OJEMD  Vol.3 No.2 , May 2013
Etiology and Diagnosis of Major Depression—A Novel Quantitative Approach
Abstract: Background: Classical psychiatric opinions are relative uncertain and treatment results are not impressive when dealing with major depression. Depression is related to the endocrine system, but despite much effort a good quantitative measure for characterizing depression has not yet emerged. Methods: Based on ACTH and cortisol levels and using clustering analysis and mixture effect modeling we propose a novel and scientifically based quantitative index, denoted the O-index. The O-index combines a weighted and scaled deviation from normal values in both ACTH and cortisol. Results: Using ANOVA we compare the O-index with opinions reach by classical psychiatric diagnostic procedure (sensitivity 83%, specificity 59%, likelihood ratio positive 2.0, and likelihood ratio negative 0.29). The O-index nicely refines the etiology of depression: Combined with clinical data for 29 subjects earlier reported three categories emerge (p = 4.4 × 10-13): hypocortisolemic depressed, non-depressed, and hypercotisolemic depressed. The O-index also reveals why it has been difficult to obtain good markers earlier. It explains that healthy subjects may have an elevated (suppressed) level of cortisol or ACTH, however, the healthy system is able to deal with such elevated (suppressed) levels by compensating through suppressing (stimulating) the other component. In contrast the O-index shows that depressed subjects are incapable of making such compensation to a satisfactory degree. We illustrate how the O-index may be used for diagnostic procedure. Discussion: The methods are discussed and based on the available data material we propose that the O-index may be used to improve the diagnostic procedure and consequently the follow-up treatment.
Cite this paper: J. Ottesen, "Etiology and Diagnosis of Major Depression—A Novel Quantitative Approach," Open Journal of Endocrine and Metabolic Diseases, Vol. 3 No. 2, 2013, pp. 120-127. doi: 10.4236/ojemd.2013.32018.

[1]   N. Sun, Y. Li, Y. Cai, J. Chen, Y. Shen, J. Sun, Z. Zhang, J. Zhang, L. Wang, L. Goo, L. Yang, L. Qiang, Y. Yang, G. Wang, B. Du, J. Xia, H. Rong, Z. Gan, B. Hu, J. Pan, C. Li, S. Sun, W. Han, X. Xiao, L. Dai, G. Jin, Y. Zhang, L. Sun, Y. Chen, H. Zhao, Y. Dang, S. Shi, K. S. Kendler, J. Flint and K. Zhang, “A Comparison of Melancholic and Nonmelancholic Recurrent Major Depression in Han Chinese Women,” Depress Anxiety, Vol. 29, No. 1, 2012, pp. 4-9.

[2]   H. U. Wittchen, F. Jacobi, J. Rehm, A. Gustavsson, M. Svensson, B. Jonsson, J. Olesen, C. Allgulander, J. Alonso, C. Faravelli, L. Fratiglioni, P. Jennum, R. Lieb, A. Maercker, J. van Os, M. Preisig, L. Salvador-Carulla, R. Simon and H.-C. Steinhausen, “The Size and Burden of Mental Disorders and Other Disorders of the Brain in Europe 2010,” European Neuropsychopharmacology, Vol. 21, No. 9, 2011, pp. 655-679. doi:10.1016/j.euroneuro.2011.07.018

[3]   National Institute of Mental Health, US Department of Health & Human Services, National Institutes of Health NIH, “Depression,” 2011.

[4]   World Health Organization, “The World Health Report 2001—Mental Health: New Understanding, New Hope,” Geneva, 2001.

[5]   D. H. Barlow, “Abnormal Psychology: An Integrative Approach,” 5th Edition, Thomson Wadsworth, Belmont, 2005, pp. 248-249.

[6]   E. Harno and A. White, “Will Treating Diabetes with 11b-HSD1 Inhibitors Affect the HPA Axis?” Trends in Endocrinology and Metabolism, Vol. 21, No. 10, 2010, pp. 619-627.

[7]   J. Jokinen and P. Nordstrom, “HPA Axis Hyperactivity and Cardiovascular Mortality in Mood Disorder Inpatients,” Journal of Affective Disorders, Vol. 116, No. 1-2, 2009, pp. 88-92.

