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Distinguishing bipolar from unipolar depression: the importance of clinical symptoms and illness features

Published online by Cambridge University Press:  08 April 2015

A. K. Leonpacher
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
D. Liebers
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
M. Pirooznia
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
D. Jancic
Affiliation:
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
D. F. MacKinnon
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
F. M. Mondimore
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
B. Schweizer
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
J. B. Potash
Affiliation:
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
P. P. Zandi
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA
F. S. Goes*
Affiliation:
Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA
*
*Address for correspondence: F. S. Goes, M.D., Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Meyer 4-119A, 600 N. Wolfe Street, Baltimore, MD 21287, USA. (Email: fgoes1@jhmi.edu)

Abstract

Background

Distinguishing bipolar disorder (BP) from major depressive disorder (MDD) has important relevance for prognosis and treatment. Prior studies have identified clinical features that differ between these two diseases but have been limited by heterogeneity and lack of replication. We sought to identify depression-related features that distinguish BP from MDD in large samples with replication.

Method

Using a large, opportunistically ascertained collection of subjects with BP and MDD we selected 34 depression-related clinical features to test across the diagnostic categories in an initial discovery dataset consisting of 1228 subjects (386 BPI, 158 BPII and 684 MDD). Features significantly associated with BP were tested in an independent sample of 1000 BPI cases and 1000 MDD cases for classifying ability in receiver operating characteristic (ROC) analysis.

Results

Seven clinical features showed significant association with BPI compared with MDD: delusions, psychomotor retardation, incapacitation, greater number of mixed symptoms, greater number of episodes, shorter episode length, and a history of experiencing a high after depression treatment. ROC analyses of a model including these seven factors showed significant evidence for discrimination between BPI and MDD in an independent dataset (area under the curve = 0.83). Only two features (number of mixed symptoms, and feeling high after an antidepressant) showed an association with BPII versus MDD.

Conclusions

Our study suggests that clinical features distinguishing depression in BPI versus MDD have important classification potential for clinical practice, and should also be incorporated as ‘baseline’ features in the evaluation of novel diagnostic biomarkers.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2015 

