Publications by authors named "Henrik Larsson"

521 Publications

Examining protective factors for substance use problems and self-harm behavior during adolescence: A longitudinal co-twin control study.

Dev Psychopathol 2022 Aug 15:1-22. Epub 2022 Aug 15.

Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.

Sports participation, physical activity, and friendship quality are theorized to have protective effects on the developmental emergence of substance use and self-harm behavior in adolescence, but existing research has been mixed. This ambiguity could reflect, in part, the potential for confounding of observed associations by genetic and environmental factors, which previous research has been unable to rigorously rule out. We used data from the prospective, population-based Child and Adolescent Twin Study in Sweden ( = 18,234 born 1994-2001) and applied a co-twin control design to account for potential genetic and environmental confounding of sports participation, physical activity, and friendship quality (assessed at age 15) as presumed protective factors for adolescent substance use and self-harm behavior (assessed at age 18). While confidence intervals widened to include the null in numerous co-twin control analyses adjusting for childhood psychopathology, parent-reported sports participation and twin-reported positive friendship quality were associated with increased odds of alcohol problems and nicotine use. However, parent-reported sports participation, twin-reported physical activity, and twin-reported friendship quality were associated with decreased odds of self-harm behavior. The findings provide a more nuanced understanding of the risks and benefits of putative protective factors for risky behaviors that emerge during adolescence.
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http://dx.doi.org/10.1017/S0954579422000724DOI Listing
August 2022

Heritability of Psychotic Experiences in Adolescents and Interaction With Environmental Risk.

JAMA Psychiatry 2022 Aug 3. Epub 2022 Aug 3.

Genes Environment Lifespan Laboratory, Centre for Brain and Cognitive Development, Department of Psychological Sciences, Birkbeck University of London, London, United Kingdom.

Importance: Genetic risk factors are known to play a role in the etiology of psychotic experiences in the general population. Little is known about whether these risk factors interact with environmental risks for psychotic experiences.

Objective: To assess etiological heterogeneity and exposure to environmental risks associated with psychotic experiences in adolescence using the twin design.

Design, Setting, And Participants: This twin study, conducted from December 1, 2014, to August 31, 2020, included a UK-based sample of twin pairs aged 16 years. This investigation evaluated the extent to which the genetic variance underlying psychotic experiences and the magnitude of the heritability of psychotic experiences was moderated by exposure to 5 environmental risk factors (bullying, dependent life events, cannabis use, tobacco use, and low birth weight). Psychotic experiences were assessed by 5 self-reported measures and 1 parent-reported measure. Participants' exposure to environmental risks was assessed at birth and age 12 to 16 years. Structural equation models were used to assess differences in the variance in and heritability of psychotic experiences across these exposures, while controlling for gene-environment correlation effects. Analyses were repeated in an independent Swedish sample. Data analyses were performed from September 1, 2018, to August 31, 2020.

Main Outcomes And Measures: Primary outcome measures were exposure to environmental factors, as measured by a composite score, and psychotic experiences.

Results: A total of 4855 twin pairs (1926 female same-sex pairs, 1397 male same-sex pairs, and 1532 opposite-sex pairs) were included from the Twins Early Development Study (TEDS), and 6435 twin pairs (2358 female same-sex pairs, 1861 male same-sex pairs, and 2216 opposite-sex pairs) were included from the Child and Adolescent Twin Study in Sweden (CATSS). Mean age of twins from TEDS was 16.5 years. Mean age of twins from CATSS was 18.6 years. More exposure to environmental risk factors was associated with having more psychotic experiences. The relative contribution of genetic influences to psychotic experiences was lower with increasing environmental exposure for paranoia (44%; 95% CI, 33%-53% to 38%; 95% CI, 14%-58%), cognitive disorganization (47%; 95% CI, 38%-51% to 32%; 95% CI, 11%-45%), grandiosity (41%; 95% CI, 29%-52% to 32%; 95% CI, 9%-48%), and anhedonia (49%; 95% CI, 42%-53% to 37%; 95% CI, 15%-54%). This pattern was replicated for the measure of psychotic experiences in the independent Swedish replication sample. The heritability of hallucinations and parent-rated negative symptoms remained relatively constant.

Conclusions And Relevance: Findings of this twin study suggest that environmental factors play a greater role in the etiology of psychotic experiences than genetic factors. The relative importance of environmental factors is even higher among individuals exposed to environmental risks for psychotic experiences, highlighting the importance of a diathesis-stress or bioecological framework for understanding adolescent psychotic experiences.
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http://dx.doi.org/10.1001/jamapsychiatry.2022.1947DOI Listing
August 2022

Association and Familial Coaggregation of Childhood-Onset Type 1 Diabetes With Depression, Anxiety, and Stress-Related Disorders: A Population-Based Cohort Study.

Diabetes Care 2022 Aug 1. Epub 2022 Aug 1.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.

Objective: To estimate the association and familial coaggregation of childhood-onset type 1 diabetes with depression, anxiety, and stress-related disorders.

Research Design And Methods: This was a population-based cohort study with use of data from Swedish nationwide registers. A total of ∼3.5 million individuals born in Sweden 1973-2007 were linked to their biological parents, full siblings and half-siblings, and cousins. Cox models were used to estimate the association and familial coaggregation of type 1 diabetes with depression, anxiety, and stress-related disorders.

Results: Individuals diagnosed with childhood-onset type 1 diabetes (n = 20,005) were found to be at greater risks of all outcomes: any psychiatric diagnosis (adjusted hazard ratio [aHR] 1.66 [95% CI 1.59-1.72]) or specific diagnoses of depression (1.85 [1.76-1.94]), anxiety (1.41[1.33-1.50]), and stress-related disorders (1.75 [1.62-1.89]), as well as use of antidepressants or anxiolytics (1.30 [1.26-1.34]), compared with individuals without type 1 diabetes. Overall, relatives of individuals with type 1 diabetes were at elevated risks of developing these outcomes, with the highest risks seen in parents (aHRs 1.18-1.25), followed by full siblings (aHRs 1.05-1.20), and the magnitudes of risk estimates appear proportional to familial relatedness.

Conclusions: These results support existing evidence that children and adolescents with type 1 diabetes are at greater risks of developing depression, anxiety, and stress-related disorders and indicate that shared familial factors might contribute to these elevated risks. Our findings highlight the need for psychological consulting for children and their families in diabetes care. Quantitative and molecular genetic studies are warranted to further understand the etiology of these psychiatric disorders in type 1 diabetes.
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http://dx.doi.org/10.2337/dc21-1347DOI Listing
August 2022

Diagnostic yield of simultaneous dynamic contrast-enhanced magnetic resonance perfusion measurements and [F]FET PET in patients with suspected recurrent anaplastic astrocytoma and glioblastoma.

