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Clinical and subclinical neuropsychiatric abnormalities in rheumatoid arthritis patients

Abstract

Background

Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease with probable autoimmune aetiology. RA has many secondary complications and a variety of neuropsychological consequences.

Aim

The aim of this study was to estimate the frequencies of neuropsychiatric disorders in RA patients and their relationship with the duration and activity of disease.

Patients and methods

Seventy-four consecutive female RA patients were recruited and compared with 25 age-matched and education status-matched female healthy volunteers. All eligible participants underwent clinical, laboratory and electrophysiological examinations (motor and sensory nerve conduction study, F-wave of four limbs, P300 event-related potential and electroencephalography). The Structured Clinical Interview for Diagnostic and statistical manual of mental disorders, 3rd ed., Revised (DSM-III-R) Axis I Disorders (SCID-I) for diagnosis of psychiatric illness and the Wechsler Adult Intelligence Scale, 3rd ed. (WAIS-III) with assessment of total scale, verbal and performance intelligence quotients (IQ) were administered to all participants.

Results

Fourteen (18.9%) patients had evidence of symptomatic peripheral neuropathy and radiculopathy, whereas 60.8% had psychiatric disorders. Depression was the most prevalent psychiatric disorder (45%), followed by anxiety (27%) and comorbid anxiety with depression (21.6%). Low IQ scores were recorded in 54% of patients. P300 latency was significantly prolonged (P = 0.0001), and seven (9.5%) RA patients recorded abnormal P300 latency (>mean ± 2 SD) compared with control values. Abnormal electroencephalography findings were observed in 48.6%. Visual analogue scale pain score was significantly higher among patients with psychiatric disorders versus patients without psychiatric disorders (P = 0.0001). Significant negative correlation was recorded between Disease Activity Score and total IQ score (P = 0.01), whereas no significant association was seen between Disease Activity Score and the presence of neuropathy or psychiatric disorders.

Conclusion

Cognitive impairment, depression, anxiety and peripheral neuropathy are common in RA patients. Early diagnosis and management of neuropsychiatric disorders in RA patients may greatly improve the patients’ health-related quality of life.

References

  1. Pollard L, Choy EH, Scott DL. The consequences of rheumatoid arthritis: quality of life measures in the individual patient. Clin Exp Rheumatol 2005; 23(Suppl 39): S43–S52.

  2. Hart FD, Golding JR. Rheumatoid neuropathy. Br Med J 1960; 1:1594–1600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Nadkar MY, Agarwal R, Samant RS, Chhugani SJ, Idgunji SS, Iyer S, Borges NE Neuropathy in rheumatoid arthritis. J Assoc Physicians India 2001; 49:217–220.

    CAS  PubMed  Google Scholar 

  4. Bharadwaj A, Haroon N. Interstitial lung disease and neuropathy as predominant extra-articular manifestations in patients with rheumatoid arthritis: a prospective study. Med Sci Monit 2005; 11:CR498–CR502.

    PubMed  Google Scholar 

  5. Agarwal V, Singh R, Wiclaf, Chauhan S, Tahlan A, Ahuja CK, et al. A clinical, electrophysiological, and pathological study of neuropathy in rheumatoid arthritis. Clin Rheumatol 2008; 27:841–844.

    Article  PubMed  Google Scholar 

  6. Chopra A, Abdel-Nasser A. Epidemiology of rheumatic musculoskeletal disorders in the developing world. Best Pract Res Clin Rheumatol 2008; 22:583–604.

    Article  PubMed  Google Scholar 

  7. Bruce TO. Comorbid depression in rheumatoid arthritis: pathophysiology and clinical implications. Curr Psychiatry Rep 2008; 10:258–264.

    Article  PubMed  Google Scholar 

  8. Covic T, Tyson G, Spencer D, Howe G. Depression in rheumatoid arthritis patients: demographic, clinical, and psychological predictors. J Psychosom Res 2006; 60:469–476.

    Article  PubMed  Google Scholar 

  9. VanDyke MM, Parker JC, Smarr KL, Hewett JE, Johnson GE, Slaughter JR, Walker SE. Anxiety in rheumatoid arthritis. Arthritis Rheum 2004; 51:408–412.

