Serotonin Transporter Polymorphism Research Articles

Abstract TMP28: Serotonin Transporter Polymorphism Impact on Cortisol Level and Outcome After Stroke

Background: The short (s) allele of a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) is related to reduced serotonin transporter efficiency and an increased vulnerability to stress and mental disorders. The 5-HTTLPR s allele was reported as associate with hypothalamic-pituitary-adrenal (HPA)-axis reactivity to stress, depression and negatively impact on memory. Acute stroke is associated with elevated cortisol levels as part of the body’s reaction to a stress provoking event. We investigated whether 5-HTT genotype interacts with physiological stress to impact on outcome after stroke. Methods: Data from 485 non-depressed cognitively intact first-ever mild to moderate stroke patients from the TABASCO study were available. Patients underwent 3T MRI scans, saliva cortisol measure and comprehensive neuropsychological assessments at admission, 6, and 12 and 24 months thereafter. Results: Carriers of the 5-HTT-s allele (23.2%) had significantly higher admission bedtime salivary cortisol (p=0.042) and more depressive symptoms 12 and 24 months after the index event (p=0.043, p=0.05, respectively) than non-carriers. Higher admission salivary cortisol levels negatively correlated with hippocampal and amigdalar volume at admission (r=-0.257, p=0.004; r=-0.177, p=0.048, respectively) as well as with lower cognitive and higher depression scores 24 months post-stroke (r=-0.2, p=0.032, r=0.245, p=0.007, respectively). The association between salivary cortisol levels, depressive and cognitive scores was stronger in 5-HTT-s carriers than non-carriers. Conclusions: We report that carriers of the 5-HTT-s allele may be at risk to develop depressive symptoms post-stroke. The interactive effects of the s allele and cortisol levels on hippocampal volume and post-stroke depressive symptoms, as well as cognitive performance, suggest that the negative effect of the serotonin polymorphism on the development of post-stroke depression and cognitive decline is mediated by the HPA axis. Since genetic factors may influence vulnerability to the adverse effects of stress, serotonin receptors may provide a novel target for therapeutics to prevent depression and cognitive deterioration in stroke patients.

Prediction of schizophrenia using MAOA-uVNTR polymorphism: A case-control study.

Context:Schizophrenia has been associated with disorder of the dopamine system, which is downregulated by projections of the serotonin pathway. Dopamine and serotonin levels are regulated by a system of transporters and enzymes. In this research, dopamine transporter polymorphism (DAT-VNTR), serotonin transporter polymorphism (5-HTTLPR), monoamine oxidase A (MAOA-uVNTR), and catechol-o-methyl transferase (COMT Val158Met) polymorphisms have been investigated.Aims:The aim of this study was to asses frequencies of these polymorphisms in the healthy control group and patients and to asses association with schizophrenia.Settings and Design:Three hundred and fourteen healthy volunteers and 306 schizophrenia patients were included. Schizophrenia was diagnosed by Diagnostic and Statistical Manual-IV of the American Psychiatric Association, and mini international neuropsychiatric interview questionnaire was used for screening of healthy population.Materials and Methods:Genotyping was performed using polymerase chain reaction (PCR) reaction followed by gel electrophoresis and PCR-restriction fragment length polymorphism.Statistical Analysis:Categorical data were analyzed using the Chi-square test, age between subgroups was compared using the Mann–Whitney test, and all polymorphisms were tested for Hardy–Weinberg equilibrium. Logistic regression analysis was used to set the prediction model of schizophrenia.Results:Difference in genotype distribution was observed for COMT Val158Met in female and DAT-VNTR polymorphism in overall sample P = 0.021 and P = 0.028, respectively. Statistically significant association of MAOA-uVNTR and schizophrenia was observed after adjustment for anamnestic predictors of disease. P = 0.010, 80.45% participants were correctly classified.Conclusion:Our results suggest an association of MAOA-uVNTR polymorphism with schizophrenia. The difference in the distribution of COMT Val158Met and DAT-VNTR polymorphism support the involvement of dopamine system components in the pathogenesis of schizophrenia.

