5-HTTLPR Polymorphism Research Articles

Interaction of Val66Met Brain-Derived Neurotrophic Factor and 5-HTTLPR Serotonin Transporter Gene Polymorphisms with Lifetime Prevalence of Post-Traumatic Stress Disorder in Primary Care Patients

Background/Objectives: Post-traumatic stress disorder (PTSD) is a complex condition influenced by both genetic and environmental factors. This longitudinal study aimed to explore the connection between two specific genetic polymorphisms, Val66Met and 5-HTTLPR, and the lifetime prevalence of PTSD in patients from primary care settings. We also examined the role of sociodemographic and psychosocial factors to provide a more comprehensive view of PTSD risk. Methods: We recruited a cohort of primary care patients and diagnosed PTSD using a standardized diagnostic interview. Genetic analyses focused on Val66Met and 5-HTTLPR polymorphisms. We applied logistic regression to assess the association between these genetic markers and PTSD, considering factors such as gender, family history of depression, and experiences of childhood maltreatment. Results: Our findings show that women, individuals with a family history of depression, and those exposed to childhood maltreatment have a higher risk of developing PTSD. While the Val66Met polymorphism was not significantly associated with PTSD, the 5-HTTLPR polymorphism showed a marginal relationship. No significant interaction was found between the two polymorphisms in relation to PTSD. Conclusions: This study underscores the multifactorial nature of PTSD, influenced by both genetic and environmental factors. The findings point to the importance of further research on genetic predispositions and highlight the value of early interventions for high-risk populations in primary care settings.

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.

The Association between Post-Traumatic Stress Disorder, 5HTTLPR, and the Role of Ethnicity: A Meta-Analysis.

The current meta-analysis looks at the effect of ethnicity on the connection between 5-HTTLPR SNPs and PTSD patients in all published genetic association studies. In accordance with PRISMA principles, the literature was searched in PubMed, Scopus, and ScienceDirect. A consistent method was followed by two reviewers who independently chose publications for inclusion and extracted data. Using a random-effects model, a meta-analysis of the biallelic and triallelic studies was conducted in order to determine the pooled OR and the associated 95% CI. The impact estimates were corrected for minor study effects, including publication bias, using the trim-and-fill approach. After 17 studies were deemed eligible for inclusion, the overall sample size was 8838 controls and 2586 PTSD patients, as opposed to 627 and 3524 in the triallelic meta-analysis. The results of our meta-analysis and comprehensive review do not point to a direct main effect of the 5-HTTLPR polymorphisms on PTSD. Nonetheless, preliminary data suggest that ethnicity influences the association between 5-HTTLPR and PTSD. According to our findings, ethnicity-especially African ethnicity-has a major influence on the relationship between 5-HTTLPR and PTSD and needs to be taken into account as a crucial moderating factor in further studies.

Association between 5-HT1A receptor C-1019G, 5-HTTLPR polymorphisms and panic disorder: a meta-analysis.

HTR1A C-1019G polymorphism (rs6295) and serotonin transporter promoter polymorphism (5-HTTLPR) have been linked with panic disorder (PD) in different ethnic backgrounds. Both these polymorphisms are in the promoter regions. However, results are inconsistent and contrasting evidence makes reliable conclusions even more challenging. A meta-analysis was conducted to test whether C-1019G polymorphism and 5-HTTLPR were involved in the etiology of PD. Articles researching the link between C-1019G, 5-HTTLPR polymorphisms, and PD were retrieved by database searching and systematically selected on the basis of selected inclusion parameters. 21 studies were included that examined the relationship of rs6295,5-HTTLPR polymorphisms with PD risk susceptibility (rs62957 polymorphism - 7 articles, and 5-HTTLPR polymorphism - 14 articles). A significant association was seen between the rs6295 polymorphism and PD pathogenesis, especially in Caucasian PD patients. No significant genetic linkage was found between the 5-HTTLPR polymorphism and PD. C-1019G polymorphism was involved in the etiology of PD in Caucasian patients. The 5-HTTLPR polymorphism was not a susceptibility factor of PD.

