Serotonin Transporter Polymorphism 5-HTTLPR Research Articles

Serotonin transporter 5-HTTLPR polymorphism and escitalopram treatment response in patients with major depressive disorder

BackgroundThere is no doubt that genetic factors have the potential to predict the therapeutic outcomes of antidepressants in patients with major depressive disorder (MDD). This study investigated the association between genetic variants involved in serotonin signaling and brain-derived neurotrophic factor (BDNF) with the response to escitalopram treatment in patients with MDD. We focused on examining the influence of 5-HTTLPR (ins/del), HTR2A rs9316233, BDNF rs962369, CYP2C19 and CYP2D6 on the clinical response to escitalopram.MethodsThe patients were recruited from outpatient psychiatric clinics in Košice between 2020 and 2022. Patients received escitalopram for 12 weeks at a fixed dose of 10 mg daily. Clinical assessment was done at baseline and after 4, 8, and 12 weeks using the 21-item Hamilton Depression Rating Scale (HAMD-21).ResultsAt the end of week 12, 57 (65%) patients were defined as responders to escitalopram treatment, while 31 (35%) patients were non-responders. Genotyping revealed that carriers of the short allele (S) of 5-HTTLPR exhibit a significantly lower therapeutic response to escitalopram measured by HAMD-21 than the long allele (L) carriers (p = 0.01). Adjusting for CYP2C19 and CYP2D6 metabolizer genotypes did not modify the observed relationship between 5-HTTLPR and treatment response. No significant associations were found for HTR2A rs9316233 or BDNF rs962369 variants and the treatment response.ConclusionsThese findings underscore the utility of 5-HTTLPR genotyping in guiding escitalopram therapy for MDD patients. Further research with larger cohorts is warranted to validate these results and elucidate additional genetic determinants of antidepressant efficacy.

Molecular genetic associations between a prominent serotonin transporter gene polymorphism (5-HTTLPR/rs25531) and individual differences in tendencies toward autistic traits and generalized internet use disorder in China and Germany.

BackgroundThe serotonin transporter polymorphism 5‐HTTLPR is an extensively investigated genetic marker of autistic traits or autism spectrum disorder, and recently has also been studied in the realm of internet use disorder (IUD), yet the findings remain controversial. Therefore, the present study aimed to explore associations between 5‐HTTLPR (also including SNP rs25531) and autistic traits/IUD tendencies and to assess whether the relationship between autistic traits and IUD tendencies varies by this genetic marker in participants from China and Germany.MethodsA total of 540 Chinese and 563 German subjects were genotyped for 5‐HTTLPR/rs25531 and completed the Adult Autism Spectrum Quotient questionnaire and the short version of the Internet Addiction Test.ResultsCarriers of the low expressing S'S’ genotype (S, LG) showed significantly higher levels of autistic traits than the high expressing allele (e.g. LA) carriers in both samples. There was no significant effect of 5‐HTTLPR/rs25531 on IUD either in the Chinese or Germany samples, whereas positive correlations between autistic traits and IUD varied by 5‐HTTLPR/rs25531 genotypes and also differed between Chinese and German samples. In the Chinese sample, positive correlations were mainly driven by S'S’ and S'L' carriers, while they were mainly determined by S'L’ and L'L' carriers in the German sample. Further analyses revealed that the associations between autistic traits and IUD tended in parts to be more strongly pronounced in the complete German sample compared to the complete Chinese sample, and also varied depending on 5‐HTTLPR/rs25531 genotypes (in S'S’ carriers: China > Germany; in S'L’ and L'L’ carriers: China < Germany; both in terms of more positive associations).ConclusionsOur findings suggest carriers of low expressing alleles (S, LG) are more likely to show higher autistic traits in both Chinese and German samples. Furthermore, the present work shows that both 5‐HTTLPR/rs25531 and cultural differences might be of relevance to understand associations between autistic traits and IUD tendencies, but this needs to be further backed up.

Cortisol awakening response and additive serotonergic genetic risk interactively predict depression in two samples: The 2019 Donald F. Klein Early Career Investigator Award Paper.

