Identification of Relationships Among Resilience Factors Using Network Analysis: A Pilot Study.

BACKGROUND: Although college life can be fulfilling, it can be stressful, particularly for health professional students. In addition, they may have had Adverse Childhood Experience (ACE) that increases their sensitivity to academic stress. Yet, students need to overcome challenges to become successful professionals. The literature suggests the following factors may be associated with resilience: ACE and academic stress as the antecedents; ego-resilience, emotion regulation, resources, social support, inflammatory markers, and genes as the defining attributes; and mental health and sense of coherence (SOC) as the consequences. AIMS: The purpose is to identify the relationships among factors associated with resilience using network analysis. METHODS: A total of 70 college students participated in this cross-sectional pilot study. They completed measures of psychosocial variables and provided saliva samples, which were analyzed for Serotonin Transporter-Linked Promoter Region (5-HTTLPR)/rs25531 and inflammatory markers. Mixed graphical models including all variables were estimated using the R-package mgm. RESULTS: Network analysis revealed positive associations between (1) mental health and SOC; (2) mental health and resources; (3) mental health and social support; (4) SOC and reappraisal of emotion regulation; (5) resources and reappraisal of emotion regulation; and (6) resources and social support. In addition, SOC and academic stress were negatively associated. Furthermore, the short variant of 5-HTTLPR/rs25531 was associated with stronger suppression of emotion regulation and fewer resources compared with the long variant. CONCLUSION: Resilience may be influenced by biopsychosocial factors, notably SOC and 5-HTTLPR/rs25531. However, longitudinal research is needed with a larger sample size to better understand how these and other factors may affect resilience.

ASSESSMENT OF THE ASSOCIATION OF SEROTONIN TRANSPORTER GENE (5-HTTVNTR & 5-HTTLPR) POLYMORPHISM IN PATIENTS WITH FIBROMYALGIA SYNDROME.

OBJECTIVE: The aim: To study the clinical and the genetic association of 5-HTTVNTR and the 5-HTTLPR polymorphisms in women with FMS. PATIENTS AND METHODS: Materials and methods: 105 FMS patients and 105 controls were enrolled in the study. Polymerase chain method was used to analyse the 5-HTTLPR & 5-HTTVNTR gene polymorphism. The psychopathology status of the 105 FMS patients and 105 healthy controls was assessed using the Beck Depression Inventory (BDI) and the Symptom Checklist-90-Revised (SCL-90-R) questionnaires. RESULTS: Results: In FMS patients and controls, the 10/10, 10/12, and 12/12 genotypes of the 5-HTTVNTR polymorphism were found in 3.8% and 2.9%, 20% and 15.2%, and 76.28% and 81.90%, respectively. Additionally, the L/L, S/L, and S/S genotypes of the 5-HTTLPR polymorphism were found in 4.8% and 2.9%, 36.2% and 40%, 59% and 57.1%, in FMS patients and healthy controls, respectively. There were no significant differences in the frequency of genotypes between FMS patients and controls. There were no significant differences in the BDI and the SCL-90-R scores according to the serotonin transporter genotypes. CONCLUSION: Conclusions: We found no significant difference between 5-HTT gene polymorphism (5-HTTVNTR and 5-HTTLPR) and the psychiatric test results (P>0.05) in FMS patients. Hence, we conclude that serotonin gene polymorphism (5-HTTLPR & 5-HTTVNTR) is not associated with FMS in north Indian women. Our results suggests that the serotonin transporter polymorphism does not seem to be a susceptibility factor for FMS.

Association of serotonin transporter-linked polymorphic region (5-HTTLPR) with heat pain stimulation and postoperative pain in gastric cancer patients.

BACKGROUND: The aim of this study was to assess whether the genotype of the serotonin transporter-linked polymorphic region (5-HTTLPR) in gastric cancer patients is associated with postoperative pain and pain threshold. METHODS: We conducted a prospective cohort study of 251 patients scheduled for gastrectomy from May to September 2019. All patients enrolled in the study were asked to complete the Hospital Anxiety and Depression Scale questionnaire. Heat pain threshold (HPT), cold pain threshold (CPT) and Pressure pain threshold (PPT) were measured for all participants one day prior to surgery. Blood samples were collected for genetic testing. All patients were connected to a patient-controlled intravenous analgesia (PCIA) pump at the end of the surgery. After exclusion of 15 patients, the postoperative conditions of 236 patients were recorded. RESULTS: Distribution of homozygous long (L/L), heterozygous (L/S), and homozygous short (S/S) 5-HTTLPR genotypes among participants were 26 (11.0%), 91 (38.6%), and 119 (50.4%), respectively. Heat pain threshold (P = 0.038) and Numerical rating scale (NRS) in the 1st postoperative 24 h (P = 0.026) were significantly different between long (L/L) and short (S/S) genotype carriers. CONCLUSIONS: In patients with gastric cancer, heat pain stimulation is associated with 5-HTTLPR polymorphism, and postoperative pain may be related to 5-HTTLPR polymorphism.

