Differences in the gut microbiome of young adults with schizophrenia spectrum disorder: using machine learning to distinguish cases from controls.

While an association between the gut microbiome and schizophrenia spectrum disorders (SSD) has been suggested, the existing evidence is still inconclusive. To this end, we analyzed bacteria and bacterial genes in feces from 52 young adult SSD patients and 52 controls using fecal shotgun metagenomic sequencing. Compared to controls, young SSD patients were found to have significantly lower α-diversity and different ß-diversity both regarding bacterial species (i.e., taxonomic diversity) and bacterial genes (i.e., functional diversity). Furthermore, the α-diversity measures 'Pielou's evenness' and 'Shannon' were significantly higher for both bacterial species, bacterial genes encoding enzymes and gut brain modules in young SSD patients on antipsychotic treatment (young SSD not on antipsychotics=9 patients, young SSD on antipsychotics=43 patients). We also applied machine learning classifiers to distinguish between young SSD patients and healthy controls based on their gut microbiome. Results showed that taxonomic and functional data classified young SSD individuals with an accuracy of ≥ 70% and with an area under the receiver operating characteristic curve (AUROC) of ≥ 0.75. Differential abundance analysis on the most important features in the classifier models revealed that most of the species with higher abundance in young SSD patients had their natural habitat in the oral cavity. In addition, many of the modules with higher abundance in young SSD patients were amino acid biosynthesis modules. Moreover, the abundances of gut-brain modules of butyrate synthesis and acetate degradation were lower in the SSD patients compared to controls. Collectively, our findings continue to support the presence of gut microbiome alterations in SSD and provide support for the use of machine learning algorithms to distinguish patients from controls based on gut microbiome profiles.

Discrepancy between Current, Desired, and Ideal Body Mass Index in Persons with Obesity: A Swedish Population-Based Study.

INTRODUCTION: Body weight dissatisfaction, when current and desired body mass index (BMI) do not align, is common in persons with obesity. The aim of this cross-sectional study was to explore factors associated with the differences between current and desired BMI, and ideal BMI (defined in the present study as BMI 25 kg/m2), in persons with obesity. METHODS: Swedish citizens aged 20-64 years residing in the Stockholm County were randomly selected from the population register at five different and evenly separated occasions in the study period 1998-2000 and invited to provide self-reported data about their current weight, height, desired weight, and other characteristics such as depressive symptoms and alcohol intake. Among the 10,441 participants with a mean BMI of 24 kg/m2, differences between desired BMI and ideal BMI were calculated to determine the discrepancy between desired BMI and ideal BMI in participants with obesity (n = 808). The discrepancy between current and desired BMI was also determined. Using linear regression, factors associated with BMI discrepancies were determined. RESULTS: Persons with BMI <40 kg/m2 desired a lower BMI than those with BMI ≥40 kg/m2 (26 ± 3 vs. 36 ± 14 kg/m2, p < 0.001). Women with obesity (n = 425) had a larger discrepancy between current and desired BMI, 32% ± 16, than men with obesity (n = 380), 24% ± 21 (p < 0.001). Persons with obesity and major depression had a 6.9% (95% CI: 2.5-11.4) larger discrepancy between current and desired BMI than persons with obesity but without major depression. Being born abroad, having a university degree, or hazardous alcohol use were not associated with discrepancy between current and desired BMI or desired BMI and ideal BMI (all p > 0.05). CONCLUSION: Desired BMI and discrepancies between current, desired, and ideal BMI vary according to current BMI, sex, and presence of major depression. This underscores the significance of a patient-centered approach in the management of obesity, where the goals and needs of each patient should be considered.

Functional Variation in the FAAH Gene Is Directly Associated with Subjective Well-Being and Indirectly Associated with Problematic Alcohol Use.

