To Örebro University

Background: Neighborhoods shape daily life through physical and social structures, such as socioeconomic conditions, population density, and resident turnover. Decades of research link neighborhood characteristics to health and behavioral outcomes. However, these factors are often studied independently, neglecting their interrelated nature.

Methods: Using Swedish population registry data, we employed latent class analyses to identify neighborhood typologies across six timepoints spanning 1991-2020. Neighborhoods, defined by Demographic Statistical Areas, were characterized by socioeconomic conditions, ethnic heterogeneity, residential instability, and urbanicity. Latent transition analyses examined changes over time.

Results: Four neighborhood types emerged in the early period (1991-2000): Rural Low-Diversity (45 %), Urban Professional (27 %), Urban Affluent (21 %), and Resource-Limited (7 %). From 2001 onwards, five types were identified, with the addition of Urban High-Diversity (9 %) and Rural Resource-Limited (3 %). Three types, Rural Low-Diversity, Urban Professional, and Urban Affluent, persisted across 30 years, representing 87-93 % of neighborhoods, with over 90 % of neighborhoods retaining their classification over time.

Conclusions: This multidimensional framework offers a foundation for future research, urban planning, and policy development.

Background: Little is known about the risk of suicide in individuals treated against their will in involuntary psychiatric care (IPC). This population-based study provides a first comprehensive description of suicide among individuals who experienced IPC.

Methods: We studied all individuals discharged from IPC in Sweden from 2010 through 2020. Clinical and sociodemographic characteristics are reported followed by suicide risk for the complete IPC population and stratified by sex, age, IPC history, and diagnostic category. Crude and adjusted relative risks compared to all individuals discharged from psychiatric in-and outpatient care and the general population were estimated using Poisson regression. Suicide methods, seasonal trends, and geographical variance are also reported.

Findings: We identified 72 275 patients treated in IPC with a total of 134 514 inpatient care episodes (mean age = 44.8 years, 37 462 [51.8%] males). Of these, 2104 (2.9%) died by suicide over a median follow-up time of 4.4 years (IQR: 1.8-7.5). Suicide decedents were younger, more often male, single, diagnosed with personality and substance use disorders, and had a history of self-harm and IPC, compared to those who did not die by suicide. The absolute risk (crude incidence rate (IR) per 100 000 person-years) for all IPC patients was highest closest to discharge (IR1month = 2941 [2538, 3408]) and decreased thereafter (IR5years = 738 [705, 773]). Suicide risk in IPC patients was elevated relative to psychiatric inpatients (crude IR ratio (IRR)5years = 1.57 [1.48, 1.65]), psychiatric outpatients (IRR5years = 3.77 [3.58, 3.97]), and the general population (IRR5years= 55.52 [52.65, 58.54]).

Interpretation: We found substantial risk differences in distinct subgroups of IPC patients and an excess suicide risk among IPC patients compared to other clinical populations. These findings warrant further investigation as they could inform clinicians and policy makers regarding potential risk stratification, monitoring, and care. Preventing suicides after IPC should be a priority.

BACKGROUND: Postinfectious autoimmune processes have been proposed as potential causal factors for obsessive-compulsive disorder (OCD). This large population-based study aimed to clarify the co-aggregation pattern between severe infections and OCD across clusters of relatives with varying degrees of relatedness.

METHODS: We identified 4,916,898 individuals born in Sweden between 1960 and 2008 and followed them until 2020. Each individual was linked to their first- and second-degree relatives, including monozygotic (MZ) and dizygotic (DZ) twins, mothers, fathers, full siblings, maternal and paternal half siblings, aunts, uncles, and cousins. OCD and infection diagnoses from inpatient and specialized outpatient units were retrieved from the Swedish National Patient Register. We compared the risk of OCD in relatives of probands with severe infections to those of probands without severe infections. Cox proportional hazard regression models, incorporating time-varying exposures, were used to estimate hazard ratios (HRs). Dose-response associations were examined using logistic regression models.

RESULTS: Relatives of probands with severe infections exhibited a higher risk of OCD, increasing with genetic relatedness, with HRs (95% CI) ranging from 1.46 (1.07-1.98) in MZ twins to 1.10 (1.09-1.11) in cousins. The results remained robust after adjusting for severe infections among relatives, OCD in probands, and comorbid autoimmune disorders in both probands and relatives. A dose-response association was observed between the number of infections in the probands and their odds of OCD, as well as in their relatives.

CONCLUSIONS: The results strongly suggest that the association between severe infections and OCD may be largely driven by shared genetic factors.

