TheUSPreventiveServicesTaskForce (USPSTF)hasoffered its updated recommendations for the screening for depression in adults. The document, published thisweek in JAMA,1 updates a 2009 review of the evidence as to the net benefit of accurate diagnosis,effectivetreatment, andappropriate follow-upafter depression screening for adults older than 18 years, including pregnant and postpartum women, complementing previousrecommendationsfordepressionscreening inchildren and adolescents (http://www.uspreventiveservicetaskforce .org). There is no question that primary care screening offers a first-line medical opportunity to identify patients with an undiagnosed major depressive episode. Use of standardized screening instruments and evidence-based treatments are a critical first step. That said, anunsettling reality remains: how, even with improved efficiency of screening and more timely diagnoses,dowesecure thenecessary resources toensure that depressed patients not only receive treatment and follow-up, but that the treatment selected is both appropriate and optimized for the individual. Compounding these challenges, neurological patients with depression, even when identified, maybereticenttoacceptpsychiatrictreatment,2andlikeinternal medicine and primary care, the time and resources needed to address the behavioral “symptoms” are often eclipsed by core demands of the principal neurological or medical condition. For apatientpresentingwithmajordepressiveepisode, an antidepressant medication or evidence-based psychotherapy is currently recommendedas first-line treatment,with remission rates to these 2options roughly equivalent in all patients except themost severely ill.3With thisperceivedequivalency, treatment selection is oftenbasedon factors suchaspatient and health care professional preference, cost and accessibility, andpotential adverse effects.However, theodds are actually against remission in patients currently treated using this approach. At best, 40% of patients achieve remission with a first treatment, and the “wrong” first choice has significant individual and societal costs due to continueddistress, risk of suicide, loss of productivity, and wasted resources associated with 2 to 3 months of an ineffective treatment.Moreover, among the roughly60%to70%ofdepressed patientswho do not remitwith their first treatment,many do not return to explore other options, with potential lethal consequences.4These sameconcernshold fordepressionpresenting inpatientswithneurological diseases andothermedical illnesses where the combined presence of a mood disorder has a magnified effect on disability.5 Clearly, treatments are highly effective in some individuals, but there is no reliableway tomatch patients to their best treatment option or to avoid those that are unlikely to be effective, even in the setting of equal access. Developing reliable biomarkers that can stratify individual patients to specific treatments is essential to achieve the goal of a more personalized level of care for patientswith depression and all neuropsychiatric disorders.6Manymedical specialties suchas those treating heart disease and cancer now routinely use patient-level biological measures to subtype and stratify patients to treatments, andtoguide treatmentmodificationswith disease progression or categories of disease risk, substantially improving patient outcomes. Toward a “precision medicine” approach for depression, various strategies have been tested, including clinical, imaging, genetic, electroencephalographic, and immunological metrics, but with limited clinical impact thus far. Motivated to translate ongoing advances in functional and structural neuroimaging methods and mounting evidence of (1) distinct patterns of brain dysfunction across clinically defined depression subgroups, (2) regional correlates of specific mood, motor, and cognitive syndrome dimensions, and (3) differential change patterns with mechanistically distinct treatments,7 investigations of brain-based biomarkers that predict treatment outcomes to standard first-line treatments have been initiated. Recent studies have identified some initial promising imaging biomarker candidates that predict remission and nonresponse to cognitive behavioral therapy or a standard selective serotonin reuptake inhibitor Related article at jama.com Opinion Editorial