Serotonin Transporter Gene Polymorphism Research Articles

The Role of Variability in Monoamine Transporter Genes in Sports Physiology

Monoamine transporters (MATs) are responsible for the reuptake of dopamine, serotonin, and noradrenaline, modulating the concentration of these essential brain neurotransmitters and thus regulating behavior, mood, and cognitive functions. The study of the role of various genes in complex physiological processes is a promising area of neurobiology and sport physiology. Here, we summarize mounting evidence linking specific genetic variants of MAT genes to various aspects of sport performance. For example, the allele 10 of the dopamine transporter gene (DAT), the allele L of the serotonin transporter gene (SERT) and single-nucleotide polymorphism rs1805065 (Thr99Ile) of the noradrenaline transporter gene (NET) appear to correlate with higher performance in athletes due to resistance to stress, maintenance of motivation and cognitive behavioral competencies – qualities necessary for achieving success in sport. Thus, physiological performance in various sports may be partially genetically determined and controlled by the MAT genes.

Functional serotonin transporter gene polymorphism and TMS-evoked cortical inhibition and facilitation in PTSD

Functional serotonin transporter gene polymorphism and TMS-evoked cortical inhibition and facilitation in PTSD

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.

Volume of Amygdala Subregions and Plasma Levels of Brain-Derived Neurotrophic Factor and Cortisol in Patients with s/s Genotype of Serotonin Transporter Gene Polymorphism of First-Episode and Drug-Naive Major Depressive Disorder: An Exploratory Study.

The amygdala is a prominent region of the brain that plays a critical role in the pathophysiology of major depressive disorder (MDD). The amygdala is formed from a collection of interconnected substructures (nuclei) that relay signals from multiple brain areas, which suggests that the amygdala has different functions depending on its subregion. There are two main alleles of serotonin transporter gene polymorphism (5-HTTLPR): a 44-bp insertion (l-allele) or deletion (s-allele). The transcriptional activity of the l-allele of the gene is twice that of the s-allele. The present study aimed to investigate the association between the volume of the whole amygdala and subregions of the amygdala in 25 first-episode and drug-naive patients with MDD and 46 healthy controls (HCs) with the s/s genotype of 5-HTTLPR and plasma levels of brain-derived neurotrophic factor (BDNF) or cortisol. No significant difference was observed in the amygdala total and subregion volumes between the HC and MDD groups. No significant difference was found in the plasma levels of BDNF and cortisol between the two groups. In addition, no correlations were found between the total and subregion amygdala volume and plasma levels of cortisol or BDNF.

Association of serotonin transporter gene polymorphism with efficacy of the antidepressant drugs sertraline and mirtazapine in newly diagnosed patients with major depressive disorders.

We examined the association of serotonin receptor transporter gene polymorphism in patients with MDD with the clinical efficacy of mirtazapine (MZ) and sertraline (ST). Newly diagnosed, treatment naïve, 80 MDD patients (aged 18-45) diagnosed using DSM-5 criteria and with Beck's depression inventory score (BDI) score ≥21 were included and randomly divided into two groups of 40 participants and were administered MZ 15-45mg/day or ST 25-200mg/day respectively. Patients were followed up for 6weeks for evaluation of BDI scores. Genotypic evaluation was done and three allele variants were identified based on the polymerase chain reaction fragment sizes: short (S; 486bp), long (L; 529bp), or extralong (XL; 612 or 654bp) and classified into five genotypes: S/S,S/L, L/L, S/XL, and L/XL. We found that 32.5% patients belonged to the S/S genotype, suggesting that individuals with the SS genotype are at higher risk of developing MDD. No statistically significant association was seen with ST or MZ groups on the basis of genotypes. Clinically significant improvement was observed with a more than 50% reduction in BDI scores at 6weeks of treatment with both drugs. Identification of risk population can be carried out by genotype testing. Prior genotyping in MDD patients might help to predict a better clinical outcome with antidepressants.

