FASDetect as a machine learning-based screening app for FASD in youth with ADHD.

Fetal alcohol-spectrum disorder (FASD) is underdiagnosed and often misdiagnosed as attention-deficit/hyperactivity disorder (ADHD). Here, we develop a screening tool for FASD in youth with ADHD symptoms. To develop the prediction model, medical record data from a German University outpatient unit are assessed including 275 patients aged 0-19 years old with FASD with or without ADHD and 170 patients with ADHD without FASD aged 0-19 years old. We train 6 machine learning models based on 13 selected variables and evaluate their performance. Random forest models yield the best prediction models with a cross-validated AUC of 0.92 (95% confidence interval [0.84, 0.99]). Follow-up analyses indicate that a random forest model with 6 variables - body length and head circumference at birth, IQ, socially intrusive behaviour, poor memory and sleep disturbance - yields equivalent predictive accuracy. We implement the prediction model in a web-based app called FASDetect - a user-friendly, clinically scalable FASD risk calculator that is freely available at https://fasdetect.dhc-lab.hpi.de .

Effects of baclofen on insular gain anticipation in alcohol-dependent patients - a randomized, placebo-controlled, pharmaco-fMRI pilot trial.

RATIONALE: One hallmark of addiction is an altered neuronal reward processing. In healthy individuals (HC), reduced activity in fronto-striatal regions including the insula has been observed when a reward anticipation task was performed repeatedly. This effect could indicate a desensitization of the neural reward system due to repetition. Here, we investigated this hypothesis in a cohort of patients with alcohol use disorder (AUD), who have been treated with baclofen or a placebo. The efficacy of baclofen in AUD patients has been shown to have positive clinical effects, possibly via indirectly affecting structures within the neuronal reward system. OBJECTIVES: Twenty-eight recently detoxified patients (13 receiving baclofen (BAC), 15 receiving placebo (PLA)) were investigated within a longitudinal, double-blind, and randomized pharmaco-fMRI design with an individually adjusted daily dosage of 30-270 mg. METHODS: Brain responses were captured by functional magnetic resonance imaging (fMRI) during reward anticipation while participating in a slot machine paradigm before (t1) and after 2 weeks of individual high-dose medication (t2). RESULTS: Abstinence rates were significantly higher in the BAC compared to the PLA group during the 12-week high-dose medication phase. At t1, all patients showed significant bilateral striatal activation. At t2, the BAC group showed a significant decrease in insular activation compared to the PLA group. CONCLUSIONS: By affecting insular information processing, baclofen might enable a more flexible neuronal adaptation during recurrent reward anticipation, which could resemble a desensitization as previously observed in HC. This result strengthens the modulation of the reward system as a potential mechanism of action of baclofen. TRIAL REGISTRATION: Identifier of the main trial (the BACLAD study) at clinical.gov: NCT0126665.

Non-Substance Addiction in Childhood and Adolescence­The Internet, Computer Games and Social Media.

BACKGROUND: Around 5.8% of adolescents and 2.8% of young adults have an Internet-related disorder. These figures underline the widespread concerns in our society regarding the potential dangers and risks associated with Internet and digital media use. METHODS: Selective literature search for records on Internet-related disorders in children and adolescents. RESULTS: Internet-related disorders are now viewed as belonging to the behavioral addiction. Research has revealed similarities to substance-related disorders. There are often associations with other mental illnesses such as depression, anxiety, attention deficit/hyperactivity disorder, and personality disorders, as well as disturbed sleep patterns, increased risk taking, nicotine abuse, an unbalanced diet, and lack of exercise. Female adolescents are statistically significantly more often affected than male adolescents (7.1% versus 4.5%). The German STICA study, the first randomized controlled trial worldwide, demonstrated that cognitive behavioral therapy was effective compared with a waiting group (odds ratio 10.10, 95% confidence interval [3.69; 27.65]). CONCLUSION: Internet-related disorders have not yet been conclusively conceptualized and operationalized. Further work is urgently required to refine the concepts of both the illness and and its treatment.

