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The association between COMT rs4680 and 5-HTTLPR genotypes and concussion history in South African rugby union players
Journal of Sports Sciences
Abstract
The objective was to investigate the relationship between Catechol-O-methyltransferase (COMT) rs4680 and serotonin-transporter-linked polymorphic region (5-HTTLPR) genotypes with concussion history and personality traits. Rugby players (“all levels”: n = 303), from high schools (“junior”, n = 137), senior amateur, and professional teams (“senior”, n = 166), completed a self-reported concussion history questionnaire, Cloninger’s Tridimensional Personality Questionnaire, and donated a DNA sample. Participants were allocated into control (non-concussed, n = 140), case (all) (previous suspected or diagnosed concussions, n = 163), or case (diagnosed only) (previous diagnosed concussion, n = 140) groups. COMT rs4680 Val/Val genotypes were over-represented in controls in all levels (P = 0.013, OR:2.00, 95% CI:1.15–3.57) and in juniors (P = 0.003, OR:3.57, 95% CI:1.45–9.09). Junior Val/Val participants displayed increased “anticipatory worry” (P = 0.023). The 5-HTTLPR low expressing group was under-represented in controls when all levels were considered (P = 0.032; OR:2.02, 95% CI:1.05–3.90) and in juniors (P = 0.021; OR:3.36, 95% CI:1.16–9.72). Junior 5-HTTLPR low and intermediate expressing groups displayed decreased “harm avoidance” (P = 0.009), “anticipatory worry” (P = 0.041), and “fear of uncertainty” (P < 0.001). This study provides preliminary indications that personality associated genetic variants can influence concussion in rugby.
... Heritability of concussion has not been determined, but it is likely that a substantial genetic component exists for concussion risk and recovery, as heritability of brain structure is shown to be~90% and cognitive performance~60% [20][21][22][23]. Previous candidate gene studies have identified potential genetic risk factors associated with the risk of concussion and recovery [6,7,[24][25][26][27][28][29][30][31][32][33]. Those genetic variants influencing concussion risk and recovery may confer an advantage/disadvantage for rugby athletes by affecting the ability to train and compete and thus advance their careers, and investigating this could provide additional information to support the management of the cumulative effects of concussions [14]. ...
... In addition, the brain-derived neurotrophic factor (BDNF) gene Met/Met homozygotes have been reported to be at a higher risk of sustaining a concussion than Val/Val homozygotes [31]. The catechol-O-methyltransferase (COMT) gene rs4680 Val allele carriers performed poorer on tests of executive function post-TBI [32], and Met carrying RU players have been reported to be approximately three-fold more likely to have a history of concussion [33]. Indeed, elite rugby athletes have~1.4 ...
... Recently, it has been observed that elite rugby athletes have 1.4 times the odds of possessing the GG genotype of COMT (rs4680) compared to non-athletes [34]. In addition, Mc Fie et al. [33] observed that A allele carriers in a cohort of youth and professional South African RU players were approximately three-fold more likely to have a history of concussion. Considering the pleiotropic nature of COMT (rs4680), G carriers could possess greater stress resilience and reduced anxiety in competitive environments and be at lower risk of experiencing concussions but also be at risk of poorer cognitive function post-concussion [34,57,58]. ...
Due to the high-velocity collision-based nature of elite rugby league and union, the risk of sustaining a concussion is high. Occurrence of and outcomes following a concussion are probably affected by the interaction of multiple genes in a polygenic manner. This study investigated whether suspected concussion-associated polygenic profiles of elite rugby athletes differed from non-athletes and between rugby union forwards and backs. We hypothesised that a total genotype score (TGS) using eight concussion-associated polymorphisms would be higher in elite rugby athletes than non-athletes, indicating selection for protection against incurring or suffering prolonged effects of, concussion in the relatively high-risk environment of competitive rugby. In addition, multifactor dimensionality reduction was used to identify genetic interactions. Contrary to our hypothesis, TGS did not differ between elite rugby athletes and non-athletes (p ≥ 0.065), nor between rugby union forwards and backs (p = 0.668). Accordingly, the TGS could not discriminate between elite rugby athletes and non-athletes (AUC ~0.5), suggesting that, for the eight polymorphisms investigated, elite rugby athletes do not have a more ‘preferable’ concussion-associated polygenic profile than non-athletes. However, the COMT (rs4680) and MAPT (rs10445337) GC allele combination was more common in rugby athletes (31.7%; p < 0.001) and rugby union athletes (31.8%; p < 0.001) than non-athletes (24.5%). Our results thus suggest a genetic interaction between COMT (rs4680) and MAPT (rs10445337) assists rugby athletes in achieving elite status. These findings need exploration vis-à-vis sport-related concussion injury data and could have implications for the management of inter-individual differences in concussion risk.
... However, a further step to better understanding inter-individual variability involves genetic variation and its association with concussion and related phenotypes. Evidence already exists suggesting an association between several genetic factors and inter-individual variability in traumatic brain injury incidence and severity [20][21][22][23][24][25][26][27][28]. ...
... However, Lipsky et al. [116] employed a battery of executive function tests including the Wisconsin Card Sorting Test, while Willmott et al. [169] used the Glasgow Outcome Scale-Extended as a measure of functional outcome post-TBI. Mc Fie et al. [21] reported that Met carriers in a cohort of youth and professional South African RU players were~3-fold more likely to have a history of concussion and, accordingly, it has been postulated that elevated dopamine could increase impulsivity and risk taking meaning Met allele carriers could place themselves at increased risk of sustaining a concussion [170,171]. ...
... However, children and adolescents carrying the S allele showed more impulsive behaviour such as delay aversion during target-game activity [131]. Recently, it has been observed that 5-HTTLPR low (S A /S A ) and intermediate (S A /L A , S A /L G , L A /L G , L G /L G )-possessing junior RU players displayed less harm avoidance behaviour [21]. These findings suggest that genetic variants associated with personality and thus behavioural traits could influence concussion risk in rugby. ...
Elite rugby league and union have some of the highest reported rates of concussion (mild traumatic brain injury) in professional sport due in part to their full-contact high-velocity collision-based nature. Currently, concussions are the most commonly reported match injury during the tackle for both the ball carrier and the tackler (8–28 concussions per 1000 player match hours) and reports exist of reduced cognitive function and long-term health consequences that can end a playing career and produce continued ill health. Concussion is a complex phenotype, influenced by environmental factors and an individual’s genetic predisposition. This article reviews concussion incidence within elite rugby and addresses the biomechanics and pathophysiology of concussion and how genetic predisposition may influence incidence, severity and outcome. Associations have been reported between a variety of genetic variants and traumatic brain injury. However, little effort has been devoted to the study of genetic associations with concussion within elite rugby players. Due to a growing understanding of the molecular characteristics underpinning the pathophysiology of concussion, investigating genetic variation within elite rugby is a viable and worthy proposition. Therefore, we propose from this review that several genetic variants within or near candidate genes of interest, namely APOE, MAPT, IL6R, COMT, SLC6A4, 5-HTTLPR, DRD2, DRD4, ANKK1, BDNF and GRIN2A, warrant further study within elite rugby and other sports involving high-velocity collisions.
... The COMT rs4680 polymorphism effects dopamine levels within the brain which can in turn influence behavioural traits and concussion risk. For example, rugby players who possess the A allele are 3-fold more likely to have a history of concussion (34). In contrast, elite rugby players are more likely to possess the G allele than nonathletes, which can be considered advantageous for stress resilience but also prone to poorer postconcussion recovery (4). ...
Genetic profiling and direct-to-consumer (DTC) genetic testing have seen an exponential growth in the last decade, driven by advancements in knowledge and technology making genetic information far more accessible to the population. Specifically in the sports industry there are claims that the results from these tests can inform training and dietary practises and even identify children's athletic talents. However, in some cases how this information is being utilised or promoted can be far removed from the evidence base. Due to this it is very important for anyone involved in the sports industry, such as strength and conditioning coaches, sports scientists, coaches, and parents to have a sound grasp of what can and cannot be taken from genetic tests. Thus, the purpose of this article is to provide a brief overview of genetics and heredity, highlight some of the key genetic findings to date regarding athletic performance and injury and then finally to provide context as to how this information can be utilised.
... High levels of dopamine are also known to lead to cellular dysfunction and oxidative stress, as well as increased inflammation in the central nervous system [43]. Still, other personality factors with associated genetic variants, such as catechol-O-methyltransferase, have been shown to be correlated with SRC susceptibility [55][56][57]. ...
Purpose of Review
Sport-related concussion (SRC) is a significant public health problem. Understanding the behavioral and personal factors that influence risk and incidence of SRC is critically important for appropriate care and management. Sensation-seeking and impulsivity have been posited to be two such factors that may be significantly associated with SRC. We performed a focused review of recent evidence of the relationships between sensation-seeking and impulsivity in athletes with SRC.
Recent Findings
While the research is relatively limited, extant findings demonstrate a significant relationship between sensation-seeking and contact sport participation and risk of prior and future SRC. Impulsivity appears to be common among athletes competing in high contact sports and may contribute to neural and functional brain changes following SRC; however, causal relationships between impulsivity, contact sport participation, and SRC have not been demonstrated.
Summary
Both sensation-seeking and impulsivity are significantly associated with SRC in collegiate athletes. Interventions designed to ameliorate high levels of these constructs may prove to be beneficial avenues to reducing SRC risk and improving patient care and outcomes.
... Some studies report different results such as an association of the lower expressing serotonin transporter S allele or S/S genotype of 5-HTTLPR polymorphism with extreme criminal behavior in Chinese male prisoners 76 and violent behavior in adult German criminal offenders with history of childhood ADHD 77 . Other studies also reported association of S allele or S/S genotype with antisocial alcoholism 78 , concussion history and personality traits in rugby players 79 , suicidal ideation in acute coronary syndrome patients 80 , higher impulsivity, hostility and neuroticism in anxiety phenotype 81 , hyperactivity-impulsivity in children moderated by peer problems earlier in childhood 82 and increased exposure to life stressors moderated by ADHD symptoms early in life 83 . Some meta-analyses also describe association of low expression allele/genotype of 5-HTTLPR polymorphism with anti-social behavior 84 , violent suicide attempts 85 and bipolar disorder 86 . ...