Biological Connection to the Feeling of Happiness

Happiness is a psychological state, resulting from the secretion of certain chemicals by specialist cells in the brain. It is a very tricky multifaceted theory that is challenging to comprehend. Humans desire to be happy and strive for the same throughout their lives. There is nothing else that can give more pleasure than being happy. Without knowing how happiness is achieved, humans tend to slog for worldly things that are perceived to bring joy. But the fact is that the human brain is a master programmer that controls when and how one feels happy. The determinants that offer happiness are numerous like biological, cognitive, behavioural, sociocultural, etc. Amongst these the biological factors are the endogenic constituents that top the table in defining human happiness. Today, happiness is a typical problem that is being examined by several researchers. It is thus, obligatory to comprehend the biological outlook of joy and understand the quality of life. Therefore, this paper intends to reflect on the biological factors that hold happiness. The data acquired from the database search is categorised under the subheadings hormones/ neurotransmitters, genetics, and the anthropometric typology. The neurotransmitters identified to offer happiness are dopamine, oxytocin, serotonin, endocannabinoids, endorphins, epinephrine, norepinephrine, cortisol, and melatonin. These are secreted in humans and have a designated purpose in ascertaining happiness. Although there is no extensive proof available on the genetics of happiness, studies suggest that 35-50% of the joy is hereditary. Genes like Serotonin Transporter Polymorphism (5-HTTLPR) and Monoamine Oxidase (MAOA) and their role in happiness are explored through various research studies. Also, the physical features of an individual have a link to human happiness. Therefore, the existing knowledge points out that the biological factors’ role is vital in determining happiness which is undebatable.

Farmakogenetika antidepresiva - korak ka individualizaciji terapije

Pharmacogenetics analyzes interindividual differences that lead to variable patient responses to therapy, with the aim of indicating how individual genes and interindividual genetic variations can affect the pharmacokinetics and pharmacodynamics of drugs. It is a critical component of personalized medicine in psychopharmacology. Most studies to date indicate the great potential of pharmacogenetic studies in the individualization of antidepressant therapy. So far, the determination of the genetic profile and metabolic phenotype for CYP2C19 in patients on escitalopram and sertraline, and CYP2C19 and CYP2D6 in patients on amitriptyline, has shown clinical significance. Although less studied, pharmacodynamic variability is no less significant than pharmacokinetic variability. Serotonin transporter polymorphisms significantly influence the therapeutic response to selective serotonin reuptake inhibitors. The pharmacogenetic approach is an innovative model in understanding the heterogeneity of the therapeutic response to antidepressants. The advantage of this approach is the permanence of the genotype over time. On the other hand, there are numerous challenges and limitations to performing these analyses routinely, such as the availability of these tests and the complexity of interpreting the results. The effect of the drug is a complex phenomenon and single mutations in individual genes cannot explain all the variability of psychopharmacotherapy. Although pharmacogenetics clearly has great potential in drug development and individualization of therapy, further research is needed to fully implement this potential in clinical practice.

Cortico-limbic functional connectivity mediates the effect of early life stress on suicidality in bipolar depressed 5-HTTLPR*s carriers

BackgroundIn bipolar disorder (BD) the risk of suicide in adult life can be influenced by the interaction of adverse childhood experiences with the serotonin transporter polymorphism (5-HTTLPR). The cortico-limbic connectivity is a candidate endophenotype for the disorder, also related to suicidality and affected by the 5-HT system. MethodsIn 64 (*s carriers = 41; l/l = 23) depressed BD patients, we explored the effect of 5-HTTLPR on corticolimbic functional connectivity (FC) during emotional processing, and the role of FC in moderating/mediating the effect of early stressful events on suicidality among 5-HTTLPR groups, by implementing Generalized Structural Equation Model. Results5-HTTLPR affects FC between amygdala (Amy) and anterior cingulate cortex (ACC), temporal pole, putamen/thalamus, and precuneus. The short allele was associated to a more inefficient corticolimbic connectivity. In 5-HTTLPR*s carriers, but not in l/l, the Amy-ACC functional coupling mediated the relationship between stress load and current suicidality. LimitationsPatients were not drug-naive, and the recruitment took place in a single center, thus raising the possibility of population stratifications. The sample size is relatively small, but our findings can provide the background for replication study in independent and larger datasets. ConclusionsOur results confirm the link between the 5-HTT promoter polymorphism and susceptibility to stress in BD, and suggest that cortico-limbic functional connectivity mediates these effects. This pattern could identify a vulnerability factor for the exacerbation of mood episodes after stressful life events particularly relevant in *s carriers.

