Lateral asymmetry of emotional arousal as a biomarker of attributional style during darts competitions.

According to the Multiple Arousal Theory, electrodermal activity (EDA) is not uniform across the body. However, the psychological meaning of a left or right-sided EDA dominance is still not clear. We explored EDA lateral asymmetry as a psychophysiological marker of optimistic and pessimistic attributional style regarding success and failure in a darts competition. Bilateral EDA pattern of 230 throws of a competing pair was measured by Obimon EDA including accelerometer measurements of movements. First, we confirmed that lateral asymmetry can be measured reliably based on EDA data from both wrists. Second, we assessed attributional styles related to lateral asymmetry based on 80 individual throws. We recorded participants' expectations regarding their upcoming performance, and their attribution of success and failure based on Seligman's definition as optimist (internal cause attributed to success, or external cause ascribed to failure) or pessimist. The ratio of optimist and pessimist attributions was significantly different for throws with right or left-sided EDA dominance (p = 0.001). Optimistic attribution characterized 84% of right dominant, while pessimist 63% of left-dominant EDA during throws. We replicated these findings on 50 throws from 10 more individuals (p = 0.034). All individuals were right-handed. We conclude that wrist EDA can be reliably measured during physical movements, such as in a darts game. Lateral EDA asymmetry is a consistent psychophysiological marker of the attitude toward success and failure in a competitive setting, suggesting that lateral asymmetry of emotional arousal may serve as a novel psychophysiological biomarker for attribution style. Results underlie the psychophysiological relevance of bilateral arousal assessment and provide evidence-based verification for the Multiple Arousal Theory.

Severity of behavioral addiction symptoms among young adults using non-prescribed sedatives/hypnotics.

Introduction: Young adulthood is considered a critical period in terms of non-medical use of sedatives/hypnotics (NMUSH) as well as different types of behavioral addictions (BAs). However, the relationship between these behaviors has received scarce attention among young adult samples. Therefore, the aim of the present study was to investigate the association between NMUSH and symptoms of distinct BAs among young adults. Materials and methods: Analyses were conducted based on the data of two large sample studies (including a representative sample) carried out with young adult samples. The following BAs were assessed: problematic internet use, problematic video gaming, problematic social media use, problem gambling, exercise addiction, eating disorders, compulsive buying behavior, problematic mobile phone use, work addiction, and hair pulling. Symptoms of distinct BAs were analyzed in three groups formed based on the NMUSH: non-users, lifetime users, and current users. Results: The symptoms of problematic internet use, problematic social media use, problem gambling, exercise addiction, eating disorders, compulsive buying behavior and work addiction were significantly more severe among lifetime and/or current non-medical sedative and hypnotic users, compared to the non-user participants. The symptoms of problematic mobile phone use were the most severe in the non-user group. Conclusions: The results suggest co-occurrence between NMUSH and distinct BAs among young adults. These findings draw attention to the need for preventive interventions for this high-risk population.

FOXN3 and GDNF Polymorphisms as Common Genetic Factors of Substance Use and Addictive Behaviors.

Epidemiological and phenomenological studies suggest shared underpinnings between multiple addictive behaviors. The present genetic association study was conducted as part of the Psychological and Genetic Factors of Addictions study (n = 3003) and aimed to investigate genetic overlaps between different substance use, addictive, and other compulsive behaviors. Association analyses targeted 32 single-nucleotide polymorphisms, potentially addictive substances (alcohol, tobacco, cannabis, and other drugs), and potentially addictive or compulsive behaviors (internet use, gaming, social networking site use, gambling, exercise, hair-pulling, and eating). Analyses revealed 29 nominally significant associations, from which, nine survived an FDRbl correction. Four associations were observed between FOXN3 rs759364 and potentially addictive behaviors: rs759364 showed an association with the frequency of alcohol consumption and mean scores of scales assessing internet addiction, gaming disorder, and exercise addiction. Significant associations were found between GDNF rs1549250, rs2973033, CNR1 rs806380, DRD2/ANKK1 rs1800497 variants, and the "lifetime other drugs" variable. These suggested that genetic factors may contribute similarly to specific substance use and addictive behaviors. Specifically, FOXN3 rs759364 and GDNF rs1549250 and rs2973033 may constitute genetic risk factors for multiple addictive behaviors. Due to limitations (e.g., convenience sampling, lack of structured scales for substance use), further studies are needed. Functional correlates and mechanisms underlying these relationships should also be investigated.

