{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T10:06:10Z","timestamp":1769076370488,"version":"3.49.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T00:00:00Z","timestamp":1614211200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"DFG","award":["402170461 \u2013 TRR 265"],"award-info":[{"award-number":["402170461 \u2013 TRR 265"]}]},{"DOI":"10.13039\/501100018936","name":"Universit\u00e4tsklinikum Heidelberg","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018936","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Arch Psychiatry Clin Neurosci"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Recent studies on the pathophysiology of alcohol dependence suggest a link between peripheral calcium concentrations and alcohol craving. Here, we investigated the association between plasma calcium concentration, cue-induced brain activation, and alcohol craving. Plasma calcium concentrations were measured at the onset of inpatient detoxification in a sample of <jats:italic>N<\/jats:italic>\u2009=\u2009115 alcohol-dependent patients. Alcohol cue-reactivity was assessed during early abstinence (mean 11.1\u00a0days) using a functional magnetic resonance imaging (fMRI) alcohol cue-reactivity task. Multiple regression analyses and bivariate correlations between plasma calcium concentrations, clinical craving measures and neural alcohol cue-reactivity (CR) were tested. Results show a significant negative correlation between plasma calcium concentrations and compulsive alcohol craving. Higher calcium levels predicted higher alcohol cue-induced brain response in a cluster of frontal brain areas, including the dorsolateral prefrontal cortex (dlPFC), the anterior prefrontal cortex (alPFC), and the inferior (IFG) and middle frontal gyri (MFG). In addition, functional brain activation in those areas correlated negatively with craving for alcohol during fMRI. Higher peripheral calcium concentrations during withdrawal predicted increased alcohol cue-induced brain activation in frontal brain areas, which are associated with craving inhibition and cognitive control functions. This might indicate that higher plasma calcium concentrations at onset of detoxification could modulate craving inhibition during early abstinence.<\/jats:p><jats:p><jats:bold>Trial registration number<\/jats:bold>: DRKS00003388; date of registration: 14.12.2011.<\/jats:p>","DOI":"10.1007\/s00406-021-01240-4","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T08:02:58Z","timestamp":1614240178000},"page":"341-348","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Plasma calcium concentration during detoxification predicts neural cue-reactivity and craving during early abstinence in alcohol-dependent patients"],"prefix":"10.1007","volume":"272","author":[{"given":"Patrick","family":"Bach","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rilana","family":"Schuster","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Koopmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Vollstaedt-Klein","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Spanagel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Falk","family":"Kiefer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,2,25]]},"reference":[{"key":"1240_CR1","doi-asserted-by":"publisher","first-page":"173","DOI":"10.4103\/0972-5229.178182","volume":"20","author":"A Ahmed","year":"2016","unstructured":"Ahmed A, Azim A, Gurjar M, Baronia AK (2016) Hypocalcemia in acute pancreatitis revisited. Indian J Crit Care Med 20:173\u2013177","journal-title":"Indian J Crit Care Med"},{"key":"1240_CR2","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1001\/archpsyc.1996.01830030047008","volume":"53","author":"RF Anton","year":"1996","unstructured":"Anton RF, Moak DH, Latham PK (1996) The obsessive compulsive drinking scale: a new method of assessing outcome in alcoholism treatment studies. Arch Gen Psychiatry 53:225\u2013231","journal-title":"Arch Gen Psychiatry"},{"key":"1240_CR3","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1038\/nrn3531","volume":"14","author":"H Bading","year":"2013","unstructured":"Bading H (2013) Nuclear calcium signalling in the