Bipolar disorders and retinal electrophysiological markers (BiMAR): Study protocol for a comparison of electroretinogram measurements between subjects with bipolar disorder and a healthy control group

Grégory Gross, Katelyne Tursini, Eliane Albuisson, Karine Angioi-Duprez, Jean-Baptiste Conart, Valérie Louis Dorr, Raymund Schwan, Thomas Schwitzer, Grégory Gross, Katelyne Tursini, Eliane Albuisson, Karine Angioi-Duprez, Jean-Baptiste Conart, Valérie Louis Dorr, Raymund Schwan, Thomas Schwitzer

Abstract

Background: Bipolar disorders (BD) is a common, chronic and disabling psychiatric condition. In addition to being characterized by significant clinical heterogeneity, notable disturbances of sleep and cognitive function are frequently observed in all phases of the disease. Currently, there is no readily available biomarker in current clinical practice to help diagnose or predict the disease course. Thus, identification of biomarkers in BD is today a major challenge. In this context, the study of electrophysiological biomarkers based on electroretinogram (ERG) measurements in BD seems highly promising. The BiMAR study aims to compare electrophysiological data measured with ERG between a group of euthymic patients with BD and a group of healthy control subjects. Secondarily, we will also describe the existing potential relationship between clinical, sleep and neuropsychological phenotypes of patients and electrophysiological data.

Methods: The BiMAR study is a comparative and monocentric study carried out at the Expert Center for BD in Nancy, France. In total, 70 euthymic adult patients with BD and 70 healthy control subjects will be recruited. Electrophysiological recordings with ERG and electroencephalogram (EEG) will be performed with a virtual reality headset after a standardized clinical evaluation to all participants. Then, an actigraphic monitoring of 21 consecutive days will be carried out. At the end of this period a neuropsychological evaluation will be performed during a second visit. The primary outcome will be electrophysiological measurements with ERG flash and pattern. Secondary outcomes will be EEG data, sleep settings, clinical and neuropsychological assessments. For patients only, a complementary ancillary study, carried out at the University Hospital of Nancy, will be proposed to assess the retinal structure and microvascularization using Optical Coherence Tomography. Recruitment started in January 2022 and will continue until the end of July 2023.

Discussion: The BiMAR study will contribute to identifying candidate ERG electrophysiological markers for helping the diagnosis of BD and identify subgroups of patients with different clinical profiles. Eventually, this would allow earlier diagnosis and personalized therapeutic interventions.

Clinical trial registration: The study is registered at Clinicaltrials.gov, NCT05161546, on 17 December 2021 (https://ichgcp.net/clinical-trials-registry/NCT05161546).

Keywords: actigraphy; biomarkers; bipolar disorder; electroencephalogram; electroretinogram; neuropsychology.

Conflict of interest statement

The authors declare that they have a scientific collaboration with BioSerenity in this study using the Retinaute® (BioSerenity).

Copyright © 2022 Gross, Tursini, Albuisson, Angioi-Duprez, Conart, Louis Dorr, Schwan and Schwitzer.

Figures

Figure 1
Figure 1
Flowdiagram. D, Day; EEG, Electroencephalogram; ERG, Electroretinogram; OCT, Optical Coherence Tomography.
Figure 2
Figure 2
Schedule of enrolment, interventions and assessments. *, Only concerns patients; BD, Bipolar Disorder; CPT, Conners' Continuous Performance Test; CVLT, California Verbal Learning Test; D, Day; EEG, Electroencephalogram; EHI, Edinburgh Handedness Inventory; ERG, Electroretinogram; fERG, electroretinogram flash; MADRS, Montgomery and Asberg Depression Rating Scale; MINI, Mini International Neuropsychiatric Interview; MoCA, Montreal Cognitive Assessment; OCT, Optical Coherence Tomography; PERG, electroretinogram pattern; TAP, Test of Attentional Performance; VOSP, Visual Object and Spatial Perception; YMRS, Young Mania Rating Scale.

