Neurodevelopmental disorders and subsequent risk of violent victimization: exploring sex differences and mechanisms

Abstract Background Neurodevelopmental disorders (NDs) are associated with experiences of victimization, but mechanisms remain unclear. We explored sex differences and the role of familial factors and externalizing problems in the association between several NDs and violent victimization in adolescence and young adulthood. Methods Individuals born in Sweden 1985–1997, residing in Sweden at their 15th birthday, were followed until date of violent victimization causing a hospital visit or death, death due to other causes, emigration, or December 31, 2013, whichever came first. The exposures were diagnoses of attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), intellectual disability (ID) and other NDs. We used three different Cox regression models: a crude model, a model adjusted for familial confounding using sibling-comparisons, and a model additionally adjusted for externalizing problems. Results Among 1 344 944 individuals followed, on average, for 5 years, 74 487 were diagnosed with NDs and 37 765 had a hospital visit or died due to violence. ADHD was associated with an increased risk of violent victimization in males [hazard ratio (HR) 2.56; 95% confidence interval (CI) 2.43–2.70) and females (HR 5.39; 95% CI 4.97–5.85). ASD and ID were associated with an increased risk of violent victimization in females only. After adjusting for familial factors and externalizing problems, only ADHD was associated with violent victimization among males (HR 1.27; 95% CI 1.06–1.51) and females (HR 1.69; 95% CI 1.21–2.36). Conclusions Females with NDs and males with ADHD are at greater risk of being victim of severe violence during adolescence and young adulthood. Relevant mechanisms include shared familial liability and externalizing problems. ADHD may be independently associated with violent victimization.

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Actionable and incidental neuroradiological findings in twins with neurodevelopmental disorders

Scientific Reports ◽

10.1038/s41598-020-79959-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Lynnea Myers ◽

Mai-Lan Ho ◽

Elodie Cauvet ◽

Karl Lundin ◽

Torkel Carlsson ◽

...

Keyword(s):

Neurodevelopmental Disorders ◽

Copy Number Variants ◽

Cross Sectional Study ◽

Autism Spectrum ◽

Molecular Signaling ◽

Mri Findings ◽

Cross Sectional ◽

Increased Risk ◽

Magnetic Resonance Imaging Mri ◽

Morphological Variants

AbstractWhile previous research has investigated neuroradiological findings in autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD), the entire range of neurodevelopmental disorders (NDDs) has not yet been well-studied using magnetic resonance imaging (MRI). Considering the overlap among NDDs and simultaneous development of the brain and face, guided by molecular signaling, we examined the relationship of actionable and incidental (non-actionable) MRI findings and NDD diagnoses together with facial morphological variants and genetic copy number variants (CNVs). A cross-sectional study was conducted with a twin cohort 8–36 years of age (57% monozygotic, 40% dizygotic), including 372 subjects (46% with NDDs; 47% female) imaged by MRI, 280 with data for facial morphological variants, and 183 for CNVs. Fifty-one percent of participants had MRI findings. Males had a statistically significantly higher percentage of MRI findings (57.7%) compared with females (43.8%, p = 0.03). Twin zygosity was not statistically significantly correlated with incidence or severity of specific MRI findings. No statistically significant association was found between MRI findings and any NDD diagnosis or facial morphological variants; however, MRI findings were statistically significantly associated with the number of CNVs (OR 1.20, 95% CI 1.00–1.44, p = 0.05, adjusted OR for sex 1.24, 95% CI 1.03–1.50, p = 0.02). When combining the presence of MRI findings, facial morphological variants, and CNVs, statistically significant relationships were found with ASD and ADHD diagnoses (p = 0.0006 and p = 0.002, respectively). The results of this study demonstrate that the ability to identify NDDs from combined radiology, morphology, and CNV assessments may be possible. Additionally, twins do not appear to be at increased risk for neuroradiological variants.

