Transdiagnostic and tailored internet intervention to improve mental health among university students: Research protocol for a randomized controlled trial.

BACKGROUND: Emerging adulthood is often associated with mental health problems. About one in three university students report symptoms of depression and anxiety that can negatively affect their developmental trajectory concerning work, intimate relationships, and health. This can interfere with academic performance, as mood and anxiety disorders are key predictors of dropout from higher education. A treatment gap exists, where a considerable proportion of students do not seek help for mood and anxiety symptoms. Offering internet interventions to students with mental health problems could reduce the treatment gap, increase mental health, and improve academic performance. A meta-analysis on internet interventions for university students showed small effects for depression and none for anxiety. Larger trials are recommended to further explore effects of guidance, transdiagnostic approaches, and individual treatment components. METHODS: This study will offer 1200 university students in Sweden participation in a three-armed randomized controlled trial (RCT) evaluating a guided or unguided transdiagnostic internet intervention for mild to moderate depression and anxiety, where the waitlist control group accesses the intervention at 6-month follow-up. Students reporting suicidal ideation/behaviors will be excluded and referred to treatment within the existing healthcare system. An embedded study within the trial (SWAT) will assess at week 3 of 8 whether participants in the guided and unguided groups are at higher risk of failing to benefit from treatment. Those at risk will be randomized to an adaptive treatment strategy, or to continue the treatment as originally randomized. Primary outcomes are symptoms of depression and anxiety. Follow-ups will occur at post-treatment and at 6-, 12-, and 24-month post-randomization. Between-group outcome analyses will be reported, and qualitative interviews about treatment experiences are planned. DISCUSSION: This study investigates the effects of a transdiagnostic internet intervention among university students in Sweden, with an adaptive treatment strategy employed during the course of treatment to minimize the risk of treatment failure. The study will contribute knowledge about longitudinal trajectories of mental health and well-being following treatment, taking into account possible gender differences in responsiveness to treatment. With time, effective internet interventions could make treatment for mental health issues more widely accessible to the student group.

Predictors of beverage-specific, alcohol consumption trajectories: A Swedish population-based cohort study.

Aim: The aim of the study was to examine whether changes in alcohol consumption over time differ according to beverage types, and to what extent socioeconomic, lifestyle and health-related factors predict beverage-specific trajectories in Sweden. Study design: We included participants from the Stockholm Public Health Cohort who were surveyed repeatedly in 2002, 2010 and 2014. Alcohol consumption trajectories were constructed for 13,152 individuals with valid information on amount and frequency of drinking. Preferred beverage types (i.e., beer, wine or spirits) were defined based on the most consumed beverages. Multinomial logistic regression was used to quantify individual predictors of different trajectories, overall and by beverage type. Results: Overall 56.9% of respondents were women, the mean age was 49.2 years, SD (13.1). Wine was cited as the preferred beverage for 72.4% of participants, and stable moderate drinking was the most common trajectory regardless of beverage type (68.2%, 54.9% and 54.2% in individuals with wine, beer and spirits as preferred beverages, respectively). Associations between drinking trajectories and baseline lifestyle factors did not differ by beverage type. Lower socioeconomic position (SEP) was associated with unstable moderate wine drinking (for unskilled manual SEP: adjusted odds ratio [aOR] 1.54, 95% confidence interval [CI] 1.23, 1.93), unstable heavy beer drinking (for skilled manual SEP: aOR 1.99, 95% CI 1.14, 3.52; and unskilled manual SEP: aOR 1.72, 95% CI 1.05, 2.82), and former beer drinking trajectory (for skilled manual SEP: aOR 1.81; 95% CI 1.21, 2.72; and unskilled manual SEP: aOR 1.66; 95% CI 1.17, 2.37). Conclusion: Lower SEP was associated with unstable heavy drinking of beer, former beer drinking, and unstable moderate wine drinking trajectories indicating that targeted alcohol prevention programmes need to focus on these groups.