Subclinical hypomanic experiences in young adults after sleep deprivation are independent of depressive disorders, chronotype or 5-HTTLPR polymorphism

Introduction The acute antidepressant effect of sleep deprivation (SD) in patients with depressive disorders has been studied for more than 60 years. However, hypomanic mood swings after partial or total SD have also been described in people without diagnosed mental disorders. Studying this phenomenon in the general population may yield insights about the mechanisms of therapeutic SD, mania and bipolar disorders. Methods A cross-sectional sample of young adults was recruited and classified into those who described having regularly occurring subclinical hypomanic experiences (ROHE) after SD and those who did not. History of psychiatric and physical illness, with screening for depression and mania, as well as alcohol or drug consumption, family history of depressive disorders or suicide, 5-HTTLPR polymorphism, and MEQ-SA chronotype were collected. Results A total of 251 participants were included; 39.0% indicated regularly having subclinical hypomanic experiences after SD. These experiences were not associated with depressive or mania screening, history of psychiatric illness, family history, 5-HTTLPR polymorphism, or MEQ-SA chronotype. Conclusions ROHE after non-therapeutic SD seem to be a relatively common phenomenon in young adults, independent of depressive mood state. Our results suggest that therapeutic SD may depend on a physiological phenomenon of subclinical affective disturbance after SD that affects a part of the general population, independent of psychiatric diagnosis. Further studies could elucidate associated factors and contribute to our understanding of (hypo-)manic mood states.

Genetic polymorphisms and their association with neurobiological and psychological factors in anorexia nervosa: a systematic review.

Anorexia nervosa (AN) is a complex neuropsychiatric disorder. This systematic review synthesizes evidence from diverse studies to assess and investigate the association between gene polymorphisms and psychological and neurobiological factors in patients with AN. A systematic search across PubMed, PsycINFO, Scopus, and Web of Science databases, along with manual searching, was conducted. The review protocol was approved by PROSPERO (CRD42023452548). Out of 1,250 articles, 11 met the inclusion criteria. The quality of eligible articles was assessed using the Newcastle-Ottawa Scale (NOS) tool. The systematic review followed the PRISMA guidelines. The serotoninergic system, particularly the 5-HTTLPR polymorphism, is consistently linked to altered connectivity in the ventral attention network, impaired inhibitory control, and increased susceptibility to AN. The 5-HTTLPR polymorphism affects reward processing, motivation, reasoning, working memory, inhibition, and outcome prediction in patients with AN. The dopaminergic system, involving genes like COMT, DRD2, DRD3, and DAT1, regulates reward, motivation, and decision-making. Genetic variations in these dopaminergic genes are associated with psychological manifestations and clinical severity in patients with AN. Across populations, the Val66Met polymorphism in the BDNF gene influences personality traits, eating behaviors, and emotional responses. Genes like OXTR, TFAP2B, and KCTD15 are linked to social cognition, emotional processing, body image concerns, and personality dimensions in patients with AN. There was an association linking multiple genes to the susceptibly and/or severity of AN. This genetic factor contributes to the complexity of AN and leads to higher diversity of its clinical presentation. Therefore, conducting more extensive research to elucidate the underlying mechanisms of anorexia nervosa pathology is imperative for advancing our understanding and potentially developing targeted therapeutic interventions for the disorder.Systematic review registration: [https://clinicaltrials.gov/], identifier [CRD42023452548].

From parents to children: associations of traffic risks with impulsivity, family relationships and serotonin transporter genotype.

