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Depressive residual symptoms are associated with illness course characteristics in a sample of outpatients with bipolar disorder

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Abstract

Rates of 50–70% of residual symptoms referring to subsyndromal manifestations between episodes that do not meet the required criteria for episode definition were reported in bipolar disorder (BD). However, the specific role of these symptoms on the course of BD patients is poorly understood; thus, we aimed to investigate factors associated with depressive residual symptoms. Overall, 255 currently euthymic BD outpatients on maintenance treatment, including 95 (37.2%) males and 160 (62.8%) females, were consecutively recruited at the Section of Psychiatry, Department of Neuroscience, University of Genoa (Italy) and underwent detailed structured interviews, comprehensive clinical interviews, and clinical record reviews for assessment/collection of relevant information concerning the course of illness and clinical status including cross-referral of all available information. After categorizing subjects according to the presence/absence of residual symptoms, groups were compared along clinical variables and variables associated with residual symptoms were analyzed using multivariate analyses. Subjects with residual symptoms were less likely to report substance abuse (χ2(2) = 11.937, p ≤ 0.005) and lifetime psychotic symptoms (χ2(2) = 10.577, p = 0.005), and more likely to report higher illness episodes, longer duration of illness (t253 = 67.282, p ≤ 0.001; t253 = 10.755, p ≤ 0.001), and longer duration of current illness episode (t253 = 7.707, p ≤ 0.001) than those without residual symptoms. After multivariate analyses, a significant positive contribution to residual symptoms was given only by duration of current illness episode (β = 0.003; p ≤ 0.05), and lifetime psychotic symptoms (β = 1.094; p ≤ 0.005). Clinicians have to pay attention to minimize residual symptoms that may significantly impact on the course of BD and achievement of full remission between episodes.

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  • 06 March 2018

    Depressive residual symptoms are.

References

  1. Solomon DA, Leon AC, Coryell WH, Endicott J, Li C, Fiedorowicz JG, Boyken L, Keller MB (2010) Longitudinal course of bipolar I disorder: duration of mood episodes. Arch Gen Psychiatry 67:339–347. https://doi.org/10.1001/archgenpsychiatry.2010.15

    Article  PubMed  PubMed Central  Google Scholar 

  2. Judd LL, Akiskal HS, Schettler PJ, Endicott J, Maser J, Solomon DA, Leon AC, Rice JA, Keller MB (2002) The long-term natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry 59:530–537. https://doi.org/10.1001/archpsyc.59.6.530

    Article  PubMed  Google Scholar 

  3. Prien RF, Kocsis JH (1995) Long-term treatment of mood disorders. In: Bloom FE, Kupfer DJ (Eds) Psychopharmacology: the fourth generation of progress. Raven Press, New York

    Google Scholar 

  4. Perlis RH, Ostacher MJ, Patel JK, Marangell LB, Zhang H, Wisniewski SR, Ketter TA, Miklowitz DJ, Otto MW, Gyulai L, Reilly-Harrington NA, Nierenberg AA, Sachs GS, Thase ME (2006) Predictors of recurrence in bipolar disorder: primary outcomes from the systematic treatment enhancement program for bipolar disorder (STEP-BD). Am J Psychiatry 163:217–224. https://doi.org/10.1176/appi.ajp.163.2.217

    Article  PubMed  Google Scholar 

  5. Deckersbach T, Nierenberg AA, Kessler R, Lund HG, Ametrano RM, Sachs G, Rauch SL, Dougherty D (2010) RESEARCH: Cognitive rehabilitation for bipolar disorder: an open trial for employed patients with residual depressive symptoms. CNS Neurosci Ther 16:298–307. https://doi.org/10.1111/j.1755-5949.2009.00110.x

    Article  PubMed  PubMed Central  Google Scholar 

  6. Samalin L, Reinares M, de Chazeron I, Torrent C, Bonnin CM, Hidalgo-Mazzei D, Murru A, Pacchiarotti I, Geoffroy PA, Bellivier F, Llorca PM, Vieta E (2016) Course of residual symptoms according to the duration of euthymia in remitted bipolar patients. Acta Psychiatr Scand 134(1):57–64. https://doi.org/10.1111/acps.12568