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References

Akiskal, HS, Maser, JD, Zeller, PJ, Endicott, J, Coryell, W, Keller, M, Warshaw, M, Clayton, P, Goodwin, F (1995). Switching from ‘unipolar’ to bipolar II. An 11-year prospective study of clinical and temperamental predictors in 559 patients. Archives of General Psychiatry 52, 114123.CrossRefGoogle Scholar
Altshuler, LL, Kupka, RW, Hellemann, G, Frye, MA, Sugar, CA, McElroy, SL, Nolen, WA, Grunze, H, Leverich, GS, Keck, PE, Zermeno, M, Post, RM, Suppes, T (2010). Gender and depressive symptoms in 711 patients with bipolar disorder evaluated prospectively in the Stanley Foundation bipolar treatment outcome network. American Journal of Psychiatry 167, 708715.CrossRefGoogle ScholarPubMed
Altshuler, LL, Post, RM, Leverich, GS, Mikalauskas, K, Rosoff, A, Ackerman, L (1995). Antidepressant-induced mania and cycle acceleration: a controversy revisited. American Journal of Psychiatry 152, 11301138.Google ScholarPubMed
Angst, J (1966). On the etiology and nosology of endogenous depressive psychoses. A genetic, sociologic and clinical study [article in German]. Monographien aus dem Gesamtgebiete der Neurologie und Psychiatrie 112, 1118.CrossRefGoogle ScholarPubMed
Angst, J, Azorin, JM, Bowden, CL, Perugi, G, Vieta, E, Gamma, A, Young, AH, BRIDGE Study Group (2011). Prevalence and characteristics of undiagnosed bipolar disorders in patients with a major depressive episode: the BRIDGE study. Archives of General Psychiatry 68, 791798.CrossRefGoogle Scholar
Benazzi, F (2007). Bipolar disorder – focus on bipolar II disorder and mixed depression. Lancet 369, 935945.CrossRefGoogle ScholarPubMed
Bromet, E, Andrade, LH, Hwang, I, Sampson, NA, Alonso, J, de Girolamo, G, de Graaf, R, Demyttenaere, K, Hu, C, Iwata, N, Karam, AN, Kaur, J, Kostyuchenko, S, Lépine, J-P, Levinson, D, Matschinger, H, Mora, MEM, Browne, MO, Posada-Villa, J, Viana, MC, Williams, DR, Kessler, RC (2011). Cross-national epidemiology of DSM-IV major depressive episode. BMC Medicine 9, 90.CrossRefGoogle ScholarPubMed
Cardoso de Almeida, JR, Phillips, ML (2013). Distinguishing between unipolar depression and bipolar depression: current and future clinical and neuroimaging perspectives. Biological Psychiatry 73, 111118.CrossRefGoogle ScholarPubMed
Cook, NR (2012). Clinically relevant measures of fit? A note of caution. American Journal of Epidemiology 176, 488491.CrossRefGoogle Scholar
Das, AK, Olfson, M, Gameroff, MJ, Pilowsky, DJ, Lantigua, R, Shea, S, Weissman, MM (2005). Screening for bipolar disorder in a primary care practice. Journal of the American Medical Association 293, 956963.CrossRefGoogle Scholar
Fernandes, BS, Gama, CS, Kauer-Sant'Anna, M, Lobato, MI, Belmonte-de-Abreu, P, Kapczinski, F (2009). Serum brain-derived neurotrophic factor in bipolar and unipolar depression: a potential adjunctive tool for differential diagnosis. Journal of Psychiatric Research 43, 12001204.CrossRefGoogle ScholarPubMed
Ghaemi, SN, Boiman, EE, Goodwin, FK (2000). Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. Journal of Clinical Psychiatry 61, 804808; quiz 809.CrossRefGoogle ScholarPubMed
Ghaemi, SN, Sachs, GS, Chiou, AM, Pandurangi, AK, Goodwin, K (1999). Is bipolar disorder still underdiagnosed? Are antidepressants overutilized? Journal of Affective Disorders 52, 135144.CrossRefGoogle ScholarPubMed
Goes, FS, Sadler, B, Toolan, J, Zamoiski, RD, Mondimore, FM, Mackinnon, DF, Schweizer, B, Raymond Depaulo, J, Potash, JB (2007). Psychotic features in bipolar and unipolar depression. Bipolar Disorders 9, 901906.CrossRefGoogle ScholarPubMed
Henry, C, Sorbara, F, Lacoste, J (2001). Antidepressant-induced mania in bipolar patients: identification of risk factors. Journal of Clinical Psychiatry 62, 249255.CrossRefGoogle ScholarPubMed
