Different factors affecting athletic performance are well established: intensity and type of training, anthropometric characteristics as well as an important psychological component. However, the contribution of the genetic background has been less investigated. The aim of the present study was to investigate the influence of polymorphisms within genes associated with stress and anxiety (5HTT, CRH2R, ACE, NK1R, 5HT1AR and CRF-BP) on the physical capability and sports performance in triathletes. One hundred and ninety two (192) unrelated Chilean triathletes who participated in the 2014 70.3 Pucón city triathlon were divided into opposite subgroups of sports performance according to their time results. We identified significant associations for five polymorphisms (5HTT 5-HTTLPR, ACE I/D, NK1R rs6715729, 5HT1AR -1019C>G and CRF-BP CRF-BPs11) with athletic performance. Our results indicate that these polymorphisms are associated with differential sports performance in Chilean triathletes, establishing an initial background for better understanding the relationship between physical performance, genetics and anxiety disorders.
Genetic factors influencing sports performance in the Chilean population are unknown.
Differential outcomes from athletes who completed a triathlon competition were associated with five polymorphisms ( 5-HTTLPR, I/D, rs6715729, -1019C>G and CRF-BPs11).
We show that genetic variants within stress- and anxiety-related genes affect athletic performance.
The effects of anxiety on athletic performance have been the main target of study in sports psychology recently. Each anxiety disorder has different symptoms, but they cluster around an irrational and excessive fear or dread (Issler et al., 2014). In triathletes, changing situations during training and competition together with the pre-sence of anxiety disorders might cause the maladaptive fatigue syndrome (overtraining syndrome) characterized by: anger, hostility, anxiety, confusion, depression, sadness, lack of energy and apathy, finally resulting in poor performance and/or abandonment of training and competition (Patel et al., 2010). The mental health and athletic performance current model suggests a relationship bet-ween psychopathology and athletic performance (Patel et al., 2010). Studies have shown that between 70% to 85% of successful and unsuccessful athletes can be identified using general psychological measures of personality structure and mood, a level above chance, but insufficient for the purpose of athletes selection (Del Coso et al., 2014). Other studies show a deleterious effect of stress and anxiety on athletic performance in various sports (Raglin, 2001).
The biological basis of anxiety disorders focuses on a dysfunctional hypothalamus-pituitary-adrenal (HPA) axis, leading to increased activity and exaggerated response mediated by the neuroendocrine system of cortisol and catecholamines (Drabant et al., 2012). An important modulator is the serotonergic system, controlling HPA axis function on at least two levels: on one hand, activa-ting the corticotropin-releasing factor (CRF) and secondly, by regulating cortisol and CRF activity at the synaptic level (Drabant et al., 2012). In this context, the serotonin transporter (SERT or 5-HTT) regulates serotonin (5-HT) concentrations at the synaptic level (Lee et al., 2004), and more than twelve different traits of human behavior and other systemic diseases have been linked to SERT variations (SLC6A4) (Sysoeva et al., 2009). SLC6A4 repression and the function of important variations in the trans-criptional control region (serotonin transporter gene linked polymorphic region; 5-HTTLPR) have been linked to multiple psychopathological conditions, including anxiety disorder (Gonda et al., 2008).
The 5-HTTLPR polymorphism corresponds to a genetic variant in which an insertion-deletion of a 44 base pairs (bp) fragment occurs within SLC6A4, where the shorter variant (deletion, short/short or s/s) results in reduced transcriptional activity and increased vulnerability to affective disorders (Trushkin et al., 2011).
Within the serotonergic system, a crucial study target corresponds to the 5-HT1A receptor, which plays an important role in the self-regulatory function of the central serotonergic system (Noro et al., 2010). Studies evaluating the C(-1019)G polymorphism within this gene show an association with suicide risk, without being associated with depression (Lemonde et al., 2003). Dysfunctions associated with this receptor in knockout 5-HT1A -/- mice show increased anxious features and stress sensitivity (Lesch, 2001). Animal and cell culture studies demonstrate that increased activity of the HPA axis is associated with decreased expression of the postsynaptic 5-HT1A receptor (Lanfumey et al., 2008).
