Hostname: page-component-6bb9c88b65-vpjdr Total loading time: 0 Render date: 2025-07-26T06:59:12.925Z Has data issue: false hasContentIssue false
  • English
  • Français

An ecological study of objective rest–activity markers of lithium response in bipolar-I-disorder

Published online by Cambridge University Press:  13 November 2020

Jan Scott Open the ORCID record for Jan Scott [Opens in a new window] ,
Vincent Hennion ,
Manon Meyrel ,
Frank Bellivier  and
Bruno Etain
Jan Scott*
Affiliation:
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK Centre for Affective Disorders, IoPPN, Kings College, London, UK Université de Paris, Paris, France
Vincent Hennion
Affiliation:
Université de Paris, Paris, France AP-HP.Nord, DMU Neurosciences, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand Widal, Département de Psychiatrie et de Médecine Addictologique, Paris, France
Manon Meyrel
Affiliation:
Université de Paris, Paris, France AP-HP.Nord, DMU Neurosciences, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand Widal, Département de Psychiatrie et de Médecine Addictologique, Paris, France
Frank Bellivier
Affiliation:
Université de Paris, Paris, France AP-HP.Nord, DMU Neurosciences, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand Widal, Département de Psychiatrie et de Médecine Addictologique, Paris, France INSERM, UMR-S 1144, Optimisation Thérapeutique en Neuropsychopharmacologie, Université de Paris, Paris, France
Bruno Etain
Affiliation:
Centre for Affective Disorders, IoPPN, Kings College, London, UK Université de Paris, Paris, France AP-HP.Nord, DMU Neurosciences, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand Widal, Département de Psychiatrie et de Médecine Addictologique, Paris, France INSERM, UMR-S 1144, Optimisation Thérapeutique en Neuropsychopharmacologie, Université de Paris, Paris, France
*
Author for correspondence: Jan Scott, E-mail: jan.scott@newcastle.ac.uk
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Despite its pivotal role in prophylaxis for bipolar-I-disorders (BD-I), variability in lithium (Li) response is poorly understood and only a third of patients show a good outcome. Converging research strands indicate that rest–activity rhythms can help characterize BD-I and might differentiate good responders (GR) and non-responders (NR).

Methods

Seventy outpatients with BD-I receiving Li prophylaxis were categorized as GR or NR according to the ratings on the retrospective assessment of response to lithium scale (Alda scale). Participants undertook 21 consecutive days of actigraphy monitoring of sleep quantity (SQ), sleep variability (SV) and circadian rhythmicity (CR).

Results

Twenty-five individuals were categorized as GR (36%). After correcting statistical analysis to minimize false discoveries, four variables (intra-daily variability; median activity level; amplitude; and relative amplitude of activity) significantly differentiated GR from NR. The odds of being classified as a GR case were greatest for individuals showing more regular/stable CR (1.41; 95% confidence interval (CI) 1.08, 2.05; p < 0.04). Also, there was a trend for lower SV to be associated with GR (odds ratio: 0.56; 95% CI 0.31, 1.01; p < 0.06).

Conclusions

To our knowledge, this is the largest actigraphy study of rest–activity rhythms and Li response. Circadian markers associated with fragmentation, variability, amount and/or amplitude of day and night-time activity best-identified GR. However, associations were modest and future research must determine whether these objectively measured parameters, singly or together, represent robust treatment response biomarkers. Actigraphy may offer an adjunct to multi-platform approaches aimed at developing personalized treatments or stratification of individuals with BD-I into treatment-relevant subgroups.

Keywords

Actigraphybipolar disordersclinical cohortlithiumresponse

Information

Type
Original Article
Information
Psychological Medicine , Volume 52 , Issue 12 , September 2022 , pp. 2281 - 2289
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