    Article  CAS  PubMed  Google Scholar 

  7. Fagiolini A, Kupfer DJ, Masalehdan A, Scott JA, Houck PR, Frank E (2005) Functional impairment in the remission phase of bipolar disorder. Bipolar Disord 7:281–285. https://doi.org/10.1111/j.1399-5618.2005.00207.x

    Article  PubMed  Google Scholar 

  8. Kaya E, Aydemir O, Selcuki D (2007) Residual symptoms in bipolar disorder: the effect of the last episode after remission. Prog Neuro-Psychopharmacol Biol Psychiatry 31:1387–1392. https://doi.org/10.1016/j.pnpbp.2007.06.003

    Article  Google Scholar 

  9. Keitner GI, Solomon DA, Ryan CE, Miller IW, Mallinger A, Kupfer DJ, Frank E (1996) Prodromal and residual symptoms in bipolar I disorder. Compr Psychiatry 37:362–367. https://doi.org/10.1016/S0010-440X(96)90018-8

    Article  CAS  PubMed  Google Scholar 

  10. Wells KB, Burnam MA, Rogers W, Hays R, Camp P (1992) The course of depression in adult outpatients. Results from the medical outcomes study. Arch Gen Psychiatry 49:788–794. https://doi.org/10.1001/archpsyc.1992.01820100032007

    Article  CAS  PubMed  Google Scholar 

  11. American Psychiatric Association (1993) Practice guideline for major depressive disorder in adults. Am J Psychiatry 150:1–26. https://doi.org/10.1176/ajp.150.4.1

    Article  Google Scholar 

  12. Azorin JM (2012) Bipolar disorder: inter-episode symptoms. Encephale 38 (Suppl 4):S147–S150. https://doi.org/10.1016/S0013-7006(12)70091-X

    Article  PubMed  Google Scholar 

  13. Judd LL, Schettler PJ, Akiskal HS, Coryell W, Leon AC, Maser JD, Solomon DA (2008) Residual symptom recovery from major affective episodes in bipolar disorders and rapid episode relapse/recurrence. Arch Gen Psychiatry 65:386–394. https://doi.org/10.1001/archpsyc.65.4.386

    Article  PubMed  Google Scholar 

  14. Judd LL, Akiskal HS, Schettler PJ, Coryell W, Endicott J, Maser JD, Solomon DA, Leon AC, Keller MB (2003) A prospective investigation of the natural history of the long-term weekly symptomatic status of bipolar II disorder. Arch Gen Psychiatry 60:261–269. https://doi.org/10.1001/archpsyc.60.3.261

    Article  PubMed  Google Scholar 

  15. Fagiolini A, Frank E, Axelson DA, Birmaher B, Cheng Y, Curet DE, Friedman ES, Gildengers AG, Goldstein T, Grochocinski VJ, Houck PR, Stofko MG, Thase ME, Thompson WK, Turkin SR, Kupfer DJ (2009) Enhancing outcomes in patients with bipolar disorder: results from the bipolar disorder center for pennsylvanians study. Bipolar Disord 11:382–390. https://doi.org/10.1111/j.1399-5618.2009.00700.x

    Article  PubMed  PubMed Central  Google Scholar 

  16. Sierra P, Livianos L, Arques S, Castello J, Rojo L (2007) Prodromal symptoms to relapse in bipolar disorder. Aust N Z J Psychiatry 41:385–391. https://doi.org/10.1080/00048670701266854

    Article  PubMed  Google Scholar 

  17. Henry C, Etain B, Godin O, Dargel AA, Azorin JM, Gard S, Bellivier F, Bougerol T, Kahn JP, Passerieux C, Aubin V, Courtet P, Leboyer M, FACE-BD group (2015) Bipolar patients referred to specialized services of care: not resistant but impaired by sub-syndromal symptoms. Results from the FACE-BD cohort. Aust N Z J Psychiatry 49:898–905. https://doi.org/10.1177/0004867415585582