Role of serotonin transporter and receptor gene polymorphisms in treatment response to selective serotonin reuptake inhibitors in major depressive disorder.

Significant challenges in the management of major depressive disorder include the lag period from treatment initiation to an evident response, low response rates and unpredictable disparities in outcome between patients. As a large part of these has been linked to genetic mechanisms, we tried to establish a relationship between genes associated with serotonin neurotransmission and outcome to selective serotonin reuptake inhibitor (SSRI) treatment. One hundred and twenty-five patients with moderate to severe depression [at least 15 on the Hamilton Depression (HAM-D) Rating Scale] being started on SSRI were recruited. Those with a reduction of at least 50% from baseline or an absolute score of 7 or less after 8weeks of treatment were considered as responders. The serotonin transporter linked polymorphic region 5HTTLPR, serotonin transporter intron 2 (STin2) polymorphism and the 5-HT receptor 1A rs6295 polymorphisms were studied in association with outcome. The l/l genotype of the 5HTTLPR was associated with greater likelihood of response (OR: 4.65, CI: 1.74-12.38, p=0.003). Patients with the 12/12 repeat variant of the STin2 VNTR polymorphism showed a greater reduction in HAM-D score, compared to patients with the 10/10 genotype (OR: 0.12, CI: 0.03-0.44, p=0.001). We found no association of the 5HTR1Ars6295 polymorphism with response. The 5HTTLPR polymorphism and the SLC6A4 intron 2 polymorphism were associated with treatment response, with the l/l genotype and 12-copy allele showing a tendency towards better outcomes, respectively.

Relationship of Serotonin Transporter Gene Polymorphism With Temperament in Persian Medicine in Fars Province, Iran

Background: Despite its effectiveness, there are still many concerns and questions about the principles and therapeutic methods of Traditional Medicine (TM). In other words, to accept TM as a reliable healthcare system, modern scientific research should approve the principles of this system. Temperament is one of the major determinants of Persian Medicine (PM), which is practically utilized to diagnose and cure diseases. Considering the association of depression with the coldness temperament and the serotonin-Tansporter-Linked Promoter Region (5-HTTLPR) polymorphism, we proposed that the serotonin transporter gene could be one of the candidate genes contributing to the specification of temperament. To test this hypothesis, we examined the association of 5-HTTLPR polymorphism with the hot/cold status of temperament in healthy individuals. Materials and Methods: The study included 351 healthy men (aged 20-40 years) referred to the organization of blood transfusion in Shiraz City, southern Iran. The participants’ temperament (warm, temperate, and cold) was determined using a standard self-reported scale. Then, we performed Polymerase Chain Reaction (PCR) to determine their 5-HTTLPR polymorphism genotype. Multinomial logistic regression was used to evaluate a 95% CI and odds ratios for the association of temperament with the 5-HTTLPR genotypes. Statistical analysis was performed using the SPSS at a significance level of less than 0.05. Results: Regarding the warm temperament, no association with the 5-HTTLPR genotypes was observed. However, regarding cold temperament, although our data showed no association with the SS, the LS genotype showed some association. With reference to LL, the LS genotype decreased the possibility of coldness rather than temperateness for the temperament (OR=0.471, P=0.040). Conclusion: Our data revealed the association of temperament with the 5-HTTLPR polymorphism, suggesting that the serotonergic system may influence temperament. Further studies are required to explore the relation of genetic factors with temperament.