The role of maternal touch in the association between SLC6A4 methylation and stress response in very preterm infants.

Very preterm (VPT) infants requiring hospitalization in the Neonatal Intensive Care Unit (NICU) are exposed to several stressful procedural experiences. One consequence of NICU-related stress is a birth-to-discharge increased serotonin transporter gene (SLC6A4) methylation that has been associated with poorer stress regulation at 3 months of age. Maternal touch is thought to support infants' stress response, but its role in moderating the effects of SLC6A4 methylation changes is unknown. The aim of this study was to assess the role of maternal touch in moderating the association between increased SLC6A4 methylation and stress response in 3-month-old VPT infants. Twenty-nine dyads were enrolled and at 3 months (age corrected for prematurity), participated in the Face-to-Face Still-Face paradigm to measure infants' stress response (i.e., negative emotionality) and the amount of maternal touch (i.e., dynamic and static). Results showed that low level of maternal touch is associated with high level of negative emotionality during social stress. Furthermore, during NICU stay SLC6A4 methylation in VPT exposed to low level of maternal touch at 3 months was associated with increased negative emotionality. Thus, low levels of maternal static touch can intensify the negative effects of SLC6A4 epigenetic changes on stress response in 3-month-old VPT infants.

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

BACKGROUND: The 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. METHODS: 628 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. RESULTS: The 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 CONCLUSIONS: The 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.

Maternal neglect and the serotonin system are associated with daytime sleep in infant rhesus monkeys.

Environmental and biological factors contribute to sleep development during infancy. Parenting plays a particularly important role in modulating infant sleep, potentially via the serotonin system, which is itself involved in regulating infant sleep. We hypothesized that maternal neglect and serotonin system dysregulation would be associated with daytime sleep in infant rhesus monkeys. Subjects were nursery-reared infant rhesus macaques (n = 287). During the first month of life, daytime sleep-wake states were rated bihourly (0800-2100). Infants were considered neglected (n = 16) if before nursery-rearing, their mother repeatedly failed to retrieve them. Serotonin transporter genotype and concentrations of cerebrospinal fluid 5-hydroxyindoleacetic acid (5-HIAA) were used as markers of central serotonin system functioning. t tests showed that neglected infants were observed sleeping less frequently, weighed less, and had higher 5-HIAA than non-neglected nursery-reared infants. Regression revealed that serotonin transporter genotype moderated the relationship between 5-HIAA and daytime sleep: in subjects possessing the Ls genotype, there was a positive correlation between 5-HIAA and daytime sleep, whereas in subjects possessing the LL genotype there was no association. These results highlight the pivotal roles that parents and the serotonin system play in sleep development. Daytime sleep alterations observed in neglected infants may partially derive from serotonin system dysregulation.

The Return of Fear: Variation of the Serotonin Transporter Gene Predicts Outcome of a Highly Standardized Exposure-Based One-Session Fear Treatment.

BACKGROUND: Methodological problems of existing research, such as the application of unstandardized treatments in heterogeneous samples, has hampered clear conclusions about the extent and direction to which allelic variation of the serotonin transporter gene-linked polymorphic region (5- HTTLPR) is associated with a differential response to psychological treatment. The present study aimed to investigate the effects of the 5-HTTLPR genotype on treatment outcome under highly standardized environmental conditions. METHODS: We treated 222 medication-free adults highly fearful of spiders, dental surgeries or blood, injuries and injections with a highly standardized exposure-based 1-session treatment and genotyped them for the 5-HTTLPR. Participants' subjective fear was assessed before, immediately after treatment and at 7 months of follow-up. RESULTS: There were no differences between 5-HTTLPR genotypes in treatment outcome effects at the immediate posttreatment assessment. However, we observed a highly significant genotype × treatment effect (p = 0.004) at the 7-month follow-up. Fear levels of homozygous S allele carriers differed from those heterozygous (p = 0.026) and homozygous (p = 0.012) for the L allele. Compared to posttreatment assessment, LL allele carriers exhibited a further fear decrease at the follow-up assessment. In contrast, SS allele carriers displayed a strong return of fear. CONCLUSIONS: Results suggest that genetic variation of the serotonin transporter is associated with differential stability of inhibitory learning processes, potentially reflecting heightened susceptibility for context-related processes that facilitate a return of fear in S allele carriers. If replicated, results suggest the 5-HTTLPR might represent a biomarker for the long-term outcome of brief exposure-based fear treatments and might inform genotype-based selection of psychotherapeutic interventions.