Ioannidis, JP, Tzoulaki, I (2012). Minimal and null predictive effects for the most popular blood biomarkers of cardiovascular disease. Circulation Research 110, 658662.CrossRefGoogle ScholarPubMed
Judd, LL, Akiskal, HS, Schettler, PJ, Coryell, W, Maser, J, Rice, JA, Solomon, DA, Keller, MB (2003). The comparative clinical phenotype and long term longitudinal episode course of bipolar I and II: a clinical spectrum or distinct disorders? Journal of Affective Disorders 73, 1932.CrossRefGoogle ScholarPubMed
Kendler, KS (2014). DSM issues: incorporation of biological tests, avoidance of reification, and an approach to the “Box Canyon Problem”. American Journal of Psychiatry 171, 12481250.CrossRefGoogle Scholar
Kessler, RC, Barker, PR, Colpe, LJ, Epstein, JF, Gfroerer, JC, Hiripi, E, Howes, MJ, Normand, SL, Manderscheid, RW, Walters, EE, Zaslavsky, AM (2003). Screening for serious mental illness in the general population. Archives of General Psychiatry 60, 184189.CrossRefGoogle ScholarPubMed
Kessler, RC, McGonagle, KA, Zhao, S, Nelson, CB, Hughes, M, Eshleman, S, Wittchen, HU, Kendler, KS (1994). Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Archives of General Psychiatry 51, 819.CrossRefGoogle ScholarPubMed
Leonhard, K, Korff, I, Schulz, H (1962). Temperament in families with monopolar and bipolar phasic psychoses. Psychiatria et Neurologia 143, 416434.CrossRefGoogle ScholarPubMed
Li, Z, Zhang, C, Fan, J, Yuan, C, Huang, J, Chen, J, Yi, Z, Wang, Z, Hong, W, Wang, Y, Lu, W, Guan, Y, Wu, Z, Su, Y, Cao, L, Hu, Y, Hao, Y, Liu, M, Yu, S, Cui, D, Xu, L, Song, Y, Fang, Y (2014). Brain-derived neurotrophic factor levels and bipolar disorder in patients in their first depressive episode: 3-year prospective longitudinal study. British Journal of Psychiatry: The Journal of Mental Science 205, 2935.CrossRefGoogle ScholarPubMed
Lish, JD, Dime-Meenan, S, Whybrow, PC, Price, RA, Hirschfeld, RM (1994). The National Depressive and Manic-depressive Association (DMDA) survey of bipolar members. Journal of Affective Disorders 31, 281294.CrossRefGoogle ScholarPubMed
Merikangas, KR, Jin, R, He, J-P, Kessler, RC, Lee, S, Sampson, NA, Viana, MC, Andrade, LH, Hu, C, Karam, EG, Ladea, M, Medina-Mora, ME, Ono, Y, Posada-Villa, J, Sagar, R, Wells, JE, Zarkov, Z (2011). Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Archives of General Psychiatry 68, 241251.CrossRefGoogle ScholarPubMed
Mitchell, PB, Frankland, A, Hadzi-Pavlovic, D, Roberts, G, Corry, J, Wright, A, Loo, CK, Breakspear, M (2011). Comparison of depressive episodes in bipolar disorder and in major depressive disorder within bipolar disorder pedigrees. British Journal of Psychiatry: The Journal of Mental Science 199, 303309.CrossRefGoogle ScholarPubMed
Mitchell, PB, Wilhelm, K, Parker, G, Austin, MP, Rutgers, P, Malhi, GS (2001). The clinical features of bipolar depression: a comparison with matched major depressive disorder patients. Journal of Clinical Psychiatry 62, 212216; quiz 217.CrossRefGoogle ScholarPubMed
Moreno, C, Hasin, DS, Arango, C, Oquendo, MA, Vieta, E, Liu, S, Grant, BF, Blanco, C (2012). Depression in bipolar disorder versus major depressive disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Bipolar Disorders 14, 271282.CrossRefGoogle ScholarPubMed
