Abstract Aims Migrants use less mental healthcare than non-migrants, but it is unclear how much this reflects differing needs and whether this gap has changed over time. We examined differences in mental healthcare use by migrant status between 2006 and 2022 while considering probable mental healthcare needs. Methods We used data from four cross-sectional surveys conducted in Stockholm County (2006, 2010, 2014 and 2021) in which self-reported need indicators, including psychological distress, were measured. Survey participants, 81,650 adults (18–64), were linked to administrative registries to estimate differences in mental healthcare use (both likelihood and frequency), within 6 months of survey response. Logistic regression and zero-truncated negative binomial regression were used, with survey weights and adjustments for sex, age, income, education, psychological distress (main need-indicator), general health status and long-term limiting illness. Results Non-Nordic migrants were more likely to report increased levels of psychological distress but were less likely to use services than non-migrants. The gap in mental healthcare use was initially marginal but increased with adjustment for mental healthcare needs, as well as over time (2006–2022). The odds ratios comparing the likelihood of mental healthcare use between European migrants with Swedish-born individuals decreased from 0.93 (95% confidence intervals: 0.77–1.11) in 2006/2007 to 0.48 (0.39–0.59) in 2021/2022, adjusting for sociodemographic factors and psychological distress. For non-European migrants, the corresponding odds ratios decreased from 0.72 (0.62–0.85) to 0.46 (0.39–0.54). Further adjustments for general health status and long-term limiting illness widened the gap even more. In 2021/2022, the gap was larger in secondary than in primary care and for online than in-office services. Nordic-born migrants had similar utilization patterns as Swedish-born individuals. Differences in the frequency of outpatient visits between migrants and Swedish-born individuals, conditional on having at least one visit, were marginal. For instance, the rate ratios comparing non-European migrants with Swedish-born individuals changed from 0.67 (0.48–0.93) in 2006/2007 to 0.90 (0.65–1.26) in 2021/2022. Conclusions Despite indicating greater needs, non-Nordic migrants faced persistent inequities in mental healthcare access, but differences in intensity/continuity of care were marginal among those who accessed services. Inequities in access grew over the study period and were largest during the COVID-19 pandemic, particularly in access to online mental healthcare services and specialized care. These findings should be interpreted cautiously given potential selection bias from declining survey participation and changes in distress scales.

BackgroundEvidence on whether arsenic in groundwater is associated with the risk of Alzheimer's disease (AD) is limited.ObjectiveTo investigate the association between long-term exposure to different levels of arsenic and the risk of AD.MethodsWe conducted a population-based cohort study included individuals born in Sweden during 1932-1950 (n = 1,549,700), with follow-up from 1970 until 2016. We classified study individuals by groundwater arsenic levels reported by the Geological Survey of Sweden and identified AD diagnoses through the Swedish National Patient Register and Cause of Death Register. The association between arsenic exposure and AD risk was evaluated using Cox models.ResultsAmong the 1,549,700 individuals [761,055 female (49.1%); mean (SD) age at baseline: 26.5 (5.2) years], 42,219 (2.7%) individuals were exposed to high (>10 µg/l), 7356 (0.5%) to high-middle (5-10 µg/l), 60,799 (3.9%) to low-middle (2-5 µg/l), and 1,439,326 (92.9%) to low (<2 µg/l) levels of arsenic in groundwater at baseline, respectively. A dose-response association was observed for exposure to arsenic at birth, which individuals born in areas with high, high-middle, and low-middle arsenic levels in groundwater had 156% [2.56 (2.43-2.70)], 98% [1.98 (1.80-2.17)], and 47% [1.47 (1.39-1.56)] higher AD risk than those born in low arsenic exposure areas. Similar dose-response relationship exhibited for arsenic exposure defined by the place of residence at young adulthood (at baseline). The sibling analysis yielded similar results for arsenic exposure evaluated at baseline.ConclusionsExposure to higher arsenic levels in groundwater at birth or young adulthood was associated with an increased risk of AD.

