In addition, a pharmacological trial of olanzapine in a nonclinical sample found that individuals with the long Trametinib manufacturer allele of the DRD4 VNTR demonstrated greater reduction in craving after alcohol consumption during the medication condition, as compared with individuals

with the short allele.65 These results were later expanded using a Inhibitors,research,lifescience,medical clinical sample, in which patients with the long allele of the DRD4 VNTR experienced greater reductions in craving for alcohol and reduced alcohol consumption during the course of treatment, as compared with individuals with the short allele.66 The fact that craving has been linked to specific biological mechanisms and has both etiological Inhibitors,research,lifescience,medical and clinical implications demonstrates its utility as an endophenotype for studying genetic and pharmacological factors

associated with alcoholism and its treatment. Neuroimaging-derived endophenotypes Advances in imaging technology have provided the field with an opportunity to refine and expand the conceptualization of phenotypes that lend themselves to the identification of genetic variations that influence the etiology of alcohol and drug dependence. For example, Inhibitors,research,lifescience,medical there have been a number of studies that have utilized functional magnetic resonance imaging (fMRI) technology to investigate craving for alcohol by examining the hemodynamic response of brain structures after exposure to alcohol cues.67-69 Specifically, one study has found that alcoholrelated stimuli increased activation in the prefrontal cortex and anterior thalamus,67 whereas another study noted activation in the prefrontal cortex and anterior limbic areas.68 Furthermore, a study utilizing alcohol odor as Inhibitors,research,lifescience,medical an alcohol cue found significant increases in activation of the cerebellum and amygdala in alcoholics, but not controls.69 These differences, however, were not observed after treatment and no evidence of a correlation

between brain activation and subjective Inhibitors,research,lifescience,medical craving was presented. Imaging techniques provide the opportunity to examine endophenotypes that are more proximal to the biological mechanisms Sitaxentan that underlie risk for the development of alcohol use disorders. For example, the interplay of the mesocortical and mesolimbic structures represents a potential endophenotype for alcoholism, given that these structures are putatively associated with alcohol craving. An important advantage of the neuroimaging approach is the fact that the output does not rely on subjective reports of effect, which can induce a great deal of experimental variability. Measuring a more biologically based expression of the incentive salience of alcohol provides an objective means of defining the endophenotype. Major psychiatric disorders Psychiatric disorders, such as mood disorders and anxiety, are common comorbidities of alcoholism.