Academic self-efficacy: Associations with self-reported COVID-19 symptoms, mental health, and trust in universities' management of the pandemic-induced university lockdown.

Objective: To investigate perceived changes in academic self-efficacy associated with self-reported symptoms of COVID-19, changes in mental health, and trust in universities' management of the pandemic and transition to remote education during lockdown of Swedish universities in the spring of 2020. Methods: 4495 participated and 3638 responded to self-efficacy questions. Associations were investigated using multinomial regression. Results: Most students reported self-experienced effects on self-efficacy. Lowered self-efficacy was associated with symptoms of contagion, perceived worsening of mental health and low trust in universities' capacity to successfully manage the lockdown and transition to emergency remote education. Increased self-efficacy was associated with better perceived mental health and high trust in universities. Conclusion: The initial phase of the pandemic was associated with a larger proportion of students reporting self-experienced negative effects on academic self-efficacy. Since self-efficacy is a predictor of academic performance, it is likely that students' academic performance will be adversely affected.

Symptoms of COVID-19 contagion in different social contexts in association to self-reported symptoms, mental health and study capacity in Swedish university students.

OBJECTIVE: The present study investigates if symptoms of COVID-19 contagion in different social contexts (cohabitants, family, acquaintances, and others) are associated with university students' own self-reported symptoms of COVID-19 contagion, mental health, and study capacity. This was investigated by a cross-sectional survey administrated in Sweden during the first wave of the COVID-19 pandemic, at the time when universities were locked down to limit viral spread and contagion. RESULTS: Mild to moderate symptoms of COVID-19 in cohabitants and family members were associated with student's self-reported symptoms of contagion, while no associations could be seen in relation to mental health and study capacity. Symptoms of COVID-19 contagion in acquaintances and others were not associated with students' self-reported symptoms, nor with their mental health and study capacity. To conclude, during the initial lockdown of universities students' self-reported symptoms of contagion were mainly associated with cohabitants and family members, while symptoms of contagion in different social contexts were not associated with mental health and study capacity. Findings suggest that lockdown of universities may have contributed to limiting infection pathways, while still allowing students to focus on their studies despite significant contagion among others known to the student.

Perfluoroalkyl substances influence DNA methylation in school-age children highly exposed through drinking water contaminated from firefighting foam: a cohort study in Ronneby, Sweden.

Perfluoroalkyl substances (PFASs) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFASs is via epigenetic changes, such as DNA methylation. Previous studies have evaluated associations between PFAS exposure and DNA methylation among newborns and adults. However, no study has evaluated how PFASs influence DNA methylation among children of school age. In this exploratory study with school-age children exposed to PFASs through drinking water highly contaminated from firefighting foams, we aimed to investigate whether exposure to PFASs was associated with alteration in DNA methylation and epigenetic age acceleration. Sixty-three children aged 7-11 years from the Ronneby Biomarker Cohort (Sweden) were included. The children were either controls with only background exposure (n = 32; perfluorooctane sulfonic acid: median 2.8 and range 1-5 ng/ml) or those exposed to very high levels of PFASs (n = 31; perfluorooctane sulfonic acid: median 295 and range 190-464 ng/ml). These two groups were matched on sex, age, and body mass index. Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip kit. Epigenetic age acceleration was derived from the DNA methylation data. Twelve differentially methylated positions and seven differentially methylated regions were found when comparing the high-exposure group to the control group. There were no differences in epigenetic age acceleration between these two groups (P = 0.66). We found that PFAS exposure was associated with DNA methylation at specific genomic positions and regions in children at school age, which may indicate a possible mechanism for linking PFAS exposure to health effects.

Maternal exposure to cadmium during pregnancy is associated with changes in DNA methylation that are persistent at 9 years of age.