Ancoli-Israel, S., Cole, R., Alessi, C., Chambers, M., Moorcroft, W., & Pollak, C. P. (2003). The role of actigraphy in the study of sleep and circadian rhythms. Sleep, 26(3), 342–392.CrossRefGoogle Scholar
Barnett, J. H., & Smoller, J. W. (2009). The genetics of bipolar disorder. Neuroscience, 164(1), 331–343.CrossRefGoogle ScholarPubMed
Bei, B., Wiley, J. F., Trinder, J., & Manber, R. (2016). Beyond the mean: a systematic review on the correlates of daily intraindividual variability of sleep/wake patterns. Sleep Medicine Review, 2(8), 108–124.CrossRefGoogle Scholar
Bellivier, F., Geoffroy, P., Etain, B., & Scott, J. (2015). Sleep- and circadian rhythm-associated pathways as therapeutic targets in bipolar disorder. Expert Opinion Therapeutic Targets, 19, 747–763.CrossRefGoogle ScholarPubMed
Bellivier, F., Geoffroy, P., Scott, J., Schurhoff, F., Leboyer, M., & Etain, B. (2013). Biomarkers of bipolar disorder: specific or shared with schizophrenia? Frontiers Bioscience (Elite Ed), 5, 845–863.CrossRefGoogle ScholarPubMed
Benedetti, F., Dallaspezia, S., Fulgosi, M. C., Barbini, B., Colombo, C., & Smeraldi, E. (2007). Phase advance is an actimetric correlate of antidepressant response to sleep deprivation and light therapy in bipolar depression. Chronobiology International, 24(5), 921–937.CrossRefGoogle ScholarPubMed
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. Journal Royal Statistical Society, 1995, 289–300.Google Scholar
Carr, O., Saunders, K., Tsanas, A., Bilderbeck, A., Palmius, N., Geddes, J. (2018). Variability in phase and amplitude of diurnal rhythms is related to variation of mood in bipolar and borderline personality disorder. Scientific Reports, 8(1), 1649.CrossRefGoogle ScholarPubMed
De Crescenzo, F., Economou, A., Sharpley, A., Gormez, A., & Quested, D. (2017). Actigraphic features of bipolar disorder: a systematic review and meta-analysis. Sleep Medicine Review, 33, 58–69.CrossRefGoogle ScholarPubMed
Etain, B., Milhiet, V., Bellivier, F., & Leboyer, M. (2011). Genetics of circadian rhythms and mood spectrum disorders. European Neuropsychopharmacology, 21, S676–S682.CrossRefGoogle ScholarPubMed
First, M. B. (2016). The importance of developmental field trials in the revision of psychiatric classifications. Lancet Psychiatry, 3(6), 579–584.CrossRefGoogle ScholarPubMed
Frey, B., Andreazza, A. C., Houenou, J., Jamain, S., Goldstein, B., Frye, M. (2013). Biomarkers in bipolar disorder: a positional paper from the international society for bipolar disorders biomarkers task force. Australia New Zealand Journal Psychiatry, 47(4), 321–332.CrossRefGoogle ScholarPubMed
Geoffroy, P., Curis, E., Courtin, C., Moreira, J., Morvillers, T., Etain, B. (2018). Lithium response in bipolar disorders and core clock gene expression. World Journal Biological Psychiatry, 19(8), 619–632.CrossRefGoogle Scholar
Geoffroy, P., Scott, J., Boudebesse, C., Lajnef, M., Henry, C., Leboyer, M. (2015). Sleep in patients with remitted bipolar disorders: a meta-analysis of actigraphy studies. Acta Psychiatrica Scandinavica, 131(2), 89–99.CrossRefGoogle ScholarPubMed
Grillaut-Laroche, D., Etain, B., Severus, E., Scott, J., & Bellivier, F. (2020). Socio-demographic and clinical predictors of outcome to long-term treatment with lithium in bipolar disorders: a systematic review of the contemporary literature and recommendations from the ISBD/IGSLI task force on treatment with lithium. International Journal Bipolar Disorders. In press.Google Scholar
Grof, P., Duffy, A., Cavazzoni, P., Grof, E., Garnham, J., MacDougall, M. (2002). Is response to prophylactic lithium a familial trait? Journal Clinical Psychiatry, 63, 942–947.CrossRefGoogle ScholarPubMed
Harwood, A. (2005). Lithium and bipolar mood disorder: the inositol-depletion hypothesis revisited. Molecular Psychiatry, 10(1), 117–126.CrossRefGoogle ScholarPubMed