Murray, CJL, Vos, T, Lozano, R, Naghavi, M, Flaxman, AD, Michaud, C, Ezzati, M, Shibuya, K, Salomon, JA, Abdalla, S, Aboyans, V, Abraham, J, Ackerman, I, Aggarwal, R, Ahn, SY, Ali, MK, Alvarado, M, Anderson, HR, Anderson, LM, Andrews, KG, Atkinson, C, Baddour, LM, Bahalim, AN, Barker-Collo, S, Barrero, LH, Bartels, DH, Basáñez, MG, Baxter, A, Bell, ML, Benjamin, EJ, Bennett, D, Bernabé, E, Bhalla, K, Bhandari, B, Bikbov, B, Bin Abdulhak, A, Birbeck, G, Black, JA, Blencowe, H, Blore, JD, Blyth, F, Bolliger, I, Bonaventure, A, Boufous, S, Bourne, R, Boussinesq, M, Braithwaite, T, Brayne, C, Bridgett, L, Brooker, S, Brooks, P, Brugha, TS, Bryan-Hancock, C, Bucello, C, Buchbinder, R, Buckle, G, Budke, CM, Burch, M, Burney, P, Burstein, R, Calabria, B, Campbell, B, Canter, CE, Carabin, H, Carapetis, J, Carmona, L, Cella, C, Charlson, F, Chen, H, Cheng, AT, Chou, D, Chugh, SS, Coffeng, LE, Colan, SD, Colquhoun, S, Colson, KE, Condon, J, Connor, MD, Cooper, LT, Corriere, M, Cortinovis, M, de Vaccaro, KC, Couser, W, Cowie, BC, Criqui, MH, Cross, M, Dabhadkar, KC, Dahiya, M, Dahodwala, N, Damsere-Derry, J, Danaei, G, Davis, A, De Leo, D, Degenhardt, L, Dellavalle, R, Delossantos, A, Denenberg, J, Derrett, S, Des Jarlais, DC, Dharmaratne, SD, Dherani, M, Diaz-Torne, C, Dolk, H, Dorsey, ER, Driscoll, T, Duber, H, Ebel, B, Edmond, K, Elbaz, A, Ali, SE, Erskine, H, Erwin, PJ, Espindola, P, Ewoigbokhan, SE, Farzadfar, F, Feigin, V, Felson, DT, Ferrari, A, Ferri, CP, Fèvre, EM, Finucane, MM, Flaxman, S, Flood, L, Foreman, K, Forouzanfar, MH, Fowkes, FG, Fransen, M, Freeman, MK, Gabbe, BJ, Gabriel, SE, Gakidou, E, Ganatra, HA, Garcia, B, Gaspari, F, Gillum, RF, Gmel, G, Gonzalez-Medina, D, Gosselin, R, Grainger, R, Grant, B, Groeger, J, Guillemin, F, Gunnell, D, Gupta, R, Haagsma, J, Hagan, H, Halasa, YA, Hall, W, Haring, D, Haro, JM, Harrison, JE, Havmoeller, R, Hay, RJ, Higashi, H, Hill, C, Hoen, B, Hoffman, H, Hotez, PJ, Hoy, D, Huang, JJ, Ibeanusi, SE, Jacobsen, KH, James, SL, Jarvis, D, Jasrasaria, R, Jayaraman, S, Johns, N, Jonas, JB, Karthikeyan, G, Kassebaum, N, Kawakami, N, Keren, A, Khoo, JP, King, CH, Knowlton, LM, Kobusingye, O, Koranteng, A, Krishnamurthi, R, Laden, F, Lalloo, R, Laslett, LL, Lathlean, T, Leasher, JL, Lee, YY, Leigh, J, Levinson, D, Lim, SS, Limb, E, Lin, JK, Lipnick, M, Lipshultz, SE, Liu, W, Loane, M, Ohno, SL, Lyons, R, Mabweijano, J, MacIntyre, MF, Malekzadeh, R, Mallinger, L, Manivannan, S, Marcenes, W, March, L, Margolis, DJ, Marks, GB, Marks, R, Matsumori, A, Matzopoulos, R, Mayosi, BM, McAnulty, JH, McDermott, MM, McGill, N, McGrath, J, Medina-Mora, ME, Meltzer, M, Mensah, GA, Merriman, TR, Meyer, AC, Miglioli, V, Miller, M, Miller, TR, Mitchell, PB, Mock, C, Mocumbi, AO, Moffitt, TE, Mokdad, AA, Monasta, L, Montico, M, Moradi-Lakeh, M, Moran, A, Morawska, L, Mori, R, Murdoch, ME, Mwaniki, MK, Naidoo, K, Nair, MN, Naldi, L, Narayan, KM, Nelson, PK, Nelson, RG, Nevitt, MC, Newton, CR, Nolte, S, Norman, P, Norman, R, O'Donnell, M, O'Hanlon, S, Olives, C, Omer, SB, Ortblad, K, Osborne, R, Ozgediz, D, Page, A, Pahari, B, Pandian, JD, Rivero, AP, Patten, SB, Pearce, N, Padilla, RP, Perez-Ruiz, F, Perico, N, Pesudovs, K, Phillips, D, Phillips, MR, Pierce, K, Pion, S, Polanczyk, GV, Polinder, S, Pope, CA 3rd, Popova, S, Porrini, E, Pourmalek, F, Prince, M, Pullan, RL, Ramaiah, KD, Ranganathan, D, Razavi, H, Regan, M, Rehm, JT, Rein, DB, Remuzzi, G, Richardson, K, Rivara, FP, Roberts, T, Robinson, C, De Leòn, FR, Ronfani, L, Room, R, Rosenfeld, LC, Rushton, L, Sacco, RL, Saha, S, Sampson, U, Sanchez-Riera, L, Sanman, E, Schwebel, DC, Scott, JG, Segui-Gomez, M, Shahraz, S, Shepard, DS, Shin, H, Shivakoti, R, Singh, D, Singh, GM, Singh, JA, Singleton, J, Sleet, DA, Sliwa, K, Smith, E, Smith, JL, Stapelberg, NJ, Steer, A, Steiner, T, Stolk, WA, Stovner, LJ, Sudfeld, C, Syed, S, Tamburlini, G, Tavakkoli, M, Taylor, HR, Taylor, JA, Taylor, WJ, Thomas, B, Thomson, WM, Thurston, GD, Tleyjeh, IM, Tonelli, M, Towbin, JA, Truelsen, T, Tsilimbaris, MK, Ubeda, C, Undurraga, EA, van der Werf, MJ, van Os, J, Vavilala, MS, Venketasubramanian, N, Wang, M, Wang, W, Watt, K, Weatherall, DJ, Weinstock, MA, Weintraub, R, Weisskopf, MG, Weissman, MM, White, RA, Whiteford, H, Wiebe, N, Wiersma, ST, Wilkinson, JD, Williams, HC, Williams, SR, Witt, E, Wolfe, F, Woolf, AD, Wulf, S, Yeh, PH, Zaidi, AK, Zheng, ZJ, Zonies, D, Lopez, AD, AlMazroa, MA, Memish, ZA (2012). Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 21972223.CrossRefGoogle ScholarPubMed