Road traffic injuries are the leading cause of death for young adults, and parents play a major role in shaping their traffic behaviour. Higher impulsivity (predictor of higher traffic risk) has been shown to be dependent on family relations and the serotonin transporter gene promoter polymorphism (5-HTTLPR). The specific mechanisms for the inheritance of risky traffic behaviour from parents to children are not clear, and the genetic aspect has not been studied before. We used data of Estonian Children Personality Behaviour and Health Study subjects (n = 596, mean age = 25.2 ± 0.6) and their parents (mothers, n = 460, mean age = 52.1 ± 5.8; fathers, n = 339, mean age = 54.1 ± 6.5). Family relationships scale, traffic risk questionnaires and Adaptive and Maladaptive Impulsivity Scale were filled out. The increased risk-taking behaviour of parents and worse quality of family relationship were significant predictors of higher traffic risk among subjects. Family support and impulsivity of fathers significantly predicted the subjects' traffic risk score in interaction with 5-HTTLPR genotype: l'/l' homozygous subjects with adaptively impulsive fathers had higher traffic risk, whereas for s'-allele carrying subjects family support was more significant. Parental role modelling and family relationships are significant predictors of future traffic behaviour of the child. Whether the behavioural example of the father or the influence of family relationships is more important in predicting future risky traffic behaviour, depends on the 5-HTTLPR genotype of the child.

Association of 5-HTTLPR With Post-Traumatic Stress Disorder in US Service Members

Objective Post-traumatic stress disorder (PTSD) is a mental disorder that manifests after exposure to a stressful traumatic event, such as combat experience. Accumulated evidence indicates an important genetic influence in the development of PTSD. The serotonin transporter (5-HTT) gene has been identified as a candidate for PTSD and a polymorphism of the serotonin transporter-linked promoter region (5-HTTLPR) is associated with the disorder in the general population. However, whether it is associated with PTSD in active military service members has not been investigated. This study aimed to investigate the relationship between 5-HTTLPR and PTSD in service members. Methods Leucocyte genomic DNA was extracted from service members, including those with PTSD (n = 134) or without PTSD (n = 639). The 5-HTTLPR polymorphism was detected by means of 2 stages of TaqMan fluorescent PCR assay. PTSD symptoms and symptom severity were assessed using the PTSD Checklist (PCL), a 17-item, DSM-based, self-report questionnaire with well-established validity and reliability. PTSD was determined based on endorsement of DSM-IV criteria and a PCL total score ≥ 44. Results Significant differences in biallele distribution were observed between PTSD and controls (χ2 = 7.497, P = .024). The frequency of SS, SL, and LL genotypes in the PTSD group was 0.17, 0.56, and 0.27 respectively, compared to the frequencies of 0.27, 0.43, and 0.29 in non-PTSD controls. Carriers of the L allele had higher scores for reexperiencing and arousal symptoms on the PCL, compared to SS homozygote carriers (P < .05). The triallele genotypes showed no significant differences in distribution between the PTSD and control groups (P > .05) and no relationship with PTSD symptom severity. The interaction of triallelic genotypes of 5-HTTLPR and traumatic life events was associated with re-experiencing, avoidance, and arousal (P < .05 for all). Multiple regression analysis revealed significant correlations between both biallelic and triallelic genotypes of 5-HTTLPR, the interaction of the number of stressful lifetime events, and 5-HTTLPR genotypes with PCL total score (P < .001). Conclusion Our findings suggested that 5-HTT might play a minor role in PTSD, and the interaction between 5-HTTLPR and the environment had effects on PCL score, complementing and emphasizing 5-HTT for PTSD, especially in the military population.