Robustly High Hippocampal BDNF levels under Acute Stress in Mice Lacking the Full-length p75 Neurotrophin Receptor.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) exerts its effects on neural plasticity via 2 distinct receptor types, the tyrosine kinase TrkB and the p75 neurotrophin receptor (p75NTR). The latter can promote inflammation and cell death while TrkB is critically involved in plasticity and memory, particularly in the hippocampus. Acute and chronic stress have been associated with suppression of hippocampal BDNF expression and impaired hippocampal plasticity. We hypothesized that p75NTR might be involved in the hippocampal stress response, in particular in stress-induced BDNF suppression, which might be accompanied by increased neuroinflammation. METHOD: We assessed hippocampal BDNF protein concentrations in wild-type mice compared that in mice lacking the long form of the p75NTR (p75NTRExIII-/-) with or without prior exposure to a 1-hour restraint stress challenge. Hippocampal BDNF concentrations were measured using an optimized ELISA. Furthermore, whole-brain mRNA expression of pro-inflammatory interleukin-6 (Il6) was assessed with RT-PCR. RESULTS: Deletion of full-length p75NTR was associated with higher hippocampal BDNF protein concentration in the stress condition, suggesting persistently high hippocampal BDNF levels in p75NTR-deficient mice, even under stress. Stress elicited increased whole-brain Il6 mRNA expression irrespective of genotype; however, p75NTRExIII-/- mice showed elevated baseline Il6 expression and thus a lower relative increase. CONCLUSIONS: Our results provide evidence for a role of p75NTR signaling in the regulation of hippocampal BDNF levels, particularly under stress. Furthermore, p75NTR signaling modulates baseline but not stress-related Il6 gene expression in mice. Our findings implicate p75NTR signaling as a potential pathomechanism in BDNF-dependent modulation of risk for neuropsychiatric disorders.

No evidence for altered plasma NGF and BDNF levels in fibromyalgia patients.

There has been a surging interest in the putative role of peripheral growth factors in the pathophysiology of fibromyalgia, specifically in the peripheral sensitization that occurs in chronic pain disorders. This cross-sectional study set out to assess and compare brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in plasma samples from fibromyalgia patients and healthy controls. Plasma BDNF and NGF were measured in 89 fibromyalgia patients and 36 pain-free controls, and compared using ANCOVA controlling for potential confounders, as well as Bayesian methods for parameter estimation and model evaluation. BDNF and NGF levels in fibromyalgia patients did not differ from those in pain-free controls. Statistical methods were consistent, with both frequentist and Bayesian approaches leading to the same conclusions. Our study fails to replicate the finding that peripheral BDNF is altered in fibromyalgia, and instead our findings suggest that plasma levels of growth factor appear normative in fibromyalgia.

Total and acylated ghrelin plasma levels as potential long-term response markers in alcohol-dependent patients receiving high-dose of the GABA-B receptor agonist baclofen.

The orexigenic hormone ghrelin is involved in the regulation of food intake and energy balance. Previous findings suggest its involvement in the modulation of mesolimbic reward pathways, thus potentially being relevant in the pathophysiology of substance use disorders such as alcohol dependence. In the present study, we assessed plasma levels of total and acylated ghrelin within the BACLAD trial, where alcohol-dependent patients received individually titrated high-dose baclofen (30-270 mg/d) within a randomized, placebo-controlled design. Plasma levels of total ghrelin and acylated ghrelin were measured at baseline, during treatment with individually titrated high-dose baclofen and after termination of the study medication within a timeframe of up to 20 weeks. Multivariate longitudinal non-parametric analysis revealed that plasma levels of total ghrelin significantly decreased in the group of abstinent patients receiving high-dose baclofen. In addition, plasma levels of total ghrelin correlated negatively with days of abstinence during treatment with high-dose baclofen. Plasma levels of acylated ghrelin increased during the study in the group of relapsed patients under baclofen and placebo treatment. These findings suggest that the long-term response to baclofen treatment in alcohol use disorder (AUD) might be monitored by assessing total and acylated ghrelin plasma levels.

Hypothalamic-Pituitary-Adrenocortical Axis Activity in Alcohol-Dependent Patients During Treatment with High-Dose Baclofen.

AIMS: Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis has been reported to be affected in alcohol use disorder (AUD). It has been suggested that pharmacological relapse prevention in AUD might exert its effects partly by modulation of HPA axis activity. Here, we assessed the effects of high-dose treatment with baclofen on HPA axis activity in alcohol-dependent patients within a 24-week randomized, placebo-controlled trial (BACLAD study). METHODS: Plasma levels of copeptin, adrenocorticotropic hormone (ACTH), and cortisol were measured at 3 timepoints in alcohol-dependent patients during the study. Corresponding plasma levels in healthy controls were assessed once. RESULTS: ACTH blood levels were significantly higher in the group of alcohol-dependent patients compared to controls. In patients receiving individually titrated high-dose baclofen, plasma cortisol levels decreased significantly, whereas no significant alterations were found in the placebo group. CONCLUSIONS: Our study underlines again the role of HPA axis alterations in AUD. Furthermore, a decrease in hormonal stress levels during treatment with high-dose baclofen might contribute to the relapse preventive effects of this compound.