Eur J Nucl Med Mol Imaging 2022 Jul 30. Epub 2022 Jul 30.

Dept. of Clinical Physiology Nuclear Medicine and PET, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Purpose: Both amino acid positron emission tomography (PET) and magnetic resonance imaging (MRI) blood volume (BV) measurements are used in suspected recurrent high-grade gliomas. We compared the separate and combined diagnostic yield of simultaneously acquired dynamic contrast-enhanced (DCE) perfusion MRI and O-(2-[F]-fluoroethyl)-L-tyrosine ([F]FET) PET in patients with anaplastic astrocytoma and glioblastoma following standard therapy.

Methods: A total of 76 lesions in 60 hybrid [F]FET PET/MRI scans with DCE MRI from patients with suspected recurrence of anaplastic astrocytoma and glioblastoma were included retrospectively. BV was measured from DCE MRI employing a 2-compartment exchange model (2CXM). Diagnostic performances of maximal tumour-to-background [F]FET uptake (TBR), maximal BV (BV) and normalised BV (nBV) were determined by ROC analysis using 6-month histopathological (n = 28) or clinical/radiographical follow-up (n = 48) as reference. Sensitivity and specificity at optimal cut-offs were determined separately for enhancing and non-enhancing lesions.

Results: In progressive lesions, all BV and [F]FET metrics were higher than in non-progressive lesions. ROC analyses showed higher overall ROC AUCs for TBR than both BV and nBV in both lesion-wise (all lesions, p = 0.04) and in patient-wise analysis (p < 0.01). Combining TBR with BV metrics did not increase ROC AUC. Lesion-wise positive fraction/sensitivity/specificity at optimal cut-offs were 55%/91%/84% for TBR, 45%/77%/84% for BV and 59%/84%/72% for nBV. Combining TBR and best-performing BV cut-offs yielded lesion-wise sensitivity/specificity of 75/97%. The fraction of progressive lesions was 11% in concordant negative lesions, 33% in lesions only BV positive, 64% in lesions only [F]FET positive and 97% in concordant positive lesions.

Conclusion: The overall diagnostic accuracy of DCE BV imaging is good, but lower than that of [F]FET PET. Adding DCE BV imaging did not improve the overall diagnostic accuracy of [F]FET PET, but may improve specificity and allow better lesion-wise risk stratification than [F]FET PET alone.
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http://dx.doi.org/10.1007/s00259-022-05917-3DOI Listing
July 2022

Childhood-onset type 1 diabetes and attention-deficit/hyperactivity disorder with educational attainment: a population-based sibling-comparison study.

Acta Paediatr 2022 Jul 27. Epub 2022 Jul 27.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.

Aim: To examine the association of childhood-onset type 1 diabetes (T1D) and attention-deficit/hyperactivity disorder (ADHD) with educational outcomes from compulsory school to university.

Methods: Using multiple Swedish nationwide registers, we followed up on 1,474,941 individuals born in Sweden from 1981-1995 to December 31, 2013. Associations of T1D and ADHD with achieving educational milestones (from compulsory school to university) and school performances were estimated using logistic and linear regression models and sibling comparison models.

Results: Compared to their peers, children with both T1D and ADHD were less likely to achieve any of the educational attainments, including completing compulsory school (adjusted OR [aOR] [95% CI]: 0.43[0.26,0.72]), be eligible to and finishing upper secondary school (0.26[0.19,0.36], 0.24[0.17,0.35], respectively), and starting university (0.38[0.17,0.90]). The odds of achieving these educational milestones were substantially lower in children with ADHD alone (aORs: 0.14-0.44), but were slightly worse or no differences in children with T1D alone (aORs: 0.86-1.08). All associations above remained similar in the sibling comparison models.

Conclusion: Children and adolescents with both T1D and ADHD had long-term educational underachievement, with ADHD being the major contributor. Our findings suggest the importance of assessing ADHD in children with T1D and targeted support for minimizing the education gap between the affected children and their peers.
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http://dx.doi.org/10.1111/apa.16500DOI Listing
July 2022

Paediatric asthma and non-allergic comorbidities: A review of current risk and proposed mechanisms.

Clin Exp Allergy 2022 Jul 21. Epub 2022 Jul 21.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.

It is increasingly recognized that children with asthma are at a higher risk of other non-allergic concurrent diseases than the non-asthma population. A plethora of recent research has reported on these comorbidities and progress has been made in understanding the mechanisms for comorbidity. The goal of this review was to assess the most recent evidence (2016-2021) on the extent of common comorbidities (obesity, depression and anxiety, neurodevelopmental disorders, sleep disorders and autoimmune diseases) and the latest mechanistic research, highlighting knowledge gaps requiring further investigation. We found that the majority of recent studies from around the world demonstrate that children with asthma are at an increased risk of having at least one of the studied comorbidities. A range of potential mechanisms were identified including common early life risk factors, common genetic factors, causal relationships, asthma medication and embryologic origins. Studies varied in their selection of population, asthma definition and outcome definitions. Next, steps in future studies should include using objective measures of asthma, such as lung function and immunological data, as well as investigating asthma phenotypes and endotypes. Larger complex genetic analyses are needed, including genome-wide association studies, gene expression-functional as well as pathway analyses or Mendelian randomization techniques; and identification of gene-environment interactions, such as epi-genetic studies or twin analyses, including omics and early life exposure data. Importantly, research should have relevance to clinical and public health translation including clinical practice, asthma management guidelines and intervention studies aimed at reducing comorbidities.
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http://dx.doi.org/10.1111/cea.14207DOI Listing
July 2022

Mortality among twin individuals exposed to loss of a co-twin.

Int J Epidemiol 2022 Jul 18. Epub 2022 Jul 18.

Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavík, Iceland.

Background: Although the death of a child, sibling or spouse has been associated with elevated risk of mortality, less is known about the survival of twin siblings exposed to a co-twin loss.

Methods: In a Swedish population-based sibling-matched cohort, we compared the mortality of 5548 twin individuals who lost their co-twin between 1932 and 2011 with that of 27 740 age-matched and sex-matched twin individuals without such a loss and 6772 full siblings of these exposed twin individuals. Cox regression models were used to estimate the hazard ratios (HRs) of all-cause and cause-specific mortality.

