Good parent-child relationship protects against alcohol use in maltreated adolescent females carrying the MAOA-uVNTR susceptibility allele.

Introduction: Risk-allele carriers of a Monoamine oxidase A (MAOA) gene, short-allele (MAOA-S) in males and long-allele (MAOA-L) in females, in the presence of a negative environment, are associated with alcohol misuse. Whether MAOA-S/L alleles also present susceptibility to a positive environment to mitigate the risk of alcohol misuse is unknown. Thus, we assessed the association of the three-way interaction of MAOA, maltreatment, and positive parent-child relationship with alcohol consumption among adolescents. Methods: This prospective study included 1416 adolescents (females: 59.88%) aged 16 - 19 years from Sweden, enrolled in the "Survey of Adolescent Life in Västmanland" in 2012. Adolescents self-reported alcohol consumption, maltreatment by a family (FM) or non-family member (NFM), parent-child relationship, and left saliva for MAOA genotyping. Results and discussion: We observed sex-dependent results. Females carrying MAOA-L with FM or NFM and a good parent-child relationship reported lower alcohol consumption than those with an average or poor parent-child relationship. In males, the interactions were not significant. Results suggest MAOA-L in females, conventionally regarded as a "risk", is a "plasticity" allele as it is differentially susceptible to negative and positive environments. Results highlight the importance of a good parent-child relationship in mitigating the risk of alcohol misuse in maltreated individuals carrying genetic risk. However, the interactions were not significant after adjusting to several environmental and behavioural covariates, especially parent's alcohol use, negative parent-child relationship, and nicotine use (smoking and/or snus), suggesting predictor and outcome intersection. Future studies and frameworks for preventive strategies should consider these covariates together with alcohol consumption. More studies with larger sample sizes are needed to replicate the findings.

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.

Monoamine oxidase A genotype and methylation moderate the association of maltreatment and aggressive behaviour.

BACKGROUND: The association between childhood maltreatment and subsequent aggressive behaviour is modified by monoamine oxidase A (MAOA) functional polymorphism (MAOA-uVNTR) genotype, MAOA-Long (MAOA-L) in females, MAOA-Short (MAOA-S) in males. Childhood maltreatment is associated with differential DNA methylation in several genes. Consistent with recent proposals, we hypothesized that the association of the interaction of MAOA genotype and maltreatment with aggressive behaviour is further moderated by methylation of a region of interest (ROI) spanning the first exon and partial first intron of MAOA. METHOD: The sample included 117 women and 77 men who completed interviews and questionnaires to report maltreatment and aggressive behaviour towards others and provided saliva samples for DNA extraction. The MAOA-uVNTR polymorphism was genotyped, and methylation of the MAOA ROI was assessed. RESULTS: Following adjustment for substance misuse, psychoactive medication use, and in males tobacco use, the highest levels of aggressive behaviour were found among maltreated male carriers of MAOA-S with high levels of exonic methylation. CONCLUSION: Methylation levels within the MAOA ROI further contributed to the interaction of MAOA risk genotypes and maltreatment on aggressive behaviours among men.

Adolescent non-drinkers: Who are they? Social relations, school performance, lifestyle factors and health behaviours.

INTRODUCTION AND AIMS: Traditionally, non-drinking adults or young adults have been associated with health deficits rather than health benefits. However, as the proportion of Swedish non-drinking adolescents has doubled since 2000, their health profiles are of interest. The aim of the present study is to examine whether social relations, school characteristics, lifestyle factors or health behaviours distinguish adolescent non-drinkers from adolescent drinkers, and if their health profiles have changed from 2004 to 2012. DESIGN AND METHODS: Data from the Survey of Adolescent Life in Vestmanland, a health survey biennially distributed to all 9th graders (15-16 years) in a medium-sized Swedish county, was used. In total, 2872 students in 2004 and 2045 students in 2012 were included. RESULTS: Non-drinkers were distinguished from drinkers in both 2004 and 2012 by elevated parental supervision, a lower rate of school truancy and lower rates of cannabis use, use of other illicit drugs, daily smoking and lower scores on antisocial behaviour, but more problems of getting new friends. No differences between 2004 and 2012 were found. DISCUSSION AND CONCLUSIONS: Non-drinkers presented more adaptive and healthier behaviours than their drinking peers, but it is difficult to determine whether their health benefits were related to their improved alcohol status or to the more general trend towards adaptation that occurred from 2004 to 2012 among adolescents.

