Dr. Petryshen received Ph.D. training in Medical Genetics and postdoctoral training in Psychiatric Genetics. Her research focuses on the genetic causes and treatment of major psychiatric disorders bridging human genetic, model system, and preclinical behavioral pharmacology studies. She is an Associate Editor of Molecular Neuropsychiatry and Frontiers in Genetics: Behavioral and Psychiatric Genetics, and a member of the Molecular Psychiatry Association Organizing Board. Her research is funded by US and European agencies and private foundations. 

Questions being addressed in the lab

  1. Do genetic variants that confer risk of psychiatric illness contribute to brain abnormalities that occur in patients?
  2. How do psychiatric risk genes function in the brain to influence disease?
  3. Can we develop better therapeutics for treating psychiatric illness?

Projects underway to answer these questions

  1. We are leading the Genetics of Endophenotypes of Neurofunction to Understand Schizophrenia (GENUS) Consortium, which seeks to elucidate the role of psychiatric genetic risk variants in cognitive deficits and brain structural changes that occur in schizophrenia. The GENUS Consortium currently consists of 16 international research groups that have contributed data for ~7,000 schizophrenia, control, and familial high-risk participants.

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  3. We are studying the neuronal functions of the ankyrin 3 (ANK3) bipolar disorder GWAS gene using mouse and cellular model systems.

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  5. We are examining the efficacy of novel drugs in mouse behavioral paradigms that have predictive validity for psychiatric treatment.

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Answers Found

  1. We have reported significant association between the schizophrenia GWAS risk gene ZNF804A (a zinc finger protein that regulates gene transcription) with P300 amplitude, a component of the brain event-related potential evoked by novel auditory stimuli that indexes attention processing (del Re et al. Translational Psychiatry 4:e346, 2014). Our unpublished GENUS genetic association studies suggest that several schizophrenia GWAS risk loci and polygenic risk are associated with variation in several cognitive domains and brain structure across schizophrenia patients and unaffected individuals.

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  3. We have reported that reducing ankyrin 3 expression in mouse hippocampus by RNA interference, or more broadly throughout brain using a mouse transgenic model, induces behavioral changes that mimic features of bipolar mania (Leussis et al. Biological Psychiatry 73:683-690, 2013). In the same report, we provided evidence that reduced ankyrin 3 expression in transgenic mice increases sensitivity to stress, a trigger of mood episodes in patients. This led us to study the role of ANK3 genetic variation in other stress-related human conditions, where we discovered significant association with post-traumatic stress disorder (PTSD) and related externalizing behaviors in military veterans (Logue et al. Psychoneuroendocrinology 38:2249-2257, 2013).

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  5. We have reported that novel inhibitors of glycogen synthase kinase 3 (GSK3), a target of lithium, as well as inhibitors of histone deacetylases (HDACs), which regulate gene transcription, are effective in attenuating mood-related behaviors in mice (Pan et al. Neuropsychopharmacology 36:1397-1411, 2011; Schroeder et al. PLoS One 8:e71323, 2013). We have also reported that co-treatment with low doses of two drugs that have rapid anti-depressant effects in human major depression patients are equally effective in mouse behavioral models of antidepressant efficacy, suggesting that low dose co-treatment may be a viable treatment option in patients (Petryshen et al. Neuroscience Letters 620:70-73, 2016).

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