    Article  PubMed  Google Scholar 

  10. Wright GE, Parker JC, Smarr KL, Johnson JC, Hewett JE, Walker SE. Age, depressive symptoms, and rheumatoid arthritis. Arthritis Rheum 1998; 41:298–305.

    Article  CAS  PubMed  Google Scholar 

  11. Dickens C, McGowan L, Clark-Carter D, Creed F. Depression in rheumatoid arthritis: a systematic review of the literature with meta-analysis. Psychosom Med 2002; 64:52–60.

    Article  PubMed  Google Scholar 

  12. Frank RG, Kashani JH, Parker JC, Beck NC, Brownlee-Duffeck M, Elliott TR, et al. Antidepressant analgesia in rheumatoid arthritis. J Rheumatol 1988; 15:1632–1638.

    CAS  PubMed  Google Scholar 

  13. Murphy S, Creed F, Jayson MI. Psychiatric disorder and illness behaviour in rheumatoid arthritis. Br J Rheumatol 1988 ; 27:357–363.

    CAS  Google Scholar 

  14. Ahles TA, Khan SA, Yunus MB, Spiegel DA, Masi AT. Psychiatric status of patients with primary fibromyalgia, patients with rheumatoid arthritis, and subjects without pain: a blind comparison of DSM-III diagnoses. Am J Psychiatry 1991; 148:1721–1726.

    Article  CAS  PubMed  Google Scholar 

  15. Uguz F, Akman C, Kucuksarac S, Tufekci O. Anti-tumor necrosis factor-alpha therapy is associated with less frequent mood and anxiety disorders in patients with rheumatoid arthritis. Psychiatry Clin Neurosci 2009; 63:50–55.

    Article  CAS  PubMed  Google Scholar 

  16. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31:315–324.

    Article  CAS  PubMed  Google Scholar 

  17. van Gestel AM, Prevoo ML, van’t Hof MA, van Rijswijk MH, van de Putte LB, van Riel PL. Development and validation of the European League Against Rheumatism response criteria for rheumatoid arthritis. Comparison with the preliminary American College of Rheumatology and the World Health Organization/International League Against Rheumatism Criteria. Arthritis Rheum1996; 39:34–40.

    Google Scholar 

  18. Spitzer RL, Williams JBW, Gibbon M, First MB. Structured Clinical Interview for DSM-III-R, Patient Edition/Non-patient Edition, (SCID-P/SCID-NP), Washington, DC: American Psychiatric Press, Inc., 1990.

  19. Wechsler D. Wechsler Adult Intelligence Scale. 3rd ed. San Antonia, TX: The Psychological Corporation; 1997.

    Google Scholar 

  20. Polich J. P300 clinical utility and control of variability. J Clin Neurophysiol 1998; 15:14–33.

    Article  CAS  PubMed  Google Scholar 

  21. Bayrak AO, Durmus D, Durmaz Y, Demir I, Canturk F, Onar MK. Electrophysiological assessment of polyneuropathic involvement in rheumatoid arthritis: relationships among demographic, clinical and laboratory findings. Neurol Res 2010; 32:711–714.

    Article  PubMed  Google Scholar 

  22. Aneja R, Singh M, Shankar S, et al. Prevalence of peripheral neuropathy in patients with newly diagnosed rheumatoid arthritis. Indian J Rheumatol 2007; 2:47–50.

    Article  Google Scholar 

  23. Sakini RA, Abdul-Zehra IK, Al-Nimer MS. Neuropathic manifestations in rheumatoid arthritis: a clinical and electrophysiological assessment in a small sample of Iraqi patients. Ann Saudi Med 2005; 25:247–249.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Biswas M, Chatterjee A, Ghosh SK, Dasgupta S, Ghosh K, Ganguly PK. Prevalence, types, clinical associations, and determinants of peripheral neuropathy in rheumatoid patients. Ann Indian Acad Neurol 2011; 14:194–197.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Hamed S, Hamed E, Elattar AM, Rahman MSA, Amine NF. Cranial and peripheral neuropathy in rheumatoid arthritis with special emphasis to II, V, VII and XI cranial nerves. Aplar J Rheumatol 2006; 9:216–226.