Heninger, G. R., & Kirstein, L. (1977). Effects of lithium carbonate on motor activity in mania and depression. Journal Nervous Mental Diseases, 164(3), 168–175.CrossRefGoogle ScholarPubMed
Henriksen, T., Gronli, J., Assmus, J., Fasmer, O., Schoeyen, H., & Leskauskaite, I. (2020). Blue-blocking glasses as additive treatment for mania: effects on actigraphy-derived sleep parameters. Journal Sleep Research, 5, e12984.Google Scholar
Hou, L., Heilbronner, U., Degenhardt, F., Adli, M., Akiyama, K., Akula, N. (2016). Genetic variants associated with response to lithium treatment in bipolar disorder: a genome-wide association study. Lancet, 387(10023), 1085–1093.CrossRefGoogle ScholarPubMed
Howes, O. D., McCutcheon, R., Agid, O., de Bartolomeis, A., van Beveren, N. J., Birnbaum, M. L. (2017). Treatment-resistant schizophrenia: treatment response and resistance in psychosis (TRRIP) working group consensus guidelines on diagnosis and terminology. American Journal of Psychiatry, 174(3), 216–229.CrossRefGoogle Scholar
Insel, T. R. (2014). The NIMH research domain criteria (RDoC) project: precision medicine for psychiatry. American Journal of Psychiatry, 171, 395–397.CrossRefGoogle ScholarPubMed
Kessing, L. V., Bauer, M., Nolen, W. A., Severus, E., Goodwin, G. M., & Geddes, J. (2018). Effectiveness of maintenance therapy of lithium vs other mood stabilizers in monotherapy and in combinations: a systematic review of evidence from observational studies. Bipolar Disorders. doi: 10.1111/bdi.12623. [Epub ahead of print].CrossRefGoogle ScholarPubMed
Kim, S. J., Lee, Y. J., Lee, Y. J., & Cho, S. J. (2014). Effect of quetiapine XR on depressive symptoms and sleep quality compared with lithium in patients with bipolar depression. Journal Affective Disorders, 157, 33–40.CrossRefGoogle ScholarPubMed
Klein, E., Lavie, P., Meiraz, R., Sadeh, A., & Lenox, R. H. (1992). Increased motor activity and recurrent manic episodes: predictors of rapid relapse in remitted bipolar disorder patients after lithium discontinuation. Biological Psychiatry, 31(3), 279–284.CrossRefGoogle ScholarPubMed
Klein, E., Mairaz, R., Pascal, M., Hefez, A., & Lavie, P. (1991). Discontinuation of lithium treatment in remitted bipolar patients: relationship between clinical outcome and changes in sleep–wake cycles. Journal Nervous Mental Diseases, 179(8), 499–501.CrossRefGoogle ScholarPubMed
Knapen, S., Li, P., Riemersma-van der Lek, R. F., Verkooijen, S., Boks, M., & Schoevers, R. A. (2020). Fractal biomarker of activity in patients with bipolar disorder. Psychological Medicine, April, 1–8.Google ScholarPubMed
Krane-Gartiser, K., Scott, J., Nevoret, C., Benard, V., Benizri, C., Brochard, H. (2019). Which actigraphic variables optimally characterize the sleep–wake cycle of individuals with bipolar disorders? Acta Psychiatrica Scandinavica, 139(3), 269–279.CrossRefGoogle ScholarPubMed
Kripke, D. F., Judd, L. L., Hubbard, B., Janowsky, D. S., & Huey, L. Y. (1979). The effect of lithium carbonate on the circadian rhythm of sleep in normal human subjects. Biological Psychiatry, 14(3), 545–548.Google ScholarPubMed
Kripke, D. F., Mullaney, D. J., Atkinson, M., & Wolf, S. (1978). Circadian rhythm disorders in manic-depressives. Biological Psychiatry, 13(3), 335–351.Google ScholarPubMed
Kupfer, D., Weiss, B., Foster, G., Detre, T., & McPartland, R. (1974). Psychomotor activity in affective states. Archive General Psychiatry, 30(6), 765–768, Medline:4832184.CrossRefGoogle ScholarPubMed
Lewis, K., Richards, A., Karlsson, R., Leonenko, G., Jones, S., Jones, H. (2020). Comparison of genetic liability for sleep traits among individuals with bipolar disorder I or II and control participants. Journal of the American Medical Association Psychiatry, 77(3), 303–310.Google ScholarPubMed