Another important regulation mechanism of the HPA axis occurs during CRF release and its binding to type 1 and type 2 specific receptors, modulating HPA axis activity (Van Den Eede et al., 2005). Current evidence shows that CRF release regulation is mediated by CRF binding protein (CRF-BP), producing an additional feedback on the HPA axis (Issler et al., 2014). Different stu-dies showed increased expression of CRF-BP in the amygdale, anterior pituitary and portal circulation follo-wing increased CRF release (Van Den Eede et al., 2005). Furthermore, CRF-BP knockout mice showed an anxious behavior together with increased CRF concentrations and elevated ACTH and cortisol levels (Van Den Eede et al., 2005).
Corticotropin-releasing factor 2 receptor (CRF2R) is suggested to play a fundamental role in the recovery from stress to calm (Bale et al., 2002). Reports show that CRF2R receptors are required for proper 5-HT1A receptors function in the raphe nuclei, and that they are key for successful stress recovery (Issler et al., 2014).
In addition to its neurotransmitter/modulator in pain perception, substance P (SP) is involved in mood regulation, as demonstrated by its neurokinin-1 receptor (NK1R) antagonists to have antidepressant effects in humans (Noro et al., 2010). In rodents, treatment with NK1R antagonists showed increased 5-HT liberation from the dorsal raphe nucleus (DRN), suggesting local interactions between SP and serotonin in 5-HT1A receptors desensitization, representing a new element in the complex neural circuits proposed for mood regulation (Koller et al., 2006).
Multiple studies have associated angiotensin converting enzyme (ACE) with sports performance, and recently, ACE has been proposed as an important cortisol secretion and HPA axis regulator (Ancelin et al., 2013). The I/I genotype of the ACE rs1799752 polymorphism (I/D) has been associated with reduced plasma levels and tissue activity of ACE, while the D/D genotype was associated with higher plasma concentration and increased cardiac activity of the enzyme together with improved performance in sprint sports (Saber-Ayad et al., 2014). The I allele has been also associated with increased endurance in elite long distance runners, rowers and trail runners (Cam et al., 2005). Moreover, the presence of the D allele increases the ejection fraction and systolic pulmonary artery pressure (Saber-Ayad et al., 2014) together with an increase in CRH and ACTH levels of the HPA axis (Ancelin et al., 2013). In addition, higher ACE plasma levels are associated with lower performance in cycling and jogging in a group of athletes competing in the South Africa Ironman (Domingo et al., 2013).
Based on the background aforementioned, we aimed to explore a possible relationship between the presence of anxiety-related polymorphisms and their association with athletic performance in a group of Chilean long-distance triathletes.
One hundred and ninety two triathlon male competitors (1.9 km swimming, 90 km bike and 21 km of jogging) were evaluated. Clinical assessment consisted in physical measures of body composition by bioelectrical impedance, and a psychiatric interview using the MINI international neuropsychiatric interview, version 5.0, which allows categorizing various Axis I DSM-IV-TR disorders. Anthropometric characteristics are resumed in Table 1.
Every triathlete had experience on the Half Ironman as the entire group ran the same triathlon at least one time. All athletes fulfilled six mesocycles consisting of 3 microcycles each. Different categories were set to establish their performance outcomes. Following the participation of the athletes in the Half Ironman 70.3 competition (Pucón city), overall performance stratification was completed dividing the 192 participants into two opposite performance subgroups, designated as superior performance group (SP, n = 92) and inferior performance group (IP, n = 100), according to times registered in their respective categories. The study was conducted according to the Declaration of Helsinki. All participants accepted to participate by signing an informed consent previously approved by the Research Ethics Committee of Universidad de La Frontera (Protocol number CEC 112/2013).
