Atrial fibrillation ablation in heart failure patients: Where do we stand in 2023? - State of the art review.

Atrial fibrillation (AF) and heart failure are common overlapping cardiovascular disorders. Despite important therapeutic advances over the past several decades, controversy persists about whether a rate control or rhythm control approach constitutes the best option in this population. There is also considerable debate about whether antiarrhythmic drug therapy or ablation is the best approach when rhythm control is pursued.  A brief historical examination of the literature addressing this issue will be performed. An analysis of several important clinical outcomes observed in the prospective, randomized studies, which have compared AF ablation to non-ablation treatment options, will be discussed. This review will conclude with recommendations to guide clinicians on the status of AF ablation as a treatment option when considering management options in heart failure patients with atrial fibrillation.

Trends in psychosomatic symptoms among adolescents and the role of lifestyle factors.

BACKGROUND: Adolescent mental health problems are on the rise globally, including in Sweden. One indicator of this trend is increased psychosomatic symptoms (PSS) over time. Lifestyle factors such as physical activity (PA), diet, smoking, and alcohol consumption may influence the time trends in PSS; however, the evidence base is scarce. The aim of this study was to investigate associations between time trends in PSS and lifestyle factors. METHODS: The study was based on data collected from a nationally representative sample of 9,196 fifteen-year-old boys and girls in Sweden using the Health Behavior in School-aged Children (HBSC) symptom checklist. The sample comprised nearly equal proportions of girls (50.5%) and boys. The lifestyle factors examined in this study included PA, regular breakfast intake, consumption of fruits, vegetables, sweets, or soft drinks, smoking, and alcohol drunkenness. We used data from 2002 to 2018 and stratified by family affluence scale (FAS) to demonstrate how the associations varied among the FAS groups. We fitted separate regression models for the high- and low-FAS groups, where interaction terms between the year of survey and each lifestyle factor were used to estimate the level and direction of associations between the factors and trends in PSS. RESULTS: There was a generally increasing trend in PSS mean scores from 2.26 in 2002 to 2.49 in 2018 (p <.001). The changes in each survey year compared to the average mean scores during the preceding years were significant in all years except 2010. Regular breakfast intake, daily fruit and vegetable consumption, and higher PA were associated with lower PSS mean scores, while smoking and drunkenness had opposite associations with PSS. The only significant interaction between survey year and the lifestyle factors was observed regarding drunkenness in the high FAS group, suggesting that the association between trends in PSS and the experience of getting drunk at least twice got stronger over time (B = 0.057; CI:0.016, 0.097; p <.01). CONCLUSIONS: The results indicate increasing trends in PSS among young people in Sweden from 2002 to 2018, with a significant increase observed among adolescents in the high FAS group who reported getting drunk on at least two occasions.

Trends in adolescent mental health problems 2004-2020: do sex and socioeconomic status play any role?

AIMS: This study aims to investigate trends in four types of adolescent mental health problems; that is, psychosomatic symptoms, depressive symptoms, suicidal ideations, and suicide attempts 2004-2020. A second aim is to investigate the moderating roles of socioeconomic status and sex in these trends. METHODS: The analysis is based on repeated cross-sectional data 2004-2020 among grade 9 students in secondary schools in a Swedish county. In total, data from 19,873 students were included in the analysis. We fitted linear and logistic regression equations and used survey-years' coefficients to estimate the trends. We also estimated the moderating effects of socioeconomic status and sex using interactions between survey year and socioeconomic status and sex, respectively. RESULTS: The trends in all mental health problems declined over time. Through its interaction with survey year, socioeconomic status moderated the trends; psychosomatic symptoms (B = -0.115, P<0.001), depressive symptoms (B = -0.084, P<0.001) and suicidal ideations (odds ratio 0.953, confidence interval 0.924-0.983) significantly declined over time among those with high socioeconomic status. However, socioeconomic status did not have an association with the trend in suicide attempts. Interaction between sex and year of survey was associated with significant decreasing trends in depressive symptoms and suicidal ideations only among girls. CONCLUSIONS: Adolescent mental health problems have decreased over time, but only for adolescents with high socioeconomic status, or only in depressive symptoms and suicidal ideations for girls. The results shed light on the growing inequalities in health outcomes across levels of socioeconomic status.