The serotonin system and hypothalamic pituitary-adrenal (HPA)-axis are each implicated in the pathway to depression; human and animal research support these systems' cross-talk. Our work implicates a 5-variant additive serotoninergic multilocus genetic profile score (MGPS) and separately the cortisol awakening response (CAR) in the prospective prediction of depression; other work has shown that the serotonin transporter polymorphism 5HTTLPR predicts CAR and interacts with the CAR to predict depression. We tested the hypothesis that a 6-variant MGPS (original plus 5HTTLPR) would interact with CAR to predict prospective depressive episode onsets in 201 emerging adults using four annual follow-up interviews. We also tested whether MGPS predicted CAR. We attempted replication of significant findings in a sample of 77 early adolescents predicting depression symptoms. In sample 1, MGPS did not significantly predict CAR. MGPS interacted with CAR to predict depressive episodes; CAR slopes for depression steepened as MGPS increased, for risk or protection. No single variant accounted for results, though CAR's interactions with 5HTTLPR and the original MGPS were both significant. In sample 2, the 6-variant MGPS significantly interacted with CAR to predict depression symptoms. Higher serotonergic MGPS appears to sensitize individuals to CAR level-for better and worse-in predicting depression.

Serotonin transporter 5-HTTLPR polymorphism and response to citalopram in terminally ill cancer patients: report of twenty-one cases.

The aim of this study was to examine the effects of the SSRI antidepressant drug citalopram on anxiety, depression and mental adjustment to cancer in terminally ill cancer patients, considering also the 5-HTTLPR genetic polymorphism. A group of twenty-one consecutive patients admitted to the hospice of the Casa di Cura Pineta del Carso (Trieste, Italy) with different types of advanced cancer, who were clinically judged to require treatment with an antidepressive drug, was treated with citalopram for two weeks. The response was determined and related to 5-HTTLPR. Citalopram significantly reduced the scores on the depression and anxiety subscales of the Hospital Anxiety and Depression Scale (HADS). When the effects of citalopram were analyzed in relation to the 5-HTTLPR polymorphism, the HADS depression score was significantly decreased only in patients with the "l/l" allelic variant of the serotonin transporter conferring high functional activity, while the score of the Mini-MAC fatalism scale was significantly increased in patients carrying at least one "s" allele. These preliminary findings seem to indicate that two weeks of treatment with citalopram are effective in reducing depressive symptoms in terminally ill cancer patients. Moreover, the effects of citalopram on fatalism as a strategy of mental adaptation to cancer, and on depressive symptoms depend on the allelic variants of the 5-HTTLPR genotype of the patients. These results seem to encourage the examination of a larger patient sample and of different treatment schedules, as well as a more thorough characterization of fatalism as a coping strategy in cancer patients.

Investigating Direct Links between Depression, Emotional Control, and Physical Punishment with Adolescent Drive for Thinness and Bulimic Behaviors, Including Possible Moderation by the Serotonin Transporter 5-HTTLPR Polymorphism.

Objectives: To examine the relationship between psychological and social factors (depression, emotional control, sexual abuse, and parental physical punishment) and adolescent drive for Thinness and Bulimic behaviors in a large community sample, and to investigate possible genetic moderation.Method: Data were drawn from the Australian Temperament Project (ATP), a population-based cohort study that has followed a representative sample of 2443 participants from infancy to adulthood across 16 waves since 1983. A subsample of 650 participants (50.2% female) of Caucasian descent who provided DNA were genotyped for a serotonin transporter promoter polymorphism (5-HTTLPR). Adolescent disordered eating attitudes and behaviors were assessed using the Bulimia and Drive for Thinness scales of the Eating Disorder Inventory-2 (15–16 years). Depression and emotional control were examined at the same age using the Short Mood and Feelings Questionnaire, and an ATP-devised measure of emotional control. History of sexual abuse and physical punishment were assessed retrospectively (23–24 years) in a subsample of 467 of those providing DNA.Results: EDI-2 scores were associated with depression, emotional control, and retrospectively reported parental physical punishment. Although there was statistically significant moderation of the relationship between parental physical punishment and bulimic behaviors by 5-HTTLPR (p = 0.0048), genotypes in this subsample were not in Hardy–Weinberg Equilibrium. No other G×E interactions were significant. Conclusion: Findings from this study affirm the central importance of psychosocial processes in disordered eating patterns in adolescence. Evidence of moderation by 5-HTTLPR was not conclusive; however, genetic moderation observed in a subsample not in Hardy–Weinberg Equilibrium warrants further investigation.