Development and validation of the Reward Deficiency Syndrome Questionnaire (RDSQ-29).

BACKGROUND: The reward deficiency syndrome (RDS) integrates psychological, neurological, and genetic factors of addictive, impulsive, and compulsive behaviors. However, to date, no instrument has been validated to assess the RDS construct. AIMS: The present study developed and tested a tool to assess RDS. METHODS: Data were collected on two college and university samples. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were performed on Sample 1 (N = 1726), and confirmatory analysis was conducted on an independent sample (N = 253). Impulsivity and sensation-seeking were assessed. RESULTS: Based on EFAs, a 29-item Reward Deficiency Syndrome Questionnaire (RDSQ-29) was developed, containing four subscales (lack of sexual satisfaction, activity, social concerns, and risk-seeking behavior). CFA indicated good fit (comparative fit index (CFI) = 0.941; Tucker-Lewis index (TLI) = 0.933; root mean square error of approximation (RMSEA) = 0.068). Construct validity analysis showed strong relationship between sensation-seeking and the RDS scale. CONCLUSION: The RDSQ-29 is an adequate scale assessing psychological and behavioral aspects of RDS. The RDSQ-29 assesses psychological and behavioral characteristics that may contribute to addictions generally.

Hungarian validation of the Buss-Perry Aggression Questionnaire-Is the short form more adequate?

OBJECTIVE: We aim to provide a publicly available Hungarian version of the BPAQ; compare the BPAQ factors to other personality traits; and compare both the original BPAQ factor structure provided by Buss and Perry (J. Pers. Soc. Psychol., 63, 1992, 452), the revised BPAQ-SF factor structure by Bryant and Smith (J. Res. Pers., 35, 2001, 138), and the BAQ by Webster et al. (Aggress. Behav., 40, 2014, 120). METHODS: The validation of the Hungarian version of the BPAQ was carried out on a Hungarian university sample (N = 841). There were three main focuses of data analysis: descriptive statistics, correlations, and confirmatory factor analyses. RESULTS: CFA-related statistics showed an adequate fit for the BPAQ 4 factors; however, contrary to prior validations of BPAQ, we were not able to clearly define the verbal aggression factor. We found that the shorter form of the BPAQ has a better model fit on our sample than the original form, while the model fit of the BAQ was in-between these. BPAQ scales showed low to moderate relationship with the Barratt Impulsivity Scale and Hospital Anxiety and Depression Scale. CONCLUSION: Both the BPAQ and the BPAQ-SF, also the BAQ provide acceptable model fitting on a Hungarian sample of university students. While most of BPAQ items provided adequate loadings on their hypothesized factors, two items (21 and 27) did not. We argue this is the result of conceptual inaccuracy of the original items.

Bilateral comparison of traditional and alternate electrodermal measurement sites.