Do non-drinking youth drink less alcohol in young adulthood or do they catch up? Findings from a Swedish birth cohort.

BACKGROUND: Alcohol consumption among adolescents has declined considerably during the last two decades. However, it is unknown if these adolescents' alcohol consumption will remain low as they grow older. To our knowledge, this is one of the first studies that uses longitudinal data to examine if non-drinking adolescents have a lower alcohol consumption in young adulthood or if they catch up. METHODS: A self-report survey was distributed to a birth cohort (n = 794) born in 1997 in a Swedish region when cohort members attended ninth grade (age 14-15 years) in 2012. Responders were divided into non-drinkers and alcohol users and assessed again in their late teens (17-18 years) and young adulthood (20-21 years). RESULTS: In their late teens (17-18 years), non-drinkers at baseline consumed less alcohol and had a lower probability of harmful use compared with their alcohol-using peers. In young adulthood (20-21 years), these effects disappeared when adjustment was made for covariates. However, a stratified analysis showed that non-drinking adolescents low in conduct problems consumed less alcohol and had a lower probability of harmful use in young adulthood than alcohol-using peers. CONCLUSIONS: This study suggests that the decline in alcohol use among adolescents in the past decades may be associated with a lower alcohol consumption in the late teens and young adulthood among those low in conduct problems. This may have promising implications for alcohol-related morbidity and mortality.

Autonomic responses during Gambling: the Effect of Outcome Type and Sex in a large community sample of young adults.

Psychological theories consider autonomic arousal to be a reinforcer for problem gambling. Structural characteristics such as near-misses, which are non-win events that come close to a real win, have been shown to elicit win-like responses while increasing motivation and gambling persistence. This study investigated the autonomic and subjective responses of young adults to different gambling outcomes. This study also investigated sex differences in autonomic and subjective responses to different gambling outcomes.Participants from Sweden (n = 270) performed a computerized slot machine task that produced wins, near-misses (before and after payline) and full-misses. Phasic measurements of heart rate (HR) and skin conductance responses (SCR) were recorded during gambling performance and ratings of perceived chance of winning, pleasure and motivation to play were collected following each gambling outcome.Autonomic responses differed across slot machine outcomes as indicated by HR and SCR. Compared with other gambling outcomes, near-misses elicited the largest HR accelerations, and they also elicited larger HR decelerations and SCRs relative to full-misses. Near-misses before and after payline elicited differential psychophysiological responses and subjective reports, suggesting different emotional processing of near-miss subtypes. Females showed increased SCRs and motivation following win outcomes compared with males.In conclusion, wins, near-misses and full-misses generate differential physiological and subjective responses among young adults. Autonomic responses to wins differed between male and female players, emphasizing the need to consider sex differences when investigating the role of autonomic arousal in gambling.

Botulinum Toxin A for Provoked Vestibulodynia: 12 Months' Follow-up of a Randomized Controlled Trial.

