Boosting Motivation and Cognitive Deficits in Mental Illness

Boosting Motivation and Cognitive Deficits in Mental Illness

Posted: October 9, 2018
Boosting Motivation and Cognitive Deficits in Mental Illness

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Researchers may have identified a way to counter motivational and cognitive deficits, symptoms seen in multiple mental illnesses that are not usually alleviated by existing medications.  The new discoveries center around a signaling protein called G-CSF, which might be manipulated to enhance reward learning and cognition.


People with a variety of psychiatric conditions, including major depression and schizophrenia, can take a variety of medicines that control some, although often not all, of their symptoms. Two important kinds of symptoms that are frequently not affected by available medicines are deficits in motivation and cognition.

Patients with major depressive disorder, for example, often suffer from the inability to experience pleasure and hence do not seek it, a symptom called anhedonia. Another symptom seen in some patients is a decline in processing speed – the ability of the brain to process information. Similarly, people with schizophrenia often find themselves listless, their interest in engaging with others and in activities sharply diminished. Cognitive functions are often impaired in schizophrenia, and are not addressed by medicines that temper a patient’s psychotic symptoms.

Basic research by a team co-led by Erin S. Calipari, Ph.D., a 2016 BBRF Young Investigator, and Drew D. Kiraly, M.D., Ph.D., a 2017 Young Investigator, has now revealed a mechanism in brain cells that might be harnessed to reduce cognitive deficits and enhance both motivation and behavioral flexibility in patients with schizophrenia, depression, and other psychiatric disorders. The findings were published August 27, 2018 in in the Journal of Neuroscience.

Dr. Calipari, of the Vanderbilt University School of Medicine, and Dr. Kiraly of the Icahn School of Medicine at Mount Sinai, led a team that included BBRF 2017 Young Investigator Cody A. Siciliano from the Massachusetts Institute of Technology. They studied a small but important signaling protein called G-CSF (granulocyte-colony stimulating factor). This multipurpose molecule is known to protect neurons and encourage neural progenitors in the brain to give rise to new neurons. Members of the team previously identified G-CSF as a factor in cellular and behavioral plasticity, which underlie learning and the ability of neuronal circuits to change in strength in response to changing circumstances or new stimuli.

In their newly reported research, the researchers figured out the mechanism that enables G-CSF to have these vital effects. Central in the mechanism is its ability to alter immune system signaling and spur the release of the neurotransmitter dopamine in a part of the brain called the nucleus accumbens.

The discovery indicates that G-CSF acts directly on dopamine circuits to enhance their function, and in turn to enhance reward learning and motivation. These results, said the scientists, “suggests that targeting immune factors (like G-CSF) may provide a new avenue for therapeutic intervention in multiple psychiatric disorders that are characterized by motivational and cognitive deficits.”

If you found this article interesting, you may find this Meet the Scientist Webinar interesting: Finding and Fixing Broken Brain Circuits in Depression