The serotonin transporter (SLC6A4), 5-HT2A (HTR2A) and 5-HT2B (HTR2B) recepter genes, express proteins that are important regulators of serotonin reuptake and signaling, and thereby may contribute to the pathogenesis of aggressive criminal behavior. 370 sentenced murderers in Pakistani prisons and 359 men without any history of violence or criminal delinquency were genotyped for six candidate polymorphisms in SLC6A4, HTR2A and HTR2B genes. An association of higher expressing L/L and LA/LA variants of the 5-HTTLPR polymorphism was observed with homicidal behavior (bi-allelic: OR = 1.29, p = 0.016, tri-allelic: OR = 1.32, p = 0.015) and in the murderer group only with response to verbal abuse (OR = 2.11, p = 0.015), but not with other measures of self-reported aggression. L/L and LA/LA genotypes of the 5-HTTLPR polymorphism were associated with higher aggression scores on STAX1 scale of aggression compared to lower expressing genotypes (S/S, S/LG, LG/LG) in prison inmates. No associations were apparent for other serotonergic gene polymorphisms analyzed. Using the Braineac and GTEx databases, we demonstrated significant eQTL based functional effects for rs25531 in HTTLPR and other serotonergic polymorphisms analyzed in different brain regions and peripheral tissues. In conclusion, these findings implicate SLC6A4* HTTLPR as a major genetic determinant associated with criminal aggression. Future studies are needed to replicate this finding and establish the biologic intermediate phenotypes mediating this relationship.
... Lower enzymatic activity in the COMT alleles results in a decrease of dopamine levels in the prefrontal cortex [16] which can be associated with psychotic disorders [17]. A study revealed that the COMT Val allele with higher enzymatic activity was related to the increased possibility of persistent generalized anxiety and anticipatory worry of GAD [18,19]. Conversely, research showed that the COMT Met allele with lower enzymatic activity was linked with the vulnerability and symptoms of GAD [20]. ...
The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been reported to be implicated in generalized anxiety disorder (GAD) as well as the treatment response to antidepressants in patients with GAD, but the findings are inconsistent. In this study, we explore the association among COMT, GAD, and the antidepressant response in the Chinese Han population. One hundred and two patients with GAD and 120 healthy controls (HC) were recruited. All the patients were treated with escitalopram or venlafaxine for 8 weeks. The Hamilton Rating Scale for Anxiety (HAMA) was used to assess the treatment response. All the participants were genotyped for the COMT Val158Met polymorphism using the polymerase chain reaction method. No significant differences in the frequency of the COMT rs4680 polymorphism were found between the GAD and HC groups, or between patients with different genders. Further, we found no significant correlation between the COMT rs4680 polymorphism, gender, and the antidepressant treatment outcomes after eight weeks in the GAD patients. This study indicated that the COMT rs4680 genotype might not be related to GAD or to the genders of the GAD patients, nor did it have any effect on the antidepressant therapeutic response in the GAD patients. Even so, our research will be helpful by providing guidance and direction for future, more in depth, research.
... Emerging research has also shown an association between a number of polymorphisms and the skill acquisition process [68]. Finally, a number of genetic variants have been linked to an increased susceptibility to concussion injuries [69]. As a result, whilst this information could be used to bias against those with the perceived "unfavourable" genotypes, it could also be used to personalize the training process, identifying those athletes who need greater attention in these areas. ...
Elite athlete status is a partially heritable trait, as are many of the underpinning physiological, anthropometrical, and psychological traits that contribute to elite performance. In recent years, our understanding of the specific genetic variants that contribute to these traits has grown, such that there is considerable interest in attempting to utilise genetic information as a tool to predict future elite athlete status. In this review, we explore the extent of the genetic influence on the making of a sporting champion and we describe issues which, at present, hamper the utility of genetic testing in identifying future elite performers. We build on this by exploring what further knowledge is required to enhance this process, including a reflection on the potential learnings from the use of genetics as a disease prediction tool. Finally, we discuss ways in which genetic information may hold utility within elite sport in the future, including guiding nutritional and training recommendations, and assisting in the prevention of injury. Whilst genetic testing has the potential to assist in the identification of future talented performers, genetic tests should be combined with other tools to obtain an accurate identification of those athletes predisposed to succeed in sport. The use of total genotype scores, composed of a high number of performance-enhancing polymorphisms, will likely be one of the best strategies in the utilisation of genetic information to identify talent in sport.
... Emerging research has also shown an association between a number of polymorphisms and the skill acquisition process [68]. Finally, a number of genetic variants have been linked to an increased susceptibility to concussion injuries [69]. As a result, whilst this information could be used to bias against those with the perceived "unfavourable" genotypes, it could also be used to personalize the training process, identifying those athletes who need greater attention in these areas. ...
Elite athlete status is a partially heritable trait, as are many of the underpinning physiological, anthropometrical, and psychological traits that contribute to elite performance. In recent years, our understanding of the specific genetic variants that contribute to these traits has grown, such that there is considerable interest in attempting to utilise genetic information as a tool to predict future elite athlete status. In this review, we explore the extent of the genetic influence on the making of a sporting champion and we describe issues which, at present, hamper the utility of genetic testing in identifying future elite performers. We build on this by exploring what further knowledge is required to enhance this process, including a reflection on the potential learnings from the use of genetics as a disease prediction tool. Finally, we discuss ways in which genetic information may hold utility within elite sport in the future, including guiding nutritional and training recommendations, and assisting in the prevention of injury. Whilst genetic testing has the potential to assist in the identification of future talented performers, genetic tests should be combined with other tools to obtain an accurate identification of those athletes predisposed to succeed in sport. The use of total genotype scores, composed of a high number of performance-enhancing polymorphisms, will likely be one of the best strategies in the utilisation of genetic information to identify talent in sport.
... Indeed, several reports linking athletic performance and anxiety-related polymorphic variants have been published (Butovskaya et al., 2013;de Milander, Stein, & Collins, 2009;Mc Fie et al., 2018;Sanhueza, Zambrano, Bahamondes-Avila, & Salazar, 2016;Santiago et al., 2011). Sanhueza et al. (2016) found significant association of five polymorphisms in genes connected with stress and anxiety (5HTT, CRH2R, ACE, NK1R, 5HT1AR and CRF-BP) with athletic performance (Sanhueza et al., 2016). ...
Genetic factors are known to influence sport performance. The aim of the present study was to assess genetic variants in genes coding for proteins potentially modulating activity of brain emotion centres in a group of 621 elite athletes (212 endurance, 183 power and 226 combat athletes) and 672 sedentary controls. Ten statistically significant variants were identified in genes encoding elements of serotoninergic, catecholaminergic and hypothalamic-pituitary-adrenal systems in different sport groups. Of those the rs860573 variant in the FEV gene coding for transcription factor exclusively expressed in neurons of the central serotonin system is the only one whose frequency significantly differentiates all the groups of athletes studied, regardless of discipline, from the controls (p = 0.000026). Our results support the hypothesis that genetic variants potentially affecting mental processes and emotions, particularly in the serotonergic pathway, also influence the predispositions to athletic performance.
... In sports, pain symptoms are thought to be impacted primarily by social problems such as anxiety, depression, anger, nervousness, and frustration, and may greatly influence one's career. The articles were announced about the relationship between genotypes such as COMT or 5-HTTLPR and concussion history in rugby players [11]. It greatly affects daily life thought to be their physical impediment, that is to say QOL. ...
Genetic research in the field of sports sciences offers new perspectives on various crucial aspects, including the determination of individual performance, predisposition to sports injuries, and the personalization of nutrition strategies. Sports Paradigms VIII (Genetic Research in Sports) comprehensively examines the impact of genetics on sports performance, presenting scientific findings aimed at maximizing athletes' physical and mental capacities. This book provides an in-depth exploration of key topics such as the importance of genetics in sports performance, genetic predisposition to sports injuries, muscle fiber types and genetics, genetics and nutrition, psychological resilience and genetics, as well as the effects of genetics on doping in sports. The chapters, prepared by expert researchers in the field, serve as a valuable resource for both the academic community and sports professionals. We hope that this book, which presents the latest scientific advancements in sports genetics, will contribute to research aimed at enhancing athlete health and performance.
Son yıllarda, sportif yeteneklerinin belirlenmesinde psikolojik faktörlerin
önemi artmıştır. Spor psikogenetiği, spordaki psikolojik faktörlerle
genetik etmenlerin etkileşimini inceleyen bir alandır. Spor yeteneklerinin
belirlenmesinde psikolojik faktörlerin, fiziksel yeteneklerle birlikte daha fazla
önem kazandığı son yıllarda fark edilmiştir. Ancak, sporcuların psikolojik
özelliklerinin genetik temelleri hakkında yapılan çalışmalar hala sınırlıdır. Spor
psikogenetiği genetik yatkınlıkların bir sporcunun yetenekleri, motivasyonu,
kişiliği ve stresle başa çıkma gibi psikolojik özelliklerini nasıl etkilediğini
araştırır. Genetik varyasyonlar; bilişsel yetenekler, tepki süresi ve kişilik gibi
özellikleri etkileyebilir ve bu faktörlerin atletik başarıyla ilişkisi incelenmektedir.
Spor psikogenetiği, genetik varyantların psikolojik özellikleri ve performansı
nasıl etkileyebileceğini anlamaya yönelik araştırmalar yapmaktadır. Bu alanda,
serotonin ve dopamin gibi nörotransmitterlerle ilişkili genetik varyasyonlar
öne çıkmaktadır. Genetik ve çevresel etkileşimlerin, bireylerin psikolojik
dayanıklılıklarını ve spor performanslarını nasıl şekillendirdiği üzerine yapılan
araştırmalar önemli bulgular sunmaktadır. Genetik faktörler, sporcularda
kişilik ve performansı belirlemede rol oynarken, çevresel faktörler de bu
süreci etkilemektedir. Bu çalışmalar, kişiye özel antrenman programlarının
geliştirilmesine olanak tanıyacak ve spor psikogenetiği alanının potansiyelini
daha iyi kullanmamıza yardımcı olacaktır. Sonuç olarak, spor psikogenetiği,
sporcularda psikolojik başarıyı optimize etmek için önemli bir araç
sunmaktadır.
This narrative review examines the relationship between dopamine-related genetic polymorphisms, personality traits, and athletic success. Advances in sports genetics have identified specific single nucleotide polymorphisms (SNPs) in dopamine-related genes linked to personality traits crucial for athletic performance, such as motivation, cognitive function, and emotional resilience. This review clarifies how genetic variations can influence athletic predisposition through dopaminergic pathways and environmental interactions. Key findings reveal associations between specific SNPs and enhanced performance in various sports. For example, polymorphisms such as COMT Val158Met rs4680 and BDNF Val66Met rs6265 are associated with traits that could benefit performance, such as increased focus, stress resilience and conscientiousness, especially in martial arts. DRD3 rs167771 is associated with higher agreeableness, benefiting teamwork in sports like football. This synthesis underscores the multidimensional role of genetics in shaping athletic ability and advocates for integrating genetic profiling into personalized training to optimize performance and well-being. However, research gaps remain, including the need for standardized training protocols and exploring gene–environment interactions in diverse populations. Future studies should focus on how genetic and epigenetic factors can inform tailored interventions to enhance both physical and psychological aspects of athletic performance. By bridging genetics, personality psychology, and exercise science, this review paves the way for innovative training and performance optimization strategies.
