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Modifiable and non-modifiable factors associated with functional impairment during the inter-episodic periods of bipolar disorder

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Abstract

The chronic, long-term evolution of bipolar disorder (BD) requires a careful clinical characterization with prognostic implications in terms of symptom and functional control. The OPTHYMUM multicenter study was conducted in France with the objective of evaluating residual symptoms on overall functioning of BD patients during inter-episodic period. The aims of the present study were to identify the potentially modifiable (e.g., treatable) and non-modifiable variables associated with functional impairment during the inter-episodic periods of BD. Sample was divided into two groups according to level of functioning (adequate vs. impaired), based on the FAST scale total score. FAST cut-off for functional impairment is a score >11. The two subgroups were compared as per sociodemographic and clinical variables with standard univariate analyses, and a logistic regression model was created. The model as a whole contained independent non-modifiable factors (age, gender, BD type, illness duration) and modifiable factors (illness severity, predominant polarity, depressive and manic residual symptoms, comorbidities). The final model was statistically significant (χ 2 = 53.89, df = 5, p < 0.001). Modifiable factors most strongly associated with functional impairment were manic predominant polarity (OR = 1.79, CI 95% 1.09–2.96, p = 0.022), residual depressive symptoms (OR = 1.30, CI 95% 1.18–1.43, p < 0.001) and illness severity (OR = 1.24, CI 95% 1.01–1.52, p = 0.037), whilst non-modifiable factor was illness duration (OR = 1.03, CI 95% 1.01–1.05, p = 0.017). Despite intrinsic and non-modifiable illness characteristics, a clinical-wise choice of treatment may help to improve control of manic relapses. Potential improvement of residual depressive symptoms may alleviate the functional burden associated with bipolar disorder.

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References

  1. Kraepelin E (1920) Die Erscheinungsformen des Irreseins. Z Gesamte Neurol Psychiatr 62(1):29

    Article  Google Scholar 

  2. Trede K, Salvatore P, Baethge C et al (2005) Manic-depressive illness: evolution in Kraepelin’s Textbook, 1883–1926. Harv Rev Psychiatry 13:155–178. doi:10.1080/10,673,220,500,174,833

    Article  PubMed  Google Scholar 

  3. Bonnín CM, Martínez-Arán A, Torrent C et al (2010) Clinical and neurocognitive predictors of functional outcome in bipolar euthymic patients: a long-term, follow-up study. J Affect Disord 121:156–160. doi:10.1016/j.jad.2009.05.014

    Article  PubMed  Google Scholar 

  4. De Dios C, Ezquiaga E, Agud JL et al (2012) Subthreshold symptoms and time to relapse/recurrence in a community cohort of bipolar disorder outpatients. J Affect Disord 143:160–165. doi:10.1016/j.jad.2012.05.047

    Article  PubMed  Google Scholar 

  5. Martínez-Arán A, Vieta E, Colom F et al (2004) Cognitive impairment in euthymic bipolar patients: implications for clinical and functional outcome. Bipolar Disord 6:224–232. doi:10.1111/j.1399-5618.2004.00111.x

    Article  PubMed  Google Scholar 

  6. Goldberg JF, Harrow M, Grossman LS (1995) Course and outcome in bipolar affective disorder: a longitudinal follow-up study. Am J Psychiatry 152:379–384. doi:10.1176/ajp.152.3.379

    Article  CAS  PubMed  Google Scholar 

  7. Tohen M, Hennen J, Zarate CM et al (2000) Two-year syndromal and functional recovery in 219 cases of first-episode major affective disorder with psychotic features. Am J Psychiatry 157:220–228. doi:10.1176/appi.ajp.157.2.220

    Article  CAS  PubMed  Google Scholar 

  8. Samalin L, Murru A, Vieta E (2016) Management of inter-episodic periods in patients with bipolar disorder. Expert Rev Neurother. doi:10.1080/14737175.2016.1176530

    Article  PubMed  Google Scholar 

  9. Rosa AR, Magalhães PVS, Czepielewski L et al (2014) Clinical staging in bipolar disorder. J Clin Psychiatry 75:e450–e456. doi:10.4088/JCP.13m08625

    Article  PubMed  Google Scholar 

  10. Avila CC, Cabello M, Cieza A et al (2010) Functioning and disability in bipolar disorders: a systematic review of literature using the ICF as a reference. Bipolar Disord 12:473–482. doi:10.1111/j.1399-5618.2010.00833.x