OBJECTIVE: To examine the effects of drug treatment for attention deficit/hyperactivity disorder (ADHD) on suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality.

DESIGN: Emulation of target trials.

SETTING: Linkage of national registers in Sweden, 2007-20.

PARTICIPANTS: People aged 6-64 years with a new diagnosis of ADHD, who either started or did not start drug treatment for ADHD within three months of diagnosis.

MAIN OUTCOME MEASURES: First and recurrent events of five outcomes over two years after ADHD diagnosis: suicidal behaviours, substance misuse, accidental injuries, transport accidents, and criminality.

RESULTS: Of 148581 individuals with ADHD (median age 17.4 years; 41.3% female), 84282 (56.7%) started drug treatment for ADHD, with methylphenidate being the most commonly prescribed at initiation (74515; 88.4%). Drug treatment for ADHD was associated with reduced rates of the first occurrence of suicidal behaviours (weighted incidence rates 14.5 per 1000 person years in the initiation group versus 16.9 in the non-initiation group; adjusted incidence rate ratio 0.83, 95% confidence interval 0.78 to 0.88), substance misuse (58.7 v 69.1 per 1000 person years; 0.85, 0.83 to 0.87), transport accidents (24.0 v 27.5 per 1000 person years; 0.88, 0.82 to 0.94), and criminality (65.1 v 76.1 per 1000 person years; 0.87, 0.83 to 0.90), whereas the reduction was not statistically significant for accidental injuries (88.5 v 90.1 per 1000 person years; incidence rate ratio 0.98, 0.96 to 1.01). The reduced rates were more pronounced among individuals with previous events, with incidence rate ratios ranging from 0.79 (0.72 to 0.86) for suicidal behaviours to 0.97 (0.93 to 1.00) for accidental injuries. For recurrent events, drug treatment for ADHD was significantly associated with reduced rates of all five outcomes, with incidence rate ratios of 0.85 (0.77 to 0.93) for suicidal behaviours, 0.75 (0.72 to 0.78) for substance misuse, 0.96 (0.92 to 0.99) for accidental injuries, 0.84 (0.76 to 0.91) for transport accidents, and 0.75 (0.71 to 0.79) for criminality.

CONCLUSIONS: Drug treatment for ADHD was associated with beneficial effects in reducing the risks of suicidal behaviours, substance misuse, transport accidents, and criminality but not accidental injuries when considering first event rate. The risk reductions were more pronounced for recurrent events, with reduced rates for all five outcomes. This target trial emulation study using national register data provides evidence that is representative of patients in routine clinical settings.

BACKGROUND: Tourette syndrome (TS) and chronic tic disorder (CTD) may be associated with an increased risk of mortality, but specific causes of death are poorly understood. OBJECTIVES: In this matched cohort and sibling cohort study, we estimated the risk of all-cause and cause-specific mortality in individuals with TS/CTD, compared with unaffected matched individuals and unaffected full siblings.

METHODS: We identified all individuals diagnosed with TS/CTD in the Swedish National Patient Register who were living in the country between 1973 and 2020 and matched them (1:10) to individuals without TS/CTD from the general population. We also identified their siblings without TS/CTD. All-cause and cause-specific mortality outcomes, based on the International Classification of Diseases codes, were extracted from the Cause of Death Register. Covariates included sociodemographic variables and psychiatric disorders. Risks of mortality were estimated using Cox proportional hazards regression models.

RESULTS: We included 10,280 individuals with TS/CTD and 102,800 matched individuals without TS/CTD. In adjusted models, individuals with TS/CTD had an 86% increased hazard of all-cause mortality (hazard ratio: 1.86, 95% confidence interval: 1.65-2.11). The increased risk was observed for both natural (particularly nervous, digestive, and respiratory system diseases) and unnatural causes of death (including suicides and accidents). The sibling comparison showed similar results, indicating that the associations were unlikely to be explained by familial confounding.

CONCLUSIONS: Individuals with TS/CTD are at increased risk of death due to both natural and unnatural causes. As some of these deaths are potentially preventable, greater focus on the somatic health of individuals with TS/CTD is warranted.

BACKGROUND: The diagnostic prevalences of Autism Spectrum Disorder (ASD) and Attention-Deficit/Hyperactivity Disorder (ADHD) have increased dramatically over the past two decades in the western world, particularly among teenagers and young adults. Here, we aimed to investigate whether there had been a corresponding increase in parent reported symptoms of ASD and ADHD in a population-based sample of 18-year-old twins born between 1993-2001.