Results: We found increased risk of all-cause mortality among twin individuals exposed to a co-twin loss compared with matched unexposed twin individuals (HR = 1.30, 95% CI: 1.18-1.43) and their full siblings (HR = 1.10, 95% CI: 0.96-1.27) after adjusting for multiple covariates. The all-cause mortality risk was greater for loss of a co-twin due to unnatural deaths (HR = 1.54, 95% CI: 1.17-2.03) than natural deaths (HR = 1.26, 95% CI: 1.14-1.40). For cause-specific mortality, co-twin loss was associated with a higher risk of unnatural deaths both among twin individuals who lost their co-twin due to unnatural deaths (HR = 1.98, 95% CI: 1.27-3.10) and those whose loss was due to natural deaths (HR = 1.48, 95% CI: 1.07-2.06). The risk elevations were generally stronger for loss of a monozygotic co-twin than loss of a dizygotic co-twin.

Conclusion: Loss of a co-twin, especially a monozygotic co-twin, was associated with increased mortality, particularly of unnatural causes, among the surviving twin individuals. The excess mortality is likely attributable to both shared disease susceptibility within the twin pair and the adverse health sequelae of bereavement.
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http://dx.doi.org/10.1093/ije/dyac145DOI Listing
July 2022

Childhood symptoms of attention-deficit/hyperactivity disorder and borderline personality disorder.

Acta Psychiatr Scand 2022 Jul 14. Epub 2022 Jul 14.

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.

Objective: Childhood attention-deficit /hyperactivity disorder (ADHD) is known to be associated with adult Borderline Personality Disorder (BPD). We investigated if any of the subdimensions of childhood ADHD, that is, impulsivity, inattention, or hyperactivity was more prominent in this association.

Methods: In a nation-wide cohort (N = 13,330), we utilized parent reported symptoms of childhood ADHD and clinically ascertained adult BPD diagnoses. The summed total scores of ADHD symptoms and its three subdimensions were used and standardized for effect size comparison. Associations were analyzed using Cox regression with sex and birth-year adjustments. Secondary outcomes were BPD-associated traits (i.e., self-harm and substance use) analyzed using logistic- and linear regression respectively.

Results: ADHD symptom severity was positively associated with BPD with a hazard ratio (HR) of 1.47 (95% confidence interval [CI]: 1.22-1.79) per standard deviation increase in total ADHD symptoms. Impulsivity was the most prominent subdimension with the only statistically significant association when analyzed in a model mutually adjusted for all ADHD subdimensions-HR for inattention: 1.15 (95% CI: 0.85-1.55), hyperactivity: 0.94 (95% CI: 0.69-1.26), impulsivity: 1.46 (95% CI: 1.12-1.91). In secondary analyses, weak positive associations were seen between total ADHD symptom score and self-harm and substance use. In analyses by subdimensions of ADHD, associations were weak and most prominent for inattention in the model with self-harm.

Conclusion: Childhood ADHD symptoms were associated with subsequent development of BPD diagnosis and appeared to be driven primarily by impulsivity. Our findings are important for understanding the association between childhood symptoms of ADHD and subsequent BPD.
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http://dx.doi.org/10.1111/acps.13476DOI Listing
July 2022

How interactions between ADHD and schools affect educational achievement: a family-based genetically sensitive study.

J Child Psychol Psychiatry 2022 Jul 4. Epub 2022 Jul 4.

PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway.

Background: Children with ADHD tend to achieve less than their peers in school. It is unknown whether schools moderate this association. Nonrandom selection of children into schools related to variations in their ADHD risk poses a methodological problem.

Methods: We linked data on ADHD symptoms of inattention and hyperactivity and parent-child ADHD polygenic scores (PGS) from the Norwegian Mother, Father, and Child Cohort Study (MoBa) to achievement in standardised tests and school identifiers. We estimated interactions of schools with individual differences between students in inattention, hyperactivity, and ADHD-PGS using multilevel models with random slopes for ADHD effects on achievement over schools. In our PGS analyses, we adjust for parental selection of schools by adjusting for parental ADHD-PGS (a within-family PGS design). We then tested whether five school sociodemographic measures explained any interactions.

Results: Analysis of up to 23,598 students attending 2,579 schools revealed interactions between school and ADHD effects on achievement. The variability between schools in the effects of inattention, hyperactivity and within-family ADHD-PGS on achievement was 0.08, 0.07 and 0.05 SDs, respectively. For example, the average effect of inattention on achievement was β = -0.23 (SE = 0.009), but in 2.5% of schools with the weakest effects, the value was -0.07 or less. ADHD has a weaker effect on achievement in higher-performing schools. Schools make more of a difference to the achievements of students with higher levels of ADHD, explaining over four times as much variance in achievement for those with high versus average inattention symptoms. School sociodemographic measures could not explain the ADHD-by-school interactions.

Conclusions: Although ADHD symptoms and genetic risk tend to hinder achievement, schools where their effects are weaker do exist. Differences between schools in support for children with ADHD should be evened out.
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http://dx.doi.org/10.1111/jcpp.13656DOI Listing
July 2022

Cardiovascular risk factors in attention-deficit/hyperactivity disorder: A family design study of Swedish conscripts.

Int J Methods Psychiatr Res 2022 Jun 29:e1930. Epub 2022 Jun 29.

School of Medical Science, Örebro University, Örebro, Sweden.

Objective: (1) investigate the associations of attention-deficit/hyperactivity disorder (ADHD) with systolic and diastolic blood pressure, resting heart rate, pulse pressure (PP), physical fitness, and BMI; (2) explore whether cardiovascular risk factors and ADHD share genetic and environmental influences; (3) assess if pharmacological treatment for ADHD influences these associations.

Methods: We identified 395,978 individuals born between 1973 and 1991 who had military conscription examinations at a mean age of 18.3 years (SD = 0.57) and their full-siblings within the same cohort (N = 208,060) by linking population-based registers in Sweden.

Results: Significantly increased risk of ADHD was observed in individuals with low systolic blood pressure (SBP) and PP, low physical fitness, and in those who had overweight or obesity after adjustments (adjusted Odds Ratio [OR] ranging from 1.10 to 1.45). Full siblings of individuals with low SBP, low physical fitness, and obesity were more likely to receive an ADHD diagnosis compared to full siblings without those risk factors (OR ranging from 1.17 to 1.31). Additionally, analyses showed robust associations between ADHD and low SBP, low physical fitness, and obesity, even in ADHD medication-naïve individuals.

