Serotonin transporter is negatively associated with body mass index after glucose loading in humans.

Serotonin transporter (SERT) is a presynaptically localized membrane protein that regulates the serotonin transmission via its reuptake of released serotonin. We hypothesized that glucose loading may change SERT availability from brainstem in humans. An intravenous bolus injection of 18F-FP-CIT was administered after the infusion of glucose or placebo (normal saline), and the emission data were acquired over 90 mins in 33 healthy nonobese subjects. For a volume-of-interest-based analysis, an atlas involving midbrain, and pons was applied. SERT availability, binding potential (BPND), were measured via the simplified reference tissue method with a reference of cerebellum. For a voxel-based analysis, statistical parametric mapping 12 was used with parametric BPND images. BPNDs from midbrain (p=0.8937), and pons (p=0.1115) were not different between glucose and placebo loading. Both of BPNDs from midbrain after glucose, and placebo loading were negatively correlated with body mass index (BMI). BMI showed a trend of negative correlation with glucose-loaded BPND from pons, whereas, placebo-loaded BPNDs from pons did not show any significant association with BMI. In conclusion, SERT availability was negatively correlated with BMI after glucose loading in humans. SERT might have a role in eating behavior through the action of insulin. Further studies are needed to elucidate the underlying mechanism of this phenomenon.

Genetic markers of the stress generation model: A systematic review.

AIM: Robust evidence suggests that depression, and risk for depression, are associated with the generation of stressful life events. This tendency to generate stress may be genetically determined. This systematic review aimed to identify specific molecular genetic markers associated with the generation of interpersonal stressful life events, at least in part dependent on individuals' behavior. METHOD: We followed the PRISMA guidelines in searching six electronic databases (PubMed, MEDLINE, PsycINFO, CINAHL, Cochrane, and EMBASE) from inception to January 2021, and we reviewed the reference lists of eligible articles for additional records. We restricted eligibility to empirical studies involving at least one genetic marker and including proximal life events. We evaluated the risk of bias using the Newcastle Ottawa Scale for observational studies. The outcome permitted a distinction between life events dependent on the individual's agency versus independent events. RESULTS: Seven studies, including 3585 participants, met eligibility criteria. Three were longitudinal, and four were cross-sectional; six included adolescents and young adults, and one focused on middle adulthood. Four examined the serotonin-transporter-linked promoter region (5-HTTLPR), two examined the rs53576 single nucleotide polymorphism of the oxytocin receptor gene (OXTR), and one examined a multilocus genetic profile score including four hypothalamic-pituitary-adrenal (HPA) axis genes. There were no significant direct correlations between genotype and life events in any study. Instead, their relation was significantly moderated by symptoms, exposure to early adversity, or attachment. Consistent with the stress generation hypothesis, this moderation relation was significant in predicting exposure to dependent life events but was not significant in predicting independent life event exposure. CONCLUSIONS: There is evidence that genetic variation in the serotonin, HPA axis, and oxytocin systems moderates the effects of psychosocial vulnerability markers on the generation of proximal, dependent life events. Future research should examine additional genetic markers in systems known to confer risk for stress generation. PROSPERO: CRD42019136886.

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

BACKGROUND/AIMS: The 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. METHODS: Three 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. RESULTS: The 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. CONCLUSION: SS 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.

INFLUENCE OF THE SEROTONERGIC SYSTEM POLYMORPHISM ON THE EXPRESSION OF DENTAL ANXIETY.

- The aim of the study was to test the correlation between 5-HTTLPR polymorphism and dental anxiety. Research hypothesis was that positive relation between the expression of dental anxiety and the S allele exists in the population of healthy Caucasians. We conducted a prospective study on 159 subjects, volunteers made up of medical and non-medical staff of the Sestre milosrdnice University Hospital Centre. Both genders were included, age range 19 to 59, mentally and physically healthy (according to DSM-5 classification of mental disorders). For the purpose of this research, we used a sociodemographic questionnaire containing the following information: age, gender, education level, work status, marital status and residence. Corah's Dental Anxiety Scale-Revised (DAS-R) was used to measure dental anxiety. Data distribution was tested by Kolmogorov-Smirnov test, difference between the groups by ?χ2-test and one-way analysis of variance, and correlation of variables by logistic regression. In the study population, we found positive correlation between S-allele and total result in DAS-R questionnaire. The presence of S allele suggests that the person will have a higher result in DAS-R questionnaire, i.e. higher expression of dental anxiety.

Genotypes do not confer risk for delinquency but rather alter susceptibility to positive and negative environmental factors: gene-environmentinteractions of BDNF Val66Met, 5-HTTLPR, and MAOA-uVNTR [corrected].

BACKGROUND: Previous evidence of gene-by-environment interactions associated with emotional and behavioral disorders is contradictory. Differences in findings may result from variation in valence and dose of the environmental factor, and/or failure to take account of gene-by-gene interactions. The present study investigated interactions between the brain-derived neurotrophic factor gene (BDNF Val66Met), the serotonin transporter gene-linked polymorphic region (5-HTTLPR), the monoamine oxidase A (MAOA-uVNTR) polymorphisms, family conflict, sexual abuse, the quality of the child-parent relationship, and teenage delinquency. METHODS: In 2006, as part of the Survey of Adolescent Life in Västmanland, Sweden, 1 337 high-school students, aged 17-18 years, anonymously completed questionnaires and provided saliva samples for DNA analyses. RESULTS: Teenage delinquency was associated with two-, three-, and four-way interactions of each of the genotypes and the three environmental factors. Significant four-way interactions were found for BDNF Val66Met × 5-HTTLPR×MAOA-uVNTR × family conflicts and for BDNF Val66Met × 5-HTTLPR×MAOA-uVNTR × sexual abuse. Further, the two genotype combinations that differed the most in expression levels (BDNF Val66Met Val, 5-HTTLPR LL, MAOA-uVNTR LL [girls] and L [boys] vs BDNF Val66Met Val/Met, 5-HTTLPR S/LS, MAOA-uVNTR S/SS/LS) in interaction with family conflict and sexual abuse were associated with the highest delinquency scores. The genetic variants previously shown to confer vulnerability for delinquency (BDNF Val66Met Val/Met × 5-HTTLPR S × MAOA-uVNTR S) were associated with the lowest delinquency scores in interaction with a positive child-parent relationship. CONCLUSIONS: Functional variants of the MAOA-uVNTR, 5-HTTLPR, and BDNF Val66Met, either alone or in interaction with each other, may be best conceptualized as modifying sensitivity to environmental factors that confer either risk or protection for teenage delinquency.