Venous blood samples were obtained for leukocyte DNA extraction and subsequent polymorphisms genotyping by PCR, PCR-RFLP and qRT-PCR. Genomic DNA was extracted using a protocol previously described by Salazar et al. (Salazar et al., 1998). Afterwards, DNA was quantified by spectrophotometry and diluted to 100 ng/100µl.
Genotyping of ACE rs1799752 (I/D) and serotonin transporter 5HTT (5-HTTLPR) polymorphisms was completed by conventional PCR, observing for the I/D polymorphism a fragment of 190 bp in the presence of the D allele, and a fragment of 490 bp in the presence of the I allele. For the 5-HTTLPR polymorphism, a fragment of 528 bp was observed for the insertion L/L homozygote genotype, two fragments of 484 bp and 528 bp for the heterozygote S/L, and one 484 bp fragment for deletion genotype S/S.
The presence of CRF-BP rs1875999 polymorphism was detected by polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) using TaqI restriction endonuclease (Fermentas, Lithuania). Wild-type genotype (C/C) was identified by the presence of a 503 bp fragment; the heterozygous genotype (C/T) for fragments of 503, 325 and 178 bp and the homozygous genotype (T/T) by two fragments of 325 and 178 bp.
For the detection of polymorphisms CRF2R rs2267717, 5HT1AR -1019C>G and NK1R rs6715729, we used the C__15872907_10, C__11904666_10, C__25473413_10 TaqMan® SNP Genotyping Assays (Life Technologies, CA, USA), respectively. PCR assays contained 12.5 µL of Universal Master Mix (2X) (Life Technologies CA, USA), 1.25 µL of TaqMan SNP Genotyping Assay (20X) and 1 µL of DNA (20 ng) diluted in nuclease-free water. The thermal cycling protocol performed was initiated with a cycle for 10 min. at 95°C and followed by 50 cycles at 92°C for 15 sec., and 60°C for 1 min. using standard conditions for real-time system (Life Technologies). A list of the primers and assays used are provided in Table 2. Genotype calling was performed using the StepOne software v. 2.2 (Life Technologies). No template controls (NTC) were included per triplicate in each genotyping experiment plate. Genotyping was randomly repeated on 20% of the samples for quality control purposes, without finding differences.
All statistical analyses were performed using SPSS software version 20.0 for Mac OSX. Chi-square test (x2) was used to analyze differences in allelic frequencies and to verify Hardy-Weinberg equilibrium. Gaussian distribution was assessed by D’Agostino and Pearson normality test. Following ANOVA, we performed the Tukey post test to compare all pairs of columns. The OR was calculated assuming a model of genetic dominance and using the minor allele frequency as a risk factor for IP. Two-tailed p values <0.05 were considered as statistically significant.
Genotypes distribution and relative frequency of alleles was consistent with Hardy-Weinberg equilibrium for all polymorphisms evaluated (Table 3). From the 192 participants undergoing the MINI neuropsychiatric interview, 85 individuals met the criteria to be categorized into anxiety disorder, and 107 were excluded from this category. When comparing the presence of this disorder in IP (n = 57) and SP (n = 28) individuals, we observed significant differences, which indicated that the presence of anxiety disorder correlates with deficient athletic performance in IP triathletes (p = 0.011). The results from the neuropsychiatric interview according to genotypes are shown in Table 4.
In addition, significant differences were observed when evaluating genotype distributions. Considering a codominance genetic inheritance model, the presence of the genotypes affected athletic performance, being more frequent in the IP subgroup for five polymorphisms. The same results were observed when analyzing allelic frequencies, showing significant differences between both groups and identifying more frequently the presence of the minor allele in the IP subgroup (Table 5).
One of the main areas of research in sports psychology is the study of the relationship between anxiety and athletic performance. Even when the model of the inverted U determines that in the extremes, i.e., low and high anxiety levels condition poor performance, there are several sports that contradict this theory (Woodman and Hardy, 2003). Among them, Lopez-Perez and Labrador (1992) show that high anxiety levels improve athletic performance in a group of basketball players. Certainly, these results contradict those observed in our study, in which IP athletes present anxiety more frequently.