Conclusions: Individuals with several cardiovascular risk factors are more often diagnosed with ADHD, regardless of psychiatric comorbidity. These association are not explained by ADHD pharmacotherapy, rather, they are in part due to shared familial risk factors.
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http://dx.doi.org/10.1002/mpr.1930DOI Listing
June 2022

Cerebrovascular Reactivity and Neurovascular Coupling in Multiple Sclerosis-A Systematic Review.

Front Neurol 2022 1;13:912828. Epub 2022 Jun 1.

Functional Imaging Unit, Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital Rigshospitalet, Glostrup, Denmark.

The inflammatory processes observed in the central nervous system in multiple sclerosis (MS) could damage the endothelium of the cerebral vessels and lead to a dysfunctional regulation of vessel tonus and recruitment, potentially impairing cerebrovascular reactivity (CVR) and neurovascular coupling (NVC). Impaired CVR or NVC correlates with declining brain health and potentially plays a causal role in the development of neurodegenerative disease. Therefore, we examined studies on CVR or NVC in MS patients to evaluate the evidence for impaired cerebrovascular function as a contributing disease mechanism in MS. Twenty-three studies were included (12 examined CVR and 11 examined NVC). Six studies found no difference in CVR response between MS patients and healthy controls. Five studies observed reduced CVR in patients. This discrepancy can be because CVR is mainly affected after a long disease duration and therefore is not observed in all patients. All studies used CO as a vasodilating stimulus. The studies on NVC demonstrated diverse results; hence a conclusion that describes all the published observations is difficult to find. Future studies using quantitative techniques and larger study samples are needed to elucidate the discrepancies in the reported results.
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http://dx.doi.org/10.3389/fneur.2022.912828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9198441PMC
June 2022

Measuring autism in males and females with a differential item functioning approach: Results from a nation-wide population-based study.

Psychiatry Res 2022 08 8;314:114674. Epub 2022 Jun 8.

Centre for Ethics Law and Mental Health (CELAM), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Rågården hus 1, SU- Östra Sjukhuset, Gothenburg 416 85, Sweden; Gillberg Neuropsychiatry Centre, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.

Existing screening instruments for Autism Spectrum Disorder (ASD) might be prone to detect a male manifestation of ASD. Here, we examined the 17 items from the ASD domain in the Autism-Tics, ADHD and other Comorbidities inventory (A-TAC) for Differential Item Functioning (DIF). Data were obtained from the Child and Adolescent Twin Study in Sweden (CATSS) in which parents have responded to the A-TAC. Information regarding a registered diagnosis of ASD were retrieved from the National Patient Register. The cohort was divided into a developmental sample for evaluation of DIF, and a validation sample for examination of the diagnostic accuracy of the total ASD domain, and a novel male and female short form. Our main finding included the identification of DIF for six items, three favouring males and three favouring females. The full, 17 item, ASD domain and the male and female short form showed excellent ability to capture ASD diagnoses in both males and females up to the age of nine years. The full ASD domain in A-TAC is psychometrically largely equivalent across sex and the limited differences between males and females diminish the need for a sex-specific scoring when utilizing the 17 item total score.
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http://dx.doi.org/10.1016/j.psychres.2022.114674DOI Listing
August 2022

Association of Obsessive-Compulsive Disorder and Obsessive-Compulsive Symptoms With Substance Misuse in 2 Longitudinal Cohorts in Sweden.

JAMA Netw Open 2022 06 1;5(6):e2214779. Epub 2022 Jun 1.

Institute of Criminology and Legal Policy, University of Helsinki, Helsinki, Finland.

Importance: Neurobiological models have postulated shared neural mechanisms between obsessive-compulsive disorder (OCD) and substance use disorders, but results from clinical and epidemiological studies are conflicting or even suggest that OCD may be protective against substance misuse.

Objective: To investigate whether OCD and obsessive-compulsive symptoms are associated with substance misuse and the extent to which shared genetic and/or environmental factors account for this association.

Design, Setting, And Participants: In this cohort study, individuals in the general population of Sweden born between January 1, 1932, and December 31, 1997 (population cohort), were followed up through Swedish nationwide registers from January 1, 1997, to December 31, 2013. The second cohort included twin participants in the Child and Adolescent Twin Study in Sweden (CATSS) followed up from ages 18 to 24 years. Data were analyzed from March 1, 2021, to March 31, 2022.

Exposures: Lifetime International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, diagnosis of OCD in the National Patient Register (population cohort 1), and self-reported obsessive-compulsive symptoms at 18 years of age (CATSS cohort).

Main Outcomes And Measures: Substance misuse was defined as registered substance use-related disorder, criminal conviction, or death (population cohort), and self-reported alcohol and drug dependence symptoms at 18 and 24 years of age (CATSS cohort).

Results: The general population cohort included 6 304 188 individuals (48.9% women and 51.1% men; median baseline age, 30.5 [IQR, 15.0-46.4] years), of whom 27 342 had an OCD diagnosis. Obsessive-compulsive disorder was associated with an elevated risk of substance misuse (hazard ratio, 3.68 [95% CI, 3.52-3.85]). In the 9230 individuals in the CATSS cohort (5551 women [60.1%] and 3679 men [39.9%]), obsessive-compulsive symptoms at 18 years of age were associated with increased symptoms of alcohol dependence (concurrent [n = 9219], β = 0.18 [95% CI, 0.16-0.20]; longitudinal [n = 3381], β = 0.10 [95% CI, 0.06-0.14]) and drug dependence (concurrent [n = 749], β = 0.19 [95% CI, 0.11-0.27]; longitudinal [n = 452], β = 0.15 [95% CI, 0.04-0.25]). Comorbid anxiety and depression did not entirely explain the associations in either cohort. Using data from full siblings and maternal half-siblings (population cohort) and monozygotic and dizygotic twins (CATSS cohort) provided estimates of the relative contribution of genetic and environmental influences to the covariance between OCD and obsessive-compulsive symptoms and substance misuse or dependence. The associations were explained by genetic (56%-68%) and nonshared environmental (32%-44%) factors.

Conclusions And Relevance: The findings of this Swedish population-based cohort study challenge the notion that OCD is protective against developing substance misuse. The association of OCD and obsessive-compulsive symptoms with substance misuse was largely explained by shared genetics but was also compatible with partial environmental mediation.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.14779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9171556PMC
June 2022

Blood-brain barrier permeability changes in the first year after alemtuzumab treatment predict 2-year outcomes in relapsing-remitting multiple sclerosis.

Mult Scler Relat Disord 2022 Jul 18;63:103891. Epub 2022 May 18.

Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital - Rigshospitalet, Valdemar Hansens Vej 1-23, 2600 Glostrup, Denmark.