A pilot study exploring the association of morphological changes with 5-HTTLPR polymorphism in OCD patients.

BACKGROUND: Clinical and pharmacological studies of obsessive-compulsive disorder (OCD) have suggested that the serotonergic systems are involved in the pathogenesis, while structural imaging studies have found some neuroanatomical abnormalities in OCD patients. In the etiopathogenesis of OCD, few studies have performed concurrent assessment of genetic and neuroanatomical variables. METHODS: We carried out a two-way ANOVA between a variable number of tandem repeat polymorphisms (5-HTTLPR) in the serotonin transporter gene and gray matter (GM) volumes in 40 OCD patients and 40 healthy controls (HCs). RESULTS: We found that relative to the HCs, the OCD patients showed significant decreased GM volume in the right hippocampus, and increased GM volume in the left precentral gyrus. 5-HTTLPR polymorphism in OCD patients had a statistical tendency of stronger effects on the right frontal pole than those in HCs. CONCLUSIONS: Our results showed that the neuroanatomical changes of specific GM regions could be endophenotypes of 5-HTTLPR polymorphism in OCD.

DNA methylation levels of the serotonin transporter gene are not associated with the outcome of highly standardized one-session exposure-based fear treatment.

Epigenetic alterations are regarded as a potential mechanism mediating the effects of environmental risk factors on vulnerability for a range of mental health problems. Recent studies have addressed the question whether DNA methylation patterns predict the outcome of psychological interventions and whether treatment effects might be associated with changes of DNA methylation. We assessed phobic fear symptoms, treatment-relevant traits and treatment response in 308 adults free of psychotropic medication - highly fearful of either spiders, blood-injury-injections, dental-treatments or heights - all subjected to highly standardized exposure-based one-session fear treatment. DNA methylation level of the promotor region of the serotonin transporter gene (SLC6A4) was assessed in either saliva samples (spider and dental treatment fear cohorts) or oral mucosa (BII, heights) to check whether possible effects are independent of the surrogate tissue examined. Moreover, in order to examine possible DNA methylation by genotype effects, patients were assessed for genetic variation of the serotonin transporter-linked polymorphic region (5-HTTLPR). DNA methylation levels were neither associated with pre-treatment fear levels, treatment relevant traits or treatment outcome data even when allelic variation of the 5HTTLPR was considered. Overall DNA methylation levels were higher in saliva samples compared to buccal samples. In saliva samples there was a small pre- to post-treatment increase in DNA methylation, which, however, was also not associated with the investigated phenotypes. We conclude that DNA methylation of SLC6A4 is no suitable biomarker for response efficacy to highly standardized one-session exposure-based fear treatments.

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.

Associations of SLC6A4 methylation with salivary cortisol, salivary alpha-amylase, and subjective stress in everyday life.

Dysregulations of the hypothalamic-pituitary-adrenal (HPA) and sympatho-adrenal medullary (SAM) axis are associated with mental and somatic illness. However, there is lack of knowledge regarding the molecular mechanisms underlying these effects. Epigenetic states in the serotonin transporter gene (SLC6A4) were shown to be associated with stress in various forms. We hypothesized that levels of DNA methylation (DNAm) of SLC6A4 would be associated with altered SAM- and HPA regulation in daily life. N = 74 healthy persons participated in the study. An ecological momentary assessment (EMA) approach was used to assess indicators of stress in daily life. Each day included six concurrent assessments of saliva, to quantify cortisol (sCort; HPA axis) and alpha-amylase (sAA; SAM axis), and to assess self-reports on subjective stress. To assess SLC6A4 DNAm, peripheral blood was drawn and analyzed via bisulfite pyrosequencing. All data were assessed in two waves three months apart, each including two days of EMA and the assessment of SLC6A4 DNAm. Data were analyzed using multilevel models. On the between-person level, higher average levels of SLC6A4 DNAm were associated with higher average levels of sAA, but not with average levels of sCort. On the within-person level, higher levels of SLC6A4 DNAm were associated with lower levels of sAA and sCort. There were no associations of subjective stress with SLC6A4 DNAm. The results help to clarify the association between environmental stress and stress axes regulation, pointing towards an important role of differential within- and between-person effects of SLC6A4 DNAm, which might shape this association.

