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BMC Psychiatry
Published in: BMC Psychiatry 1/2017

Open Access 01-12-2017 | Research article

Blood homocysteine concentration and mood disorders with mixed features among patients with alcohol use disorder

Authors: Francesco Oliva, Maurizio Coppola, Raffaella Mondola, Daniele Ascheri, Francesco Cuniberti, Gabriele Nibbio, Rocco Luigi Picci

Published in: BMC Psychiatry | Issue 1/2017

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

Depressive symptoms seem to be mainly implicated in the BHC elevation among patients with both mixed features mood disorder and AUD.
Literature
1.
Seshadri S, Beiser A, Selhub J, Jacques PF, Rosenberg IH, D’Agostino RB, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002;346:476–83.CrossRefPubMed
2.
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
3.
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
4.
Refsum H, Smith AD, Ueland PM, Nexo E, Clarke R, McPartlin J, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem. 2004;50:3–32.CrossRefPubMed
5.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5. 5 edition. Washington: American Psychiatric Publishing; 2013.
6.
Hultberg B, Berglund M, Andersson A, Frank A. Elevated plasma homocysteine in alcoholics. Alcohol Clin Exp Res. 1993;17:687–9.CrossRefPubMed
7.
Van der Gaag MS, Ubbink JB, Sillanaukee P, Nikkari S, Hendriks HF. Effect of consumption of red wine, spirits, and beer on serum homocysteine. Lancet. 2000;355:1522.CrossRefPubMed
8.
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.
9.
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.
10.
Husemoen LLN, Thomsen TF, Fenger M, Jørgensen T. Effect of lifestyle factors on plasma total homocysteine concentrations in relation to MTHFR(C677T) genotype. Inter99 (7). Eur J Clin Nutr. 2004;58:1142–50.CrossRefPubMed
11.
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.
12.
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.
13.
Bleich S, Degner D, Javaheripour K, Kurth C, Kornhuber J. Homocysteine and alcoholism. J Neural Transm Suppl. 2000:187–96.
14.
Bleich S, Carl M, Bayerlein K, Reulbach U, Biermann T, Hillemacher T, et al. Evidence of increased homocysteine levels in alcoholism: the Franconian alcoholism research studies (FARS). Alcohol Clin Exp Res. 2005;29:334–6.CrossRefPubMed
15.
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
16.
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
17.
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.
18.
Stickel F, Choi SW, Kim YI, Bagley PJ, Seitz HK, Russell RM, et al. Effect of chronic alcohol consumption on total plasma homocysteine level in rats. Alcohol Clin Exp Res. 2000;24:259–64.CrossRefPubMed
19.
Barak AJ, Beckenhauer HC, Tuma DJ. Hepatic transmethylation and blood alcohol levels. Alcohol Alcohol Oxf Oxfs. 1991;26:125–8.CrossRef
20.
Barak AJ, Beckenhauer HC, Tuma DJ. Betaine, ethanol, and the liver: a review. Alcohol Fayettev N. 1996;13:395–8.CrossRef
21.
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
22.
Halsted CH, Villanueva JA, Devlin AM, Chandler CJ. Metabolic interactions of alcohol and folate. J Nutr. 2002;132:2367S–72S.PubMed
23.
Schalinske KL, Nieman KM. Disruption of methyl group metabolism by ethanol. Nutr Rev. 2005;63:387–91.CrossRefPubMed
24.
Halsted CH, Medici V. Vitamin-dependent methionine metabolism and alcoholic liver disease. Adv Nutr Bethesda Md. 2011;2:421–7.CrossRef
25.
Kharbanda KK, Todero SL, Thomes PG, Orlicky DJ, Osna NA, French SW, et al. Increased methylation demand exacerbates ethanol-induced liver injury. Exp Mol Pathol. 2014;97:49–56.CrossRefPubMed
26.
27.
Reynolds EH, Preece JM, Bailey J, Coppen A. Folate deficiency in depressive illness. Br J Psychiatry J Ment Sci. 1970;117:287–92.
28.
Bell IR, Edman JS, Selhub J, Morrow FD, Marby DW, Kayne HL, et al. Plasma homocysteine in vascular disease and in nonvascular dementia of depressed elderly people. Acta Psychiatr Scand. 1992;86:386–90.CrossRefPubMed
29.
Fava M, Borus JS, Alpert JE, Nierenberg AA, Rosenbaum JF, Bottiglieri T. Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry. 1997;154:426–8.CrossRefPubMed
30.
Bjelland I, Tell GS, Vollset SE, Refsum H, Ueland PM. Folate, vitamin B12, homocysteine, and the MTHFR 677C->T polymorphism in anxiety and depression: the Hordaland Homocysteine study. Arch Gen Psychiatry. 2003;60:618–26.CrossRefPubMed
31.
Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry. 2000;69:228–32.CrossRefPubMedPubMedCentral
32.
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
33.
Morris MS, Fava M, Jacques PF, Selhub J, Rosenberg IH. Depression and folate status in the US population. Psychother Psychosom. 2003;72:80–7.CrossRefPubMed
34.
Almeida OP, Lautenschlager N, Flicker L, Leedman P, Vasikaran S, Gelavis A, et al. Association between Homocysteine, depression, and cognitive function in community-dwelling older women from Australia. J Am Geriatr Soc. 2004;52:327–8.CrossRefPubMed
35.
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
36.
Osher Y, Bersudsky Y, Silver H, Sela B-A, Belmaker RH. Neuropsychological correlates of homocysteine levels in euthymic bipolar patients. J Affect Disord. 2008;105:229–33.CrossRefPubMed
37.
Osher Y, Sela B-A, Levine J, Belmaker RH. Elevated homocysteine levels in euthymic bipolar disorder patients showing functional deterioration. Bipolar Disord. 2004;6:82–6.CrossRefPubMed