METHODS: Data were collected in the Child and Adolescent Twin Study in Sweden (CATSS), in which parents report on symptoms of ASD and ADHD in connection with their children´s 18th birthday. Trends across 9 consecutive birth years in reported symptoms were analyzed as population mean scores and with percentile-based cut-offs using linear and logistic regression methods.

RESULTS: For ASD, there was no increase in the symptom phenotype across the examined birth years, neither at the population mean level nor at or above the 95th percentile of the ASD symptom score. For ADHD, there was a small - but statistically significant - increase over time of the population mean ADHD symptom score in girls (regression coefficient: 0.046 (95 % Confidence interval 0.025 - 0.066). p < 0.001), but not in boys. The prevalence at or above the 90th percentile of the ADHD symptom score was stable in boys but increased statistically significantly in girls (Odds Ratio: 1.053 (95 % Confidence interval 1.016-1.094). p = 0.005).

CONCLUSIONS: The rise in clinical diagnoses of ASD and ADHD in the adolescent/young adult population does not seem to be parallelled by a similar increase in ASD and ADHD symptoms.

There is emerging evidence to suggest that autistic individuals are at an increased risk for cognitive decline or dementia. It is unknown whether this association is due to shared familial influences between autism and dementia. The main purpose of this study was, thus, to investigate the risk of dementia in relatives of autistic individuals. We conducted a family study based on linking Swedish registers. We identified all individuals born in Sweden from 1980-2013, followed until 2020, and clinical diagnoses of autism among these individuals. We linked these index individuals with their parents, grandparents, and aunts/uncles. The risk of dementia (including any type of dementia, Alzheimer's disease, and other types of dementia) in relatives of autistic individuals was estimated using Cox proportional hazards models. Analyses were then stratified by sex of the relatives and intellectual disability in autistic individuals. Relatives of autistic individuals were at an increased risk of dementia. The risk was strongest in parents (hazards ratio [HR] = 1.36, 95% confidence intervals = 1.25-1.49), and weaker in grandparents (HR = 1.08, 1.06-1.10) and aunts/uncles (HR = 1.15, 0.96-1.38). Furthermore, there were indications of a stronger association between autism in index individuals and dementia in mothers (HR = 1.51, 1.29-1.77) compared to dementia in fathers (HR = 1.30, 1.16-1.45). There was only a small difference in relatives of autistic individuals with and without intellectual disability. Our results provide evidence of familial co-aggregation between autism and different types of dementia, and a potential genetic link. Future research now needs to clarify the risk of dementia in autistic individuals.

BACKGROUND: Mental health problems tend to run in families, with studies showing transdiagnostic associations across generations. Nevertheless, if these associations were attributable to unmeasured familial (either environmental or genetic) factors that influence both generations, then treating the parental conditions would not break the intergenerational transmission. This study aims to investigate the associations between parental psychiatric conditions and offspring psychiatric, behavioral, and psychosocial outcomes, after controlling for unmeasured familial factors shared by offspring of monozygotic (MZ) twin parents (i.e., cousins).

METHODS AND FINDINGS: We conducted a children-of-MZ twins study that consisted of 15,603 individuals (born to 7,742 MZ twin parents) born in Sweden between 1970 and 2000, and followed them from their date of birth to the date of the outcome or December 31, 2020, when the offspring were between 21 and 51 years old. The exposures were whether the MZ twin parents were diagnosed with any psychiatric condition, any internalizing condition, or any externalizing condition. The outcomes included register-based psychiatric conditions, behavioral problems, suicide, and psychosocial problems in the offspring. We performed stratified Cox regression for time-to-event outcomes and conditional logistic regression for binary outcomes to compare offspring exposed to an MZ twin parent with psychiatric conditions against their unexposed cousins. We adjusted for the highest parental educational level, maternal and paternal age at childbirth, offspring birth year, offspring sex, and psychiatric diagnosis of the nontwin parent. Offspring of parents with any parental psychiatric condition, internalizing condition, or externalizing condition had significantly higher probabilities for all the psychiatric, behavioral, and psychosocial outcomes, with hazard ratios (HRs) ranging from 1.34 (95% confidence interval [CI] [1.21, 1.49]; p < 0.001) to 2.53 (95% CI [1.96, 3.26]; p < 0.001) for time-to-event outcomes and odds ratios ranging from 1.33 (95% CI [1.17, 1.52]; p < 0.001) to 1.87 (95% CI [1.63, 2.14]; p < 0.001) for binary outcomes. Although these associations attenuated when comparing differentially exposed cousins whose parents were MZ twins (20 out of 27 associations were no longer statistically significant within cousin pairs), associations between broad spectra remained statistically significant. Specifically, across the main analysis and several sensitivity analyses, statistically significant within-twin-family associations remained between any parental psychiatric condition and any offspring psychiatric condition (HR = 1.28, 95% CI [1.13, 1.44]; p < 0.001), between parental internalizing conditions and any offspring psychiatric condition (HR = 1.26, 95% CI [1.09, 1.45]; p = 0.002), and between parental externalizing conditions and any offspring psychiatric condition (HR = 1.27, 95% CI [1.08, 1.51]; p = 0.005). The main limitations of this study were unmeasured confounders not shared by cousins, the lack of diagnostic data from primary care, and limited statistical power for some specific clustered outcomes.