    Article  PubMed  Google Scholar 

  18. Azorin JM, Kaladjian A, Adida M, Fakra E, Hantouche E, Lancrenon S (2011) Correlates of first-episode polarity in a French cohort of 1089 bipolar I disorder patients: role of temperaments and triggering events. J Affect Disord 129:39–46. https://doi.org/10.1016/j.jad.2010.08.020

    Article  PubMed  Google Scholar 

  19. American Psychiatric Association (2001) Diagnostic and statistical manual of mental disorders, text revision (DSMIV-TR), 4th edn. American Psychiatric Association. Washington, DC

    Google Scholar 

  20. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. American Psychiatric Association. Washington, DC

    Book  Google Scholar 

  21. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The mini-international neuropsychiatric interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33 (quiz 34–57)

    PubMed  Google Scholar 

  22. Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134:382–389. https://doi.org/10.1192/bjp.134.4.382

    Article  CAS  PubMed  Google Scholar 

  23. Snaith R, Harrop F, Newby D, Teale C (1986) Grade scores of the Montgomery–Asberg depression and the clinical anxiety scales. Br J Psychiatry 148:560–599

    Article  Google Scholar 

  24. Fantino B, Moore N (2009) The self-reported Montgomery–Asberg depression rating scale is a useful evaluative tool in major depressive disorder. BMC Psychiatry 9:26. https://doi.org/10.1186/1471-244X-9-26

    Article  PubMed  PubMed Central  Google Scholar 

  25. Colom F, Vieta E, Daban C, Pacchiarotti I, Sánchez-Moreno J (2006) Clinical and therapeutic implications of predominant polarity in bipolar disorder. J Affect Disord 93:13–17. https://doi.org/10.1016/j.jad.2006.01.032

    Article  CAS  PubMed  Google Scholar 

  26. de Dios C, González-Pinto A, Montes JM, Goikolea JM, Saiz-Ruiz J, Prieto E, Vieta E (2012) Predictors of recurrence in bipolar disorders in Spain (PREBIS study data). J Affect Disord 141:406–414. https://doi.org/10.1016/j.jad.2012.03.009

    Article  PubMed  Google Scholar 

  27. Martino DJ, Marengo E, Igoa A, Scápola M, Ais ED, Perinot L, Strejilevich SA (2009) Neurocognitive and symptomatic predictors of functional outcome in bipolar disorders: a prospective 1 year follow-up study. J Affect Disord 116:37–42. https://doi.org/10.1016/j.jad.2008.10.023

    Article  PubMed  Google Scholar 

  28. Bauer MS, Kirk GF, Gavin C, Williford WO (2001) Determinants of functional outcome and healthcare costs in bipolar disorder: a high-intensity follow-up study. J Affect Disord 65:231–241. https://doi.org/10.1016/S0165-0327(00)00247-0

    Article  CAS  PubMed  Google Scholar 

  29. Marangell LB, Dennehy EB, Miyahara S, Wisniewski SR, Bauer MS, Rapaport MH, Allen MH (2009) The functional impact of subsyndromal depressive symptoms inbipolar disorder: data from STEP-BD. J Affect Disord 114:58–67. https://doi.org/10.1016/j.jad.2008.07.006

    Article  PubMed  Google Scholar 

  30. Wingo AP, Baldessarini RJ, Compton MT, Harvey PD (2010) Correlates of recovery of social functioning in types I and II bipolar disorder patients. Psychiatry Res 177:131–134. https://doi.org/10.1016/j.psychres.2010.02.020

    Article  PubMed  PubMed Central  Google Scholar 

  31. Rosa AR, Reinares M, Michalak EE, Bonnin CM, Sole B, Franco C, Comes M, Torrent C, Kapczinski F, Vieta E (2010) Functional impairment and disability across mood states in bipolar disorder. Value Health 13:984–988. https://doi.org/10.1111/j.1524-4733.2010.00768.x