    Article  PubMed  Google Scholar 

  11. Samalin L, Llorca P, Giordana B et al (2014) Residual symptoms and functional performance in a large sample of euthymic bipolar patients in France (the OPTHYMUM study). J Affect Disord. doi:10.1016/j.jad.2014.02.023

    Article  PubMed  Google Scholar 

  12. Samalin L, de Chazeron I, Vieta E et al (2016) Residual symptoms and specific functional impairments in euthymic patients with bipolar disorder. Bipolar Disord 18:164–173. doi:10.1111/bdi.12376

    Article  PubMed  Google Scholar 

  13. Rosa AR, Sánchez-Moreno J, Martínez-Aran A et al (2007) Validity and reliability of the Functioning Assessment Short Test (FAST) in bipolar disorder. Clin Pract Epidemiol Ment Health 3:5. doi:10.1186/1745-0179-3-5

    Article  PubMed  PubMed Central  Google Scholar 

  14. American Psychiatric Association (2000) DSM-IV-TR: diagnostic and statistical manual of mental disorders, IV edition

  15. Tohen M, Frank E, Bowden CL et al (2009) The International Society for Bipolar Disorders (ISBD) Task Force report on the nomenclature of course and outcome in bipolar disorders. Bipolar Disord 11:453–473. doi:10.1111/j.1399-5618.2009.00726.x

    Article  PubMed  Google Scholar 

  16. Young RC, Biggs JT, Ziegler VE, Meyer DA (1978) A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry 133:429–435

    Article  CAS  PubMed  Google Scholar 

  17. Berk M, Malhi GS, Cahill C et al (2007) The Bipolar Depression Rating Scale (BDRS): its development, validation and utility. Bipolar Disord 9:571–579. doi:10.1111/j.1399-5618.2007.00536.x

    Article  PubMed  Google Scholar 

  18. Colom F, Vieta E, Daban C et al (2006) Clinical and therapeutic implications of predominant polarity in bipolar disorder. J Affect Disord 93:13–17. doi:10.1016/j.jad.2006.01.032

    Article  CAS  PubMed  Google Scholar 

  19. Spearing M, Post M, Leverich G et al (1997) Modification of the Clinical Global Impressions (CGI) Scale for use in bipolar illness (BP): the CGI-BP. Psychiatry Res 73:159–171

    Article  CAS  PubMed  Google Scholar 

  20. Pallaskorpi S, Suominen K, Ketokivi M et al (2015) Five-year outcome of bipolar I and II disorders: findings of the Jorvi Bipolar Study. Bipolar Disord 17:363–374. doi:10.1111/bdi.12291

    Article  PubMed  Google Scholar 

  21. Solé B, Jiménez E, Torrent C et al (2016) Cognitive variability in bipolar II disorder: who is cognitively impaired and who is preserved. Bipolar Disord 18:288–299. doi:10.1111/bdi.12385

    Article  PubMed  Google Scholar 

  22. López-Jaramillo C, Lopera-Vásquez J, Gallo A et al (2010) Effects of recurrence on the cognitive performance of patients with bipolar I disorder: implications for relapse prevention and treatment adherence. Bipolar Disord 12:557–567. doi:10.1111/j.1399-5618.2010.00835.x

    Article  PubMed  Google Scholar 

  23. Colom F, Vieta E, Suppes T (2015) Predominant polarity in bipolar disorders: refining or redefining diagnosis? Acta Psychiatr Scand 132:324–326. doi:10.1111/acps.12503

    Article  CAS  PubMed  Google Scholar 

  24. Rosa AR, Andreazza AC, Kunz M et al (2008) Predominant polarity in bipolar disorder: diagnostic implications. J Affect Disord 107:45–51. doi:10.1016/j.jad.2007.07.021

    Article  CAS  PubMed  Google Scholar 

  25. Murru A, Pacchiarotti I, Amann BL et al (2013) Treatment adherence in bipolar i and schizoaffective disorder, bipolar type. J Affect Disord 151:1003–1008

    Article  CAS  PubMed  Google Scholar 

  26. Nivoli AM, Colom F, Pacchiarotti I et al (2013) Treatment strategies according to clinical features in a naturalistic cohort study of bipolar patients: a principal component analysis of lifetime pharmacological and biophysic treatment options. Eur Neuropsychopharmacol 23:263–275

    Article  CAS  PubMed  Google Scholar 

  27. Colom F, Vieta E, Sánchez-Moreno J et al (2009) Group psychoeducation for stabilised bipolar disorders: 5-year outcome of a randomised clinical trial. Br J Psychiatry 194:260–265. doi:10.1192/bjp.bp.107.040485