Behavior Physiology of Workplace Bullying and It’s Role to Job Satisfaction and Psychologycal Distress among Workers at Water Supply Company

Individuals strive to fulfill their essential needs by working. Every company has different work environment. The work environment tends to have impact on each individual. One of the key issues that usually occur at workplace is bullying. Workplace bullying can happen to anyone while both bullies and their victims may experience psychological effects from bullying. This study aims to see the effect of workplace bullying on job satisfaction and psychological distress among water supply company employees. This research design is quantitative using cross sectional design. The results showed that the psychological distress variable played a significant role in workplace bullying (p. &lt;0.05). However, the job satisfaction variable does not contribute to workplace bullying (p. &gt; 0.05). The serotonin trasporter-linked promoter region (5-HTTLPR) polymorphism of the SLC6A4 gene consists of an insertion/deletion that creates a short (S) 14 repeat or a long (L) 16 repeat allele. Genotype profile on one’s serotonergic system is correlated by their dominance in the community. Individuals with allele LL type is more likely become bullies when they are encouraged by the environment. In contrast, individuals with SS allele type with in a characteristic of low transcription activity at transporter serotonin gene tend to become bullying victims in their workplace due to they more vulnerable to stress. Employee with amygdala which easily triggered and intimidated by the dominant individuals, more likely to experience workplace bullying. Those employee who work in supportive workplace show higher job satisfaction and they are not distress psychologically.

Can psychopathy be prevented? Clinical, neuroimaging, and genetic data: an exploratory study

ABSTRACT The aim of the study was to explore the relationship among brain functional activations elicited by an emotional paradigm, clinical scores (PTSD, anxiety, and depression), psychopathic traits, and genetic characteristics (5-HTTLPR) in a group of severely maltreated children compared to a healthy control group before and after the implementation of a Trauma Focused-Cognitive Behavioral Therapy. The final sample consisted of an experimental group of 14 maltreated children (mean age = 8.77 years old, S.D. = 1.83) recruited from a non-governmental shelter in Mexico City for children who had experienced child abuse and a control group of 10 children from the general population (mean age = 9.57 years old, S.D. = 1.91). Both groups were matched according to age and gender and were assessed before and after the implementation of the aforementioned therapy by means of clinical scales and an emotional paradigm that elicited brain activations which were recorded through functional magnetic resonance imaging. Genotyping of the 5-HTTLPR polymorphism was made at first assessment. A region of interest analysis showed amygdala hyperactivation during exposure to fear and anger stimuli in the maltreated children before treatment. Following therapy, a decrease in brain activity as well as a decrease in clinical symptoms were also observed. 5-HTTLPR polymorphism did not show any effect on the severity of clinical symptoms in maltreated children. Trauma-Focused Behavioral Therapy may help reorganize the brain’s processing of emotional stimuli. These observations reveal the importance of an early intervention when the mechanisms of neuroplasticity may be still recruited.

Psychobiological screening among patients affected by prostate cancer: Identification of potential psychobiological markers.

Prostate cancer is a common oncological disease of old age with the highest rates of incidence among males older than 65 years old. Diagnosis and treatment may be associated with the onset of adjustment, depressive, and anxiety disorders. The comorbidity with depression and anxiety may lead to a higher risk of suicide, and mortality as well as lower adherence to medical treatments and adverse functional outcomes in patients affected by urologic cancers. The role of genetic vulnerability and pre-morbid personality in predicting the development of mental disorders during cancer disease is debated. For instance, some genetic polymorphisms of the serotonin transporter-related promoter region (5-HTTLPR polymorphism) are associated with higher vulnerability for mental disorders as well as personality traits of neuroticism; both factors are potentially useful for identifying risk of depressive and anxious symptoms among cancer patients. This communication proposes the development of individualized psychobiological approaches to identify possible 'psychobiological' markers associated with the risk of mental disorders in prostate cancer patients.