Effects of high-dose baclofen on cue reactivity in alcohol dependence: A randomized, placebo-controlled pharmaco-fMRI study.

Increased functional brain response towards alcohol-associated stimuli is a neural hallmark of alcohol dependence and a promising target for pharmacotherapy. For the first time, we assessed the effects of individually titrated high-dose baclofen on cue reactivity and functional connectivity in alcohol-dependent (AD) patients in a randomized controlled trial (RCT). We investigated 23 recently detoxified AD patients and 23 matched healthy controls (HC) with a cue reactivity functional magnetic resonance imaging task. Patients were further scanned at baseline without medication and during treatment with high-dose baclofen/placebo (30-270 mg/d). Analyses were conducted for alcohol cue-elicited brain response, alcohol cue-modulated and stimulus-independent functional connectivity with left ventral tegmental area (VTA) as seed region. At baseline, AD patients (N = 23) showed increased cue-elicited brain activation in the ventral striatum (VS) compared to HC (N = 23), which was decreased at the second scanning session compared to baseline. Patients receiving baclofen (N = 10) showed a significant stronger decrease in cue-elicited brain activation in left orbitofrontal cortex (OFC), bilateral amygdala and left VTA than patients receiving placebo (N = 13). Treatment with baclofen further led to a decrease in alcohol cue-modulated functional connectivity between left VTA and left anterior cingulate cortex (ACC) as well as left medial prefrontal cortex (MPFC). Regarding clinical outcome, significantly more patients of the baclofen group remained abstinent during the high-dose period. Baclofen specifically decreased cue-elicited brain responses in areas known to be involved in the processing of salient (appetitive and aversive) stimuli. Treatment with high-dose baclofen seems to provide a pharmacological relief of this neural "warning signal" evoked by alcohol-related cues, thereby possibly supporting patients in remaining abstinent. Trial Registration Identifier of the main trial [BACLAD study] at clinicaltrials.gov: NCT01266655.

Plasma levels of leptin in patients with pathological gambling, internet gaming disorder and alcohol use disorder.

Leptin has been suggested to be involved in the pathophysiology of addictive disorders via modulation of mesolimbic reward pathways. Previous studies in patients with substance use disorders (alcohol, tobacco, cocaine) found positive correlations of leptin blood levels with craving. Here, we investigated leptin blood levels in patients with non-substance related addictive disorders such as pathological gambling (PG) and internet gaming disorder (IGD) in comparison to patients with alcohol use disorder (AUD) and healthy controls. Plasma levels of leptin were measured in male patients with PG (n = 14), male patients with IGD (n = 11), male patients with AUD (n = 39) and male healthy controls (n = 12). Additionally, correlation analyses with blood levels of HPA axis hormones were performed. Leptin plasma levels of patients with PG, IGD or AUD and healthy controls did not differ significantly across groups. In patients with PG, leptin plasma levels were correlated with copeptin, a surrogate for arginine vasopressin. Our findings do not suggest an involvement of leptin in abstinent patients with AUD or in patients with active IGD. In patients with active PG, leptin blood levels were not related to craving for gambling, but leptin might be involved in PG via an interaction with the HPA axis.

Serum brain-derived neurotrophic factor (BDNF) in sleep-disordered patients: relation to sleep stage N3 and rapid eye movement (REM) sleep across diagnostic entities.

Experimental and clinical evidence suggests an association between neuroplasticity, brain-derived neurotrophic factor and sleep. We aimed at testing the hypotheses that brain-derived neurotrophic factor is associated with specific aspects of sleep architecture or sleep stages in patients with sleep disorders. We included 35 patients with primary insomnia, 31 patients with restless legs syndrome, 17 patients with idiopathic hypersomnia, 10 patients with narcolepsy and 37 healthy controls. Morning serum brain-derived neurotrophic factor concentrations were measured in patients and controls. In patients, blood sampling was followed by polysomnographic sleep investigation. Low brain-derived neurotrophic factor levels were associated with a low percentage of sleep stage N3 and rapid eye movement sleep across diagnostic entities. However, there was no difference in brain-derived neurotrophic factor levels between diagnostic groups. Our data indicate that serum levels of brain-derived neurotrophic factor, independent of a specific sleep disorder, are related to the proportion of sleep stage N3 and REM sleep. This preliminary observation is in accordance with the assumption that sleep stage N3 is involved in the regulation of neuroplasticity.

