Correlation of serum homocysteine with attention and executive functions in patients with type I stable bipolar affective disorder


Bipolar affective disorder
Executive function

How to Cite

Na, W.-Q. ., Su, W., Sun, J.-S. ., Chen, H.-Z. ., Wu, L.-N. ., Li, J.-H. ., & Mei, L.-F. . (2020). Correlation of serum homocysteine with attention and executive functions in patients with type I stable bipolar affective disorder. Iranian Red Crescent Medical Journal, 22(12).


Objectives: The current study aimed to examine the correlation of the level of homocysteine (Hcy) in the serum with attention and executive functions in patients suffering from type I stable bipolar affective disorder (BPAD I).

Methods: The present cross-sectional study was conducted on 170 participants in Huzhou, Zhejiang province, China, within July 2016 to December 2017. The subjects were divided into patients with schizophrenia (n=100) as the study group and healthy volunteers (n=70) as the control group. The Hcy and folic acid levels of fasting ulnar vein serum were determined using chemiluminescent microparticle immunoassay. Patient attention was evaluated by the Trail Making Test A (TMTA), and executive functions were assessed using the Trail Making Test B (TMTB) and Stroop Color and Word Test (SCWT).

Results: The mean value of serum Hcy was significantly higher in the study group than that reported for the control group (19.01±5.83 and 11.40±4.62; P<0.001). The results of several tests of attention (59.39±19.27 and 53.26±14.82; P=0.027) and executive functions (123.75±40.60 and 107.52±29.31; P=0.013) were poorer in the study group. The serum Hcy value positively correlated with the disturbance variables of the TMTA, TMTB, and Trail Making Test. However, the duration of the Stroop-C test (SCT) and SCWT negatively correlated with the correct number of the SCT and SCWT.

Conclusions: The increase in the level of serum Hcy closely correlated with the impairment of attention and executive functions in patients suffering from stable BPAD I.