Anxiety can affect multiple sports aspects, and is often associated with a lack of continuity, loss of pleasure for competing and poor sports performance (Raglin, 2001). We show that anxiety disorder associates with inferior sports performance in Chilean triathletes, which is consistent with previous results where anxiety displays a negative impact on penalty definitions, climbing, golf and tennis (Raglin, 2001).
None of the athletes participating from this study declared their belonging to a particular ethnicity, neither orally nor written. Nonetheless, is important to point out that a rich admixture dominates the phenotype of Chileans (Lagos et al., 2015), determining a strong Amerindian background, which could affect one genetic variant that often represents a marker of successful sports performance, the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. Despite the abundant evidence showing significant associations for the I allele with enhanced sports outcomes, results can be controversial, as there seems to be a differential role for each allele of the ACE I/D polymorphism; while the I allele has been associated with endurance sports, a higher D allele frequency has been observed in power-orientated sports (Nazarov et al., 2001; Puthucheary et al., 2011). The association between IP athletes and the ACE D/D genotype is similar to previous findings obtained in 2009 in Greek athletes (Papadimitriou et al., 2009), in 2011 in Lithuanian athletes (Gineviciene et al., 2011), and other studies associating the D/D genotype with poor sports performance (Holdys, 2011). In 2006, Hruskovicova et al. (2006) observed differences in genotype and allele distributions between marathon runners compared with sedentary controls. In Koreans, no differences were observed between elite athletes and unrelated nonathletes (Oh, 2007). The ACE I/D polymorphism is one of the main reported factors impairing sports performance in athletes (Woods et al., 2000) mainly due to its effect on cardiovascular system homeostasis (Izzicupo et al., 2013). The D/D genotype has been also associated with effort intolerance in humans (Mota et al., 2013). Besides, previous reports indicate that genotype I/I enables a better energetic adaptation and vascular resistance to endurance exercises (Holdys, 2011), situation that coincides with our findings, which is also consistent with a comparative study between elite and amateur athletes, identifying the same deleterious effects of the D allele and D/D genotype on athletic performance (Cam et al., 2005). However, inconsistencies between studies evaluating this polymorphism can exist, and may rely on several factors: study design, sports evaluated, inclusion/exclusion criteria, and age of the participants, just to mention a few. Nonetheless, the most important issue that may confront results corresponds to the population’s dissimilar genetic background, which is key when considering that we are precisely determining the genetic contribution across, in our case, highly admixed individuals, an issue that can underlie different results.
On the other hand, we found a higher frequency for the 5-HTTLPR S/S genotype and S allele in IP athle-tes, which is concordant with results described by Trushkin and colleagues (2011) in a group of athletes undergoing maximum stress testing, where individuals carrying the S/S genotype had lower tolerance to fatigue than L/L carriers. A common finding is that sports have a similar effect than serotonin reuptake inhibitors (SRI) antidepre-ssants. However, Rethorst and colleagues (2010) showed that the presence of the S/S genotype and S allele reduced the positive impact of sports in depression patients. Nevertheless, SRI consumption did not improve athletic performance in another group of athletes under study (Parise et al., 2001). In addition, our results disagree with those reported in long distance South African triathletes, finding no association with this polymorphism, however, it should be noted that in the South African cohort, performance was evaluated in two different years, where diverse variables could be influencing the final outcome. For instance, the study by de Milander included Caucasian population only, where the S/S genotype is known to have a lower frequency than South Americans (Ospina-Duque et al., 2000). De Milander reported a 20% frequency for the S/S genotype, while our results showed a 33.4% frequency. Moreover, de Milander and colleagues performed their study in Ironman competitors (3.9 km swimming, 180 km biking, 42 km jogging), whilst our work included half-ironman participants (1.9 km swimming, 90 km biking and 21 km jogging). Temperatures were also different, having extremes of 9-26 °C in Pucón, and 17-23.9 °C in South Africa. Finally, de Milander divided their participants into fast, middle and low triathletes, a different measure from the lower and upper performance shown in our work (de Milander et al., 2009).