Impact of Polymorphisms in the Serotonin Transporter Gene on Oscillatory Dynamics during Inhibition of Planned Movement in Children.

The serotonin transporter plays an important role in serotonergic neuromodulation. It is known that polymorphisms in the serotonin transporter gene are linked to the dysregulation of emotions. In the current study, we aimed to investigate the impact of variation in the gene encoding serotonin transporter polymorphism on oscillatory dynamics during inhibition of planned movement in the stop signal paradigm. During performance the stop signal paradigm, electroencephalograms (EEGs) were recorded in 90 healthy Caucasian children (39 girls) from 7 to 12 years. Buccal epithelium probes were taken from all participants. The La, Lg, and S alleles of serotonin transporter-linked polymorphic region (5-HTTLPR) polymorphism were detected in the DNA samples using PCR. LaLa genotype carriers did not differ from LaS\\LgS and LgS\\LgLg\\SS carriers in a number of successful inhibitions of a prepotent response. Carriers of LaLa exhibit higher alpha and beta event-related spectral perturbations (ERSP) in parietal and occipital cortices after the presentation of signal of inhibition of movement than LaS\\LgS and LgS\\LgLg\\SS carriers. Results are consistent with current literature and confirm that S allele carriers are more predisposed to disturbances in cognitive control.

Association between the promoter region of serotonin transporter polymorphisms and recurrent aphthous stomatitis: A meta-analysis

ObjectivesTo assess the association between the promoter region of serotonin transporter (5-HTTLPR) gene polymorphism and recurrent aphthous stomatitis (RAS) occurrence. DesignsWe performed the meta-analysis to determine the potential association between 5-HTTLPR polymorphism and RAS. We retrieved revelant studies from the PubMed, Scopus, Embase, Web of Science and Cochrane Library databases up to January 2019. Data were analyzed for odd ratios with 95% confidence intervals using Revman 5.3 software. ResultsThere were 4 studies in the meta-analysis, which included 291 RAS cases and 286 controls. It indicated a substantially augmented threat of RAS with respect to S vs. L (P = 0.005), SS vs. LL+LS (P ＜ 0.0001) and SS vs. LL models (P ＜ 0.00001), respectively. No heterogeneity was found between studies in all comparisons. ConclusionsThe current meta-analysis provides evidence to prove the association between 5-HTTLPR polymorphism and RAS. Further studies should be performed to clarify the biochemical function and pathological role of 5-HTTLPR in the risk of RAS.

A serotonin transporter polymorphism is associated with postoperative nausea and vomiting: An observational study in two different patient cohorts.

Clinical risk factors for postoperative nausea and vomiting (PONV) are well described, whereas genetic findings are conflicting. The aim of this study was to investigate a possible association of genetic variants and nongenetic variables with the incidence and severity of PONV. A prospective observational study in two independent and different patient cohorts. Two independent patient cohorts differing in surgical procedures were enrolled in two tertiary care hospitals between 2008 and 2016. Consecutive patients of European origin undergoing elective surgery in two university hospitals. Clinical data were collected up to 24 h after surgery, and blood was drawn for genotyping. Of 2773 patients enrolled, 918 (Cohort A) and 1663 (Cohort B) with complete data sets were analysed. Patients were allocated to one of three groups (No PONV, Intermediate PONV or Severe PONV) depending on the frequency of vomiting, the severity of nausea and the need for antiemetics. Clinical variables and 13 genetic variants of seven candidate genes were evaluated for association with these three phenotypes. The cohorts were analysed separately by ordinal logistic regression analysis, treating PONV as a dependent ordinal three-stage variable. Odds ratios (ORs) with 95% confidence intervals were calculated. In Cohort A, the main predictors for PONV were female sex [OR (95% CI): 3.6 (2.7 to 4.8), P < 0.0001], nonsmoking status 1.8 (1.3 to 2.5), P < 0.001, the SS genotype (5-HTTLPR, rs4795541) of the promoter polymorphism in the serotonin transporter 1.5 (1.1 to 2.1), P = 0.019, and patient age 0.99 (0.98 to 0.99), P = 0.013. Analysis of Cohort B was consistent with these findings [5-HTTLPR: 1.8 (1.4 to 2.3), P < 0.00001]. Sex-specific regression models confirmed this 5-HTTLPR association in women and men. In two independent cohorts, in addition to the well known clinical factors, a polymorphism of 5-HTTLPR in the serotonin transporter was independently associated with PONV. A possible evaluation of this biomarker to improve risk prediction within the scope of precision medicine should be considered. Clinicaltrials.gov identifier NCT03490175.

