5-HTT Polymorphisms Research Articles

Tailoring Type II Diabetes Treatment: Investigating the Effect of 5-HTT Polymorphisms on HbA1c Levels after Metformin Initiation.

To investigate the effect of serotonin transporter (5-HTT) polymorphisms on change in HbA1c levels six months after metformin initiation in type 2 diabetes patients. Participants of PROVALID (PROspective cohort study in patients with type 2 diabetes mellitus for VALidation of biomarkers) within the GIANTT (Groningen Initiative to ANalyse Type 2 Diabetes Treatment) cohort who initiated metformin were genotyped for combined 5-HTTLPR/rs25531 (L∗L∗, L∗S∗, and S∗S∗) and 5-HTT VNTR (STin 2.12, 12/-, and 10/-) polymorphisms, respectively. Multiple linear regression was applied to determine the change in HbA1c level from baseline date to six months across 5-HTTLPR/VNTR genotype groups, adjusted for baseline HbA1c, age, gender, triglyceride level, low-density lipoprotein level, and serum creatinine. 157 participants were included, of which 56.2% were male. The average age was 59.3 ± 9.23 years, and the mean baseline HbA1c was 7.49% ± 1.21%. 5-HTTLPR was characterized in 46 patients as L∗L∗, 70 patients as L∗S∗, and 41 patients as S∗S∗ genotypes. No significant association was found between 5-HTTLPR and 5-HTT VNTR genotypes and change in HbA1c after adjustments. 5-HTT polymorphisms did not affect HbA1c levels six months after the start of metformin. Further long-term studies in large samples would be relevant to determine which polymorphisms can explain the variation in response to metformin treatment.

Serotonin, ghrelin, and motilin gene/receptor/transporter polymorphisms in childhood functional constipation.

Functional constipation is the most common form of constipation, and its exact aetiology is still unclear. However, it is known that deficiencies in hormonal factors cause constipation by changing physiological mechanisms. Motilin, ghrelin, serotonin acetylcholine, nitric oxide, and vasoactive intestinal polypeptide are factors that play a role in colon motility. There are a limited number of studies in the literature where hormone levels and gene polymorphisms of serotonin and motilin are examined. Our study aimed to investigate the role of motilin, ghrelin, and serotonin gene/receptor/transporter polymorphisms in constipation pathogenesis in patients diagnosed with functional constipation according to the Rome 4 criteria. Sociodemographic data, symptom duration, accompanying findings, the presence of constipation in the family, Rome 4 criteria, and clinical findings according to Bristol scale of 200 cases (100 constipated patients and 100 healthy control) who applied to Istanbul Haseki Training and Research Hospital, Pediatric Gastroenterology Outpatient Clinic, between March and September 2019 (6-month period) were recorded. Polymorphisms of motilin-MLN (rs2281820), serotonin receptor-HTR3A (rs1062613), serotonin transporter-5-HTT (rs1042173), ghrelin-GHRL (rs27647), and ghrelin receptor-GHSR (rs572169) were detected by real-time PCR. There was no difference between the two groups in terms of sociodemographic characteristics. Notably, 40% of the constipated group had a family history of constipation. The number of patients who started to have constipation under 24 months was 78, and the number of patients who started to have constipation after 24 months was 22. There was no significant difference between constipation and control groups in terms of genotype and allele frequencies in MLN, HTR3A, 5-HTT, GHRL, and GHSR polymorphisms (p<0.05). Considering only the constipated group, the rates of gene polymorphism were similar among those with/without a positive family history of constipation, constipation onset age, those with/without fissures, those with/without skin tag, and those with type 1/type 2 stool types according to the Bristol stool scale. Our study results showed that gene polymorphisms of these three hormones may not be related to constipation in children.