Advances in mobile and wireless technology have expanded the scope of electrodermal research. Since traditional electrodermal measurement sites are not always suitable for laboratory research and are rarely appropriate for ambulatory measurements, there is a need to explore and contrast alternate measurement locations. We evaluated bilateral electrodermal activity (EDA) from five measurement sites (fingers, feet, wrists, shoulders, and calves). In a counterbalanced, randomized, within-subjects design study, participants (N = 115) engaged in a 4-min-long breathing exercise and were exposed to emotionally laden and neutral stimuli. High within-subject correlations were found between the EDA measured from fingers bilaterally (r = .89), between the left fingers and both feet (r = .72). Moderate correlations were found between EDA measured from the left fingers and wrists (r = .30 and r = .33), low correlations between the left fingers and the shoulders (r = -.03 and r = -.06) or calves (r = .05 and r = .14). Response latency was the shortest on the fingers while it was the longest on the lower body. Short response windows would miss some of the responses from the palmar surfaces and a substantial number from other evaluated locations. The fingers and the feet are the most reliable locations to measure from, followed by the wrists. We suggest setting site-specific response windows for different measurement locations. An investigation of repeatability showed that within-subject correlations, response frequencies, response amplitudes show a similar pattern from the first measurement time to a later one.

Co-occurrences of substance use and other potentially addictive behaviors: Epidemiological results from the Psychological and Genetic Factors of the Addictive Behaviors (PGA) Study.

BACKGROUND AND AIMS: Changes in the nomenclature of addictions suggest a significant shift in the conceptualization of addictions, where non-substance related behaviors can also be classified as addictions. A large amount of data provides empirical evidence that there are overlaps of different types of addictive behaviors in etiology, phenomenology, and in the underlying psychological and biological mechanisms. Our aim was to investigate the co-occurrences of a wide range of substance use and behavioral addictions. METHODS: The present epidemiological analysis was carried out as part of the Psychological and Genetic Factors of the Addictive Behaviors (PGA) Study, where data were collected from 3,003 adolescents and young adults (42.6% males; mean age 21 years). Addictions to psychoactive substances and behaviors were rigorously assessed. RESULTS: Data is provided on lifetime occurrences of the assessed substance uses, their co-occurrences, the prevalence estimates of specific behavioral addictions, and co-occurrences of different substance use and potentially addictive behaviors. Associations were found between (i) smoking and problematic Internet use, exercising, eating disorders, and gambling (ii) alcohol consumption and problematic Internet use, problematic online gaming, gambling, and eating disorders, and (iii) cannabis use and problematic online gaming and gambling. CONCLUSIONS: The results suggest a large overlap between the occurrence of these addictions and behaviors and underlies the importance of investigating the possible common psychological, genetic and neural pathways. These data further support concepts such as the Reward Deficiency Syndrome and the component model of addictions that propose a common phenomenological and etiological background of different addictive and related behaviors.

Association between anxiety and non-coding genetic variants of the galanin neuropeptide.

BACKGROUND: Galanin, an inhibitory neuropeptide and cotransmitter has long been known to co-localize with noradrenaline and serotonin in the central nervous system. Several human studies demonstrated altered galanin expression levels in major depressive disorder and anxiety. Pharmacological modulation of galanin signaling and transgenic strategies provide further proof for the involvement of the galanin system in the pathophysiology of mood disorders. Little is known, however, on the dynamic regulation of galanin expression at the transcriptional level. The aim of the present study was to seek genetic association of non-coding single nucleotide variations in the galanin gene with anxiety and depression. METHODS: Six single nucleotide polymorphisms (SNP) occurring either in the regulatory 5' or 3' flanking regions or within intronic sequences of the galanin gene have been genotyped with a high-throughput TaqMan OpenArray qPCR system in 526 healthy students (40% males). Depression and anxiety scores were obtained by filling in the Hospital Anxiety and Depression Scale (HADS) questionnaire. Data were analyzed by ANCOVA and Bonferroni correction was applied for multiple testing. Linkage disequilibrium (LD) analysis was used to map two haploblocks in the analyzed region. RESULTS AND CONCLUSIONS: A single-locus and a haplotype genetic association proved to be statistically significant. In single-marker analysis, the T allele of the rs1042577 SNP within the 3' untranslated region of the galanin gene associated with greater levels of anxiety (HADS scores were 7.05±4.0 vs 6.15±.15; p = 0.000407). Haplotype analysis revealed an association of the rs948854 C_rs4432027_C allele combination with anxiety [F(1,1046) = 4.140, p = 0.042141, η2 = 0.004, power = 0.529]. Neither of these associations turned out to be gender-specific. These promoter polymorphisms are supposed to participate in epigenetic regulation of galanin expression by creating potentially methylatable CpG dinucleotides. The functional importance of the rs1042577_T allele remains to be elucidated.