    Article  CAS  PubMed  Google Scholar 

  28. Reinares M, Colom F, Sánchez-Moreno J et al (2008) Impact of caregiver group psychoeducation on the course and outcome of bipolar patients in remission: a randomized controlled trial. Bipolar Disord 10:511–519. doi:10.1111/j.1399-5618.2008.00588.x

    Article  PubMed  Google Scholar 

  29. Popovic D, Reinares M, Goikolea JM et al (2012) Polarity index of pharmacological agents used for maintenance treatment of bipolar disorder. Eur Neuropsychopharmacol 22:339–346. doi:10.1016/j.euroneuro.2011.09.008

    Article  CAS  PubMed  Google Scholar 

  30. Reinares M, Papachristou E, Harvey P et al (2013) Towards a clinical staging for bipolar disorder: defining patient subtypes based on functional outcome. J Affect Disord 144:65–71. doi:10.1016/j.jad.2012.06.005

    Article  PubMed  Google Scholar 

  31. Bonnín CM, Sánchez-Moreno J, Martínez-Arán A et al (2012) Subthreshold symptoms in bipolar disorder: impact on neurocognition, quality of life and disability. J Affect Disord 136:650–659. doi:10.1016/j.jad.2011.10.012

    Article  PubMed  Google Scholar 

  32. Fountoulakis KN, Vieta E, Young A et al (2016) The International College of Neuropsychopharmacology (CINP) treatment guidelines for bipolar disorder in adults (CINP-BD-2017), part 4: unmet needs in the treatment of bipolar disorder and recommendations for future research. Int J Neuropsychopharmacol. doi:10.1093/ijnp/pyw072

    Article  PubMed Central  Google Scholar 

  33. Kapczinski F, Dias VV, Kauer-Sant’Anna M et al (2009) Clinical implications of a staging model for bipolar disorders. Expert Rev Neurother 9:957–966. doi:10.1586/ern.09.31

    Article  PubMed  Google Scholar 

  34. Berk M, Hallam KT, McGorry PD (2007) The potential utility of a staging model as a course specifier: a bipolar disorder perspective. J Affect Disord 100:279–281. doi:10.1016/j.jad.2007.03.007

    Article  PubMed  Google Scholar 

  35. Alda M, Kapczinski F (2016) Staging model raises fundamental questions about the nature of bipolar disorder. J Psychiatry Neurosci 41:291–293. doi:10.1503/jpn.160151

    Article  PubMed  PubMed Central  Google Scholar 

  36. Vieta E, Popovic D, Rosa AR et al (2013) The clinical implications of cognitive impairment and allostatic load in bipolar disorder. Eur Psychiatry 28:21–29. doi:10.1016/j.eurpsy.2011.11.007

    Article  CAS  PubMed  Google Scholar 

  37. Schumann G, Binder EB, Holte A et al (2014) Stratified medicine for mental disorders. Eur Neuropsychopharmacol 24:5–50. doi:10.1016/j.euroneuro.2013.09.010

    Article  CAS  PubMed  Google Scholar 

  38. Murru A, Primavera D, Oliva M et al (2015) The role of comorbidities in duration of untreated illness for bipolar spectrum disorders. J Affect Disord 188:319–323. doi:10.1016/j.jad.2015.09.009

    Article  CAS  PubMed  Google Scholar 

  39. Fountoulakis KN, Young A, Yatham L et al (2016) The International College of Neuropsychopharmacology (CINP) treatment guidelines for bipolar disorder in adults (CINP-BD-2017), part 1: background and methods of the development of guidelines. Int J Neuropsychopharmacol. doi:10.1093/ijnp/pyw091

    Article  PubMed Central  Google Scholar 

  40. Carvalho AF, Quevedo J, McIntyre RS et al (2014) Treatment implications of predominant polarity and the polarity index: a comprehensive review. Int J Neuropsychopharmacol. doi:10.1093/ijnp/pyu079

    Article  PubMed  Google Scholar 

  41. Martinez-Aran A, Vieta E, Torrent C et al (2007) Functional outcome in bipolar disorder: the role of clinical and cognitive factors. Bipolar Disord 9:103–113. doi:10.1111/j.1399-5618.2007.00327.x

    Article  CAS  PubMed  Google Scholar 

  42. Kanady JC, Soehner AM, Klein AB, Harvey AG (2017) The association between insomnia-related sleep disruptions and cognitive dysfunction during the inter-episode phase of bipolar disorder. J Psychiatr Res 88:80–88. doi:10.1016/j.jpsychires.2017.01.001