Pornography consumption among adolescent girls in Sweden.

OBJECTIVES: The aims of this study were to describe patterns of pornography consumption, investigate differences between consumers and non-consumers of pornography regarding sexual experiences, health and lifestyle and determine associations between pornography consumption and sexual experiences, health and lifestyle among adolescent girls. The hypotheses were that adolescent girls categorised as pornography consumers would report sexual experiences to a greater extent, and a riskier lifestyle and poorer health, compared with non-consumers. METHODS: A classroom survey was conducted among 16-year-old girls (N = 393). RESULTS: One-third (30%) consumed pornography. In this group, almost half (43%) had fantasies about trying to copy sexual acts seen in pornography and 39% had tried to copy sexual activities seen in pornography. A higher proportion of pornography-consuming girls reported sexual experiences compared with peers. A third (30%) reported experience of anal sex compared with 15% among non-consuming peers (p = 0.001). Furthermore, peer-relationship problems (17% vs 9%; p = 0.015), use of alcohol (85% vs 69%; p = 0.001) and daily smoking (27% vs 14%; p = 0.002) were reported to a greater extent than in non-consuming peers. Pornography consumption, use of alcohol and daily smoking were associated with experience of casual sex. CONCLUSIONS: Pornography-consuming girls reported sexual experiences and a risky lifestyle to a greater extent compared with non-consuming girls. This indicates that pornography consumption may influence sexualisation and lifestyle. This is important to acknowledge when designing and implementing sexual health programmes for adolescents.

Serotonin receptor gene (5HT-2A) polymorphism is associated with provoked vestibulodynia and comorbid symptoms of pain.

INTRODUCTION: Provoked vestibulodynia (PVD) is a common type of dyspareunia among young women. The patho-physiology remains largely unclear. Women with PVD have general pain hypersensitivity and often report additional pain symptoms. Signs point towards PVD being a chronic pain disorder similar to other syndromes of longstanding pain, including a common comorbidity of anxiety and depression. Polymorphism in the serotonin receptor gene, 5HT-2A, has been associated with other chronic pain disorders such as fibromyalgia but has not been investigated in PVD patients. AIM: We aimed to investigate a possible contribution of polymorphism in the 5HT-2A gene to the etiology of PVD as well as a potential influence on pain sensitivity. METHODS: In this case-control study 98 women with PVD and 103 healthy controls between 18 and 44 years and in the same menstrual cycle phase completed questionnaires and underwent quantitative sensory testing. Venous blood samples were collected for DNA isolation. MAIN OUTCOME MEASURES: Concomitant pain was reported, a bodily pain score was created and pressure pain thresholds (PPTs) on the arm, leg, and in the vestibule were measured. Intensity of coital pain was rated on a visual analog scale, range 0-100. The T102C (rs6313) and A-1438G (rs6311) single nucleotide polymorphisms (SNPs) in the 5HT-2A gene were analyzed. RESULTS: The probability of PVD was elevated in participants carrying the 1438G- and 102C-alleles of the 5HT-2A gene (OR 2.9). The G-/C- genotypes were also associated with more concomitant bodily pain in addition to the dyspareunia, but not with experimental PPTs or coital pain ratings. PVD patients reported more concomitant bodily pain and had lower PPTs compared with controls. CONCLUSION: The results indicate a contribution of alterations in the serotonergic system to the patho-genesis of PVD and gives further evidence of PVD being a general pain disorder similar to other chronic pain disorders.

A118G polymorphism in the µ-opioid receptor gene and levels of ß-endorphin are associated with provoked vestibulodynia and pressure pain sensitivity.