0263 IMPACT OF THE 5-HTTLPR POLYMORPHISM ON NEURAL RESPONSES TO IMPLICIT THREAT AND FEAR LEARNING AND MEMORY AFTER SLEEP DEPRIVATION

The short (s) allele variant of the serotonin transporter polymorphism 5-HTTLPR, compared to the long (l) allele variant, has been associated with heightened stress reactivity. We explored the moderating impact of this polymorphism on neural correlates of implicit threat detection and fear-associated learning and memory following total and partial sleep deprivation in healthy young adults. 134 participants spent 3 night in the laboratory after being genotyped for 5-HTTLPR. After a baseline night, participants were randomized to total sleep deprivation (SD, n = 35), sleep restriction (SR or half the normal sleep time, n=40), or normal sleep (NS, n = 43). The following morning, the participants completed a fear conditioning and extinction protocol. Fear extinction recall was tested in the evening. Neural responses to implicit threat cues were assessed in the evening before and after randomization. BOLD signals in the amygdala and ventromedial prefrontal cortex (vmPFC) were compared between s/s, s/l, and l/l carriers. ROI analyses were conducted using SPM8 and SPSS. No significant Sleep Group X Genotype interaction was found for fear conditioning, extinction, or extinction recall for the amygdala or vmPFC. For the threat task, a main effect of Genotype was detected for the right amygdala (F(2,129) =3.24, p < 0.05) at baseline, where the s/l group showed lower BOLD activation in response to threatening vs. neutral cues than the l/l and s/s groups. Following the sleep manipulation, the three genotypes no longer differed. The 5-HTTLPR polymorphism does not moderate neural fear-related responses. Heterozygotes (s/l carriers) showed the greatest BOLD reactivity to threat cues in the right amygdala at baseline, but this effect was absent following the sleep manipulation. Sleep loss may override the impact of genotype on neural reactivity to salient cues. This work was supported by the Department of Defense Congressionally Directed Medical Research Program Military Operational Medicine Research Program (MOMRP; Log#11293006). The opinions and assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Army or of the US Department of Defense.

The interaction between 5-HTTLPR and stress exposure influences connectivity of the executive control and default mode brain networks

We recently reported that the serotonin transporter polymorphism 5-HTTLPR moderates the relation between stress exposure and attention-deficit/hyperactivity disorder (ADHD) severity. This gene-environment interaction (GxE) has been previously tied to the processing of emotional stimuli, which is increasingly recognized to be a key factor in ADHD-related impairment. The executive control and default mode brain networks play an important role in the regulation of emotion processing, and altered connectivity of these networks has also been associated with ADHD. We therefore investigated whether resting-state connectivity of either of these networks mediates the relation of 5-HTTLPR and stress exposure with ADHD severity. Resting-state functional magnetic resonance imaging, genetic, and stress exposure questionnaire data was available for 425 adolescents and young adults (average age 17.2 years). We found that 5-HTTLPR S-allele carriers showed a more negative relation between stress exposure and connectivity of the executive control network than L-allele homozygotes, specifically in the pre/postcentral gyrus, striatum, and frontal pole. In the default mode network, we found a positive association between the GxE and supramarginal gyrus connectivity. Connectivity of either network did not significantly mediate the effect of this GxE on ADHD. Opposite effects of stress exposure on connectivity in the executive and default mode networks may contribute to findings that stress exposure is associated with lowered cognitive control and heightened levels of rumination and worrying, for S-allele carriers but not L-allele homozygotes. When combined, these effects on connectivity of both networks may relate to the emotional problems seen in individuals with ADHD.