    Article  PubMed  PubMed Central  Google Scholar 

  43. Torrent C, Martinez-Arán A, del Mar Bonnin C et al (2012) Long-term outcome of cognitive impairment in bipolar disorder. J Clin Psychiatry 73:e899–e905. doi:10.4088/JCP.11m07471

    Article  PubMed  Google Scholar 

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Acknowledgements

This study was supported by Bristol-Myers Squibb France and Otsuka Pharmaceuticals France SAS. The funders had no further role in design study, data collection analysis and interpretation, writing of the report, and the decision to submit the paper for publication. We are greatly indebted to the many people who gave their time to participate in this study (Rosine Arnaud, Nabil Bedira, Anne Dillenschneider, Anne Filipovics, Pierre Vekoff and the investigators).

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Authors and Affiliations

  1. Bipolar Disorder Unit, Institute of Neuroscience, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain

    Andrea Murru, Isabella Pacchiarotti, Norma Verdolini, Maria Reinares, Carla Torrent & Eduard Vieta

  2. Division of Psychiatry, Clinical Psychology and Rehabilitation, Department of Medicine, Santa Maria della Misericordia Hospital, University of Perugia, Perugia, Italy

    Norma Verdolini

  3. Inserm U1144, Paris, France

    Pierre-Alexis Geoffroy & Frank Bellivier

  4. Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris, France

    Pierre-Alexis Geoffroy & Frank Bellivier

  5. AP-HP, GH Saint-Louis-Lariboisiére-F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, Paris, France

    Pierre-Alexis Geoffroy & Frank Bellivier

  6. Fondation FondaMental, Créteil, France

    Pierre-Alexis Geoffroy, Frank Bellivier, Pierre-Michel Llorca & Ludovic Samalin

  7. CHU Clermont-Ferrand, Department of Psychiatry, EA 7280, University of Auvergne, Clermont-Ferrand, France

    Pierre-Michel Llorca & Ludovic Samalin

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  1. Andrea Murru
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  2. Isabella Pacchiarotti
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  8. Pierre-Michel Llorca
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  9. Eduard Vieta
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  10. Ludovic Samalin
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Correspondence to Ludovic Samalin.

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Ethical statement

The procedures followed in the study were approved by an independent national ethics committee (CPP Sud-Méditerranée IV) and conducted in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent of the participants was obtained after the nature of the procedures had been fully explained.

Conflict of interest

Dr. Samalin has received grants, honoraria, or consulting fees from AstraZeneca, Bristol-Myers Squibb, Janssen-Cilag, Lundbeck, Otsuka, Sanofi-Aventis, and Takeda. Dr. Murru has received grants, honoraria, or consulting fees from Adamed, AstraZeneca, Bristol-Myers Squibb, Janssen, Lundbeck, and Otsuka. Dr. Pacchiarotti has received CME-related honoraria, or consulting fees from ADAMED, Janssen-Cilag and Lundbeck. Dr. Geoffroy has received travel awards or financial compensations from AstraZeneca, Lundbeck, Menarini France, and Otsuka. Pr Bellivier has received grants, honoraria, or consulting fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Eutherapie, Janssen-Cilag, Lundbeck, Otsuka, Sanofi-Aventis, and the European Space Agency. Pr Llorca has received grants, honoraria, or consulting fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Ferrer, Janssen-Cilag, Lundbeck, Otsuka, Sanofi-Aventis, Servier, and Takeda. Pr Vieta has received grants and served as consultant, advisor or CME speaker for the following entities: AB-Biotics, Allergen, AstraZeneca, Bristol-Myers Squibb, Ferrer, Forest Research Institute, Gedeon Richter, Glaxo-Smith-Kline, Janssen, Lundbeck, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier, Shire, Sunovion, Takeda, Telefonica, the Brain and Behaviour Foundation, the Spanish Ministry of Science and Innovation (CIBERSAM), the Seventh European Framework Programme (ENBREC), and the Stanley Medical Research Institute. The other authors report no financial relationships with commercial interests.

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Murru, A., Pacchiarotti, I., Verdolini, N. et al. Modifiable and non-modifiable factors associated with functional impairment during the inter-episodic periods of bipolar disorder. Eur Arch Psychiatry Clin Neurosci 268, 749–755 (2018). https://doi.org/10.1007/s00406-017-0811-0

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