Background and aims Provoked vestibulodynia (PVD) is the most common cause of dyspareunia among young women. The aetiology is largely unknown and treatment is often extensive and longstanding with varying outcomes. Patients display general pain hypersensitivity and there are correlations with other chronic pain syndromes such as fibromyalgia later in life. The A118G polymorphism in the µ-opioid receptor (OPRM1) gene influences endogenous pain regulation and pain sensitivity, but has not been studied in this patient group before. We aimed to investigate a possible association between A118G polymorphism and PVD, with correlation to plasma levels of ß-endorphin, and to explore relationships between this polymorphism and pain sensitivity among women with PVD and healthy controls. Methods This case-control study included 98 women with PVD and 103 controls. Participants filled out study-specific questionnaires and underwent quantitative sensory testing of pressure pain thresholds on the arm, leg and in the vestibular area. Levels of ß-endorphin were analyzed by radioimmunoassay using the EURIA-beta-endorphin kit, and the A118G single-nucleotide polymorphism (SNP; rs1799971) in the OPRM1 gene was analyzed using the TaqMan SNP genotyping assay. Results The 118G allele was more common in controls (44%) than in patients (30%) (p = 0.042). The odds ratio of having PVD was 1.8 in participants carrying the 118A allele compared to participants hetero- or homozygous for the 118G allele (OR = 1.846, CI: 1.03-3.31, p = 0.039). Pressure pain thresholds on the leg were higher for participants carrying the 118G allele (mean 480 kPa, SD 167.5) than for those carrying the 118A allele (mean 419, SD 150.4, p = 0.008). Levels of ß-endorphin were higher in patients (mean 17.9 fmol/ml, SD 4.71) than in controls (mean 15.8 fmol/ml, SD 4.03) (p < 0.001). Conclusion We found an association between the A118G polymorphism in the OPRM1 gene and an increased risk of PVD and increased pain sensitivity among participants carrying the 118A allele. PVD patients were more sensitive to pressure pain and had higher levels of plasma ß-endorphin than controls. The results indicate that differences in endogenous pain modulation involving the opioid system could contribute to the pathophysiology of PVD and the general pain hypersensitivity seen in these women. Implications The data support the conceptualization of PVD as part of a general pain disorder with a possible genetic predisposition. The age of onset of PVD is usually between 18 and 25 years and already at this age general pain hypersensitivity is present but rarely causing disability. We believe that early recognition and treatment, with the risk of further development of chronic pain taken into consideration, might prevent future aggravated pain problems in this patient group.

Pornography consumption, sexual experiences, lifestyles, and self-rated health among male adolescents in Sweden.

OBJECTIVE: To describe patterns of pornography use among high school boys and to investigate differences between frequent, average, and nonfrequent users of pornography with respect to sexual experiences, lifestyles, and self-rated health. METHODS: A population-based classroom survey among 16-year-old boys (n = 477), from 53 randomly selected high school classes in 2 towns in mid-Sweden. RESULTS: Almost all boys, 96% (n = 453), had watched pornography. Frequent users of pornography (everyday) (10%, n = 47) differed from average users (63%, n = 292) and nonfrequent users (27%, n = 126). Frequent users versus average users and nonfrequent users had more sexual experiences, such as one night stands (45, 32, 25%, respectively) and sex with friends more than 10 times (13, 10, 2%). A higher proportion of frequent users spent more than 10 straight hours at the computer several times a week (32, 5, 8%) and reported more relationship problems with peers (38, 22, 21%), truancy at least once a week (11, 6, 5%), obesity (13, 3, 3%), use of oral tobacco (36, 29, 20%), and use of alcohol (77, 70, 52%) versus average and nonfrequent users. One third of frequent users watched more pornography than they actually wanted. There were no differences between the groups regarding physical and psychological self-rated health. CONCLUSIONS: The boys, defined as frequent users of pornography, were more sexually experienced, spent more time at the computer, and reported an unhealthier lifestyle compared with average and nonfrequent users. No differences regarding self-rated health were detected even though obesity was twice as common among frequent users.

Social capital in relation to alcohol consumption, smoking, and illicit drug use among adolescents: a cross-sectional study in Sweden.