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O-076 Neurodevelopmental morbidity in children born after ART: a Nordic register study from the Committee of Nordic ART and Safety (CoNARTaS) group

Human Reproduction ◽

10.1093/humrep/deab125.006 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

K Rönö ◽

E Rissanen ◽

C Bergh ◽

U B Wennerholm ◽

S Opdahl ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Young Adulthood ◽

Neurodevelopmental Disorders ◽

Cox Regression ◽

Conduct Disorders ◽

Autism Spectrum ◽

Motor Functioning ◽

Icd 10 ◽

Spectrum Disorders

Abstract Study question Does the risk of neurodevelopmental disorders differ between singletons born after various assisted reproductive techniques (ART) and spontaneous conception (SC) until young adulthood? Summary answer ART children had a slightly increased rate of learning and motor functioning disorders, autism spectrum disorders (ASD), and ADHD and conduct disorders. What is known already Studies on the impact of ART on offspring have reported both increased risk and comparable incidences of neurodevelopmental disorders between ART and SC offspring. The most studied neurodevelopmental disorders with ART are autism spectrum disorders (ASD.) There is, however, no consensus on the risk of ASD for ART children. The risk for other neurodevelopmental disorders, like attention-deficit hyperactivity disorders (ADHD) or tic disorder among ART children, is also a debated issue, as studies are scarce. Study design, size, duration A Nordic register-based cohort study including all singleton live births (N = 5 076 444) after ART (n = 116 909) or SC (n = 4 959 535) between 1995 and 2014 in Denmark and Finland, 1995 and 2015 in Sweden; and 2005 and 2015 in Norway. Children with intellectual disability (ICD-10: F70-F79) are excluded. The children are followed up to young adulthood (the year 2014 in Denmark and Finland, and 2015 in Norway and Sweden). Participants/materials, setting, methods Offspring outcomes were defined as following ICD-10 diagnoses: learning and motor functioning disorders (F80-83), ASD (F84), ADHD and conduct disorders (F90-F92), and tic disorders/Tourette (F95). We calculated crude and adjusted hazard ratios (HR) for neurodevelopmental diagnoses using Cox regression. Adjustments were made for the country, maternal age at the delivery, parity, smoking, and maternal psychiatric morbidity. Main results and the role of chance The cumulative incidences of neurodevelopmental disorders in the cohort were 1.74% for F90-F92, 1.40% for F80-83, 0.66% for F84, and 0.22% for F95. In crude Cox-regression ART children had an increased likelihood during the follow-up of being diagnosed with F84 (HR 1.12 [95% CI 1.04-1.21]) and F95 (HR 1.21 [95% CI 1.06-1.38]), but not with F80-83 (HR 1.01 [95% CI 0.96-1.07]) or F90-92 (HR 0.82 [95% CI 0.77-0.86]). After adjustments the likelihood was increased for F80-83 (HR 1.20 [95% CI 1.13-1.27]), F84 (HR 1.12 [95% CI 1.03-1.24]), and F90-92 (HR 1.09 [95% CI 1.04-1.19]), but nor for F95 (HR 1.13 [95% CI 0.99-1.30]). After adjustments, intracytoplasmic sperm injection children compared with in vitro fertilization children had similar likelihood during follow-up for F80-83 (1.06 [95% CI 0.89–1.25]), for F84 (HR 0.92 [95% CI 0.76–1.11]), for F90-92 (HR 0.96 [95% CI 0.83–1.12]), and for F95 (HR 1.16 [95% CI 0.83–1.63]). After adjustments, frozen embryo transfer children compared with fresh embryo transfer children had similar likelihood during follow-up for F80-83 (HR 1.11 [95% CI 0.90–1.37]), F84 (HR 0.98 [95% CI 0.76–1.27]), F90-92 (HR 0.96 [95% CI 0.78–1.19]), and F95 (HR 0.83 [95% CI 0.51–1.35]). Limitations, reasons for caution There may be residual confounding by unknown or unmeasured confounders. We lack information on possible confounders like the reason and length of infertility, maternal substance use other than self-reported smoking status, paternal age, and parental somatic morbidity. Additional limitations are differences in registration practice and data availability between study countries. Wider implications of the findings This is the largest singleton cohort and the first multinational study on the risk for neurodevelopmental disorders among ART children. While the rate of some neurodevelopmental disorders was increased among ART children, the absolute risk was moderate. The type of ART did not associate with the incidence of neurodevelopmental disorders. Trial registration number ISRCTN11780826