BACKGROUND: Cadmium (Cd) exposure during gestation has been associated with altered DNA methylation at birth, but it is not known if the changes in methylation persist into childhood. OBJECTIVES: To evaluate whether gestational Cd-related changes of DNA methylation persist from birth to 9 years of age. METHODS: We studied mother-child dyads in a longitudinal cohort in rural Bangladesh. Cadmium concentrations in maternal blood (erythrocyte fraction; Ery-Cd) at gestational week 14 and in child urine (U-Cd, long-term exposure marker) at 9 years were measured using inductively coupled plasma mass spectrometry. The epigenome-wide DNA methylation was measured in mononuclear cells (PBMCs) prepared from cord blood and peripheral blood at 9 years in 71 children (hereafter referred to as the explorative group) by Infinium HumanMethylation450K BeadChip. Replication of one differentially methylated region (DMR; 9 CpG sites) was performed in PBMCs of 160 9-year-old children (validation group) by EpiTyper MALDI-TOF mass spectrometry. RESULTS: The median maternal Ery-Cd concentration was 1.24 µg/kg (range 0.35, 4.55) in the explorative group and 0.83 µg/kg (0.08, 2.97) in the validation group. The median U-Cd concentration in the 9-year-old children was 0.26 µg/L (0.09, 1.06) in the explorative group and 0.32 µg/L (0.07, 1.33) in the validation group. In the explorative group, we identified ten DMRs, both in cord blood and in PBMCs at 9 years, that were associated with maternal Ery-Cd. Eight out of the ten DMRs were hypomethylated and three of the hypomethylated DMRs were located in the HLA region on chromosome 6. One of the DMRs (hypomethylated) in the HLA region (upstream of the zinc finger protein 57 homolog, ZFP57 gene) was replicated in the validation group, and we found that it was hypomethylated in relation to maternal Ery-Cd, but not child U-Cd. CONCLUSION: Gestational exposure to Cd appears to be associated with regional changes, especially hypomethylated, in DNA methylation that linger from birth up to prepubertal age.

High in Utero Exposure to Perfluoroalkyl Substances from Drinking Water and Birth Weight: A Cohort Study among Infants in Ronneby, Sweden.

In 2013, the drinking water for one-third of the households in Ronneby, Sweden, was found to be contaminated by perfluorinated alkyl substances (PFAS, >10,000 ng/L) from Aqueous Film Forming Foam (AFFF). In utero PFAS exposure can influence birth weight, but little is known about the effects at very high levels. This study aimed to examine the association between in utero PFAS exposure and birth weight. Infants with mothers from Ronneby exposed to contaminated water at home (high exposure) and infants with mothers from Ronneby not exposed to contaminated water at home (low exposure) were compared to infants with mothers from Blekinge county excluding Ronneby (referents). All infants born in Blekinge county 1995-2013 were included (n = 30,360). Differences in birth weight were only seen among infants born after 2005. For boys, Ronneby high exposure had a lower mean birth weight than referents (-54 g, 95% CI -97; -11). For girls, Ronneby high exposure had a higher mean birth weight than referents (47 g, 95% CI 4; 90). There were no differences in birth weight between referents and Ronneby low exposure. In conclusion, high exposure to PFAS may influence birth weight in a sex-specific way, although the effect estimates were relatively small.

Compliance with recommendations limiting COVID-19 contagion among university students in Sweden: associations with self-reported symptoms, mental health and academic self-efficacy.

AIMS: The COVID-19 containment strategy in Sweden uses public health recommendations relying on personal responsibility for compliance. Universities were one of few public institutions subject to strict closure, meaning that students had to adapt overnight to online teaching. This study investigates the prevalence of self-reported recommendation compliance and associations with self-reported symptoms of contagion, self-experienced effects on mental health and academic self-efficacy among university students in Sweden in May-June 2020. METHODS: This was a cross-sectional 23 question online survey in which data were analysed by multinomial regression, taking a Bayesian analysis approach complemented by null hypothesis testing. RESULTS: A total of 4495 students consented to respond. Recommendation compliance ranged between 70% and 96%. Women and older students reported higher compliance than did men and younger students. Mild to moderate COVID-19 symptoms were reported by 30%, severe symptoms by fewer than 2%; 15% reported being uncertain and half of the participants reported no symptoms. Mental health effects were reported by over 80%, and changes in academic self-efficacy were reported by over 85%; in both these areas negative effects predominated. Self-reported symptoms and uncertainty about contagion were associated with non-compliance, negative mental health effects, and impaired academic self-efficacy. CONCLUSIONS: Students generally followed public health recommendations during strict closure of universities, but many reported considerable negative consequences related to mental health and academic self-efficacy. Digital interventions should be developed and evaluated to boost coping skills, build resilience and alleviate student suffering during the pandemic and future similar crises.