regulation of brain function. Nat Rev Neurosci 14:593\u2013608","journal-title":"Nat Rev Neurosci"},{"key":"1240_CR4","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1093\/cercor\/bhr381","volume":"23","author":"S Chanraud","year":"2013","unstructured":"Chanraud S, Pitel AL, Muller-Oehring EM, Pfefferbaum A, Sullivan EV (2013) Remapping the brain to compensate for impairment in recovering alcoholics. Cereb Cortex 23:97\u2013104","journal-title":"Cereb Cortex"},{"key":"1240_CR5","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1002\/(SICI)1522-2594(200003)43:3<383::AID-MRM10>3.0.CO;2-Q","volume":"43","author":"TQ Duong","year":"2000","unstructured":"Duong TQ, Silva AC, Lee SP, Kim SG (2000) Functional mri of calcium-dependent synaptic activity: cross correlation with cbf and bold measurements. Magn Reson Med 43:383\u2013392","journal-title":"Magn Reson Med"},{"key":"1240_CR6","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1093\/oxfordjournals.aje.a010295","volume":"151","author":"CL Emsley","year":"2000","unstructured":"Emsley CL, Gao S, Li Y, Liang C, Ji R, Hall KS, Cao J, Ma F, Wu Y, Ying P, Zhang Y, Sun S, Unverzagt FW, Slemenda CW, Hendrie HC (2000) Trace element levels in drinking water and cognitive function among elderly chinese. Am J Epidemiol 151:913\u2013920","journal-title":"Am J Epidemiol"},{"issue":"925\u2013939","key":"1240_CR7","doi-asserted-by":"publisher","first-page":"e925","DOI":"10.1016\/j.neuron.2018.01.025","volume":"97","author":"Y He","year":"2018","unstructured":"He Y, Wang M, Chen X, Pohmann R, Polimeni JR, Scheffler K, Rosen BR, Kleinfeld D, Yu X (2018) Ultra-slow single-vessel bold and cbv-based fmri spatiotemporal dynamics and their correlation with neuronal intracellular calcium signals. Neuron 97(925\u2013939):e925","journal-title":"Neuron"},{"key":"1240_CR8","doi-asserted-by":"publisher","first-page":"14811","DOI":"10.1073\/pnas.1007779107","volume":"107","author":"H Kober","year":"2010","unstructured":"Kober H, Mende-Siedlecki P, Kross EF, Weber J, Mischel W, Hart CL, Ochsner KN (2010) Prefrontal-striatal pathway underlies cognitive regulation of craving. Proc Natl Acad Sci USA 107:14811\u201314816","journal-title":"Proc Natl Acad Sci USA"},{"key":"1240_CR9","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1007\/s00115-006-2098-7","volume":"78","author":"C Kuhner","year":"2007","unstructured":"Kuhner C, Burger C, Keller F, Hautzinger M (2007) reliability and validity of the revised beck depression inventory (bdi-ii). Results from german samples. Der Nervenarzt 78:651\u2013656","journal-title":"Der Nervenarzt"},{"key":"1240_CR10","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1038\/nrn1589","volume":"6","author":"M Lauritzen","year":"2005","unstructured":"Lauritzen M (2005) Reading vascular changes in brain imaging: is dendritic calcium the key? Nat Rev Neurosci 6:77\u201385","journal-title":"Nat Rev Neurosci"},{"key":"1240_CR11","doi-asserted-by":"publisher","first-page":"e017703","DOI":"10.1136\/bmjopen-2017-017703","volume":"8","author":"IA Lian","year":"2018","unstructured":"Lian IA, Asberg A (2018) Should total calcium be adjusted for albumin? A retrospective observational study of laboratory data from central norway. BMJ open 8:e017703","journal-title":"BMJ open"},{"key":"1240_CR12","doi-asserted-by":"publisher","first-page":"E4678","DOI":"10.1073\/pnas.1310065110","volume":"110","author":"BL Lind","year":"2013","unstructured":"Lind BL, Brazhe AR, Jessen SB, Tan FC, Lauritzen MJ (2013) Rapid stimulus-evoked astrocyte ca2+ elevations and hemodynamic responses in mouse somatosensory cortex in vivo. Proc Natl Acad Sci 110:E4678\u2013E4687","journal-title":"Proc Natl Acad Sci"},{"key":"1240_CR13","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/npp.2015.175","volume":"41","author":"K Mann","year":"2016","unstructured":"Mann K, Hoffmann S, Pawlak CR (2016) Does acamprosate really produce its anti-relapse effects via calcium? No support from the predict study in human alcoholics. Neuropsychopharmacology 41:659\u2013660","journal-title":"Neuropsychopharmacology"},{"key":"1240_CR14","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1192\/bjp.134.4.382","volume":"134","author":"SA