[Relationship between executive functions, body mass index and the DRD4 VNTR 7-repeat allele]. / A végrehajtó funkciók összefüggése a testtömegindexszel és a DRD4-VNTR 7-es alléllal.

Introduction and aim: Earlier results in the literature suggest that overweight subjects show weaker performance in executive function tasks as compared to normal weight people. Dopaminergic system is strongly linked to executive functions, body mass regulation and ingestion. The aim of the present study was to examine the possible relationship between DRD4 VNTR 7-repeat allele, body mass index and Stroop performance in a healthy adult population, and to draw psychogenetic conclusions. Method: 152 subjects without diabetic or psychiatric history participated in the study. Along with non-invasive DNA sampling, demographic, weight and height data were collected. The participants also solved the computerized Stroop task. 11 subjects belonged to the underweight (mean body mass index = 17.9 kg/m2), 98 subjects to the normal (mean body mass index = 21.8 kg/m2), and 43 subjects to the overweight (mean body mass index = 28.9 kg/m2) category. After grouping participants according to their body mass index and DRD4 VNTR genotype, we compared their mean performance to investigate the possible psychogenetic associations. Results: Body mass index and stimuli type showed significant interaction on error number (p = 0.045): subjects with normal body mass index made significantly less error as compared to under- and overweight subjects in incongruent trials. The 7-repeat allele carriers made tendentiously more errors than non-carriers. Normal weight people made less error - independently from their genotype -, while subjects with either low or high BMI carrying the 7-repeat allele made more errors compared to non-carriers. Conclusion: Under- and overweight subjects perform weaker where inhibition is necessary in the task. This may reflect their reactions to food-related situations. Orv Hetil. 2019; 160(39): 1554-1562.

Gene-sex interaction in Hypercompetitive Attitude suggests beneficial effect of the DRD4 7-repeat allele in adaptation.

Twin studies provide evidence for the heritability of social attitudes, e.g. competitiveness, however, there are no psychogenetic association results linking competitive attitudes to genetic polymorphisms. Candidate gene studies report association with competitiveness-related phenotypes, risk taking for example was linked with the 7-repeat allele of the dopamine D4 receptor gene. This polymorphism has been studied extensively with novelty seeking and certain psychiatric disorders, as it plays a crucial role in molecular genetic mechanisms driving behavioral responses to the environment, especially modulating behavior through the reward circuitry. In the present study, we examined association of the DRD4 48-bp VNTR and competitiveness using self-report data from 399 non-related Caucasians. We found an interesting gene-sex interaction: 7-carrier males were more hypercompetitive as compared to non-carriers, while 7-carrier females were less hypercompetitive as compared to non-carriers. This finding remained significant after Bonferroni correction for multiple testing. Interestingly, among females we observed a significant positive correlation between hypercompetitiveness and mood characteristic variables, however, no such relationship could be detected in males. In 7-carrier females the association of hypercompetitiveness and anxiety or depression was more robust as compared to non-carrier females. These results highlight the importance of cultural influences in interpreting gene-sex interaction effects. Our results underlies interaction between genes and the environment; suggesting that the 7-repeat allele plays an important role in adaptivity, enabling sex-specific behavior to social expectations.

Association of GDNF and CNTNAP2 gene variants with gambling.