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Attention-deficit/hyperactivity disorder and risk for psychiatric and neurodevelopmental disorders in siblings

Psychological Medicine ◽

10.1017/s0033291718000521 ◽

2018 ◽

Vol 49 (1) ◽

pp. 84-91 ◽

Cited By ~ 4

Author(s):

Elina Jokiranta-Olkoniemi ◽

Keely Cheslack-Postava ◽

Petteri Joelsson ◽

Auli Suominen ◽

Alan S. Brown ◽

...

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Attention Deficit ◽

Neurodevelopmental Disorders ◽

Neurodevelopmental Disorder ◽

Population Based ◽

Autism Spectrum ◽

Schizophrenia Spectrum Disorders ◽

Hyperactivity Disorder ◽

Increased Risk ◽

Spectrum Disorders

AbstractBackgroundProbands with attention-deficit/hyperactivity disorder (ADHD) are at increased risk for several psychiatric and neurodevelopmental disorders. The risk of these disorders among the siblings of probands has not been thoroughly assessed in a population-based cohort.MethodsEvery child born in Finland in 1991–2005 and diagnosed with ADHD in 1995–2011 were identified from national registers. Each case was matched with four controls on sex, place, and date of birth. The full siblings of the cases and controls were born in 1981–2007 and diagnosed in 1981–2013. In total, 7369 cases with 12 565 siblings and 23 181 controls with 42 753 siblings were included in the analyses conducted using generalized estimating equations.Results44.2% of the cases and 22.2% of the controls had at least one sibling diagnosed with any psychiatric or neurodevelopmental disorder (risk ratio, RR = 2.1; 95% CI 2.0–2.2). The strongest associations were demonstrated for childhood-onset disorders including ADHD (RR = 5.7; 95% CI 5.1–6.3), conduct and oppositional disorders (RR = 4.0; 95% CI 3.5–4.5), autism spectrum disorders (RR = 3.9; 95% CI 3.3–4.6), other emotional and social interaction disorders (RR = 2.7; 95% CI 2.4–3.1), learning and coordination disorders (RR = 2.6; 95% CI 2.4–2.8), and intellectual disability (RR = 2.4; 95% CI 2.0–2.8). Also, bipolar disorder, unipolar mood disorders, schizophrenia spectrum disorders, other neurotic and personality disorders, substance abuse disorders, and anxiety disorders occurred at increased frequency among the siblings of cases.ConclusionsThe results offer potential utility for early identification of neurodevelopmental and psychiatric disorders in at-risk siblings of ADHD probands and also argue for more studies on common etiologies.

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Intrauterine Viral Infections: Impact of Inflammation on Fetal Neurodevelopment

Frontiers in Neuroscience ◽

10.3389/fnins.2021.771557 ◽

2021 ◽

Vol 15 ◽

Author(s):

Sourav Ganguli ◽

Pavithra L. Chavali

Keyword(s):

