Blood homocysteine concentration (BHC) is higher in patients with alcohol use disorder (AUD). Previous studies have found a relationship between depressive symptoms severity and BHC in AUD patients and recently some authors have found high BHC among patients with bipolar disorder, both during manic and depressive episodes and in euthymic state. However, BHC in patients with mixed mood episode has not yet been investigated. The aim of this study was to evaluate the BHC of patients with AUD and mixed mood episode.
A sample of AUD outpatients was assessed by Mini-International Neuropsychiatric Interview (MINI Plus): those with a DSM-IV-TR mood disorder with mixed features were included in the MIXED group (n = 45), whereas those without mood episode were gathered in the NO MOOD group (n = 23). Two subgroups, MIXMANIA and MIXDEPRESSION, were formed according to the prevalence of manic or depressive symptoms, assessed by Young Mania Rating Scale (YMRS), and Hamilton Rating Scale for Depression (HDRS). The Alcohol Use Disorder Identification Test (AUDIT) was used to appraise the AUD. BHC was determined by High-Performance Liquid Chromatography.
The MIXED group showed greater severity of both depressive (26.35 ± 9.96 vs. 4.77 ± 0.92; p < 0.001) and manic (22.35 ± 3.30 vs. 6.14 ± 1.12; p < 0.001) symptoms, and higher BHC (28.80 ± 11.47 vs. 10.83 ± 2.81; p < 0.001), than the NO MOOD group. BHC was strongly correlated to the HDRS, YMRS and AUDIT scores, just as HDRS was to YMRS, and AUDIT was to both HDRS and YMRS, in the MIXED group only (p < 0.001).
The MIXDEPRESSION subgroup showed higher BHC than the MIXMANIA subgroup (Mdn = 42.96, IQR = 10.44 vs. Mdn = 19.77, IQR = 5.93; p < 0.001).
A linear regression model conducted on the MIXED group found a significant predictive value for BHC of both HDRS (β = 0.560, t = 2.43, p = 0.026) and AUDIT (β = 0.348, t = 2.17, p = 0.044).
Depressive symptoms seem to be mainly implicated in the BHC elevation among patients with both mixed features mood disorder and AUD.
Bleich S, Degner D, Sperling W, Bönsch D, Thürauf N, Kornhuber J. Homocysteine as a neurotoxin in chronic alcoholism. Prog Neuro-Psychopharmacol Biol Psychiatry. 2004;28:453–64. CrossRef
Guo H, Chi J, Xing Y, Wang P. Influence of folic acid on plasma homocysteine levels & arterial endothelial function in patients with unstable angina. Indian J Med Res. 2009;129:279–84. PubMed
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5. 5 edition. Washington: American Psychiatric Publishing; 2013.
Ganji V, Kafai MR. Third National Health and nutrition examination survey. Demographic, health, lifestyle, and blood vitamin determinants of serum total homocysteine concentrations in the third National Health and nutrition examination survey, 1988–1994. Am. J Clin Nutr. 2003;77:826–33.
Mennen LI, de Courcy GP, Guilland J-C, Ducros V, Zarebska M, Bertrais S, et al. Relation between homocysteine concentrations and the consumption of different types of alcoholic beverages: the French supplementation with antioxidant vitamins and minerals study. Am J Clin Nutr. 2003;78:334–8.
Gibson A, Woodside JV, Young IS, Sharpe PC, Mercer C, Patterson CC, et al. Alcohol increases homocysteine and reduces B vitamin concentration in healthy male volunteers--a randomized, crossover intervention study. QJM Mon J Assoc Physicians. 2008;101:881–7.
Bleich S, Degner D, Wiltfang J, Maler JM, Niedmann P, Cohrs S, et al. Elevated homocysteine levels in alcohol withdrawal. Alcohol Alcohol. Oxf. Oxfs. 2000;35:351–4.
Bleich S, Degner D, Javaheripour K, Kurth C, Kornhuber J. Homocysteine and alcoholism. J Neural Transm Suppl. 2000:187–96.
Cravo ML, Glória LM, Selhub J, Nadeau MR, Camilo ME, Resende MP, et al. Hyperhomocysteinemia in chronic alcoholism: correlation with folate, vitamin B-12, and vitamin B-6 status. Am J Clin Nutr. 1996;63:220–4. PubMed
Cravo ML, Camilo ME. Hyperhomocysteinemia in chronic alcoholism: relations to folic acid and vitamins B(6) and B(12) status. Nutr Burbank Los Angel Cty Calif. 2000;16:296–302. CrossRef
De la Vega MJ, Santolaria F, González-Reimers E, Alemán MR, Milena A, Martínez-Riera A, et al. High prevalence of hyperhomocysteinemia in chronic alcoholism: the importance of the thermolabile form of the enzyme methylenetetrahydrofolate reductase (MTHFR). Alcohol Fayettev. N. 2001;25:59–67.
