Examples of biomarkers in depression, anxiety disorders, and schizophrenia Genetics Modern antidepressant drugs are, in terms of efficacy, largely similar to drugs discovered several years ago. The development of new treatments for depression is limited by the availability of validated human biomarker models.15 find more family studies have revealed that the clinical response to antidepressant treatment shows more similarities within one family compared with controls, which indicates that uptake, metabolism, transport of
drugs, and receptor binding is subjected to genetically controlled enzymes, receptor expression, and others factors. Monoamine transporters, including the serotonin, norepinephrine, Inhibitors,research,lifescience,medical and dopamine transporters are important in regulating Inhibitors,research,lifescience,medical neurotransmission by uptake of respective transmitters released from nerve terminals. Regarding serotonin transporter gene length polymorphisms, Caspi and colleagues16 concluded that in interaction with stressful life
events the genetic variation in the promoter region plays a role in predisposition to major depression. In the context of selective serotonin reuptake inhibitors in treatment of depression and the well-established link between stressful life events and depression, this finding offered a convincing biological link. This result, however, could not be confirmed Inhibitors,research,lifescience,medical by metanalyses of 14 studies17 and a birth cohort study in nearly 900 participants18: neither a Inhibitors,research,lifescience,medical risk elevation nor stable gene x environment interactions were able to be proven. These findings question the suitability of single-gene expression alterations for differentiation of patients in clinical trials. Genome-wide association studies point to multiple loci which in combination with additional clinical characteristics
may be better Inhibitors,research,lifescience,medical suited for predicting treatment responses.19 One of the largest recent cohort studies for evaluation of treatment algorithms is the Sequenced Treatment Alternative to Relieve Depression (STAR*D) trial, which provided DNA from nearly 2000 patients with nonpsychotic depression. Variants in the serotonin 2A receptor, the subunit of the glutamatekainate receptor (GRIK4) the potassium channel (KCNK2) the chaperone FKBP5, a protein Urease important for IIPA axis regulation, were associated with citalopram treatment outcome.20,21 For example, participants who were homozygous for the A allele of the serotonin 2A receptor had an 18% reduction in absolute risk of having no response to treatment.22 Analyzing the BDNF ValMet66 polymorphism, no evidence of an association with treatment outcome in STAR*D could be found.23 There is also evidence for a complex inheritance with multiple genes in the etiology of panic disorder. So far it has not been possible to identify single major responsible genes.