38.
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.
39.
Kraepelin E. Manic-depressive insanity and paranoia. Livingstone. Robertson George M: Edinburgh, Scotland; 1921.
40.
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.
41.
Perugi G, Medda P, Reis J, Rizzato S, Giorgi Mariani M, Mauri M. Clinical subtypes of severe bipolar mixed states. J Affect Disord. 2013;151:1076–82.CrossRefPubMed
42.
McElroy SL, Keck PE, Pope HG, Hudson JI, Faedda GL, Swann AC. Clinical and research implications of the diagnosis of dysphoric or mixed mania or hypomania. Am J Psychiatry. 1992;149:1633–44.CrossRefPubMed
43.
Akiskal HS, Benazzi F, Perugi G, Rihmer Z. Agitated “unipolar” depression re-conceptualized as a depressive mixed state: implications for the antidepressant-suicide controversy. J Affect Disord. 2005;85:245–58.CrossRefPubMed
44.
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
45.
Swann AC, Lafer B, Perugi G, Frye MA, Bauer M, Bahk W-M, et al. Bipolar mixed states: an international society for bipolar disorders task force report of symptom structure, course of illness, and diagnosis. Am J Psychiatry. 2013;170:31–42.CrossRefPubMed
46.
American Psychiatric Association. DSM-IV-TR: diagnostic and statistical manual of Mental disorders. 4th ed text revision edition. Washington: American Psychiatric Press Inc.; 2000.
47.
Ho PI, Ortiz D, Rogers E, Shea TB. Multiple aspects of homocysteine neurotoxicity: glutamate excitotoxicity, kinase hyperactivation and DNA damage. J Neurosci Res. 2002;70:694–702.CrossRefPubMed
48.
Lipton SA, Kim WK, Choi YB, Kumar S, D’Emilia DM, Rayudu PV, et al. Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor. Proc Natl Acad Sci U S A. 1997;94:5923–8.CrossRefPubMedPubMedCentral
49.
Mattson MP, Shea TB. Folate and homocysteine metabolism in neural plasticity and neurodegenerative disorders. Trends Neurosci. 2003;26:137–46.CrossRefPubMed
50.
Pullan LM, Olney JW, Price MT, Compton RP, Hood WF, Michel J, et al. Excitatory amino acid receptor potency and subclass specificity of sulfur-containing amino acids. J Neurochem. 1987;49:1301–7.CrossRefPubMed
51.
Sawada S, Yamamoto C. Gamma-D-glutamylglycine and cis-2,3-piperidine dicarboxylate as antagonists of excitatory amino acids in the hippocampus. Exp Brain Res. 1984;55:351–8.CrossRefPubMed
52.
Fraguas R Jr, Papakostas GI, Mischoulon D, Bottiglieri T, Alpert J, Fava M. Anger attacks in major depressive disorder and serum levels of homocysteine. Biol Psychiatry. 2006;60:270–4.CrossRefPubMed
53.
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
54.
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
55.
Stoney CM, Engebretson TO. Plasma homocysteine concentrations are positively associated with hostility and anger. Life Sci. 2000;66:2267–75.CrossRefPubMed
56.
Strakowski SM, DelBello MP, Fleck DE, et al. EFfects of co-occurring alcohol abuse on the course of bipolar disorder following a first hospitalization for mania. Arch Gen Psychiatry. 2005;62:851–8.CrossRefPubMed
57.
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
58.
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 34–57PubMed
59.
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.
60.
Bohn MJ, Babor TF, Kranzler HR. The alcohol use disorders identification test (AUDIT): validation of a screening instrument for use in medical settings. J Stud Alcohol. 1995;56:423–32.CrossRefPubMed
61.
Piccinelli M, Tessari E, Bortolomasi M, Piasere O, Semenzin M, Garzotto N, et al. Efficacy of the alcohol use disorders identification test as a screening tool for hazardous alcohol intake and related disorders in primary care: a validity study. BMJ. 1997;314:420–4.CrossRefPubMedPubMedCentral
62.
Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M. Development of the alcohol use disorders identification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption--II. Addiction. 1993;88:791–804.CrossRefPubMed
63.
64.
Zimmerman M, Martinez JH, Young D, Chelminski I, Dalrymple K. Severity classification on the Hamilton depression rating scale. J Affect Disord. 2013;150:384–8.CrossRefPubMed
65.
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
66.
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
67.
Almeida OP, Flicker L, Lautenschlager NT, Leedman P, Vasikaran S, van Bockxmeer FM. Contribution of the MTHFR gene to the causal pathway for depression, anxiety and cognitive impairment in later life. Neurobiol Aging. 2005;26:251–7.CrossRefPubMed
68.
Gilbody S, Lewis S, Lightfoot T. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidemiol. 2007;165:1–13.CrossRefPubMed
69.
Peerbooms OLJ. Van Os J, Drukker M, Kenis G, Hoogveld L, MTHFR in Psychiatry group, et al. meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: evidence for a common genetic vulnerability? Brain Behav Immun. 2011;25:1530–43.CrossRefPubMed
Metadata
Title
Blood homocysteine concentration and mood disorders with mixed features among patients with alcohol use disorder
Authors
Francesco Oliva
Maurizio Coppola
Raffaella Mondola
Daniele Ascheri
Francesco Cuniberti
Gabriele Nibbio
Rocco Luigi Picci
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2017
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/s12888-017-1342-y

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