Montgomery","year":"1979","unstructured":"Montgomery SA, Asberg M (1979) A new depression scale designed to be sensitive to change. Br J Psychiatry 134:382\u2013389","journal-title":"Br J Psychiatry"},{"key":"1240_CR15","first-page":"411","volume":"67","author":"X Parent","year":"2009","unstructured":"Parent X, Spielmann C, Hanser AM (2009) \u201cCorrected\u201d calcium: calcium status underestimation in non-hypoalbuminemic patients and in hypercalcemic patients. Ann Biol Clin 67:411\u2013418","journal-title":"Ann Biol Clin"},{"key":"1240_CR16","doi-asserted-by":"publisher","first-page":"2027","DOI":"10.1007\/s00213-018-4900-1","volume":"235","author":"G Pradhan","year":"2018","unstructured":"Pradhan G, Melugin PR, Wu F, Fang HM, Weber R, Kroener S (2018) Calcium chloride mimics the effects of acamprosate on cognitive deficits in chronic alcohol-exposed mice. Psychopharmacology 235:2027\u20132040","journal-title":"Psychopharmacology"},{"key":"1240_CR17","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jneumeth.2015.01.001","volume":"242","author":"I Reinhard","year":"2015","unstructured":"Reinhard I, Lemenager T, Fauth-Buhler M, Hermann D, Hoffmann S, Heinz A, Kiefer F, Smolka MN, Wellek S, Mann K, Vollstadt-Klein S (2015) A comparison of region-of-interest measures for extracting whole brain data using survival analysis in alcoholism as an example. J Neurosci Methods 242:58\u201364","journal-title":"J Neurosci Methods"},{"key":"1240_CR18","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/nmeth.2013","volume":"9","author":"K Schulz","year":"2012","unstructured":"Schulz K, Sydekum E, Krueppel R, Engelbrecht CJ, Schlegel F, Schroter A, Rudin M, Helmchen F (2012) Simultaneous bold fmri and fiber-optic calcium recording in rat neocortex. Nat Methods 9:597\u2013602","journal-title":"Nat Methods"},{"key":"1240_CR19","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.euroneuro.2016.11.007","volume":"27","author":"R Schuster","year":"2017","unstructured":"Schuster R, Koopmann A, Grosshans M, Reinhard I, Spanagel R, Kiefer F (2017) Association of plasma calcium concentrations with alcohol craving: new data on potential pathways. Eur Neuropsychopharmacol 27:42\u201347","journal-title":"Eur Neuropsychopharmacol"},{"key":"1240_CR20","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.psychres.2017.01.101","volume":"252","author":"A Sharma","year":"2017","unstructured":"Sharma A, Schray A, Bartolovic M, Roesch-Ely D, Aschenbrenner S, Weisbrod M (2017) Relationship between serum calcium and neuropsychological performance might indicate etiological heterogeneity underlying cognitive deficits in schizophrenia and depression. Psychiatry Res 252:80\u201386","journal-title":"Psychiatry Res"},{"key":"1240_CR21","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1037\/0021-843X.91.3.199","volume":"91","author":"HA Skinner","year":"1982","unstructured":"Skinner HA, Allen BA (1982) Alcohol dependence syndrome: Measurement and validation. J Abnorm Psychol 91:199\u2013209","journal-title":"J Abnorm Psychol"},{"key":"1240_CR22","doi-asserted-by":"publisher","first-page":"1389","DOI":"10.1097\/01.CCM.0000063044.55669.3C","volume":"31","author":"J Slomp","year":"2003","unstructured":"Slomp J, van der Voort PH, Gerritsen RT, Berk JA, Bakker AJ (2003) Albumin-adjusted calcium is not suitable for diagnosis of hyper- and hypocalcemia in the critically ill. Crit Care Med 31:1389\u20131393","journal-title":"Crit Care Med"},{"key":"1240_CR23","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1038\/npp.2013.264","volume":"39","author":"R Spanagel","year":"2014","unstructured":"Spanagel R, Vengeliene V, Jandeleit B, Fischer WN, Grindstaff K, Zhang X, Gallop MA, Krstew EV, Lawrence AJ, Kiefer F (2014) Acamprosate produces its anti-relapse effects via calcium. Neuropsychopharmacology 39:783\u2013791","journal-title":"Neuropsychopharmacology"},{"key":"1240_CR24","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1038\/npp.2015.263","volume":"41","author":"R Spanagel","year":"2016","unstructured":"Spanagel R, Vengeliene V, Kiefer F (2016) Reply to: does