References

    1. Merikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RMA, Petukhova M, et al. . Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry. (2007) 64:543–52. 10.1001/archpsyc.64.5.543
    1. Geoffroy PA, Etain B, Scott J, Henry C, Jamain S, Leboyer M, et al. . Reconsideration of bipolar disorder as a developmental disorder: importance of the time of onset. J Physiol Paris. (2013) 107:278–85. 10.1016/j.jphysparis.2013.03.006
    1. Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar AS. Grand challenges in global mental health. Nature. (2011) 475:27–30. 10.1038/475027a
    1. Conus P, Berger G, Theodoridou A, Schneider R, Umbricht D, MichaelisConus K, et al. . Intervention précoce dans les troubles bipolaires. Forum Médical Suisse. (2008) 8:316–9. 10.4414/fms.2008.06469
    1. Pitchot W, Scantamburlo G, Ansseau M, Souery D. Le trouble bipolaire: une affection bien complexe. Revue Médicale de Liège. (2012) 67: 366–73.
    1. Boland EM, Alloy LB. Sleep disturbance and cognitive deficits in bipolar disorder: toward an integrated examination of disorder maintenance and functional impairment. Clin Psychol Rev. (2013) 33:33–44. 10.1016/j.cpr.2012.10.001
    1. Geoffroy PA, Scott J, Boudebesse C, Lajnef M, Henry C, Leboyer M, et al. . Sleep in patients with remitted bipolar disorders: a meta-analysis of actigraphy studies. Acta Psychiatr Scand. (2015) 131:89–99. 10.1111/acps.12367
    1. Boudebesse C, Geoffroy PA, Bellivier F, Henry C, Folkard S, Leboyer M, et al. . Correlations between objective and subjective sleep and circadian markers in remitted patients with bipolar disorder. Chronobiol Int. (2014) 31:698–704. 10.3109/07420528.2014.895742
    1. Etain B, Milhiet V, Bellivier F, Leboyer M. Genetics of circadian rhythms and mood spectrum disorders. Eur Neuropsychopharmacol. (2011) 21(Suppl 4):S676–682. 10.1016/j.euroneuro.2011.07.007
    1. Quraishi S, Frangou S. Neuropsychology of bipolar disorder: a review. J Affect Disord. (2002) 72:209–26. 10.1016/S0165-0327(02)00091-5
    1. Torres IJ, Boudreau VG, Yatham LN. Neuropsychological functioning in euthymic bipolar disorder: a meta-analysis. Acta Psychiatr Scand Suppl. (2007) 434:17–26. 10.1111/j.1600-0447.2007.01055.x
    1. Gitlin MJ, Miklowitz DJ. The difficult lives of individuals with bipolar disorder: A review of functional outcomes and their implications for treatment. J Affect Disord. (2017) 209:147–54. 10.1016/j.jad.2016.11.021
    1. Schwitzer T, Schwan R, Bubl E, Lalanne L, Angioi-Duprez K, Laprevote V. Looking into the brain through the retinal ganglion cells in psychiatric disorders: a review of evidences. Prog Neuropsychopharmacol Biol Psychiatry. (2017) 76:155–62. 10.1016/j.pnpbp.2017.03.008
    1. Hoon M, Okawa H, Santina LD, Wong ROL. Functional architecture of the retina: development and disease. Prog Retin Eye Res. (2014) 42:44–84. 10.1016/j.preteyeres.2014.06.003
    1. Silverstein SM, Demmin DL, Schallek JB, Fradkin SI. Measures of retinal structure and function as biomarkers in neurology and psychiatry. Biomarkers in Neuropsychiatry. (2020) 2:100018. 10.1016/j.bionps.2020.100018
    1. Tan A, Schwitzer T, Conart J-B, Angioi-Duprez K. Study of retinal structure and function in patients with major depressive disorder, bipolar disorder or schizophrenia: a review of the literature. J Fr Ophtalmol. (2020) 43:e157–66. 10.1016/j.jfo.2020.04.004
    1. Garcia-Martin E, Gavin A, Garcia-Campayo J, Vilades E, Orduna E, Polo V, et al. . DISORDER. Retina. (2019) 39:2012–21. 10.1097/IAE.0000000000002252