Early Pregnancy Exposure to Ambient Air Pollution among Late-Onset Preeclamptic Cases Is Associated with Placental DNA Hypomethylation of Specific Genes and Slower Placental Maturation.

Exposure to ambient air pollution during pregnancy has been associated with an increased risk of preeclampsia (PE). Some suggested mechanisms behind this association are changes in placental DNA methylation and gene expression. The objective of this study was to identify how early pregnancy exposure to ambient nitrogen oxides (NOx) among PE cases and normotensive controls influence DNA methylation (EPIC array) and gene expression (RNA-seq). The study included placentas from 111 women (29 PE cases/82 controls) in Scania, Sweden. First-trimester NOx exposure was assessed at the participants' residence using a dispersion model and categorized via median split into high or low NOx. Placental gestational epigenetic age was derived from the DNA methylation data. We identified six differentially methylated positions (DMPs, q < 0.05) comparing controls with low NOx vs. cases with high NOx and 14 DMPs comparing cases and controls with high NOx. Placentas with female fetuses showed more DMPs (N = 309) than male-derived placentas (N = 1). Placentas from PE cases with high NOx demonstrated gestational age deceleration compared to controls with low NOx (p = 0.034). No differentially expressed genes (DEGs, q < 0.05) were found. In conclusion, early pregnancy exposure to NOx affected placental DNA methylation in PE, resulting in placental immaturity and showing sexual dimorphism.

Associations between compliance with covid-19 public health recommendations and perceived contagion in others: a self-report study in Swedish university students.

OBJECTIVE: During the COVID pandemic, government authorities worldwide have tried to limit the spread of the virus. Sweden's distinctive feature was the use of voluntary public health recommendations. Few studies have evaluated the effectiveness of this strategy. Based on data collected in the spring of 2020, this study explored associations between compliance with recommendations and observed symptoms of contagion in others, using self-report data from university students. RESULTS: Compliance with recommendations ranged between 69.7 and 95.7 percent. Observations of moderate symptoms of contagion in "Someone else I have had contact with" and "Another person" were markedly associated with reported self-quarantine, which is the most restrictive recommendation, complied with by 81.2% of participants. Uncertainty regarding the incidence and severity of contagion in cohabitants was markedly associated with the recommendation to avoid public transportation, a recommendation being followed by 69.7%. It is concluded that students largely followed the voluntary recommendations implemented in Sweden, suggesting that coercive measures were not necessary. Compliance with recommendations were associated with the symptoms students saw in others, and with the perceived risk of contagion in the student's immediate vicinity. It is recommended that voluntary recommendations should stress personal relevance, and that close relatives are at risk.

Does the management of personal integrity information lead to differing participation rates and response patterns in mental health surveys with young adults? A three-armed methodological experiment.

OBJECTIVES: This study evaluates whether initiation rates, completion rates, response patterns and prevalence of psychiatric conditions differ by level of personal integrity information given to prospective participants in an online mental health self-report survey. METHODS: A three-arm, parallel-group, single-blind experiment was conducted among students from two Swedish universities. Consenting participants following e-mail invitation answered the World Health Organization (WHO) World Mental Health-International College Student (WMH-ICS) mental health self-report survey, screening for eight psychiatric conditions. Random allocation meant consenting to respond (1) anonymously; (2) confidentially, or (3) confidentially, where the respondent also gave consent for collection of register data. RESULTS: No evidence was found for overall between-group differences with respect to (1) pressing a hyperlink to the survey in the invitation email; and (2) abandoning the questionnaire before completion. However, participation consent and self-reported depression were in the direction of higher levels for the anonymous group compared to the two confidential groups. CONCLUSIONS: Consent to participate is marginally affected by different levels of personal integrity information. Current standard participant information procedures may not engage participants to read the information thoroughly, and online self-report mental health surveys may reduce stigma and thus be less subject to social desirability bias.