BACKGROUND: Social capital has lately received much attention in public health research. However, few studies have examined the influence of social capital on alcohol consumption, smoking and drug use which have strong influence on public health. The present cross-sectional study investigated whether two measures of social capital were related to substance use in a large population of Swedish adolescents. METHODS: A total of 7757 13-18 year old students (participation rate: 78.2%) anonymously completed the Survey of Adolescent Life in Vestmanland 2008 which included questions on sociodemographic background, neighbourhood social capital, general social trust, alcohol consumption, smoking, and illicit drug use. RESULTS: Individuals within the group with low neighbourhood social capital had an approximately 60% increased odds of high alcohol consumption, more than three times increased odds of smoking and more than double the odds of having used illicit drugs compared with individuals with high neighbourhood social capital. Individuals within the group with low general social trust had approximately 50% increased odds of high alcohol consumption and double the odds of smoking and having used illicit drugs compared with individuals with high general social trust. However, social capital at the contextual level showed very weak effects on alcohol consumption, smoking, and illicit drug use. CONCLUSIONS: Social capital may be an important factor in the future development of prevention programs concerning adolescent substance use. However, further replications of the results as well as identifications of direction of causality are needed.

Combined analysis of circulating ß-endorphin with gene polymorphisms in OPRM1, CACNAD2 and ABCB1 reveals correlation with pain, opioid sensitivity and opioid-related side effects.

BACKGROUND: Opioids are associated with wide inter-individual variability in the analgesic response and a narrow therapeutic index. This may be partly explained by the presence of single nucleotide polymorphisms (SNPs) in genes encoding molecular entities involved in opioid metabolism and receptor activation. This paper describes the investigation of SNPs in three genes that have a functional impact on the opioid response: OPRM1, which codes for the µ-opioid receptor; ABCB1 for the ATP-binding cassette B1 transporter enzyme; and the calcium channel complex subunit CACNA2D2. The genotyping was combined with an analysis of plasma levels of the opioid peptide ß-endorphin in 80 well-defined patients with chronic low back pain scheduled for spinal fusion surgery, and with differential sensitivity to the opioid analgesic remifentanil. This patient group was compared with 56 healthy controls. RESULTS: The plasma ß-endorphin levels were significantly higher in controls than in pain patients.A higher incidence of opioid-related side effects and sex differences was found in patients with the minor allele of the ABCB1 gene. Further, a correlation between increased opioid sensitivity and the major CACNA2D2 allele was confirmed. A tendency of a relationship between opioid sensitivity and the minor allele of OPRM1 was also found. CONCLUSIONS: Although the sample cohort in this study was limited to 80 patients it appears that it was possible to observe significant correlations between polymorphism in relevant genes and various items related to pain sensitivity and opioid response. Of particular interest is the new finding of a correlation between increased opioid sensitivity and the major CACNA2D2 allele. These observations may open for improved strategies in the clinical treatment of chronic pain with opioids.

Smoking as a product of gene-environment interaction.

A strong hereditary influence on smoking has been demonstrated. As one of the candidate genes in relation to smoking, the serotonin transporter gene (5-HTTLPR) has been suggested, however with conflicting results. In recent studies, it has been shown that genotypic and environmental (G*E) factors interact in the shaping of a variety of phenotypic expressions. The objective of the present study was to investigate the interaction between a variation in the 5-HTTLPR and family environment in relation to smoking habits, nicotine dependence, and nicotine and cotinine levels in hair samples. A random Swedish adolescent population sample (n = 785), from which 200 individuals were stratified regarding behaviour, was genotyped for 5-HTTLPR and assessed with semi-structured interviews, a questionnaire, and hair analyses of nicotine and cotinine. The 5-HTTLPR gene interacted with a poor family environment to predict smoking habits, as well as nicotine and cotinine levels. The risk of being a smoker was increased 13 times for an individual with a combination of the 5-HTTLPR LS genotype and a poor family environment in comparison with the Homozygous Long-Long (LL) genotype and a good family environment.