Getting at the Root of Psychiatric Illness

How the biological basis of psychiatric disorders is leading to novel breakthroughs

It is estimated that globally over 350 million people suffer from depression; this startling number of people only begins to scratch the surface of the patients globally that are affected by various psychiatric illnesses. In an effort to combat the often devastating results of such disorders, Dr. Anthony Grace, of the University of Pittsburgh, is focused on understanding the biological bases of psychiatric disorders, with an emphasis on schizophrenia and depression. Using rat models that have been validated to replicate major aspects of these disorders, Dr. Grace and his team have combined evidence regarding risk factors and developmental aspects to construct models that are effective at predicting the actions of novel types of drugs and changing the course of the disease in humans. Therefore, by understanding diseases at the brain circuitry and developmental onset levels, Dr. Grace and his team are in a better position to dramatically decrease the burden of psychiatric disorders in the future.

Dr. Grace’s laboratory is unique in its systems-oriented approach to psychiatric disorders. Meaning that by studying activity in the circuits of normal animals as well as in well-validated animal models of disease states, he and his team are in a powerful position to translate their work to the human condition. Due to their high level of translatability and predictability, Dr. Grace and his team are highly sought out by clinical investigators which culminates in incredible collaborations that aim to effectively treat individuals with psychiatric disorders. Dr. Grace and his team have already made enormous advances in this endeavor; their work on schizophrenia has made large strides in the identification of treatment and preventative measures of the disorder while work with depression has helped their understanding of the disorder at a fundamental level. In short, Dr. Grace’s efforts are on the cutting-edge of preclinical research into the etiology and pathophysiology of psychiatric disorders and are bound to have a large impact on individuals and families across the globe.

Current research includes:

  • Etiology: Dr Grace and his team are studying what goes wrong in the brain when patients develop psychiatric disorders. Through fundamental research that gets at the basic underlying causes of both schizophrenia and depression, Dr. Grace and his team are able to move towards more effective means to treat the disorders.

  • Identifying At-Risk Individuals: Dr. Grace and his team are working to understand what factors in genetics, development, and environment can make an individual susceptible to schizophrenia. Dr. Grace hopes to also provide a means of early intervention for susceptible individuals in a way that may allow he and his team to prevent the onset of the disorder before further damage to the brain and to the psyche of the individual can take place.

  • Ketamine: Dr. Grace has identified the mechanism of action of rapid-onset antidepressant actions of ketamine, and has a means to discover how to target this system with more selective drugs. He and his team believe that understanding diseases at the brain circuitry and developmental onset levels, will allow them to dramatically decrease the burden of psychiatric disorders in the future.

Bio

Dr. Grace became interested in the dopamine system because of its importance in cognition and movement but also because it seemed to have a basis in major psychiatric disorders. As a graduate student, he worked for a psychiatric-scientists, Dr. Benjamin Bunney, at Yale, who gave Dr. Grace an appreciation for the clinical aspects of basic science research. It is for this reason that Dr. Grace works at a stage of animal research that allows the best translation into the human condition. He is passionate about his work because it satisfies his intellectual curiosity while at the same time may help to alleviate the massive suffering that individuals with major psychiatric disorders experience.

In his free time, aside from research, Dr. Grace enjoys taking pictures, skiing, and scuba diving.

http://www.pitt.edu/~graceaa/

 

Publications

Restoring balance in depression: ketamine reverses deficit in dopamine-dependent synaptic plasticity

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Peripubertal diazepam prevents the emergence of dopamine hyper-responsivity in the MAM model of schizophrenia

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Chronic high frequency deep brain stimulation of the nucleus accumbens drives time-dependent changes in functional connectivity

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Blinded prospective evaluation of computer-based mechanistic schizophrenia disease model for predicting drug response

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A novel α5GABAAR positive allosteric modulator reverses hyperactivation of the dopamine system in the MAM model of schizophrenia

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Ventral hippocampus, interneurons and schizophrenia: A new understanding of the pathophysiology of schizophrenia and its implica

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Awards

Lilly Basic Scientist Award – Collegium Internationale Neuropsychopharmacologicum, 2008

Dr. Paul Janssen Schizophrenia Research Award - Collegimm Internationale Neuropsychopharmacologicum, 2000

Daniel H. Efron Award, American College of Neuropsychopharmacology, 1999

National Alliance for Research on Schizophrenia and Depression Distinguished Investigator Award, 1998

Elected as Fellow to the American Association for the Advancement of Science, 2011