Studies on candidate genes for lithium prophylaxis performed at the Poznan University of Medical Sciences

Lithium is a drug of choice as a mood-stabilizer for the maintenance treatment of bipolar disorder. The prophylactic efficacy of lithium can be determined by genetic factors, partially related to a predisposition to bipolar disorder. In the field of psychiatric genetics, the first decade of the 21st century was dominated by the "candidate gene" research. In this paper, the studies on candidate genes connected with lithium prophylaxis performed at the Poznań University of Medical Sciences in 2005-2018 are presented. During this time, the polymorphisms of multiple genes have been investigated, many of which are also connected with a predisposition to bipolar illness. The associations with lithium prophylactic efficacy were found for the polymorphisms in 5HTT, ACP1, ARNTL, BDNF, COMT, DRD1, FKBP5, FYN, GLCC, NR3C1, and TIM, genes, but not those in 5HT2A, 5HT2C, DRD2, DRD3, DRD4, GRIN2B, GSK-3β, MMP-9, and NTRK2 genes. The polymorphism of the GSK-3β gene was found to be associated with the kidney side-effects occurring during lithium therapy. Possible roles for these genes in both the mechanism of lithium prophylactic activity and pathogenesis of bipolar mood disorder were discussed.

Brain gain-Is the cognitive performance of domestic hens affected by a functional polymorphism in the serotonin transporter gene?

The serotonin transporter (5-HTT) plays an important role in regulating serotonergic transmission via removal of serotonin (5-HT) from synaptic clefts. Alterations in 5-HTT expression and subsequent 5-HT transmission have been found to be associated with changes in behaviour, such as fearfulness or activity, in humans and other vertebrates. In humans, alterations in 5-HTT expression have been suggested to be able to lead to better learning performance, with more fearful persons being better at learning. Similar effects of the variation in the 5-HTT on fearfulness have been found in chickens, and in this study, we investigated effects on learning. Therefore, we tested 52 adult laying hens, differing in their functional 5-HTT genotype (W/W, W/D and D/D) in an operant learning paradigm in three different phases (initial learning, reversal learning and extinction) and in a tonic immobility test for fearfulness. We found that the 5-HTT polymorphism affects the initial learning performance of laying hens, with homogeneous wild-type (W/W) hens being the slowest learners, and the most fearful birds. W/W hens, showed significantly more choices to solve the initial learning task (LME, p = 0.031) and had the highest latencies in a tonic immobility test (p = 0.039), indicating the highest fearfulness. Our results provide interesting first insights into the role of 5-HTT in chickens and its sensitive interaction with the environment. We further suggest that the 5-HTT gene can be an interesting target gene for future breeding strategies as well as for further experimental studies.

Absence of a significant interaction of two common NOS1 and 5-HTT polymorphisms on sensorimotor gating in humans.

The neurotransmitter serotonin has been critically implicated in the pathogenesis of several mental disorders. The serotonin transporter (5-HTT) is a key regulator of serotonergic neurotransmission and its genetic variability is associated with increased risk of psychopathology. One well known polymorphic locus in the 5-HTT gene affecting its expression is a tandem repeat in the promoter region (5-HTTLPR). It has been reported that 5-HTT is functionally coupled with the neuronal nitric oxide synthase (NOS1 or nNOS), an enzyme catalyzing the production of nitric oxide (NO). We have previously demonstrated that a tandem repeat polymorphism in the promoter of NOS1 exon 1f (Ex1f-VNTR) is associated with sensorimotor gating, a marker of inhibitory processing and a well established endophenotype of several neuropsychiatric disorders. Here we investigated the combined genetic effects of NOS1 Ex1f-VNTR and 5-HTTLPR on sensorimotor gating, measured by prepulse inhibition (PPI) of the acoustic startle reflex, in 164 healthy adults. We found no evidence for the interaction between NOS1 Ex1f-VNTR and 5-HTTLPR on PPI. PPI was associated with NOS1 Ex1f-VNTR, but not 5-HTTLPR. Our data suggest that while NOS1 plays a role in sensorimotor gating, the nitrergic pathway of gating regulation does not involve the action of 5-HTT.

Association of antibody titers and 5-HTTLPR gene polymorphisms in pediatric autoimmune neuropsychiatric disorder associated with streptococci