Serum levels of brain-derived neurotrophic factor in alcohol-dependent patients receiving high-dose baclofen.

The neurotrophin brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the development and maintenance of addictive and other psychiatric disorders. Also, interactions of γ-aminobutyric acid (GABA)-ergic compounds and BDNF have been reported. The objective of this study was to investigate serum levels of BDNF over time in alcohol-dependent patients receiving individually titrated high-dose treatment (30-270mg/d) with the GABA-B receptor agonist baclofen or placebo for up to 20 weeks. Serum levels of BDNF were measured in patients of the baclofen/placebo group at baseline (t0), 2 weeks after reaching individual high-dose of baclofen/placebo treatment (t1) and after termination of study medication (t2) in comparison to carefully matched healthy controls. No significant differences in serum levels of BDNF between the baclofen and the placebo group or healthy controls were found at t0, t1, or at t2. Based on these findings, it seems unlikely that baclofen exerts a direct effect on serum levels of BDNF in alcohol-dependent patients. Future studies are needed to further explore the mechanism of action of baclofen and its possible relationship to BDNF in alcohol use disorders.

Effects of repetitive imagination of alcohol consumption on craving in alcohol-dependent patients: A pilot study.

BACKGROUND: In the majority of patients with alcohol use disorder (AUD), the clinical course is characterized by multiple relapses to drinking, frequently preceded by intense craving for alcohol. The present pilot study aimed to assess the effects of a repetitive imaginary cue-exposure protocol in reducing craving in recently abstinent alcohol-dependent patients. METHODS: Sixty-four patients were randomly assigned to six intervention groups and were instructed to repetitively imagine: i) drinking a glass of their preferred alcoholic drink (low vs. high number of repetitions); or ii) drinking a glass of water (low vs. high number of repetitions); or iii) performing an analogous movement or performed no imagination. Additionally, 10 healthy controls were instructed to repetitively imagine drinking a glass of their preferred alcoholic drink (high number of repetitions). The levels of craving before and after intervention were measured using the Alcohol Urge Questionnaire (AUQ) and the Visual Analogue Scale for Craving (VASC). RESULTS: Repetitive imagination of alcohol consumption did not lead to a significant decrease in craving in alcohol-dependent patients as measured by the AUQ and VASC. In contrast, healthy controls showed a nearly significant decrease of the urge to drink alcohol after applying the protocol with a high number of repetitions. CONCLUSIONS: The findings of this pilot study might indicate an aberrant ability to habituate to alcohol-related stimuli in patients with AUD compared to healthy subjects. Future studies in larger samples are needed to further explore the effectiveness of imaginary cue-exposure interventions in alcohol dependence.

Characteristics of Social Network Gamers: Results of an Online Survey.

Current research on Internet addiction (IA) reported moderate to high prevalence rates of IA and comorbid psychiatric symptoms in users of social networking sites (SNS) and online role-playing games. The aim of this study was to characterize adult users of an Internet multiplayer strategy game within a SNS. Therefore, we conducted an exploratory study using an online survey to assess sociodemographic variables, psychopathology, and the rate of IA in a sample of adult social network gamers by Young's Internet Addiction Test (IAT), the Toronto Alexithymia Scale (TAS-26), the Beck Depression Inventory-II (BDI-II), the Symptom Checklist-90-R (SCL-90-R), and the WHO Quality of Life-BREF (WHOQOL-BREF). All participants were listed gamers of "Combat Zone" in the SNS "Facebook." In this sample, 16.2% of the participants were categorized as subjects with IA and 19.5% fulfilled the criteria for alexithymia. Comparing study participants with and without IA, the IA group had significantly more subjects with alexithymia, reported more depressive symptoms, and showed poorer quality of life. These findings suggest that social network gaming might also be associated with maladaptive patterns of Internet use. Furthermore, a relationship between IA, alexithymia, and depressive symptoms was found that needs to be elucidated by future studies.

High-dose baclofen for the treatment of alcohol dependence (BACLAD study): a randomized, placebo-controlled trial.