acamprosate really produce its anti-relapse effects via calcium? No support from the predict study in human alcoholics. Neuropsychopharmacology 41:661\u2013662","journal-title":"Neuropsychopharmacology"},{"key":"1240_CR25","first-page":"2423","volume":"151","author":"J Thode","year":"1989","unstructured":"Thode J, Juul-Jorgensen B, Bhatia HM, Kjaerulf-Nielsen M, Bartels PD, Fogh-Andersen N, Siggaard-Andersen O (1989) Ionized calcium, total calcium and albumin corrected calcium in the serum in 1213 patients with suspected calcium metabolic diseases. A prospective multicenter study. Ugeskr Laeger 151:2423\u20132425","journal-title":"Ugeskr Laeger"},{"key":"1240_CR26","doi-asserted-by":"publisher","first-page":"2536","DOI":"10.1016\/j.neuroimage.2009.10.088","volume":"49","author":"ND Volkow","year":"2010","unstructured":"Volkow ND, Fowler JS, Wang GJ, Telang F, Logan J, Jayne M, Ma Y, Pradhan K, Wong C, Swanson JM (2010) Cognitive control of drug craving inhibits brain reward regions in cocaine abusers. NeuroImage 49:2536\u20132543","journal-title":"NeuroImage"},{"key":"1240_CR27","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1111\/j.1369-1600.2011.00352.x","volume":"17","author":"S Vollstadt-Klein","year":"2012","unstructured":"Vollstadt-Klein S, Loeber S, Richter A, Kirsch M, Bach P, von der Goltz C, Hermann D, Mann K, Kiefer F (2012) Validating incentive salience with functional magnetic resonance imaging: association between mesolimbic cue reactivity and attentional bias in alcohol-dependent patients. Addict Biol 17:807\u2013816","journal-title":"Addict Biol"},{"key":"1240_CR28","doi-asserted-by":"publisher","first-page":"E1647","DOI":"10.1073\/pnas.1711692115","volume":"115","author":"M Wang","year":"2018","unstructured":"Wang M, He Y, Sejnowski TJ, Yu X (2018) Brain-state dependent astrocytic ca2+signals are coupled to both positive and negative bold-fmri signals. Proc Natl Acad Sci 115:E1647\u2013E1656","journal-title":"Proc Natl Acad Sci"},{"key":"1240_CR29","doi-asserted-by":"publisher","first-page":"6268","DOI":"10.1523\/JNEUROSCI.4801-06.2007","volume":"27","author":"IR Winship","year":"2007","unstructured":"Winship IR, Plaa N, Murphy TH (2007) Rapid astrocyte calcium signals correlate with neuronal activity and onset of the hemodynamic response in vivo. J Neurosci 27:6268\u20136272","journal-title":"J Neurosci"},{"key":"1240_CR30","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1016\/j.neubiorev.2011.12.004","volume":"36","author":"Y Yalachkov","year":"2012","unstructured":"Yalachkov Y, Kaiser J, Naumer MJ (2012) Functional neuroimaging studies in addiction: multisensory drug stimuli and neural cue reactivity. Neurosci Biobehav Rev 36:825\u2013835","journal-title":"Neurosci Biobehav Rev"}],"container-title":["European Archives of Psychiatry and Clinical Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00406-021-01240-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00406-021-01240-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00406-021-01240-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T16:05:47Z","timestamp":1645632347000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00406-021-01240-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,25]]},"references-count":30,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["1240"],"URL":"https:\/\/doi.org\/10.1007\/s00406-021-01240-4","relation":{},"ISSN":["0940-1334","1433-8491"],"issn-type":[{"value":"0940-1334","type":"print"},{"value":"1433-8491","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,25]]},"assertion":[{"value":"11 May 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 February 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"All authors declare that they have no conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study adhered to the Declaration of Helsinki and was approved by the ethics committee of the University Medical Center in Mannheim, Germany, and was registered at the national study registry (DRKS00003388).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed consent was obtained from all individual participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}