Introduction. It has been hypothesized that pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) etiology results from an abnormal immune response to streptococcal infection. There is evidence that the serotonergic system is involved in both obsessive-compulsive disorder (OCD) physiopathology and immunological processes. In the 5’ promoter region of 5-HTT, gene encoding for the serotonin transporter we can find the 5-HTTLPR polymorphism that has been associated with OCD. Being PANDAS a disorder with OCD symptoms and likely immune abnormalities, 5-HTT polymorphisms may be particularly relevant for this disorder. Objective. This study aimed to test the association between the 5-HT genotypes and the presence of serum antibodies in patients with PANDAS. Method. We compared the genotype frequencies and serum anti-streptococcal, anti-neural, and anti-enolase antibodies titers between 56 patients with PANDAS and 20 healthy controls from Mexico and Cuba. Results. Antibody titers were higher (anti-enolase, anti-streptococcal) in PANDAS patients compared to healthy controls. No differences in anti-neural antibody levels between both groups were detected. The anti-enolase and anti-neural antibody titer increased according to the polymorphism of the PANDAS patients as follows: LL &gt;SL &gt;SS. Discussion and conclusion. This is the first study evaluating the association between the 5-HTTLPR genotypes and antibody titers in PANDAS patients. Associations between polymorphisms in serotonergic genes and immune response could provide valuable information about the interaction between both systems. Our results suggest an association between the S allele and elevated antibody levels in PANDAS patients.

Examination of associations between personality traits, and polymorphisms of MAO-A and 5-HTT with the severity of menopausal symptoms and depression levels.

The aim of the present study was to investigate the association between different personality traits with monoamine oxidase A (MAO-A) and serotonin transporter (5-HTT), and to examine their effects on the severity of menopause symptoms as well as the levels of depression in menopausal women. The study was designed as an analytical cross-sectional study, performed on 132 healthy post-menopausal women in Iran. Personality was assessed using the Revised Edition of the NEO Personality Index (Neuroticism-Extroversion-Openness-Five Factor Inventory). The symptoms score sheet, used for measuring menopausal symptoms, was used to classify the participants according to their menopausal symptoms. Furthermore, Beck Depression Inventory short version was also used to assess depressive symptoms. Examination of blood samples taken from all participants was to identify DNA polymorphisms of 5-HTT using PCR. The results of the present study showed that a high level of neuroticism (P<0.0001), low levels of extroversion (P<0.002), an openness to experience (P=0.039) and conscientiousness (P=0.001) were all positively associated with the severity of menopausal symptoms. In addition, a high level of neuroticism (P<0.0001), low levels of extroversion (P<0.0001), and a low level of agreeableness (P<0.024) and conscientiousness (P<0.0001) were all positively associated with depressive symptoms. There was no statistically significant association between MAO-A and 5-HTT polymorphisms with menopause and depression scores. Based on these results, there appears to be a significant association between personality traits with both depression and menopausal symptoms. Identification of homogeneous groups of women who are predisposed to depression and severe menopausal symptoms may allow for the implementation of early prevention programs.

The association of genetic polymorphisms in serotonin transporter and catechol-O-methyltransferase on temporomandibular disorders and anxiety in adolescents.

Temporomandibular disorder (TMD) is a multifactorial condition involving environmental, psychological and genetic factors. The aim of this case-control study was to evaluate the influence of genetic polymorphisms in 5HTT and COMT on TMD and anxiety in adolescents. TMD was diagnosed and classified according to the RDC/TMD criteria. For case group, the following TMD categories were used: myofascial pain, disc displacement, arthralgia and painful TMD (myofascial and arthralgia). Anxiety levels were assessed according to the State-Trait Anxiety Inventory. Genomic DNA was extracted, and genetic polymorphisms were genotyped by TaqMan chemistry and endpoint analysis. Logistic multivariate regression was used to analyse the associations between TMD types and genotypes, anxiety level and genotypes, using an adjusted odds ratio (ORa ; CI 95%) that considered the gender. In 5HTT, the rs1042173 was associated with painful TMD (arthralgia and myofascial pain) (ORc =1.97; CI 95%: 1.02-3.77; P=0.04). Polymorphisms in COMT rs4818 were significantly associated with myofascial pain (ORc =2.15; CI 95%: 1.08-4.29; P=0.02) and were borderline for painful TMD (ORc =1.85; CI 95%: 0.97-3.51; P=0.06) and disc displacement (ORc =2.42; CI 95%: 1.00-5.87; P=0.05). The rs6269 was borderline for myofascial pain (ORc =1.82; CI 95%: 0.92-3.59; P=0.08) and disc displacement (ORc =2.38; CI 95% 0.95-5.97; P=0.06) and also was associated with anxiety (ORa =2.34; CI 95% 1.04-5.25; P=0.03). Polymorphisms in 5HTT and COMT are associated with TMD in adolescents. Moreover, polymorphism in COMT is associated with anxiety in adolescents.