    1. Polo V, Satue M, Gavin A, Vilades E, Orduna E, Cipres M, et al. . Ability of swept source OCT to detect retinal changes in patients with bipolar disorder. Eye. (2019) 33:549–56. 10.1038/s41433-018-0261-6
    1. Holder GE. Pattern electroretinography (PERG) and an integrated approach to visual pathway diagnosis. Prog Retin Eye Res. (2001) 20:531–61. 10.1016/S1350-9462(00)00030-6
    1. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. . 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. (1998) 59(Suppl 20):22–33.
    1. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. (1979) 134:382–9. 10.1192/bjp.134.4.382
    1. Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry. (1978) 133:429–35. 10.1192/bjp.133.5.429
    1. Bach M, Brigell MG, Hawlina M, Holder GE, Johnson MA, McCulloch DL, et al. . standard for clinical pattern electroretinography (PERG): 2012 update. Doc Ophthalmol. (2013) 126:1–7. 10.1007/s10633-012-9353-y
    1. Robson AG, Frishman LJ, Grigg J, Hamilton R, Jeffrey BG, Kondo M, et al. . Standard for full-field clinical electroretinography (2022 update). Doc Ophthalmol. (2022) 144:165–77. 10.1007/s10633-022-09872-0
    1. Buysse DJ, Reynolds CF, Monk TH, Berman SR, Kupfer DJ. The pittsburgh sleep quality index: a new instrument for psychiatric practice and research. Psychiatry Res. (1989) 28:193–213. 10.1016/0165-1781(89)90047-4
    1. Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep. (1991) 14:540–5. 10.1093/sleep/14.6.540
    1. Morin CM, Belleville G, Bélanger L, Ivers H. The insomnia severity index: psychometric indicators to detect insomnia cases and evaluate treatment response. Sleep. (2011) 34:601–8. 10.1093/sleep/34.5.601
    1. Smith CS, Reilly C, Midkiff K. Evaluation of three circadian rhythm questionnaires with suggestions for an improved measure of morningness. J Appl Psychol. (1989) 74:728–38. 10.1037/0021-9010.74.5.728
    1. Smith PA, Brown DF, di Milia L, Wragg C. The use of the Circadian Type Inventory as a measure of the circadian constructs of vigour and rigidity. Ergonomics. (1993) 36:169–75. 10.1080/00140139308967869
    1. Horne JA, Ostberg O. A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol. (1976) 4:97–110. 10.1037/t02254-000
    1. Netzer NC, Stoohs RA, Netzer CM, Clark K, Strohl KP. Using the Berlin Questionnaire to identify patients at risk for the sleep apnea syndrome. Ann Intern Med. (1999) 131:485–91. 10.7326/0003-4819-131-7-199910050-00002
    1. Elwood RW. The California verbal learning test: psychometric characteristics and clinical application. Neuropsychol Rev. (1995) 5:173–201. 10.1007/BF02214761
    1. Leclercq M, Zimmermann P. Applied Neuropsychology of Attention: Theory, Diagnosis and Rehabilitation. London: Psychology Press; (2004). p. 415.
    1. Cardebat D, Doyon B, Puel M, Goulet P, Joanette Y. [Formal and semantic lexical evocation in normal subjects. Performance and dynamics of production as a function of sex, age and educational level. Acta Neurol Belg. (1990) 90:207–17.
    1. Ord AS, Miskey HM, Lad S, Richter B, Nagy K, Shura RD. Examining embedded validity indicators in Conners continuous performance test-3 (CPT-3). Clin Neuropsychol. (2020) 35:1–16. 10.1080/13854046.2020.1751301
    1. Nasreddine ZS, Phillips NA, Bédirian V, Charbonneau S, Whitehead V, Collin I, et al. . The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment. J Am Geriatr Soc. (2005) 53:695–9. 10.1111/j.1532-5415.2005.53221.x
    1. Rapport LJ, Millis SR, Bonello PJ. Validation of the warrington theory of visual processing and the visual object and space perception battery. J Clin Exp Neuropsychol. (1998) 20:211–20. 10.1076/jcen.20.2.211.1169