Fatty acid amide hydrolase (FAAH) is an enzyme that degrades anandamide, an endocannabinoid that modulates mesolimbic dopamine release and, consequently, influences states of well-being. Despite these known interactions, the specific role of FAAH in subjective well-being remains underexplored. Since well-being is a dynamic trait that can fluctuate over time, we hypothesized that we could provide deeper insights into the link between FAAH and well-being using longitudinal data. To this end, we analyzed well-being data collected three years apart using the WHO (Ten) Well-Being Index and genotyped a functional polymorphism in the FAAH gene (rs324420, Pro129Thr) in a sample of 2822 individuals. We found that the A-allele of rs324420, which results in reduced FAAH activity and elevated anandamide levels, was associated with lower well-being scores at both time points (Wave I, B: -0.52, p = 0.007; Wave II, B: -0.41, p = 0.03, adjusted for age and sex). A subsequent phenome-wide association study (PheWAS) affirmed our well-being findings in the UK Biobank (N = 126,132, alternative C-allele associated with elevated happiness, p = 0.008) and revealed an additional association with alcohol dependence. In our cohort, using lagged longitudinal mediation analyses, we uncovered evidence of an indirect association between rs324420 and problematic alcohol use (AUDIT-P) through the pathway of lower well-being (indirect effect Boot: 0.015, 95% CI [0.003, 0.030], adjusted for AUDIT in Wave I). We propose that chronically elevated anandamide levels might influence disruptions in the endocannabinoid system-a biological contributor to well-being-which could, in turn, contribute to increased alcohol intake, though multiple factors may be at play. Further genetic studies and mediation analyses are needed to validate and extend these findings.

The Major Depression Inventory for diagnosing according to DSM-5 and ICD-11: Psychometric properties and validity in a Swedish general population.

OBJECTIVES: The Major Depression Inventory (MDI) was constructed to assess DSM-IV and ICD-10 depression symptoms, and does not fully cover the symptoms listed in DSM-5 and ICD-11. This study aimed to augment the MDI to the new diagnostic standards by adding a new item, and to assess and compare the measurement performance of the MDI items and diagnostic algorithms for major depression according to DSM-IV, ICD-10, DSM-5 and ICD-11. METHODS: Surveys collected 2001-2003 and 2021, including self-assessed MDI were used. A new hopelessness item was constructed and analyzed alongside the hopelessness item in the Symptom Checklist. The performance of items was compared using Rasch and Mokken analyses. Criterion validity was examined using equivalent diagnoses from psychiatric interview (Schedules for Clinical Assessments in Neuropsychiatry [SCAN]) as standard. RESULTS: MDI information was provided by 8511 individuals in 2001-2003 (SCAN subsample n = 878), and 8863 in 2021. All items, including hopelessness had good psychometric properties. Sensitivity ranged between 56% and 70%, and specificity between 95% and 96%, indicating similar criterion validity. CONCLUSIONS: Hopelessness and the MDI items had good psychometrics. MDI for DSM-5 and ICD-11 had similar validity as for DSM-IV and ICD-10. We recommend that MDI is updated to DSM-5 and ICD-11 by adding a hopelessness item.

Long-term stability in obsessive thoughts and compulsive behavior in the general population: a longitudinal study in Sweden.

OBJECTIVE: Obsessive thoughts and compulsive behavior and their related disorder Obsessive-Compulsive Disorder (OCD) commonly occur in the general population. Clinical populations indicate a high level of stability, although there are few longitudinal studies in the general population. The recommended drug treatments are SSRIs/TCAs. However, there are few long-term follow up studies. The goal of this study was to 1) examine the occurrence and stability of obsessions, compulsions, and OCD in a longitudinal population-based survey, 2) investigate the use of SSRI and TCA and the potential effect on symptoms. METHODS: A ten-year longitudinal general population in Stockholm was used (2000 and 2010, n = 5650) Obsessional washing, checking, intrusive unpleasant thoughts and the level of suffering due to these symptoms were measured by self-report. Information on use of SSRIs and TCAs by these individuals was obtained from registers. Stability was examined using contingency tables and multinomial logistic regression. RESULTS: At baseline, 2.1, 11.7 and 11.9% reported obsessional washing, checking and intrusive thoughts. A total of 5% reported considerable suffering from these (i.e. OCD). Based on psychiatric interview only 0.4% had OCD. Ten years later a quarter of OCD cases were still classified as having OCD, one quarter reported any obsessive or compulsive symptom and half were classified as symptom-free. Treatment receipt was low and controlling for medication did not change the stability. CONCLUSION: Obsessive thoughts and compulsive behavior are common and stable. While this group is potentially undertreated, there is no indication that those treated display a different pattern of recovery.