Background: In relapsing-remitting multiple sclerosis (RRMS), early disease control reduces the risk of permanent disability. The blood-brain barrier (BBB) is compromised in MS, and its permeability is a potential biomarker.

Objective: To investigate BBB permeability measured by MRI as a marker of alemtuzumab efficacy.

Methods: Patients with RRMS initiating alemtuzumab treatment were recruited prospectively. BBB permeability was assessed as the Patlak-derived influx constant (K) by dynamic contrast-enhanced MRI before and 6, 12, and 18 months after the first course of alemtuzumab. No Evidence of Disease Activity-3 (NEDA-3) status was ascertained two years after treatment initiation.

Results: Patients who maintained NEDA-3 status at two years (n = 7) had a larger decrease in K between baseline and six months (-0.029 ml/100 g/min [CI -0.005 - -0.053]) and between baseline and 12 months in normal appearing white matter (0.043 [CI 0.022 - -0.065]), than those who experienced disease activity (n = 8). ROC curve analysis of the K change between baseline and 12 months in NAWM predicted a loss of NEDA status at 2 years with 86% sensitivity and 86% specificity (AUC 0.98, p = 0.002).

Conclusion: BBB permeability predicted alemtuzumab efficacy at two years, indicating that BBB permeability is a biomarker of treatment response in RRMS.
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http://dx.doi.org/10.1016/j.msard.2022.103891DOI Listing
July 2022

Subclinical cognitive deficits are associated with reduced cerebrovascular response to visual stimulation in mid-sixties men.

Geroscience 2022 Jun 1. Epub 2022 Jun 1.

Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine, and PET, Copenhagen University Hospital Rigshospitalet, Valdemar Hansens Vej 1-23, 2600, Glostrup, Denmark.

Reduced cerebrovascular response to neuronal activation is observed in patients with neurodegenerative disease. In the present study, we examined the correlation between reduced cerebrovascular response to visual activation (ΔCBF) and subclinical cognitive deficits in a human population of mid-sixties individuals without neurodegenerative disease. Such a correlation would suggest that impaired cerebrovascular function occurs before overt neurodegenerative disease. A total of 187 subjects (age 64-67 years) of the Metropolit Danish Male Birth Cohort participated in the study. ΔCBF was measured using arterial spin labelling (ASL) MRI. ΔCBF correlated positively with cognitive performance in: Global cognition (p = 0.046), paired associative memory (p = 0.025), spatial recognition (p = 0.026), planning (p = 0.016), simple processing speed (p < 0.01), and with highly significant correlations with current intelligence (p < 10), and more complex processing speed (p < 10), the latter two explaining approximately 11-13% of the variance. Reduced ΔCBF was independent of brain atrophy. Our findings suggest that inhibited cerebrovascular response to neuronal activation is an early deficit in the ageing brain and associated with subclinical cognitive deficits. Cerebrovascular dysfunction could be an early sign of a trajectory pointing towards the development of neurodegenerative disease. Future efforts should elucidate if maintenance of a healthy cerebrovascular function can protect against the development of dementia.
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http://dx.doi.org/10.1007/s11357-022-00596-2DOI Listing
June 2022

Maternal Serotonergic Antidepressant Use in Pregnancy and Risk of Seizures in Children.

Neurology 2022 May 11. Epub 2022 May 11.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Objective: To evaluate whether children born to women who use serotonergic antidepressants during pregnancy have higher risk of neonatal seizures and epilepsy.

Methods: We used Swedish register-based data to examine associations between maternal-reported use of selective-serotonin reuptake inhibitor (SSRI) and selective serotonin-norepinephrine reuptake inhibitors (SNRI) in pregnancy and diagnosis of neonatal seizures and/or epilepsy in over 1.2 million children. To account for systematic differences between exposed and unexposed children we adjusted for a wide range of measured confounders. After first evaluating the role of maternal indication for SSRI/SNRI use (i.e., depression and anxiety) and parental epilepsy, we adjusted for remaining parental background factors (e.g., age, co-morbidities, education, and family socioeconomic indices) and pregnancy-specific characteristics (e.g., maternal use of other psychotropic medications and tobacco smoking in early pregnancy).

Results: Compared with all other children, children of women that reported use of SSRI/SNRI in pregnancy had an elevated risk of neonatal seizures and epilepsy (risk ratio [RR]=1.41, 95% confidence interval [CI]=1.03-1.94; hazard ratio [HR]=1.21, 95% CI=1.03-1.43 respectively). The estimates of association were attenuated by adjustment for maternal indications for SSRI/SNRI use (RR=1.30, 95% CI=0.94-1.79; HR = 1.13, 95% CI = 0.95-1.33), but not by additional adjustment for parental history of epilepsy. Full adjustment for all measured parental and pregnancy-specific factors resulted in substantial attenuation of the remaining associations (RR = 1.10, 95% CI = 0.79-1.53; HR = 0.96, 95% CI = 0.81-1.14).

Conclusions: The present study found no support for the concern that maternal SSRI/SNRI use in pregnancy increases children's risk for neonatal seizures or epilepsy.

Classification Of Evidence: This study provides Class II evidence that exposure to SSRI/SNRI's in the first trimester of pregnancy is not associated with an increased incidence of neo-natal seizures/epilepsy.
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http://dx.doi.org/10.1212/WNL.0000000000200516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9202527PMC
May 2022

Association Between Pharmacological Treatment of Attention-Deficit/Hyperactivity Disorder and Long-term Unemployment Among Working-Age Individuals in Sweden.

JAMA Netw Open 2022 04 1;5(4):e226815. Epub 2022 Apr 1.

School of Medical Sciences, Örebro University, Örebro, Sweden.

Importance: Adults with attention-deficit/hyperactivity disorder (ADHD) are at greater risk for unemployment. Pharmacological treatment is effective in reducing the core symptoms of ADHD, but whether it helps to reduce the unemployment rate among adult patients remains unclear.

Objective: To investigate the association between use of ADHD medication and long-term unemployment in working-age adults with ADHD.

Design, Setting, And Participants: Data for this population-based cohort study were extracted from Swedish national registers. Among 25 358 individuals with ADHD born from 1958 to 1978, 12 875 middle-aged adults among the workforce were included. The longitudinal cohort was followed up from January 1, 2008, to December 31, 2013. Data were analyzed from March 1, 2020, through May 31, 2021.

Exposures: Use of medication for ADHD during the previous 2 years was the main exposure, as both categorical and continuous variables.

Main Outcomes And Measures: Yearly accumulated unemployed days were derived from the Public Employment Service, and long-term unemployment was defined as 90 or more days of unemployment per year. Overall and sex-specific relative risks (RRs) with 95% CIs were estimated using generalized estimating equations.