Importance:There is a lack of comprehensive evidence on the burden and management of depression or anxiety in health care systems that leverage multiple health care and prescription registers, including primary care datasets in which these conditions typically first present. Objective:To examine the distribution of depression or anxiety among people 10 years or older in Sweden by region, small-area deprivation, and health care level of first diagnosis. Design, Setting, and Participants:This nationwide, register-based, cross-sectional study included people aged 10 years or older who were living in Sweden from January 1, 2015, to December 31, 2023. Data were analyzed from January to June 2026. Exposure:Small-area deprivation was defined for 5984 small geographic areas in 2015 using a published Index for Multiple Deprivation in Sweden categorized into quartiles. Main outcomes and measures:Depression or anxiety was defined as the first diagnosis, or first prescription date if no diagnosis was recorded in the study period. Crude and age-standardized rates of depression or anxiety per 1000 persons were tabulated at national and subnational levels. Multilevel logistic regression quantified associations between small-area deprivation and the outcome adjusted for confounders. Health care level for the first diagnosis was compared by region, small-area deprivation, and patient characteristics. Results:Among 8 528 198 individuals aged 10 years or older (50.2% female), 2 087 413 had recorded depression or anxiety between 2015 and 2023, corresponding to a rate of 244.8 (95% CI, 244.4-245.1) cases per 1000 persons. Higher odds of depression or anxiety were found in the most vs least deprived areas (OR, 1.18; 95% CI, 1.16-1.20). Among 1 359 196 patients with depression and anxiety between 2015 and 2017, 56.2% (95% CI, 56.1%-56.3%), 18.1% (95% CI, 18.0%-18.1%), and 3.2% (95% CI, 3.2%-3.2%) were first diagnosed in primary, outpatient, and inpatient care, respectively. Conclusions and Relevance:This cross-sectional study using administrative registers found lower rates of depression or anxiety among residents of Sweden than reported in population surveys, likely due to underestimating individuals not seeking health care. Higher odds of depression or anxiety in most vs least deprived areas could underscore the association of these conditions with socioeconomically disadvantaged contexts. Variation by region and patient characteristics in the health care level for first diagnosis merits further investigation.

Migraine is a major cause of disability affecting a person’s health, well-being, working life and social relationships. In Sweden, it was previously estimated that approximately one in eight people experience migraine with lower socioeconomic groups disproportionately affected. Yet there is a lack of recent evidence on the burden and geographic distribution of migraine within Sweden including by small-area deprivation. A nationwide register-based cross-sectional study was conducted of persons ten years or older in Sweden on 31 December 2023 and who were diagnosed with or prescribed drugs for migraine during the study period (2015–2023). Crude and age-standardized migraine rates per 1,000 persons were tabulated nationally and sub-nationally by region and small-area deprivation measured using the Index for Multiple Deprivation in Sweden (IMDIS). Logistic regression models quantified the association between small-area deprivation level and other covariates (age, sex, area of residence, birthplace) on migraine. Among migraine patients, the healthcare source for the first recorded diagnosis was compared at national and regional levels as well as by patient characteristics. A total of 372,926 people aged ten years or older had recorded migraine during the study period corresponding to a rate of 43.7 cases per 1,000 persons. Higher migraine occurrence was found in the least versus the most deprived areas (OR: 1.05, 95

BackgroundResidential deprivation is a long-established risk factor for poor health outcomes including migraine, depression and anxiety that are significant public health problems in Sweden and globally. Yet the relationship between residential deprivation and patterns of comorbidity among these three conditions is less understood. We aimed to estimate the magnitude and determinants of comorbid depression or anxiety among migraine patients in Sweden including the relationship between residential deprivation and comorbidity prevalence.MethodsA nationwide register-based cross-sectional study was conducted of persons aged ten years or older in Sweden in 2015-2023. Comorbid depression or anxiety was defined as any depression or anxiety diagnosis or treatment during the migraine-exposed period (from three months before until three months after the first and last recorded migraine exposure in the study period). Small-area deprivation was based on an Index for Multiple Deprivation in Sweden (IMDIS) applied to 5984 small geographic areas. Prevalence ratios (PR) estimated the association between comorbidity and small-area deprivation adjusted for other covariates (age, sex, area of residence, birthplace) using Poisson regression models with robust error variance. We compared sick leave utilization (over fourteen days) for any reason in the migraine-affected years among migraine patients with or without comorbidity.ResultsThere were 372,926 migraine patients in the study, and 35.7% (n = 133,219) had comorbid depression or anxiety. There was higher comorbidity prevalence among migraine patients in the most versus the least deprived areas (PR: 1.18, 95% CI: 1.17-1.20). Although the data have limitations, we found that one-third (31.9%) of migraine patients took sick leave (over fourteen days) for any reason during the migraine-exposed years, which rose to 50.9% among migraine patients with comorbid depression or anxiety.ConclusionsMore than one-third of migraine patients had comorbid depression or anxiety with higher prevalence of comorbidity in the most deprived areas. Common comorbid depression or anxiety among migraine patients underscores the need to consider all three conditions in clinical encounters especially for residents of more deprived residential areas.