Fear but not social behaviour is affected by a polymorphism in the 5’-flanking region of the serotonin transporter (5-HTT) gene in adult hens

The serotonin transporter gene (5-HTT) is involved in the regulation of the neural serotonin. Polymorphisms in the 5-HTT gene have been described in many species to be involved in physiological processes and emotions. A functional polymorphism in the 5´-flanking region of the 5-HTT gene is known from chickens, with a deletion-allele (D), which is associated with an increased 5-HTT expression, in comparison to the wild-type-allele (W). In domestic populations, the majority of hens carry the W-allele. The regulatory changes of the 5-HTT are accompanied in chickens, as in humans, by modulations of fear. Beside these effects on fear, the understanding of potential functional consequences on the social behaviour in the gregarious chicken is lacking. Thus, we here investigated whether the 5-HTT polymorphism with three genotypes (WW, WD, DD), is not only linked to fear-related behaviour, but affects also socio-positive and -negative behaviours of adult hens. Our data confirmed the effects on fear-related behaviour. WW hens showed highest levels of fear. Interestingly, no differences in the social behaviours were present between the hens of the different 5-HTT genotypes. We further discuss implications for potential evolutionary pathways via natural selection and / or artificial selection through domestication of the 5-HTT polymorphism, which might have enabled a stable social lifestyle in the wild ancestors of modern chickens.

Polymorphism of serotonin transporter gene in male subjects with antisocial behavior and MMA fighters

In our study, the frequencies of serotonin transporter gene (5-HTT) polymorphisms and their combinations are compared in the healthy male subjects with antisocial behavior, in general, and in those with its particular forms, as well as in the reference group of MMA fighters. Subjects convicted of unlawful actions were classified into those convicted of violent crimes or non-violent ones. The group of subjects convicted of violent crimes was further subdivided into those convicted of murder, or robbery, or of inflicting grave body injuries. The group of MMA fighters was selected from the subjects without a prior history of antisocial behavior or criminal record in the subjects or their relatives. The frequency of D allele in the groups of convicted subjects and MMA fighters was higher, than in the population sample. Furthermore, the frequencies of D/D and 12/12 genotype combinations were shown to be higher in the group of convicted subjects, especially, in habitual criminals and those convicted of grave crimes or murder. The predisposition of MMA fighters to violent behavior and physical aggressive suppression of an opponent is successfully implemented in their professional career; however, this behavioral pattern appears to represent the controlled aggression.

Anxiety and genetic polymorphisms in catechol-O-methyltransferase (COMT) and serotonin transportation gene (5HTT) are associated with benign migratory glossitis

The aim of this case-control study was to investigate whether benign migratory glossitis (BMG) is associated with catechol-O-methyltransferase (COMT) and serotonin transportation gene (5HTT) polymorphisms and anxiety. The study comprised 43 patients with BMG and 114 patients without a history of BMG. We used the Hamilton Anxiety (HAM-A) rating scale to assess each individual's anxiety. We collected DNA from buccal cells and analyzed polymorphisms of COMT and 5HTT. We conducted statistical evaluations by using SPSS software (SPSS Inc., Chicago, IL) and STATA (StataCorp, College Station, TX). Alpha value was set at 0.05. Overall anxiety level was significantly higher in the case group than in the control group (P < .001). In adjusted multiple logistic regression, the COMT markers were not associated with BMG. Individuals with the CC genotype, in rs3813034 of 5HTT, presented an odds ratio (OR) of 2.85 (95% confidence interval [CI] 1.03-7.82; P = .042). Individuals with the TT genotype, in the rs1042173 of 5HTT, presented an OR of 3.77 (95% CI 1.32-10.74; P = .013). For each incremental increase in the anxiety score, there was an 8% increase in the probability of BMG (ORa=1.08; 95% CI 1.03-1.14; P = .007). Anxiety increases the risk of BMG. Moreover, the occurrence of BMG was associated with polymorphisms in the 5HTT gene.

