated with emotional responses.

The goal was to discover which mechanisms truly explained the clinical improvement. Interestingly, the most important changes appeared in the participants' own subjective reports: as people regained pleasure, hope, and interest in life, their depressive and anxious symptoms decreased significantly.

The results showed that therapy focused on positive emotions produced greater improvements than the traditional approach focused on negative emotions. Participants reported increased pleasure, a greater ability to enjoy positive experiences, and a significant reduction in emotional symptoms.

The effects continued even after the sessions ended. For the researchers, the study suggests that restoring brain circuits linked to reward may be one of the most important keys to treating depression more deeply and lastingly. Instead of just reducing suffering, the new approach attempts to restore something that many patients describe as lost: the ability to feel joy again.

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Positive Affect Treatment for Depression, Anxiety, and Low Positive Affect

A Randomized Clinical Trial

Alicia E. Meuret, David Rosenfield, Emily Wang, Christina M. Hough, Thomas Ritz, and Michelle G. Craske

JAMA, April 24, 2026. 2026;9;(4):e267403. 

doi:10.1001/jamanetworkopen.2026.7403

Abstract: 

Targeting impaired reward processing that underlies anhedonia and diminished positive affect is essential for reducing key risk factors in depression and anxiety, including suicidality and relapse. However, mechanistic research in this area remains limited.

Objectives  To assess whether a novel psychosocial intervention engages reward systems more than a mechanistically distinct comparison therapy, and whether alterations in reward and threat processing differentially mediate clinical outcomes. This was an assessor-blinded, parallel-group, multisite, 2-arm randomized clinical superiority trial. Study recruitment was from December 2021 to January 2024, with final assessment in July 2024. Participants were recruited from academic outpatient treatment centers in Los Angeles, California, and Dallas, Texas, and included treatment-seeking adults with severely low positive affect and moderate to severe depression or anxiety that was functionally impairing. Analyses were conducted with intent-to-treat principles. Participants underwent 15 weekly individual therapy sessions of positive affect treatment (PAT) or negative affect treatment (NAT). Clinical status was self-reported positive affect (using the Positive and Negative Affect Schedule–Positive subscale), interviewer-rated anhedonia (embedded within the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), and self-reported depression and anxiety (using the Depression, Anxiety, and Stress Scale). Target measures were 14 self-reported, behavioral, and physiological measures of reward anticipation-motivation, response to reward attainment, reward learning, and threat. Analyses included mixed-effects multilevel models. In total, 98 participants (mean [SD] age, 32.8 [12.2] years; 65 [66.3%] female) were randomized to receive PAT (n = 51) or NAT (n = 47). Multivariate multilevel model analyses of the 3 clinical status variables as a multivariate outcome showed that clinical status improved more with PAT than NAT (b = −0.06 [95% CI, −0.11 to −0.01]; t3039 = 2.43; P = .02; d = 0.27) and that PAT had better (higher) scores on clinical status than NAT at the 1-month follow-up (b = −0.21 [95% CI, −0.41 to −0.02]; t3039 = 2.11; P = .04; d = 0.21). Improvements in reward anticipation-motivation (b = 0.02 [95% CI, 0.01-0.03]; t1307 = 4.36; P < .001; d = 0.40) and reward attainment (b = 0.04 [95% CI, 0.01-0.06]; t1405 = 3.16; P = .002; d = 0.18) targets were comparable for PAT and NAT. Of 7 reward and threat self-reported target measures, 6 mediated improvements in clinical status, but none of the behavioral or physiological measures did. There was limited evidence for moderated mediation. In this randomized clinical trial of 98 adults with severely low positive affect, depression, and anxiety, findings suggested that modulation of reward and threat processes was a central mechanism of therapeutic improvement, with a reward-focused intervention producing superior clinical outcomes. ClinicalTrials.gov Identifier: NCT05203861