Insula serotonin 2A receptor binding and gene expression contribute to serotonin transporter polymorphism anxious phenotype in primates

Genetic variation in the serotonin transporter gene (SLC6A4) is associated with vulnerability to affective disorders and pharmacotherapy efficacy. We recently identified sequence polymorphisms in the common marmoset SLC6A4 repeat region (AC/C/G and CT/T/C) associated with individual differences in anxiety-like trait, gene expression, and response to antidepressants. The mechanisms underlying the effects of these polymorphisms are unknown, but a key mediator of serotonin action is the serotonin 2A receptor (5HT2A). Thus, we correlated 5HT2A binding potential (BP) and RNA gene expression in 16 SLC6A4 genotyped marmosets with responsivity to 5HT2A antagonism during the human intruder test of anxiety. Voxel-based analysis and RNA measurements showed a reduction in 5HT2A BP and gene expression specifically in the right posterior insula of individuals homozygous for the anxiety-related variant AC/C/G. These same marmosets displayed an anxiogenic, dose-dependent response to the human intruder after 5HT2A pharmacological antagonism, while CT/T/C individuals showed no effect. A voxel-based correlation analysis, independent of SLC6A4 genotype, revealed that 5HT2A BP in the adjacent right anterior insula and insula proisocortex was negatively correlated with trait anxiety scores. Moreover, 5HT2A BP in both regions was a good predictor of the size and direction of the acute emotional response to the human intruder threat after 5HT2A antagonism. Our findings suggest that genetic variation in the SLC6A4 repeat region may contribute to the trait anxious phenotype via neurochemical changes in brain areas implicated in interoceptive and emotional processing, with a critical role for the right insula 5HT2A in the regulation of affective responses to threat.

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 gene methylation predicts long-term cortisol concentrations in hair

Epigenetic signatures, such as DNA methylation (DNAM), have been implicated in long-term dysregulation of the hypothalamus–pituitary–adrenal (HPA) axis and related health risks. Based on a wealth of neuroendocrine studies on genetic polymorphisms in the serotonin transporter gene (SLC6A4), this locus constitutes a key candidate to explore associations of DNAM patterns and HPA-axis functioning. The few studies addressing this link so far exclusively relied on spot measurements of HPA-axis activity, which may not adequately reflect cortisol output over prolonged periods of time. To address this gap, hair cortisol concentrations (HCC), a valid measure of integrated long-term cortisol levels, were utilized to investigate endocrine correlates of SLC6A4 DNAM in 183 adults. Whole blood samples were drawn for DNAM analyses of 83 CpG sites within a 799-bp promoter-associated CpG island of SLC6A4 via bisulfite pyrosequencing. In addition, all participants were genotyped for the serotonin transporter polymorphism (5-HTTLPR). First, results revealed a significant negative association of SLC6A4 DNAM and HCC. Second, there was no significant main effect of 5-HTTLPR genotype on HCC when analyses were conducted on the basis of both bi-allelic classification and the 5-HTTLPR/rs25531 mini-haplotype. Third, the current data revealed a significant interaction of SLC6A4 DNAM and 5-HTTLPR genotype on HCC. Comparable to the pattern we had previously observed concerning cortisol stress reactivity, the S allele relates to increased HCC in individuals displaying low levels of SLC6A4 DNAM. By contrast, no such effect occurred under conditions of high SLC6A4 DNAM, indicating that epigenetic changes may compensate for genotype-dependent differences in long-term cortisol output. Together, respective findings support the idea of an epigenetic contribution to long-term HPA-axis activity and further highlight the usefulness of combining genetic and epigenetic information in future neuroendocrine studies.