Results: Among 12 875 individuals with ADHD (5343 women [41.50%] and 7532 men [58.50%]; mean [SD] age, 37.9 [5.6] years), the use of ADHD medications during the previous 2 years was associated with a 10% lower risk of long-term unemployment in the following year (adjusted RR, 0.90 [95% CI, 0.87-0.95]). An association between use of ADHD medications and long-term unemployment was found among women (RR, 0.82 [95% CI, 0.76-0.89]) but not men (RR, 0.96 [95% CI, 0.91-1.01]). Longer treatment duration was associated with a lower risk of subsequent long-term unemployment among women (RR for use of 1-6 months, 0.86 [95% CI, 0.78-0.95]; RR for use of 18-24 months, 0.72 [95% CI, 0.58-0.90]; P < .001 for trend). Within-individual comparisons showed that the long-term unemployment rate was lower during periods of ADHD medication treatment compared with nontreatment periods (RR, 0.89; 95% CI, 0.85-0.94).

Conclusions And Relevance: The findings of this cohort study suggest that the use of ADHD medication is associated with a lower risk of subsequent long-term unemployment for middle-aged women. These findings should be considered together with the existing knowledge of risks and benefits of ADHD medication when developing treatment plans for working-age adults.
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http://dx.doi.org/10.1001/jamanetworkopen.2022.6815DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047436PMC
April 2022

Childhood-onset versus adolescent-onset anxiety and depression: Epidemiological and neurodevelopmental aspects.

Psychiatry Res 2022 06 14;312:114556. Epub 2022 Apr 14.

Centre for Ethics, Law and Mental Health, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Gillberg Neuropsychiatry Centre, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.

Anxiety and depression are common in youth and are frequently accompanied by attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). However, it is unclear how common ADHD, ASD, and other neurodevelopmental disorders (NDDs, i.e., ADHD, ASD, developmental coordination disorder, learning disorder, and tic disorders) are in children versus adolescents with anxiety and depression. We aimed to delineate whether different anxiety/depression age-of-onset groups show distinguishable NDD patterns. The study was based on 4492 twins born in Sweden between 1998 and 2003 from the nation-wide population-based Child and Adolescent Twin Study in Sweden. Prevalence and odds ratios were calculated using screening measures of anxiety and depression at ages 9 and 15, and NDDs at age 9. Individuals with childhood-onset anxiety/depression had a substantially higher NDD prevalence compared to individuals with adolescent-onset anxiety/depression. Highest prevalence was found for individuals with anxiety/depression both in childhood and adolescence. In this group, individuals also had substantially higher odds of having at least one NDD (14.7, 95% CI 6.3 - 34.0) compared to individuals without anxiety/depression. This emphasizes the need to further investigate the etiology of childhood and adolescent anxiety/depression, as they most likely represent different constructs depending on age-of-onset, lending support for possibly different treatment approaches.
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http://dx.doi.org/10.1016/j.psychres.2022.114556DOI Listing
June 2022

Associations between mental and physical conditions in children and adolescents: An umbrella review.

Neurosci Biobehav Rev 2022 06 12;137:104662. Epub 2022 Apr 12.

Centre for Innovation in Mental Health, School of Psychology, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK; Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK; Solent NHS Trust, Southampton, UK; Division of Psychiatry and Applied Psychology, School of Medicine, University of Nottingham, Nottingham, UK; Hassenfeld Children's Hospital at NYU Langone, New York University Child Study Center, New York City, NY, US.

We mapped the evidence on the type and strength of associations between a broad range of mental and physical conditions in children and adolescents, by carrying out an umbrella review, i.e., a quantitative synthesis of previous systematic reviews and meta-analyses. We also assessed to which extent the links between mental and physical conditions vary across disorders or, by contrast, are transdiagnostic. Based on a pre-established protocol, we retained 45 systematic reviews/meta-analyses, encompassing around 12.5 million of participants. In analyses limited to the most rigorous estimates, we found evidence for the following associations: ADHD-asthma, ADHD-obesity, and depression-asthma. A transdiagnostic association was confirmed between asthma and anxiety/ASD/depression/bipolar disorder, between obesity and ADHD/ASD/depression, and between dermatitis and ASD/ADHD. We conclude that obesity and allergic conditions are likely to be associated with mental disorders in children and adolescents. Our results can help clinicians explore potential links between mental and physical conditions in children/adolescent and provide a road map for future studies aimed at shading light on the underlying factors.
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http://dx.doi.org/10.1016/j.neubiorev.2022.104662DOI Listing
June 2022

A neuroimaging study of interpersonal distance in identical and fraternal twins.

Hum Brain Mapp 2022 08 13;43(11):3508-3523. Epub 2022 Apr 13.

Department of Psychology and Social Work, Mid Sweden University, Östersund, Sweden.

Keeping appropriate interpersonal distance is an evolutionary conserved behavior that can be adapted based on learning. Detailed knowledge on how interpersonal space is represented in the brain and whether such representation is genetically influenced is lacking. We measured brain function using functional magnetic resonance imaging in 294 twins (71 monozygotic, 76 dizygotic pairs) performing a distance task where neural responses to human figures were compared to cylindrical blocks. Proximal viewing distance of human figures was compared to cylinders facilitated responses in the occipital face area (OFA) and the superficial part of the amygdala, which is consistent with these areas playing a role in monitoring interpersonal distance. Using the classic twin method, we observed a genetic influence on interpersonal distance related activation in the OFA, but not in the amygdala. Results suggest that genetic factors may influence interpersonal distance monitoring via the OFA whereas the amygdala may play a role in experience-dependent adjustments of interpersonal distance.
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http://dx.doi.org/10.1002/hbm.25864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9248319PMC
August 2022

The role of ADHD genetic risk in mid-to-late life somatic health conditions.