Serotonin Transporter Gene Polymorphism in Patients with Schizophrenic Disorders

Objective: Studies performed to solve the genetic basis of schizophrenia have focused on the role of serotonin in the etiology of schizophrenia and the function of serotonin transporter gene. This study aimed to investigate whether there was a relationship between schizophrenia and polymorphism of the Variable Number of Tandem Repeats (VTNR) and 5-HTT Gene-Linked Polymorphic Region (5-HTTLPR) variants in the transcriptional control region of the serotonin transporter gene or not.Method: A total of 55 schizophrenia patients who were diagnosed according to the diagnostic criteria of DSM-IV-TR and 32 healthy volunteers (the control group) were included in the study. DNAs were extracted from the bloods collected from the patient and control groups with the salting-out method. Alleles of the serotonin transporter gene polymorphism were determined with the polymerase chain reaction (PCR) method.Results: Based on the serotonin transporter gene intron 2 VNTR polymorphism, the distribution of 12/12, 12/10, 10/10, and 12/9 genotypes was 47.3%, 47.3%, 3.6%, and 1.8% in the patients and 46.9%, 46.9% and 6.3% respectively in the control group. There was no 12/9 genotype in the control group. The distribution of L/L, L/S and S/S genotypes according to the 5-HTTLPR polymorphism was 30.9%, 41.8% and 27.3% in the patients and 28.1%, 50.0% and 21.9% respectively in the control group. Conclusion: Although the allele and genotype distributions of the serotonin transporter gene polymorphism relatively differed between the patient and control groups this difference was not statistically significant.

Impact of serotonin transporter gene polymorphism on gut motility in patients with type 2 Diabetes mellitus.

Background/AimsThe pathogenesis of gastrointestinal (GI) symptoms in patients with type 2 diabetes mellitus (T2DM) is yet to be delineated clearly. Serotonin, a monoamine neurotransmitter, resides primarily in the gut and plays a vital role in GI system. However, no study has been documented the role of serotonin and serotonin transporter gene (SLC6A4) polymorphism in the development of GI symptoms in T2DM patients.MethodsThree hundred diabetes patients attending diabetes clinic at Postgraduate Institute of Medical Education and Research, Chandigarh, and matched healthy controls were enrolled for this study. Plasma from collected blood sample was used for serotonin measurement by enzyme-linked immunosorbent assay method and buffy coat was used for isolation of DNA by phenol chloroform method. Serotonin transporter gene polymorphism was analyzed by polymerase chain reaction method.ResultsThe frequency of short allele (S) and SS genotype was significantly higher in patients with T2DM than controls and was associated with increased risk of T2DM. The frequency of LS genotype showed an association with protection from the disease. Regarding GI symptoms, 78.2% of patients with constipation showed LL and LS genotypes, and 97.7% of patients with diarrhea had SS genotype. The patients without GI symptoms did not show any association of gut motility with genotype. Furthermore, serotonin was significantly higher in diabetic patients who belonged to SS genotype compared to LS or LL genotype and who presented with diarrhea.ConclusionSS genotypes are prone to develop diarrhea because of faster gut motility resulting from higher serotonin levels as compared to LS and LL genotype in T2DM patients.

Long acting aripiprazole influences cognitive functions in recent onset schizophrenia.

Beneficial effects of aripiprazole on cognition in schizophrenia have been previously reported, but not in recent onset schizophrenia. Cognitive impairments have also been associated with catechol-O-methyltransferase (COMT), methylenetetrahydrofolate reductase (MTHFR), and serotonin transporter (SERT) gene polymorphisms which were earlier implicated in the pathophysiology of schizophrenia. This study examined the short-term influence of aripiprazole long-acting injectable (LAI) as well as of COMT, MTHFR, and SERT gene polymorphisms and their interactions on clinical features and cognitive functions in inpatients with recent onset schizophrenia. This study included 98 inpatients suffering from recent onset schizophrenia diagnosed according to DSM-5 criteria. Three months after initiating aripiprazole LAI, the severity of symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS), while cognitive functions were measured by 5-KOG test for cognition. Genotypes of SERT, MTHFR, and COMT gene were determined by different polymerase chain reaction (PCR) methods. Three-month aripiprazole LAI treatment was associated with a statistically significant change of PANSS total (p<0.001) and subscale scores as well as cognitive parameters of delayed recall (p<0.03), attention (p<0.01), and executive functions in the form of less perseverations (p<0.03), without influencing other examined cognitive functions. However, it significantly influenced composite cognitive score (p<0.02). In regard to the investigated genetic polymorphisms, we established a positive association between the COMT polymorphism (M/M allele carriers) and attention (p<0.01). Additionally, we also established a positive association between the COMT - MTHFR interaction and attention (p<0.02), as well as perseveration item belonging to executive functions (p<0.01). Two other investigated polymorphisms (MTHFR and SERT) were not significantly associated with cognitive indices. Investigated genetic polymorphisms and their interactions were not associated with PANSS scores. Our findings suggest that aripiprazole LAI improves individual cognitive functions in recent onset schizophrenia. Investigated COMT polymorphism (Met/Met genotype), as well as the COMT-MTHFR interaction, were positively associated with attention and executive functioning (perseveration), potentially implying COMT's biomarker potential in terms of cognition in schizophrenia.