Association Between Polymorphism (5-HTTLPR) of the Serotonin Transporter Gene and Behavioral Response to Unfair Distribution.

Behavioral responses to unfair distribution have been measured mainly using the Ultimatum Game (UG). Recent studies examining the biological basis of behavioral responses to unfair distribution have focused attention on the role of the serotonin transporter gene. However, studies, to date, have been conducted on non-Asians, and it has not been confirmed whether similar results can be seen in other ethnic groups. It has also been shown that behavioral responses to unfair distribution are not only seen in the case of victims themselves but also in the case of third parties not directly affected. This study aimed to determine whether the results of the previous study would be replicated in an Asian population and whether the serotonin transporter gene would also be associated with behavior toward unfair distribution by third parties. We examined the association between polymorphisms (5-HTTLPR) of the serotonin transporter gene and participants' behavior in the UG and the third-party punishment game (TPPG). The results did not show an association between punishment for unfair proposals in the TPPG and genetic polymorphisms, while participants with the SL/LL genotype were more likely to reject unfair offers in the UG than those with the SS genotype. These results indicate that 5-HTTLPR is associated with behavior when unfair intentions are directed at oneself.

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.

BACKGROUND: The 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. METHODS: A 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. RESULTS: Carriers 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). CONCLUSIONS: Our 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.

Preliminary Evidence That the Short Allele of 5-HTTLPR Moderates the Association of Psychiatric Symptom Severity on Suicide Attempt: The Example in Obsessive-Compulsive Disorder.

Background: The severity of symptoms represents an important source of distress in patients with a psychiatric disease. However, the extent to which this endogenous stress factor interacts with genetic vulnerability factors for predicting suicide risks remains unclear. Methods: We evaluated whether the severity of symptoms interacts with a genetic vulnerability factor (the serotonin transporter gene-linked promoter region variation) in predicting the frequency of lifetime suicide attempts in patients with a psychiatric disease. Symptom severity and 5-HTTLPR polymorphism were collected from a sample of 95 patients with obsessive-compulsive disorder (OCD). Lifetime suicide attempt was the primary outcome, and antecedent of multiple suicide attempts was the secondary outcome. Results: The gene-by-symptoms interaction was associated with an excess risk of suicide attempts (OR = 4.39, 95CI[1.44, 13.38], p < 0.009) and of multiple suicide attempts (OR = 4.18, 95CI[1.04, 16.77], p = 0.043). Symptom severity (moderate, severe, or extreme) was associated with an approximately five-fold increase in the odds of a lifetime suicide attempt in patients carrying one or two copies of the short allele of 5-HTTLPR. No such relationship was found for patients carrying the long allele. Conclusion: This study provides preliminary evidence for the gene-by-stress interaction on suicide attempt when stress is operationalized as symptom severity. Progress in suicide research may come from efforts to investigate the gene-by-symptoms interaction hypothesis in a variety of diseases.

The Interaction between Serotonin Transporter Allelic Variation and Maternal Care Modulates Instagram Sociability in a Sample of Singaporean Users.

Human social interactions ensure recognition and approval from others, both in offline and online environments. This study applies a model from behavioral genetics on Instagram sociability to explore the impact of individual development on behavior on social networks. We hypothesize that sociable attitudes on Instagram resulted from an interaction between serotonin transporter gene alleles and the individual's social relationship with caregivers. We assess the environmental and genetic components of 57 Instagram users. The self-report questionnaire Parental Bonding Instrument is adopted to determine the quality of parental bonding. The number of posts, followed users ("followings"), and followers are collected from Instagram as measures of online social activity. Additionally, the ratio between the number of followers and followings ("Social Desirability Index") was calculated to estimate the asymmetry of each user's social network. Finally, buccal mucosa cell samples were acquired, and the polymorphism rs25531 (T/T homozygotes vs. C-carriers) within the serotonin transporter gene was examined. In the preliminary analysis, we identified a gender effect on the number of followings. In addition, we specifically found a gene-environment interaction on the standardized Instagram "Social Desirability Index" in line with our predictions. Users with the genotype more sensitive to environmental influences (T/T homozygotes) showed a higher Instagram "Social Desirability Index" than nonsensitive ones (C-carriers) when they experienced positive maternal care. This result may contribute to understanding online social behavior from a gene*environment perspective.

Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders: A meta-analysis.

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.

Developmental Antecedents of Adult Macaque Neurogenesis: Early-Life Adversity, 5-HTTLPR Polymorphisms, and Adolescent Hippocampal Volume.