  1. Lee RS, Hermens DF, Scott J, Redoblado-Hodge MA, Naismith SL, Lagopoulos J, et al. A meta-analysis of neuropsychological functioning in first-episode bipolar disorders. J Psychiatr Res. 2014;57:1-11. doi: 10.1016/j.jpsychires.2014.06.019. [PubMed: 25016347].
  2. Rosa AR, Magalhães PV, Czepielewski L, Sulzbach MV, Goi PD, Vieta E, et al. F. Clinical staging in bipolar disorder: focus on cognition and functioning. J Clin Psychiatry. 2014;75(5):e450-6. doi: 10.4088/JCP.13m08625. [PubMed: 24922497].
  3. Galimberti C, Bosi MF, Caricasole V, Zanello R, Dell'Osso B, Viganò CA. Using network analysis to explore cognitive domains in patients with unipolar versus bipolar depression: a prospective naturalistic study. CNS Spectr. 2020;25(3):380-91. doi: 10.1017/S1092852919000968. [PubMed: 31060642]. 
  4. de Filippis R, Aloi M, Bruni A, Gaetano R, Segura-Garcia C, De Fazio P. Bipolar disorder and obsessive compulsive disorder: The comorbidity does not further impair the neurocognitive profile. J Affect Disord. 2018;235:1-6. doi: 10.1016/j.jad.2018.03.010. [PubMed: 29627704]. 
  5. Anaya C, Torrent C, Caballero FF, Vieta E, Bonnin Cdel M, Ayuso-Mateos JL; CIBERSAM Functional Remediation Group. Cognitive reserve in bipolar disorder: relation to cognition, psychosocial functioning and quality of life. Acta Psychiatr Scand. 2016;133(5):386-98. doi: 10.1111/acps.12535. [PubMed: 26719018].
  6. Schwarz K, Moessnang C, Schweiger JI, Baumeister S, Plichta MM, Brandeis D, et al. Transdiagnostic prediction of affective, cognitive, and social function through brain reward anticipation in schizophrenia, bipolar disorder, major depression, and autism spectrum diagnoses. Schizophr Bull. 2020;46(3):592-602. doi: 10.1093/schbul/sbz075. [PubMed: 31586408].
  7. Tian X, Gong L, Jin A, Wang Y, Zhou X, Tan Y. E3 ubiquitin ligase siah‑1 nuclear accumulation is critical for homocysteine‑induced impairment of C6 astroglioma cells. Mol Med Rep. 2019;20(3):2227-35. doi: 10.3892/mmr.2019.10449. [PubMed: 31322210].
  8. El-Missiry MA, ElKomy MA, Othman AI, AbouEl-Ezz AM. Punicalagin ameliorates the elevation of plasma homocysteine, amyloid-β, TNF-α and apoptosis by advocating antioxidants and modulating apoptotic mediator proteins in brain. Biomed Pharmacother. 2018;102:472-80. doi: 10.1016/j.biopha.2018.03.096. [PubMed: 29579708]. 
  9. Pierozan P, Biasibetti-Brendler H, Schmitz F, Ferreira F, Netto CA, Wyse ATS. Synergistic toxicity of the neurometabolites quinolinic acid and homocysteine in cortical neurons and astrocytes: implications in alzheimer's disease. Neurotox Res. 2018;34(1):147-63. doi: 10.1007/s12640-017-9834-6. [PubMed: 29124681].
  10. Karkhah A, Ataee R, Ataie A. Morphine pre- and post-conditioning exacerbates apoptosis in rat hippocampus cells in a model of homocysteine-induced oxidative stress. Biomed Rep. 2017;7(4):309-13. doi: 10.3892/br.2017.962. [PubMed: 28928969].
  11. Dittmann S, Seemüller F, Grunze HC, Schwarz MJ, Zach J, Fast K, et al.The impact of homocysteine levels on cognition in euthymic bipolar patients: a cross-sectional study. J Clin Psychiatry. 2008;69(6):899-906. doi: 10.4088/jcp.v69n0603. [PubMed: 18399726].
  12. Dias VV, Brissos S, Cardoso C, Andreazza AC, Kapczinski F. Serum homocysteine levels and cognitive functioning in euthymic bipolar patients. J Affect Disord. 2009;113(3):285-90. doi: 10.1016/j.jad.2008.05.011. [PubMed: 18579214].
  13. Osher Y, Bersudsky Y, Silver H, Sela BA, Belmaker RH. Neuropsychological correlates of homocysteine levels in euthymic bipolar patients. J Affect Disord. 2008;105(1-3):229-33. doi: 10.1016/j.jad.2007.04.005. [P{ubMed: 17490752].
  14. Salagre E, Vizuete AF, Leite M, Brownstein DJ, McGuinness A, Jacka F, et al. Homocysteine as a peripheral biomarker in bipolar disorder: A meta-analysis. Eur Psychiatry. 2017;43:81-91. doi: 10.1016/j.eurpsy.2017.02.482. [PubMed: 28371745].
  15. Weiner L, Doignon-Camus N, Bertschy G, Giersch A. Thought and language disturbance in bipolar disorder quantified via process-oriented verbal fluency measures. Sci Rep. 2019;9(1):14282. doi: 10.1038/s41598-019-50818-5. [PubMed: 31582814].
  16. Fontana E, Mandolini GM, Delvecchio G, Bressi C, Soares JC, Brambilla P. Intravenous valproate in the treatment of acute manic episode in bipolar disorder: A review. J Affect Disord. 2020;260:738-43. doi: 10.1016/j.jad.2019.08.071. [PubMed: 31581039].
  17. Alosaimi FD, AlAteeq DA, Bin Hussain SI, Alosaimi FD, AlAteeq DA, Bin Hussain SI, et al. Public awareness, beliefs, and attitudes toward bipolar disorder in saudi arabia. Neuropsychiatr Dis Treat. 2019;15:2809-18. doi: 10.2147/NDT.S209037. [PubMed: 31579220]. 
  18. Nguyen TT, Kovacevic S, Dev SI, Lu K, Liu TT, Eyler LT. Dynamic functional connectivity in bipolar disorder is associated with executive function and processing speed: A preliminary study. Neuropsychology. 2017;31(1):73-83. doi: 10.1037/neu0000317. [PubMed: 27775400].
  19. Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, et al. Global burden of disease attributable to mental and substance use disorders: findings from the global burden of disease study 2010. Lancet. 2013;382(9904):1575-86. doi: 10.1016/S0140-6736(13)61611-6. [PubMed: 23993280].
  20. Newton DF, Naiberg MR, Andreazza AC, Scola G, Dickstein DP, Goldstein BI. Association of lipid peroxidation and brain-derived neurotrophic factor with executive function in adolescent bipolar disorder. Psychopharmacology (Berl). 2017;234(4): 647-56. doi: 10.1007/s00213-016-4500-x. [PubMed: 27957714].
  21. Bora E, Hıdıroğlu C, Özerdem A, Kaçar ÖF, Sarısoy G, Civil Arslan F, et al. Executive dysfunction and cognitive subgroups in a large sample of euthymic patients with bipolar disorder. Eur Neuropsychopharmacol. 2016;26(8):1338-47. doi: 10.1016/j.euroneuro.2016.04.002. [PubMed: 27139077].
  22. Mann-Wrobel MC, Carreno JT, Dickinson D. Meta-analysis of neuropsychological functioning in euthymic bipolar disorder: an update and investigation of moderator variables. Bipolar Disord. 2011;13(4):334-42. doi: 10.1111/j.1399-5618.2011.00935.x. [PubMed: 21843273].
  23. Strakowski SM, DelBello MP, Adler C, Cecil DM, Sax KW. Neuroimaging in bipolar disorder. Bipolar disord. 2000;2(3 Pt 1):148-64. doi: 10.1034/j.1399-5618.2000.020302.x. [PubMed: 11256682].
  24. Dev SI, McKenna BS, Sutherland AN, Shin DD, Liu TT, Wierenga CE, et al. Increased cerebral blood flow associated with better response inhibition in bipolar disorder. J Int Neuropsycbol Soc. 2015;21(2):105-15. doi: 10.1017/S135561771400112X. [PubMed: 25771682].
  25. Dittmann S, Seemüller F, Grunze HC, Schwarz MJ, Zach J, Fast K, et al.The impact of homocysteine levels on cognition in euthymic bipolar patients: a cross-sectional study. J Clin Psychiatry. 2008;69(6):899-906. doi: 10.4088/jcp.v69n0603. [PubMed: 18399726].[WU1] 
  26. Zou CG, Banerjee R. Homocysteine and redox signaling. Antioxid Redox Signal. 2005;7(5-6):547-59. doi: 10.1089/ars.2005.7.547. [PubMed: 15890000].
  27. Normala I, Abdul HA, Azlin B, Nik Ruzyanei NJ, Hazli Z, Shah SA. Executive function and attention span in euthymic patients with bipolar 1 disorder. Med J Malaysia. 2010;65(3):199-203. [PubMed: 21939168].