Serial killers: a review about the genetic influence on violent behavior

Introduction: Since the beginning of time, violence has accompanied man's behavior. In this sense, the transgressions committed by the so-called Serial Killers involve the existence of heinous crimes. Thus, there is great interest in understanding how various elements can influence or predispose individuals to violence and crime. Objective: To analyze the influence between violent behavior and genetic factors, taking into consideration elements such as hormones and genes that have a relationship with such human conduct. Methodology: This is a literature review with 12 studies published between 2011 and 2021, in the PubMed, BVS, Scielo, NLM Catalog, PubMed, LILACS, and PMC databases after combining the operators "Genetics" AND "Crime" AND "Violence". Development: The following factors were found to be related to violent and potentially criminal behavior: low levels of serotonin in the brain and of 5-HIAA in the CSF; 5-HTTLPR polymorphism of the SLC6A4 gene and the HTR2A and HTR2B encoders. In the dopaminergic system, genes encoding COMT; the DAT1 and the DRD2 and DRD 4 receptors; the Val158MET COMT polymorphism; the low activity of the MAOA gene and its MAOA-uVNTR polymorphism and six other variants; the CDH13 and RBOFOX1 genes and 4 of its polymorphisms; Bipolarity and Schizophrenia disorders and, finally, Klinefelter Syndrome. Conclusions: It was possible to conclude that, even under some limitations, there is a relevant influence of genetic issues on a violent and potentially criminal person. Although this relationship is permeated by several other coefficients, genetics offers important findings for the understanding of criminal conduct.

Analytical description of adolescent binge drinking patients

BackgroundBinge drinking is a widespread health compromising behavior among adolescents and young adults, leading to significant health problems, injuries and mortality. However, data on alcohol consumption is often unreliable, as it is mainly based on self-reporting surveys. In this five-year study (2014–2019) at the University Children’s Hospital Zurich, we analyzed blood samples from adolescent binge drinking patients to investigate blood alcohol concentrations (BACs), co-ingestion of drugs, assess compliance between self-reported and measured substance use, and test for genetic components of innate alcohol tolerance. Furthermore, hair analysis was performed to retrospectively access drug exposure and to evaluate the potential of hair analysis to assess binge drinking.MethodsIn a prospective, single-center study, patients with alcohol intoxications aged 16 years and younger were included. Blood and hair samples were analyzed by sensitive liquid chromatography – tandem mass spectrometry drug analysis. HTTLPR genotyping was performed with PCR and fragment analysis.ResultsAmong 72 cases, 72 blood and 13 hair samples were analyzed. BACs ranged from 0.08–3.20‰ (mean 1.63‰, median 1.60‰), while a mean concentration of 3.64 pg/mg hair (median 3.0 pg/mg) of the alcohol marker ethyl glucuronide (EtG) was detected in eleven hair samples, providing no evidence of chronic excessive drinking. In 47% of the cases, co-ingested drugs were qualitatively detected next to ethanol, but only 9% of the detected drugs had blood concentrations classified as pharmacologically active. Cannabis consumption (22%) and stimulant intake (16%) were the most frequently observed drugs. Compliance between patients’ statements and measured substances matched well. Although we investigated the genetic contribution to innate alcohol tolerance via the 5-HTTLPR polymorphism, the diverse genetic background of the cohort and small sample size did not allow any conclusions to be drawn.ConclusionAlmost half of our binge drinking patients tested positive for other substances, primarily cannabis. We anticipate that our study enhances understanding of consumption behavior of young people and encourage continued efforts to address the harmful effects of binge drinking and co-occurring substance use.

Interaction of Val66Met BDNF and 5-HTTLPR polymorphisms with prevalence of post-earthquake 27-F PTSD in Chilean population.