Nurnberger, JI, Blehar, MC, Kaufmann, CA, York-Cooler, C, Simpson, SG, Harkavy-Friedman, J, Severe, JB, Malaspina, D, Reich, T (1994). Diagnostic Interview for Genetic Studies. Rationale, unique features, and training. NIMH Genetics Initiative. Archives of General Psychiatry 51, 849859; discussion 863–864.CrossRefGoogle ScholarPubMed
Pacchiarotti, I, Bond, DJ, Baldessarini, RJ, Nolen, WA, Grunze, H, Licht, RW, Post, RM, Berk, M, Goodwin, GM, Sachs, GS, Tondo, L, Findling, RL, Youngstrom, EA, Tohen, M, Undurraga, J, González-Pinto, A, Goldberg, JF, Yildiz, A, Altshuler, LL, Calabrese, JR, Mitchell, PB, Thase, ME, Koukopoulos, A, Colom, F, Frye, MA, Malhi, GS, Fountoulakis, KN, Vázquez, G, Perlis, RH, Ketter, TA, Cassidy, F, Akiskal, H, Azorin, J-M, Valentí, M, Mazzei, DH, Lafer, B, Kato, T, Mazzarini, L, Martínez-Aran, A, Parker, G, Souery, D, Ozerdem, A, McElroy, SL, Girardi, P, Bauer, M, Yatham, LN, Zarate, CA, Nierenberg, AA, Birmaher, B, Kanba, S, El-Mallakh, RS, Serretti, A, Rihmer, Z, Young, AH, Kotzalidis, GD, MacQueen, GM, Bowden, CL, Ghaemi, SN, Lopez-Jaramillo, C, Rybakowski, J, Ha, K, Perugi, G, Kasper, S, Amsterdam, JD, Hirschfeld, RM, Kapczinski, F, Vieta, E (2013). The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. American Journal of Psychiatry 170, 12491262.CrossRefGoogle ScholarPubMed
Perlis, RH, Brown, E, Baker, RW, Nierenberg, AA (2006). Clinical features of bipolar depression versus major depressive disorder in large multicenter trials. American Journal of Psychiatry 163, 225231.CrossRefGoogle ScholarPubMed
Perris, C (1966). A study of bipolar (manic–depressive) and unipolar recurrent depressive psychoses. Acta Psychiatrica Scandinavica 194, 914.CrossRefGoogle ScholarPubMed
Psychiatric GWAS Consortium Bipolar Disorder Working Group (2011). Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4. Nature Genetics 43, 977983.CrossRefGoogle Scholar
Redlich, R, Almeida, JJR, Grotegerd, D, Opel, N, Kugel, H, Heindel, W, Arolt, V, Phillips, ML, Dannlowski, U (2014). Brain morphometric biomarkers distinguishing unipolar and bipolar depression: a voxel-based morphometry-pattern classification approach. JAMA Psychiatry 71, 12221230.CrossRefGoogle ScholarPubMed
Robins, LN, Regier, DA (1991). Introduction. In Psychiatric Disorders in America: the Epidemiologic Catchment Area Study (ed. Robins, L. N. and Regier, D. A.), pp. 110. The Free Press: New York.Google Scholar
Serretti, A, Mandelli, L, Lattuada, E, Cusin, C, Smeraldi, E (2002). Clinical and demographic features of mood disorder subtypes. Psychiatry Research 112, 195210.CrossRefGoogle ScholarPubMed
Souery, D, Zaninotto, L, Calati, R, Linotte, S, Mendlewicz, J, Sentissi, O, Serretti, A (2012). Depression across mood disorders: review and analysis in a clinical sample. Comprehensive Psychiatry 53, 2438.CrossRefGoogle Scholar
Swets, JA (1988). Measuring the accuracy of diagnostic systems. Science 240, 12851293.CrossRefGoogle ScholarPubMed
Tondo, L, Visioli, C, Preti, A, Baldessarini, RJ (2014). Bipolar disorders following initial depression: modeling predictive clinical factors. Journal of Affective Disorders 167, 4449.CrossRefGoogle ScholarPubMed
Wehr, TA, Goodwin, FK (1987). Can antidepressants cause mania and worsen the course of affective illness? American Journal of Psychiatry 144, 14031411.Google ScholarPubMed
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