Country differences in the cross-sectional associations between smoking and depressive symptoms in adolescence.

BACKGROUND: The aim of the present study was to compare the cross-sectional association between smoking and depressive symptoms among adolescents between Sweden and Italy, two countries historically characterized by different norms about tobacco use and different tobacco control efforts. METHODS: A cross-sectional study including 3283 adolescents 15-16 years of age participating in the Swedish KUPOL study and 1947 same-age adolescents from the Italian BE-TEEN study. Current smoking was defined as any smoking in the past 30 days. Depressive symptoms were assessed using the Centre for Epidemiological Studies Depression Scale for Children (CES-DC) and the internalizing score of the Strengths and Difficulties Questionnaire (SDQ). Country differences were explored in stratified and interaction analyses. RESULTS: Current smoking was associated with a 2- to 3-fold increased odds of depressive symptoms among Swedish adolescents using both CES-DC and SDQ internalizing scale. Among Italian adolescents, slightly lower increased odds of 1.5-2.5 for depressive symptoms with smoking were found using the CES-DC but not the SDQ scale. Both multiplicative and additive interactions for country were significant. The association between smoking and depressive symptoms was weaker among Italian compared with Swedish adolescents for both scores. CONCLUSIONS: Countries with different tobacco norms and control show different associations between smoking and depressive symptoms in adolescence, probably due to different psychosocial profiles of smokers. These findings need to be considered when planning tobacco prevention programmes, e.g. by focusing on early detection of mental health distress among adolescents in settings with declining smoking prevalence and restrictive tobacco control environments.

How the Shift Toward Working From Home Has Impacted People's Work and Private Life.

OBJECTIVE: In this study, we aimed to describe the effect of working from home on work conditions and private life by analyzing reported changes in different work-related factors. METHODS: We used descriptive analyses on cross-sectional data of 4985 people aged 20 to 67 years from Stockholm, Sweden collected in 2021. The prevalence of reported changes for factors related to work and private life was analyzed by degree of work from home and stratified by age, sex, and educational level. RESULTS: Participants who worked from home reported increased opportunities to structure the workday and combine work and private life, while at the same time experiencing increased isolation from the workplace. More females reported increased workload, whereas younger adults reported more changes overall. CONCLUSIONS: Working from home was related to experiencing both positive and negative changes in work conditions and private life.

Death of a Parent and the Risk of Ischemic Heart Disease and Stroke in Denmark and Sweden.

Importance: Increasing evidence suggests that parental death is associated with unhealthy behaviors and mental ill-health. Knowledge regarding the link between parental death and the risk of ischemic heart disease (IHD) and stroke remains limited. Objectives: To investigate whether parental death is associated with an increased risk of IHD and stroke and whether these associations differ by the characteristics of the loss. Design, Setting, and Participants: This population-based cohort study, involving linkages between several nationwide registers, included 3 766 918 individuals born between 1973 and 1998 in Denmark and between 1973 and 1996 in Sweden. Participants were followed up until 2016 in Denmark and 2014 in Sweden. Data were analyzed from December 2019 to May 2021. Exposures: Death of a parent. Main Outcomes and Measures: Diagnosis with or death due to IHD or stroke. Poisson regression was used to analyze the associations between parental death and IHD and stroke risk. Results: Altogether, 48.8% of the participants were women, and 42.7% were from Denmark. A total of 523 496 individuals lost a parent during the study period (median age at loss, 25 years; IQR, 17-32 years). Parental death was associated with a 41% increased risk of IHD (incidence rate ratio [IRR], 1.41; 95% CI, 1.33-1.51) and a 30% increased risk of stroke [IRR, 1.30; 95% CI, 1.21-1.38). The associations were observed not only if the parent died because of cardiovascular or other natural causes but also in cases of unnatural deaths. The associations were stronger when both parents had died (IHD: IRR, 1.87; 95% CI, 1.59-2.21; stroke: IRR, 1.64; 95% CI, 1.35-1.98) than when 1 parent had died (IHD: IRR, 1.37; 95% CI, 1.28-1.47; stroke: IRR, 1.27; 95% CI, 1.19-1.36) but did not differ substantially by the offspring's age at loss or the deceased parents' sex. The risk of acute myocardial infarction was highest in the first 3 months after loss. Conclusions and Relevance: In this cohort study, parental death in the first decades of life was associated with an increased risk of IHD and stroke. The associations were observed not only in cases of parental cardiovascular and other natural deaths but also in cases of unnatural deaths. Family members and health professionals may need to pay attention to the cardiovascular disease risk among parentally bereaved individuals.