Social and sex differences in psychiatric comorbidity and psychosocial functioning among adolescents with depression.

BACKGROUND: To determine social and sex differences in psychosocial functioning and psychiatric comorbidity among adolescents with depression. METHODS: A cohort-based study in Stockholm, Sweden. Adolescents who turned 13 years during 2001-2007, were followed in registers until they turned 18 in 2005-2011, (n = 169,262). In the current study, those with depression at age 13-17 were included (n = 6,439). RESULTS: Adolescents with parents with low (OR=1.5, CI 1.1-2.2) education were more likely to have low psychosocial functioning. Those with parents with low education and low household income were more likely to have comorbid internalizing (OR=1.3, CI 1.0-1.7/1.3, CI 1.0-1.7) and externalizing disorders (OR=2.5, CI 1.5-4.0/2.4, CI 1.4-4.2). Adolescents with parents born outside the Nordic countries were more likely to have comorbid externalizing disorders (OR=1.6, CI 1.1-2.4). No social differences were evident in relation to family receipt of unemployment benefits. Social differences were found for both girls and boys in relation to psychosocial functioning and comorbidity but the magnitude of social differences in depression with comorbidity was overall larger for boys than girls. LIMITATIONS: The findings of the current study can only be generalized to adolescents that have sought care for and been diagnosed with depression, within a setting similar to this study, e.g. with free access to care. CONCLUSION: Adolescents with depression and with more disadvantaged social circumstances in the childhood run a higher risk of psychiatric comorbidity and low psychosocial functioning, which can indicate a lengthy clinical course and poorer response to treatment. Both boys and girls follow this path but partly in different kinds of psychiatric comorbidity.

The Importance of Pedagogical and Social School Climate to Bullying: A Cross-Sectional Multilevel Study of 94 Swedish Schools.

BACKGROUND: Bullying is a public health issue with long-term effects for victims. This study investigated if there was an association between pedagogical and social school climate and student-reported bullying victimization, which dimensions of pedagogical and social school climate were associated with bullying, and if these associations were modified by individual-level social factors. METHODS: The study had a cross-sectional multilevel design with individual-level data on bullying from 3311 students nested in 94 schools over 3 consecutive school years. School climate was measured with student and teacher questionnaires, aggregated at the school level. The association between school climate and bullying victimization was estimated with multilevel mixed-model logistic regression. RESULTS: In schools with the most favorable school climate, fewer students reported being bullied. This was especially evident when school climate was measured with the student instrument. Students in schools with favorable climate had an adjusted odds ratio of bullying of 0.74 (95% CI: 0.55-1.00) compared to students in schools with the worst climate. Results from the teacher instrument were in the same direction, but less consistent. CONCLUSIONS: Improvement in school climate has the potential to affect students both academically, and socially, as well as decrease the prevalence of bullying.

Serum perfluoroalkyl substances in residents following long-term drinking water contamination from firefighting foam in Ronneby, Sweden.