    Article  Google Scholar 

  26. Lanzillo B, Pappone N, Crisci C, di Girolamo C, Massini R, Caruso G. Subclinical peripheral nerve involvement in patients with rheumatoid arthritis. Arthritis Rheum 1998; 41:1196–1202.

    Article  CAS  PubMed  Google Scholar 

  27. Al-Ghamdi A, Attar SM. Extra-articular manifestations of rheumatoid arthritis: a hospital-based study. Ann Saudi Med 2009; 29:189–193.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Albani G, Ravaglia S, Cavagna L, Caporali R, Montecucco C, Mauro A. Clinical and electrophysiological evaluation of peripheral neuropathy in rheumatoid arthritis. J Peripher Nerv Syst 2006; 11:174–175.

    Article  PubMed  Google Scholar 

  29. Lang AH, Kalliomäki JL, Puusa A, Halonen JP. Sensory neuropathy in rheumatoid arthritis: an electroneurographic study. Scand J Rheumatol 1981; 10:81–84.

    Article  CAS  PubMed  Google Scholar 

  30. Kho LK, Kermode AG. Leflunomide-induced peripheral neuropathy. J Clin Neurosci 2007; 14:179–181.

    Article  CAS  PubMed  Google Scholar 

  31. Dickens C, Jackson J, Tomenson B, Hay E, Creed F. Association of depression and rheumatoid arthritis. Psychosomatics 2003; 44:209–215.

    Article  PubMed  Google Scholar 

  32. Dickens C, Creed F. The burden of depression in patients with rheumatoid arthritis. Rheumatology (Oxford) 2001; 40:1327–1330.

    Article  CAS  Google Scholar 

  33. Lok EY, Mok CC, Cheng CW, Cheung EF. Prevalence and determinants of psychiatric disorders in patients with rheumatoid arthritis. Psychosomatics 2010; 51:338–338.e8.

    Article  PubMed  Google Scholar 

  34. Dean C, Surtees PG, Sashidharan SP. Comparison of research diagnostic systems in an Edinburgh community sample. Br J Psychiatry 1983; 142:247–256.

    Article  CAS  PubMed  Google Scholar 

  35. Maier SF, Watkins LR. Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychol Rev 1998; 105:83–107.

    Article  CAS  PubMed  Google Scholar 

  36. Raison CL, Capuron L, Miller AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006; 27:24–31.

    Article  CAS  PubMed  Google Scholar 

  37. Sato E, Nishimura K, Nakajima A, Okamoto H, Shinozaki M, Inoue E, et al. Major depressive disorder in patients with rheumatoid arthritis. Mod Rheumatol 2013; 23:237–244.

    Article  CAS  PubMed  Google Scholar 

  38. Kojima M, Kojima T, Suzuki S, Oguchi T, Oba M, Tsuchiya H, et al. Depression, inflammation, and pain in patients with rheumatoid arthritis. Arthritis Rheum 2009; 61:1018–1024.

    Article  PubMed  Google Scholar 

  39. Lisitsyna TA, Zeltyn’ AE, Vel’tishchev DIu, Kovalevskaia OB, Seravina OF, Novikova DS, et al. Cognitive impairment and anxiety-depressive disorders in patients with rheumatoid arthritis. Zh Nevrol Psikhiatr Im S S Korsakova 2012; 112(Pt 2): 96–103.

  40. Shelley BP, Trimble MR, Boutros NN. Electroencephalographic cerebral dysrhythmic abnormalities in the trinity of nonepileptic general population, neuropsychiatric, and neurobehavioral disorders. J Neuropsychiatry Clin Neurosci 2008; 20:7–22.

    Article  PubMed  Google Scholar 

  41. Sillanpää M, Lang AH, Kalimo H. Natural history of juvenile rheumatoid arthritis. A follow-up study of a case with special reference to clinical, electroencephalographic and neuropathological findings. Acta Paediatr Scand 1978; 67:537–541.

    PubMed  Google Scholar 

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Correspondence to Eman M. Khedr MD.

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Khedr, E.M., El Fetoh, N.A., Herdan, O. et al. Clinical and subclinical neuropsychiatric abnormalities in rheumatoid arthritis patients. Egypt Rheumatol Rehabil 42, 11–18 (2015). https://doi.org/10.4103/1110-161X.155625

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