    1. Rush AJ, Trivedi MH, Ibrahim HM, Carmody TJ, Arnow B, Klein DN, et al. . The 16-Item Quick Inventory of Depressive Symptomatology (QIDS), clinician rating (QIDS-C), and self-report (QIDS-SR): a psychometric evaluation in patients with chronic major depression. Biol Psychiatry. (2003) 54:573–83. 10.1016/S0006-3223(02)01866-8
    1. Altman EG, Hedeker D, Peterson JL, Davis JM. The altman self-rating mania scale. Biol Psychiatry. (1997) 42:948–55. 10.1016/S0006-3223(96)00548-3
    1. Henry C, M'Bailara K, Mathieu F, Poinsot R, Falissard B. Construction and validation of a dimensional scale exploring mood disorders: MAThyS (Multidimensional Assessment of Thymic States). BMC Psychiatry. (2008) 8:82. 10.1186/1471-244X-8-82
    1. Spielberger CD, Gorsuch RL, Lushene R, Vagg PR, Jacobs GA. Manual for the State-Trait Anxiety Inventory. CA: Consulting Psychologists Press Palo Alto; (1983).
    1. Rush AJ, O'Neal BL. Patient Rated Inventory of Side Effects (PRISE): unpublished rating scale. Dallas: University of Texas Southwestern Medical Center; (1999).
    1. Thompson K, Kulkarni J, Sergejew AA. Reliability and validity of a new medication adherence rating scale (MARS) for the psychoses. Schizophr Res. (2000) 42:241–7. 10.1016/S0920-9964(99)00130-9
    1. Grof P, Duffy A, Cavazzoni P, Grof E, Garnham J, MacDougall M, et al. . Is response to prophylactic lithium a familial trait? J Clin Psychiatry. (2002) 63:942–7. 10.4088/JCP.v63n1013
    1. Rosa AR, Sánchez-Moreno J, Martínez-Aran A, Salamero M, Torrent C, Reinares M, et al. . Validity and reliability of the functioning assessment short test (FAST) in bipolar disorder. Clin Pract Epidemiol Ment Health. (2007) 3:5. 10.1186/1745-0179-3-5
    1. Busner J, Targum SD. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry (Edgmont). (2007) 4:28–37.
    1. Larsen RJ, Diener E. A multitrait-multimethod examination of affect structure: hedonic level and emotional intensity. Pers Individ Dif. (1985) 6:631–6. 10.1016/0191-8869(85)90013-3
    1. Harvey PD, Greenberg BR, Serper MR. The affective lability scales: development, reliability, and validity. J Clin Psychol. (1989) 45:786–93.
    1. Buss AH, Durkee A. An inventory for assessing different kinds of hostility. J Consult Psychol. (1957) 21:343–9. 10.1037/h0046900
    1. Patton JH, Stanford MS, Barratt ES. Factor structure of the Barratt impulsiveness scale. J Clin Psychol. (1995) 51:768–74.
    1. Ward MF, Wender PH, Reimherr FW. The Wender Utah Rating Scale: an aid in the retrospective diagnosis of childhood attention deficit hyperactivity disorder. Am J Psychiatry. (1993) 150:885–90. 10.1176/ajp.150.6.885
    1. Bernstein DP, Ahluvalia T, Pogge D, Handelsman L. Validity of the childhood trauma questionnaire in an adolescent psychiatric population. J Am Acad Child Adolesc Psychiatry. (1997) 36:340–8. 10.1097/00004583-199703000-00012
    1. Fagerström KO. Towards better diagnoses and more individual treatment of tobacco dependence. Br J Addict. (1991) 86:543–7. 10.1111/j.1360-0443.1991.tb01805.x
    1. Oldfield RC. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia. (1971) 9:97–113. 10.1016/0028-3932(71)90067-4
    1. Pekár S, Brabec M. Generalized estimating equations: a pragmatic and flexible approach to the marginal GLM modelling of correlated data in the behavioural sciences. Ethology. (2018) 124:86–93. 10.1111/eth.12713
    1. Lizano P, Bannai D, Lutz O, Kim LA, Miller J, Keshavan M, et al. . Meta-analysis of retinal cytoarchitectural abnormalities in schizophrenia and bipolar disorder. Schizophr Bull. (2020) 46:43–53. 10.1093/schbul/sbz029

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