Objective:
Concussions are common match injuries in elite rugby, and reports exist of reduced cognitive function and long-term health consequences that can interrupt or end a playing career and produce continued ill health. The aim of this study was to investigate the association between elite rugby status and 8 concussion-associated risk polymorphisms. We hypothesized that concussion-associated risk genotypes and alleles would be underrepresented in elite rugby athletes compared with nonathletes.
Design:
A case-control genetic association study.
Setting:
Institutional (university).
Participants:
Elite White male rugby athletes [n = 668, mean (SD) height 1.85 (0.07) m, mass 102 (12) kg, and age 29 (7) years] and 1015 nonathlete White men and women (48% men).
Interventions:
Genotype was the independent variable, obtained by PCR of genomic DNA using TaqMan probes.
Main outcome measure:
Elite athlete status with groups compared using χ2 and odds ratio (OR).
Results:
The COMT rs4680 Met/Met (AA) genotype, Met allele possession, and Met allele frequency were lower in rugby athletes (24.8%, 74.6%, and 49.7%, respectively) than nonathletes (30.2%, 77.6%, and 54.0%; P < 0.05). The Val/Val (GG) genotype was more common in elite rugby athletes than nonathletes (OR 1.39, 95% confidence interval 1.04-1.86). No other polymorphism was associated with elite athlete status.
Conclusions:
Elite rugby athlete status is associated with COMT rs4680 genotype that, acting pleiotropically, could affect stress resilience and behavioral traits during competition, concussion risk, and/or recovery from concussion. Consequently, assessing COMT rs4680 genotype might aid future individualized management of concussion risk among athletes.
Concussion is a relatively common head injury in sports, with millions of athletes affected annually. Accurate concussion diagnosis and safe return to play are vital to ensure player welfare. However, concussions are difficult to diagnose and manage due to the nonspecificity of symptoms, the absence of a validated diagnostic test or biomarker and the lack of observable changes on standard neuroimaging. Recently, epigenetic changes, and specifically microRNA profiles, have been touted as potential biomarkers to aid concussion diagnosis and identify those at risk for prolonged symptoms. Several studies have investigated miRNA profiles following concussion and found promising diagnostic capabilities with either a single or a combination of microRNAs isolated from blood or saliva samples. However, the field is still in its infancy and would benefit from future high-quality research, following which, it is likely to provide significant benefits towards understanding and management of sport-related concussion.
This chapter introduces the epigenetic processes that govern how exercise affects the aging processes. We begin with an introduction to the molecular changes that occur with aging including methylation and histone and noncoding RNA modifications. We then present the evidence for changes in these processes by exercise and physical activity, Lastly, we present evidence for and against a role for exercise on changes in telomere length and aging.
Variation between individuals in response to a stimulus is a well-established phenomenon. This thesis discusses the drivers of this inter-individual response, identifying three major determinants; genetic, environmental, and epigenetic variation between individuals. Focusing on genetic variation, the thesis explores how this information may be useful in elite sport, aiming to answer the question “Is there utility to genetic information in elite sport?” The current literature was critically analysed, with a finding that the majority of exercise genomics research explains what has happened previously, as opposed to assisting practitioners in modifying athlete preparation and enhancing performance. An exploration of the potential ways in which genetic information may be useful in elite sport then follows, including that of inter- individual variation in response to caffeine supplementation, the use of genetic information to assist in reducing hamstring injuries, and whether genetic information may help identify future elite athletes. These themes are then explored via empirical work. In the first study, an internet-based questionnaire assessed the frequency of genetic testing in elite athletes, finding that around 10% had undertaken such a test. The second study determined that a panel of five genetic variants could predict the magnitude of improvements in Yo-Yo test improvements following a standardised training programme in youth soccer players. The third study demonstrated the effectiveness of a panel of seven genetic variants in predicting the magnitude of neuromuscular fatigue in youth soccer players. The fourth and final study recruited five current or former elite athletes, including an Olympic Champion, and created the most comprehensive Total Genotype Score in the published literature to date, to determine whether their scores deviated significantly from a control population of over 500 non-athletes. The genetic panels were unable to adequately discriminate the elite performers from non-athletes, suggesting that, at this time, genetic testing holds no utility in the identification of future elite performers. The wider utilisation of genetic information as a public health tool is discussed, and a framework for the implementation of genetic information in sport is also proposed. In summary, this thesis suggests that there is great potential for the use of genetic information to assist practitioners in the athlete management process in elite sport, and demonstrates the efficacy of some commercially available panels, whilst cautioning against the use of such information as a talent identification tool. The major limitation of the current thesis is the low sample sizes of many of the experimental chapters, a common issue in exercise genetics research. Future work should aim to further explore the implementation of genetic information in elite sporting environments.
Compared to sprint/power and endurance sports, the genetic contribution to success in sports that require a mixture of anaerobic and aerobic qualities has received relatively limited attention. This chapter evaluates research findings on the potential genetic variants influencing the team sports athletic status and the key factors for team sports performance, with particular emphasis on football (soccer) and rugby. Despite the great potential of the genetic studies in team sports and some promising progress recently made, there is very much more yet to be discovered than is understood at present. So far, only 10 genetic markers associated with team sports athlete status have been identified, and replication studies are needed to confirm those associations. In view of the foregoing, large collaborative projects with sound experimental designs (e.g. clearly defined phenotypes, consideration and control of sources of variability, and necessary replications) are needed to improve understanding in this area.
Sports psychogenetics is a novel field of scientific research that aims to use genetic methods to investigate the nature and origins of individual differences in cognitive abilities and personal traits of athletes. This chapter describes the heritability estimates of psychological traits (e.g., cognitive ability, memory, reaction time, temperament), their potential relationship with success in sport, as well as polymorphisms of genes expressed in the nervous system, which might be associated with athlete status and personality. Despite success in discovery of genetic variants associated with intelligence and personality in non-athletic cohorts (more than 7000 DNA polymorphisms have been identified in candidate-gene or genome-wide association studies, involving large sample sizes), there has been limited progress to date in the field of sports psychogenetics. To date, 16psychogenetics-specific genetic markers have been reported to be associated with predisposition to specific sports (via case-control designs), and 12 markers have been linked with personality traits (via genotype-phenotype designs) in athletes. Future genetic research with large cohorts of athletes, with further validation and replication, will substantially contribute to the discovery of causal genetic variants (i.e., mutations and DNA polymorphisms) that may partly explain the heritability of athlete status and related psychological phenotypes.
The functional Val ¹⁵⁸ Met polymorphism (rs4680) of the Catechol-O-Methyltransferase (COMT) gene has been implicated in generalized anxiety disorder (GAD); however, the underlying neural mechanisms remain unexamined. Recent evidence reveals that low resting parasympathetic (vagal) control is an endophenotypic predictor of anxiety, while the effect of COMT rs4680 differs at different ages. Thus, we examined whether the COMT Val ¹⁵⁸ Met variant could increase the risk of GAD through decreased resting parasympathetic nervous control in an age-specific manner. COMT rs4680 polymorphism was genotyped in 1,655 Han Chinese adults (1,142 healthy subjects and 513 patients with GAD; age: 20–65). High-frequency power (HF) of heart rate variability (HRV) was used to measure resting state parasympathetic nervous regulation. Non-genetic factors, such as gender, smoking status, medication use and comorbidity conditions, were treated as covariates. After adjusting for relevant covariates, there was a significant age x COMT genotype interaction on resting HF of HRV. In younger adults, Met allele carriers had a significantly lower HF index; however, older adults exhibited the opposite pattern, with Val/Val homozygotes exhibiting decreased HF values. Moreover, reduced HF-HRV is associated with increased risk of GAD. Finally, pathway analysis revealed a significant indirect effect of COMT on the risk of GAD via reduced resting HF-HRV, in the aforementioned age-dependent manner. Our findings are the first to demonstrate that COMT Val ¹⁵⁸ Met polymorphism is associated with risk of GAD via reduced resting parasympathetic nervous control, an age-specific risk pathway.
Objective: Recent reports suggest that exposure to repetitive concussions in sports is associated with an increased risk of symptoms of distress, anxiety and depression, sleep disturbance or substance abuse/dependence (typically referred as symptoms of common mental disorders[CMD]) and of later development of neurodegenerative disease, in particular chronic traumatic encephalopathy (CTE). The primary aim of this study was to explore the relationship between sports career-related concussions and the subsequent occurrence of symptoms of CMD among former male professional athletes retired from football (soccer), ice hockey and rugby (union).
Methods: Cross-sectional analyses performed on baseline electronic questionnaires from three prospective cohort studies among former male professional athletes retired from football (soccer), ice hockey and rugby (union). The number of confirmed concussions was examined through a single question, while symptoms of distress, anxiety and depression, sleep disturbance and adverse alcohol use were assessed using validated questionnaires.
Results: From 1,957 former professional athletes contacted, a total of 576 (29%) completed the questionnaire. Of these, 23% had not incurred a concussion during their career, 34% had two or three, 18% four or five, and 11% six or more concussions. The number of sports career-related concussions was a predictor for all outcome measures (β=0.072-0.109; P≤0.040). Specifically, former professional athletes who reported a history of four or five concussions were approximately 1.5 times more likely to report symptoms of CMD, rising to a two- to five-fold increase in those reporting a history of six or more sports career-related concussions.
Conclusions: These data demonstrate an association between exposure to sports concussion and subsequent risk of symptoms of CMD in former professional athletes across a range of contact sports. Further work to explore the association between sports concussion and symptoms of CMD is required; in the meanwhile, strategies for effective risk reduction and improved management appear indicated.
Chronic levels of physical activity have been associated with increased dopamine (D2) receptors resulting in increased sensitivity to dopamine release. The catechol-O-methyltransferase enzyme, responsible for dopamine degradation, contains a functional polymorphism, which plays an important role in dopamine regulation within the prefrontal cortex. This polymorphism has previously beenshown to affect human cognition and personality. However, the effect of this polymorphism has not been shown in ultra-endurance athletes.
To examine the association of the COMT val(158)met variant with personality traits (harm avoidance, novelty seeking, reward dependence, resilience) and psychological distress (K10) of habitual physically active Ironman athletes compared to recreationally active controls.