Brain-Derived Neurotrophic Factor (Val66Met) and Serotonin Transporter (5-HTTLPR) Polymorphisms Modulate Plasticity in Inhibitory Control Performance Over Time but Independent of Inhibitory Control Training.

Several studies reported training-induced improvements in executive function tasks and also observed transfer to untrained tasks. However, the results are mixed and there is a large interindividual variability within and across studies. Given that training-related performance changes would require modification, growth or differentiation at the cellular and synaptic level in the brain, research on critical moderators of brain plasticity potentially explaining such changes is needed. In the present study, a pre-post-follow-up design (N = 122) and a 3-weeks training of two response inhibition tasks (Go/NoGo and Stop-Signal) was employed and genetic variation (Val66Met) in the brain-derived neurotrophic factor (BDNF) promoting differentiation and activity-dependent synaptic plasticity was examined. Because Serotonin (5-HT) signaling and the interplay of BDNF and 5-HT are known to critically mediate brain plasticity, genetic variation in the 5-HTT gene-linked polymorphic region (5-HTTLPR) was also addressed. The overall results show that the kind of training (i.e., adaptive vs. non-adaptive) did not evoke genotype-dependent differences. However, in the Go/NoGo task, better inhibition performance (lower commission errors) were observed for BDNF Val/Val genotype carriers compared to Met-allele ones supporting similar findings from other cognitive tasks. Additionally, a gene-gene interaction suggests a more impulsive response pattern (faster responses accompanied by higher commission error rates) in homozygous l-allele carriers relative to those with the s-allele of 5-HTTLPR. This, however, is true only in the presence of the Met-allele of BDNF, while the Val/Val genotype seems to compensate for such non-adaptive responding. Intriguingly, similar results were obtained for the Stop-Signal task. Here, differences emerged at post-testing, while no differences were observed at T1. In sum, although no genotype-dependent differences between the relevant training groups emerged suggesting no changes in the trained inhibition function, the observed genotype-dependent performance changes from pre- to post measurement may reflect rapid learning or memory effects linked to BDNF and 5-HTTLPR. In line with ample evidence on BDNF and BDNF-5-HT system interactions to induce (rapid) plasticity especially in hippocampal regions and in response to environmental demands, the findings may reflect genotype-dependent differences in the acquisition and consolidation of task-relevant information, thereby facilitating a more adaptive responding to task-specific requirements.

Serotonin transporter polymorphism moderates the effects of caregiver intrusiveness on ADHD symptoms among institutionalized preschoolers.

Research consistently chronicles a variety of mental health difficulties that plague institutionally reared children, including attention-deficit/hyperactivity disorder (ADHD), even if not all institutionalized children evince such problems. In seeking to extend work in this area, this research on gene×environment (GXE) interplay investigated whether the effect of the quality of institutional care-most notably, caregiver intrusiveness-on ADHD symptoms is moderated by the serotonin transporter (5-HTTLPR) polymorphism. One hundred and twenty-seven institutionalized preschoolers were evaluated using the Child Behavior Checklist. Caregiver-rated attention problems and hyperactivity were unrelated to both 5-HTTLPR polymorphism and caregiver intrusiveness. A significant GXE effect, independent of age at placement or duration of institutionalization, emerged, however, consistent with the differential-susceptibility hypothesis: s/s homozygotes manifest the most and least ADHD symptoms when they experienced, respectively, more and less intrusive caregiving. These results provide new insight into the reasons why some institutionalized children, but not others, exhibit ADHD symptoms.

Meta-analysis of the association between a serotonin transporter 5-HTTLPR polymorphism and smoking cessation.