The cannabinoid receptor-1 gene interacts with stressful life events to increase the risk for problematic alcohol use.

Problematic alcohol use is a major contributor to the global burden of death and disabilities, and it represents a public health concern that has grown substantially following the COVID-19 pandemic. The available treatment options remain limited and to develop better pharmacotherapies for alcohol misuse we need to identify suitable biological targets. Previous research has implicated the brain's endocannabinoid system (ECS) in psychiatric and stress-related outcomes, including substance use and habituation to repeated stress. Moreover, genetic variants in the cannabinoid-1 receptor gene (CNR1; CB1R) have been associated with personality traits, which are in turn predictors of substance use disorders. To date, however, no human genome-wide association study has provided evidence for an involvement of the ECS in substance use outcomes. One reason for this ECS-related "missing heritability" may be unexamined gene-environment interactions. To explore this possibility, we conducted cross-sectional analyses using DNA samples and stress-exposure data from a longitudinal Swedish population-based study (N = 2,915). Specifically, we genotyped rs2023239, a functional C/T single nucleotide polymorphism in CNR1, previously reported to be associated with CNR1 binding in the brain, subjective reward following alcohol intake, and alcohol cue-elicited brain activation. Our two outcomes of interest were (i) problematic alcohol use based on the Alcohol Use Disorders Identification Test (AUDIT), and (ii) personality trait scores based on the Five Factor Model. We found no baseline association between rs2023239 and problematic alcohol use or personality traits. However, there was a clear trend for interaction between rs2023239's risk allele (C) and stressful life events (SLEs) in both childhood and adulthood, which predicted problematic alcohol use. Although not significant, there was also some indication that the risk allele interacted with child SLEs to increase scores on neuroticism. Our study supports the notion that the ECS can affect alcohol intake behaviors by interacting with life adversities and is-to the best of our knowledge-the first to focus on the interaction between CNR1 and stressors in both childhood and adulthood in humans. Further studies are warranted to confirm these findings.

Utilization of healthcare and prescription medicines after non-pharmacological interventions for depression - A 3-year register follow-up of an RCT in primary care.

Depression is a common, recurrent disorder. There is a need for readily available treatments with few negative side effects, that demands little resources and that are effective both in the short- and long term. Our aim was to investigate the long-term effectiveness of two different interventions; physical exercise and internet-based cognitive behavioural therapy (internet-CBT), compared to usual care in patients with mild to moderate depression in a Swedish primary care setting. We performed a register-based 3-year follow-up study of participants in the randomized controlled trial REGASSA (n = 940) using healthcare utilization and dispensed medicines as outcomes. We found no difference between the three groups regarding proportion of participants consulting healthcare due to mental illness or pain during follow-up. Regarding number of consultations, there was no difference between the groups, except for consultations related to pain. For this outcome both treatment arms had significantly fewer consultations compared to usual care, during year 2-3, the risk ratio (RR) for physical exercise and internet-CBT was 0.64 (95% CI = 0.43-0.95) and 0.61 (95% CI = 0.41-0.90), respectively. A significantly lower proportion of patients in both treatment arms were dispensed hypnotics and sedatives year 2-3 compared to the usual care arm, RR for both physical exercise and internet-CBT was 0.72 (95% CI = 0.53-0.98). No other differences between the groups were found. In conclusion, considering long-term effects, both physical exercise and internet-CBT, being resource-efficient treatments, could be considered as appropriate additions for patients with mild to moderate depression in primary care settings. Trial registration: The original RCT was registered with the German Clinical Trial Register (DRKS study ID: DRKS00008745).