Neurodevelopmental Disorders ◽

Viral Infections ◽

Inflammatory Responses ◽

Fetal Brain ◽

Preterm Births ◽

Autism Spectrum ◽

Future Research ◽

Increased Risk ◽

Mechanistic Basis ◽

Simplex Virus

Intrauterine viral infections during pregnancy by pathogens such as Zika virus, Cytomegalovirus, Rubella and Herpes Simplex virus can lead to prenatal as well as postnatal neurodevelopmental disorders. Although maternal viral infections are common during pregnancy, viruses rarely penetrate the trophoblast. When they do cross, viruses can cause adverse congenital health conditions for the fetus. In this context, maternal inflammatory responses to these neurotropic pathogens play a significant role in negatively affecting neurodevelopment. For instance, intrauterine inflammation poses an increased risk of neurodevelopmental disorders such as microcephaly, schizophrenia, autism spectrum disorder, cerebral palsy and epilepsy. Severe inflammatory responses have been linked to stillbirths, preterm births, abortions and microcephaly. In this review, we discuss the mechanistic basis of how immune system shapes the landscape of the brain and how different neurotropic viral pathogens evoke inflammatory responses. Finally, we list the consequences of neuroinflammation on fetal brain development and discuss directions for future research and intervention strategies.

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Risk Factors for Behavioral and Emotional Difficulties in Siblings of Children With Autism Spectrum Disorder

American Journal on Intellectual and Developmental Disabilities ◽

10.1352/1944-7558-121.6.533 ◽

2016 ◽

Vol 121 (6) ◽

pp. 533-549 ◽

Cited By ~ 11

Author(s):

Katherine M. Walton

Keyword(s):

Risk Factors ◽

Externalizing Problems ◽

Family Income ◽

Emotional Problems ◽

Children With Autism ◽

Autism Spectrum ◽

Behavioral And Emotional Problems ◽

Internalizing And Externalizing Problems ◽

Increased Risk ◽

Internalizing And Externalizing

Abstract This study examined risk factors for behavioral and emotional problems in 1973 siblings of children with autism spectrum disorders (ASD). Results revealed six correlates of sibling internalizing and externalizing problems: male gender, smaller family size, older age of the child with ASD, lower family income, child with ASD behavior problems, and sibling Broader Autism Phenotype. Siblings with few risk factors were at low risk for behavioral and emotional problems. However, siblings with many risk factors were at increased risk for both internalizing and externalizing problems. These results highlight the need to assess risk for individual siblings to best identify a sub-population of siblings who may be in need of additional support.

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Higher weight in adolescence and young adulthood is associated with an earlier age at multiple sclerosis onset

Multiple Sclerosis Journal ◽

10.1177/1352458514555787 ◽

2014 ◽

Vol 21 (7) ◽

pp. 858-865 ◽

Cited By ~ 38

Author(s):

Katelyn S Kavak ◽

Barbara E Teter ◽

Jesper Hagemeier ◽

Karen Zakalik ◽

Bianca Weinstock-Guttman ◽

...

Keyword(s):

Multiple Sclerosis ◽

Young Adulthood ◽

Symptom Onset ◽

Age At Onset ◽

Early Adulthood ◽

New York State ◽

Disease Onset ◽

Future Research ◽

Increased Risk ◽

Adolescence And Young Adulthood

Background: Growing evidence suggests an association between adolescent obesity and increased risk of multiple sclerosis (MS). Objective: The objective of this paper is to investigate whether weight or body mass index (BMI) in adolescence and young adulthood was associated with age at MS symptom onset. Methods: Our cohort is comprised of a sub-group of 184 women enrolled in the New York State MS Consortium registry. Individuals were asked to recall their weight at the time of first menstruation and at age 25. BMI was calculated accordingly for age 25. Regression analyses were carried out to investigate the association between weight or BMI and age at onset. Results: Weight at menarche was significantly related to younger age at symptom onset (β = −0.073, p = 0.001). These results were also found at age 25 for weight (β = −0.080, p < 0.001) and BMI (β = −0.448, p = 0.001). Significantly earlier disease onset (26.9 years ±9.9) was observed in individuals who were overweight at 25 compared to those who were not overweight (32.1 years ±9.2, p = 0.006). Conclusions: Women who reported higher weight in adolescence and BMI in early adulthood were younger at MS onset. Future research should investigate whether there is a causal link between body weight and MS, as prevention lifestyle and dietary interventions could be implemented.