BACKGROUND AND AIMS: Some form of gambling can be observed in nearly every society, as the gratification felt upon winning in uncertain conditions is universal. A culturally distinct form of gambling, associated with a traditional sporting event of archery known as "teer," is innate to the province of Meghalaya, India. The objective of this study was to find genetic variants underlying this unique form of behavioral addiction. To better understand game-based gambling, we studied genetic variants related to dopaminergic pathways and other genes previously linked to various psychological disorders. METHODS: This study was carried out on a sample of 196 Indo-Aryan adults from Shillong, Meghalaya. Genotyping of glial cell line-derived neurotrophic factor (GDNF) polymorphisms was carried out using real-time PCR. We further investigated 32 single nucleotide polymorphisms located in the 3' UTR of additional genes of interest using an OpenArray® real-time PCR platform. RESULTS: Case-control analysis revealed a significant association between GDNF variant rs2973033 (p = .00864, χ2 = 13.132, df = 2) and contactin-associated protein-like 2 (CNTNAP2) variant rs2530311 (p = .0448, χ2 = 13.132, df = 2) with gambling. DISCUSSION AND CONCLUSIONS: Association of the GDNF gene with gambling could be attributed to its involvement in the development and survival of dopaminergic neurons. Our result is in good agreement with previous data indicating the role of GDNF in certain substance addictions. Several rare variants in the CNTNAP2 gene were also implicated in alcohol addiction in a previous study. This pilot study provides further support for the role of GDNF and CNTNAP2 in addiction behaviors.

Obimon: An open-source device enabling group measurement of electrodermal activity.

Electrodermal activity (EDA) provides the means to gauge the activity of the sympathetic nervous system. Assessment of EDA for research purposes requires measurement systems that are sensitive to small changes in arousal in the full measurement range, collecting, storing, and monitoring data. The objective behind designing a new open-source device was to be able to measure EDA simultaneously on many subjects, monitoring their activity in real time remotely and collecting high precision data suitable for analyses. To assure feasibility of simultaneous measurements on multiple subjects, the devices must be compact and wearable, without compromising data quality. Experiments were carried out using synchronized devices in group and single subject environments. Validity of EDA measurements of Obimon was demonstrated compared to a reference system (Nexus) during a breathing exercise, a short movie, and while exposed to loud computer-generated tones, using Pearson correlation, Passing-Bablok regression, and Bland-Altman analysis. Seamless management of several Obimons and real-time visualization of EDA via Android phone/tablet application from a large number of participants was demonstrated. Based on analyses of the data collected, we conclude that the Obimon device presented here is a valid and feasible tool for collecting EDA in single or multisubject environments.

The psychological and genetic factors of the addictive behaviors (PGA) study.

OBJECTIVES: Most of the addiction studies focus on very specific aspects of addictions, often with contradictory results, and integrated studies are quite rare. Experimental studies comparing underlying mechanisms of addictions and analyzing data from an integrative psychological and genetic perspective are almost nonexistent. The aim of the present paper is to describe the research protocol of the Psychological and Genetic Factors of Addictive Behaviors (PGA) study, which applies an integrative approach to understanding the acquisition, development, and maintenance of addictive behaviors. METHODS: A wide-spectrum national study was carried out. Data were collected from 3,003 adolescents. Addictions to both psychoactive substances and behaviors were thoroughly assessed via psychometrically robust scales, which also included assessment related to a wide range of related psychological dimensions. Additionally, a DNA sample was also collected from participants. RESULTS: The paper presents the detailed methodology of the PGA study. Data collection procedures, instrumentation, and the analytical approach used to attain the research objectives are described. CONCLUSIONS: Future plans, along with potential contributions of the PGA study, are also discussed. It is envisaged that the study will provide a unique opportunity to test possible mechanisms and causal pathways mediating the associations of genetic factors, psychological characteristics, and addictions.

From genomes to diaries: a 3-year prospective, real-life study of ragweed-specific sublingual immunotherapy.