Transl Psychiatry 2022 04 11;12(1):152. Epub 2022 Apr 11.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Growing evidence suggests that ADHD, an early onset neurodevelopmental disorder, is associated with poor somatic health in adulthood. However, the mechanisms underlying these associations are poorly understood. Here, we tested whether ADHD polygenic risk scores (PRS) are associated with mid-to-late life somatic health in a general population sample. Furthermore, we explored whether potential associations were moderated and mediated by life-course risk factors. We derived ADHD-PRS in 10,645 Swedish twins born between 1911 and 1958. Sixteen cardiometabolic, autoimmune/inflammatory, and neurological health conditions were evaluated using self-report (age range at measure 42-88 years) and clinical diagnoses defined by International Classification of Diseases codes in national registers. We estimated associations of ADHD-PRS with somatic outcomes using generalized estimating equations, and tested moderation and mediation of these associations by four life-course risk factors (education level, body mass index [BMI], tobacco use, alcohol misuse). Results showed that higher ADHD-PRS were associated with increased risk of seven somatic outcomes (heart failure, cerebro- and peripheral vascular disease, obesity, type 1 diabetes, rheumatoid arthritis, and migraine) with odds ratios ranging 1.07 to 1.20. We observed significant mediation effects by education, BMI, tobacco use, and alcohol misuse, primarily for associations of ADHD-PRS with cardiometabolic outcomes. No moderation effects survived multiple testing correction. Our findings suggests that higher ADHD genetic liability confers a modest risk increase for several somatic health problems in mid-to-late life, particularly in the cardiometabolic domain. These associations were observable in the general population, even in the absence of medical treatment for ADHD, and appear to be in part mediated by life-course risk factors.
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http://dx.doi.org/10.1038/s41398-022-01919-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8995388PMC
April 2022

Validity of eating disorder diagnoses in the Swedish national patient register.

J Psychiatr Res 2022 06 4;150:227-230. Epub 2022 Apr 4.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Nobels Väg 12A, 171 77, Stockholm, Sweden.

The Swedish National Patient Register (NPR) includes population-level longitudinal data, and determining the validity of NPR diagnoses is critical to undergirding the research and policy recommendations they inform. Sweden also has the integrated "Riksät" and "Stepwise" National Quality Registers (QR), with data from specialized eating disorder (ED) treatment based on structured, valid assessment methods. To validate NPR ED diagnoses, we compared ICD-10-based anorexia nervosa (AN), bulimia nervosa (BN), and unspecified ED in NPR to DSM-IV-based AN, BN, and ED not otherwise specified category (EDNOS) in QR. Patients' first diagnoses registered in QR between February 2008 and August 2013 were compared with NPR diagnoses entered within ±1 month (N = 2074). QR registration includes the semi-structured DSM-IV-based Structured ED Interview. Each ED diagnosis was analyzed separately for degree of match using several indices: overall agreement, sensitivity, positive predictive value, specificity, negative predictive value, area under the curve, and Cohen's kappa. Results showed moderate to excellent agreement depending on estimate (e.g. positive predictive values AN: 0.747; BN:.836; EDNOS: 0.761), except for a somewhat low sensitivity for BN, and EDNOS agreement was overall the lowest. Case prevalence in the NPR and QR was highly similar for AN, and within five percentage points for BN and EDNOS. Generalizability is hampered by limited age range and diagnostic resolution as well as few males. Available data precluded study of presence/absence of ED, and complementary approaches are considered for future research. We conclude that NPR ED diagnoses have acceptable validity and are appropriate for use in research.
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http://dx.doi.org/10.1016/j.jpsychires.2022.03.064DOI Listing
June 2022

The impact of educational attainment, intelligence and intellectual disability on schizophrenia: a Swedish population-based register and genetic study.

Mol Psychiatry 2022 May 5;27(5):2439-2447. Epub 2022 Apr 5.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

Schizophrenia (SCZ) is highly heterogenous and no subtypes characterizing treatment response or longitudinal course well. Cognitive impairment is a core clinical feature of SCZ and a determinant of poorer outcome. Genetic overlap between SCZ and cognitive traits is complex, with limited studies of comprehensive epidemiological and genomic evidence. To examine the relation between SCZ and three cognitive traits, educational attainment (EDU), premorbid cognitive ability, and intellectual disability (ID), we used two Swedish samples: a national cohort (14,230 SCZ cases and 3,816,264 controls) and a subsample with comprehensive genetic data (4992 cases and 6009 controls). Population-based analyses confirmed worse cognition as a risk factor for SCZ, and the pedigree and SNP-based genetic correlations were comparable. In the genotyped cases, those with high EDU and premorbid cognitive ability tended to have higher polygenetic risk scores (PRS) of EDU and intelligence and fewer rare exonic variants. Finally, by applying an empirical clustering method, we dissected SCZ cases into four replicable subgroups characterized by EDU and ID. In particular, the subgroup with higher EDU in the national cohort had fewer adverse outcomes including long hospitalization and death. In the genotyped subsample, this subgroup had higher PRS of EDU and no excess of rare genetic burdens than controls. In conclusion, we found extensive evidence of a robust relation between cognitive traits and SCZ, underscoring the importance of cognition in dissecting the heterogeneity of SCZ.
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http://dx.doi.org/10.1038/s41380-022-01500-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135619PMC
May 2022

Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms.

J Am Acad Child Adolesc Psychiatry 2022 Jul 1;61(7):934-945. Epub 2022 Apr 1.

Institute for Behavioral Genetics, University of Colorado Boulder.

Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence.

Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument.

Results: The meta-analysis of overall internalizing symptoms (INT) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, n = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|r| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |r| = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa.

Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success.
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http://dx.doi.org/10.1016/j.jaac.2021.11.035DOI Listing
July 2022

Prenatal exposure to benzodiazepines and Z-drugs in humans and risk of adverse neurodevelopmental outcomes in offspring: A systematic review.

Neurosci Biobehav Rev 2022 06 1;137:104647. Epub 2022 Apr 1.

Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.

When used during pregnancy, benzodiazepines (BZDs) and related z-drugs could pass readily through the placenta and the foetal blood-brain barrier, where they can bind to γ-amino butyric acid (GABA) receptors in the developing foetal brain. Yet, data on long-term safety of prenatal BZD and z-drug use and its impact on offspring neurodevelopment are inconclusive. In this systematic review, we qualitatively synthetize the existing evidence on maternal exposure to various BZDs and z-drugs during pregnancy and offspring cognitive, emotional, behavioural, and motor skills developmental outcomes. Nineteen studies were included. We used harvest plots to visualize the directions of reported associations. Despite several associations between distinct types of BZDs and z-drugs and an increased risk of outcomes within different neurodevelopmental domains were observed, a remarkable scarcity of overall research on the topic and considerable discrepancies in methodology, particularly towards controlling for confounding by indication, precluded drawing conclusions with a reasonable degree of certainty. We outline various research strategies to mitigate methodological limitations and provide directions for future empirical studies on the topic.
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http://dx.doi.org/10.1016/j.neubiorev.2022.104647DOI Listing
June 2022

Internalizing symptoms in adolescence are modestly affected by symptoms of anxiety, depression, and neurodevelopmental disorders in childhood.