Post-traumatic stress (PTSD) disorder is a mental health condition that can occur after experiencing or witnessing a traumatic event. The 27-F earthquake that struck Chile in 2010 was one such event that had a significant impact on the mental health of the population. A study was conducted to investigate the prevalence of PTSD and its associated factors among survivors of this earthquake. The study was a longitudinal design, involving a sample of 913 patients aged 18 to 75 years who attended 10 Primary Care Centers in Concepción, Chile. The Composite International Diagnostic Interview (CIDI) was used to assess both depressive episodes (DE) and PTSD before and after the earthquake. The study also involved genotyping studies using saliva samples from the participants, specifically focusing on the Val66Met and 5-HTTLPR polymorphisms. Statistical analysis was performed to examine the association between different variables and the presence of PTSD. These variables included demographic factors, family history of psychiatric disorders, DE, childhood maltreatment experiences, and critical traumatic events related to the earthquake. The results showed that the incidence of post-earthquake PTSD was 11.06%. No significant differences were found between the groups of participants who developed post-earthquake PTSD regarding the Val66Met or 5-HTTLPR polymorphisms. However, a significant association was found between the concomitant diagnosis of DE and the development of post-earthquake PTSD. The presence of DE doubled the risk of developing post-earthquake PTSD. The number of traumatic events experienced also had a statistically significant association with an increased risk of developing post-earthquake PTSD. The study's limitations include the potential interference of different DE subtypes, the complexity of quantifying the degree of earthquake exposure experienced by each individual, and events entailing social disruption, such as looting, that can profoundly influence distress. In conclusion, the study found that PTSD following the 27-F earthquake in Chile was associated with a concomitant diagnosis of DE and the number of traumatic events experienced. The study did not find a significant association between PTSD and the Val66Met or 5-HTTLPR polymorphisms. The researchers recommend that mental health professionals should prioritize the detection and treatment of concomitant depressive episodes and exposure to critical traumatic events in survivors of disasters. They also suggest that further research is needed to better understand the relationship between genetic factors and post-disaster PTSD.

Antidepressant-Associated Treatment Emergent Mania: A Meta-Analysis to Guide Risk Modeling Pharmacogenomic Targets of Potential Clinical Value.

The purpose of this study was to review the association between the SLC6A4 5-HTTLPR polymorphism and antidepressant (AD)-associated treatment emergent mania (TEM) in bipolar disorder alongside starting a discussion on the merits of developing risk stratification models to guide when not to provide AD treatment for bipolar depression. Studies that examined the association between clinical and genetic risk factors, specifically monoaminergic transporter genetic variation, and TEM were identified. A meta-analysis was performed using the odds ratio to estimate the effect size under the Der-Simonian and Laird model. Seven studies, referencing the SLC6A4 5-HTTLPR polymorphism and TEM (total N = 1578; TEM+ =594, TEM- = 984), of 142 identified articles were included. The time duration between the start of the AD to emergence of TEM ranged from 4 to 12 weeks. There was a nominally significant association between the s allele of the 5-HTTLPR polymorphism and TEM (odds ratio, 1.434; 95% confidence interval, 1.001-2.055; P = 0.0493; I2 = 52%). No studies have investigated norepinephrine or dopamine transporters. Although the serotonin transporter genetic variation is commercially available in pharmacogenomic decision support tools, greater efforts, more broadly, should focus on complete genome-wide approaches to determine genetic variants that may contribute to TEM. Moreover, these data are exemplary to the merits of developing risk stratification models, which include both clinical and biological risk factors, to guide when not to use ADs in bipolar disorder. Future studies will need to validate new risk models that best inform the development of personalized medicine best practices treating bipolar depression.

Genetic predictors of cultural values variation between societies

Associations between the STin2 and 5-HTTLPR polymorphisms within the serotonin transporter gene, SLC6A4, and culture across societies were examined. Based on an analysis of 75 primary studies (28,726 individuals), STin2 allelic frequencies were found to vary widely across countries, ranging from 26% in Germany to 85% in Singapore. Across 53 countries, and after controlling for all major environmental influences of culture, STin2 and 5-HTTLPR were found to explain 23.6% unique variance in monumentalism but none in individualism. Our findings evidence a significant role of genetics in predicting cross-societal cultural values variation, and potentially speak to the need for and importance of incorporating both nature and nurture in theories of cultural values variation across societies.

The Relationship between Maternal Antibodies to Fetal Brain and Prenatal Stress Exposure in Autism Spectrum Disorder.