Clinical and Biochemical Correlations of Aggression in Young Patients with Mental Disorders

Hyperdopaminergia has been identified at impulsive or psychotic patients, the polymorphism of COMT or other enzymes that metabolize dopamine could be involved. The deficiencies of the serotoninergic system in suicidal behaviour has been mentioned by many studies that indicate the reduction of 5-HT, 5-HIAA in CSF or 5-HTT polymorphism. Young patients with psychotic or depression symptoms manifest, frequently, aggressive and self-harm behaviour. Besides the association between the young age and the aggressivity of the patients with serious mental disorders, our study shows gender differences and this matter is sustained by hormonal factors. The study was conducted at the Gheorghe Preda Psychiatric Hospital in Sibiu. The study comprises 52 patients aged between 18 and 35 who were diagnosed with the diagnosis of Schizophrenia, Bipolar Affective Disorder, Depressive Episode and Major depressive disorder according to the DSM-5 criteria. Evaluation of the severity of psychiatric and depressive symptomathology were assessed with Brief Psychiatric Rating Scale and Beck Depression Inventory; aggression and self-aggression in the patients with Schizophrenia, respectively with Bipolar disorder, depressive episode and Major depression disorder were assessed with Buss Perry Aggression Questionnaire and Suicide Intent Scale. Regarding the severity of aggression in the young patients from our study (Buss Perry scale score), male gender is higher than female gender: higher percentages in males (35% and 10%) than in females (16 and 0%). Determining aggression in schizophrenia is possible due to COMT polymorphism that lead to impulsivity or psychotic symptoms. The study show a significant positive correlation between the severity of symptoms of schizophrenia and aggression. From the analysis of the severity of depression in young patients (SIS score) it is noted that its severity is higher in the female gender. Women had higher scores of moderate depression (58%) and severe (26%) than men (37 and 25%, respectively). This relationships could be possible due to the polymorphism of the gene encoding the 5-HTT serotonin transporter related with serotonin deficiency.The study do not show a significant positive correlation between the severity of the depressive symptomatology and the degree of the suicide intent.

5-HTT mRNA level as a potential biomarker of treatment response in patients with major depression in a clinical trial

ObjectivesTo investigate whether the serotonin transporter (5-HTT or SERT or SLC6A4) mRNA level could be used as a biomarker of treatment response in patients with major depression treated with different antidepressants while controlling related factors. MethodsOne hundred and nineteen patients with major depression were recruited; all genotyped for the 5-HTT polymorphism concerning 5-HTTLPR, rs25531, and STin2 VNTR, provided demographic data and completed relevant questionnaires. Duloxetine and paroxetine were administered over 32 weeks to these patients. The Hamilton depression rating scale (HDRS) and 5-HTT mRNA level were evaluated at baseline (Week 0), and at 8, 16, 24 and 32 weeks. ResultsImprovement in depressive symptoms (HDRS score declined) and increasing in 5-HTT mRNA level were found with longer duration of antidepressant treatment in patients with major depression. Patients with more 5-HTTPR long-form alleles and STin2.12 alleles had poor antidepressant treatment response. Duloxetine may give a better treatment response than paroxetine. Using structural equation modeling (SEM), the 5-HTTLPR long-form had a direct positive association with the 5-HTT mRNA level and an indirect adverse relationship with the 5-HTT mRNA level through neuroticism and previous suicide attempts. ConclusionThe 5-HTT mRNA level increased and correlated with the treatment response (HDRS score improvement) under 32-weeks antidepressants treatment clinical trial. We speculate that the 5-HTT mRNA level may be used as a potential biomarker of antidepressant treatment response.

Effects of genes to psychological factors in sports

With the human genome project, in addition to determining the number, structure and physical maps of our genes which were previously supposed to be between 20-25 thousands, genetic regions affecting athletic performance have also been identified.It has been determined that endurance, athletic ability and musculoskeletal as well as central nervous system (CNS) are effective in succeeding in todayÂ’s sporting events and play an important role in performance. Parameters affecting psychological performance such as stress, anxiety, aggression are effective in determining sportive achievements. Determining the genetic predisposition of the athletes in stressful environments or in sports where stress is prominent allows them to be guided by psychologists at an early age and contributes to sporting success. Related to the behavioral characteristics of the athletes, genes leading to resistance to stress, personality traits and aggressive behaviours like 5-HTT, DRD4, DRD5, ADRD1, COMT, BDNF, NRG1, GLUT4 and SLC2A4 and polymorphisms within these genes have been investigated in our review.