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Hypertensive disorders of pregnancy and risk of neurodevelopmental disorders in the offspring: a systematic review and meta-analysis protocol

BMJ Open ◽

10.1136/bmjopen-2017-018313 ◽

2017 ◽

Vol 7 (10) ◽

pp. e018313 ◽

Cited By ~ 8

Author(s):

Gillian M Maher ◽

Gerard W O’Keeffe ◽

Louise C Kenny ◽

Patricia M Kearney ◽

Ted G Dinan ◽

...

Keyword(s):

Systematic Review ◽

Neurodevelopmental Disorders ◽

Meta Analysis ◽

Autism Spectrum ◽

Chronic Hypertension ◽

Hypertensive Disorders Of Pregnancy ◽

Hypertensive Disorders ◽

Increased Risk ◽

Meta Analyses ◽

The Impact

IntroductionHypertensive disorders of pregnancy (HDPs), that is chronic hypertension, gestational hypertension, pre-eclampsia (de novo or superimposed on chronic hypertension) and white coat hypertension, affect approximately 5%–15% of pregnancies. HDP exposure has been linked to an increased risk of autism spectrum disorder, attention deficit/hyperactivity disorder and other neurodevelopmental disorders in children. However, findings are inconsistent, and a clear consensus on the impact of HDPs on the risk of neurodevelopmental disorders is needed. Therefore, we aim to synthesise the published literature on the relationship between HDPs and the risk of neurodevelopmental disorders in the form of a systematic review and meta-analysis.Methods and analysisWe will include cohort, case–control and cross-sectional studies in which diagnosis of an HDP was reported, and neurodevelopmental disorders were the outcome of interest based on a preprepared protocol. A systematic search of PubMed, CINAHL, Embase, PsycINFO and Web of Science will be conducted in accordance with a detailed search strategy. Two authors will independently review the titles and abstracts of all studies, perform data extraction using a standardised data collection form and assess study quality using a bias classification tool. Meta-analyses will be performed to calculate overall pooled estimates using the generic inverse variance method. This systematic review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses.Ethics and disseminationThis proposed systematic review and meta-analysis is based on published data, therefore, does not require ethics approval. Findings will be presented at scientific conferences and disseminated through publication in a peer-reviewed journal.RegistrationCRD42017068258.

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What’s the Link Between Theory of Mind and Other Cognitive Abilities – A Co-twin Control Design of Neurodevelopmental Disorders

Frontiers in Psychology ◽

10.3389/fpsyg.2021.575100 ◽

2021 ◽

Vol 12 ◽

Author(s):

Johan Isaksson ◽

Janina Neufeld ◽

Sven Bölte

Keyword(s):

Theory Of Mind ◽

Cognitive Functions ◽

Neurodevelopmental Disorders ◽

Control Design ◽

Mental States ◽

Autism Spectrum ◽

Central Coherence ◽

Shared Environment ◽

Core Element ◽

Familial Factors

Theory of mind (ToM), or the ability to attribute mental states to oneself and others, is a core element of social cognition (SC). Even though its importance for social functioning in general, and neurodevelopmental disorders (NDDs), in particular, is well established, the links between ToM and other cognitive functions are not. Especially the familial underpinnings of such links remain unclear. Using a co-twin control design, we examined N = 311 twins (mean age M = 17.19 years, 47% females) diagnosed with autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), other NDDs, or typically developing individuals. We used the Reading the Mind in the Eyes Test to operationalize ToM, the Fragmented Pictures Test for central coherence (CC), the Tower Test for executive functioning (EF), and the general ability index in the Wechsler Intelligence Scales for IQ. In the linear regressions, weak CC and a lower IQ were associated with a reduced ToM ability across pairs. Female sex and higher age were robustly associated with increased ToM ability, whereas EF was not associated with ToM. In the within-pair analyses, where unmeasured familial confounders are implicitly adjusted, the associations between ToM and other cognitive functions, were attenuated and the association with CC was non-significant. The result suggests that familial factors shared by the twins, such as genetic and shared environment, influence the association between CC, IQ, and ToM. Future studies need to include a larger sample of monozygotic twins, who are genetically identical, in order to draw more firm conclusions regarding the influence of familial factors, and to differentiate between shared environmental and genetic effects on the associations between cognitive functions.

