ABSTRACT
BACKGROUND: Recently, surrogate neurobiological biomarkers that correlate with target engagement and therapeutic response have been developed and tested in early phase studies of mood disorders. OBJECTIVE: The identification of biomarkers could help develop personalized psychiatric treatments that may impact public health. METHODS: These biomarkers, which are associated with clinical response post-treatment, can be directly validated using multimodal approaches including genetic tools, proteomics/metabolomics, peripheral measures, neuroimaging, biostatistical predictors, and clinical predictors. RESULTS: To date, early phase biomarker studies have sought to identify measures that can serve as "biosignatures", or biological patterns of clinical response. These studies have also sought to identify clinical predictors and surrogate outcomes associated with pathophysiological domains consistently described in the National Institute of Mental Health's (NIMH) new Research Domain Criteria (RDoC). Using the N-methyl-D-aspartate (NMDA) antagonist ketamine as an example, we identified changes in several domains (clinical, cognitive, and neurophysiological) that predicted ketamine's rapid and sustained antidepressant effects in individuals with treatment-resistant major depressive disorder (MDD) or bipolar depression. DISCUSSION: These approaches may ultimately provide clues into the neurobiology of psychiatric disorders and may have enormous impact Backon the development of novel therapeutics.
ABSTRACT
Mood disorders such as major depressive disorder (MDD) and bipolar disorder (BPD) are common, chronic, recurrent mental illnesses that affect the lives and functioning of millions of individuals worldwide. Growing evidence suggests that the glutamatergic system is central to the neurobiology and treatment of these disorders. Here, we review data supporting the involvement of the glutamatergic system in the pathophysiology of mood disorders as well as the efficacy of glutamatergic agents as novel therapeutics.