title: Biomarkers for antipsychotic therapies.
abstract: Molecular biomarkers for antipsychotic treatments have been conceptually linked to the measurements of dopamine functions, mostly D(2) receptor occupancy, either by imaging using selective PET/SPECT radioactive tracers or by assessing plasma prolactin levels. A quest for novel biomarkers was recently proposed by various academic, health service, and industrial institutions driven by the need for better treatments of psychoses. In this review we conceptualize biomarkers within the Translational Medicine paradigm whose goal was to provide support to critical decision-making in drug discovery. At first we focused on biomarkers as outcome measure of clinical studies by searching into the database clinicaltrial.gov. The results were somewhat disappointing, showing that out of 1,659 antipsychotic trials only 18 used a biomarker as an outcome measure. Several of these trials targeted plasma lipids as sentinel marker for metabolic adverse effects associated with the use of atypical antipsychotics, while only few studies were aimed to new disease specific biological markers. As an example of a mechanistic biomarker, we described the work done to progress the novel class of glycine transporter inhibitors as putative treatment for negative symptoms of schizophrenia. We also review how large-scale multiplex biological assays were applied to samples from tissues of psychiatric patients, so to learn from changes of numerous analytes (metabolic products, lipids, proteins, RNA transcripts) about the substrates involved in the disease. We concluded that a stringent implementation of these techniques could contribute to the endophenotypic characterization of patients, helping in the identification of key biomarkers to drive personalized medicine and new treatment development.
authors.affiliation: Respiratory Therapeutic Area, GlaxoSmithKline R&D, King of Prussia, PA, USA. emilio.merlo_pich@roche.com
authors.forename: Emilio Merlo
authors.initials: EM
authors.lastname: Pich
authors.forename: Gabriel
authors.initials: G
authors.lastname: Vargas
authors.forename: Enrico
authors.initials: E
authors.lastname: Domenici
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D002986:Clinical Trials as Topic; D005998:Glycine / Q000134:cerebrospinal fluid; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D055432:Metabolomics; D057285:Precision Medicine; D040901:Proteomics; D012559:Schizophrenia / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D015415:Biomarkers; D050487:Glycine Plasma Membrane Transport Proteins; C493268:SLC6A9 protein, human; D005998:Glycine