Background: We aimed to identify modifiable individual and contextual factors underlying migrant inequalities in mental health service (MHS) use using hypothetical intervention scenarios. Methods: We conducted a survey-registry linked study of 15,943 adults aged 18-64 who participated in a 2021 survey in Stockholm County, Sweden. The association between migrant status (non-Nordic vs Nordic-born individuals) and MHS use within 6 months of survey response (yes/no) was estimated using logistic regression. We leveraged causal mediation methods to decompose inequalities (total effect, TE) into residual inequalities (controlled direct effect, CDE) and proportion eliminated (PE), under hypothetical modifications to (8) mediators. Findings: Non-Nordic migrants were less likely to use MHS than Nordic-born individuals (TE; odds ratio [OR] = 0∙55; 95% CI: 0∙49–0∙61), adjusting for sociodemographic factors. Hypothetically removing cost barriers to care, increasing residential stability, and strengthening trust in healthcare services was associated with reduced inequalities (PEs: 8∙9%–18%). Also, hypothetical modifications to neighbourhood deprivation, migrant density, and trust in public institutions were associated with upto 30% reduction in inequalities. Larger reductions were observed in primary care and among less affluent groups.In contrast, no reductions were observed for modifying COVID-19-related barriers or proximity to primary MHS. Interpretation: Cost barrier, residential stability (as a proxy for familiarity with local MHS), trust in healthcare services, and contextual factors such as deprivation were identified as potentially modifiable factors behind migrant inequalities. Residual confounding limits causal inference but these findings may inform intervention studies.

Growing evidence indicates that migraine could increase the risk of depression or anxiety in affected persons. Residential deprivation, with its links to stressful environments and access to quality services, could exacerbate the risk of developing depression or anxiety among migraine patients, but evidence remains limited. We aimed to examine the subsequent risk of depression or anxiety in persons with migraine and to determine if this association varies by small-area deprivation. A nationwide register-based cohort study was conducted of persons aged 10–50 years registered in Sweden from 2015 to 2023 who did not have recorded depression or anxiety in the previous ten years (n = 4,065,375). We generated matched (n = 1,455,352) and sibling (n = 179,888) samples for analyses. The exposure (migraine) and outcome (depression or anxiety) were defined as the first diagnosis, or the first prescription date if no diagnosis was recorded in the study period. Follow-up started six months after migraine exposure and hazard ratios (HR) for depression or anxiety through 31 December 2023 were computed for the matched and sibling cohorts using stratified cox regression models with robust error variance. We tested for an interaction between small-area deprivation and migraine on the association with depression or anxiety. Incidence rates for depression or anxiety among people with or without migraine in the matched cohort were 39.2 and 21.9 per 1,000 person-years with an adjusted HR of 1.78 (95