Physical exercise is associated with a reduction in plasma levels of fractalkine, TGF-ß1, eotaxin-1 and IL-6 in younger adults with mobility disability.

Mobility disability (MD) refers to substantial limitations in life activities that arise because of movement impairments. Although MD is most prevalent in older individuals, it can also affect younger adults. Increasing evidence suggests that inflammation can drive the development of MD and may need to be targeted for MD prevention. Physical exercise has anti-inflammatory properties and has been associated with MD prevention. However, no studies to date have examined whether exercise interventions affect the peripheral inflammatory status in younger adults with MD. To this end, we used blood samples from young and middle-aged adults with MD (N = 38; median age = 34 years) who participated in a 12-week intervention that included aerobic and resistance exercise training. A pre-post assessment of inflammatory biomarkers was conducted in plasma from two timepoints, i.e., before the exercise trial and at follow-up (3-7 days after the last exercise session). We successfully measured 15 inflammatory biomarkers and found that exercise was associated with a significant reduction in levels of soluble fractalkine, transforming growth factor beta 1 (TGF-ß1), eotaxin-1 and interleukin (IL) 6 (corrected α = 0.004). We also found significant male-specific effects of exercise on (i) increasing IL-16 and (ii) decreasing vascular endothelial growth factor-A (VEGF-A). In line with our results, previous studies have also found that exercise can reduce levels of TGF-ß1, eotaxin-1 and IL-6. However, our finding that exercise reduces plasma levels of fractalkine in younger adults with MD, as well as the sex-dependent findings, have not been previously reported and warrant replication in larger cohorts. Given the suggested role of inflammation in promoting MD development, our study provides additional support for the use of physical exercise as a treatment modality for MD.

Association of Preeclampsia and Perinatal Complications With Offspring Neurodevelopmental and Psychiatric Disorders.

Importance: Maternal preeclampsia has been reported to increase the risk of autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability in offspring. However, the association between maternal preeclampsia combined with perinatal complications and neurodevelopmental and psychiatric disorders in offspring is less well documented. Objective: To examine the association of maternal preeclampsia, separately and together with perinatal complications, with neurodevelopmental and psychiatric disorders in offspring. Design, Setting, and Participants: This population-based cohort study used data from nationwide registries in Finland to assess all singleton live births (N = 1 012 723) between January 1, 1996, and December 31, 2014. Offspring were followed up until December 31, 2018 (when the oldest reached age 22 years). Exclusion criteria were maternal inpatient psychiatric diagnoses and pregestational diabetes. The study and data analysis were conducted from May 1, 2020, to June 1, 2021. Exposures: Preeclampsia and perinatal complications (delivery earlier than 34 weeks' gestation and/or small for gestational age). Main Outcomes and Measures: The primary outcomes were neurodevelopmental and psychiatric diagnoses and dispensation of psychotropic drugs among offspring until December 31, 2018. Cox proportional hazards regression analyses were performed to assess the associations. Results: Of 1 012 723 singleton live births (51.1% boys; mean [SD] maternal age at birth, 30.0 [5.4] years; specific data on race and ethnicity were not available in the data set), 21 010 children (2.1%) were exposed to preeclampsia alone, 33 625 children (3.3%) were exposed to perinatal complications alone, and 4891 children (0.5%) were exposed to both preeclampsia and perinatal complications. A total of 93 281 children (9.2%) were diagnosed with a neurodevelopmental or psychiatric disorder. Offspring exposed to both preeclampsia and perinatal complications had an increased risk of any neurodevelopmental or psychiatric disorder after adjusting for potential confounding (adjusted hazard ratio [aHR], 2.11; 95% CI, 1.96-2.26) compared with those not exposed to either preeclampsia or perinatal complications; this risk was higher than exposure to either preeclampsia alone (aHR, 1.18; 95% CI, 1.12-1.23) or perinatal complications alone (aHR, 1.77; 95% CI, 1.72-1.82). Sibling pair analyses did not detect any increase in the risk of neurodevelopmental or psychiatric disorders after exposure to preeclampsia alone, but offspring exposed to both preeclampsia and perinatal complications had increased risks of intellectual disabilities (aHR, 3.24; 95% CI, 1.05-10.06), specific developmental disorders (aHR, 3.56; 95% CI, 2.35-5.41), ADHD and conduct disorders (aHR, 2.42; 95% CI, 1.09-5.39), and other behavioral and emotional disorders (aHR, 2.45; 95% CI, 1.17-5.13). The risk estimates for specific developmental disorders (aHR, 2.82; 95% CI, 2.60-3.05) and ADHD and conduct disorders (aHR, 1.88; 95% CI, 1.65-2.14) were higher among offspring exposed to both preeclampsia and perinatal complications compared with those exposed to perinatal complications alone (aHR, 2.26 [95% CI, 2.18-2.33] and 1.60 [95% CI, 1.52-1.68], respectively). Conclusions and Relevance: In this study, exposure to both maternal preeclampsia and perinatal complications was associated with intellectual disabilities, specific developmental disorders, ADHD and conduct disorders, and other behavioral and emotional disorders in offspring. For specific developmental disorders and ADHD and conduct disorders, the risk estimates were higher among offspring exposed to both preeclampsia and perinatal complications compared with those exposed to perinatal complications only.