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

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

Effect of genetic polymorphism of brain-derived neurotrophic factor and serotonin transporter on smoking phenotypes: A pilot study of Japanese participants

PurposeThis study investigated whether a gene polymorphism causing a Val66Met substitution (rs6265) in brain-derived neurotrophic factor (BDNF) is associated with smoking initiation, smoking cessation, nicotine dependence and age of smoking initiation, in Japanese participants. Additionally, this study examined whether the S allele of the serotonin transporter gene-linked polymorphic region (5-HTTLPR) is associated with the BDNF Val66Met polymorphism on smoking phenotypes. Patients and methodsThe genotypic proportion of the polymorphism responsible for BDNF Val66Met was determined in 148 participants including 88 current smokers, 21 former smokers, and 39 never smokers, and Fisher's exact test was used to investigate the relationship between this polymorphism and smoking cessation and initiation as well as the association between the genotypes of current smokers with a heavy smoking index (HSI) and the age of smoking initiation. In addition to the BDNF Val66Met polymorphism, the 5-HTTLPR polymorphism has also been evaluated in a specific subset of participants. ResultsWe found statistically significant correlations between the BDNF Val66Met polymorphism and the HSI, both in the whole study sample (P = 0.017) and in the male subgroup (P = 0.049). Moreover, the 5-HTTLPR polymorphism was associated with the age of smoking initiation in current smokers carrying the BDNF Met allele, in both the whole study sample (P = 0.041) and the male subgroup (P = 0.041). On the other hand, no association was observed between the BDNF Val66Met polymorphism, either alone or in combination with the 5-HTTLPR polymorphism, and the age of smoking cessation. Finally, no independent effects of the BDNF Val66Met genotype on the age of smoking initiation were detected. ConclusionThis pilot study provides preliminary findings regarding the influence of BDNF Val66Met on smoking phenotypes and the interacting effect of 5-HTTLPR on the association between BDNF Val66Met and smoking phenotypes in Japanese participants.

SA45 - AFFECTIVE TEMPERAMENT AND DEPRESSIVE SYMPTOMS IN OBESE INDIVIDUALS IN THE CONTEXT OF SEROTONERGIC TRANSCRIPTIONAL GENE POLYMORPHISMS

Background Patients with obesity experience many psychological burdens. Some of them result directly from the load that jets excessive weight. Nevertheless, it seems that the susceptibility of obese people to accompanying mental disorders can be ingested not only by the environment, but also genetically. The aim of this work was to determine the correlation of the genetic aspects of serotoninergic (SERT, 5-HT2A) transmission with the severity of depressive symptoms and the affective temperament profile in subjects with simple obesity. Methods The study included 506 patients with simple obesity who were excluded secondary causes of obesity and significant mental illness. Clinical, psychological and genetic analyzes were performed. To assess the severity of depressive symptoms, Beck Depression Inventory and the Hamilton Depression Scale were used. Affective temperament was assessed using the TEMPS-A questionnaire. Polymorphism of serotonin transporter (SERT 44-bp insertion/deletion) and serotonin receptor 2 A type (1438 G/A) were evaluated as potential genetic markers of psychological factors. Results The long allele of SERT gene was associated with significantly higher BMI and more pronounced depressive, cyclothymic and hyperthymic dimensions of affective temperament. Interestingly, these subjects obtained the lowest scores of both scales, which measured the severity of depressive symptoms. Adenine homozygotes in examined 5-HT2A polymorphism were characterized by higher BMI and more pronounced anxious and, in particular, hyperthymic dimension of temperament. Carriers of particular polymorphisms in this gene did not differ significantly in the clinical scale evaluating the severity of depressive symptoms. Discussion Polymorphisms of both examined genes revealed correlations in affective temperamental dimensions. Acknowledgments in the SERT polymorphism seems to play a more important role in the regulation of reactive depressive symptoms.

Interdependence and Depression: Does an Interdependent Culture Provide Effective Buffer Against Depression?