Polymorphism of the Serotonin Transporter Gene and the Peripheral 5-Hydroxytryptamine in Obstructive Sleep Apnea: What Do We Know and What are We Looking for? A Systematic Review of the Literature.

BackgroundObstructive sleep apnea (OSA) is a highly prevalent disease with substantial public health burden. In most of the cases, there is a genetic predisposition to OSA. Serotonin/T-HydroxyTriptamine (5-HT) plays a key role in ventilatory stimulation, while the polymorphism of the serotonin transporter gene (STG) leads to alterations in serotonin level, making it important in OSA.ObjectiveTo examine whether the 5-HydroxyTriptamine and the genetic predisposition influence the incidence and evolution of OSA, we reviewed randomized, controlled trials and observational studies on the selected topic. The secondary objective was to determine the metabolic effects of the circulating serotonin in other tissues (liver, pancreas, gut, brown adipose tissue, and white adipose tissue) and its role in the development of obesity.Data SourcesA systematic review of English articles was performed based on PubMed and the Cochrane Library databases. Search filters included randomized controlled trial, controlled clinical trial, random allocation, double-blind method, and case–control studies and used the following keywords: Brain Serotonin OR Serotonin Transporter Gene Polymorphism OR Peripheral 5-HydroxyTryptamine AND Obstructive Sleep Apnea OR Sleep Disorder Breathing OR brain serotonin AND OSA OR serotonin transporter gene OR Peripheral 5-Hydroxytryptamine AND Sleep.Study Eligibility CriteriaThe inclusion criteria for the current review were previous diagnosis of OSA, age above 18 years, and articles including quantitative data about serotonin transporter gene or peripheral serotonin. Language and time criteria were added – English articles published in the last 15 years. Studies that were not included were reviews and case reports.Study Appraisal and Synthesis MethodsIn order to study the serotonin function, a literature research was conducted in the databases Pubmed and Cochrane Library. The following search terms were used: serotonin, 5-hydroxytryptamine, serotonin transporter gene. A critical appraisal of the included studies was performed with the Newcastle-Ottawa scale (NOS) and Delphi list.ResultsThe search yielded 1210 articles, from which 43 were included. The included studies suggest that the two polymorphisms of serotonin transporter gene (5HTT) – variable number of tandem repeats (VNTR) and linked polymorphic region (LPR) – are strong candidates in the pathogenesis of OSA. The allele 10 of 5HTTVNTR and the long/long (L/L) allele genotype were associated with a higher prevalence of OSA and the L allele with a higher apnea-hypopnea index and a longer time during sleep with oxygen desaturation.LimitationsThe main limitation of the present study consists of heterogeneity of the information. Being a less studied subject, randomized trials are not widely available and most data were obtained from case–control trials. Moreover, the included material indirectly approached the subject by demonstrating the effects of serotoninergic system over the metabolism, the connection between serotonin and obesity, factors which are implied in the pathogenesis of OSA.Conclusion and Implications of Key FindingsThe two polymorphisms of serotonin gene can be considered important factors in the diagnosis and management of OSA.

