Personalized medicine in psychiatry

Response to specific psychotropic medications treatments varies widely among individuals. Understanding and predicting that variation could have great benefits for people living with psychiatric problems. The central theme of personalized medicine is the premise that an individual’s unique physiologic characteristics play a significant role in both disease vulnerability and in response to specific therapies. The major goals of personalized medicine are therefore to predict an individual’s susceptibility to developing an illness, achieve accurate diagnosis, and optimize the most efficient and favorable response to treatment. Individual’s unique characteristics play a significant role in tailoring their therapies. Such characteristics include: genetic alterations and epigenetic modifications, clinical symptomatology, observable biomarker changes, and environmental factors. When studying drug action in individuals, researchers focus on two major determinants: 1. Pharmacokinetics: how much of a drug is needed to reach its target in the body, and 2. Pharmacodynamics: how well the target cells, such as heart tissue or neurons, respond to the drug. The scientific terms for these two determinants are pharmacokinetics and pharmacodynamics, and both are critical considerations in the field of pharmacogenomics. At psychiatric diseases; many genes are implicated in determining variability at pharmacokinetic and pharmacodynamics level. Only 35-45% of the patients respond to psychotropic therapies and return to functional level 30-50% of the patients will not respond sufficiently. Pharmacodynamic factors of Personalized Medicine In Psychiatry One major expectation of personalized medicine is the ability to determine susceptibility or protective factors imparted through genetic change. Major depressive disorder (MDD) has a strong genetic component, with an estimated 40 to 70% of the risk for developing MDD thought to be genetic. Prominent findings in susceptibility studies of MDD include several polymorphisms in the serotonergic system, and in various elements of the hypothalamicpituitary-adrenocortical axis. Genes that have an effect on serotonin signaling have been a major focus of study for the pharmacogenomics of depression. Evidence from family, twin, and adoption studies show that bipolar disorder (BD) is highly heritable, with genetic variables estimated to account for 60 to 85% of risk. With estimates of heritability of 50 to 80% schizophrenia (SZ) Numerous studies have begun to pinpoint associations between genetic variants in some individuals with SZ and the tolerability and therapeutic efficacy of antipsychotic medications. Pharmacokinetic factors of Personalized Medicine In Psychiatry Pharmacokinetics encompasses four processes: absorption, distribution, metabolism, and excretion. Beyond the effects specific to particular illnesses or drugs are the genetic changes in drug-metabolizing genes that underlie differential response to pharmacologic agents. The important area for consideration in determining the relationship between genes and drug response in psychiatric disorders is the contribution of genetic polymorphism in drug-metabolizing genes. The most studied group of drug-metabolizing enzymes in psychiatry are the cytochrome P450 (CYP) enzyme family. CYP enzymes are expressed predominantly in the liver, although they are also found in many extra-hepatic locations, including in the brain, where their levels are approximately 0.5 to 2% of those in the liver. Moreover, the genes coding for the CYP enzyme family are highly polymorphic, and the effects of many of the genetic differences contribute to differential metabolism of psychotropic agents. DME phenotypes are broadly grouped into four categories based on genotype effect on enzyme activity: 1) poor metabolizers (PM), 2) intermediate metabolizers (IM), 3) extensive metabolizers (EM), and 4) ultra-rapid metabolizers (UM). CYP2D6 is an important member of the CYP enzyme family, because it is responsible for metabolizing nearly 50% of the most commonly prescribed psychotropics, and evidence in animal models indicates its involvement in the biosynthesis of dopamine and 5-HT. Common substrates metabolized by CYPD26 are tricyclic antidepressants, many SSRIs, venlafaxine, and antipsychotics. Pharmacogenomic developments hold promise for personalized medicine in psychiatry with adjusted therapeutic doses, predictable responses, reduced adverse drug reactions, early diagnosis, and personal health planning. The prospect of personalized medicine in psychiatry more or less reşects ideals still largely unrealized. Currently, the field is at the information-gathering infancy stage. The goal of achieving personalized medicine in psychiatry is a laudable one, because its attainment should be associated with a marked reduction in morbidity and mortality.