For the 5HT1AR -1019C>G polymorphism, our results show that the G/G genotype is more frequent in the IP group (p = 0.0001), which is similar to the presence of the G allele (p = 0.0001). However, there are no previous reports linking athletic performance and the presence of this polymorphism, but there could be a connection if the -1019C>G polymorphism can be related to the presence of anxiety disorders. Reports show that 5-HT1A receptors are distributed in high density in the limbic system, and are involved in the regulation of emotional states, being found pre and post-synaptically (Huang et al., 2004). Recent studies in animal models indicate that knockout mice for this protein show and increased overall response to anxiety states (Zetzsche et al., 2008). In human, studies revealed an association between -1019C>G polymorphism and the presence of panic disorder and agoraphobia, two determinants of anxiety disorders (Bosia et al., 2011; Rothe et al., 2004).
For the NK1R rs6715729 polymorphism, our results show an association between G/G genotype and G allele with the IP group, which could possibly be due to changes in relation to stress homeostasis. Human and animal studies suggest that the P substance mediates the response to stress, where the biological responses of the P substance are mainly transduced through NK1R, widely expressed in pathways controlling stress, and tissues such as intestine, joints, tendons and skin (Seneviratne et al., 2009); antagonists for this receptor are very effective in treating depression and anxiety (Stein et al., 2006). This polymorphism is also associated with alcohol dependence and abuse (Seneviratne et al., 2009). Nonetheless, we associated the presence of the G/G genotype with agoraphobia (p = 0.029) and generalized anxiety disorder (p = 0.024), major determinants of anxiety disorder. Finally, although reporting significant findings, some issues may be limiting the extent of the results and need to be further considered. For instance, the lack of a control group, therefore, we cannot conclusively rule out other unaccounted factors that may be influencing the differential performance observed as well. Secondly, the small sample size, which brings the necessity to replicate this study encompassing a greater number of participants to reproduce the associations identified.
Multiple physiological, pathophysiological and psychological aspects influence athletic performance. Clarifying how these factors affect the organism in endurance sports is critical to achieve a better understanding in long-distance competitions outcomes. Here, we show that genetic variants within stress- and anxiety-related genes affect athletic performance in long-distance Chilean triathletes; contributing evidence that includes a novel factor to consider is sports physiology, which is an important advance in the comprehension of the HPA axis functionality. Further studies are necessary to disclose the role of additional components involved affecting sports performance.
This work was supported by Fund for Innovation and Competitiveness (FIC) of the Chilean Ministry of Economy, Development and Tourism, through the Millennium Scientific Initiative under Grant number IS130005; FONDECYT under Grant numbers 1130810 and 1150166; FIDUM under Grant numbers 100512 and 100514. We declare that the experiments comply with the current Chilean laws, the country in which the experiments were performed. There is no conflict of interest.
Medicine School, Universidad Mayor, Temuco, Chile
interests: Stress neurobiology, physical performance
Ancelin M.L., Carrière I., Scali J., Ritchie K., Chaudieu I., Ryan J. (2013) Angiotensin-converting enzyme gene variants are associated with both cortisol secretion and late-life depression. Translational Psychiatry 3, e322-.
Bale T.L., Lee K.-F., Vale W.W. (2002) The Role of Corticotropin-Releasing Factor Receptors in Stress and Anxiety. Integrative and Comparative Biology 42, 552-555.
Bosia M., Anselmetti S., Bechi M., Lorenzi C., Pirovano A., Cocchi F., Buonocore M., Bramanti P., Smeraldi E., Cavallaro R. (2011) Effect of 5-HT1A-receptor functional polymorphism on Theory of Mind performances in schizophrenia. Psychiatry Research 188, 187-190.
