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A New Reliable Blood Test Can Detect Depression

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“If we can make the correct diagnosis the healing can begin”, recalcitrant medical expert Andrew Weil carefully formulated in a critical blog in the Huffington Post. That quote exposes one of the challenges for the treatment of depression, a very prevalent mental illness. To clarify, the World Health Organization (WHO) reported that approximately 350 million people worldwide of all age groups suffer from depression. In the worst case, these depressions can lead to suicide, which accounts for about 1 million deaths each year, and/or harm others. To prevent such terrible outcomes, treatment should improve from the start: How can one optimize the diagnosis of depression?

 Depression or Major Depressive Disorder (MDD) has multiple genetic and environmental causes. Genetic factors are hard to find and the discovered factors usually are also associated with other mood disorders. Furthermore, twin studies reveal that genetics can predict 37% of the depressions, which is a much lower heritability than in bipolar disorder, a comparable mood disorder (reviewed in Belmaker et al., 2008). Common environmental causes for MDD are loss of loved ones or isolation, but the following highly investigated biological aspects may be causative as well: (i) more inflammatory factors, lowering the threshold for inflammations (Raison et al., 2013), (ii) an overactive hypothalamic-pituitary-adrenal (HPA) axis, causing a higher stress response (reviewed in Pariante and Lightman, 2008) and (iii) less neurotrophins, which are involved in neuronal survival and plasticity (Nibuya et al., 1995).

Back to the disease itself: MDD is a chronic mood disorder that is characterized by a low mood and a noticeable loss of interest and/or amusement in daily activities for at least two weeks. Common symptoms are changes in sleep, indecisiveness, crying and suicidal thoughts. Potential patients can get diagnosed based on a doctor’s questionnaire about their well-being, medical history, family history and the observed symptoms during the interview. Unfortunately, no additional laboratory test can support or undermine this diagnosis.

Fortunately, a convincing study of a Harvard research group (Papakostas et al., 2013) describes a novel blood serum test to diagnose MDD in humans (Figure 1). This was done by comparing the levels of nine serum biomarkers in two independent groups of diseased individuals (n=36 and n=34) and non-psychiatric controls (n=43). The biomarkers are divided in four groups:  inflammatory factors (alpha-1-antitrypsin, apolipoprotein CIII, myeloperoxidase and soluble TNF-alpha receptor II), factors of the HPA-axis (cortisol and epidermal growth factor), metabolites (prolactin and resistin) and neurotrophin BDNF. These biomarkers were carefully selected from 110 candidates based on their concentrations in diseased blood and their relative independence on one another (to minimize redundancy).  After their concentrations were measured, the blood results were used in multiple formulas, forming the MDD-score that predicts the sensitivity and the specificity of the test. The sensitivity is the ability to observe MDD, whereas the specificity is the way to detect the absence of the disease. If the subjects’ MDD-score is above 50%, he/she tested positive for MDD.

The two independent investigations revealed a higher concentration of three inflammatory factors (alpha-1-antitrypsin, myeloperoxidase and soluble TNF-alpha receptor II) and a factor of the HPA-axis (epidermal growth factor) in MDD-patients. The MDD-scores from the first and second experiment gave almost the same scores, namely 85.5% and 81% for the MDD-patients and 32.9% for the negative controls. This leads to a sensitivity of 91-92% and a specificity 81% in both investigations.

The new serum-based diagnosis for MDD showed a high sensitivity and specificity of >90% and 81%, respectively. The sensitivity is surprisingly equal between the diseased groups. In comparison, the fasting plasma glucose test – important in diagnosing diabetes – has a slightly higher specificity (more than 90%), however, its sensitivity clearly less (between 40% and 65%). Therefore, this new serum-based test is not only cheap, but also very reliable, which makes it very complementary to the good-old questionnaires. However, these promising results were derived from only 113 depressed and non-depressed subjects from the US. Before this serum-based diagnosis gets clinically available, large-scaled clinical trials should be performed containing results from all over the world. Furthermore, this test might be further optimized if only the four different biomarkers were tested.

Moreover, it is interesting whether this new test distinguishes between two similar clinical conditions, namely MDD and depressive episodes of bipolar disorder. In addition, knowing that prevention is better than curing: Can this diagnostic test be prognostic as well?

In conclusion, this new serum-based laboratory test may become a cheap and very reliable diagnostic tool in the near future.

References:

Papakostas, G., Shelton, R., Kinrys, G., Henry, M., Bakow, B., Lipkin, S., Pi, B., Thurmond, L., & Bilello, J. (2011). Assessment of a multi-assay, serum-based biological diagnostic test for major depressive disorder: a Pilot and Replication Study Molecular Psychiatry, 18 (3), 332-339 DOI: 10.1038/mp.2011.166

Pariante, C., & Lightman, S. (2008). The HPA axis in major depression: classical theories and new developments Trends in Neurosciences, 31 (9), 464-468 DOI: 10.1016/j.tins.2008.06.006

Raison, C. (2012). A Randomized Controlled Trial of the Tumor Necrosis Factor Antagonist Infliximab for Treatment-Resistant DepressionThe Role of Baseline Inflammatory BiomarkersInfliximab for Treatment-Resistant Depression Archives of General Psychiatry DOI: 10.1001/2013.jamapsychiatry.4

Pariante, C., & Lightman, S. (2008). The HPA axis in major depression: classical theories and new developments Trends in Neurosciences, 31 (9), 464-468 DOI: 10.1016/j.tins.2008.06.006

Nibuya M, Morinobu S, & Duman RS (1995). Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. The Journal of neuroscience : the official journal of the Society for Neuroscience, 15 (11), 7539-47 PMID: 7472505

Sources:

http://www.who.int/mediacentre/factsheets/fs369/en/index.html

http://depression.about.com/od/diagnosis/a/howdiagnosed.htm

http://depression.about.com/cs/diagnosis/a/mdd.htm

http://www.psnpaloalto.com/wp/wp-content/uploads/2010/12/Depression-Diagnostic-Criteria-and-Severity-Rating.pdf

http://www.who.int/diabetes/publications/en/screening_mnc03.pdf

blood test use, prevention with blood test, how we can prevent depression

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