BACKGROUND: Provoked vestibulodynia (PVD) is a common pain disorder afflicting primarily young women, and botulinum toxin A (BTA) has been to a limited extent tested as a treatment. AIM: Evaluate outcome 12 months after injection with BTA as a treatment for PVD. METHODS: We conducted a double-blinded, placebo-controlled trial of twice repeated injections of 50 units of BTA or placebo in the bulbocavernosus muscles, 3 months apart, in women with PVD. Treatment outcome after six months', failed to show any significant difference in pain reduction between the groups, as previously reported. Here, we report treatment outcomes 12 months after the first injections. In addition to injections, participants where instructed to perform pelvic floor exercises during month 6-12. 38 participants/group was calculated to achieve a statistical power of 80% based on an effect size of 20 VAS units (mean score range 56-76±31 SD). OUTCOMES: Primary outcome was self-reported dyspareunia or pain at tampon use, using a visual analogue scale (VAS) 0-100. Secondary outcomes were vaginal pressure measurements, psychological health, sexual function and distress. RESULTS: From the initial 88 randomized women with PVD, 75 remained at 12 months; 38 in the BTA and 37 in the placebo group. There was no significant difference in primary outcome between the groups. Vaginal pressure in the BTA group had been restored to pre-treatment levels, with no differences between the groups at 12 months. There was an increase in sexual function in the BTA group, with a Female Sexual Function Index of 22.8 (±4.8) compared to the placebo group to 19.7 (±5.0), P=.048. No differences were observed in sexual distress, stress and anxiety. There was an increase in number of women attempting intercourse in the BTA group (74%) compared with placebo (43%), P=.005. Too few patients performed the pelvic floor exercises for this intervention to be analyzed. CLINICAL IMPLICATIONS: This study highlights BTA as a safe treatment option for patients with PVD. STRENGTHS AND LIMITATIONS: The randomized, double-blinded design and repeated treatments are the major strengths of this study and it is the first study to objectively evaluate muscular effect after BTA injections. The major shortcoming is that few participants performed the pelvic floor exercises, preventing analyses. CONCLUSION: At 12 months' follow up, no significant difference in reduction of dyspareunia or pain at tampon use was observed. Women receiving BTA attempted intercourse more often and improved their sexual function compared with women receiving placebo. Haraldson P, Mühlrad H, Heddini U, et al. Botulinum Toxin A for Provoked Vestibulodynia: 12 Months' Follow-up of a Randomized Controlled Trial. J Sex Med 2022;19:1670-1679.

Psychometric validation of two versions of the adolescent Depression Self-Rating Scale (DSRS-A and DSRS-A Screener).

AIM: Examination of psychometric properties and diagnostic accuracy of the Depression Self-Rating Scale for Adolescents (DSRS-A) as well as development and evaluations of a shorter version, DSRS-A-Screener. METHODS: Analyses of component structure and internal consistency were performed in a community-based sample of adolescents N = 4,506 and among consecutive outpatients from three child psychiatric settings in Sweden (n = 137). Concurrent validity was measured as a correlation between a summation index of the scale items and the total major depressive disorder (MDD) symptom severity score from the Kiddie Schedule of Affective Disorders and Schizophrenia (K-SADS). Diagnostic accuracy was examined in the clinical sample, with the K-SADS interview as the reference test, by receiver operating characteristic analysis (ROC), calculations of sensitivity, specificity among other measures. With the purpose to select items for a shorter scale, associations between scale items and MDD were examined with binary logistic regression. This shorter scale was thereafter examined similarly. RESULTS: Based on association with MDD, five items were selected for the brief DSRS-A Screener that showed one component structure, internal consistency Cronbach's alpha .80 and.82, respectively. In the clinical population concurrent validity was Spearman's rho .63 and ROC analysis showed AUC .84 (95% CI .78-.91; p < .001). The optimal cut-off for screening was 2 with sensitivity .85 and specificity of .64. CONCLUSION: The DSRS-A Screener compared to the original scale, maintained or improved reliability, validity, and showed moderate diagnostic accuracy.

Three-way interaction effects of early life stress, positive parenting and FKBP5 in the development of depressive symptoms in a general population.

FKBP5 gene-environment interaction (cG × E) studies have shown diverse results, some indicating significant interaction effects between the gene and environmental stressors on depression, while others lack such results. Moreover, FKBP5 has a potential role in the diathesis stress and differential susceptibility theorem. The aim of the present study was to evaluate whether a cG × E interaction effect of FKBP5 single-nucleotide polymorphisms (SNPs) or haplotype and early life stress (ELS) on depressive symptoms among young adults was moderated by a positive parenting style (PASCQpos), through the frameworks of the diathesis stress and differential susceptibility theorem. Data were obtained from the Survey of Adolescent Life in Västmanland Cohort Study, including 1006 participants and their guardians. Data were collected during 2012, when the participants were 13 and 15 years old (Wave I: DNA), 2015, when participants were 16 and 18 years old (Wave II: PASCQpos, depressive symptomology and ELS) and 2018, when participants were 19 and 21 years old (Wave III: depressive symptomology). Significant three-way interactions were found for the FKBP5 SNPs rs1360780, rs4713916, rs7748266 and rs9394309, moderated by ELS and PASCQpos, on depressive symptoms among young adults. Diathesis stress patterns of interaction were observed for the FKBP5 SNPs rs1360780, rs4713916 and rs9394309, and differential susceptibility patterns of interaction were observed for the FKBP5 SNP rs7748266. Findings emphasize the possible role of FKBP5 in the development of depressive symptoms among young adults and contribute to the understanding of possible differential susceptibility effects of FKBP5.