Individual Differences in Autistic Traits are Associated with Serotonin Transporter Gene Polymorphism Through Medial Prefrontal Function: A Study Using NIRS

Autism spectrum disorder (ASD) is a heritable neurodevelopmental disorder that can vary considerably in severity. Autistic traits are distributed continuously across populations, even in sub-clinical individuals. Serotonin transporter-gene polymorphic region (5-HTTLPR) has been studied as a candidate genetic factor related to ASD, however results have been inconsistent. 5-HTTLPR is implicated in the function of medial prefrontal cortex (mPFC), a region associated with the social abnormalities found in ASD. Here we hypothesize that autistic traits are affected by the 5-HTTLPR genotype indirectly through mPFC mediation. Using near-infrared spectroscopy (NIRS), we first examined mPFC activation in people with ASD when they performed a facial affect-labeling task. Compared with a typical development group, the ASD group showed significantly lower mPFC activation during the task. Using the same task paradigm, we next investigated the relationship between autistic traits and 5-HTTLPR in sub-clinical participants, and whether associations were mediated by mPFC function. Correlation analyses indicated that participants with a large number of 5-HTTLPR L-alleles had high-level autistic traits related to social skills and low right mPFC activation. We also observed a significant negative correlation between autistic traits related to social skills and right mPFC activation. Structural equation analysis suggested a significant indirect effect of 5-HTTLPR on Autism-Spectrum Quotients, with right mPFC activation acting as a mediator. These results suggest that the diverse autistic traits related to social skills seen in the general population are associated with the 5-HTTLPR genotype, and that this association is mediated by right mPFC function.

The effects of 5-HTTLPR/rs25531 serotonin transporter gene polymorphisms on antisocial personality disorder among criminals in a sample of the Turkish population.

Antisocial personality disorder (ASPD) is a cluster B personality disorder characterized by a disposition for criminal behaviors. It has been determined by previous studies that ASPD may have a genetic origin and the human serotonin transporter gene (SLC6A4) is one of the two serotonergic genes expected to be associated with this disorder. 5-HTT-linked polymorphic promoter region (5-HTTLPR) is a degenerate repeat polymorphic region in SLC6A4, the gene that codes for the serotonin transporter. Among many polymorphisms in SLC6A4, 5-HTTLPR an insertion/deletion (indel) polymorphism and rs25531 single nucleotide polymorphism (SNP) in the 5-HTTLPR polymorphic region contribute to the regulation of SLC6A4 expression. In this study, we aimed to reveal the relationship between frequencies of 5-HTTLPR variants and ASPD among criminals in the Turkish population. Moreover, it was also attempted to figure out the SLC6A4 gene expression level differences regarding these polymorphisms. The 5-HTTLPR/rs25531 genotypes were determined by PCR and restriction length polymorphism (RFLP) analyses and quantitative real-time-PCR was done for measuring the gene expression levels in the case and control groups. Although no significant difference was observed in the distributions of the 5-HTTLPR/rs25531 polymorphisms between the case and control groups, SLC6A4 expression level in the control group was found significantly higher than the case group (p < 0.0001). There was also no significant difference between genotypes in terms of mRNA expression levels in either the control or the case group. According to our results, ASPD in Turkish society is associated with the SLC6A4 gene expression levels, though the distributions of 5-HTTLPR polymorphisms are not different. This study sheds light on future relevant studies as the first study which is conducted in criminals with ASPD in the Turkish community.