CONCLUSIONS: Although the intergenerational transmission between parental psychiatric conditions and offspring psychiatric, behavioral, and psychosocial outcomes appeared partially attributable to unmeasured familial (environmental or genetic) factors that influenced both generations, there was also evidence of either nonshared factors or direct causal effects. If the latter, then treating parental psychiatric conditions would reduce the risk of psychiatric vulnerability in offspring.

Quasi-experimental and randomized controlled studies suggest that an enriched childhood rearing environment for at-risk individuals can reduce the risk for several psychiatric conditions. However, it remains uncertain if the reduced risk might be attributable to a general psychopathology factor common to all psychiatric conditions, versus specific psychopathology factors unique to only subsets of psychiatric conditions. In an at-risk sample, we estimated the association between an enriched childhood rearing environment and a latent bifactor model that captured both general and several specific psychopathology factors. The sample consisted of 881 full sibships where (a) the biological parents had (at least) one psychiatric diagnosis, suicide, or crime at any time in their lives, and (b) where (at least) one sibling was adopted away and raised by non-biological parents and (at least) one sibling raised by the biological parents. The exposure was whether a sibling was raised by biological versus adoptive parents. The outcome was a latent bifactor model based on nine conditions, including 7 in- or outpatient psychiatric diagnoses, suicide, and crimes. We recorded these outcomes from the birth of the siblings until the end of 2013, when the siblings were 34-64 years old. We used the marginal between-within model to estimate whether the adopted-away sibling(s) had lower scores on the latent factors. The latent bifactor model based on the nine conditions consisted of one general and three specific (externalizing, internalizing, and psychotic) psychopathology factors. The adopted-away siblings scored 0.27 (95% CI: -0.36, -0.18) standard deviations lower on the latent general psychopathology factor and 0.26 (95% CI: -0.38, -0.14) standard deviations lower on the latent specific externalizing factor, compared to their biological siblings who were raised by the biological parents. This result indicates that although genetics appears important for psychiatric comorbidity, the rearing environment also appears to play a systematic role in influencing the liability toward all mental health conditions among at-risk individuals. Improving the childhood rearing environment in high-risk families could potentially mitigate children's liability toward all psychiatric conditions.

Background: The cumulative effect of early medical events has been shown to be associated with autism. It is unclear whether this effect is specific to autism or if it is associated to other neurodevelopmental conditions (NDCs) as well.

Methods: We established a registry-linked population-based twin cohort of 10,254 pairs within the child and adolescent twin study in Sweden. Participants were evaluated for symptoms of autism, attention deficit hyperactivity disorder, tics, and learning difficulties at age 9. Three early medical events previously associated with autism, beyond familial confounding (low birth weight, congenital malformations, and perinatal respiratory stress), were summed up creating an individual cumulative exposure load. Confirmatory Factor Analysis was performed on the measure of NDCs and a standardized common latent NDC factor was regressed on level of cumulative exposure.

Results: Cumulative exposure to early medical events was associated with a non-linear increase in the common latent NDC factor, ss = 0.12 (95% CI, 0.07-0.17) for exposure level 1, ss = 0.25 (0.17-0.33) for exposure level 2, and ss = 0.62 (0.34-0.90) for exposure level 3. In a monozygotic twin difference analysis, with familial confounding being fully accounted for, the whole exposure effect was captured by the common factor, with residual associations fully attenuated for all four NDC outcomes, at all levels of cumulative exposure.

Conclusion: The result suggests a possibly causal environmental pathway. The cumulative effect of early medical events previously associated with autism, are not specific for autism, but rather associated with NDCs in a broad sense.