This literature review examines the cultural factor which potentially contributes to the difference between high rates of depression in Western nations and significantly lower rates in the East. Somatisation of depressive symptoms by the Chinese is addressed and attempted to be explained from the perspective of emotion as a relational component of self as opposed to residing discretely within a person. The possibility of an interdependent cultural environment which provides a buffer against the higher risk of depression amongst Asians as observed from their greater frequency of serotonin transporter polymorphism genotype may explain the low prevalence of depression in East-Asian countries. The lower risk-taking tendency of East Asians, promoted by interdependent cultural philosophy and mediated by increased amygdala reactivity, may serve as an additional means to counter greater genetic susceptibility to clinical depression. Upon analysing the trend in the United States shortly after World War II, it is possible to link together the concurrent increase in individualism and rates of depression in the country. Social factors appeared to have affected the surging rates amongst high-risk groups of women and the young population. The rate of depression in more interdependent rural areas was lower than urban regions of the United States, with a similar difference observed between rural and urban Canada. The lower rate in rural settings was related to its residents’ stronger sense of community belonging. Overall, research findings give further weight to the relationship between the interdependence of a culture and the depression rates of its people.

Mechanisms of Early Adversity Associated Increases In Risk For Psychiatric Disorders

Overall Abstract Early adverse exposures, such as maternal stress or toxins during pregnancy and childhood adversity are thought to result in long-lasting consequences on many systems, including the brain and ultimately in an increased risk for psychiatric disorders. The impact of these environmental risk factors is moderated by genetic variation. The biological mechanisms underlying this increased risk are still unclear. This symposium will focus on potential mechanisms mediating these lasting effects and their moderation by genetic variation, with epigenetics, specifically DNA methylation as main candidate. The developing brain is highly sensitive to environmental exposures during the in utero period and three of the presentations will focus on how environmental factors during pregnancy alter risk for psychiatric symptoms as well as brain structure and function and have lasting influences on the epigenome at birth. Prenatal exposures such as cigarette smoke, heavy metals, and folic acid are associated with changes in DNA methylation measured in infants at birth Kelly Bakulski (University of Michigan) will report on data generated in an autism enriched-risk birth cohort that examines the sensitivity of DNA methylation at birth, measured in placental tissue and cord blood, to in utero environmental exposures and the development of autism spectrum disorder or related traits by age three. Margit Burmeister (University of Michigan) will present a study of iron deficiency in newborns in China, demonstrating the detrimental effects of pre-and postnatal iron deficiency with regards to brain structure and function. This is complemented by genome-wide epigenetic analyses that investigate the impact of iron deficiency in the presence of lead exposure and pesticides. Another set of pregnancy-related risk factors associated with increased risk for emotional and behavioral problems in children are stress and depression during pregnancy. Katri Raikkonen (University of Helsinki, Finland) will present data from a large prospective study of pregnancy risk factors and their effects on cord blood DNA methylation and child behavior up to 3.5 years of age. Maternal depression during pregnancy was related to significant changes in a recently established epigenetic predictors of gestational age, with increasing depression, associated with more “immature” epigenetic age. This epigenetic marker was then in turn predicting total behavioral, emotionally reactive, and withdrawn problems in boys. Finally, risk for psychiatric symptoms following exposure to childhood adversity is moderated by genetic variation. Understanding the mechanisms of this moderation may help in targeting specific treatments to children with combined genetic and environmental risk. Sara Jaffee (University of Pennsylvania) showed that 8- to 11-year-old children from the UK who carried two copies of the serotonin transporter polymorphism had elevated levels of internalizing and externalizing problems following exposure to adverse life events because of their coping strategies. Influencing the coping styles of these children may be an effective treatment strategy in this subgroup of children. At the end of the symposium, Elisabeth Binder (MPI of Psychiatry, Munich) will comment of common mechanisms emerging from the data presented in the individuals talk and how a better understanding of these factors will aid biology-based diagnoses of psychiatric disorders and individualized treatment approaches.

