ABSTRACT
Major depressive disorder (MDD) is the most prevalent psychiatric disorder, but it can be underdiagnosed or misdiagnosed. Most people with depression are seen in primary care settings, where there are limited resources to diagnose and treat the patient. There is a lack of clinically validated objective laboratory-based diagnostic tests to diagnose MDD; however, it is clear that these tests could greatly improve the correct and timely diagnosis. This review aims to give a cross-sectional view of current efforts of DNA methylomic, transcriptomic, and proteomic approaches to identify biomarkers. We outline our view of the biomarker developmental steps from discovery to clinical application. We then propose that better cooperation will lead us closer to the common goal of identifying biological biomarkers for major depression. "The important thing is not to stop questioning. Curiosity has its own reason for existing." Albert Einstein.
Subject(s)
Biomarkers , Depressive Disorder, Major/blood , Depressive Disorder, Major/diagnosis , Primary Health Care , Gene Expression Profiling , Genetic Markers , Humans , Primary Health Care/methods , Primary Health Care/standards , Primary Health Care/trends , Proteomics , Sensitivity and SpecificityABSTRACT
Depression is a heterogeneous disorder and, similar to other spectrum disorders, its manifestation varies by age of onset, severity, comorbidity, treatment responsiveness, and other factors. A laboratory blood test based on specific biomarkers for major depressive disorder (MDD) and its subgroups could increase diagnostic accuracy and expedite the initiation of treatment. We identified candidate blood biomarkers by examining genome-wide expression differences in the blood of animal models representing both the genetic and environmental/stress etiologies of depression. Human orthologs of the resulting transcript panel were tested in pilot studies. Transcript abundance of 11 blood markers differentiated adolescent subjects with early-onset MDD from adolescents with no disorder (ND). A set of partly overlapping transcripts distinguished adolescent patients who had comorbid anxiety disorders from those with only MDD. In adults, blood levels of nine transcripts discerned subjects with MDD from ND controls. Even though cognitive behavioral therapy (CBT) resulted in remission of some patients, the levels of three transcripts consistently signaled prior MDD status. A coexpression network of transcripts seems to predict responsiveness to CBT. Thus, our approach can be developed into clinically valid diagnostic panels of blood transcripts for different manifestations of MDD, potentially reducing diagnostic heterogeneity and advancing individualized treatment strategies.
Subject(s)
Depressive Disorder, Major/blood , Gene Expression Profiling/methods , RNA/blood , Adolescent , Adult , Animals , Anxiety Disorders/blood , Anxiety Disorders/physiopathology , Anxiety Disorders/therapy , Biomarkers/blood , Cognitive Behavioral Therapy , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/therapy , Disease Models, Animal , Female , Humans , Pilot ProjectsABSTRACT
Abnormal intrinsic functional connectivity, measured by resting-state functional MRI, has been reported in major depressive disorder (MDD). Our study is the first to demonstrate hypo- and hyperconnectivity between the hippocampus and cortical, subcortical regions in a genetic animal model of depression, similar to connectivity anomalies found in MDD.
