Understanding causes and

improving treatments

At Mass General, many of our researchers are clinicians actively involved in the treatment of schizophrenia patients. Their goal is to better understand the causes and symptoms of the disease in order to develop new and more effective treatments.

Quality of life is a key area of focus. Today's treatments rely on antipsychotic medication. This approach is often effective for controlling delusions and hallucinations, but it does not address negative symptoms (apathy, withdrawal, loss of emotional expression) or cognitive deficits (impaired memory and concentration) that can have affect the patients' overall health.

We are researching new ways to translate developments in brain imaging, genetics and basic neuroscience into more comprehensive treatments.

Our team concentrates on four main fields of study:


The development of schizophrenia has been linked to genetic responses to environmental factors.

Researchers at Mass General found one of the first examples. Certain people have a genetic deficiency in enzymes that activate the vitamin folate. When they get inadequate folate in their diet, they exhibit negative symptoms of schizophrenia, as well as cognitive deficits.

Dr. Josh Roffman has further demonstrated with brain imaging that genes associated with folate influence brain functions that underlie negative symptoms and cognitive deficits. As part of a current study, our researchers are giving supplemental folate to people with a genetic vulnerability to low folate levels, then using brain imaging to examine how it effects brain function.


Some people with schizophrenia lose brain volume. As a result, they may have more difficulty functioning during the first few years of the illness.

One protection against this brain loss is neurotrophins a naturally-occurring chemical in the brain that can be released by antidepressants.

Mass General researchers are leading the DECIFER (Depression and Citalopram In First Episode Recovery) Study, a multi-year effort to study the effects of the antidepressant citalopram during the first year of the illness.

Brain scans and genetic analysis are being used to evaluate whether boosting neurotrophin levels can improve long-term outcomes.

All DECIFER participants receive state-of-the-art treatment along with cognitive behavioral therapy.


One objective of schizophrenia treatment is to improve patients’ cognition and motivation—and then apply these improvements to their everyday lives.

Mass General researchers have learned that a low weekly dose of D-cycloserine (a drug once used as an antibiotic) can improve motivation and memory. We combine this treatment with cognitive remediation, using computerized exercises to improve brain functioning.

This approach is designed to enhance neuroplasticity, the brain’s natural ability to recover and improve functioning. Several studies have shown improved outcomes in work programs.


Members of the Mass General faculty pioneered successful treatments to help people with schizophrenia stop smoking. They were also among the first to recognize and treat medical complications, particularly metabolic abnormalities, associated with some newer antipsychotic medications.

Today we are studying genetic factors that increase the likelihood of cigarette smoking, metabolic abnormalities and diabetes in people with schizophrenia.

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