Cam F.S., Colakoglu M., Sekuri C., Colakoglu S., Sahan C., Berdeli A. (2005) Association between the ACE I/D gene polymorphism and physical performance in a homogeneous non-elite cohort. Canadian Journal of Applied Physiology 30, 74-86.
de Milander L., Stein D.J., Collins M. (2009) The interleukin-6, serotonin transporter, and monoamine oxidase A genes and endurance performance during the South African Ironman Triathlon. Applied Physiology, Nutrition, and Metabolism 34, 858-865.
Del Coso J., Areces F., Salinero J.J., Gonzalez-Millan C., Abian-Vicen J., Soriano L., Ruiz D., Gallo C., Lara B., Calleja-Gonzalez J. (2014) Compression stockings do not improve muscular performance during a half-ironman triathlon race. European Journal of Applied Physiology 114, 587-595.
Domingo R., Sturrock E.D., Collins M. (2013) ACE activity and endurance performance during the South African Ironman triathlons. International Journal of Sports Medicine 34, 402-408.
Drabant E.M., Ramel W., Edge M.D., Hyde L.W., Kuo J.R., Goldin P.R., Hariri A.R., Gross J.J. (2012) Neural mechanisms underlying 5-HTTLPR-related sensitivity to acute stress. American Journal of Psychiatry 169, 397-405.
Gineviciene V., Pranculis A., Jakaitiene A., Milasius K., Kucinskas V. (2011) Genetic variation of the human ACE and ACTN3 genes and their association with functional muscle properties in Lithuanian elite athletes. Medicina (Kaunas) 47, 284-290.
Gonda X., Lazary J., Rihmer Z., Bagdy G. (2008) Association of 5HTTLPR with factors related to risk of suicide. European Psychiatry 23, S175-S176.
Holdys J., Kryściak J., Stanisławski D., Gronek P. (2011) ACE I/D Gene Polymorphism in Athletes of Various Sports Disciplines. Human Movement 12, 216-197.
Hruskovicova H., Dzurenkova D., Selingerova M., Bohus B., Timkanicova B., Kovacs L. (2006) The angiotensin converting enzyme I/D polymorphism in long distance runners. Journal of Sports Medicine and Physical Fitness 46, 509-513.
Huang Y.Y., Battistuzzi C., Oquendo M.A., Harkavy-Friedman J., Greenhill L., Zalsman G., Brodsky B., Arango V., Brent D.A., Mann J.J. (2004) Human 5-HT1A receptor C(-1019)G polymorphism and psychopathology. International Journal of Neuropsychopharmacology 7, 441-451.
Issler O., Carter R.N., Paul E.D., Kelly P.A., Olverman H.J., Neufeld-Cohen A., Kuperman Y., Lowry C.A., Seckl J.R., Chen A., Jamieson P.M. (2014) Increased anxiety in corticotropin-releasing factor type 2 receptor-null mice requires recent acute stress exposure and is associated with dysregulated serotonergic activity in limbic brain areas. Biology of Mood & Anxiety Disorders 4, 1-.
Izzicupo P., Ghinassi B., D'Amico M.A., Di Blasio A., Gesi M., Napolitano G., Gallina S., Di Baldassarre A. (2013) Effects of ACE I/D Polymorphism and Aerobic Training on the Immune-Endocrine Network and Cardiovascular Parameters of Postmenopausal Women. Journal of Clinical Endocrinology and Metabolism 98, 4187-4194.
Koller G., Bondy B., Preuss U.W., Zill P., Soyka M. (2006) The C(-1019)G 5-HT1A promoter polymorphism and personality traits: no evidence for significant association in alcoholic patients. Behavioral and Brain Functions 2, 7-.
Lagos J., Zambrano T., Rosales A., Salazar L.A. (2015) APOE Polymorphisms Contribute to Reduced Atorvastatin Response in Chilean Amerindian Subjects. International Journal of Molecular Sciences 16, 7890-7899.
Lanfumey L., Mongeau R., Cohen-Salmon C., Hamon M. (2008) Corticosteroid–serotonin interactions in the neurobiological mechanisms of stress-related disorders. Neuroscience Biobehavioral Reviews 32, 1174-1184.