During the last decades, the prevalence of allergy has dramatically increased. Allergen-specific immunotherapy is the only currently available medical intervention that has the potential to affect the natural course of the disease, but there are still many questions and unmet needs hindering its widespread use to fulfill its treatment potential and maximize its benefits for the society. To provide a comprehensive phenome-wide overview in sublingual immunotherapy, using ragweed allergy as a target, we planned and carried out a longitudinal, prospective, observational, open-label study (DesensIT). In this paper we present challenges of using deep and comprehensive phenotypes embracing biological, clinical and patient-reported outcomes in allergen-specific immunotherapy and show how we designed the DesensIT project to optimize data collection, processing and evaluation.

Association between Age and the 7 Repeat Allele of the Dopamine D4 Receptor Gene.

Longevity is in part (25%) inherited, and genetic studies aim to uncover allelic variants that play an important role in prolonging life span. Results to date confirm only a few gene variants associated with longevity, while others show inconsistent results. However, GWAS studies concentrate on single nucleotide polymorphisms, and there are only a handful of studies investigating variable number of tandem repeat variations related to longevity. Recently, Grady and colleagues (2013) reported a remarkable (66%) accumulation of those carrying the 7 repeat allele of the dopamine D4 receptor gene in a large population of 90-109 years old Californian centenarians, as compared to an ancestry-matched young population. In the present study we demonstrate the same association using continuous age groups in an 18-97 years old Caucasian sample (N = 1801, p = 0.007). We found a continuous pattern of increase from 18-75, however frequency of allele 7 carriers decreased in our oldest age groups. Possible role of gene-environment interaction effects driven by historical events are discussed. In accordance with previous findings, we observed association preferentially in females (p = 0.003). Our results underlie the importance of investigating non-disease related genetic variants as inherited components of longevity, and confirm, that the 7-repeat allele of the dopamine D4 receptor gene is a longevity enabling genetic factor, accumulating in the elderly female population.

Association between smoking behaviour and genetic variants of glial cell line-derived neurotrophic factor.

Glial cell line-derived neurotrophic factor (GDNF) promotes development and differentiation of dopaminergic neurons, thus it has an important role in dopamine-related neuropsychiatric disorders. Since the role of dopamine system in smoking is well established, we hypothesized that GDNF gene variants may affect smoking behaviour. Self-reported data on smoking behaviour (never smoked, quit, occasional, or regular smokers) and level of nicotine addiction (Hooked on Nicotine Checklist and Fagerstrom Nicotine Addiction Scale), anxiety, as well as buccal samples were obtained from 930 Hungarian young adults (18-35 years). Genetic analysis involved eight GDNF single-nucleotide polymorphisms (SNP) (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111). Allele-wise association analyses of the eight GDNF SNPs provided a significant association between smoking behaviour and rs3096140 (P=0.0039). The minor allele (C) was more frequent in those groups who smoked in some form (quit, occasional or regular smokers) as compared to those who never smoked (P = 0.0046). This result remained significant after Bonferroni correction for multiple testing. In the ever smoking group, no significant differences were found in the level of nicotine addiction by the alleles of these polymorphisms. Also, no significant interaction of rs3096140 and smoking categories were observed on anxiety mean scores. Although previous data demonstrated an association between GDNF rs2910704 and severity of methamphetamine use to the best of our knowledge, this is the first study on the role of GDNF genetic variations in smoking behaviour. Our results suggest that GDNF rs3096140 might be involved in the genetic background of smoking, independent of anxiety characteristics.

Individual differences in flow proneness are linked to a dopamine D2 receptor gene variant.

Flow is a special mental state characterized by deep concentration that occurs during the performance of optimally challenging tasks. In prior studies, proneness to experience flow has been found to be moderately heritable. In the present study, we investigated whether individual differences in flow proneness are related to a polymorphism of the dopamine D2 receptor coding gene (DRD2 C957T rs6277). This polymorphism affects striatal D2 receptor availability, a factor that has been shown to be related to flow proneness. To our knowledge, this is the first study to investigate the association between this trait and a specific gene variant. In a sample of 236 healthy Hungarian adults, we found that CC homozygotes report higher flow proneness than do T allele carriers, but only during mandatory activities (i.e., studying and working), not during leisure time. We discuss implications of this result, e.g., the potential mediators of the relationship.