Is There a Dose-Response Relationship between Acute Physical Activity and Sleep Length? A Longitudinal Study with Children and Adolescents Living in Sweden.

A declining physical activity (PA) and sleep in children and adolescents have been observed during the previous decades. PA could benefit sleep, but the findings are mixed. The aim of the present study was to examine if there is a dose-response relationship between time spent in acute moderate and vigorous physical activity (MVPA) and sleep length in children and adolescents. Additional aims were to examine if the sleep length is higher for children and adolescents who conduct at least an average of 60 min in MVPA/day and to study differences between sex and school years. The study population consists of 262 participants in school year 5 (aged 11 years), 7 (aged 13 years), and 9 (aged 15 years). Accelerometers measured MVPA while sleep diaries measured sleep length. A linear and longitudinal mixed effect linear regression was conducted to study the primary aim. The secondary aims were studied with linear regressions. Included confounders were sex, school year, school stress, screen time, menstruation onset, family household economy, and health status. A stratified regression for sex and school year was conducted. The linear regression showed no statistically significant findings in the crude or adjusted model. The stratified linear regression found a significant positive association for girls but a negative association for school year 5. No associations were found in the longitudinal regression or when comparing sleep length for participants that did and did not spend an average of at least 60 min in MVPA/day. A dose-response relationship was found in the stratified linear regression, implying a possible weak association. The statistically non-significant differences between participants that did and did not spend an average of at least 60 min in MVPA/day implies that spending an average of at least 60 min in MVPA/day may not be associated with a higher mean sleep length.

DNA methylation of the glucocorticoid receptor gene predicts substance use in adolescence: longitudinal data from over 1000 young individuals.