51 ultra-endurance Ironman athletes and 56 recreationally active controls were genotyped for the catechol-O-methyltransferase val(158)met polymorphism. Of the 107 participants, 55 ultra-endurance athletes and 32 recreationally active controls completed online personality questionnaires (harm avoidance, novelty seeking, reward dependence, resilience) and a psychological distress questionnaire (K10).
The personality trait, harm avoidance (p=0.001) and psychological distress (p=0.003) were significantly lower in Ironman athlete participants. Novelty seeking was significantly higher (p=0.02) in Ironman athlete participants with a significantly higher (p=0.04) score in Met(158) homozygous allele carriers.
Chronic levels of physical activity, as seen in ultra-endurance athletes, show increased novelty seeking scores in Met(158) homozygous allele carriers.
Copyright © 2015. Published by Elsevier Inc.
The existing research on the association between concussion and mental health outcomes is largely limited to former professional athletes. This cross-sectional study estimated the association between recurrent concussion and depression, impulsivity, and aggression in former collegiate athletes.
Former collegiate athletes who played between 1987–2012 at a Division I university completed an online questionnaire. The main exposure, total number of self-recalled concussions (sport-related and non-sport-related), were categorized as: zero (referent), one, two, or three or more concussions. The main outcomes were the depression module of The Patient Health Questionnaire (PHQ-9), the Short Form of the Barratt Impulsiveness scale (BIS15); and the 12-item Short Form of the Buss-Perry Aggression Questionnaire (BPAQ-SF). Depression was categorized into a binomial severity classification that differentiated between no or mild depression (PHQ-9 scores <10) and moderate to severe depression (PHQ-9 scores ≥10). Impulsivity and aggression were kept as continuous outcomes. Binomial regression estimated adjusted prevalence ratios (PR). Linear regression estimated adjusted mean differences (MD).
Of the 797 respondents with complete data (21.9% completion rate), 38.8% reported at least one concussion. Controlling for alcohol dependence and family history of depression, the prevalence of moderate to severe depression among former collegiate athletes reporting three or more concussions in total was 2.4 times that of those reporting zero concussions [95% Confidence Interval (CI): 1.0, 5.7]. Controlling for alcohol dependence, family history of anxiety, relationship status, obtaining a post-graduate degree, and playing primary college sport professionally, former collegiate athletes reporting two or more concussions in total had higher mean scores for impulsivity, compared to those reporting no concussions (2 concussions MD = 2.7; 95% CI: 1.2, 4.1; 3+ concussions MD = 1.9; 95% CI: 0.6, 3.2). Controlling for alcohol dependence, sex, and relationship status, former collegiate athletes reporting three or more concussions in total had a higher mean score for aggression, compared to those reporting no concussions (MD = 3.0; 95% CI: 1.4, 4.7).
Our study found an association between former concussion and greater risk of severe depression and higher levels of impulsivity and aggression among former collegiate athletes. Additional prospective studies better addressing causality and ascertaining valid lifetime concussion histories and medical histories are needed.
This paper aims to establish to what extent participants engaged in different levels of physical risk sports differ in levels of Sensation Seeking (SS) trait. A systematic searching of the literature gave 36 peer-reviewed studies published until September 2010. Results suggested that high scores on Thrill and Adventure Seeking seem characteristic of participants engaged in sports with high and medium levels of risk, and to a lesser extent of low risk sports as well. High scores on Experience Seeking seem characteristic only of participants engaged in sports with high levels of risk. Scores on Boredom Susceptibility only differ when comparing participants engaged in high risk with those engaged in low risk sports. Finally, high scores on Disinhibition and high Total score seem characteristic of athletes at any level of risk as compared to controls, and of athletes engaged in high risk sports as compared to those engaged in low risk sports. We conclude that the SS scale is a useful tool to assess and interpret individual differences in personality that exist between sportspersons practicing sports with different levels of risk.
To determine the self-reported, seasonal rates of concussion and the reporting practices among Irish rugby union players.
Descriptive epidemiology study.
The study was conducted at the training grounds of four professional Irish rugby union clubs.
One hundred seventy-two players (24.97 ± 4.11 years of age, 13.49 ± 5.79 years playing experience) gave consent to participate.
Number of concussions reported during the 2010-2011 season, reasons for not reporting, and positions of concussed players.
Forty-five percent of players reported at least one concussion during the 2010-2011 season, but only 46.6% of these presented to medical staff. The reasons for not reporting their concussions included, not thinking the injury was serious enough, and not wanting to be removed from the game. The relative proportion of concussions was higher for backs than forwards; however, the severity of injury was greater for forwards. Scrum-halves (12.0%) and flankers (10.9%) accounted for the majority of concussions reported.
The self-reported rate of concussion in elite rugby union players in Ireland is higher than reported in other countries or other sports. Many concussions remain unreported and, therefore, unmanaged. However, recent changes in concussion management guidelines by the International Rugby Board may impact future reporting practices of players.
Context:
Many athletes continue to participate in practices and games while experiencing concussion-related symptoms, potentially predisposing them to subsequent and more complicated brain injuries. Limited evidence exists about factors that may influence concussion-reporting behaviors.
Objective:
To examine the influence of knowledge and attitude on concussion-reporting behaviors in a sample of high school athletes.
Design:
Cross-sectional study.
Setting:
Participants completed a validated survey instrument via mail.
Patients or other participants:
A total of 167 high school athletes (97 males, 55 females, 5 sex not indicated; age = 15.7 ± 1.4 years) participating in football, soccer, lacrosse, or cheerleading.
Intervention(s):
Athlete knowledge and attitude scores served as separate predictor variables.
Main outcome measure(s):
We examined the proportion of athletes who reported continuing to participate in games and practices while symptomatic from possible concussion and the self-reported proportion of recalled concussion and bell-ringer events disclosed after possible concussive injury.
Results:
Only 40% of concussion events and 13% of bell-ringer recalled events in the sample were disclosed after possible concussive injury. Increased athlete knowledge of concussion topics (increase of 1 standard deviation = 2.8 points) was associated with increased reporting prevalence of concussion and bell-ringer events occurring in practice (prevalence ratio [PR] = 2.27, 95% confidence interval [CI] = 1.60, 3.21) and the reporting prevalence of bell-ringer-only events overall (PR = 1.87, 95% CI = 1.38, 2.54). Athlete attitude scores (increase of 1 standard deviation = 11.5 points) were associated with decreases in the proportion of athletes stating they participated in games (PR = 0.74, 95% CI = 0.66, 0.82) and practices (PR = 0.67, 95% CI = 0.59, 0.77) while symptomatic from concussions.
Conclusions:
Most recalled concussion events in our study were not reported to a supervising adult. Clinicians should be aware that knowledge and attitude influence concussion reporting. Clinicians and administrators should make concussion education a priority and encourage an optimal reporting environment to better manage and prevent concussive injuries in young athletes.
Currently, there is much interest in the extent to which adolescents engage in risk-taking behavior (RTB), particularly drinking alcohol, smoking cigarettes, and having unprotected sex. However, there is little research on adolescents' perceptions of the benefits and consequences of these and other risk-taking behaviors, or how these perceptions are related to their behavioral involvement. College students were chosen for this study specifically because older adolescents (a) engage in a wide variety of RTBs and (b) have been relatively understudied with regard to RTBs. Using the Risk Involvement and Perception Scale (RIPS) (Parsons, Siegel, & Cousins, in press), researchers asked 26 adolescents ages 18 years to 21 years on two occasions (2 weeks apart) to rate their involvement in and perceptions of the risks and benefits of 19 behaviors representing a wide range of behavioral health risks. The RIPS was developed, pilot tested, and found to be highly reliable and internally consistent. Subjects reported a wide range of involvement across the behaviors. In general, subjects' perceived benefits were strongly and positively related to their reported involvements; their perceived risks were negatively and less strongly related. A factor analysis of the subjects' involvement yielded six independent clusters of risk-taking behaviors: alcohol use, illegal drug use, sexual activity, stereotypical male behaviors, imprudent behaviors, and socially acceptable behaviors. In regression analyses, perceived benefits accounted for most of the variance in subjects' involvement in these clusters of behaviors. Results are discussed in the context of current theories of adolescent risk taking.
• A systematic method for clinical description and classification of both normal and abnormal personality variants is proposed based on a general biosocial theory of personality. Three dimensions of personality are defined in terms of the basic stimulus-response characteristics of novelty seeking, harm avoidance, and reward dependence. The possible underlying genetic and neuroanatomical bases of observed variation in these dimensions are reviewed and considered in relation to adaptive responses to environmental challenge. The functional interaction of these dimensions leads to integrated patterns of differential response to novelty, punishment, and reward. The possible tridimensional combinations of extreme (high or low) variants on these basic stimulusresponse characteristics correspond closely to traditional descriptions of personality disorders. This reconciles dimensional and categorical approaches to personality description. It also implies that the underlying structure of normal adaptive traits is the same as that of maladaptive personality traits, except for schizotypal and paranoid disorders.
Background:
The increasing incidence of injuries related to playing ice hockey is an important public health issue. We conducted a systematic review to evaluate the effectiveness of interventions designed to reduce injuries related to aggressive acts in ice hockey.
Methods:
We identified relevant articles by searching electronic databases from their inception through July 2012, by using Internet search engines, and by manually searching sports medicine journals, the book series Safety in Ice Hockey and reference lists of included articles. We included studies that evaluated interventions to reduce aggression-related injuries and reported ratings of aggressive behaviour or rates of penalties or injuries.
Results:
We identified 18 eligible studies. Most involved players in minor hockey leagues. Of 13 studies that evaluated changes in mandatory rules intended to lessen aggression (most commonly the restriction of body-checking), 11 observed a reduction in penalty or injury rates associated with rule changes, and 9 of these showed a statistically significant decrease. The mean number of penalties decreased by 1.2-5.9 per game, and injury rates decreased 3- to 12-fold. All 3 studies of educational interventions showed a reduction in penalty rates, but they were not powered or designed to show a change in injury rates. In 2 studies of cognitive behavioural interventions, reductions in aggressive behaviours were observed.
Interpretation:
Changes to mandatory rules were associated with reductions in penalties for aggressive acts and in injuries related to aggression among ice hockey players. Effects of educational and cognitive behavioural interventions on injury rates are less clear. Well-designed studies of multifaceted strategies that combine such approaches are required.