Associations of age, sex, sexual abuse, and genotype with monoamine oxidase a gene methylation.

Epigenome-wide studies report higher methylation among women than men with decreasing levels with age. Little is known about associations of sex and age with methylation of monoamine oxidase A (MAOA). Methylation of the first exonic and partial first intronic region of MAOA has been shown to strengthen associations of interactions of MAOA-uVNTR genotypes and adversity with aggression and substance misuse. Our study examined associations of sex and age with MAOA first exon and intron methylation levels in 252 women and 157 men aged 14-73 years. Participants included adolescents recruited at a substance misuse clinic, their siblings and parents, and healthy women. Women showed ~ 50% higher levels of exonic, and ~ 15% higher intronic, methylation than men. Methylation levels were similar between younger (M = 22.7 years) and older (M = 46.1 years) participants, and stable across age. Age modified few associations of methylation levels with sex. MAOA genotypes modified few associations of methylation with sex and age. Higher methylation levels among women were not explained by genotype, nor interaction of genotype and sexual abuse. Findings were similar after adjusting for lifetime diagnoses of substance dependence (women = 24.3%; men = 34.2%). Methylation levels were higher among women who experienced sexual abuse than women who did not. Results extend on prior studies by showing that women display higher levels of methylation than men within first intronic/exonic regions of MAOA, which did not decrease with age in either sex. Findings were not conditioned by genotype nor interactions of genotype and trauma, and indicate X-chromosome inactivation.

Characteristic patterns of emergency ambulance assignments for older adults compared with adults requiring emergency care at home in Sweden: a total population study.

BACKGROUND: Since the vast majority of older adults in Sweden live in their private homes throughout life, the emergency medical services need to adapt accordingly. Hence, we aimed to describe characteristic patterns of dyadic staffed emergency ambulance assignments for older adults aged > 70 years compared with adults aged 18-69 years requiring emergency care at home in Sweden. METHODS: A descriptive retrospective study was performed using anonymized registry data from the emergency medical services in a region of Sweden during 2017-2018. One-sample χ2 test, one-way analysis of variance, and binary logistic regression models were used for investigating group differences. Variables for analysis were age, gender, clinical assessments, on-scene time, priority levels, result of response, and temporal patterns. RESULTS: Of all included emergency ambulance assignments (n = 28,533), 59.9% involved older adults, of which 53.8% were women. The probability for older adults to receive the highest priority was decreased for both dispatch (p < 0.001, odds ratio [OR] 0.63, 95% confidence interval [CI] 0.59-0.66), and transport priorities (p < 0.001, OR 0.74, 95% CI 0.68-0.80). Older adults were more likely to receive dispatch priority levels 2 (p < 0.001, OR 1.48, 95% CI 1.40-1.56), and 3 (p < 0.001, OR 1.73, 95% CI 1.46-2.06). The older adults were similarly more likely to receive transport priority level 3 (p < 0.001, OR 1.40, 95% CI 1.28-1.52) compared with adults. Age had a small but additive effect in relation to on-scene time (p < 0.001, R2 = 0.01, F = 53.82). Distinguishing initial clinical assessments for older adults were circulatory, respiratory, trauma, infection, and nonspecific assessments. Emergency ambulance assignments for older adults were more frequently occurring on Mondays (p < 0.001, χ2 = 232.56), and in the 08:00-11:59 interval (p < 0.001, χ2 = 1224.08). CONCLUSION: The issues of the lower priority level preponderance, and the decreased probability for receiving the highest priority warrant further attention in future research and clinical practice.

The increased trend of non-drinking alcohol among adolescents: what role do internet activities have?

