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Background: Maternal infections during pregnancy are associated with intellectual disability and autism in exposed children. Whether these associations are causal, and therefore should be targets of preventive strategies, remains unknown. We aimed to investigate these associations, to determine whether there is a causal role of maternal infection during pregnancy for children's risk of autism and intellectual disability, by accounting for unmeasured familial factors., Methods: We used a register-based cohort study design, and included children living in Stockholm County, Sweden, who were born in 1987-2010. We excluded children not born in Sweden, adopted children, and children with unknown biological mothers or fathers. Maternal infections during pregnancy, defined by ICD-8, ICD-9, and ICD-10 codes, were identified in the National Patient Register and Medical Birth Register. Children were followed up from birth to an outcome or a censoring event (death, migration from Stockholm, age 18 years, or Dec 31, 2016, whichever occurred first). The primary outcomes were diagnosis of autism or diagnosis of intellectual disability. We did a survival analysis to examine the association between inpatient and outpatient specialised care for any infection during pregnancy and likelihood of autism or intellectual disability in the child. To address potential residual confounding, we also estimated the relationship between maternal infection in the year preceding pregnancy as a negative control exposure and conducted a matched sibling analysis of sibling pairs who were discordant for autism or intellectual disability., Findings: 647 947 children living in Stockholm County were identified and, after excluding 97 980 children, we included 549 967 in the study (267 995 [48·7%] were female and 281 972 [51·3%] were male; mean age at censoring 13·5 years [SD 5·0; range <1 to 18]; 142 597 [25·9%] had a mother who was not born in Sweden). 445 (1·3%) of 34 013 children exposed to maternal infection during pregnancy were diagnosed with intellectual disability and 1123 (3·3%) with autism. 5087 (1·0%) of 515 954 unexposed children were diagnosed with intellectual disability and 13 035 (2·5%) with autism. Maternal infection during pregnancy was associated with autism (hazard ratio [HR] 1·16, 95% CI 1·09-1·23) and intellectual disability (1·37, 1·23-1·51) in exposed children compared with unexposed children. Maternal infection in the year before pregnancy (negative control exposure) was also associated with autism (HR 1·25, 95% CI 1·14-1·36), but was not associated with intellectual disability (1·09, 0·94-1·27). In sibling comparisons, the associations with maternal infection during pregnancy were attenuated for autism (HR 0·94, 95% CI 0·82-1·08; n=21 864), but not to the same extent for intellectual disability (1·15, 0·95-1·40; n=9275)., Interpretation: Although infections in pregnant women are associated with both autism and intellectual disability in their children, the association with autism does not appear to reflect a causal relationship, but is more likely to be explained by factors shared between family members such as genetic variation or aspects of the shared environment. Thus, infection prevention is not expected to reduce autism incidence. For intellectual disability, unmeasured familial factors might not fully explain the observed associations, and a causal role of maternal infections cannot be excluded. Causal effects of specific but rare infections or infections not requiring health care contact cannot be excluded in either autism or intellectual disability., Funding: Swedish Research Council, Stanley Medical Research Institute, and Autism Speaks., Translation: For the Swedish translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Being not in education, employment, or training (NEET) has been associated with poor health outcomes. This study aimed to investigate the association between NEET during emerging adulthood and later drug use disorder (DUD) among males and females., Method: A national cohort comprising 383,116 Swedish males and 362,002 females born between 1984 and 1990. NEET exposure was assessed annually between the ages 17 and 24 years, and follow-up for DUD between ages 25-33. Trajectories of NEET were estimated using group-based trajectory analysis. Cox regression analysis was used to estimate hazard ratios (HR) of DUD. Sibling-comparison model was performed to account for potential shared genetic and environmental factors., Results: Four trajectories of NEET were identified: "constant low", "transient peak", "late increase", and "constant high". Compared with the "constant low", all other trajectories were associated with increased HRs of DUD. HR was highest among males and females in the "late increase trajectory"; HR = 4.10 (3.79-4.44, 95% CI) and HR = 3.73 (3.29-4.24, 95% CI), after adjusting for domicile, origin, birth year, psychiatric diagnoses, and parental psychiatric diagnoses. This association was reduced to about a twofold increased risk in the sibling comparison analysis., Conclusion: Being NEET during emerging adulthood was associated with later DUD for both males and females. Neither origin, psychiatric diagnoses, parental psychiatric diagnoses, nor shared familial factors did fully explain the association. Males and females belonging to the late increase NEET trajectory had about a twofold increased risk of DUD., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Pharmacotherapy for alcohol use disorders (AUD) is effective. However, knowledge about utilization of, and patient characteristics associated with prescriptions is scarce. The aim is to investigate prescriptions of pharmacotherapy for AUD in Sweden across time, sociodemographics, domicile and comorbid conditions., Method: This is a national cohort study, comprising 132 733 adult patients with AUD diagnosis between 2007 and 2015. The exposure variables were age, sex, income, education, family constellation, domicile, origin, concurrent psychiatric and somatic co-morbid diagnoses. Logistic regression analyses were used to obtain odds ratios (OR) for any filled prescription of AUD pharmacotherapy; Acamprosate, Disulfiram, Naltrexone or Nalmefene during 12 months after AUD diagnosis., Results: During the study period, the proportion of individuals who received pharmacotherapy ranged between 22.80 and 23.94 % (χ2(64) = 72.00, p = .23). Female sex, age 31-45, higher education and income, living in a big city, co-habiting and born in Sweden, bar Norway, Denmark and Iceland, were associated with higher odds of pharmacotherapy. Concurrent somatic diagnosis was associated with lower odds of pharmacotherapy but psychiatric diagnosis higher (aOR = 0.61 95 % CI 0.59-0.63 and aOR = 1.61 95 % CI 1.57-1.66 respectively)., Conclusions: Pharmacotherapy for AUD is underutilized. The proportion of individuals with a prescription did not change between 2007 and 2015. Provision of treatment is unequal across different groups in society, where especially older age, lower income and education, and co-morbid somatic diagnosis were associated with lower odds of prescription. There is a need to develop treatment provision, particularly for individuals with co-morbid somatic conditions., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Immune signaling pathways influence neurodevelopment and are hypothesized to contribute to the etiology of autism spectrum disorder (ASD). We aimed to assess risk of ASD in relation to levels of neonatal acute phase proteins (APPs), key components of innate immune function, measured in neonatal dried blood spots., Methods: We included 924 ASD cases, 1092 unaffected population-based controls, and 203 unaffected siblings of ASD cases in this case-control study nested within the register-based Stockholm Youth Cohort. Concentrations of 9 different APPs were measured in eluates from neonatal dried blood spots from cases, controls, and siblings using a bead-based multiplex assay., Results: Neonatal C-reactive protein was consistently associated with odds of ASD in case-control comparisons, with higher odds associated with the highest quintile compared with the middle quintile (odds ratio [OR] = 1.50, 95% confidence interval [CI] = 1.10-2.04) in adjusted analyses. In contrast, the lowest quintiles of α-2-macroglobulin (OR = 3.71, CI = 1.21-11.33), ferritin (OR = 4.20, CI = 1.40-12.65), and serum amyloid P (OR = 3.05, CI = 1.16-8.01) were associated with odds of ASD in the matched sibling comparison. Neonatal APPs varied with perinatal environmental factors and maternal/fetal phenotypes. Significant interactions in terms of risk for ASD were observed between neonatal APPs and maternal infection during late pregnancy, maternal anemia, and maternal psychiatric history., Conclusions: Indicators of the neonatal innate immune response are associated with risk of ASD, although the nature of these associations varies considerably with factors in the perinatal environment and the genetic background of the comparison group., (Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Endometriosis is a common gynecologic condition affecting women of reproductive age. It has been linked with greater rates of depression and anxiety in small, cross-sectional, and clinical studies. Other studies have reported that women with endometriosis have increased risk of bipolar disorder. These reports suggest that psychiatric disorders might be more common among women with endometriosis, contributing to increased burden of mental ill-health in this population of women. However, this hypothesis has not been adequately studied., Objectives: In this population-based study, we investigated the overall psychiatric comorbidity among women with endometriosis, and the role of familial liability., Study Design: Several Swedish national registers were linked and used to follow all women born in Sweden in 1973-1990 for diagnosed psychiatric disorders and endometriosis from age 14 years until year 2016. Sibling comparison analyses were performed in a subsample of 173,650 families., Results: After adjustment for birth characteristics and education, women with endometriosis had an increased risk of being later diagnosed with depressive-, anxiety and stress-related disorders, alcohol/drug dependence, and attention-deficit hyperactivity disorder compared with the general population and with their sisters without endometriosis. The adjusted hazard ratios ranged from 1.56 (95% confidence interval, 1.29-1.88) for depressive disorders to 1.98 (95% confidence interval, 1.34-2.93) for attention-deficit hyperactivity disorder in the sibling analysis. Also, women with previous affective psychotic disorders, depressive-, anxiety and stress-related disorders, eating disorders, personality disorders, and attention-deficit hyperactivity disorder were more likely to be later diagnosed with endometriosis. The adjusted hazard ratios ranged from 1.51 (95% confidence interval, 1.30-1.76) for depressive disorders to 1.93 (95% confidence interval, 1.47-2.52) for personality disorders., Conclusion: These findings reveal a high degree of comorbidity between endometriosis and many psychiatric disorders that was not entirely explained by shared familial confounding. Clinical practice may consider psychosocial support to women with endometriosis and treating them from a multidisciplinary perspective., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: To evaluate the association of acne in late adolescence with the risk for subsequent malignant melanoma (MM) in men., Methods: Swedish register-based cohort study of 242,096 males born between 1952 and 1956, who took part in compulsory assessments for Swedish military conscription in late adolescence between 1969 and 1975, with subsequent diagnoses of MM (n=1,058) up to December 31, 2009. Covariates included measures of childhood circumstances and information from adolescence on presence of acne, physical fitness, cognitive function, body mass index (BMI), and a summary of diagnoses. Cox regression was used for the analysis., Results: In total 1,058 men were diagnosed with MM. Acne was not associated with subsequent MM, with an adjusted hazard ratio (and 95% confidence interval) of 0.95 (0.61 to 1.49). Men with parents who were agricultural workers, and men who lived in northern Sweden, had lower physical fitness, or lower cognitive function had a lower risk of MM. Overweight and obesity was associated with a raised risk, with an adjusted hazard ratio of 1.39 (1.14, 1.71)., Conclusions: Acne in late adolescence is unlikely to represent a raised risk for subsequent MM in men. Overweight or obesity was identified as a raised risk for MM, possibly due to the associated increased skin surface area., (Copyright © 2017 Elsevier Ltd. All rights reserved.)