Abstract

Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models. Most studies aim at characterising the animal model by including the assessment of analytes or hormones affected in depressive patients. The ultimate objective is to validate the model to better understand the neurobiological basis of MDD. Stress hormones or inflammation-related analytes associated with MDD are frequently measured. In contrast, other investigators evaluate peripheral analytes in preclinical models to translate the results in clinical settings afterwards. Large-scale, hypothesis-free studies are performed in MDD models to identify candidate biomarkers. Other studies wish to propose new targets for drug discovery. Animal models endowed with predictive validity are investigated, and the assessment of peripheral analytes, such as stress hormones or immune molecules, is comprised to increase the confidence in the target. Finally, since the mechanism of action of antidepressants is incompletely understood, studies investigating molecular alterations associated with antidepressant treatment may include peripheral analyte levels. In conclusion, preclinical biomarker studies aid the identification of new candidate analytes to be tested in clinical trials. They also increase our understanding of MDD pathophysiology and help to identify new pharmacological targets.

Highlights

  • Investigations of preclinical biomarkers for major depressive disorder (MDD) encompass the quantification of proteins, peptides, mRNAs, or small molecules in blood or urine of animal models

  • The selected biomarker is measured in the tissues of an animal model of MDD, levels are compared with those evaluated in the respective controls, and an association is discovered between biomarker levels and diseased state

  • Since MDD is posing a heavy burden of disease and mortality, utmost efforts should be carried out to understand the neurobiological basis of the disease

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Summary

Major Depressive Disorder

Major depressive disorder (MDD) is a severe disease that is widely diffused all over the world, exerting a heavy toll in terms of morbidity and mortality [1, 2]. In Europe, mood disorders are the second most frequent group of mental disorders, dominated by MDD, which affects 7% of the population [2]. Affected patients experience heavy impact on everyday life, due to the characteristic of the symptoms that influence the ability to enjoy life. The diagnosis of MDD as based on the Diagnostic and Statistical Manual of Mental disorders [5] requires the occurrence of a set of symptoms, which seldom present all together. In addition to the main features of MDD, including depressed mood, loss of interest, and inability to experience pleasure, the diagnosis requires the presence of at least four symptoms among feeling of worthlessness, thoughts of death, inability to concentrate, fatigue, psychomotor retardation or agitation, sudden weight loss or gain, and sleep disturbances in either direction [5]. A single episode of depression may occur in a lifetime, a frequent development of the disease is towards a recurring disorder with frequent relapses intermingled with intervals of well-being, displaying a tendency for chronicity

Therapeutic Options for MDD
Unmet Medical Needs
Identification of Clinical Biomarkers
Biomarker Investigations in Preclinical Models
Animal Models of MDD
Preclinical Biomarkers to Investigate the Relevance of the Animal Model
Preclinical Studies to Identify Candidate Clinical Biomarkers
Preclinical Biomarkers to Identify New Pharmacological Targets
Findings
11. Conclusions
Full Text
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