BDNF and GDNF serum levels in alcohol-dependent patients during withdrawal Annemarie Heberlein a,b, ⁎, Marc Muschler a , Julia Wilhelm a,b , Helge Frieling a,b , Bernd Lenz b Michael Gröschl c , Johannes Kornhuber b , Stefan Bleich a,b , Thomas Hillemacher a,b a Center for Addiction Research, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Germany b Department of Psychiatry and Psychotherapy, University Hospital Erlangen, Germany c Department of Pediatrics, University Hospital Erlangen, Germany abstract article info Article history: Received 7 April 2010 Received in revised form 20 May 2010 Accepted 21 May 2010 Available online 27 May 2010 Keywords: Alcohol dependence Alcohol withdrawal BDNF GDNF Neurotrophic growth factors Craving Preclinical study results suggest that brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) modulate addictive behaviour. Therefore we investigated alterations in BDNF (81 male patients) and GDNF serum levels (52 male patients) in alcohol-dependent patients during alcohol withdrawal (day 1, 7 and 14) in comparison to healthy controls (41 male controls). BDNF serum levels were not significantly altered in alcohol-dependent patients compared to healthy controls (p = 0.685). GDNF serum levels were significantly reduced in the alcohol-dependent patients (p b 0.001). BDNF (p = 0.265) and GDNF (p = 0.255) serum levels did not change significantly during alcohol withdrawal. BDNF serum levels were significantly negatively associated with alcohol withdrawal severity on day 1 (CIWA-Ar score, p = 0.004). GDNF serum levels were significantly negatively associated with individual estimation of alcohol tolerance (SESA-XT score, p = 0.028). There was no further association with psychometric dimensions of alcohol withdrawal. In conclusion we found that GDNF serum levels are significantly reduced in alcohol-dependent patients. GDNF serum levels were negatively associated with alcohol tolerance. Moreover BDNF serum levels were found to be associated with withdrawal severity. © 2010 Elsevier Inc. All rights reserved. 1. Introduction The activity of the mesocorticolimbic dopaminergic reward circuit has been frequently associated with mediation of drug-specific rewarding effects and drug seeking behaviour (Pierce and Kumaresan, 2006). Brain-derived neurotrophic factor (BDNF) and glial cell line- derived neurotrophic factor (GDNF) are both neurotrophic neuropep- tides (Chao et al., 2006) that have been implicated in the survival and differentiation of adult dopamine neurons (Airaksinen and Saarma, 2002; Akaneya et al., 1995; Altar et al., 1994; Altar et al., 1992). There are various study results that show a modulating role of BDNF in the development and maintenance of addictive behaviour (for review see (Corominas et al., 2007)). Regarding alcohol dependence it has been hypothesized that BDNF expression is associated with decreased alcohol consumption (Jeanblanc et al., 2006). In particular, acute ethanol intake in rats has been associated with increased BDNF expression, whereas prolonged ethanol intake (in excess of 24 h) resulted in decreased BDNF expression in the investigated brain regions (Logrip et al., 2009; McGough et al., 2004). Moreover, decreased expression of BDNF was associated with increased ethanol preference in the investigated rats (McGough et al., 2004). Regarding peripheral blood levels of BDNF in alcohol- dependent patients contradictory results have been reported. For example, Huang et al. (Huang et al., 2008) reported significantly increased BDNF serum levels on day 7 of alcohol withdrawal compared to healthy controls. Moreover, they found a positive association between baseline BDNF levels and withdrawal severity measured by the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar). Lee et al. (Lee et al., 2009) reported significantly increased BDNF blood levels in male alcohol-dependent patients compared to healthy controls. In contrast, Joe et al. (Joe et al., 2007) found BDNF blood levels to be significantly reduced in alcohol-dependent patients that had abstained for more than 30 days. GDNF has also been hypothesized to be involved in the regulation of addictive behaviours (Ron and Janak, 2005): preclinical study Progress in Neuro-Psychopharmacology & Biological Psychiatry 34 (2010) 1060–1064 Abbreviations: AAT, aspartate aminotransferase; ALAT, alanine aminotransferase; AUDIT-C, Alcohol Use Disorder Identification Test–Alcohol Consumption Questions; BAC, Breath Alcohol Concentration; BDI, Beck's Depression Inventory; BDNF, Brain- derived neurotrophic factor; BMI, body mass index; CIWA-Ar, Clinical Institute Withdrawal Assessment for Alcohol; DI, daily intake of alcohol in grams; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders; GDNF, Glial cell-line derived neurotrophic factor; GGT, gamma glutamyl transferase; ICD-10, International Classi- fication of Diseases; LC, leukocyte count; N.A., not available; OCDS, Obsessive and Compulsive Drinking Scale; SD, standard deviation; SESA, Severity Scale of Alcohol Dependence; STAI-I, State Anxiety, State and Trait Anxiety Inventory; STAI-II, Trait Anxiety, State and Trait Anxiety Inventory; TC, thrombocyte count; YD, years of drinking. ⁎ Corresponding author. Center for Addiction Research, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Carl-Neuberg-Straβe 1, D-30625 Hannover, Germany. Tel.: + 49 511 532 0. E-mail address: heberlein.annemarie@mh-hannover.de (A. Heberlein). 0278-5846/$ – see front matter © 2010 Elsevier Inc. All rights reserved. doi:10.1016/j.pnpbp.2010.05.025 Contents lists available at ScienceDirect Progress in Neuro-Psychopharmacology & Biological Psychiatry journal homepage: www.elsevier.com/locate/pnp