5-HTTLPR is one of the candidate genes influencing addiction. Recent studies have reported that the 5-HTTLPR genotype is associated with smoking behaviour, but its influence is still controversial. Thus, we reviewed the smoking-cessation outcomes among previously reported studies by comparing the 5-HTTLPR polymorphism. In total, eight studies including 3206 participants for the present meta-analysis were assessed and the S/S, S/L and L/L genotypes were compared with respect to smoking-cessation outcomes. The results of comparing 5-HTTLPR genotypes were as follows: odds ratio (OR)=1.044 and 95% confidence interval (CI)=0.751-1.078 for S/S versus S/L; OR=0.862 and 95% CI=0.690-1.077 for S/L versus L/L; and OR=0.924 and 95% CI=0.689-1.433 for S/S versus L/L. We found no significant association between 5-HTTLPR and smoking cessation, but 5-HTTLPR remains an important smoking-related candidate gene.

The serotonin transporter 5-HTTLPR polymorphism in the association between sleep quality and affect

A link between sleep and affect is well-known. Serotonin (5-HT) is associated with the regulation of affective as well as sleep-related processes. A functional polymorphism in the serotonin transporter gene (5-HTTLPR) has been associated with serotonergic functioning. The present study investigated whether allelic variation of this gene moderates the association between nighttime subjective sleep quality and affect the following day. A population-based sample of 361 ethnically homogenous adult female twins underwent a five day protocol based on the experience sampling method (ESM), assessing momentary negative affect, positive affect, and subjective sleep quality repeatedly and prospectively. There was a significant interaction between sleep quality and genotype in predicting positive affect the next day: carriers of one (n=167) or two S-alleles (n=78) had a significantly steeper slope compared to LL carriers (n=116) (χ2=4.16, p=.042 and χ2=3.90, p=.048 respectively). The association between subjective sleep quality and positive affect the next day varied as a function of 5-HTTLPR: it was stronger in carriers of at least one copy of the S-allele compared to homozygous L-carriers, supporting a link between sleep and affect regulation, in which serotonin may play a role. However, these results are preliminary and require replication.

Effect of BDNF Val66Met and serotonin transporter 5-HTTLPR polymorphisms on psychopathological characteristics in a sample of university students

The aims of this study were to evaluate the impact of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on several psychological characteristics in a group of Greek University students and to explore putative interactions with the serotonin-transporter-linked polymorphic region (5-HTTLPR) and serious past adverse experiences. A total of 224 students were genotyped and classified as (a) carriers or noncarriers of the Met allele of the BDNF Val66Met polymorphism and (b) carriers or noncarriers of the S or Lg alleles (S') of the 5-HTTLPR polymorphism. Students were evaluated using a battery of standard psychological tests and answered questionnaires on serious past adverse experiences. The Val/Val BDNF genotype was associated with higher scores in several psychopathological dimensions. When the effect of the BDNF Met allele was examined in relation to 5-HTTLPR, it was restricted to S' noncarriers. Among these students, BDNF Met allele carriers had lower scores compared with noncarriers. The effects of the Met allele on the S' allele noncarriers in the anxiety and phobic anxiety dimensions were more pronounced among individuals who had reported no serious life adversities. There may be a protective role of the BDNF Met allele in several psychopathological features and it is suggested that some of these effects are moderated by 5-HTTLPR.

Genotyping serotonin transporter polymorphisms 5-HTTLPR and rs25531 in European- and African-American subjects from the National Institute of Mental Health’s Collaborative Center for Genomic Studies

A number of studies have suggested DNA sequence variability in the serotonin transporter gene (SLC6A4) between European-American (EA) and African-American (AA) populations, which could be clinically important, given the central role SLC6A4 has in serotonin transmission. However, these studies have had relatively small samples, used self-reported measures of race, and have only tested the promoter-linked polymorphism 5-HTTLPR. Here we genotype 5-HTTLPR and rs25531, a neighboring functional polymorphism, in 954 AA and 2622EA subjects from a National Institute of Mental Health repository sample. Genotyping was performed using fragment analysis by capillary electrophoresis. AA, as compared with EA, groups had lower frequencies of the S allele (0.25 vs 0.43) and SS genotype (0.06 vs 0.19) at 5-HTTLPR, and higher rates of the G allele at rs25531 (0.21 vs 0.075). A rare xL variant at 5-HTTLPR was also more common among AAs (0.017 vs 0.008). When the polymorphisms were redefined into a high- and low-transcription haplotypes, the AA group showed significantly fewer low-transcription variants (χ2=4.8, P=0.03). No genotypes were associated with major depression, any anxiety disorder, or neuroticism in either EA or AA populations. This is the largest study to show SLC6A4 genotype differences between EA and AA populations, and the first to include rs25531. Lack of associations with clinical outcomes may reflect untested moderating environmental influences.