Lee M.S., Lee H.Y., Lee H.J., Ryu S.H. (2004) Serotonin transporter promoter gene polymorphism and long-term outcome of antidepressant treatment. Psychiatric Genetics 14, 111-1115.
Lemonde S., Turecki G., Bakish D., Du L., Hrdina P.D., Bown C.D., Sequeira A., Kushwaha N., Morris S.J., Basak A., Ou X.-M., Albert P.R. (2003) Impaired Repression at a 5-Hydroxytryptamine 1A Receptor Gene Polymorphism Associated with Major Depression and Suicide. The Journal of Neuroscience 23, 8788-8799.
Lesch K.P. (2001) Mouse anxiety: the power of knockout. Pharmacogenomics J 1, 187-192.
López-Pérez B., L.F., José María Buceta Casas, Bueno A. (1992) Ansiedad y rendimiento deportivo: estudio de la relación entre ambas variables. Revista de psicología general y aplicada:. Revista de la Federación Española de Asociaciones de Psicología 45, 315-320.
Mota M.R., Oliveira R.J., Terra D.F., Pardono E., Dutra M.T., de Almeida J.A., Silva F.M. (2013) Acute and chronic effects of resistance exercise on blood pressure in elderly women and the possible influence of ACE I/D polymorphism. International Journal of General Medicine 6, 581-587.
Nazarov I.B., Woods D.R., Montgomery H.E., Shneider O.V., Kazakov V.I., Tomilin N.V., Rogozkin V.A. (2001) The angiotensin converting enzyme I/D polymorphism in Russian athletes. European Journal of Human Genetics 9, 797-801.
Noro M., Antonijevic I., Forray C., Kasper S., Kocabas N.A., Lecrubier Y., Linotte S., Mendlewicz J., Montgomery S., Snyder L., Souery D., Verbanck P., Zohar J., Massat I. (2010) 5HT1A and 5HT2A receptor genes in treatment response phenotypes in major depressive disorder. International Clinical Psychopharmacology 25, 228-231.
Oh S.D. (2007) The distribution of I/D polymorphism in the ACE gene among Korean male elite athletes. The Journal of Sports Medicine and Physical Fitness 47, 250-254.
Ospina-Duque J., Duque C., Carvajal-Carmona L., Ortiz-Barrientos D., Soto I., Pineda N., Cuartas M., Calle J., Lopez C., Ochoa L., Garcia J., Gomez J., Agudelo A., Lozano M., Montoya G., Ospina A., Lopez M., Gallo A., Miranda A., Serna L., Montoya P., Palacio C., Bedoya G., McCarthy M., Reus V., Freimer N., Ruiz-Linares A. (2000) An association study of bipolar mood disorder (type I) with the 5-HTTLPR serotonin transporter polymorphism in a human population isolate from Colombia. Neuroscience Letters 292, 199-202.
Papadimitriou I.D., Papadopoulos C., Kouvatsi A., Triantaphyllidis C. (2009) The ACE I/D polymorphism in elite Greek track and field athletes. The Journal of Sports Medicine and Physical Fitness 49, 459-463.
Parise G., Bosman M.J., Boecker D.R., Barry M.J., Tarnopolsky M.A. (2001) Selective serotonin reuptake inhibitors: Their effect on high-intensity exercise performance. Archives of Physical Medicine and Rehabilitation 82, 867-871.
Patel D.R., Omar H., Terry M. (2010) Sport-related performance anxiety in young female athletes. Journal of Pediatric and Adolescent Gynecology 23, 325-335.
Puthucheary Z., Skipworth J.R., Rawal J., Loosemore M., Van Someren K., Montgomery H.E. (2011) Genetic influences in sport and physical performance. Sports Med 41, 845-859.
Raglin J.S. (2001) Psychological factors in sport performance: the Mental Health Model revisited. Sports Medicine 31, 875-890.