BACKGROUND: In December 2013, it was discovered that drinking water supplied to one third of the households in Ronneby, southern Sweden, was highly contaminated by PFAS (sum level >10,000 ng/L) originated from firefighting foams used at a nearby military airport. OBJECTIVES: To report serum PFAS levels of Ronneby residents participating in a biomonitoring program, and to describe the variation by age, sex and calendar period for residential exposure. In addition, a reference group living in a neighboring municipality without PFAS contaminated drinking water was examined. METHODS: Blood samples and demographic data were collected for 3297 Ronneby residents and 226 individuals from the reference group. Yearly residence addresses were available for 3086 Ronneby residents from the national population registry. Serum concentrations of PFHxS, PFOS and PFOA were determined in all participants, with additional PFHpA, PFNA and PFDA in subsets of the participants. RESULTS: The population geometric means for serum PFHxS, PFOS and PFOA were 114, 135 and 6.8 ng/mL for all Ronneby residents, i.e.135, 35 and 4.5 times higher than for the reference group. Ronneby residents who resided in the area with contaminated water supply during 2005-2013 showed much higher PFAS levels in 2014 than those exposed only before 2005. Ronneby residents who never resided in the area with contaminated water supply also had higher serum PFAS levels than the reference group. All three PFAS were highly correlated (rs > 0.9 for each pair). Serum PFAS levels were lowest in teenage years and then increased with age. Adult females had lower PFAS levels on average than males under the age of 60 but higher above 60. DISCUSSION: The results reveal high serum PFAS levels dominated by PFHxS and PFOS in the Ronneby residents highly exposed to PFAS originated from firefighting foams. The PFAS exposure in Ronneby permits studies of associations to a range of health parameters, as well as studies of the toxicokinetics of PFAS exposure.

Associations between serum concentrations of perfluoroalkyl substances and DNA methylation in women exposed through drinking water: A pilot study in Ronneby, Sweden.

BACKGROUND: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFAS is via epigenetic changes, such as DNA methylation. However, few studies have evaluated associations between PFAS exposure and DNA methylation among adults, and data is especially scarce for women. Furthermore, exposure to environmental pollutants has been associated with epigenetic age acceleration, but no studies have yet evaluated whether PFAS is associated with epigenetic age acceleration. OBJECTIVES: To investigate whether exposure to PFAS is associated with alteration of DNA methylation and epigenetic age acceleration among women. METHODS: In this observational pilot study, 59 women (aged 20-47 years at enrollment in 2014) from Ronneby, Sweden, an area with historically high PFAS exposure due to local drinking water contamination, were divided into three PFAS exposure groups (low, medium, and high). Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip. Ingenuity Pathway Analysis was used for in silico functional assessment. Epigenetic age acceleration was derived from the DNA methylation data using Horvath's epigenetic skin and blood clock. RESULTS: 117 differentially methylated positions (q < 0.017) and one near-significantly differentially methylated region (S100A13, FWER = 0.020) were identified. In silico functional analyses suggested that genes with altered DNA methylation (q < 0.05) were annotated to cancer, endocrine system disorders, reproductive system disease, as well as pathways such as estrogen receptor signaling, cardiac hypertrophy signaling, PPARα/RXRα activation and telomerase signaling. No differences in epigenetic age acceleration between PFAS exposure groups were noted (p = 0.43). CONCLUSION: The data suggests that PFAS exposure alters DNA methylation in women highly exposed to PFAS from drinking water. The observed associations should be verified in larger cohorts, and it should also be further investigated whether these changes in methylation also underlie potential phenotypic changes and/or adverse health effects of PFAS.

Adolescents' Experiences of the Staff's Different Interaction Styles in Coercive Youth Care in Sweden: A Qualitative Study.

We interviewed 20 adolescents who were coercively placed in residential or psychiatric care. The aim was to explore their views on the way staff relate and perform their duties, favorable characteristics in staff, consequences of different treatment from staff and their safety experiences. Thematic analysis identified the following themes: Situational triggers of frustration; Care-based; rule-based; or passive-avoidant interaction styles toward adolescents and their responses; Adolescents' reflections about staff's interaction styles; and the Consequences on the unit atmosphere depending on different interaction styles toward the adolescents. Adolescents preferred staff who showed them respect and a clear wish to make life easier.

Maternal Long-Chain Polyunsaturated Fatty Acid Status, Methylmercury Exposure, and Birth Outcomes in a High-Fish-Eating Mother-Child Cohort.

