Ann Psychiatr Clin Neurosci | Volume 2, Issue 1 | Review Article | Open Access

Genetic Markers for the Diagnosis and Management of Treatment-Resistant Depression

Yoshiyuki Nakano1*, Baltazar Gomez-Mancilla2, Heii Arai1

1Department of Psychiatry, Juntendo University Graduate School of Medicine, Japan
2Department of Neuroscience, Novartis Institutes for Biomedical Research, Switzerland

*Correspondance to: Yoshiyuki Nakano 

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The incidence of depression is increasing worldwide, yet its diagnosis and management remain difficult, particularly in the case of Treatment-Refractory Depression (TRD). Herein, we review recent advances in the diagnosis and treatment of TRD, with a focus on genetic biomarkers for diagnosis and N-Methyl-D-Aspartate (NMDA) receptor blockers for treatment. TRD may be difficult to diagnose because of comorbidity with other psychological disorders. Criteria proposed in the International Classification of Diseases, Tenth Revision (ICD-10) and the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) are currently used to diagnose depression, but the use of genetic biomarkers would make the diagnosis more objective. Improvements in technology have made genetic analysis faster and less expensive; however, to date, there is no established medically objective test for the diagnosis of depression. Various genomic analyses, such as Genome-Wide Association Studies (GWAS), studies of single-nucleotide polymorphisms, pharmaco genetic studies, epigenetic studies, and studies of micro Ribo Nucleic Acid (miRNA), have been performed. Although genetic differences related to depression have emerged from these types of studies, the importance and utility of the biomarkers identified remain unclear. Depression is generally treated with various antidepressants, with physicians switching their patients from one drug to another as needed. Antidepressants may be used concomitantly with atypical antipsychotics as well as lithium, thyroid hormone, dopamine agonists, and/or electroconvulsive therapy. New antidepressants affecting the glutamatergic system, such as ketamine (which blocks NMDA receptors), are currently under investigation. Genetic factors also play a role in the response to medication. Therefore, genetic testing holds promise for personalizing the patient’s response to therapy. Therefore, objective genetic tests and new types of drugs may improve the outcomes of patients with TRD.


Treatment-Refractory Depression; Ketamine; N-Methyl-D-Aspartate receptor blockers; Epigenetics; Hydroxy Methylation; miRNA


Nakano Y, Gomez-Mancilla B, Arai H. Genetic Markers for the Diagnosis and Management of Treatment-Resistant Depression. Ann Psychiatr Clin Neurosci. 2019;2(1):1011.

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