Associations between stress and depression symptom profiles vary according to serotonin transporter polymorphism in rural Australians

PurposeDepression remains difficult to treat in all cases, and further investigation of the role of genetic and environmental factors may be valuable. This study was designed to investigate the association between the short (s) versus non-short (non-s) 5HTTLPR variants, presence of childhood stressors and recent life stressors, and depression, and to do so at two levels that would expose the associations between total depression scores and also individual depression items.Materials and methodsTwo hundred and forty-nine volunteers from one of the Australian Electoral Office electorates covering a large rural land area completed a series of questionnaires about childhood and recent life stress and depression, and provided a buccal cell sample for genotyping the 5-HTTLPR polymorphism into s versus non-s carriers.ResultsAlthough there were no significant differences in the depression scores of the s-carriers versus the non-s carriers, each subtype of the 5-HTTLPR polymorphism showed different patterns of association between childhood stress and depression symptoms, and between recent life stress and depression symptoms.ConclusionIndividualization of therapy for depression may be achieved through consideration of the specific associations that patients exhibit between life stress, 5-HTTLPR polymorphism, and depression symptomatology.

Association of Polymorphisms of Serotonin Transporter (5HTTLPR) and 5-HT2C Receptor Genes with Criminal Behavior in Russian Criminal Offenders

Background: Human aggression is a heterogeneous behavior with biological, psychological, and social backgrounds. As the biological mechanisms that regulate aggression are components of both reward-seeking and adversity-fleeing behavior, these phenomena are difficult to disentangle into separate neurochemical processes. Nevertheless, evidence exists linking some forms of aggression to aberrant serotonergic neurotransmission. We determined possible associations between 6 serotonergic neurotransmission-related gene variants and severe criminal offenses. Methods: Male Russian prisoners who were convicted for murder (n = 117) or theft (n = 77) were genotyped for variants of the serotonin transporter (5HTTLPR), tryptophan hydroxylase, tryptophan-2,3-dioxygenase, or type 2C (5-HT2C) receptor genes and compared with general-population male controls (n = 161). Prisoners were psychologically phenotyped using the Buss-Durkee Hostility Inventory and the Beck Depression Inventory. Results: No differences were found between murderers and thieves either concerning genotypes or concerning psychological measures. Comparison of polymorphism distribution between groups of prisoners and controls revealed highly significant associations of 5HTTLPR and 5-HTR2C (rs6318) gene polymorphisms with being convicted for criminal behavior. Conclusions: The lack of biological differences between the 2 groups of prisoners indicates that the studied 5HT-related genes do not differentiate between the types of crimes committed.

Variation in the serotonin transporter polymorphism (5-HTTLPR) and inertia of negative and positive emotions in daily life.

An important element of understanding the genotype-phenotype link in psychiatric disorders lies in identifying the psychological mechanisms through which genetic variation impacts mental health. Here we examined whether emotional inertia, the tendency for a person's emotions to carry over from 1 moment to the next and a prospective predictor of the development of depression, is associated with a known genetic risk factor for emotional dysregulation, a polymorphism in the serotonin transporter gene (5-HTTLPR). Two hundred thirty-six adolescents recorded their positive and negative emotions in daily life 9 times a day for 6 consecutive days using smartphones, completed a depression questionnaire, and were genotyped for the 5-HTTLPR polymorphism. Carriers of the short 5-HTTLPR were characterized by higher inertia for negative emotions, even after controlling for depressive symptoms. These findings suggest a possible psychological pathway how the serotonin transporter gene contributes to risk for depression. (PsycINFO Database Record

The relation between temporomandibular disorders, mood status and serotonin transporter gene polymorphism. Study in Syrian population.

The purpose of this study was to evaluate the relationship betweentemporomandibular disorders, mood status and serotonin transporter (5-HTT) genepolymorphisms in Syrian population. Twenty patients with temporomandibular jointdisorder (TMD), and 36 healthy control subjects were examined. The sample consistsof 23 males, and 33 females aged between (19-30 years old), visited the department offixed prosthodontic of the faculty of dentistry, Damascus University. This studyshows that S/L allele of 5-HTTLPR was the most frequently observed allele in TMDpatients; whereas statistical analysis did not show significant difference betweenpatient and control groups by neither genotype distribution analysis nor allelefrequency analysis. S\S allele analysis showed a relation between it and mood status.Although the study did not show significant relation between TMD and serotonintransporter polymorphism gene, but according to the importance of serotonintransporter polymorphism gene and its relation to psychological factors we suggestother studies which focus on the relation between the genetics, psychology and TMD.