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Attention-deficit/hyperactivity disorder and clinically diagnosed obesity in adolescence and young adulthood: a register-based study in Sweden

Psychological Medicine ◽

10.1017/s0033291718002532 ◽

2018 ◽

Vol 49 (11) ◽

pp. 1841-1849 ◽

Cited By ~ 9

Author(s):

Qi Chen ◽

Catharina A. Hartman ◽

Ralf Kuja-Halkola ◽

Stephen V. Faraone ◽

Catarina Almqvist ◽

...

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Genetic Correlation ◽

Young Adulthood ◽

Attention Deficit ◽

Genetic Relatedness ◽

High Body Mass Index ◽

Hyperactivity Disorder ◽

A Genome ◽

Increased Risk ◽

Adolescence And Young Adulthood

AbstractBackgroundA recent family study of young adult males suggests a shared familial liability between attention-deficit/hyperactivity disorder (ADHD) and high body mass index (BMI), and a genome-wide meta-analysis reported a genetic correlation of 0.26 between ADHD and BMI. To date, it is unclear whether these findings generalize to the relationship between ADHD and clinically diagnosed obesity.MethodBy linking the Swedish national registers, we identified 25 38 127 individuals born between 1973 and 2000, together with their siblings and cousins. The risk of clinical obesity in individuals with ADHD was compared with the risk in those without ADHD. The relative contributions of genetic and environmental factors to the association between ADHD and clinical obesity were examined via assessment of the familial co-aggregation of the two conditions and quantitative genetic analysis.ResultsIndividuals with ADHD were at an increased risk of clinical obesity compared with those without (risk difference 3.73%, 95% confidence interval (CI) 3.55–3.90%; risk ratio 3.05, 95% CI 2.95–3.15). Familial co-aggregation of ADHD and clinical obesity was detected and the strength of the co-aggregation decreased by decreasing genetic relatedness. The correlation between the liabilities to ADHD and clinical obesity can be entirely attributed to their genetic correlation (rg 0.30, 95% CI 0.17–0.44).ConclusionThe association between ADHD and clinical obesity in adolescence and young adulthood can be entirely attributed to genetic underpinnings shared by the two conditions. Children with ADHD should be monitored for weight gain so that preventive measures can be taken for those on a suboptimal trajectory.

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The association between gestational diabetes and ASD and ADHD: a systematic review and meta-analysis

Scientific Reports ◽

10.1038/s41598-021-84573-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jennifer Rowland ◽

Claire A. Wilson

Keyword(s):

Gestational Diabetes ◽

Neurodevelopmental Disorders ◽

Data Extraction ◽

Meta Analysis ◽

Maternal Diabetes ◽

Autism Spectrum ◽

Cochrane Library ◽

Hyperactivity Disorder ◽

Increased Risk ◽

Specific Association

AbstractThere is growing evidence for a role of maternal diabetes in the pathogenesis of neurodevelopmental disorders. However, the specific association between gestational diabetes (GDM), as opposed to pre-gestational diabetes, has been poorly isolated. Thus the aim was to systematically review and meta-analyse literature pertaining to prevalence and risk for two neurodevelopmental disorders: autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), when exposed to GDM. PubMed, Cochrane Library, EMBASE, PsycINFO and CINAHL were systematically searched for eligible literature, with forward and backward citation tracking. Screening for eligibility, risk of bias assessment and data extraction were performed by two independent reviewers. 18 studies measuring ASD and 15 measuring ADHD met inclusion criteria. On meta-analysis there was an increased risk of ASD (OR 1.42; 95% CI 1.22, 1.65) but not ADHD (OR 1.01; 95% CI 0.79, 1.28). We discuss potential mechanisms for these differing risks. Greater understanding of risk factors, including GDM, for these neurodevelopmental disorders and potential mechanisms may help inform strategies aimed at prevention of exposure to these adversities during pregnancy.

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