Previous randomized, placebo-controlled trials (RCTs) assessing the efficacy of the selective γ-aminobutyric acid (GABA)-B receptor agonist baclofen in the treatment of alcohol dependence have reported divergent results, possibly related to the low to medium dosages of baclofen used in these studies (30-80mg/d). Based on preclinical observations of a dose-dependent effect and positive case reports in alcohol-dependent patients, the present RCT aimed to assess the efficacy and safety of individually titrated high-dose baclofen for the treatment of alcohol dependence. Out of 93 alcohol-dependent patients initially screened, 56 were randomly assigned to a double-blind treatment with individually titrated baclofen or placebo using dosages of 30-270mg/d. The multiple primary outcome measures were (1) total abstinence and (2) cumulative abstinence duration during a 12-week high-dose phase. More patients of the baclofen group maintained total abstinence during the high-dose phase than those receiving placebo (15/22, 68.2% vs. 5/21, 23.8%, p=0.014). Cumulative abstinence duration was significantly higher in patients given baclofen compared to patients of the placebo group (mean 67.8 (SD 30) vs. 51.8 (SD 29.6) days, p=0.047). No drug-related serious adverse events were observed during the trial. Individually titrated high-dose baclofen effectively supported alcohol-dependent patients in maintaining alcohol abstinence and showed a high tolerability, even in the event of relapse. These results provide further evidence for the potential of baclofen, thereby possibly extending the current pharmacological treatment options in alcohol dependence.

Hypothalamic-pituitary-adrenal axis activity in patients with pathological gambling and internet use disorder.

Alterations in secretion of stress hormones within the hypothalamic-pituitary-adrenal (HPA) axis have repeatedly been found in substance-related addictive disorders. It has been suggested that glucocorticoids might contribute to the development and maintenance of substance use disorders by facilitatory effects on behavioral responses to substances of abuse. The objective of this pilot study was to investigate HPA axis activity in patients with non-substance-related addictive disorders, i.e. pathological gambling and internet use disorder. We measured plasma levels of copeptin, a vasopressin surrogate marker, adrenocorticotropic hormone (ACTH) and cortisol in male patients with pathological gambling (n=14), internet use disorder (n=11) and matched healthy controls for pathological gambling (n=13) and internet use disorder (n=10). Plasma levels of copeptin, ACTH and cortisol in patients with pathological gambling or internet use disorder did not differ among groups. However, cortisol plasma levels correlated negatively with the severity of pathological gambling as measured by the PG-YBOCS. Together with our findings of increased serum levels of brain-derived neurotrophic factor (BDNF) in pathological gambling but not internet use disorder, these results suggest that the pathophysiology of pathological gambling shares some characteristics with substance-related addictive disorders on a neuroendocrinological level, whereas those similarities could not be observed in internet use disorder.

Focus on ECT seizure quality: serum BDNF as a peripheral biomarker in depressed patients.

Electroconvulsive therapy (ECT) is a well-established, safe and effective treatment in severest or drug-resistant affective disorders. The potential relation between any peripheral biological marker and the seizure quality as a surrogate for treatment efficacy has not been investigated so far. We prospectively examined serum brain-derived neurotrophic factor (BDNF) levels in 20 patients with major depression before and after electroconvulsive therapy. A seizure quality sum score for every ECT session was build up on the basis of the seizure duration, seizure amplitude, central inhibition, interhemispheric coherence and sympathetic activation. Serum BDNF levels were significantly higher after ECT (P = 0.036). In the linear regression analysis, a significant correlation of the serum BDNF levels and the time between the last ECT and the blood withdrawal (P = 0.01) was observed. The ANOVA revealed a significant influence of the interval between the last ECT and the blood withdrawal (P = 0.0017) as well as the seizure quality (P = 0.038) on the variance of BDNF serum levels. Our data corroborate the neurotrophin hypothesis suggesting an ECT-induced central BDNF rise leading to a delayed (>6 days) and increased equilibrium of the peripheral BDNF. The association of seizure adequacy with a BDNF rise might underline the importance of monitoring seizure quality markers in daily practice.

Current pharmacological treatment approaches for alcohol dependence.