Lyall, L. M., Wyse, C. A., Graham, N., Ferguson, A., Lyall, D. M., Cullen, B. (2018). Association of disrupted circadian rhythmicity with mood disorders, subjective wellbeing, and cognitive function: a cross-sectional study of 91105 participants from the UK biobank. Lancet Psychiatry, 5(6), 507–514.CrossRefGoogle Scholar
Manchia, M., Adli, M., Akula, N., Ardau, R., Aubry, J., Backlund, L. (2013). Assessment of response to lithium maintenance treatment in bipolar disorder: a ConLiGen (international consortium on lithium genetics) report. PLoS One, 8, e65636.CrossRefGoogle Scholar
McCarthy, M., Nievergelt, C., Kelsoe, J., & Welsh, D. (2012). A survey of genomic studies supports association of circadian clock genes with bipolar disorder spectrum illnesses and lithium response. PLoS ONE, 7, e32091.CrossRefGoogle ScholarPubMed
McCarthy, M., Wei, H., Nievergelt, C., Stautland, A., Maihofer, A., & Welsh, D. K. (2019). Chronotype and cellular circadian rhythms predict the clinical response to lithium maintenance treatment in patients with bipolar disorder. Neuropsychopharmacology, 44, 620–628.CrossRefGoogle ScholarPubMed
McClung, C. (2013). How might circadian rhythms control mood? Let me count the ways. Biological Psychiatry, 74, 242–249.CrossRefGoogle ScholarPubMed
McDonald, J. H. (2009). Handbook of biological statistics (pp. 254–260). London: Sparky House Publishing.Google Scholar
McGowan, N. M., Goodwin, G. M., Bilderbeck, A., & Saunders, K. (2020). Actigraphic patterns, impulsivity and mood instability in bipolar disorder, borderline personality disorder and healthy controls. Acta Psychiatrica Scandinavica, 141(4), 374–384.CrossRefGoogle ScholarPubMed
Meyer, N., Faulkner, S. M., McCutcheon, R. A., Pillinger, T., Dijk, D. J., & MacCabe, J. H. (2020). Sleep and circadian rhythm disturbance in remitted schizophrenia and bipolar disorder: a systematic review and meta-analysis. Schizophrenia Bulletin. pii: sbaa024.Google ScholarPubMed
Montgomery, S. A., & Asberg, M. (1979). A new depression scale designed to be sensitive to change. British Journal Psychiatry, 134, 382–389.CrossRefGoogle ScholarPubMed
Moon, J., Cho, C., Son, G., Geum, D., Chung, S., Kim, H. (2016). Advanced circadian phase in mania and delayed circadian phase in mixed mania and depression returned to normal after treatment of bipolar disorder. EBioMedicine, 11, 285–295.CrossRefGoogle ScholarPubMed
Novak, D., Albert, F., & Spaniel, F. (2014). Analysis of actigraph parameters for relapse prediction in bipolar disorder: a feasibility study. Conference Proceedings IEEE England Medical Biological Society, 2014, 4972–4975.Google ScholarPubMed
Nurnberger, J. I. Jr., Berrettini, W., Tamarkin, L., Hamovit, J., Norton, J., & Gershon, E. (1988). Supersensitivity to melatonin suppression by light in young people at high risk for affective disorder. A preliminary report. Neuropsychopharmacology, 1(3), 217–223.CrossRefGoogle ScholarPubMed
Pagani, L., St Clair, P. A., Teshiba, T. M., Service, S. K., Fears, S. C., Araya, C. (2016). Genetic contributions to circadian activity rhythm and sleep pattern phenotypes in pedigrees segregating for severe bipolar disorder. Proceedings of the National Academy Sciences USA, 113(6), E754–E761.CrossRefGoogle ScholarPubMed
R Core Team (2018). R: A language and environment for statistical computing. (Accessed at https://cran.r-project.org/metafor).Google Scholar
Salvatore, P., Ghidini, S., Zita, G., De Panfilis, C., Lambertino, S., Maggini, C., & Baldessarini, R. (2008). Circadian activity rhythm abnormalities in ill and recovered bipolar I disorder patients. Bipolar Disorders, 10, 256–265.CrossRefGoogle ScholarPubMed
Schulze, T., Alda, M., Adli, M., Akula, N., Ardau, R., Bui, E. (2010). Conligen (the international consortium on lithium genetics): an initiative by the NIMH and IGSLI to study the genetic basis of response to lithium. Neuropsychobiology, 62, 72–78.CrossRefGoogle Scholar