    Article  PubMed  Google Scholar 

  32. Altshuler LL, Post RM, Black DO, Keck PE Jr, Nolen WA, Frye MA, Suppes T, Grunze H, Kupka RW, Leverich GS, McElroy SL, Walden J, Mintz J (2006) Subsyndromal depressive symptoms are associated with functional impairment in patients with bipolar disorder: results of a large, multisite study. J Clin Psychiatry 67:1551–1560

    Article  PubMed  Google Scholar 

  33. Tohen M, Bowden CL, Calabrese JR, Lin D, Forrester TD, Sachs GS, Koukopoulos A, Yatham L, Grunze H (2006) Influence of sub-syndromal symptoms after remission from manic or mixed episodes. Br J Psychiatry 189:515–519. https://doi.org/10.1192/bjp.bp.105.020321

    Article  PubMed  Google Scholar 

  34. Belzeaux R, Correard N, Boyer L, Etain B, Loftus J, Bellivier F, Bougerol T, Courtet P, Gard S, Kahn JP, Passerieux C, Leboyer M, Henry C, Azorin JM, Fondamental Academic Centers of Expertise for Bipolar Disorders (FACE-BD) collaborators (2013) Depressive residual symptoms are associated with lower adherence to medication in bipolar patients without substance use disorder: results from the FACE-BD cohort. J Affect Disord 151:1009–1015. https://doi.org/10.1016/j.jad.2013.08.028

    Article  PubMed  Google Scholar 

  35. Montes JM, Maurino J, de Dios C, Medina E (2013) Suboptimal treatment adherence in bipolar disorder: impact on clinical outcomes and functioning. J Patient Prefer Adherence 7:89–94. https://doi.org/10.2147/PPA.S39290

    Article  Google Scholar 

  36. Gutierrez-Rojas L, Jurado D, Martinez-Ortega JM, Gurpegui M (2010) Poor adherence to treatment associated with a high recurrence in a bipolar disorder outpatient sample. J Affect Disord 127:77–83. https://doi.org/10.1016/j.jad.2010.05.021

    Article  PubMed  Google Scholar 

  37. Tondo L, Visioli C, Preti A, Baldessarini RJ (2014) Bipolar disorders following initial depression: modeling predictive clinical factors. J Affect Disord 167:44–49. https://doi.org/10.1016/j.jad.2014.05.043

    Article  PubMed  Google Scholar 

  38. Serafini G, Nebbia J, Cipriani N, Conigliaro C, Erbuto D, Pompili M, Amore M (2018) Number of illness episodes as predictor of residual symptoms in major depressive disorder. Psychiatry Res. https://doi.org/10.1016/j.psychres.2017.09.026

    Article  PubMed  Google Scholar 

  39. Reinares M, Papachristou E, Harvey P, Mar Bonnín C, Sánchez-Moreno J, Torrent C, Ayuso-Mateos JL, Ploubidis GB, Vieta E, Frangou S (2013) Towards a clinical staging for bipolar disorder: defining patient subtypes based on functional outcome. J Affect Disord 144:65–71. https://doi.org/10.1016/j.jad.2012.06.005

    Article  PubMed  Google Scholar 

  40. Baek JH, Park DY, Choi J, Kim JS, Choi JS, Ha K, Kwon JS, Lee D, Hong KS (2011) Differences between bipolar I and bipolar II disorders in clinical features, comorbidity, and family history. J Affect Disord 131:59–67. https://doi.org/10.1016/j.jad.2010.11.020

    Article  PubMed  Google Scholar 

  41. Vieta E, Gasto C, Otero A, Nieto E, Vallejo J (1997) Differential features between bipolar I and bipolar II disorder. Compr Psychiatry 38:98–101. https://doi.org/10.1016/S0010-440X(97)90088-2