Revisión sistemática de la evidencia de existencia de marcadores genéticos en la respuesta al litio en pacientes con trastorno bipolar tipo i

IntroductionThe optimisation of the treatment and the prevention of bipolar disorder typeI is essential. Several studies have described a possible relationship between genetic factors and lithium responders. The aim of this study is to present a systematic review on the evidence of this relationship. Material and methodsThe review is based on PRISMA recommendations. The PubMed, Scopus, Web of Science and PsycInfo databases were used. ResultsA total of 396 articles were found, of which only 5 were critically read, 2 of medium quality and the rest of low quality (due to the methods). DiscussionLike the studies included in the introduction, it can be shown that biomarkers of lithium response could lead to individualised treatment. ConclusionsVariants rs17026651, GADL1 IVS8+48delG and rs17026688 and patients carrying 5-HTT polymorphisms associated with reduced transcriptional activity could be useful biomarkers of lithium response in patients with bipolar disorder typeI. Further studies are required in order to check these results and to analyse other genetic relationships.

Suicide attempt in mental disorders (MeDi): Association with 5-HTT, IL-10 and TNF-alpha polymorphisms

BackgroundMental disorders (MeDi) and suicide attempts (SA) are influenced by environmental and genetic factors. Genetic polymorphism studies have identified some candidate genes for suicidal behaviour in people with MeDi. ObjectiveTo evaluate MeDi and SA in relation to the presence of rs2020933 (5-HTT), rs1800871 (IL-10) and rs1800629 (TNF-α) polymorphisms. MethodsA questionnaire for identification and general data, a brief quality of life assessment (WHOQOL-brief), the scale of suicide ideation by Beck and the MINI International Neuropsychiatric Interview were used in this study. DNA was obtained using buccal mucosa swab samples, and genotyping was performed using real-time polymerase chain reaction. A total of 306 patients were assessed with MeDi; 161 patients had MeDi and a history of SA, and 145 patients had MeDi and no history of SA. The study had 175 subjects in the control group. ResultsThe TNF-α rs1800629 -308A/G genotype was significantly associated with function as a protection factor in the control group compared with MeDi without SA. The TNF-α rs1800629 -308G allele appeared as risk factor for MeDi compared to the control group, for female gender. Additionally, the −308A/G + A/A genotype appeared as protection factor for the control group compared to the group with MeDi. For TNF-α, the −308G allele appeared as risk factor for the number of SA (1 time) compared to the control group. ConclusionThe IL-10 (rs1800871) and 5-HTT (rs2020933) SNPs were considered to have inadequate statistical power. The rs1800629 (TNF-α) polymorphism may be associated with MeDi without SA, MeDi in females and the number of SA (1 time) in the studied group.

The 5-HTT gene polymorphisms correlated with the clinical manifestations of depression

Objective To determine the potential correlation of 5-HTT gene polymorphisms (5-HTTLPR and STin2) with clinical manifestations in depression. Methods A total of 401 depressed patients, all of Chinese Han region, were collected and genotyped by polymerase chain reactions (PCR). All patients were evaluated using a 17-item Hamilton depression rating scale (HAMD-17) and Hamilton anxiety rating scale (HAMA), and then associated analysis was applied. Results (1) The age of onset in patients with L/S genotype of 5-HTLPR polymorphism were much younger than that of patients with L/L and S/S genotype (F=3.281, P=0.039). Besides, there was also a significant difference of HAMA1 (anxious mood) scores among patients with different genotypes for 5-HTTLPR polymorphism, where the scores of those with L/S genotype were the highest (2.34±0.80, P=0.010). (2) The scores of HAMD10 (mental anxiety), HAMA1 (anxious mood), HAMA3 (fear) and mental anxiety factor were higher in patients with 12/10 genotype than patients with 12/12 and 10/10 genotype for STin2 polymorphism (2.40±0.83, 2.38±0.90, 1.42±1.04, 14.60±4.26 respectively; P value: 0.014, 0.044, 0.03 and 0.006 respectively). The scores of HAMD10(mental anxiety) and mental anxiety factor were (2.11±0.77), ( 12.96±3.78) in the 12/12 genotype patients, and significantly lower than that in the 12/10 genotype patients (adjusted P value: 0.018, 0.006). Conclusions A positive association of the 5-HTT polymorphisms with anxious symptoms in depressed patients is revealed. These findings might provide some evidences for the clinical phenotype and optimization of depression treatment. Key words: 5-HTT; Gen polymorphism; Depression

The analysis of anxiety and mood in healthy late-reproductive-stage women with regard to hormonal and genetic factors.