Serotonin transporter gene polymorphisms and depressive symptoms in patients with chronic obstructive pulmonary disease

ABSTRACT Background: We examined the relationship between polymorphisms in the promoter region of the serotonin transport (SERT) gene (5-HTTLPR, short ‘S’ and long ‘L’ alleles) and in intron 2 variable number tandem repeat (STin2VNTR, 9, 10, or 12-repeat alleles) with depression or anxiety in patients with COPD. Methods: 302 patients with moderate to severe COPD participated in SERT study. History and number of prior depressive episodes were measured using the Structured Clinical Interview for Depression; Hospital Anxiety Depression Scale (HAD) depression ≥8 or a Patient Health Questionnaire-9 (PHQ-9) >,10. Results: 240 (80%) male sample had a mean age of 68.0 years. Current depression was 22% (HAD) or 21% (PHQ-9), anxiety was 25% (HAD), and suicidal ideation (6%). 5-HTTLPR or STin2 VNTR genotypes were not associated with current depressive or anxiety symptoms. The mean number of prior depressive episodes was higher for patients with the 5-HTTLPR genotype S/S or S/L compared with L/L (4.4 ± 6.1; 5.3 ± 6.8; 4.0 ± 6.1, p < 0.001) and with STin2VNTR high-risk genotype (9/12 or 12/12), medium risk (9/10 or 10/12) compared to low risk (10/10) genotypes (5.1 ± 6.8; 4.9 ± 6.7; 2.7 ± 4.5, p < 0.001). Conclusions: SERT 5-HTTLPR and STin2-VNTR polymorphisms were not associated with current depressive and anxiety symptoms, but the high-risk STin2-VNTR genotypes and S/L were associated with the number of prior depressive episodes.

P.677 Serotonin transporter gene polymorphisms and confidence in adult relationships affect the number of followed people on Instagram

Maternal undernutrition during pregnancy impairs offspring behaviours and thereby their survival rate indirectly by decreasing lamb birth weight or by deteriorating milk production which in turn limits bonding of the dam with the neonate. This study was aimed to investigate the effect of maternal feed restriction during late pregnancy on performance and behaviours of ewes and their lambs. Twenty-four Ghezel ewes were allocated to the three experimental treatments including ad libitum intake (AL); restricted feed intake by 60 % (FR); and propylene glycol- supplemented restricted diet (FR + PG). AL and FR + PG ewes had higher circulating oestradiol (P < 0.001) but not progesterone (P < 0.0001) than FR ewes during late pregnancy and parturition. Prepartum undernutrition of FR ewes resulted in lower milk yield (P < 0.001) and higher milk fat percentage (P < 0.0001) than AL and FR+PG ewes during the initial three weeks of lactation. In the case of offspring behaviours, lambs born to ewes offered PG+FR treatment were quicker to kneel, stand up, reach to the udder, suck and play within the first 2 h of birth compared with those born to ewes offered FR and AL treatments (P < 0.0001). Lambs from FR+PG ewes had a higher birth weight (P < 0.05), weaning weight (P < 0.0001) and average daily gain (P < 0.0001) than those from the other groups. Concerning maternal behaviours, FR+PG ewes started grooming their lambs faster than ewes in other groups (P < 0.01). Moreover, it took more time for FR ewes to deliver their lambs or deliver their second lamb in multiple deliveries compared with those in the other groups (P < 0.01). The maternal recognition test revealed lambs born to AL and FR+PG ewes preferred to spend more time with their dams than did lambs born to FR ewes at 12 h of age (P < 0.0001). The results also showed that the time taken for the lambs to reach the contact zone or to reach their dam was substantially longer for lambs from FR ewes than those from AL and FR+PG ewes at 12 h and 24 h of age (P < 0.0001). There was a positive correlation between lamb birth weight and average daily gain (r= 0.36), weaning weight (r=0.64), survival rate (r=0.62). It can be concluded that although maternal under nutrition can adversely affect maternal and neonatal behaviours, supplementing glucogenic precursor as a strategy can alleviate the majority of physiological and behavioural abnormalities and might have beneficial outcomes for farmers.