Environmental and genetic factors contribute to the etiology of autism spectrum disorder (ASD), but their interaction is less well understood. Mothers that are genetically more stress-susceptible have been found to be at increased risk of having a child with ASD after exposure to stress during pregnancy. Additionally, the presence of maternal antibodies for the fetal brain is associated with a diagnosis of ASD in children. However, the relationship between prenatal stress exposure and maternal antibodies in the mothers of children diagnosed with ASD has not yet been addressed. This exploratory study examined the association of maternal antibody response with prenatal stress and a diagnosis of ASD in children. Blood samples from 53 mothers with at least one child diagnosed with ASD were examined by ELISA. Maternal antibody presence, perceived stress levels during pregnancy (high or low), and maternal 5-HTTLPR polymorphisms were examined for their interrelationship in ASD. While high incidences of prenatal stress and maternal antibodies were found in the sample, they were not associated with each other (p = 0.709, Cramér's V = 0.051). Furthermore, the results revealed no significant association between maternal antibody presence and the interaction between 5-HTTLPR genotype and stress (p = 0.729, Cramér's V = 0.157). Prenatal stress was not found to be associated with the presence of maternal antibodies in the context of ASD, at least in this initial exploratory sample. Despite the known relationship between stress and changes in immune function, these results suggest that prenatal stress and immune dysregulation are independently associated with a diagnosis of ASD in this study population, rather than acting through a convergent mechanism. However, this would need to be confirmed in a larger sample.

Association analysis of serotonin transporter gene polymorphism among the South-Indian migraineurs.

Background: Migraine is a multifactorial neurological disorder characterized by frequent moderate to severe intensity headaches. The genetic variations in synaptic and post-receptor signalling proteins have direct effect on the process of serotonergic neurotransmission. Methods: We aimed to investigate the genetic association of serotonin transporter (SERT) 5-hydroxytryptamine transporter-linked promoter region (5-HTTLPR) polymorphism and migraine risk in South-Indian population. A total of 304 subjects with migraine including with aura (MA) and without aura (MO) and 308 controls were included in the present study. The single nucleotide polymorphism (SNP) was detected using polymerase chain reaction (PCR) and confirmed by deoxyribonucleic acid (DNA) sequencing. Results: The genotyping analysis revealed insignificant relationship with migraine subjects when compared with controls (P > 0.05). The minor 'S' allele showed no association with odds ratio (OR) = 1.23 [95% confidence interval (CI): 0.90-1.66], heterozygote with OR = 1.18 (95% CI: 0.82-1.69), and homozygote with OR = 1.51 (95% CI: 0.52-4.35). Conclusion: Further clinical studies are required to validate the results of SERT 5-HTTLPR promoter polymorphism in diverse ethnic descents especially in Asian populations.

Relationship Between Maternal Antibodies to Fetal Brain and Prenatal Stress Exposure in Autism Spectrum Disorder (P10-9.002)