    Article  CAS  PubMed  Google Scholar 

  42. Leverich GS, Post RM (1996) Life charting the course of bipolar illness. In: Rush AJ (ed) Current review of mood and anxiety disorders 1. Karger, New York, pp 48–61

    Google Scholar 

  43. Leverich GS, Post RM (1998) Life charting of affective disorders. CNS Spectr 3:21–37

    Article  Google Scholar 

  44. Sibille E, French B (2013) Biological substrates underpinning diagnosis of major depression. Int J Neuropsychopharmacol 16:1893–1909. https://doi.org/10.1017/S1461145713000436

    Article  CAS  PubMed  Google Scholar 

  45. Paykel ES, Scott J, Teasdale JD, Johnson AL, Garland A, Moore R, Jenaway A, Cornwall PL, Hayhurst H, Abbott R, Pope M (1999) Prevention of relapse in residual depression by cognitive therapy. A controlled trial. Arch Gen Psychiatry 56:829–835. https://doi.org/10.1001/archpsyc.56.9.829

    Article  CAS  PubMed  Google Scholar 

  46. Prien RF, Kupfer DJ (1986) Continuation drug therapy for major depressive episodes: how long should it be maintained? Am J Psychiatry 143:18–23. https://doi.org/10.1176/ajp.143.1.18

    Article  CAS  PubMed  Google Scholar 

  47. Paykel ES, Scott J, Cornwall PL, Abbott R, Crane C, Pope M, Johnson AL (2005) Duration of relapse prevention after cognitive therapy in residual depression: follow-up of controlled trial. Psychol Med 35:59–68. https://doi.org/10.1017/S003329170400282X

    Article  CAS  PubMed  Google Scholar 

  48. Parikh SV, Zaretsky A, Beaulieu S, Yatham LN, Young LT, Patelis-Siotis I, Macqueen GM, Levitt A, Arenovich T, Cervantes P, Velyvis V, Kennedy SH, Streiner DL (2012) A randomized controlled trial of psychoeducation or cognitive-behavioral therapy in bipolar disorder: a Canadian Network for Mood and Anxiety treatments (CANMAT) study. J Clin Psychiatry 73:803–810. https://doi.org/10.4088/JCP.11m07343

    Article  PubMed  Google Scholar 

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Acknowledgements

Xenia Gonda is recipient of the Janos Bolyai Research Fellowship of the Hungarian Academy of Sciences.

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Authors and Affiliations

  1. Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI), Section of Psychiatry, University of Genoa, IRCCS Ospedale Policlinico San Martino, Largo Rosanna Benzi 10, 16132, Genoa, Italy

    Gianluca Serafini & Mario Amore

  2. International Consortium for Bipolar and Psychotic Disorder Research, McLean Hospital, Belmont, MA, USA

    Gustavo H. Vazquez

  3. Department of Neuroscience, Palermo University, Buenos Aires, Argentina

    Gustavo H. Vazquez

  4. Department of Psychiatry, Queens University, Kingston, Ontario, Canada

    Gustavo H. Vazquez

  5. Department of Psychiatry and Psychotherapy, Kutvolgyi Clinical Center, Semmelweis University, Budapest, Hungary

    Xenia Gonda & Zoltan Rihmer

  6. MTA-SE Neuropsychopharmacology Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary

    Xenia Gonda

  7. NAP-A-SE New Antidepressant Target Research Group, Semmelweis University, Budapest, Hungary

    Xenia Gonda

  8. Department of Neurosciences, Suicide Prevention Center, Sant’Andrea Hospital, University of Rome, Rome, Italy

    Maurizio Pompili

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  1. Gianluca Serafini
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Correspondence to Gianluca Serafini.

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The study design was approved by the local Ethical Review Board. The present study has been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Serafini, G., Vazquez, G.H., Gonda, X. et al. Depressive residual symptoms are associated with illness course characteristics in a sample of outpatients with bipolar disorder. Eur Arch Psychiatry Clin Neurosci 268, 757–768 (2018). https://doi.org/10.1007/s00406-018-0875-5

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