Rethorst C.D., Landers D.M., Nagoshi C.T., Ross J.T.D. (2010) Efficacy of Exercise in Reducing Depressive Symptoms across 5-HTTLPR Genotypes. Medicine Science in Sports Exercise 42, 2141-2147.
Rothe C., Gutknecht L., Freitag C., Tauber R., Mossner R., Franke P., Fritze J., Wagner G., Peikert G., Wenda B., Sand P., Jacob C., Rietschel M., Nothen M.M., Garritsen H., Fimmers R., Deckert J., Lesch K.P. (2004) Association of a functional 1019C>G 5-HT1A receptor gene polymorphism with panic disorder with agoraphobia. International Journal of Neuropsychopharmacology 7, 189-192.
Saber-Ayad M.M., Nassar Y.S., Latif I.A. (2014) Angiotensin-converting enzyme I/D gene polymorphism affects early cardiac response to professional training in young footballers. Journal of the Renin Angiotensin Aldosterone System 15, 236-242.
Salazar L.A., Hirata M.H., Cavalli S.A., Machado M.O., Hirata R.D. (1998) Optimized procedure for DNA isolation from fresh and cryopreserved clotted human blood useful in clinical molecular testing. Clinical Chemistry 44, 1748-1750.
Seneviratne C., Ait-Daoud N., Ma J.Z., Chen G., Johnson B.A., Li M.D. (2009) Susceptibility Locus in Neurokinin-1 Receptor Gene Associated with Alcohol Dependence. Neuropsychopharmacology 34, 2442-2449.
Stein M.B., Seedat S., Gelernter J. (2006) Serotonin transporter gene promoter polymorphism predicts SSRI response in generalized social anxiety disorder. Psychopharmacology (Berl) 187, 68-72.
Sysoeva O.V., Maluchenko N.V., Timofeeva M.A., Portnova G.V., Kulikova M.A., Tonevitsky A.G., Ivanitsky A.M. (2009) Aggression and 5HTT polymorphism in females: Study of synchronized swimming and control groups. International Journal of Psychophysiology 72, 173-178.
Trushkin E.V., Timofeeva M.A., Sysoeva O.V., Davydov Y.I., Knicker A., Struder H., Tonevitsky A.G. (2011) Association of SLC6A4 gene 5-HTTLPR polymorphism with parameters of simple and complex reaction times and critical flicker frequency threshold in athletes during exhaustive exercise. Bulletin of Experimental Biology and Medicine 150, 471-474.
Van Den Eede F., Van Broeckhoven C., Claes S.J. (2005) Corticotropin-releasing factor-binding protein, stress and major depression. Ageing Research Reviews 4, 213-239.
Woodman T., Hardy L. (2003) The relative impact of cognitive anxiety and self-confidence upon sport performance: a meta-analysis. Journal of Sports Sciences 21, 443-457.
Woods D.R., Humphries S.E., Montgomery H.E. (2000) The ACE I/D polymorphism and human physical performance. Trends in Endocrinology and Metabolism 11, 416-420.
Zetzsche T., Preuss U.W., Bondy B., Frodl T., Zill P., Schmitt G., Koutsouleris N., Rujescu D., Born C., Reiser M., Moller H.J., Meisenzahl E.M. (2008) 5-HT1A receptor gene C -1019 G polymorphism and amygdala volume in borderline personality disorder. Genes, Brain and Behavior 7, 306-313.
Jorge A. Sanhueza, Tomás Zambrano, Carlos Bahamondes-Avila, Luis A. Salazar,
Association of Anxiety-Related Polymorphisms with Sports Performance in Chilean Long Distance Triathletes: A Pilot Study.
Journal of Sports Science and Medicine(15), 554 - 561.
| Copyright 2001-2017 | All rights reserved. | LEGAL
NOTICES | Publisher
It is forbidden the total or partial reproduction
of this web site and the published materials, the treatment of its database,
of transition and for any means, either electronic, mechanic or other
methods, without the previous written permission of the JSSM.