113 It remains uncertain whether widespread genotyping prior to the onset of treatment therapy can contribute substantially to therapeutic outcome. Challenges facing the field include phenotypic and etiological heterogeneity, technological limitations, and contemporary research approaches. It seems that genetic testing for side-effect prediction has the highest likelihood of being incorporated into clinical practice. Supporting this, a test for clozapine-induced

agranulocytosis is now available with satisfying sensitivity and specificity.114 Computational Inhibitors,research,lifescience,medical models that include gene variants and other factors associated with antipsychoticinduced weight gain have yielded promising results.115 Tests related to treatment response may follow through the inclusion of more sophisticated genotyping techniques (eg, sequencing) and the analysis of refined endophenotypes, Inhibitors,research,lifescience,medical such as specific symptoms or symptom clusters. Future development of algorithm-based approaches requires the integration of additional genetic and nongenetic factors. Neuroimaging research has produced encouraging

associations between imaging endophenotypes and treatment outcome, such as the 5-HTTLPR x PFC/amygdala interaction. Nonetheless, these observations Inhibitors,research,lifescience,medical lack the positive and negative predictive value required to reliably distinguish responders from nonresponders to be used clinically. Based on current research, imaging markers explain a significant, but modest, portion Inhibitors,research,lifescience,medical of the

total variance. More research is required with larger, less heterogeneous samples in conjunction with other markers, eg, genotyping and electrophysiological measures. Most neuroscience research thus far involves the application of various theoretical approaches (ie, neuroimaging, genetics, neuropsychological, and physiological, etc) in isolation. The next step in the development of personalized medicine Inhibitors,research,lifescience,medical is the formation of standardized multimodal research models to better characterize markers of treatment response. Now is a time for optimism in the emerging ability of pharmacogenetics and neuroimaging to Wortmannin order provide meaningful help to the physician in developing individually tailored treatments for complex, heterogeneous psychiatric disorders. Selected abbreviations Metalloexopeptidase and acronyms 5-HT serotonin 5-HTTLPR serotonin transporter-linked polymorphic region ACC Anterior cingulate cortex BDNF brain-derived neurotrophic factor CYP cytochrome P450 PM poor drug metabolizer UM ultrarapid drug metabolizer
Schizophrenia (SCZ) is a disease with an estimated lifetime morbid risk approaching 1% worldwide,1 and its public health consequences (mortality- and morbidity) are severe.