The serotonin transporter gene polymorphism (SLC6A4) and risk for psychiatric morbidity and comorbidity in the Baltimore ECA follow-up study

BackgroundThe human serotonin transporter (SERT) gene polymorphism (5HTTLPR) has been associated with multiple psychiatric disorders, including major depression, anxiety disorders, and substance use disorders. This study investigated the association between 5HTTLPR and psychiatric morbidity and comorbidity in a psychiatrist-examined population sample. Methods628 participants, mean age 48.3 years old, were assessed by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry. Associations between 5HTTLPR and the prevalence, comorbidity, and time-to-diagnoses for 16 psychiatric conditions were evaluated, using several analytical approaches. ResultsThe SERT S allele was significantly associated with an increased lifetime prevalence of panic disorder. There was a “protective” association between SERT gene S allele carrier status and the risk of obsessive-compulsive disorder (OCD) in time-to-event analysis. Carriers of the S allele had a significant increased risk of two specific comorbid disorder pairs: major depressive disorder (MDD) and social phobia, and MDD and agoraphobia. Overall, there was no increased risk of receiving an initial or an additional diagnosis for a mental disorder in the SERT S allele carriers ConclusionsThe findings suggest that the S allele carrier status is associated with an increased prevalence of panic disorder in a community sample. There was an increased risk for comorbidity in a more homogeneous subgroup of cases with MDD and social phobia, as well as or agoraphobia. Our findings suggest a specific effect of the SERT promoter gene polymorphism on a subgroup of individuals identifiable by their comorbidity.

Association between functional polymorphisms in serotonin transporter gene (SLC6A4) and escitalopram treatment response in depressive patients in a South Indian population.

Ethnicity plays a key role in deciding the direction of the association between serotonin transporter gene polymorphisms and treatment response of selective serotonin reuptake inhibitors (SSRIs). The present study explored the association of 5HTTLPR and 5HTTLPR-rs25531 polymorphisms with the treatment response of escitalopram in South Indian patients with major depressive disorder. A total of 148 depressive patients receiving escitalopram 10-20mg/day were genotyped for 5HTTLPR and rs25531 polymorphisms. Clinical assessment was done at baseline and after 4, 8, and 12weeks using the 17-item Hamilton Depression Rating Scale (HDRS-17), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression Scale (CGI). At the end of week 12, patients were defined as responders and non-responders based on HDRS17 and MADRS scores. Chi-square test and logistic regression analysis were performed to investigate the genotypic influence on treatment response. Comparison of continuous variables among different groups was done using Student's t test or one-way ANOVA. Out of 148 study subjects, 65 (43.9%) were responders and 83 (56.08%) were non-responders. We observed a significant (p value < 0.001) association between LL genotype, LALA haplotypes, and 2 LA functional group with better treatment response to escitalopram. The decline in HDRS17 and MADRS score from baseline was significantly higher (p value < 0.001) in LL genotypes and homozygous LA carriers compared with other groups. Results suggest that 5HTTLPR and rs-25531 polymorphisms can influence escitalopram treatment response in depressive patients in a South Indian population, LL genotypes and LALA haplotypes being the predictors of better treatment response.

Antidepressant-Associated Mania in Bipolar Disorder: A Review and Meta-analysis of Potential Clinical and Genetic Risk Factors.

Antidepressants (ADs) play a valuable role in treating the depressive episodes of bipolar disorder. However, 14% of these individuals taking ADs experience AD-associated mania (AAM) within a few weeks of starting treatment. Numerous studies have suggested potential clinical and genetic risk factors. We aimed to conduct a comprehensive systematic review and meta-analysis that integrates the past literature with the recent studies and identifies important predictors for AAM. The review was limited to experimentally designed studies that contain the relevant search terms in PubMed and PsychInfo. After removing studies that were in discordance with our criteria, the review included 24 reports examining clinical risk factors and 10 investigating genetic risk factors. Our meta-analysis was conducted on 5 clinical risk factors, each of which had at least 4 articles with extractable data. The only clinical factors in the literature that have been shown to be more indicative of AAM risk are AD monotherapy and tricyclic ADs. Among genetic factors, the serotonin transporter gene polymorphism may play a minor role in AAM. Our meta-analysis provided support for the number of prior depressive episodes. Prevention of AAM may be served by early detection of recurrent depression episodes. Further large-scale longitudinal studies are required to determine the underpinnings of AAM.

