Cognitive Enhancement for Persistent Negative Symptoms in Schizophrenia Spectrum Disorder

How can we help individuals with schizophrenia build an enjoyable quality of life and participate in meaningful activities that enrich their recovery? The question has eluded mental health practitioners for over a century. When one asks affected individuals and family members, a theme of lack of inclusion, meaningful activity, motivation, and social participation emerges.

Such challenges largely describe the “negative symptoms” of schizophrenia — those that involve social isolation, reduced motivation, slowed thinking and motor movement, and unelaborated speech. These are some of the most functionally impairing symptoms of the condition, which at their extreme, can be expressed as catatonia and a complete inability to move.

Advances in psychiatric medications have helped many individuals gain good control over the more commonly recognized symptoms of schizophrenia, such as hearing voices or holding delusional beliefs. Unfortunately, there are currently no medications available that are effective for the treatment of negative symptoms, which too often prevent individuals from obtaining work, forming meaningful relationships, and building a life that most would consider minimally sufficient.

Dr. Shaun Eack, Professor and James and Noel Browne Chair, and his colleagues hope to arrive at the first effective treatment for the negative symptoms of schizophrenia with their recently awarded R01 from the National Institute of Mental Health. This work builds on Eack’s previous research with Cognitive Enhancement Therapy, where he has shown cognitive rehabilitation approaches to be effective at improving thinking, social understanding, and key outcomes such as employment.

In 2013, Eack and his colleagues published the first signals that cognitive and other psychosocial rehabilitation approaches are likely to be effective at addressing some of the negative symptoms of schizophrenia (Negative symptom improvement during cognitive rehabilitation: results from a 2-year trial of Cognitive Enhancement Therapy). They observed marked reductions in social withdrawal and other negative symptoms after cognitive rehabilitation, and were surprised by this given that the treatment was not focused on negative symptoms. In 2019, Eack was part of a team of scientists at Harvard Medical School that further linked the cognitive challenges of schizophrenia to negative symptoms (Cerebellar-prefrontal network connectivity and negative symptoms in schizophrenia).

“When we review the last several decades of clinical trials of Cognitive Enhancement Therapy for schizophrenia, we see an unexpected but consistent pattern of negative symptom improvement,” says Dr. Eack.

These observations set the stage for his current National Institute of Mental Health-supported project, Cognitive Enhancement for Persistent Negative Symptoms in Schizophrenia, which hopes to demonstrate the efficacy of cognitive and other psychosocial rehabilitation approaches for the treatment of negative symptoms.

The project will consist of an 18-month parallel arm randomized controlled trial that includes 90 outpatients with schizophrenia with persistent negative symptoms being treated with novel cognitive and psychosocial rehabilitation approaches based on Gerard E. Hogarty’s, MSW Personal Therapy and Cognitive Enhancement Therapy.

“This study hopes to arrive at better treatment options for the largely untreated domain of negative symptoms in schizophrenia through the use cognitive rehabilitation and psychosocial treatment” said Dr. Eack.

If effective, Eack and his team will have developed one of the only treatments that addresses negative symptoms in schizophrenia and the findings will also underscore the importance of cognitive rehabilitation in this population.