Impulsive people have a strong urge to act without thinking. It is sometimes regarded as a positive trait but rash impulsiveness is also widely present in clinical disorders such as attention deficit hyperactivity disorder (ADHD), drug dependence, mania, and antisocial behaviour. Contemporary research has begun to make major inroads into unravelling the brain mechanisms underlying impulsive behaviour with a prominent focus on the limbic cortico-striatal systems. With this progress has come the understanding that impulsivity is a multi-faceted behavioural trait involving neurally and psychologically diverse elements. We discuss the significance of this heterogeneity for clinical disorders expressing impulsive behaviour and the pivotal contribution made by the brain dopamine and serotonin systems in the aetiology and treatment of behavioural syndromes expressing impulsive symptoms.
The factors that influence individual differences in decision making are not yet fully characterized, but convergent evidence is accumulating that implicates serotonin (5-HT) system function. Therefore, both genes and environments that influence serotonin function are good candidates for association with risky decision making. In the present study we examined associations between common polymorphisms in the serotonin transporter gene (SLC6A4; 5-HTTLPR and rs25531), the experience of childhood trauma and decision making on the Iowa gambling task (IGT) in 391 (64.5% female) healthy Caucasian adults. Homozygosity for the 5-HTTLPR L allele was associated with riskier decision making in the first block of 20 trials (i.e., decision making under ambiguity, p = 0.004). In addition, mean IGT performance was significantly worse in blocks 3–5 (i.e., decision making under risk, p ≤ 0.05) for those participants who reported experiencing higher levels of childhood trauma. Our findings add to the growing evidence that genetic variation in the 5-HT system is associated with individual differences in decision making under ambiguity; and we report that the experience of childhood trauma is associated with relatively poor decision making under risk.
Previous research has shown inconsistent findings regarding the relations between the functional Val158Met polymorphisms of the catechol-O-methyltransferase (COMT) gene and individual differences in personality traits. This study attempts to overcome some of the weaknesses of previous research, namely, small sample sizes, clinical samples, ethnic stratification, wide age ranges, neglecting sex differences, and single measures of personality traits. A large sample (n = 556, 250 male, 306 female) of healthy Chinese college students (mean age = 20.5 ± 1 years) was given a battery of personality scales, including the temperament and character inventory-revised, the behavioral inhibition system and behavioral approach system scale, the Beck depression inventory, and the Beck anxiety inventory. Factor analysis of the affect-related personality traits revealed two factors that corresponded to positive (PEM) and negative emotionality (NEM). We found a consistent COMT-by-sex interaction effect on affect-related personality traits. Compared with males with Met/Met alleles, males with Val/Val alleles showed significantly higher scores on NEM, but lower scores on PEM. Females, however, showed an opposite but nonsignificant pattern. Our results supported the role of the COMT gene in personality traits for males and contributed to the growing literature on sex differences in gene-behavior connections.
A genetic liability for anxiety-related personality traits in healthy subjects has been associated with the functional serotonin transporter promoter polymorphism (5-HTTLPR), although the data are somewhat conflicting. Moreover, only one study has investigated the functional significance of the 5-HTTLPR/rs25531 haplotypes in relation to anxiety traits in healthy subjects. We tested whether the 5-HTTLPR polymorphism and the 5-HTTLPR/rs25531 haplotypes are linked to Harm Avoidance (HA) using an association study (STUDY I) and a meta-analytic approach (STUDY II).
STUDY I: A total of 287 unrelated Italian volunteers were screened for DSM-IV Axis I disorders and genotyped for the 5-HTTLPR and rs25531 (A/G) polymorphisms. Different functional haplotype combinations were also analyzed. STUDY II: A total of 44 studies were chosen for a meta-analysis of the putative association between 5-HTTLPR and anxiety-related personality traits.
STUDY I: In the whole sample of 287 volunteers, we found that the SS genotype and S'S' haplotypes were associated with higher scores on HA. However, because the screening assessed by Mini-International Neuropsychiatric Interview (M.I.N.I.) showed the presence of 55 volunteers affected by depression or anxiety disorders, we analyzed the two groups ("disordered" and "healthy") separately. The data obtained did indeed confirm that in the "healthy" group, the significant effects of the SS genotype and S'S' haplotypes were lost, but they remained in the "disordered" group. STUDY II: The results of the 5-HTTLPR meta-analysis with anxiety-related traits in the whole sample confirmed the association of the SS genotype with higher anxiety-related traits scores in Caucasoids; however, when we analyzed only those studies that used structured psychiatric screening, no association was found.
This study demonstrates the relevance to perform analyses on personality traits only in DSM-IV axis I disorder-free subjects. Furthermore, we did not find an association between functional serotonin transporter gene polymorphisms and anxiety traits in healthy subjects screened through a structured psychiatric interview.
Impulsivity has been associated with serotonergic system functions. However, few researchers have investigated the relationship between a polymorphism in the promoter of the serotonin transporter gene (5-HTTLPR) and the different components of impulsivity in a non-clinical population. The aim of this study was to investigate the relationship between a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) and the different components of impulsivity in a non-clinical population.
We administered two neuropsychological tests, the Continuous Performance Task and the Iowa Gambling Task, to 127 healthy participants to measure their levels of motor, attentional and non-planning impulsivity. Then, these participants were grouped by genotype and gender, and their scores on impulsivity measures were compared. There were no significant differences between group scores on attentional, motor and non-planning impulsivity.
Our results suggest that 5-HTTLPR genotype is not significantly associated with subsets of impulsive behavior in a non-clinical sample when measured by neuropsychological tests. These findings are discussed in terms of the sensitivity of neuropsychological tests to detect impulsivity in a non-clinical population and the role of gender and race in the relationship between the 5-HTTLPR and impulsivity.
The objectives of the study were to compare personality features according to age and sex cohorts in a community sample of Mexico City using the Temperament and Character Inventory-Revised (TCI-R) and to examine the TCI-R psychometric properties according to age and sex parameters.
A total of 2076 adults filled out the Spanish version of TCI-R.
Younger subjects exhibited higher novelty seeking. Self-directedness and cooperativeness scores increased with age. Harm avoidance and self-transcendence were lower in younger adults when compared with older subjects. Women scored higher than men in harm avoidance and reward dependence. Men between 26 and 45 years old reported higher novelty seeking. Women older than 25 years scored higher in self-transcendence, and those older than 45 years exhibited higher cooperativeness scores. The identified TCI-R structure corresponded to the original one. Internal consistency of the higher-order dimensions was good in all age cohorts, in men and women, and in the total sample (αs >.80).
Our results give further support to personality specific dominant features in men and women. Differences in age cohorts may be explained by maturity and personal experiences acquired during life. The TCI-R psychometric properties and score distributions by age and sex cohorts may be useful for future studies with clinical samples and for cross-cultural comparison purposes.
Objective: A longitudinal, prospective design was used to investigate a moderation effect in the association between early adolescent substance use and risky sexual behavior 2 years later. A genetic vulnerability factor, a variable nucleotide repeat polymorphism (VNTR) in the promoter region of the serotonin transporter gene SLC6A4, known as 5-HTTLPR, was hypothesized to moderate the link between substance use at age 14 and risky sexual behavior at age 16. This VNTR has been associated with risk-taking behavior. Design: African American youths in rural Georgia (N = 185) provided 2 waves of data on their substance use and sexual behavior. Genetic data were obtained via saliva samples. Main Outcome Measures: Substance use and sexual risk behavior were assessed using youth self-report items developed for this investigation. Results: Multiple regression analyses indicated that the presence of 1 or 2 copies of the short allele of the VNTR interacted with substance use to predict sexual behavior. Substance use had little effect on sexual behavior for youths without the short allele; this effect was greatly increased for youths with the short allele. Conclusion: Genetic vulnerability affected the implications of early onset substance use for later sexual behavior.
Disordered dopamine neurotransmission is implicated in mediating impulsiveness across a range of behaviors and disorders including addiction, compulsive gambling, attention-deficit/hyperactivity disorder, and dopamine dysregulation syndrome. Whereas existing theories of dopamine function highlight mechanisms based on aberrant reward learning or behavioral disinhibition, they do not offer an adequate account of the pathological hypersensitivity to temporal delay that forms a crucial behavioral phenotype seen in these disorders. Here we provide evidence that a role for dopamine in controlling the relationship between the timing of future rewards and their subjective value can bridge this explanatory gap. Using an intertemporal choice task, we demonstrate that pharmacologically enhancing dopamine activity increases impulsivity by enhancing the diminutive influence of increasing delay on reward value (temporal discounting) and its corresponding neural representation in the striatum. This leads to a state of excessive discounting of temporally distant, relative to sooner, rewards. Thus our findings reveal a novel mechanism by which dopamine influences human decision-making that can account for behavioral aberrations associated with a hyperfunctioning dopamine system.
Brain monoamines, and serotonin in particular, have repeatedly been shown to be linked to different psychiatric conditions such as depression, anxiety, antisocial behaviour, and dependence. Many studies have implicated genetic variability in the genes encoding monoamine oxidase A (MAOA) and the serotonin transporter (5HTT) in modulating susceptibility to these conditions. Paradoxically, the risk variants of these genes have been shown, in vitro, to increase levels of serotonin, although many of the conditions are associated with decreased levels of serotonin. Furthermore, in adult humans, and monkeys with orthologous genetic polymorphisms, there is no observable correlation between these functional genetic variants and the amount or activity of the corresponding proteins in the brain. These seemingly contradictory data might be explained if the association between serotonin and these behavioural and psychiatric conditions were mainly a consequence of events taking place during foetal and neonatal brain development. In this review we explore, based on recent research, the hypothesis that the dual role of serotonin as a neurotransmitter and a neurotrophic factor has a significant impact on behaviour and risk for neuropsychiatric disorders through altered development of limbic neurocircuitry involved in emotional processing, and development of the serotonergic neurons, during early brain development.
Mild traumatic brain injury (mTBI) is an emerging public health issue in high-contact sports. Understanding the incidence along with the risk and protective factors of mTBI in high-contact sports such as rugby is paramount if appropriate preventive strategies are to be developed.
To estimate the incidence and identify the risk and protective factors of mTBI in Australian nonprofessional rugby players.
Cohort study; Level of evidence, 2.
A cohort of 3207 male nonprofessional rugby players from Sydney, Australia, was recruited and followed over 1 or more playing seasons. Demographic information, history of recent concussion, and information on risk and protective factors were collected. The incidence of mTBI was estimated and the putative risk and protective factors were modeled in relation to mTBI.
The incidence of mTBI was 7.97 per 1000 player game hours, with 313 players (9.8%) sustaining 1 or more mTBIs during the study. Players who reported always wearing protective headgear during games were at a reduced risk (incident rate ratio [IRR], 0.57; 95% confidence interval [CI], 0.40-0.82) of sustaining an mTBI. In contrast, the likelihood of mTBI was almost 2 times higher among players who reported having sustained either 1 (IRR, 1.75; 95% CI, 1.11-2.76) or more mTBIs (IRR, 1.65; 95% CI, 1.11-2.45) within the 12 months before recruitment.