<h3>Objective:</h3> To examine the relationship between prenatal stress exposure and maternal antibodies in mothers of children diagnosed with ASD. <h3>Background:</h3> Environmental and genetic factors contribute to the etiology of ASD, but their interaction is less well understood. Mothers that are genetically more stress susceptible have been found to be at increased risk of having a child with ASD after exposure to stress during pregnancy. Additionally, presence of maternal antibodies to fetal brain are associated with a diagnosis of ASD in the child. However, the relationship between prenatal stress exposure and maternal antibodies in mothers of children diagnosed with ASD has not yet been addressed. <h3>Design/Methods:</h3> This exploratory study examined the association of maternal antibody response with prenatal stress and a diagnosis of ASD in the child. Blood samples from 53 mothers who have at least one child diagnosed with ASD were examined by ELISA. Maternal antibody presence, perceived stress level during pregnancy (high or low), and maternal 5-HTTLPR polymorphisms were examined for their interrelationship in ASD. <h3>Results:</h3> While a high incidence of prenatal stress and maternal antibodies was found in the sample, they were not associated with each other (<i>p</i>=0.709, Cramer’s <i>V</i>=0.051). Furthermore, results revealed no significant association between maternal antibody presence and the interaction between 5-HTTLPR genotype and stress (<i>p</i>=0.729, Cramer’s <i>V</i>=0.157). <h3>Conclusions:</h3> Prenatal stress was not found to be associated with presence of maternal antibodies in the context of ASD. Despite the known relationship between stress and changes in immune function, these results suggest that prenatal stress and immune dysregulation are independently associated with a diagnosis of ASD in this study population, rather than acting through a convergent mechanism. <b>Disclosure:</b> Dr. Beversdorf has received personal compensation in the range of $0-$499 for serving as a Consultant for Yamo pharmaceuticals. Dr. Beversdorf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Human Biosciences. Dr. Beversdorf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Impel Neuropharma. Dr. Beversdorf has received personal compensation in the range of $0-$499 for serving as a Consultant for Stalicla. Dr. Beversdorf has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Scioto. Dr. Beversdorf has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier (Research in Autism Spectrum Disorders). The institution of Dr. Beversdorf has received research support from Department of Defense. The institution of an immediate family member of Dr. Beversdorf has received research support from BionexusKC. Dr. Beversdorf has received personal compensation in the range of $10,000-$49,999 for serving as a Case Consultant with Best Doctors. Ms. Costa has nothing to disclose. Bradley Ferguson has received research support from United States Department of Defense. Miss Hawkins has nothing to disclose. Adriana Coman has nothing to disclose. Mr. Schauer has nothing to disclose. Alex Ramierez-Celis has nothing to disclose. Dr. Hecht has received personal compensation for serving as an employee of AbbVie. Dr. Hecht has stock in AbbVie. Danielle Bruce has nothing to disclose. Michael Tilley has nothing to disclose. Dr. Talebizadeh has nothing to disclose. Judy Van De Water has received personal compensation in the range of $500-$4,999 for serving as a Consultant for MARAbio. Judy Van De Water has stock in MARAbio. Judy Van De Water has received intellectual property interests from a discovery or technology relating to health care.

HTR1A, TPH2, and 5-HTTLPR Polymorphisms and Their Impact on the Severity of Depressive Symptoms and on the Concentration of Tryptophan Catabolites during Hepatitis C Treatment with Pegylated Interferon-α2a and Oral Ribavirin (PEG-IFN-α2a/RBV).

Seeing that there are no data about associations between serotonin gene polymorphism and tryptophan catabolite concentration during PEG-IFN-α2a treatment, the aim of the current study is to examine (a) the associations between polymorphisms within the HTR1A, TPH2, and 5-HTT genes and the severity of depression symptoms and (b) the relationships among rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms and indoleamine 2,3-dioxygenase (IDO) activity, as well as kynurenine (KYN), tryptophan (TRP), kynurenic acid (KA), and anthranilic acid (AA) concentrations. The study followed a prospective, longitudinal, single-center cohort design. The severity of the depressive symptoms of 101 adult patients with chronic HCV infections was measured during PEG-IFN-α2a/RBV treatment. We used the Montgomery-Åsberg Depression Rating Scale (MADRS) to assess the severity of depressive symptoms. The subjects were evaluated six times-at baseline and at weeks 2, 4, 8, 12, and 24. At all the time points, MADRS score, as well as KYN, TRP, KA, and AA concentrations, and IDO activity were measured. At baseline, rs6295, rs4570625, and 5-HTTLPR rs25531polymorphisms were assessed. Subjects with C/C genotypes of 5-HT1A and lower-expressing alleles (S/S, LG/LG, and S/LG) of 5-HTTLPR scored the highest total MADRS scores and recorded the highest increase in MADRS scores during treatment. We found associations between TRP concentrations and the TPH-2 and 5-HTTLPR rs25531 genotypes. Our findings provide new data that we believe can help better understand infection-induced depression as a distinct type of depression.