BMC Psychiatry 2022 04 1;22(1):233. Epub 2022 Apr 1.

Centre for Ethics, Law and Mental Health (CELAM), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Background: Internalizing disorders, such as anxiety and depressive disorders, are common mental disorders in young people, but a detailed understanding of the symptom continuity from childhood to adolescence that additionally includes a variety of neurodevelopmental disorder (NDD) symptoms is lacking. We therefore aimed to assess the extent to which parent-reported anxiety, depression, and NDD symptoms in childhood predict parent-reported internalizing symptoms in adolescence.

Methods: We used the nation-wide population-based Child and Adolescent Twin Study in Sweden, comprising 4492 twins born in Sweden between 1998 and 2003 that were assessed at age 9, and then again at age 15. Linear regression in a structural equation modelling framework was used to analyze the data.

Results: Overall, our results indicate that 15.9% of the variance in internalizing symptoms at age 15 can be predicted by anxiety, depression, and NDD symptoms at age 9. Anxiety and NDD symptoms in childhood predicted the largest amount of internalizing symptoms in adolescence.

Conclusions: Adolescent internalizing symptoms are modestly affected by childhood symptoms of anxiety, depression, and NDDs, suggesting that they may represent different constructs across age. Future studies should further empirically investigate differences in etiology and trajectories of childhood versus adolescent internalizing symptoms.
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http://dx.doi.org/10.1186/s12888-022-03875-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8976364PMC
April 2022

Association of Tourette Syndrome and Chronic Tic Disorder With Violent Assault and Criminal Convictions.

JAMA Neurol 2022 05;79(5):459-467

Institute of Criminology and Legal Policy, University of Helsinki, Helsinki, Finland.

Importance: Tic disorders are associated with multiple social adversities, but little is known about the experience of violent assault (including sexual assault) and criminality in this group.

Objective: To establish if Tourette syndrome (TS) and chronic tic disorder (CTD) are associated with an increased risk of experiencing violent assault and criminal convictions.

Design, Setting, And Participants: In this cohort study, all individuals living in Sweden at any time between January 1, 1973, and December 31, 2013, were identified from Swedish nationwide health and administrative registers. Cox proportional hazards regression models were used to estimate the risk of violent assault and criminal convictions among people with TS or CTD, compared with the general population and unaffected full siblings. Data analyses were conducted between September 1 and October 22, 2021.

Exposures: The Swedish version of the International Classification of Diseases, Eighth Revision (ICD-8), ICD-9, and ICD-10 diagnoses of TS or CTD in the Swedish National Patient Register.

Main Outcomes And Measures: Records of sexual and nonsexual violent assault and death due to violent assaults were obtained from the National Patient Register and the Cause of Death Register, respectively. Convictions for violent and nonviolent criminal offenses were obtained from the Crime Register. Covariates included sex and birth year.

Results: The study cohort included 13 819 284 individuals living in Sweden between 1973 and 2013. A total of 7791 individuals with TS or CTD were identified (median [IQR] age at first diagnosis, 13.4 [10.0-21.8] years; 5944 [76%] male). Compared with unaffected individuals from the general population, people with TS or CTD had a 2-fold increased risk of experiencing any violent assault (sexual and nonsexual) (adjusted hazard ratio [aHR], 2.21; 95% CI, 2.00-2.43), a 3-fold increased risk of violent convictions (aHR, 3.13; 95% CI, 2.92-3.36), and a 1.6-fold increased risk of nonviolent crime convictions (aHR, 1.62; 95% CI, 1.54-1.71). Among people with TS or CTD, 37.0% (114 of 308; 95% CI, 31.6%-42.4%) of individuals who had experienced violent assault also had a violent crime conviction, compared with 17.9% (16 067 of 89 920; 95% CI, 17.6%-18.1%) in the general population. Exclusion of individuals with attention-deficit/hyperactivity disorder and substance use disorders partially attenuated the associations. Similarly, within-sibling models attenuated but did not eliminate the associations (any violent assault: aHR, 1.32; 95% CI, 1.08-1.61; violent crime: aHR, 2.23; 95% CI, 1.86-2.67; nonviolent crime: aHR, 1.34; 95% CI, 1.20-1.50).

Conclusions And Relevance: Results of this cohort study suggest that most individuals with TS or CTD are not assaulted nor are perpetrators of crime. However, individuals with TS or CTD diagnosed in specialist settings were more likely to both experience violent assault and be perpetrators of violence compared with the general population. The risk was highest in individuals with comorbid attention-deficit/hyperactivity disorder and substance use disorders. The increased risk found in specialty clinics will need to be better understood in the general population.
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http://dx.doi.org/10.1001/jamaneurol.2022.0167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938899PMC
May 2022

Borderline personality disorder: associations with psychiatric disorders, somatic illnesses, trauma, and adverse behaviors.

Mol Psychiatry 2022 May 18;27(5):2514-2521. Epub 2022 Mar 18.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Solna, Sweden.

In one of the largest, most comprehensive studies on borderline personality disorder (BPD) to date, this article places into context associations between this diagnosis and (1) 16 different psychiatric disorders, (2) eight somatic illnesses, and (3) six trauma and adverse behaviors, e.g., violent crime victimization and self-harm. Second, it examines the sex differences in individuals with BPD and their siblings. A total of 1,969,839 Swedish individuals were identified from national registers. Cumulative incidence with 95% confidence intervals (CI) was evaluated after 5 years of follow-up from BPD diagnosis and compared with a matched cohort. Associations were estimated as hazard ratios (HR) with 95% CIs from Cox regression. 12,175 individuals were diagnosed with BPD (85.3% female). Individuals diagnosed with BPD had higher cumulative incidences and HRs for nearly all analyzed indicators, especially psychiatric disorders. Anxiety disorders were most common (cumulative incidence 95% CI 33.13% [31.48-34.73]). Other notable findings from Cox regressions include psychotic disorders (HR 95% CI 24.48 [23.14-25.90]), epilepsy (3.38 [3.08-3.70]), violent crime victimization (7.65 [7.25-8.06]), and self-harm (17.72 [17.27-18.19]). HRs in males and females with BPD had overlapping CIs for nearly all indicators. This indicates that a BPD diagnosis is a marker of vulnerability for negative events and poor physical and mental health similarly for both males and females. Having a sibling with BPD was associated with an increased risk for psychiatric disorders, trauma, and adverse behaviors but not somatic disorders. Clinical implications include the need for increased support for patients with BPD navigating the health care system.
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http://dx.doi.org/10.1038/s41380-022-01503-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9135625PMC
May 2022
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