Long Non-Coding RNA: Potential Diagnostic and Therapeutic Biomarker for Major Depressive Disorder

Background The criteria for diagnosing depression are based on behavioral observation and self-reporting of symptoms by the patients or guardians without any biological validation of the disease. This study aimed to identify long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) as robust and predictive biomarkers for diagnosis and therapy response in major depressive disorder (MDD). Material/Methods We used human lncRNA 3.0 microarray profiling (which covers 30,586 human lncRNAs), using PBMCs from five MDD patients and five controls. Differentially expressed lncRNAs in the PBMCs of MDD patients were identified, of which 10 candidate lncRNAs were selected for real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis in a larger cohort of 138 MDD patients and 63 healthy controls. Then among the 138 MDD patients who received standard antidepressant treatment, 30 were randomly selected for lncRNAs expression retesting and symptomatology assessments after three-weeks and six-weeks of antidepressant treatment. Results Six lncRNAs (TCONS_00019174, ENST00000566208, NONHSAG045500, ENST00000517573, NONHSAT034045, and NONHSAT142707) were significantly downregulated in MDD patients compared to control patients, and the area under the receiver operator curve (ROC) of these six lncRNAs cases, combined, was 0.719 (95% confidence interval (CI): 0.617–0.821). There was no difference in the expression of these six lncRNAs based on gender (p>0.05) or age (p>0.05). Conclusions These results suggest that the combined expression of six lncRNAs in PBMCs may serve as a potential biomarker for diagnosis and therapy response of MDD in the clinical setting.

[1]  Wei Yang,et al.  Microarray profiling of long non-coding RNA (lncRNA) associated with hypertrophic cardiomyopathy , 2015, BMC Cardiovascular Disorders.

[2]  Ronald S Duman,et al.  Functional Biomarkers of Depression: Diagnosis, Treatment, and Pathophysiology , 2011, Neuropsychopharmacology.

[3]  E. Castrén,et al.  The role of BDNF and its receptors in depression and antidepressant drug action: Reactivation of developmental plasticity , 2010, Developmental neurobiology.

[4]  E. Nestler,et al.  Epigenetic mechanisms of depression and antidepressant action. , 2013, Annual review of pharmacology and toxicology.

[5]  T. Ebner,et al.  Bidirectional expression of CUG and CAG expansion transcripts and intranuclear polyglutamine inclusions in spinocerebellar ataxia type 8 , 2006, Nature Genetics.

[6]  Shuhan Sun,et al.  Long noncoding RNA high expression in hepatocellular carcinoma facilitates tumor growth through enhancer of zeste homolog 2 in humans , 2011, Hepatology.

[7]  Ning Sun,et al.  Microarray Profiling and Co-Expression Network Analysis of Circulating lncRNAs and mRNAs Associated with Major Depressive Disorder , 2014, PloS one.

[8]  Jian-fei Shi,et al.  CSF miR-16 is decreased in major depression patients and its neutralization in rats induces depression-like behaviors via a serotonin transmitter system. , 2015, Journal of affective disorders.

[9]  P. Rath,et al.  Age-dependent differential expression profile of a novel intergenic long noncoding RNA in rat brain , 2015, International Journal of Developmental Neuroscience.

[10]  Stephanie Roessler,et al.  MicroRNA expression, survival, and response to interferon in liver cancer. , 2009, The New England journal of medicine.

[11]  Lin Zhao,et al.  Differential expression of microRNA in peripheral blood mononuclear cells as specific biomarker for major depressive disorder patients. , 2014, Journal of psychiatric research.

[12]  A. Gottlieb,et al.  Effects of etanercept therapy on fatigue and symptoms of depression in subjects treated for moderate to severe plaque psoriasis for up to 96 weeks , 2007, The British journal of dermatology.

[13]  S. Preskorn,et al.  How Biomarkers Will Change Psychiatry: From Clinical Trials to Practice. Part I Introduction , 2012, Journal of psychiatric practice.

[14]  Charles L. Raison,et al.  Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression , 2009, Biological Psychiatry.

[15]  M. Ota,et al.  [The hypothalamic-pituitary-adrenal axis and depressive disorder: recent progress]. , 2012, Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology.

[16]  M. Hamilton,et al.  Development of a rating scale for primary depressive illness. , 1967, The British journal of social and clinical psychology.

[17]  Song Hong-tao,et al.  A preliminary analysis of association between plasma microRNA expression alteration and symptomatology improvement in Major Depressive Disorder (MDD) patients before and after antidepressant treatment , 2014 .

[18]  Lin Zhao,et al.  A preliminary analysis of association between the down-regulation of microRNA-181b expression and symptomatology improvement in schizophrenia patients before and after antipsychotic treatment. , 2014, Journal of psychiatric research.

[19]  M. Szyf,et al.  Maternal depression is associated with DNA methylation changes in cord blood T lymphocytes and adult hippocampi , 2015, Translational Psychiatry.

[20]  B. Hankin.  Journal of Clinical Child & Adolescent Psychology Future Directions in Vulnerability to Depression among Youth: Integrating Risk Factors and Processes across Multiple Levels of Analysis , 2022 .

[21]  B. Barraclough,et al.  Excess mortality of mental disorder , 1998, British Journal of Psychiatry.

[22]  Uwe Völker,et al.  Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study , 2015, BMC Medical Genomics.

[23]  Li Liu,et al.  Identification of Differential MicroRNAs in Cerebrospinal Fluid and Serum of Patients with Major Depressive Disorder , 2015, PloS one.

[24]  I. Imoto,et al.  Blood diagnostic biomarkers for major depressive disorder using multiplex DNA methylation profiles: discovery and validation , 2015, Epigenetics.

[25]  J. Mattick,et al.  Long Noncoding RNAs in Cardiac Development and Pathophysiology , 2012, Circulation research.

[26]  Supriyo De,et al.  Age-related changes in microRNA levels in serum , 2013, Aging.

[27]  Wei Chen,et al.  MicroRNAs in brain function and disease , 2008, Current neurology and neuroscience reports.

[28]  Christina Backes,et al.  Influence of the confounding factors age and sex on microRNA profiles from peripheral blood. , 2014, Clinical chemistry.

[29]  BIOMARKER STUDIES AND THE FUTURE OF PERSONALIZED TREATMENT FOR DEPRESSION , 2014, Depression and anxiety.

[30]  A. Arntz,et al.  Patient-informant concordance on the Structured Clinical Interview for DSM-III-R personality disorders (SCID-II). , 1998, Journal of personality disorders.

[31]  C. Ponting,et al.  Genomic and Transcriptional Co-Localization of Protein-Coding and Long Non-Coding RNA Pairs in the Developing Brain , 2009, PLoS genetics.

[32]  R. Baldessarini,et al.  Suicidal risk factors in bipolar I and II disorder patients. , 2012, The Journal of clinical psychiatry.

[33]  Bruce S. McEwen,et al.  Metabolism, mood and cognition in aging: The importance of lifestyle and dietary intervention , 2005, Neurobiology of Aging.

[34]  Yunchun Chen,et al.  Efficacy of repetitive transcranial magnetic stimulation in the prevention of relapse of depression: study protocol for a randomized controlled trial , 2013, Trials.

[35]  W. Niu,et al.  Aberrant microRNA expression in peripheral plasma and mononuclear cells as specific blood-based biomarkers in schizophrenia patients , 2015, Journal of Clinical Neuroscience.

[36]  H. Schmidt,et al.  Future Antidepressant Targets: Neurotrophic Factors and Related Signaling Cascades. , 2008, Drug discovery today. Therapeutic strategies.