[8]   R. Rosmond and P. Bjorntorp, “The Hypothalamic-Pituitary-Adrenal Axis Activity as a Predictor of Cardiovascular Disease, Type 2 Diabetes and Stroke,” Journal of Internal Medicine, Vol. 247, No. 2, 2000, pp. 188-197. doi:10.1046/j.1365-2796.2000.00603.x

[9]   C. M. Pariante and S. L. Lightman, “The HPA Axis in Major Depression: Classical Theories and New Developments,” Trends in Neurosciences, Vol. 31, No. 9, 2008, pp. 464-468. doi:10.1016/j.tins.2008.06.006

[10]   C. L. Bowden, “Strategies to Reduce Misdiagnosis of Bipolar Depression,” Psychiatric Services, Vol. 52, No. 1, 2001, pp. 51-55. doi:10.1176/

[11]   D. E. Henley, J. A. Leendertz, G. M. Russell, S. A. Wood, S. Taheri, W. W. Woltersdorf and S. L. Lightman, “Development of an Automated Blood Sampling System for Use in Humans,” al of Medical Engineering & Technology, Vol. 33, No. 3, 2009, pp. 199-208. doi:10.1080/03091900802185970

[12]   M. Deuschle, U. Schweiger, B. Weber, U. Gothardt, A. Korner, J. Schmider, H. Standhardt, C.-H. Lammers and I. Heuser, “Diurnal Activity and Pulsatility of the Hypothalamus-Pituitary-Adrenal System in Male Depressed Patients and Healthy Controls,” Journal of Clinical Endocrinology & Metabolism, Vol. 82, No. 1, 1997, pp. 234-238. doi:10.1210/jc.82.1.234

[13]   R. A. Sarabdjitsingh, F. Spiga, M. S. Oitzl, Y. Kershaw, O. C. Meijer, S. L. Lightman and E. R. De Kloet, “Recovery from Disrupted Ultradian Glucocorticoid Rhythmicity Reveals a Dissociation Between Hormonal and Behavioural Stress Responsiveness,” Journal of Neuroendocrinology, Vol. 22, No. 8, 2010, pp. 862-871.

[14]   B. J. Carroll, F. Cassidy, D. Naftolowitz, N. E. Tatham, W. H. Wilson, A. Iranmanesh, P. Y. Liu and J. D. Veldhuis, “Pathophysiology of Hypercortisolismin Depression,” Acta Psychiatrica Scandinavica, Vol. 115, Suppl. 433, 2007, pp. 90-103. doi:10.1111/j.1600-0447.2007.00967.x

[15]   J. L. Mershon, C. S. Sehlhost, R. W. Rebar and J. H. Liu, “Evidence of a Corticotropin-Releasing Hormone Pulse Generator in Macaque Hypothalamus,” Endocrinology, Vol. 130, No. 5, 1992, pp. 2991-2996. doi:10.1210/en.130.5.2991

[16]   P. Monteleone, “Endocrine Disturbances and Psychiatric Disorders,” Current Opinion in Psychiatry, Vol. 14, No. 6, 2001, pp. 605-610. doi:10.1097/00001504-200111000-00020

[17]   B. J. Carroll, “Carrolls Depression Scales-Revised,” 2004.

[18]   T. T. Ngo, M. Bellalij and Y. Saad, “The Trace Ration Optimization Problem,” SIAM Review, Vol. 54, No. 3, 2012, pp. 545-569. doi:10.1137/120864799

[19]   D. P. O’Leary, “Scientific Computing with Case Studies,” SIAM Press, Philadelphia, 2009.

[20]   G. J. McLachlan and D. Peel, “Finite Mixture Models,” John Wiley & Sons Inc., New York, 2000. doi:10.1002/0471721182

[21]   R. Matlab, “Statistic Toolbox,” The Math Works, Inc., 2012.

[22]   L. Kaufman and P. J. Rousseeuw, “Finding Groups in Data: An Introduction to Cluster Analysis,” John Wiley & Sons, Inc., New York, 2005.