The purpose of this study was to determine whether anxiety and mood disorders in late-reproductive-stage women are related to the serotonin transporter and monoamine oxidase A gene polymorphisms. Research instrument used in this study were the State-Trait Anxiety Inventory and the UWIST Mood Adjective Checklist. The 44-bp VNTR polymorphism in the 5-HTT (SLC 6A4) promoter region and the 30-bp VNTR polymorphism in the MAO-A promoter region were analyzed. The study included 345 healthy Polish women in the late reproductive stage. The mean age of the participants was 42.3 ± 4.5 years. State anxiety was observed in 16.8 % of the women and trait anxiety in 14.5 %. There were no statistically significant differences in the mood and the mean levels of anxiety depending on the presence of the polymorphisms analyzed in this study. Depressed mood is frequent among healthy women in the late reproductive stage. Anxiety is definitely less common. The study did not demonstrate the relationship between the 5-HTT and MAO-A gene polymorphisms, and the severity of anxiety and mood disorders in healthy late-reproductive-stage women.

The Relationship between Personality Traits, the 5HTT Polymorphisms, and the Occurrence of Anxiety and Depressive Symptoms in Elite Athletes.

The purpose of this study was to determine the relationship between personality, the serotonin transporter (5HTT) polymorphisms and the occurrence of anxiety and depressive symptoms in elite athletes. 133 healthy participants completed the NEO Five-Factor Inventory (NEO-FFI). The mood states were assessed using the Profile of Mood States (POMS) questionnaire. The athlete’s mental skills were assessed through the Sport Performance Psychological Inventory (IPPS-48). The occurrence of psychiatric and personality disorders was assessed using the Clinical Interview for DSM-IV Disorders. A polymerase chain reaction was employed to identify genotypes at the 5HTTLPR polymorphism. The 5HTTLPR s/s genotype was associated with both neuroticism (p< 0.001) and tension/anxiety symptoms according to the POMS (p<0.02), cognitive anxiety and emotional arousal control according to the IPPS-48 (p<0.01). Significant correlations were proved between neuroticism and symptoms of anxiety and depression (p<0.05). Neuroticism mediates the association between the 5HTTLPR polymorphism and symptoms of cognitive anxiety and emotional arousal control (p<0.05). These results suggest a significant interaction between the 5HTTLPR polymorphism, neuroticism and sport related stress that predict adverse mental health outcomes in athletes. Identification of homogeneous groups of athletes having predispositions to anxiety and depressive symptoms may help to implement early prevention programs.

Serotonin transporter gene (5-HTT) polymorphism and major depressive disorder in patients in Bogotá, Colombia.

The 5-HTT short allele has been controversially associated with an increased risk of major depressive disorder. To determine the association of 5-HTT short allele with major depression in Bogotá, Colombia. We carried out a study of cases (n=68) matched 1:1 with controls by gender and age (±5 years). Major depression was diagnosed using the Mini-International Neuropsychiatric Interview, and 5-HTT polymorphism using PCR. Females were predominant (82.4%). The S (short) allele predominated in cases compared with controls (S: 72.1% vs. 63.2; L (long): 27.9% vs. 36.8%), and the SL genotype was more frequent in cases (SL: 45.6% vs. 36.8%; LL: 27.9% vs. 36.8%; SS: 26.5% vs. 26.5%), although not significantly. There were significant differences in those under age 37, with a predominance of the S allele in cases (p=0.038; OR=2.75; 95% CI: 0.88-8.64). Multivariate analysis, adjusted for comorbid anxiety disorders, showed a significant association of major depression with the SL genotype (p=0.049; OR=3.20; 95% CI: 1.00-10.23); the S allele was close to statistical significance (p=0.063; OR=2.94; 95% CI: 0.94-9.13), and it was statistically significant in cases under 37 years of age (p=0.026; OR=10.79; 95% CI: 1.32-80.36). The SL genotype was associated with major depressive disorder in patients of all ages. The S allele was significantly associated with major depressive disorder in patients under age 37, adjusted for comorbid anxiety disorders.