Public Release: 

Study finds brain marker of poor memory in schizophrenia patients

Possible key to understanding and treating cognitive symptoms of the disease

Columbia University Medical Center

A new study has identified a pattern of brain activity that may be a sign of memory problems in people with schizophrenia. The biomarker, which the researchers believe may be the first of its kind, is an important step toward understanding and treating one of the most devastating symptoms of schizophrenia.

The study, led by researchers at Columbia University Medical Center (CUMC) and the New York State Psychiatric Institute (NYSPI), was published today in the journal Biological Psychiatry.

While schizophrenia typically causes hallucinations and delusions, many people with the disorder also have cognitive deficits, including problems with short- and long-term memory.

"Of all the symptoms linked to schizophrenia, memory issues may have the greatest impact on quality of life, as they can make it difficult to hold down a job and maintain social relationships," said first author Jared X. Van Snellenberg, PhD, assistant professor of clinical psychology (in psychiatry) at CUMC and research scientist in the division of translational imaging at NYSPI. "Unfortunately, we know very little about the cause of these memory problems and have no way to treat them."

Researchers have long hypothesized that memory problems in schizophrenia stem from disruptions in the brain's dorsolateral prefrontal cortex (DLPFC). This area of the brain plays a key role in working memory--the system for temporarily storing and managing information required to carry out complex cognitive tasks. However, previous studies, which used functional magnetic resonance imaging (fMRI) to compare DLPFC activation in healthy individuals and those with schizophrenia while taking memory tests, have not shown clear differences.

Dr. Van Snellenberg hypothesized that the studies failed to detect a difference because the memory tests did not have enough levels of difficulty. In 2014 he and his colleagues designed a computerized test that includes eight levels of increasingly difficulty in a single working memory task.

In the current study, 45 healthy controls and 51 schizophrenia patients, including 21 who were not taking antipsychotic medications, were given the eight-level memory test while undergoing fMRI imaging. As expected, the healthy controls demonstrated a gradual increase in DLPFC activation, followed by a gradual decrease in activation as the task gets harder. But in both medicated and unmedicated schizophrenia patients, the overall response was significantly weaker, with the weakest response occurring in those who had the most difficulty with the memory task.

The researchers believe this may be the first time a brain signal in DLPFC has been directly linked to working memory performance in patients with schizophrenia.

"Our findings provide evidence that the DLPFC is compromised in patients with schizophrenia," said Dr. Van Snellenberg. "What they don't tell us is why, which is something we ultimately hope to figure out. In the meantime, we now have a specific target for treatment, and a new way to measure whether a treatment is working."

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The study was led by Anissa Abi-Dargham, MD, professor of psychiatry (in radiology) at CUMC and director of the division of translational imaging and of clinical and imaging research in the Lieber Center for Schizophrenia Research at NYSPI.

The article I, "Mechanisms of Working Memory Impairment in Schizophrenia," by Jared X. Van Snellenberg, Ragy R. Girgis, Guillermo Horga, Mark Slifstein, Najate Ojeil, Jodi J. Weinstein, Holly Moore, Jeffrey A. Lieberman (CUMC and NYSPI); Elsmarieke van de Giessen (CUMC, NYSPI, University of Amsterdam, The Netherlands), Daphna Shohamy (Columbia University, New York, NY), and Edward E. Smith (NYSPI, CUMC, and Columbia University, New York, NY). DOI: http://dx.doi.org/10.1016/j.biopsych.2016.02.017. It appears in Biological Psychiatry published by published by Elsevier.

Full text of the article is available to credentialed journalists upon request; contact Rhiannon Bugno at +1 214 648 0880 or Biol.Psych@utsouthwestern.edu.

The study was supported by grants from the National Institute of Mental Health (1P50MH086404, T32MH018870, 1K01MH107763, and 1K23MH101637) and the National Institutes of Health (5U01MH076544).

Dr. Girgis has received research support from Otsuka, Genentech, and Pharmanac. Dr. Slifstein has received research support from Forest Laboratories, Pierre-Fabre, CHDI, and Otsuka and has provided consultation for Amgen. Dr. Lieberman serves on the advisory boards of Clintara and Intra-Cellular Therapies. He receives grant support from Alkermes, Forum, Novartis, and Sunovion. Dr Abi-Dargham has received research support from Takeda and Forest Laboratories and has served on advisory boards for Roche, Forum, Lundbeck, and Otsuka. No other conflicts of interest were reported.

Columbia University Medical Center provides international leadership in basic, preclinical, and clinical research; medical and health sciences education; and patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Columbia University Medical Center is home to the largest medical research enterprise in New York City and State and one of the largest faculty medical practices in the Northeast. For more information, visit cumc.columbia.edu or columbiadoctors.org.

New York State Psychiatric Institute and Columbia University Department of Psychiatry (NYSPI/Columbia Psychiatry)

NYSPI/Columbia Psychiatry holds the #1 ranking in US News and World Report and in NIH research funding among the psychiatric departments and research facilities in the nation, and has contributed greatly to the understanding and treatment of psychiatric disorders. Located at the New York State Psychiatric Institute on the NewYork-Presbyterian Hospital/Columbia University Medical Center campus in Washington Heights, the institute and department enjoy a rich and productive collaborative relationship with physicians in various disciplines at Columbia University's College of Physician's and Surgeons. NYSPI/Columbia Psychiatry is home to distinguished clinicians and scientists noted for advancing the field in basic research and in the diagnosis and treatment of depression, suicide, schizophrenia, bipolar and anxiety disorders, eating disorders, and childhood psychiatric disorders. For more information, visit http://columbiapsychiatry.org/and and http://nyspi.org.

Biological Psychiatry

Biological Psychiatry is the official journal of the Society of Biological Psychiatry, whose purpose is to promote excellence in scientific research and education in fields that investigate the nature, causes, mechanisms and treatments of disorders of thought, emotion, or behavior. In accord with this mission, this peer-reviewed, rapid-publication, international journal publishes both basic and clinical contributions from all disciplines and research areas relevant to the pathophysiology and treatment of major psychiatric disorders.

The journal publishes novel results of original research which represent an important new lead or significant impact on the field, particularly those addressing genetic and environmental risk factors, neural circuitry and neurochemistry, and important new therapeutic approaches. Reviews and commentaries that focus on topics of current research and interest are also encouraged.

Biological Psychiatry is one of the most selective and highly cited journals in the field of psychiatric neuroscience. It is ranked 6th out of 140 Psychiatry titles and 10th out of 252 Neurosciences titles in the Journal Citations Reports® published by Thomson Reuters. The 2014 Impact Factor score for Biological Psychiatry is 10.255.

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