Associations between the STin2VNTR Serotonin Transporter Gene Polymorphism and Background EEG in Younger and Older Adults

Spontaneous electrical brain activity is considered as a state of tonic activation or inhibition, which is the physiological basis for normal brain function and pathology. Projections of the serotonergic system are widely widespread in the cerebral cortex and affect both the processes of neuroplasticity and the formation of fundamental neural networks that determine the brain activity at rest. The STin2VNTR gene appears to be an allele-dependent enhancer of the expression of the serotonin transporter gene. This study was conducted to identify the associations of STin2VNTR polymorphism with the characteristics of background EEG in healthy older (51 men (64.5 ± 7.13 years of age) and 48 women (63.56 ± 5.4 years)) and younger (86 men (22.5 ± 3.5 years) and 110 women (21.17 ± 2.7 years)) adults. The endophenotypes of brain electrical activity associated with the STin2VNTR polymorphism of the serotonin transporter gene are characterized by specific patterns of α3 power asymmetry in parietal–occipital regions of the brain hemispheres and differ in younger and older subjects. In the younger age group, the 12'/12' genotype carriers had significantly higher values of the asymmetry index of the α3 power (right > left) in the parietal–occipital regions as compared with other genotypes. The presence of allele 12 in the genotype positively correlates with the value of asymmetry index of the α3 rhythm. In young carriers of allele 12 (10'/12' and 12'/12'), lateral differences were statistically significant. In the older age group, the 10'/10' genotype carriers had the lowest values of asymmetry index; only the carriers of this genotype had statistically significant lateral differences due to higher rhythm power in the parietal–occipital region of the right hemisphere as compared to the left one. Lateral differences due to high α-rhythm power values in the posterior region of the right hemisphere may be considered as electrophysiological endophenotype and may be associated with predisposition to the possible occurrence of schizoid disorders in young carriers of the 12'/12' genotype.

Predictors for wellbeing and characteristics of mental health after stroke

BackgroundPoor mental health after stroke is common and complex. We aimed to identify predictors of poor wellbeing and to examine the overlap of poor wellbeing, fatigue, and depression. MethodConsecutive first-ever ischemic stroke-patients filled in questionnaires on wellbeing, fatigue, and depression at baseline and at one and six months. The World Health Organization 5-Item Wellbeing-Index (WHO-5), the Major Depression Inventory, and the Multidimensional Fatigue Inventory were used. Patients were genotyped according to serotonin-transporter gene polymorphisms. Multivariable logistic regression was used to identify potential predictors of poor wellbeing (WHO-5 score <50). Overlap between wellbeing, fatigue, and depression was examined using an Euler diagram. ResultsWe included 919 patients. The prevalence of poor wellbeing was 279 (30.4%) six months after stroke. Living alone at stroke onset was the strongest predictor of poor wellbeing with a mutually adjusted odds ratio of 1.53 (95% confidence interval (CI): 1.03 to 2.28) at one month and 1.77 (CI: 1.13 to 2.76) at six months. Severe stroke at admission also predicted poor wellbeing at six months. Abnormal fatigue occurred in half and incorporated almost all patients with poor wellbeing. Less than 5% fulfilled the criteria for depression at any point and almost all of these patients had poor wellbeing and abnormal fatigue. Antidepressants were used by 292 (31.8%) during follow-up. LimitationsCognitive impairment was not measured and could interact with wellbeing post-stroke. ConclusionLiving alone strongly predicted poor wellbeing after stroke. Satisfactory mental health-recovery seems to require psychosocial interventions when indicated in combination with antidepressant treatment.