Background Psychotic major depressive disorder (MDD), a subtype of MDD characterised by psychotic symptoms that occur exclusively during mood episode, is clinically significant yet underexplored genetically due to its rarity. This study comprehensively examines the genetic basis of psychotic MDD and elucidates its position within the mood- psychotic spectrum. Methods This population-based cohort study used Swedish and Danish registry data for over 5.1 M individuals born between 1958 and 1993/1996. Specialist-diagnosed psychotic MDD was defined using ICD-10 sub-codes of MDD, F32.2/F32.3. We estimated familial aggregation/coaggregation using generalised estimating equations, heritability and genetic correlations using structural equation modelling. We also analysed similar to 30,000 genotyped MDD cases from the UK Biobank and a Swedish cohort to explore which polygenic risk score (PRS) may predispose individuals to psychotic MDD. Findings With over 10,000 psychotic MDD identified from the two nationwide patient registers, this study highlights the familial aggregation of psychotic MDD, co-aggregation with mood and psychotic disorders, and its stronger genetic correlation with schizophrenia compared to non-psychotic MDD. The familial risks increased with closer biological relatedness, suggesting genetic influence. Pedigree-heritability of psychotic MDD was 30.17% (95% CI 23.53-36.80%). While the genetic correlation between psychotic and non-psychotic MDD was high (0.82, 95% CI 0.73-0.92), the psychotic subgroup showed a higher genetic correlation with schizophrenia than non-psychotic MDD (0.67 vs 0.46, p-value 7.55*10-4). Within 30,000 genotyped MDD cases, individuals with psychotic MDD had higher mean PRS for schizophrenia and BD but a lower MDD PRS than non-psychotic MDD. PRS for BD type-I was associated with increased odds of psychotic MDD, while BD type-II PRS showed no significant association with psychotic MDD. Interpretation This study provides evidence for the genetic basis of psychotic MDD, underscoring its unique position bridging the spectrum of mood and psychotic disorders. These findings advance our understanding of the aetiology of psychotic MDD and contribute to the limited body of evidence on this phenotype by utilising large-scale population-based data. Copyright (c) 2025 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

BACKGROUND:Suicide is more common among males and in older age, but the understanding of sex-specific and age-specific risk indicators is limited. OBJECTIVE:To describe the sex-specific and age-specific prevalence of 25 suicide risk indicators in the year preceding suicide and estimate their associations with suicide. METHODS:Register-based population-nested case-control study in Sweden, 2009-2021, comprising 19 741 suicide cases and 197 296 general population controls matched by sex, age and county of residence. Death by suicide was collected from the cause of death register. 25 suicide risk indicators covering psychiatric history, somatic disorders, bereavement and sociodemographic factors in the previous year were collected from nationwide registers. Sex-specific and age-specific ORs of suicide for the presence/absence of each risk indicator in the prior year were estimated and complemented by risk differences. FINDINGS:Suicide cases were 70% male, 9% were aged 15-24 years, 29% 25-44 years, 36% 45-64 years and 26% 65+ years. In the year preceding suicide, the prevalence of most risk indicators was the lowest among males and people aged 65+ years. Most risk indicators also showed weaker 1-year associations with suicide in these groups. The median OR (IQR) of suicide across the 25 risk indicators was 14.6 (5.2, 29.1) in females versus 10.3 (4.3, 21.3) in males, and 17.4 (6.5, 28.9) in 24-44 year-olds versus 8.0 (3.6, 23.7) in people aged 65+years. Risk differences of suicide were larger in males across nearly all risk indicators. CONCLUSIONS:There was considerable heterogeneity across sex and age groups, both in the prevalence of risk indicators preceding suicide and in their associations with suicide. Risk indicators were generally less common and displayed weaker associations with suicide on the relative risk scale among males and older people. CLINICAL IMPLICATIONS:Suicides in males and older people may be harder to predict, as indicators are rarer. When males present with risk indicators, they generally have a higher absolute risk of suicide, making them important targets for prevention even when risk indicators do not cause suicide. Our findings underscore the importance of considering sex-specific and age-specific risk indicators for individualised suicide prediction and prevention.

Social capital-the trust and cohesion within communities-has been linked to mental health, yet longitudinal evidence remains scarce. Here we show that neighborhood-level personal trust predicts the incidence of severe mental illness in a large, population-based cohort in Stockholm County, Sweden. Among 1.47 million Swedish-born residents followed over 15 years, higher personal trust at baseline was associated with reduced rates of non-affective psychotic disorder and bipolar disorder without psychosis over the follow-up period, but only among individuals of Swedish or European heritage. In contrast, the same exposure increased incidence rates among those of North African, Middle Eastern or Sub-Saharan African heritage. Political and welfare trust showed no consistent associations. These findings suggest that social capital may confer mental health benefits or risks depending on one's own social position, highlighting the need for nuanced public mental health strategies that consider structural and cultural contexts in promoting mental wellbeing.

