Innovations In Clinical Neuroscience

MAY-JUN 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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Innovations in CLINICAL NEUROSCIENCE [ V O L U M E 1 4 , N U M B E R 5 – 6 , M A Y – J U N E 2 0 1 7 ] 21 ABSTRACT The rate of completed suicides continues to rise across nations, cultures, socioeconomic classes, age groups, sexes, military personnel, veterans, and civilians from different backgrounds. Most concerning is the absence of diagnosed mental health disorders in the majority of these cases, per current literature reports. Efforts in the identification and possible prevention of this ultimate, tragic act of self- destruction have been minimally successful. In this article, the authors discuss the possible biological mechanisms including the role for potential markers, single nucleotide polymorphisms (SNPs), and their association with suicidal behaviors. INTRODUCTION Single nucleotide polymorphisms (SNPs) are commonly associated with pharmacogenomics (the study of the role of genetics in drug response) and personalized medicine, and are mediated, at least in part, by P450 enzymatic activity in the liver, impacting different genotypes and their corresponding phenotypes. So far, pharmacogenomics has led to significant progress in our understanding of the mechanisms of drug actions and the different pathways in which psychotropic medications are metabolized. Pharmacogenomics, therefore, has the potential to improve treatment outcomes. Recent scientific advances, however, have broadened the scope of SNP function to encompass cognitive activity in the central nervous system. This extension of SNP function to the brain is novel and provides insight into a comprehensive approach to a better understanding of neuropsychiatric conditions. 1 BACKGROUND A thorough understanding of the underlying endogenous processes is essential prior to exploring the impact of the introduction of exogenous compounds, such as psychotropic medications. SNPs are known to have existed for millennia as the so-called defective CYP genes, having been identified in Neanderthal genetic sequences. 2 The two most common cytochrome P450 polymorphisms that are the focus of pharmacogenomics are CYP2D6 and CYP2C19. Increasing evidence points to the presence of these two polymorphisms in brain tissue as well, extending the possibility of comprehensive organ system involvement beyond the liver. 3 Thus, exogenous introduction of psychotropics could interfere with the endogenous cellular mechanisms involved in biotransformation and eventual production of neurotransmitters, or neurons. Formation of neurotransmitters involves the oldest of organic by ATMARAM YARLAGADDA, MD; KEVIN P. ROSENBLATT, MD, PhD; and ANITA H. CLAYTON, MD Dr. Yarlagadda is Chief, Behavioral Health Services, McDonald Army Health Center in Newport News, Virginia, and Assistant Professor, Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, Virginia; Dr. Rosenblatt is Adjunct Associate Professor, UT Health at Houston, Department of Internal Medicine, Division of Oncology, Houston, Texas; and Dr. Clayton is Professor, Department of Psychiatry, University of Virginia, Charlottesville, Virginia. Innov Clin Neurosci. 2017;14(5–6):21–24 FUNDING: No funding was received for the preparation of this article. FINANCIAL DISCLOSURES: Dr. Rosenblatt is a founder, employee, and Lab Director, CMO, CSO for Companion Dx Reference Lab, Houston, Texas. Drs. Yarlagadda and Clayton have no conflicts of interest relevant to the content of this article. ADDRESS CORRESPONDENCE TO: Anita H. Clayton, MD; KEY WORDS: XXxx R E V I E W SINGLE NUCLEOTIDE POLYMORPHISMS and the Central Nervous System: Potential Biomarkers in Identifying Suicide Risk

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