Nonprofessional rugby has a high incidence of mTBI, with the absence of headgear and a recent history of mTBI associated with an increased risk of subsequent mTBI. These findings highlight that both use of headgear and the management of prior concussion would likely be beneficial in reducing the likelihood of mTBI among nonprofessional rugby players, who compose more than 99% of rugby union players in Australia.
A general theory of heritable personality traits and their neurobiological basis is described. Three independent dimensions of personality are defined and related to heritable variation in patterns of response to specific types of environmental stimuli: 'novelty seeking' is due to a heritable tendency toward frequent exploratory activity and intense excitement in response to novel stimuli; 'harm avoidance' is due to a heritable tendency to respond intensely to aversive stimuli and to learn to avoid punishment, novelty, and non-reward passively; and 'reward dependence' is due to a heritable tendency to respond intensely to reward and succorance and to learn to maintain rewarded behavior. Evidence suggests that variation in each dimension is strongly correlated with activity in a specific central monoaminergic pathway: novelty seeking with low basal dopaminergic activity, harm avoidance with high serotonergic activity, and reward dependence with low basal noradrenergic activity. These neurobiological dimensions interact to give rise to integrated patterns of differential responses to punishment, reward, and novelty. The combination of high novelty seeking, high reward dependence, and low harm avoidance (histrionic personality) or the combination of high harm avoidance, low reward dependence, and low novelty seeking (obsessional personality) are each associated with information-processing patterns that lead to unreliable discrimination of safe and dangerous situations and hence to chronic anxiety. In individuals with high novelty seeking, chronic anxiety is characterized by global uneasiness or alarm without specific premonitory cues, frequent bodily pains due to low pain and sensation thresholds, low sedation threshold, and slow fatigability. In contrast, in individuals with high harm avoidance, chronic anxiety is characterized by frequent anticipatory worries based on specific cues, high pain and sedation thresholds, and easy fatigability. In response to frustrative non-reward, individuals with high reward dependence are susceptible to compensatory noradrenergic hyperactivity and hence acute or recurrent states of agitated dysphoria associated with reward-seeking behaviors such as overeating and increased sexual activity. Specific predictions are made about normal personality development as well as the development and familial aggregation of anxiety, somatoform, depressive and personality disorders. These predictions are compared with available information, and recommendations are made for future research.
Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal
models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter
(5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the
polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and
5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT
polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality
traits in individuals as well as sibships.
A common 44-base pair insertion/deletion polymorphism in the promoter region of the human serotonin transporter (5-HTT) gene has been observed to be associated with affective illness and anxiety-related traits. This biallelic functional polymorphism, designated long (L) and short (S), affects 5-HTT gene expression since the S promoter is less active than the L promoter. Since there is strong evidence of a disturbance in brain serotonergic transmission among antisocial, impulsive, and violent type 2 alcoholic subjects, we decided to test the hypothesis that the frequency of the S allele, which is associated with reduced 5-HTT gene expression, is higher among habitually violent type 2 alcoholics when compared with race and gender-matched healthy controls and non-violent late-onset (type 1) alcoholics. The 5-HTT promoter genotype was determined by a PCR-based method in 114 late onset (type 1) non-violent alcoholics, 51 impulsive violent recidivistic offenders with early onset alcoholism (type 2), and 54 healthy controls. All index subjects and controls were white Caucasian males of Finnish origin. The S allele frequency was higher among type 2 alcoholics compared with type 1 alcoholics (chi2 = 4.86, P = 0.028) and healthy controls (chi2 = 8.24, P = 0.004). The odds ratio for SS genotype vs LL genotype was 3.90, 95% Cl 1.37-11.11, P = 0.011 when type 2 alcoholics were compared with healthy controls. The results suggest that the 5-HTT 'S' promoter polymorphism is associated with an increased risk for early onset alcoholism associated with antisocial personality disorder and impulsive, habitually violent behavior.
Background
Recent reports suggest that exposure to repetitive concussions in sports is associated with an increased risk of symptoms of Common Mental Disorders (CMD) and of later development of neurodegenerative diseases, in particular chronic traumatic encephalopathy (CTE).
Objective
To explore the relationship between sports career-related concussions and the subsequent occurrence of symptoms of CMD among former male professional athletes.
Design
Cross-sectional analyses performed on baseline electronic questionnaires from three prospective cohort studies.
Setting
National unions or players' associations in professional football, ice hockey and rugby.
Patients (or Participants)
A total of 576 former male professional athletes were enrolled. Mean age at recruitment was 37 years; mean duration of sports career was 10 years.
Interventions (or Assessment of Risk Factors)
The total number of confirmed concussion incidents during an athlete's career and diagnosed by a medical professional was examined.
Main Outcome Measurements
Several Patient Reported Outcome Measures (PROMs) were included and assessed with validated scales, namely symptoms of distress, anxiety/depression, sleep disturbance, adverse alcohol use.
Results
The number of sports career-related concussions was a predictor for all outcome measures (β=0.072–0.100; P≤0.035). Specifically, former professional athletes who reported a history of four or five concussions were approximately 1.5 times more likely to report symptoms of CMD, rising to a two- to four-fold increase in those reporting a history of six or more sports career-related concussions.
Conclusions
These data demonstrate a direct relationship between exposure to sports concussion and subsequent risk of symptoms of CMD in former professional athletes across a range of contact sports. Further work to explore the association between sports concussion and symptoms of CMD is required; in meantime strategies for effective risk reduction and improved management appear indicated.
Introduction:
This systematic review examined the association between genetics and risk for sustaining a traumatic brain injury.
Methods:
Articles published in English from 1980 to July 2016 obtained from the online databases PubMed, PsycINFO®, MEDLINE®, EMBASE, and Web of Science.
Results:
5,903 articles were identified, 77 underwent full-text screening, and six were included in this review. Five studies examined the risk of concussion associated with Apolipoprotein E alleles (APOE-ε2 ,ε3 ,ε4,), and polymorphisms of the APOE promoter (rs405509), Brain Derived Neurotrophic Factor (BDNF, rs6265), and Dopamine Receptor D2 (DRD2, rs1800497) were each considered in two studies. Microtubule Associated Protein Tau [TAU exon 6 polymorphisms His47Tyr (rs2258689) and Ser53Pro (rs10445337)], and Neurofilament Heavy (NEHF, rs165602) genotypic variants, were the focus of single studies. No study showed an increased risk associated solely with the presence of the APOE-ε4 allele, nor were there any significant findings for the NEFH, TAU, or DRD2 genotypic variants. Two studies examined the APOE promoter -219G/T polymorphism in athletes, and both found an association with concussion. Both BDNF studies also found a significant association with concussion incidence; U.S. soldiers with the Met/Met genotype were more likely to report a history of concussion prior to deployment and to sustain a concussion during deployment.
Discussion:
The APOE promoter -219 G/T polymorphism and the BDNF Met/Met genotype might confer risk for sustaining a TBI. Based on research to date, the APOE-ε4 allele does not appear to influence risk. More research is needed to determine if these findings replicate.
Objective:
To determine the concussion incidence and to identify factors associated with concussion in South African youth rugby union players.
Design:
Prospective cohort study.
Setting:
Injury surveillance was completed at the South African Rugby Union Youth Week tournaments (under-13, under-16, and under-18 age groups).
Participants:
South African youth rugby union players. A total of 7216 players participated in 531 matches between 2011 and 2014.
Interventions:
None.
Main outcome measures:
Concussion incidence was calculated per 1000 player-match-hours with 95% CIs. Poisson regression was used to calculate the incidence rate ratio (IRR) between factors (age, time period, playing position, and activity at the time of concussion) potentially associated with concussions.
Results:
The concussion incidence was 6.8/1000 player-match-hours (95% CI, 5.5-8.1) across all age groups. Under-13s (IRR, 1.5; P = 0.09) and under-16s (IRR, 1.7; P = 0.03) had higher concussion incidence rates than the under-18 age group. The incidence was higher in the third (IRR, 2.1; P = 0.04) and fourth (IRR, 2.5; P = 0.01) quarters of matches compared with the first quarter. Sixty-two percent of concussions occurred in the tackle situation. The tackler had a 4-fold greater concussion rate (IRR, 4.3; P < 0.001) compared with the ball carrier. The hooker and loose forwards had higher incidence rates than several other player positions (P < 0.05).
Conclusions:
The reported concussion incidence falls within the broad range previously reported in youth rugby. The evidence highlighted in this study may contribute to targeted concussion prevention strategies and provide a baseline against which the effectiveness of future interventions can be measured.
Making sense of rapidly evolving evidence on genetic associations is crucial to making genuine advances in human genomics and the eventual integration of this information in the practice of medicine and public health. Assessment of the strengths and weaknesses of this evidence, and hence the ability to synthesize it, has been limited by inadequate reporting of results. The STrengthening the REporting of Genetic Association studies (STREGA) initiative builds on the STrengthening the Reporting of OBservational Studies in Epidemiology (STROBE) Statement and provides additions to 12 of the 22 items on the STROBE checklist. The additions concern population stratification, genotyping errors, modelling haplotype variation, Hardy–Weinberg equilibrium, replication, selection of participants, rationale for choice of genes and variants, treatment effects in studying quantitative traits, statistical methods, relatedness, reporting of descriptive and outcome data and the volume of data issues that are important to consider in genetic association studies. The STREGA recommendations do not prescribe or dictate how a genetic association study should be designed, but seek to enhance the transparency of its reporting, regardless of choices made during design, conduct or analysis.
The aims of this study were (i) to examine genotypic association of the catechol-O-methyltransferase (COMT) val158met polymorphism with anxiety-related traits with a meta-analysis; (ii) to examine sex and ethnicity as moderators of the association; and (iii) to evaluate whether the association differed by particular anxiety traits.
Association studies of the COMT val158met polymorphism and anxiety traits were identified from the PubMed or PsycInfo databases, conference abstracts, and listserv postings. Exclusion criteria were (a) pediatric samples, (b) exclusively clinical samples, and (c) samples selected for a nonanxiety phenotype. Standardized mean differences in anxiety between genotypes were aggregated to produce mean effect sizes across all available samples, and for subgroups stratified by sex and ethnicity (Whites vs. Asians). Construct-specific analysis was conducted to evaluate the association of COMT with neuroticism, harm avoidance, and behavioral inhibition.