Background: Recently, an increased trend toward non-drinking among adolescents has been observed in several countries. The aim of the present study is to evaluate a common suggestion in literature, that adolescents do not drink alcohol because they spend more time on the internet, monitored at home, by examining associations between internet activities (social media/chatting and computer gaming) and non-drinking. Methods: A health questionnaire was distributed to all 9th graders (15-16 years) in a mid-sized Swedish county in 2008, 2010 and 2012. In total, 7089 students returned the questionnaire. Results: In contrast to the suggestion, no association was found between total time spent on computers and non-drinking. Social media/chatting was robustly associated with a decreased probability of non-drinking across the three survey years. On the other hand, computer gaming during weekends only (OR = 1.74, CI = 1.13-2.69) or both on weekdays and weekends increased the probability of non-drinking (OR = 1.82, CI = 1.31-2.54) in 2012 only. However, neither social media/chatting nor computer gaming was associated with the increased trend of non-drinking from 2008 to 2012. Conclusions: Internet activities were in general not associated with non-drinking among adolescents aged 15-16 years in Sweden. Although, a weak positive association between computer gaming and non-drinking was found in 2012, this effect benefited the vast majority of the boys. The larger alcohol use among those with extensive social media use/chatting may indicate that these online platforms are arenas where adolescents are exposed for positive alcohol preferences and alcohol advertising without parental supervision.

VGLUT2 rs2290045 genotype moderates environmental sensitivity to alcohol-related problems in three samples of youths.

The importance of Vesicular Glutamate Transporter 2 (VGLUT2)-mediated neurotransmission has been highlighted in studies on addiction-related phenotypes. The single nucleotide polymorphism rs2290045 in VGLUT2 has been associated with alcohol dependence, but it is unknown whether or how this association is affected by environmental factors. The present study determined whether the association of alcohol-related problems with the rs2290045 in the VGLUT2 gene was modified by negative and positive environmental factors. Three samples were included: a clinical sample of 131 adolescents followed from age 17 to 22; a general population sample of 1794 young adults; and a general population sample of 1687 adolescents followed from age 14 to 17. DNA was extracted from saliva and the rs2290045 (T/C) was genotyped. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test. Stressful life events (SLE) and parenting were assessed by questionnaires. Gene-environment interactions were investigated using a dual statistical approach. In all samples (effect sizes 0.6-6.2%), and consistent with the differential susceptibility framework, T carriers exposed to SLE reported more alcohol-related problems if they had experienced poor parenting, and lower alcohol-related problems if they had received supportive parenting. T carriers not exposed to SLE reported higher alcohol-related problems if they had received supportive parenting and lower alcohol-related problems if they had received poor parenting. Among CC carriers, alcohol-related problems did not vary as a function of negative and positive environmental factors. In conclusion, in three samples of youths, alcohol-related problems were associated with an interaction of VGLUT2 rs2290045, SLE, and parenting.

MR-Conditional SMA-Based Origami Joint.

Foldable origami structures have been implemented into robotics as a way of compacting joints and circuitry into smaller structures. This technique is especially useful in minimally invasive surgical instruments, where the goal is to create slimline devices that can be inserted through small incisions. Origami also has the potential to cut costs by reducing the amount of material required for assembly. Origami devices are especially suitable for MRI-guided procedures, where instruments must be nonmagnetic because origami is more suitable for flexible, non-metallic materials. MR conditional surgical instruments enable intraoperative MRI procedures that provide superior imaging capabilities to physicians to allow for safer procedures. This work presents an MR conditional joint developed using origami techniques that reduces costs by eliminating assembly of various components and has potential applications in endoscopy. The joint is a compliant rolling-contact element that employs curved-folding origami techniques. A chain of these joints can be constructed from a single sheet of material, eliminating assembly of numerous materials to produce a final product, which is specifically advantageous for constructing low-cost, disposable surgical devices. The prototype contains a degree of bending of ±9 degrees per joint, a response time of less than 4 seconds and an actuation force of 0.5 N using a 1.25 A current. The MRI results showed a minimal artifact of less than 1 mm measured from the boundary of the joint chain and a SNR reduction of less than 10%.

Individual biological sensitivity to environmental influences: testing the differential susceptibility properties of the 5HTTLPR polymorphism in relation to depressive symptoms and delinquency in two adolescent general samples.