Early life stress has been linked to increased methylation of the Nuclear Receptor Subfamily 3 Group C Member 1 (NR3C1) gene, which codes for the glucocorticoid receptor. Moreover, early life stress has been associated with substance use initiation at a younger age, a risk factor for developing substance use disorders. However, no studies to date have investigated whether NR3C1 methylation can predict substance use in young individuals. This study included adolescents 13-14 years of age that reported no history of substance use at baseline, (N = 1041; males = 46%). Participants contributed saliva DNA samples and were followed in middle adolescence as part of KUPOL, a prospective cohort study of 7th-grade students in Sweden. Outcome variables were self-reports of (i) recent use, (ii) lifetime use, and (iii) use duration of (a) alcohol, (b) tobacco products, (c) cannabis, or (d) any substance. Outcomes were measured annually for three consecutive years. The predictor variable was DNA methylation at the exon 1 F locus of NR3C1. Risk and rate ratios were calculated as measures of association, with or without adjustment for internalizing symptoms and parental psychiatric disorders. For a subset of individuals (N = 320), there were also morning and afternoon salivary cortisol measurements available that were analyzed in relation to NR3C1 methylation levels. Baseline NR3C1 hypermethylation associated with future self-reports of recent use and use duration of any substance, before and after adjustment for potential confounders. The overall estimates were attenuated when considering lifetime use. Sex-stratified analyses revealed the strongest association for cigarette use in males. Cortisol analyses revealed associations between NR3C1 methylation and morning cortisol levels. Findings from this study suggest that saliva NR3C1 hypermethylation can predict substance use in middle adolescence. Additional longitudinal studies are warranted to confirm these findings.

Informal care and the impact on depression and anxiety among Swedish adults: a population-based cohort study.

BACKGROUND: As the population is ageing, the need for informal caregivers increases, and thus we need to know more about the effects on caregivers. This study aims to determine both cross-sectional and longitudinal associations between perceived limitation of informal caregiving and mental health of caregivers. METHODS: This population-based cohort study was based on the Swedish Psykisk hälsa, Arbete och RelaTioner (PART) study, and 9346 individuals aged 18-65 were included. Data were collected through questionnaires, interviews and Swedish registers. Informal care was defined as care given to a family member. Self-reported and diagnosed depression and anxiety were included as outcomes. Covariates included sex, age, social support and socio-economic position. Ordinal logistic regression and Cox regression were performed to determine the associations between caregiving and anxiety or depression. RESULTS: Self-reported depression and anxiety was only increased among those experiencing limitations (adjusted odds ratios [aOR] 2.00, 95% confidence intervals [CI] 1.63-2.47 for depression; aOR 2.07, 95% CI 1.57-2.74 for anxiety) compared to those not giving care, respectively. The adjusted hazard ratio (aHR) were increased for diagnosed depression (aHR 1.97, 95% CI 1.27-3.05) and for diagnosed anxiety (aHR 1.86, 95% CI 1.06-3.25) among those giving care and experiencing limitations, compared to those not giving care. No significant associations were found in caregivers without limitations. CONCLUSION: Caregivers experiencing limitations showed a significant association with short- and long-term anxiety and depression. This study implies the importance of exploring the degree to which informal caregiving can be provided without adding burden to caregivers.

No association of cigarette smoking and depressive symptoms with cortisol concentration in adolescents. Results from a population-based Swedish cohort.

Several studies have shown that smoking increases the risk of depressive symptoms, and suggested a possible role of the hypothalamic-pituitary-adrenal axis in the smoking-depression pathway. This study aimed to assess if smokers have higher cortisol levels than non-smokers, and if higher cortisol levels are associated with depressive symptoms. Saliva samples were collected from a subgroup of 409 participants at enrolment (13-14 years old) and two years later (15-16 years old). First, we examined the association between smoking phenotypes and cortisol concentration. Second, we evaluated whether these associations differed between adolescents with and without depressive symptoms. The mean difference between smokers and non-smokers in cortisol concentrations was close to zero at both time points. For instance, the adjusted mean difference for morning cortisol concentration between current and non-current smokers was 0.000 µg/dl [95% CI -0.055, 0.056]. In addition, there were no differences in cortisol concentration at the second time-point between those who had smoked and those who did not during the two previous years. Moreover, cortisol levels were not associated with depressive symptoms. The hypothesis that dysregulation of the hypothalamic-pituitary-adrenal axis might be involved in the association between smoking behavior and depressive symptoms during adolescence was not supported by this data.

Death of a parent during childhood and blood pressure in youth: a population-based cohort study of Swedish men.