BACKGROUND: Maternal status of long-chain PUFAs (LC-PUFAs) may be related to fetal growth. Maternal fish consumption exposes the mother to the neurotoxicant methylmercury (MeHg), which, in contrast, may restrict fetal growth. OBJECTIVE: Our aim was to examine relations between maternal LC-PUFA status at 28 wk and birth outcomes (birth weight, length, and head circumference), controlling for MeHg exposure throughout pregnancy, in the Seychelles Child Development Study Nutrition Cohort 2. Our secondary aim was to examine the influence of maternal variation in genes regulating the desaturation of LC-PUFAs [fatty acid desaturase (FADS)] on birth outcomes. METHODS: From nonfasting blood samples collected at 28 wk of gestation, we measured serum total LC-PUFA concentrations and FADS1 (rs174537, rs174561), FADS1-FADS2rs3834458, and FADS2rs174575 genotypes, with hair total mercury concentrations assessed at delivery. Data were available for n = 1236 mother-child pairs. Associations of maternal LC-PUFAs, MeHg, and FADS genotype with birth outcomes were assessed by multiple linear regression models, adjusting for child sex, gestational age, maternal age, BMI, alcohol use, socioeconomic status, and parity. RESULTS: In our cohort of healthy mothers, neither maternal LC-PUFA status nor MeHg exposure were significant determinants of birth outcomes. However, when compared with major allele homozygotes, mothers who were heterozygous for the minor allele of FADS1 (rs174537 and rs174561, GT compared with TT, ß = 0.205, P = 0.03; TC compared with CC, ß = 0.203, P = 0.04) and FADS1-FADS2 (rs3834458, Tdel compared with DelDel, ß = 0.197, P = 0.04) had infants with a greater head circumference (all P < 0.05). Homozygosity for the minor allele of FADS2 (rs174575) was associated with a greater birth weight (GG compared with CC, ß = 0.109, P = 0.04). CONCLUSIONS: In our mother-child cohort, neither maternal LC-PUFA status nor MeHg exposure was associated with birth outcomes. The observed associations of variation in maternal FADS genotype with birth outcomes should be confirmed in other populations.

Association between serum concentrations of perfluoroalkyl substances (PFAS) and expression of serum microRNAs in a cohort highly exposed to PFAS from drinking water.

BACKGROUND: Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. Not much is known about the modes of action of PFAS toxicity, but one likely mechanism is alteration of microRNA expression. OBJECTIVES: To investigate whether PFAS exposure is associated with altered microRNA expression in serum. METHODS: We selected women from the Ronneby cohort, with high exposure to perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS), emanating from drinking water contaminated by firefighting foam, and a control group of women from a neighbouring municipality without drinking water contamination. Serum levels of PFAS were analysed using LC/MS/MS. High coverage microRNA expression was analysed by next generation sequencing (NGS) in 53 individuals to screen for microRNAs associated with PFAS exposure. After verification by qPCR, associations between PFAS exposure and expression of 18 selected microRNAs were validated by qPCR in 232 individuals. In silico functional analyses were performed using Ingenuity pathway analysis (IPA). RESULTS: Three microRNAs were consistently associated with PFAS exposure in the different steps of the study: miR-101-3p, miR-144-3p and miR-19a-3p (all downregulated with increasing exposure). In silico functional analyses suggested that these PFAS-associated microRNAs were annotated to e.g. cardiovascular function and disease, Alzheimer's disease, growth of cancer cell lines and cancer. Seven predicted target genes for the downregulated microRNAs were annotated to PFAS in IPA knowledge database: DNA methyltransferase 3 alpha (DNMT3a), epidermal growth factor receptor (EGFR), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), nuclear receptor subfamily 1, group H, member 3 (NR1H3), peroxisome proliferator-activated receptor alpha (PPARα), prostaglandin-endoperoxide synthase 2 (PTGS2), and tumour growth factor alpha (TGFα). DISCUSSION: PFAS exposure was associated with downregulation of specific microRNAs. Further, in silico functional analyses suggest potential links between the specific PFAS-associated microRNAs, specific microRNA target genes and possibly also health effects.

Alcohol consumption trajectories and self-rated health: findings from the Stockholm Public Health Cohort.