The gene-environment interaction research field in psychiatry has traditionally been dominated by the diathesis-stress framework, where certain genotypes are assumed to confer increased risk for adverse outcomes in a stressful environment. In later years, theories of differential susceptibility, or biological sensitivity, suggest that candidate genes that interact with environmental events do not exclusively confer a risk for behavioural or psychiatric disorders but rather seem to alter the sensitivity to both positive and negative environmental influences. The present study investigates the susceptibility properties of the serotonin transporter-linked polymorphic region (5HTTLPR) in relation to depressive symptoms and delinquency in two separate adolescent community samples: n = 1457, collected in 2006; and n = 191, collected in 2001. Two-, three-, and four-way interactions between the 5HTTLPR, positive and negative family environment, and sex were found in relation to both depressive symptoms and delinquency. However, the susceptibility properties of the 5HTTLPR were distinctly less pronounced in relation to depressive symptoms. If the assumption that the 5HTTLPR induces differential susceptibility to both positive and negative environmental influences is correct, the previous failures to measure and control for positive environmental factors might be a possible explanation for former inconsistent findings within the research field.

Gene-environment interaction of monoamine oxidase A in relation to antisocial behaviour: current and future directions.

Since the pioneering finding of Caspi and co-workers in 2002 that exposure to childhood maltreatment predicted later antisocial behaviour (ASB) in male carriers of the low-activity MAOA-uVNTR allele, frequent replication studies have been published. Two meta-analyses, one in 2006 and the other in 2014, confirmed the original findings by Caspi and co-workers. In the present paper, we review the literature, note some methodological aspects of candidate gene-environment interaction (cG×E) studies and suggest some future directions. Our conclusions are as follows. (1) The direction of the effect in a cG×E model may differ according to the positive and negative environmental background of the population. (2) There is a predictor-intersection problem such that when measuring one type of maltreatment in a person, other kinds of maltreatment often co-occur. Other forms of abuse are implicitly considered in statistical models; therefore, it is difficult to draw conclusions about the effects of timing and the severity of different forms of stressful life events in relation to ASB. (3) There is also an outcome-intersection problem because of the major intersection of ASB and other forms of mental health problems. It is likely that the G×E with MAOA is related to a common unmeasured factor. (4) For the G×E model, in which the effect of the gene on the outcome variable is dependent on other predictor variables, theoretically, hypothesis-driven statistical modelling is needed.

Associations of monoamine oxidase A gene first exon methylation with sexual abuse and current depression in women.

Childhood physical abuse (PA) and sexual abuse (SA) interact with monoamine oxidase A (MAOA) gene polymorphism to modify risk for mental disorders. In addition, PA and SA may alter gene activity through epigenetic mechanisms such as DNA methylation, thereby further modifying risk for disorders. We investigated whether methylation in a region spanning the MAOA first exon and part of the first intron was associated with PA and/or SA, MAOA genotype, alcohol dependence, drug dependence, depression disorders, anxiety disorders, and conduct disorder. 114 Swedish women completed standardized diagnostic interviews and questionnaires to report PA and SA, and provided saliva samples for DNA extraction. DNA was genotyped for MAOA-uVNTR polymorphisms, and methylation of a MAOA region of interest (chrX: 43,515,544-43,515,991) was measured. SA, not PA, was associated with hypermethylation of the MAOA first exon relative to no-abuse, and the association was robust to adjustment for psychoactive medication, alcohol and drug dependence, and current substance use. SA and MAOA-uVNTR genotype, but not their interaction, was associated with MAOA methylation. SA associated with all measured mental disorders. Hypermethylation of MAOA first exon mediated the association of SA with current depression, and both methylation levels and SA independently predicted lifetime depression. Much remains to be learned about the independent effects of SA and MAOA-uVNTR genotypes on methylation of the MAOA first exon.

Personality as an intermediate phenotype for genetic dissection of alcohol use disorder.