A Genetic Variant (COMT) Coding Dopaminergic Activity Predicts Personality Traits in Healthy Elderly.

Association studies between the NEO five factor personality inventory and COMT rs4680 have focused on young adults and the results have been inconsistent. However, personality and cortical changes with age may put older adults in a more sensitive range for detecting a relationship. The present study examined associations of COMT rs4680 and personality in older adults. Genetic association analyses were carried out between the NEO and the targeted COMT rs4680 in a large, well-characterized sample of healthy, cognitively normal older adults (N = 616, mean age = 69.26 years). Three significant associations were found: participants with GG genotype showed lower mean scores on Neuroticism (p = 0.039) and higher scores on Agreeableness (p = 0.020) and Conscientiousness (p = 0.006) than participants with AA or AG genotypes. These results suggest that older adults with higher COMT enzymatic activity (GG), therefore lower dopamine level, have lower Neuroticism scores, and higher Agreeableness and Conscientiousness scores. This is consistent with a recent model of phasic and tonic dopamine release suggesting that even though GG genotype is associated with lower tonic dopamine release, the phasic release of dopamine might be optimal for a more adaptive personality profile.

[Neurocognitive endophenotypes in psychiatric genetics]. / Neurokognitív endofenotípusok a pszichiátriai genetikában.

Psychiatric genetics aims to map genetic factors of psychiatric disorders with complex inheritance. The most commonly used phenotype is the categorical variable of the presence or absence of a disease (case-control model). However, the biological background of various psychiatric disease categories often overlaps. Thus, the use of endophenotypes based on specific biological mechanisms seems to be a more efficient approach in genetic association studies. Results confirm that categorical variables as phenotypes are statistically not so sensitive in identification of a genetic association as well-chosen endophenotypes. Current literature advocates a growing significance of analyzing dimensional neurocognitive endophenotypes in genetic association studies, as well as in developing diagnostic category systems with biological backgrounds.

Glial cell line-derived neurotrophic factor (GDNF) as a novel candidate gene of anxiety.

Glial cell line-derived neurotrophic factor (GDNF) is a neurotrophic factor for dopaminergic neurons with promising therapeutic potential in Parkinson's disease. A few association analyses between GDNF gene polymorphisms and psychiatric disorders such as schizophrenia, attention deficit hyperactivity disorder and drug abuse have also been published but little is known about any effects of these polymorphisms on mood characteristics such as anxiety and depression. Here we present an association study between eight (rs1981844, rs3812047, rs3096140, rs2973041, rs2910702, rs1549250, rs2973050 and rs11111) GDNF single nucleotide polymorphisms (SNPs) and anxiety and depression scores measured by the Hospital Anxiety and Depression Scale (HADS) on 708 Caucasian young adults with no psychiatric history. Results of the allele-wise single marker association analyses provided significant effects of two single nucleotide polymorphisms on anxiety scores following the Bonferroni correction for multiple testing (p = 0.00070 and p = 0.00138 for rs3812047 and rs3096140, respectively), while no such result was obtained on depression scores. Haplotype analysis confirmed the role of these SNPs; mean anxiety scores raised according to the number of risk alleles present in the haplotypes (p = 0.00029). A significant sex-gene interaction was also observed since the effect of the rs3812047 A allele as a risk factor of anxiety was more pronounced in males. In conclusion, this is the first demonstration of a significant association between the GDNF gene and mood characteristics demonstrated by the association of two SNPs of the GDNF gene (rs3812047 and rs3096140) and individual variability of anxiety using self-report data from a non-clinical sample.