No Moderating Effect of 5-HTTLPR on Associations Between Antenatal Anxiety and Infant Behavior

ObjectiveMaternal antenatal anxiety is associated with an increased risk of behavioral disturbances in offspring. Recent work has suggested that the effect of maternal antenatal anxiety on infant temperament at 6 months is moderated by the serotonin transporter polymorphism 5-HTTLPR, with carriers of the short allele more susceptible to the adverse behavioral outcomes of maternal antenatal anxiety. These findings, however, are yet to be replicated and extended beyond infancy. The aim of the current study was to assess this same potential moderator (5-HTTLPR) in a large population-based cohort study, and to determine whether or not the effects persist into childhood and early adolescence.MethodData from the Avon Longitudinal Study of Children and Parents (ALSPAC) cohort (N = 3,946) were used to assess whether the 5-HTTLPR genotype moderated the association between self-reported maternal antenatal anxiety (Crown Crisp Index) in pregnancy, and child temperament at 6 months (Infant Temperament Questionnaire), and also later behavioral and emotional problems on the Strengths and Difficulties Questionnaire from age 4 to 13 years.ResultsWe found no evidence to suggest that the 5-HTTLPR polymorphism moderated the effects of maternal antenatal anxiety on infant temperament at 6 months or infant behavioral and emotional problems from childhood through to adolescence.ConclusionOur results, based on a large prospective community sample that assessed children from infancy to early adolescence, provide a thorough test of, but no evidence for, a genetic moderation of the effects of maternal antenatal anxiety by 5-HTTLPR.

Analysis of monoaminergic genes, childhood abuse, and dimensions of psychopathy.

Psychopathy is a multidimensional construct characterized by an interpersonally manipulative and emotionally detached personality profile that differentiates it from other antisocial syndromes. Previous research with youth has linked the long allele of the serotonin transporter gene in the presence of environmental stress with the interpersonal and affective traits of psychopathy, but these relationships have yet to be examined in relation to adult psychopathy. Consequently, we examined how serotonin transporter (5-HTTLPR) polymorphisms, monoamine oxidase-A (MAO-A) variants, and childhood abuse measured with the Childhood Trauma Questionnaire relate to dimensions of psychopathy in a forensic sample of 237 men with elevated levels of environmental adversity. We found that the emotional deficits characterizing the affective factor of psychopathy, as measured by the Psychopathy Checklist: Screening Version, were highest among carriers of the 5-HTT long allele. Furthermore, the impulsive and irresponsible lifestyle features of psychopathy were higher among low-activity than high-activity MAO-A carriers. These genetic effects were unexpectedly not moderated by a history of childhood abuse. Results provide evidence on the molecular genetics correlates of psychopathic traits in adulthood, relationships that should be investigated further in future research.

セロトニントランスポーター遺伝子多型(5HTTLPR)による個人差を考慮した森林散策頻度とメンタルヘルスとの関連

セロトニントランスポーター遺伝子多型(5HTTLPR)による個人差を考慮した森林散策頻度とメンタルヘルスとの関連

Human fear reconsolidation and allelic differences in serotonergic and dopaminergic genes

Fear memory persistence, central for the development and maintenance of anxiety disorders, is partially genetically controlled. Recently, consolidation and reconsolidation processes have been reported to affect fear memory stability and integrity. This study explored the impact of reconsolidation processes and genetic make-up on fear reacquisition by manipulating reconsolidation, using extinction performed outside or inside a reconsolidation interval. Reacquisition measured by skin conductance responses was stronger in individuals that extinguished outside (6 h) than inside (10 min) the reconsolidation interval. However, the effect was predominantly present in val/val homozygotes of the functional val158met polymorphism of the catechol O-methyltransferase (COMT) enzyme and in short-allele carriers of the serotonin-transporter length 5-HTTLPR polymorphism. These results demonstrate that reconsolidation of human fear memory is influenced by dopamine and serotonin-related genes.