Twenty-seven eligible studies (N=15 979) with available data were identified. Overall findings indicate sex-specific and ethnic-specific effects: valine homozygotes had higher neuroticism than methionine homozygotes in studies of White males [mean effect sizeES=0.13; 95% CI 0.02, 0.25; P=0.03], and higher harm avoidance in studies of Asian males (ES=0.43; 95% CI 0.14, 0.72; P=0.004). No significant associations were found in women and effect sizes were diminished when studies were aggregated across ethnicity or anxiety traits.
This meta-analysis provides evidence for sex and ethnic differences in the association of the COMT val158met polymorphism with anxiety traits. Our findings contribute to current knowledge on the relation between prefrontal dopaminergic transmission and anxiety.
The heritability of human personality traits is by now well established. However, since the first reports on associations between specific genetic variants and personality traits, only modest progress has been made in identifying loci that robustly support these associations. The aim of this study was to provide a summary of literature data on association studies focused on the genetic modulation of personality, according to the Cloninger, Eysenck and Costa and McCrae models. PubMed was searched for papers investigating the association between any gene variant and personality traits, which were grouped into five clusters: (a) anxiety, (b) impulsivity, (c) determination-activity, (d) socialization and (e) spirituality, in healthy individuals, populations and psychiatric patients. A total of 369 studies were included. No clear consensus on the role of any individual gene variant in personality modulation emerged, although SLC6A4 haplotypes and the DRD4 rs1800955 promoter variant seemed to be more reliably related to anxiety and impulsivity-related traits, respectively. Because conflicting results emerged from the literature, plausibly as a result of the combined influence of many loci of small effects on personality, larger sample sizes and more narrow and specific phenotype will be the minimum requirements for future genetic studies on personality. Moreover, gene×gene and gene×environment interaction studies deserve further attention.
Concussion and the potential threat of associated chronic traumatic encephalopathy (CTE) have attracted unprecedented media attention. The public debate regarding the link between CTE and head injuries in sport is emotive as well as distracting. This media focus has been positive in that it has raised public awareness of concussion but the same media focus could have negative consequences by
Dr Patricios and Dr Kemp have called for leadership from Rugby in this area and have also called for collision sports to unite and provide a unified, unemotive and consistent message regarding possible neurocognitive effects associated with concussion in sport.
The International Rugby Board (IRB) supports this call for collision sport unity and outlines below an overview of our risk management strategy related to concussion.
The risk of long-term neurodegenerative illness following head injury is unknown.1 This uncertainty is the fuel that fires the public debate. The lack of concrete evidence allows both sides to publically claim a position that is neither supported nor refuted by science.
What we do know is that a single moderate-to-severe traumatic brain injury (TBI) can lead not only to acute neurological deficits but also to long-term neurodegenerative issues, in 40–50% of patients.2 We also know that repetitive head injuries in boxers and recently within other sports have been linked with long-term neurological sequelae.3 ,4
What we do not know is
Is there a link between concussion (mild TBI) …
The Sport Concussion Assessment Tool 2 (SCAT2), which evolved from the 2008 Concussion in Sport Group (CISG) Consensus meeting, has been widely used internationally for the past 4 years. Although the instrument is considered very practical and moderately effective for use by clinicians who manage concussion, the utility and sensitivity of a 100-point scoring system for the SCAT2 has been questioned. The 2012 CISG Consensus Meeting provided an opportunity for several of the world's leading concussion researchers and clinicians to present data and to share experiences using the SCAT2. The purpose of this report is to consider recommendations by the CISG, and to review the current literature to identify the most sensitive and reliable concussion assessment components for inclusion in a revised version-the SCAT3. Through this process, it was determined that important clinical information can be ascertained in a streamlined manner through the use of a multimodal instrument such as the SCAT3. This test battery should include an initial assessment of injury severity using the Glasgow Coma Scale, immediately followed by observing and documenting concussion signs. Once this is complete, symptom endorsement and symptom severity, neurocognitive function and balance function should be assessed in any athlete suspected of sustaining a concussion. There is no evidence to support the use of a composite/total score; however, there is good evidence to support the use of each component (scored independently) in a revised assessment tool.
Dopamine (DA) is considered to be an important neurotransmitter in the control of impulsive behavior, however, its underlying mechanisms have not been fully elucidated. Catechol-O-methyltransferase (COMT) is a key enzyme in the catabolism of DA within the prefrontal cortex (PFC) and has been suggested to play a role in the mediation of impulsive behavior. The COMT single nucleotide polymorphism (SNP) rs4680 (Val158Met) Met allele has been shown to decrease COMT enzyme activity and is associated with improved PFC cognitive function (intelligence and executive functions). Studies have associated the rs4680 genotype with impulsivity as a symptom in attention deficit hyperactivity disorder and substance abuse. However, only a few studies have assessed the effects of rs4680 on impulsiveness in healthy subjects, the results of which remain controversial. The Barratt Impulsiveness Scale (BIS-11) was applied to 82 healthy volunteers (including 42 females) who were genotyped for COMT rs4680. Subjects carrying the Met/Met genotype scored higher for the BIS-11 second-order factor Non-planning than carriers of the Val/Val genotype. No interaction between gender*genotype was detected. Age, gender and education had no effect on the results. The COMT rs4680 Met/Met genotype was associated with higher impulsivity on the BIS-11 second-order factor Non-planning. These results suggest that COMT enzyme activity may be important in the regulation of impulsiveness among young adults. Further studies involving larger samples should be conducted to confirm the results of the present study.
For most of this past century, scholarship on the topics of personality and emotion has emerged from the humanities and social sciences. In the past decade, a remarkable change has occurred in the influence of neuroscience on the conceptualization and study of these phenomena. This article argues that the categories that have emerged from psychiatric nosology and descriptive personality theory may be inadequate, and that new categories and dimensions derived from neuroscience research may produce a more tractable parsing of this complex domain. The article concludes by noting that the discovery of these biological differences among individuals does not imply that the origins of these differences lie in heritable influences. Experiential shaping of the brain circuitry underlying emotion is powerful. The neural architecture provides the final common pathway through which culture, social factors, and genetics all operate together.
Mood, emotion, cognition, and motor functions as well as circadian and neuroendocrine rhythms, including food intake, sleep, and reproductive activity, are modulated by the midbrain raphe serotonin (5-HT) system. By directing the magnitude and duration of postsynaptic responses, carrier-facilitated 5-HT transport into and release from the presynaptic neuron are essential for the fine tuning of serotonergic neurotransmission. Interest in the mechanism of environmental factor-, disease-, and therapy-induced modification of 5-HT transporter (5-HTT) function and its impact on early brain development, event-related synaptic plasticity, and neurodegeneration is widespread and intensifying. We have recently characterized the human and murine 5-HTT genes and performed functional analyses of their 5′-flanking regulatory regions. A tandemly repeated sequence associated with the transcriptional apparatus of the human 5-HTT gene displays a complex secondary structure, represses promoter activity in nonserotonergic neuronal cells, and contains positive regulatory components. We now report a novel polymorphism of this repetitive element and provide evidence for allele-dependent differential 5-HTT promoter activity. Allelic variation in 5-HTT-related functions may play a role in the expression and modulation of complex traits and behavior.
Between 1976 and 1983, 42 spinal cord injuries among ice hockey participants were documented in Canada; within a recent 3-week period, three cases involving fractured necks were reported in a metropolitan area of Minnesota. The purpose of this comprehensive epidemiological study was to document rates, types, and severities of injuries incurred among high school varsity hockey players in Minnesota, as a result of participation in the 1982–1983 season, and to determine the variables associated with these injuries. Within a 30-mile radius of the state's major metropolitan area, 12 high school varsity hockey teams were selected for participation. Specific techniques were used to ensure confidentiality, high response rates, and validation of information. Among the players an injury rate of 75 injuries per 100 players was documented. Head and neck injuries accounted for 22% of the total injuries. Increased risks of injury were associated with multiple health-care provision variables and equipment utilized. Potential strategies are identified as a result of these findings.
Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease thought to be caused, at least in part, by repetitive brain trauma, including concussive and subconcussive injuries. It is thought to result in executive dysfunction, memory impairment, depression and suicidality, apathy, poor impulse control, and eventually dementia. Beyond repetitive brain trauma, the risk factors for CTE remain unknown. CTE is neuropathologically characterized by aggregation and accumulation of hyperphosphorylated tau and TDP-43. Recent postmortem findings indicate that CTE may affect a broader population than was initially conceptualized, particularly contact sport athletes and those with a history of military combat. Given the large population that could potentially be affected, CTE may represent an important issue in public health. Although there has been greater public awareness brought to the condition in recent years, there are still many research questions that remain. Thus far, CTE can only be diagnosed post-mortem. Current research efforts are focused on the creation of clinical diagnostic criteria, finding objective biomarkers for CTE, and understanding the additional risk factors and underlying mechanism that causes the disease. This review examines research to date and suggests future directions worthy of exploration.
This review provides a short overview of the most significant biologically oriented theories of human personality. Personality concepts of Eysenck, Gray and McNaughton, Cloninger and Panksepp will be introduced and the focal evidence for the heritability of personality will be summarized. In this context, a synopsis of a large number of COMT genetic association studies (with a focus on the COMT Val158Met polymorphism) in the framework of the introduced biologically oriented personality theories will be given. In line with the theory of a continuum model between healthy anxious behavior and related psychopathological behavior, the role of the COMT gene in anxiety disorders will be discussed. A final outlook considers new research strategies such as genetic imaging and epigenetics for a better understanding of human personality.
Low capacity of the central serotonergic system has been associated with impulsive behaviour. Both low platelet monoamine oxidase (MAO) activity and the short (S) allele of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) are proposed to be markers of less efficient serotonergic functioning.
The effect of the two markers for serotonin system efficiency on performance in a visual comparison task (VCT) and self-reported impulsiveness (Barratt Impulsiveness Scale, BIS-11) were investigated in healthy adolescents participating in the Estonian Children Personality Behaviour and Health Study. Possible confounding effect of general cognitive abilities on the performance in VCT was controlled for.
Low platelet MAO activity and carrying of the S allele of 5-HTTLPR were both associated with higher error-rate and more impulsive performance in VCT. Platelet MAO activity and 5-HTTLPR S allele had a significant interactive effect on self-reported impulsivity (BIS-11). The effect of platelet MAO activity on both self-reported and performance impulsivity was significant only in the S allele carriers. The effect of 5-HTTLPR S allele on impulsive performance remained significant after controlling for general cognitive abilities.
The two markers of lower serotonergic capacity, 5-HTTLPR S allele and low platelet MAO activity, have a similar and partly synergistic influence on self-reported as well as performance measures of impulsivity.