Somatic symptom and related disorders (SSRD) are characterized by a mixture of neurological and psychiatric features and include functional neurological (FND) and somatic symptom disorders (SomD). While these complex neuropsychiatric disorders show evidence of genetic susceptibility, there are no genome-wide association studies (GWAS) of SSRD, and the heritability is unknown. We did a GWAS of a total of 22,203 patients with SSRD, and 1,831,107 controls of European ancestry. We identified one genome-wide significant locus (chromosome 8:65565084) in SSRD, and one additional locus (chromosome 16:49074278) in the SomD subgroup (n cases = 18,536). The observed-scale SNP heritability was estimated to be 7.3 % for SSRD, 15.7 % for FND and 7.7 % for SomD. FND and SomD were strongly genetically correlated (rg=0.94, SE=0.11, p=3.9E-18). SSRD showed significant genetic correlation with psychiatric disorders (highest with anxiety, post-traumatic stress disorders, depression, rg=0.3- 0.8), neurological disorders (migraine, chronic pain, rg=0.4-0.6) and immune-related diseases (rg=0.2-0.3). Functional follow-up analysis of SSRD loci implicated the genes CYP7B1, BHLHE22, and CBLN1, which are involved in metabolic and brain-related processes, suggesting common underlying pathways. We identified genomic loci associations with SSRD and showed strong genetic correlation between FND and SomD and with neurological and psychiatric disorders, as well as immune-related diseases. The current findings highlight shared underlying pathophysiological processes between SSRD diagnostic categories.

BACKGROUND:The first aim of the study was to assess the validity of non-affective psychosis diagnoses, including schizophrenia, for migrants and Swedish-born to determine if the registered diagnoses were of sufficient quality for epidemiological research. If the validity was insufficient, the second aim was to find out what the non-valid cases have in common to see if there was a feasible way to handle these cases in future studies. STUDY DESIGN:We validated the register-diagnoses of 179 randomly selected patients aged 18-48 living in municipalities with a high proportion of migrants, diagnosed with non-affective psychotic disorder (F20-F29 according to ICD-10), drawn from the Region of Stockholm's medical records database by comparing them to their case notes to see if they fulfilled the DSM-5 criteria. RESULTS:We found acceptable validity for non-affective psychotic disorder for migrant men (70.5%), low for Swedish-born men (60.0%), and even lower for women (50.0% for Swedish-born and 40.0% for migrants). There was no statistically significant difference between Swedish-born and migrants. The case notes revealed that by excluding cases with an additional diagnosis equivalent of psychotic disorder due to psychoactive substance (ICD10: F11X.5 and F11X.7) the validity was good for both Swedish-born and migrant men. CONCLUSIONS:This study supports continued use of the register-diagnoses but only after taking appropriate measures to avoid that patients with additional psychotic disorder due to psychoactive substance are not violating the validity. It also suggests caution when studying non-affective psychosis diagnoses among migrant women as the validity is low, possibly due to difficulties in separating non-affective psychosis from symptoms of other disorders with psychotic features.

The Swedish Phenylketonuria screening biobank contains neonatal dried blood spots from over five million individuals born in Sweden since 1975. While its value has been proven in several research areas, the feasibility of DNA methylation profiling from decades-old samples with ultra-low DNA inputs using the Illumina Infinium MethylationEPIC v2.0 remains uncertain. We selected samples from seven random individuals born between 1985 and 2003. We used the EPIC v2.0 for DNA methylation analysis. To asses its performance, we conducted a quality control; examining probe call rate, signal intensity, beta value density, sample-to-sample correlation, and nine control probes built into the array. Despite using DNA input quantities as low as 19.2 ng (less than 10