INTRODUCTION: Attenuated adult hippocampal neurogenesis may manifest in affective symptomatology and/or resistance to antidepressant treatment. While early-life adversity and the short variant ('s') of the serotonin transporter gene's long polymorphic region (5-HTTLPR) are suggested as interacting risk factors for affective disorders, no studies have examined whether their superposed risk effectuates neurogenic changes into adulthood. Similarly, it is not established whether reduced hippocampal volume in adolescence, variously identified as a marker and antecedent of affective disorders, anticipates diminished adult neurogenesis. We investigate these potential developmental precursors of neurogenic alterations using a bonnet macaque model. METHODS: Twenty-five male infant bonnet macaques were randomized to stressed [variable foraging demand (VFD)] or normative [low foraging demand (LFD)] rearing protocols and genotyped for 5-HTTLPR polymorphisms. Adolescent MRI brain scans (mean age 4.2y) were available for 14 subjects. Adult-born neurons were detected post-mortem (mean age 8.6y) via immunohistochemistry targeting the microtubule protein doublecortin (DCX). Models were adjusted for age and weight. RESULTS: A putative vulnerability group (VG) of VFD-reared 's'-carriers (all 's/l') exhibited reduced neurogenesis compared to non-VG subjects. Neurogenesis levels were positively predicted by ipsilateral hippocampal volume normalized for total brain volume, but not by contralateral or raw hippocampal volume. LIMITATIONS: No 's'-carriers were identified in LFD-reared subjects, precluding a 2×2 factorial analysis. CONCLUSION: The 's' allele (with adverse rearing) and low adolescent hippocampal volume portend a neurogenic deficit in adult macaques, suggesting persistent alterations in hippocampal plasticity may contribute to these developmental factors' affective risk in humans.

Modulation of Instagram Number of Followings by Avoidance in Close Relationships in Young Adults under a Gene x Environment Perspective.

Social networking sites have determined radical changes in human life, demanding investigations on online socialization mechanisms. The knowledge acquired on in-person sociability could guide researchers to consider both environmental and genetic features as candidates of online socialization. Here, we explored the impact of the quality of adult attachment and the genetic properties of the Serotonin Transporter Gene (5-HTTLPR) on Instagram social behavior. Experiences in Close Relationships-Revised questionnaire was adopted to assess 57 Instagram users' attachment pattern in close relationships with partners. Genotypes from the 5-HTTLPR/rs25531 region were extracted from the users' buccal mucosa and analyzed. Users' Instagram social behavior was examined from four indexes: number of posts, number of followed users ("followings") and number of followers, and the Social Desirability Index calculated from the followers to followings ratio. Although no interaction between rs25531 and ECR-R dimensions was found, an association between avoidance in close relationships and Instagram number of followings emerged. Post hoc analyses revealed adult avoidance from the partner predicts the Instagram number of followings with good evidence. Moreover, users reporting high avoidance levels displayed fewer followings than users who reported low levels of avoidance. This research provides a window into the psychobiological understanding of online socialization on Instagram.

The 5-HTTLPR-rs25531 S-A-S-A Haplotype and Chronic Stress Moderate the Association Between Acute Stress and Internalizing Mental Disorders Among HIV+ Children and Adolescents in Uganda.

Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2. Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs. Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ children and adolescents (aged 5-17 years) with any internalizing mental disorder (depression, anxiety disorders, or posttraumatic stress disorder), and 368 age- and sex-matched controls, who were also HIV+. Chronic and acute stress categories were derived by hierarchical cluster analysis. Logistic regression analysis was used to assess the independent moderating effect of chronic stress and each selected polymorphism on the association between acute stress and IMDs. Results: We observed a statistically significant association between severe acute stress and IMDs (p = 0.001). Children and adolescents who experienced severe acute stress were twice as likely to develop IMDs, compared to children and adolescents who experienced mild acute stress (p = 0.001). Chronic stress interacted with severe acute stress to increase the risk of IMDs (p = 0.033). Acute stress was found to interact with 5-HTTLPR-rs25531 S-A-S-A haplotype to increase the risk for IMDs among Ugandan HIV+ children and adolescents (p = 0.049). We found no evidence for a combined interaction of acute stress, chronic stress, and 5-HTTLPR-rs25531 on IMDs. Conclusion: The odds of having an internalizing mental disorder (IMD) were higher among HIV+ children and adolescents who experienced severe acute stress compared to HIV+ children and adolescents who experienced mild acute stress. Chronic stress and 5-HTTLPR-rs25531 independently moderated the association between acute stress and IMDs.