Barak AJ, Beckenhauer HC, Tuma DJ. Hepatic transmethylation and blood alcohol levels. Alcohol Alcohol Oxf Oxfs. 1991;26:125–8. CrossRef
Barak AJ, Beckenhauer HC, Tuma DJ. Betaine, ethanol, and the liver: a review. Alcohol Fayettev N. 1996;13:395–8. CrossRef
Barak AJ, Beckenhauer HC, Tuma DJ. Methionine synthase. A possible prime site of the ethanolic lesion in liver. Alcohol Fayettev N Y. 2002;26:65–7. CrossRef
Halsted CH, Villanueva JA, Devlin AM, Chandler CJ. Metabolic interactions of alcohol and folate. J Nutr. 2002;132:2367S–72S. PubMed
Halsted CH, Medici V. Vitamin-dependent methionine metabolism and alcoholic liver disease. Adv Nutr Bethesda Md. 2011;2:421–7. CrossRef
Reynolds EH, Preece JM, Bailey J, Coppen A. Folate deficiency in depressive illness. Br J Psychiatry J Ment Sci. 1970;117:287–92.
Lok A, Mocking RJT, Assies J, Koeter MW, Bockting CL, de Vries GJ, et al. The one-carbon-cycle and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in recurrent major depressive disorder; influence of antidepressant use and depressive state? J Affect Disord. 2014;166:115–23. CrossRefPubMed
Refsum H, Nurk E, Smith AD, Ueland PM, Gjesdal CG, Bjelland I, et al. The Hordaland Homocysteine study: a community-based study of homocysteine, its determinants, and associations with disease. J Nutr. 2006;136:1731S–40S. PubMed
Chiarani F, Tramontina JF, Ceresér KM, Kunz M, Paim L, Vargas CR, et al. Homocysteine and other markers of cardiovascular risk during a manic episode in patients with bipolar disorder. Rev. Bras. Psiquiatr. São Paulo Braz. 1999;2013(35):157–60.
Kraepelin E. Manic-depressive insanity and paranoia. Livingstone. Robertson George M: Edinburgh, Scotland; 1921.
Maina G, Bertetto N, Domene Boccolini F, Di Salvo G, Rosso G, Bogetto F. The concept of mixed state in bipolar disorder: from Kraepelin to DSM-5. J Psychopathol. 2013;19:287–95.
Perugi G, Medda P, Zanello S, Toni C, Cassano GB. Episode length and mixed features as predictors of ECT nonresponse in patients with medication-resistant major depression. Brain Stimulat. 2012;5:18–24. CrossRef
American Psychiatric Association. DSM-IV-TR: diagnostic and statistical manual of Mental disorders. 4th ed text revision edition. Washington: American Psychiatric Press Inc.; 2000.
Hapuarachchi JR, Chalmers AH, Winefield AH, Blake-Mortimer JS. Changes in clinically relevant metabolites with psychological stress parameters. Behav Med Wash DC. 2003;29:52–9. CrossRef
Levine J, Sela B-A, Osher Y, Belmaker RH. High homocysteine serum levels in young male schizophrenia and bipolar patients and in an animal model. Prog Neuro-Psychopharmacol Biol Psychiatry. 2005;29:1181–91. CrossRef
Sawuła W, Banecka-Majkutewicz Z, Kadziński L, Jakóbkiewicz-Banecka J, Wegrzyn G, Nyka W, et al. Improved HPLC method for total plasma homocysteine detection and quantification. Acta Biochim Pol. 2008;55:119–25. PubMed
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. quiz 34–57 PubMed
Van Vliet IM, de Beurs E. [the MINI-international Neuropsychiatric interview. A brief structured diagnostic psychiatric interview for DSM-IV en ICD-10 psychiatric disorders]. Tijdschr. Voor Psychiatr. 2007;49:393–7.
Young RC, Biggs JT, Ziegler VE, Meyer DA. A rating scale for mania: reliability, validity and sensitivity. Br J Psychiatry J Ment Sci. 1978;133:429–35. CrossRef
Lukasiewicz M, Gerard S, Besnard A, Falissard B, Perrin E, Sapin H, et al. Young mania rating scale: how to interpret the numbers? Determination of a severity threshold and of the minimal clinically significant difference in the EMBLEM cohort. Int J Methods Psychiatr Res. 2013;22:46–58. CrossRefPubMed
- Blood homocysteine concentration and mood disorders with mixed features among patients with alcohol use disorder
Rocco Luigi Picci
- BioMed Central