Horizontal equity is defined as equal care for equal needs, regardless of socioeconomic factors. This study investigated trends in horizontal equity in mental health care (MHC) utilization in Sweden from 2006 to 2022. Monitoring equity provides valuable information for healthcare system governance (e.g., planning and resource allocation) necessary for ensuring equitable provision of services. A total of 81,650 Stockholm residents aged 18–64, who participated in the Hälsa Stockholm surveys of 2006, 2010, 2014 or 2021, were analysed. Their subsequent use of MHC (primary, in- and outpatient specialized care, and psychotropic medication) within six months after survey response was collected from registries between 2006 and 2022. Concentration index (CI) and need-standardized CI (Horizontal inequity index, HI), summative measures of inequalities, were used in this study. HI was estimated using self-reported psychological distress (measured with the General health questionnaire 12 in 2006–2014 and Kessler 6 in 2021) as the primary need indicator, with general health status and long-term limiting illness as additional need indicators. Equivalized disposable household income was used as the ranking variable, while education status, migration status, age, and sex were included as non-need variables that we controlled for in the analyses. Lower-income individuals used MHC services more than their higher-income counterparts with comparable levels of psychological distress. These “pro-poor” inequities in the probability of MHC use increased from HI = -0.057 [95

Abstract Aims Although individuals with lower socio-economic position (SEP) have a higher prevalence of mental health problems than others, there is no conclusive evidence on whether mental healthcare (MHC) is provided equitably. We investigated inequalities in MHC use among adults in Stockholm County (Sweden), and whether inequalities were moderated by self-reported psychological distress. Methods MHC use was examined in 31,433 individuals aged 18–64 years over a 6-month follow-up period, after responding to the General Health Questionnaire-12 (GHQ-12) in 2014 or the Kessler Six (K6) in 2021. Information on their MHC use and SEP indicators, education, and household income, were sourced from administrative registries. Logistic and negative binomial regression analyses were used to estimate inequalities in gained MHC access and frequency of outpatient visits, with psychological distress as a moderating variable. Results Individuals with lower education or income levels were more likely to gain access to MHC than those with high SEP, irrespective of distress levels. Education-related differences in gained MHC access diminished with increasing distress, from a 74% higher likelihood when reporting no distress (odds ratio, OR = 1.74 [95% confidence interval, 95% CI: 1.43–2.12]) to 30% when reporting severe distress (OR = 1.30 [0.98–1.72]). Comparable results were found for secondary care but not primary care i.e., lower education predicted reduced access to primary care in moderate-to-severe distress groups (e.g., OR = 0.63 [0.45–0.90]), and for physical but not digital services. Income-related differences in gained MHC access remained stable or increased with distress, especially for secondary care and physical services. Among MHC users, we found marginal socio-economic differences in the frequency of outpatient visits, and these differences decreased with increasing distress. Yet, having only primary education with severe distress was associated with fewer outpatient visits compared with having post-secondary education (rate ratio, RR = 0.82; 95% CI: 0.67–1.00). These inequities were especially evident among women and for visits to psychologists, counsellors, or psychotherapists. Although lower-income groups used services more than others, they still had higher odds of not using services when reporting distress (i.e., those not in contact with services despite scoring ≥3 on the GHQ-12 or ≥8 on the K6; OR = 1.27; 95% CI: 1.15–1.40). Conclusions Overall, individuals with lower education and income used MHC services more than their counterparts with higher socio-economic status; however, low-educated individuals faced inequities in primary care and underutilized non-physician services such as visits to psychologists.

( JAMA . 2024;331(14):1205–1214. doi:10.1001/jama.2024.3172) The potential link between acetaminophen (paracetamol) use during pregnancy and increased risks of neurodevelopmental disorders in children, such as autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability, has been a major subject of concern. Confounding bias may play a role in existing findings. If such a link were found, it could significantly impact how fever and pain are managed during pregnancy.