Suicide behavior is very frequent in Bipolar Disorder (BD) and they are both closely associated with impulsivity. Furthermore they are, impulsivity, BD and suicide behavior, associated with serotonergic function, at least partially, under genetic determinism and somewhat associated with the serotonin transporter gene polymorphism, the 5-HTTLPR. We aimed to assess different impulsivity components in BD sub-grouped by suicidal attempt and healthy controls. We hypothesized that the non-planning/cognitive impulsivity, could be more closely associated with suicidal behavior. We further associated 5-HTTLPR genotypes with neuropsychological results to test the hypothesis that this polymorphism is associated with cognitive impulsivity.
We assessed 95 euthymic bipolar patients sub-grouped by suicidal attempt history in comparison with 94 healthy controls. All subjects underwent a laboratory assessment of impulsivity (Continuous Performance Test and Iowa Gambling Test). Furthermore the genotyping of 5-HTTLPR was performed in all subjects.
We found that bipolar patients are more impulsive than healthy controls in all impulsivity dimensions we studied. Furthermore bipolar patients with a suicide attempt history have a greater cognitive impulsivity when compared to both bipolar patients without such a history as well when compared to healthy controls. No association was found between 5-HTTLPR genotypes and neuropsychological measures of impulsive behavior.
The sample studied can be considered small and a potentially confounding variable - medication status - was not controlled.
A lifetime suicide attempt seems associated with cognitive impulsivity independently of the socio-demographic and clinical variables studied as well with 5-HTTLPR genotype. Further studies in larger samples are necessary.
Impulsive drive for immediate reward (IDIR) and delay aversion are dissociable elements of the preference for immediate over delayed rewards seen in attention-deficit/hyperactivity disorder (ADHD). We hypothesized that IDIR would be associated with dopamine regulating genes and delay aversion would be associated with serotonin-regulating genes.
Impulsive drive for immediate reward and delay aversion were measured in 459 male children and adolescents (328 ADHD and 131 unaffected siblings) with a laboratory choice task. The sample was genotyped for the 5HTT (SLC6A4) promoter serotonin-transporter-linked polymorphic region polymorphism and a DAT1 (SLC6A3) 40-base pair variable number tandem repeat located in the 3'-untranslated region of the gene.
There was no effect of dopamine transporter (DAT)1 on IDIR. As predicted, serotonin-transporter-linked polymorphic region s-allele carriers were more delay averse. This effect was driven by the s/l genotype in the ADHD group. These results were not altered by taking account of the rs25531 A/G single nucleotide polymorphism and were independent of age, IQ, and oppositional defiant disorder symptoms.
The results support the genetic distinctiveness of IDIR and delay aversion in ADHD and implicate serotonin function in delay aversion. Possible explanations of the heterosis effect in the ADHD cases are presented.
Reduced serotonergic neurotransmission is implicated in impulsive behavior. We studied the triallelic system of the serotonin transporter gene linked polymorphic region (5-HTTLPR) and acute manipulation of serotonin together to further delineate the mechanisms by which serotonergic neurotransmission affects impulsivity. Fifty-two healthy participants (38 men and 14 women) underwent acute tryptophan depletion (ATD) or placebo in a randomized, double-blind, parallel group experiment. Impulsive response style was measured on two versions of the Continuous Performance Task (CPT), and calculated using signal detection theory. We observed a dose-dependent effect for the short (S') allele of the 5-HTTLPR on impulsive response style. Individuals who had the S'/S' genotype were more impulsive than individuals with the L/S' genotype. Participants with the L/S' genotype were more impulsive than those with the L/L genotype. ATD increased impulsivity in men, and decreased impulsivity in women. These data demonstrate for the first time that reduced serotonergic tone as a result of either 5-HTTLPR genotype, or experimental ATD, are both independently and additively, associated with elevated impulsive response style in Caucasian men.
Since the 1920s, it has been known that the repetitive brain trauma associated with boxing may produce a progressive neurological deterioration, originally termed dementia pugilistica, and more recently, chronic traumatic encephalopathy (CTE). We review 48 cases of neuropathologically verified CTE recorded in the literature and document the detailed findings of CTE in 3 profession althletes, 1 football player and 2 boxers. Clinically, CTE is associated with memory disturbances, behavioral and personality changes, parkinsonism, and speech and gait abnormalities. Neuropathologically, CTE is characterized by atrophy of the cerebral hemispheres, medial temporal lobe, thalamus, mammillary bodies, and brainstem, with ventricular dilatation and a fenestrated cavum septum pellucidum. Microscopically, there are extensive tau-immunoreactive neurofibrillary tangles, astrocytic tangles, and spindle-shaped and threadlike neurites throughout the brain. The neurofibrillary degeneration of CTE is distinguished from other tauopathies by preferential involvement of the superficial cortical layers, irregular patchy distribution in the frontal and temporal cortices, propensity for sulcal depths, prominent perivascular, periventricular, and subpial distribution, and marked accumulation of tau-immunoreactive astrocytes. Deposition of beta-amyloid, most commonly as diffuse plaques, occurs in fewer than half the cases. Chronic traumatic encephalopathy is a neuropathologically distinct slowly progressive tauopathy with a clear environmental etiology.
The association between different impulsive-disinhibited personality traits with 5-HTTLPR and 5-HTTVNTR genetic polymorphisms was examined in an imprisoned male sample. Higher scores of the impulsive-disinhibited personality traits tended to be associated with carrying one or two copies of the 5-HTTPLR S allele (S/S homozygous and S/L heterozygous), and carrying two copies of the 5-HTTVNTR 12 allele (12/12 homozygous). Genotype, allele, haplotype and extended genotype distribution between low and high impulsive-disinhibited groups confirmed this association. Allele S and genotypes S/S+S/L at the 5-HTTLPR locus and allele 12 and genotype 12/12 at the 5-HTTVNTR locus were overrepresented in the high scoring group. Accordingly, allele S and allele 12 conferred a trend for risk to be in the high scoring group with an odds ratio (OR) of 1.8 (p < 0.035) and 1.7 (p < 0.014), respectively. In addition, extended genotype distribution shows that those S allele carriers (S/S homozygote and S/L heterozygote) that were also 12/12 homozygote, were overrepresented in the high scoring group (OR = 3.2; p < 0.004). The main risk of being in the high scoring group was assigned to those carrying two copies of the S-12 haplotype (OR = 5.7; p < 0.0007). We discuss the possible relationship between the two genetic serotonin polymorphisms and the personality impulsive-disinhibited traits investigated.
A unique type of craniofacial dysostosis, Crouzon syndrome with acanthosis nigricans (CAN), has been attributed to a specific substitution (Ala391Glu) in the fibroblast growth factor receptor 3 (FGFR3) gene. At birth, individuals with this disorder have craniosynostosis, ocular proptosis, midface hypoplasia, choanal atresia, hydrocephalus, and they experience the onset of acanthosis nigricans during childhood. We report three cases and compare the clinical characteristics of our cases with the previously reported cases of this disorder. Since the Ala391Glu substitution in FGFR3 is close to the substitutions in the transmembrane domain that result in achondroplasia, we carefully reviewed the skeletal findings in six patients. We identified subtle radiographic findings of achondroplasia in all six cases including narrow sacrosciatic notches, short vertebral bodies, lack of the normal increase in interpediculate distance from the upper lumbar vertebrae caudally, and broad, short metacarpals and phalanges. Even before acanthosis nigricans appears, the presence of choanal atresia and hydrocephalus in an individual with features of Crouzon syndrome should suggest the diagnosis of CAN, and subtle skeletal findings can lend further support to this diagnosis.
A key step toward the discovery of a gene related to a trait is the finding of an association between the trait and one or more haplotypes. Haplotype analyses can also provide critical information regarding the function of a gene; however, when unrelated subjects are sampled, haplotypes are often ambiguous because of unknown linkage phase of the measured sites along a chromosome. A popular method of accounting for this ambiguity in case-control studies uses a likelihood that depends on haplotype frequencies, so that the haplotype frequencies can be compared between the cases and controls; however, this traditional method is limited to a binary trait (case vs. control), and it does not provide a method of testing the statistical significance of specific haplotypes. To address these limitations, we developed new methods of testing the statistical association between haplotypes and a wide variety of traits, including binary, ordinal, and quantitative traits. Our methods allow adjustment for nongenetic covariates, which may be critical when analyzing genetically complex traits. Furthermore, our methods provide several different global tests for association, as well as haplotype-specific tests, which give a meaningful advantage in attempts to understand the roles of many different haplotypes. The statistics can be computed rapidly, making it feasible to evaluate the associations between many haplotypes and a trait. To illustrate the use of our new methods, they are applied to a study of the association of haplotypes (composed of genes from the human-leukocyte-antigen complex) with humoral immune response to measles vaccination. Limited simulations are also presented to demonstrate the validity of our methods, as well as to provide guidelines on how our methods could be used.
In light of the classic examples of population stratification, as well as the population heterogeneity in allele frequencies and disease rates, we believe that population stratification is a sufficiently serious concern to merit careful consideration in interpreting the results of any candidate-gene association that is not based on the use of family-member controls. This concern would be mitigated by careful attention to the standard principles of epidemiological study design, including the choice of a mechanism for selecting controls that are representative of the source population of cases and by making some effort to control ethnicity by restriction, matching, or stratified or multivariate analysis. For any of these approaches to be successful, information on ethnic origin should be obtained in the greatest detail that is practically feasible. Although there will always be some risk of residual confounding by ethnicity in case-control studies using unrelated controls, we do not feel that this problem is qualitatively different from the problem of uncontrolled confounding in virtually any other observational epidemiological study. However, the considerable range of variation in allele frequencies across and within ethnic groups and the enormous magnitude of some genetic risks (compared with those from most environmental agents) suggests that the problem of confounding by population stratification could be more serious in magnitude than in traditional environmental epidemiology. The availability of family-based case-control designs that completely eliminate these concerns suggests that no candidate gene association should be considered "confirmed" until replicated by such a study, or at least by multiple well-designed studies in different populations where any effects of population stratification or other methodologic biases are unlikely to act in a consistent manner. Rather than continued debate about whether population stratification is or is not a serious concern, we call for a systematic program of research to understand the magnitude of the problem in general. Additional studies of the variation in allele frequencies of many genes and of the variation in baseline rates for a wide range of disease and the correlation between the two would be extremely useful, as would further meta-analyses of candidate gene associations, with particular attention to study of the determinants of observed heterogeneity in findings (71). Finally, we suggest that the promising approaches to use of genomic information as a means of detecting and controlling for population stratification merit further application and development.