INTRODUCTION: At present, the substances acamprosate, naltrexone and disulfiram are available for pharmacotherapy in alcohol dependence, but clinical studies found only modest effect sizes of these treatment options. AREAS COVERED: This article focuses on current pharmacological treatment approaches for alcohol dependence, which have been evaluated in randomized, placebo-controlled trials (RCTs). EXPERT OPINION: Besides the opioid system modulator nalmefene, which has recently been approved as a medication for the reduction of alcohol consumption, several compounds have been investigated in patients with alcohol dependence using a randomized, placebo-controlled design. In these studies, the antiepileptic drugs topiramate and gabapentin were found to be effective in improving several drinking-related outcomes, whereas levetiracetam failed to show efficacy in the treatment of alcohol dependence. Clinical studies using (low-dose) baclofen, a selective GABA-B receptor agonist, produced conflicting results, so that results of further trials are needed. Varenicline has also shown mixed results in two RCTs, but might possibly be useful in patients with comorbid nicotine dependence. The α1 adrenergic antagonist prazosin is currently under investigation in alcohol dependence with and without comorbid posttraumatic stress disorder (PTSD). Finally, first clinical evidence suggests that the 5-HT3 antagonist ondansetron might possibly be used in future within a pharmacogenetic treatment approach in alcohol dependence.

Serum levels of brain-derived neurotrophic factor in patients with internet use disorder.

Internet use disorder (IUD) is characterised by excessive internet gaming use and has temporarily been conceptualised as a behavioural addiction. Since brain-derived neurotrophic factor (BDNF) has been hypothesised to be involved in the development and maintenance of addictive disorders, we investigated BDNF expression in IUD. We measured BDNF serum levels in male patients with IUD (n=11) and individually matched healthy controls (n=10). There was no significant difference in BDNF serum levels of patients with IUD in comparison to control subjects. Serum levels of BDNF were not correlated with severity of IUD or clinical and demographic variables in our study. These preliminary findings possibly suggest a different underlying pathophysiology in IUD compared to addictive disorders. Thus, further studies are needed to clarify, whether IUD represents an addictive spectrum disorder, an impulse control disorder or finally an individual diagnostic entity that overlaps with both disease categories.

Genetic risk factors for depression in Alzheimer`s disease patients.

OBJECTIVE: Alzheimer's Disease (AD) is often associated with depressive symptoms developing at any time before and after AD onset. The aetiology of depression in AD has not sufficiently been characterized, but biological aspects due to neurodegeneration and/ or genetic risk factors may play a plausible role and may distinguish it from common depressive disorders. METHOD: To investigate the possible relationship between genetic risk factors and depression in AD, we assessed genetic polymorphisms reported to be associated with depression (MAOA VNTR, ACE 288bp Insertion/ Deletion, 5HTTLPR, COMT Val158Met, BDNF Val66Met, TPH1 A218C, HTR2A T102C, P2RX7 Q460R, FKBP5 rs1360780 and CRHR1 rs242941) in a cross-sectional study on 246 AD patients with or without clinically significant major depressive disorder (MDD) according to DSM-IV. RESULTS: Significant associations between AD and MDD have been found for three polymorphisms mainly in females (TPH1 A218C, MAOA VNTR and BDNF Val66Met) and one polymorphism in the total population only (FKBP5 rs1360780). There was an increased risk of having MDD in homozygous female carriers of the TPH1 A-allele (odds ratio: 4.35) and homozygous carriers of the MAOA VNTR low activity allele 3R (odds ratio: 3.37). CONCLUSION: We detected allelic or genotypic associations of MAOA, TPH1, FKBP5 and BDNF in clinically significant MDD in AD. Odds-ratios were generally higher in female AD-patients, which might be due to the composition of the study population. Further studies on the neurotransmitter systems affected by the genetic polymorphisms found to be associated with MDD in AD may help to elucidate the underlying pathomechanisms of MDD.

Altered serum levels of brain-derived neurotrophic factor in patients with pathological gambling.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays important roles in neurotransmitter release and synaptic plasticity and has been hypothesized to be involved in the development and maintenance of addictive disorders. The objective of this study was to investigate alterations of BDNF expression in a non-substance-related addiction, i.e. pathological gambling (PG). METHODS: Serum levels of BDNF were assessed in male patients with PG (n = 14) and healthy control subjects (n = 13) carefully matched for sex, age, body mass index, smoking status and urbanicity. Symptoms and severity of PG were measured by the adapted form of the Yale-Brown Obsessive-Compulsive Scale. RESULTS: BDNF serum levels were significantly increased in patients with PG in comparison to healthy control subjects (p = 0.016). There were no significant correlations between BDNF serum levels and severity of PG or clinical and demographic variables. CONCLUSIONS: Our results show alterations of BDNF serum levels in patients suffering from a behavioural addiction and suggest that non-substance-related addictions like PG might be associated with neuroendocrinological changes similar to the changes observed in substance-related addictions.