Parental mental illness’ effects on risk of childhood cancers is largely unknown. This study determined the association between maternal or paternal mental illness and risk of childhood cancers. Retrospective cohort studies and meta-analysis using population-based registers from England and Sweden. 591,092 children born 1996–2017 (England) and 2,192,476 children born 1991–2011 (Sweden) were linked to their mothers (both countries) and fathers (Sweden), followed until latest December 2016 (Sweden) or July 2017 (England). Parental mental illness (depression/anxiety, psychosis, alcohol/substance use disorders, eating/personality disorders) were identified through primary (England) or secondary care (Sweden) databases as time-varying exposure, measured from one year before birth until the end of follow-up. Childhood cancer were identified from secondary care data. Hazard ratios (HRs) were estimated using Cox models separately in both countries, adjusted for potential confounders. Random-effects meta-analyses were used to estimate the association for maternal exposure. All estimates were characterised by uncertainty, with 95

Levels of neonatal Acute Phase Proteins (APPs) have been associated with autism and schizophrenia. The relative contributions of genetic and environmental factors to variation in APP levels in the neonatal period are not known. Therefore, we used one of the largest twin samples to date to map the proportions of heritable and non-heritable factors to variations in APPs measured shortly after birth. Moreover, we investigated if any association existed between neonatal APP levels and autism, among monozygotic and dizygotic twins discordant for autism. Twins were identified and enrolled from registers and a clinical twin study of autism in Sweden. The distributions of APPs measured in dried blood spots taken a few days after birth as part of a national screening program were standardized to reduce any analytical artifacts. The additive genetic (A), common (C) and unique (E) environment components were estimated, using the ACE model, on a sample of 92 twin pairs. We included 61 autism discordant twin pairs for estimating the association between the APPs and autism, using both non-fixed (between) and fixed (within) effects regression models. For the ACE models, variations in α-2 macroglobulin, C-reactive protein, ferritin, fibrinogen, haptoglobin, serum amyloid A and serum amyloid P were all largely explained by additive genetic factors (70-90 %). Variation in tissue plasminogen activator and procalcitonin were predominantly explained by common environmental factors (60-70 %) with a negligible contribution by genetic factors. Variations in levels of tissue plasminogen activator and procalcitonin in the neonatal period appear to be mainly explained by pregnancy and birth related factors. Variations in levels of other investigated acute phase proteins were largely explained by additive genetic factors. None of the APPs exhibited any significant association with autism in discordant mono- or dizygotic twin pairs. Our findings highlight the importance of considering potential familial confounding in future studies of association between any APP and autism.

BACKGROUND:We assessed the risk of anxiety disorders in children of clinically anxious parents, focusing on the influence of parent and child sex, parental care level, depressive comorbidity, and anxiety subtype, while controlling for socioeconomic factors and other parental psychiatric conditions. METHODS:We conducted a population-based study utilizing comprehensive healthcare data. A cohort of children (N = 516,134), born in 1998-2015 and residing in Stockholm, Sweden, was followed until they were diagnosed with anxiety, moved, or turned 18. The primary and secondary exposures were parental specified and unspecified anxiety diagnoses, respectively. The outcome was child specified anxiety diagnosis. Associations were estimated using hazard ratios (HRs) with 95% confidence intervals (CIs). RESULTS:Among exposed children, 4.3% were diagnosed with specified anxiety disorders, compared to 3.0% of unexposed (HR: 1.44, 95% CI: 1.38, 1.51). Adjustment for socioeconomic factors and other parental psychiatric disorders attenuated the risk (HR: 1.27, 95% CI: 1.21, 1.34). The risk was higher when parental anxiety was recorded in specialized psychiatric care (HR: 1.69, 95% CI: 1.60, 1.79) than in primary care (HR: 1.24, 95% CI: 1.17, 1.32). Maternal anxiety was linked to a higher risk (HR: 1.49, 95% CI: 1.41, 1.56) than paternal (HR: 1.31, 95% CI: 1.21, 1.42). Children were most likely to develop the same anxiety disorder as their parents, in cases of social anxiety, specific phobia, and panic disorder. Parental unspecified anxiety diagnoses were not associated with an increase in risk (HR: 1.02, 95% CI: 0.98, 1.07). CONCLUSIONS:Parental specified anxiety modestly increased the risk of child anxiety disorders. While the overall risk was lower than previously reported, it varied across diagnosis types and care levels.