Should pharmacogenetics be incorporated in major depression treatment? Economic evaluation in high- and middle-income European countries

The serotonin transporter 5-HTTLPR polymorphism moderates response to SSRIs and side-effect burden. The aim of this study is to quantify the cost-utility of incorporating 5-HTTLPR genotyping in drug treatment of major depressive disorder (MDD). We previously reported a theoretical model to simulate antidepressant treatment with citalopram or bupropion for 12 weeks. The drugs were alternatively selected according to an 'as usual' algorithm or based on response and tolerability predicted by 5-HTTLPR profile. Here we apply this model to conduct a cost-utility analysis in three European regions with high GDP (Euro A), middle GDP (Euro B) and middle-high GDP (Euro C). In addition we test a verification scenario in which citalopram+bupropion augmentation is administered to individuals with the least favorable 5-HTTLPR genotype. Treatment outcomes are remission and Quality Adjusted-Life Weeks (QALW). Cost data (international $, year 2009) are retrieved from the World Health Organization (WHO) and national official sources. In base-case scenario incremental cost-effectiveness ratio (ICER) values are $1147 (Euro A), $1185 (Euro B) and $1178 (Euro C). From cost-effectiveness acceptability curve (CEAC), the probability of having an ICER value below WHO recommended cost-utility threshold (3 GDP per capita=$1926) is >90% in high-income countries (Euro A). In middle- income regions, these probabilities are <30% (Euro B) and <55% (Euro C) respectively. All estimates are robust against variations in treatment parameters, but if genetic test cost decreases to $100, pharmacogenetic approach becomes cost-effective in middle-income countries (Euro B). This simulation using data from 27 European states suggests that choosing antidepressant treatment from the results of 5-HTTLPR might be a cost-effective solution in high income countries. Its feasibility in middle income countries needs further research.

Carrot or stick? Impact of serotonin transporter (5-HTTLPR) polymorphism and reward and punishment signaling in the brain

Carrot or stick? Impact of serotonin transporter (5-HTTLPR) polymorphism and reward and punishment signaling in the brain

No association between the serotonin transporter gene polymorphism 5-HTTLPR and cyclothymic temperament as measured by TEMPS-A

Background Temperaments are stable personality traits that can be considered subsyndromal risk factors of psychiatric illnesses. The 5-HTTLPR polymorphism of the serotonin transporter gene has been found to be associated with affective temperaments, particularly the cyclothymic temperament, as measured with the Temperament Evaluation of Memphis, Pisa, Paris and San Diego—autoquestionnaire version (TEMPS-A). In this study we have attempted to replicate this finding in a population-based sample which is five times as large as the sample used in the original study. Methods The 21 items of the cyclothymic subscale of TEMPS-A was filled in by 691 individuals (404 females, 287 males, 18–40 years) randomly recruited from the general population. DNA was isolated from saliva, and the serotonin transporter polymorphism 5-HTTLPR was genotyped using the polymerase chain reaction and fragment analysis. Results No significant association was found between 5-HTTLPR genotype and TEMPS-A score, neither when analysing by an additive allelic model nor when the different genotypes and allelic dominance were examined. Furthermore, no association was observed after gender stratification, or when TEMPS-A was analysed as a dichotomous measure, using a cut-off of ≥ 11 positive item responses. Limitations Although being used in clinical settings, TEMPS-A has not been officially validated in Norway. Conclusions This study suggests that there is no association between the 5-HTTLPR polymorphism and cyclothymic temperament as measured by TEMPS-A.