Scott, J. (2011). Clinical parameters of circadian rhythms in affective disorders. European Neuropsychopharmacology, 21(suppl 4), S671–S675.CrossRefGoogle ScholarPubMed
Scott, J., Etain, B., & Bellivier, F. (2018). Can an integrated science approach to precision medicine research improve lithium treatment in bipolar disorders? Frontiers Psychiatry, 9, 360.CrossRefGoogle ScholarPubMed
Scott, J., Etain, B., Manchia, M., Brichant-Petitjean, C., Geoffroy, P., Schulze, T., ConLiGen collaborators (2019 a). An examination of the quality and performance of the Alda scale for classifying lithium response phenotypes. Bipolar Disorders. doi: 10.1111/bdi.12829. [Epub ahead of print].Google ScholarPubMed
Scott, J., Etain, B., Nierenberg, A., & Bellivier, F. (2020). A taxonomy of response to mood stabilizers. Bipolar Disorders, (in press).Google ScholarPubMed
Scott, J., Hidalgo-Mazzei, D., Strawbridge, R., Young, A., Resche-Rigon, M., Etain, B. (2019 b). Prospective cohort study of early biosignatures of response to lithium in bipolar-I-disorders: overview of the H2020-funded R-LiNK initiative. International Journal Bipolar Disorders, 7(1), 20.CrossRefGoogle ScholarPubMed
Scott, J., Murray, G., Henry, C., Morken, G., Scott, E., Angst, J. (2017). Activation in bipolar disorders: a systematic review. Journal American Medical Association Psychiatry, 74(2), 189–196.Google ScholarPubMed
Shou, H., Cui, L., Hickie, I., Lameira, D., Lamers, F., Zhang, J. (2017). Dysregulation of objectively assessed 24-hour motor activity patterns as a potential marker for bipolar I disorder: results of a community-based family study. Translational Psychiatry, 7(8), e1211.CrossRefGoogle ScholarPubMed
Smoller, J. W., & Finn, C. T. (2003). Family, twin, and adoption studies of bipolar disorder. American Journal of Medical Genetics, 123C, 48–58.Google ScholarPubMed
Suh, S., Nowakowski, S., & Bernert, R. (2012). Clinical significance of night-to-night sleep variability in insomnia. Sleep Medicine, 13(5), 469–475.CrossRefGoogle ScholarPubMed
Takaesu, Y., Inoue, Y., Ono, K., Murakoshi, A., Futenma, K., Komada, Y., & Inoue, T. (2018). Circadian rhythm sleep-wake disorders predict shorter time to relapse of mood episodes in euthymic patients with bipolar disorder: a prospective 48-week study. Journal of Clinical Psychiatry, 79(1), pii: 17m11565.CrossRefGoogle ScholarPubMed
van Someren, E. J., Lijzenga, C., Mirmiran, M., & Swaab, D. F. (1997). Long-term fitness training improves the circadian rest–activity rhythm in healthy elderly males. Journal of Biological Rhythms, 12(2), 146–156.CrossRefGoogle ScholarPubMed
Walker, W., Walton, J., DeVries, A., & Nelson, R. (2020). Circadian rhythm disruption and mental health. Translational Psychiatry, 10(1), 28.CrossRefGoogle ScholarPubMed
Weiss, B., Foster, F., Reynolds, C., & Kupfer, D. (1974). Psychomotor activity in mania. Archives General Psychiatry, 31(3), 379–383.CrossRefGoogle ScholarPubMed
Whiteford, H. A., Degenhardt, L., Rehm, J., Baxter, A. J., Ferrari, A. J., Erskine, H. E. (2013). Global burden of disease attributable to mental and substance use disorders: findings from the global burden of disease study 2010. Lancet, 382, 1575–1586.CrossRefGoogle ScholarPubMed
Wolff, E., Putnam, F., & Post, R. (1985). Motor activity and affective illness. The relationship of amplitude and temporal distribution to changes in affective state. Archives of General Psychiatry, 42(3), 288–294.CrossRefGoogle ScholarPubMed
Young, R. C., Biggs, J. T., Ziegler, V. E., & Meyer, D. A. (1978). A rating scale for mania: Reliability, validity, and sensitivity. British Journal of Psychiatry, 133, 429–435.CrossRefGoogle Scholar
Supplementary material: File

Scott et al. supplementary material

Scott et al. supplementary material

Download Scott et al. supplementary material(File)
File 736.3 KB