OBJECTIVE: Compelling evidence suggests that childhood adversities are associated with an increased risk of hypertension in middle age and old age. The link between childhood adversities and blood pressure in youth is less clear. In this cohort study, we examined the association between death of a parent during childhood and blood pressure in early adulthood in men. SETTING: Sweden. PARTICIPANTS: We studied 48 624 men born in 1949-1951 who participated in the compulsory military conscription in 1969/1970 in Sweden. Information on death of a parent during childhood was obtained from population-based registers. Information on covariates was obtained from the questionnaire and the clinical examination completed at conscription and from population-based registers. OUTCOME MEASURES: Blood pressure was measured at conscription according to standard procedures. RESULTS: The multivariable least square means of systolic and diastolic blood pressure did not differ between bereaved (128.25 (127.04-129.46) and 73.86 (72.89-74.84) mm Hg) and non-bereaved study participants (128.02 (126.86-129.18) and 73.99 (73.06-74.93) mm Hg). Results were similar when considering the cause of the parent's death, the gender of the deceased parent or the child's age at loss. Loss of a parent in childhood tended to be associated with an increased hypertension risk (OR and 95% CI: 1.10 (1 to 1.20)); the association was present only in case of natural deaths. CONCLUSION: We found no strong support for the hypothesis that stress following the loss of a parent during childhood is associated with blood pressure or hypertension in youth in men.

Latent class growth modelling for the evaluation of intervention outcomes: example from a physical activity intervention.

Intervention studies often assume that changes in an outcome are homogenous across the population, however this assumption might not always hold. This article describes how latent class growth modelling (LCGM) can be performed in intervention studies, using an empirical example, and discusses the challenges and potential implications of this method. The analysis included 110 young adults with mobility disability that had participated in a parallel randomized controlled trial and received either a mobile app program (n = 55) or a supervised health program (n = 55) for 12 weeks. The primary outcome was accelerometer measured moderate to vigorous physical activity (MVPA) levels in min/day assessed at baseline, 6 weeks, 12 weeks, and 1-year post intervention. The mean change of MVPA from baseline to 1-year was estimated using paired t-test. LCGM was performed to determine the trajectories of MVPA. Logistic regression models were used to identify potential predictors of trajectories. There was no significant difference between baseline and 1-year MVPA levels (4.8 min/day, 95% CI: -1.4, 10.9). Four MVPA trajectories, 'Normal/Decrease', 'Normal/Increase', 'Normal/Rapid increase', and 'High/Increase', were identified through LCGM. Individuals with younger age and higher baseline MVPA were more likely to have increasing trajectories of MVPA. LCGM uncovered hidden trajectories of physical activity that were not represented by the average pattern. This approach could provide significant insights when included in intervention studies. For higher accuracy it is recommended to include larger sample sizes.

Childhood adversity increases methylation in the GRIN2B gene.

Childhood adversity is an early life stressor associated with increased risk of several psychiatric disorders such as depression. Epigenetic changes, primarily DNA methylation, can be affected by early life stress, which in turn might contribute to altered disease susceptibility later in life. One plausible biomarker of early life stress is methylation of the ionotropic glutamate receptor NMDA type subunit 2B (GRIN2B) gene, which has been previously shown to be epigenetically affected by prenatal environmental stressors. Here, we set out to investigate if stress-inducing adversity during childhood is associated with changes in methylation of GRIN2B in adulthood. We studied 186 individuals from a Swedish naturalistic population-based cohort who had provided saliva samples (DNA) as well as information regarding both childhood adversity (CA) and depressive symptoms (dep) (nCA,dep = 41, nCA,no-dep = 56, nno-CA,dep = 40, Nno-CA,no-dep = 49). Methylation at four CpG sites in a regulatory region of GRIN2B was analysed using bisulfite pyrosequencing. Associations for methylation status to childhood adversity and to depression status were investigated using linear regression models. Our study shows that childhood adversity is associated with increased methylation levels of GRIN2B in adulthood, for three of the measured CpGs (p = 0.007, 0.006 and 5 × 10-14). This indicates that GRIN2B methylation is susceptible to early life stress, and that methylation at this gene is persistent over time. No association was found between GRIN2B methylation and depression status. Yet, this does not rule out a role for alterations in GRIN2B methylation for other neuropsychological outcomes not studied here.