OBJECTIVE: To investigate whether poor self-rated health and psychological distress are differentially associated with drinking trajectories over time. METHODS: From the Stockholm Public Health Cohort, two subcohorts surveyed in 2002-2010-2014 and 2006-2010-2014 (n=23 794 and n=34 667 at baseline, respectively) were used. Alcohol consumption, self-rated health, psychological distress (measured by General Health Questionnaire-12), lifestyle factors and longstanding illness were assessed by questionnaires. Demographic and socioeconomic variables were obtained by register linkage. Logistic regression was fitted to assess the associations with eight alcohol consumption trajectories, which were constructed among 30 228 individuals (13 898 and 16 330 from the 2002 and 2006 subcohorts, respectively) with measures of consumption at three time points. RESULTS: Compared with stable moderate drinkers, all other trajectories were associated with poor self-rated health with multiadjusted OR for stable non-drinkers of 2.35 (95% CIs 1.86 to 2.97), unstable non-drinkers (OR=2.58, 95% CI 1.54 to 3.32), former drinkers (OR=2.81, 95% CI 2.31 to 3.41) and stable heavy drinkers (OR=2.16, 95% CI 1.47 to 3.20). The associations were not fully explained by sociodemographic and lifestyle factors and longstanding illness. Former drinking, but no other trajectories, was associated with psychological distress (OR=1.24; 95% CI 1.10 to 1.41). CONCLUSION: We found a U-shape association between alcohol trajectories and self-rated health, but not with psychological distress. Compared with stable moderate drinking, former drinking was associated with the highest odds of both poor self-rated health and psychological distress. The study confirms the importance of a life-course approach to examining the effect of alcohol consumption on health and highlights the poorer general and mental health status of non-drinkers who were former drinkers.

Polymorphisms in potential mercury transporter ABCC2 and neurotoxic symptoms in populations exposed to mercury vapor from goldmining.

BACKGROUND: Artisanal small-scale gold miners have high levels of mercury in human specimens often above recommended threshold values. There are differences reported in the manifestation of neurological symptoms of individuals with a comparable level of exposure to mercury, suggesting a genetic component influencing the susceptibility to mercury neurotoxicity. OBJECTIVE: To investigate associations between polymorphisms (rs1885301, rs717620, rs2273697) in the potential Hg-transporter ABCC2 gene and neurological effects. METHODS: 968 participants from the Philippines, Indonesia, Tanzania and Zimbabwe were included in this study (age 12-59 years). For the statistical analysis the countries were categorized into Africa (Philippines, Indonesia) and Asia (Tanzania, Zimbabwe). Study participants were from three exposure groups: without mercury exposure from goldmining (n = 129); living in mercury-contaminated areas (n = 281) and mercury working exposure (n = 558). To identify chronic inorganic mercury intoxication we applied a modified neurological score sum including eight binary coded parameters (from anamnestic, clinical and neurophysiological examinations). Associations between genotype and neurological score sum, as well as between genotype and separate neurological tests (ataxia of gait, dysdiadochokinesia, ataxia heel to shin, pencil tapping test and matchbox test) were evaluated. RESULTS: We found that ABCC2 genotype were associated with performance on certain neurological tests: for rs1885301, A-allele carriers in the African populations showed significantly worse performance than GG carriers on the pencil tapping test; whereas for rs2273697, A-allele carriers in the African and Asian populations showed a significantly better performance than GG carriers on this test. When including an interaction term between genotype and exposure subgroup, interaction effects were also seen for the pencil tapping test and matchbox tests for rs2273697 in Asia. CONCLUSIONS: The results suggest that certain ABCC2 polymorphisms may influence the neurotoxic effects in mercury-burdened individuals. ABCC2 alleles associated with worse neurological performance in the present study. These alleles have previously been correlated with higher levels of urinary mercury concentrations in the same cohort. Taken together, these associations between ABCC2 genotype, mercury levels, and neurological effects support the hypothesis that some ABCC2 genotypes may have a higher neurotoxic potential, although further functional studies are needed to prove causation.