Genetic and environmental interactive influences on predisposition to develop alcohol use disorder (AUD) account for the high heterogeneity among AUD patients and make research on the risk and resiliency factors complicated. Several attempts have been made to identify the genetic basis of AUD; however, only few genetic polymorphisms have consistently been associated with AUD. Intermediate phenotypes are expected to be in-between proxies of basic neuronal biological processes and nosological symptoms of AUD. Personality is likely to be a top candidate intermediate phenotype for the dissection of the genetic underpinnings of different subtypes of AUD. To date, 38 studies have investigated personality traits, commonly assessed by the Cloninger's Tridimensional Personality Questionnaire (TPQ) or Temperament and Character Inventory (TCI), in relation to polymorphisms of candidate genes of neurotransmitter systems in alcohol-dependent patients. Particular attention has been given to the functional polymorphism of the serotonin transporter gene (5-HTTLPR), however, leading to contradictory results, whereas results with polymorphisms in other candidate monoaminergic genes (e.g., tryptophan hydroxylase, serotonin receptors, monoamine oxidases, dopamine receptors and transporter) are sparse. Only one genome-wide association study has been performed so far and identified the ABLIM1 gene of relevance for novelty seeking, harm avoidance and reward dependence in alcohol-dependent patients. Studies investigating genetic factors together with personality could help to define more homogenous subgroups of AUD patients and facilitate treatment strategies. This review also urges the scientific community to combine genetic data with psychobiological and environmental data to further dissect the link between personality and AUD.

Associations Between MAOA-uVNTR Genotype, Maltreatment, MAOA Methylation, and Alcohol Consumption in Young Adult Males.

BACKGROUND: Epigenetic mechanisms are candidate moderators of the effect of maltreatment on brain and behavior. Interactions between maltreatment and the monoamine oxidase A upstream variable number tandem repeat genotype (MAOA-uVNTR) are associated with alcohol-related problems. However, presently it is not known whether DNA methylation moderates this association. The study focused on 53 young adult males and aimed to determine whether MAOA methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment, and whether alcohol consumption moderated the association of MAOA methylation with the interaction of MAOA-uVNTR and maltreatment. METHODS: MAOA-uVNTR genotypes with ≤ 3 and > 3 repeats were categorized as short (S) and long (L), respectively. Data on maltreatment were obtained retrospectively, using self-reported questionnaires. DNA methylation of 16 candidate CpGs within part of the MAOA first exon and intron was assessed and grouped based on principal component analyses. Alcohol-related problems were assessed using the Alcohol Use Disorders Identification Test (AUDIT). Alcohol consumption was measured using AUDIT-C. Moderation effects were assessed and probed using the moderated moderation model and Johnson-Neyman's method, respectively. RESULTS: Carriers of the S allele, who experienced maltreatment and displayed lower Component 1 (mean of CpGs 13-16 in the first intron) MAOA methylation levels, reported higher AUDIT score in contrast to L-allele carriers. Carriers of the S allele, who reported higher AUDIT-C score and experienced maltreatment, displayed lower Component 3 (mean of CpGs 2-6 in the first exon) MAOA methylation levels than L-allele carriers. CONCLUSIONS: Intronic methylation moderated the association of alcohol-related problems with the interaction of MAOA-uVNTR and maltreatment. Alcohol consumption moderated the association of exonic methylation with the interaction of MAOA-uVNTR and maltreatment. These results suggest that epigenetic factors as well as genotype and maltreatment play a role in the development of alcohol misuse among young adult males.

Differential susceptibility effects of oxytocin gene (OXT) polymorphisms and perceived parenting on social anxiety among adolescents.

Social anxiety is one of the most commonly reported mental health problems among adolescents, and it has been suggested that parenting style influences an adolescent's level of anxiety. A context-dependent effect of oxytocin on human social behavior has been proposed; however, research on the oxytocin gene (OXT) has mostly been reported without considering contextual factors. This study investigated the interactions between parenting style and polymorphic variations in the OXT gene in association with social anxiety symptoms in a community sample of adolescents (n = 1,359). Two single nucleotide polymorphisms linked to OXT, rs4813625 and rs2770378, were genotyped. Social anxiety and perceived parenting style were assessed by behavioral questionnaires. In interaction models adjusted for sex, significant interaction effects with parenting style were observed for both variants in relation to social anxiety. The nature of the interactions was in line with the differential susceptibility framework for rs4813625, whereas for rs2770378 the results indicated a diathesis-stress type of interaction. The findings may be interpreted from the perspective of the social salience hypothesis of oxytocin, with rs4813625 affecting social anxiety levels along a perceived unsafe-safe social context dimension.