Measuring autism-associated traits in the general population: Factor structure and measurement invariance across sex and diagnosis status of the Social Communication Questionnaire.

Using questionnaires in research relies on the expectation that they measure the same things across different groups of individuals. If this is not true, then interpretations of results can be misleading when researchers compare responses across different groups of individuals or use in it a group that differs from that in which the questionnaire was developed. For the questionnaire we investigated, the Social Communication Questionnaire (SCQ), we found that parents of boys and girls responded to questionnaire items in largely the same way but that the SCQ measured traits and behaviors slightly differently depending on whether the children had autism. Based on these results, we concluded that researchers using this questionnaire should carefully consider these differences when deciding how to interpret findings. SCQ scores as a reflection of autism-associated traits in samples that are mostly or entirely made up of individuals without an autism diagnosis may be misleading and we encourage a more precise interpretation of scores as a broader indication of social-communicative and behavioral traits

Risk of attention-deficit hyperactivity disorder in offspring of mothers with infections during pregnancy

Background Maternal infections during pregnancy are common events that have been suggested to be risk factors for Attention-deficit hyperactivity disorder (ADHD) in offspring. Only a few studies have been conducted to date and results are conflicting. The current study investigates the associations between specific groups of prenatal maternal infections and offspring ADHD, considering timing of exposure and the role of fever. Methods We used data from the prospective Norwegian Mother, Father and Child Cohort Study (MoBa), including more than 112,000 pregnancies, linked with data from the Medical Birth Registry of Norway and the Norwegian Patient Registry to estimate odds ratios for the likelihood that children develop ADHD after being exposed to maternal infections during gestation. Results Children exposed to any maternal infection during pregnancy showed increased risk of receiving an ADHD diagnosis (OR = 1.15, CI = 1.03–1.27). Specifically, increased ADHD risk was observed after exposure to genitourinary infections in second (OR = 1.42, CI = 1.06–1.90) or third trimester (OR = 2.04, CI = 1.19–3.49), and to respiratory infections in second trimester (OR = 1.31, CI = 1.12–1.54), provided these infections were accompanied by episodes of fever. Increased ADHD risk was also observed after exposure to diarrhea without fever in the third trimester (OR = 1.25, CI = 1.07–1.46). Conclusions Overall, our results suggest that prenatal exposure to maternal infections, particularly with co-occurring episodes of fever, are risk factors for ADHD. Fever (or severity of the infection) appears to be more important in mid-pregnancy associations. Our results indicate that type of infection and timing of exposure might influence the associations, but small effect sizes require careful interpretations. The association between infection and ADHD should be estimated using discordant siblings or other negative control designs that give better adjustment for unmeasured familial confounding.publishedVersio

Early manifestations of genetic risk for neurodevelopmental disorders

Background: Attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (autism) and schizophrenia are highly heritable neurodevelopmental disorders, affecting the lives of many individuals. It is important to increase our understanding of how the polygenic risk for neurodevelopmental disorders manifests during childhood in boys and girls. Methods: Polygenic risk scores (PRS) for ADHD, autism and schizophrenia were calculated in a subsample of 15 205 children from the Norwegian Mother, Father and Child Cohort Study (MoBa). Mother-reported traits of repetitive behavior, social communication, language and motor difficulties, hyperactivity and inattention were measured in children at 6 and 18 months, 3, 5 and 8 years. Linear regression models in a multigroup framework were used to investigate associations between the three PRS and dimensional trait measures in MoBa, using sex as a grouping variable. Results: Before the age of 2, the ADHD PRS was robustly associated with hyperactivity and inattention, with increasing strength up to 8 years, and with language difficulties at age 5 and 8. The autism PRS was robustly associated with language difficulties at 18 months, motor difficulties at 36 months, and hyperactivity and inattention at 8 years. We did not identify robust associations for the schizophrenia PRS. In general, the PRS associations were similar in boys and girls. The association between ADHD PRS and hyperactivity at 18 months was, however, stronger in boys. Conclusions: Polygenic risk for autism and ADHD in the general population manifests early in childhood and broadly across behavioral measures of neurodevelopmental traits.publishedVersio

Genetic liability for schizophrenia and childhood psychopathology in the general population

Abstract Genetic liability for schizophrenia is associated with psychopathology in early life. It is not clear if these associations are time dependent during childhood, nor if they are specific across different forms of psychopathology. Using genotype and questionnaire data on children (N = 15 105) from the Norwegian Mother, Father and Child Cohort Study, we used schizophrenia polygenic risk scores to test developmental stability in associations with measures of emotional and behavioral problems between 18 months and 5 years, and domain specificity in associations with symptoms of depression, anxiety, conduct problems, oppositionality, inattention, and hyperactivity at 8 years. We then sought to identify symptom profiles—across development and domains—associated with schizophrenia polygenic liability. We found evidence for developmental stability in associations between schizophrenia polygenic risk scores and emotional and behavioral problems, with the latter being mediated specifically via the rate of change in symptoms (β slope = 0.032; 95% CI: 0.007–0.057). At age 8, associations were better explained by a model of symptom-specific polygenic effects rather than effects mediated via a general psychopathology factor or by domain-specific factors. Overall, individuals with higher schizophrenia polygenic risk scores were more likely (OR = 1.310 [95% CIs: 1.122–1.528]) to have a profile of increasing behavioral and emotional symptoms in early childhood, followed by elevated symptoms of conduct disorder, oppositionality, hyperactivity, and inattention by age 8. Schizophrenia-associated alleles are linked to specific patterns of early-life psychopathology. The associations are small, but findings of this nature can help us better understand the developmental emergence of schizophrenia

Identification of genetic overlap and novel risk loci for attention-deficit/hyperactivity disorder and bipolar disorder

Differential diagnosis between childhood onset attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) remains a challenge, mainly due to overlapping symptoms and high rates of comorbidity. Despite this, genetic correlation reported for these disorders is low and non-significant. Here we aimed to better characterize the genetic architecture of these disorders utilizing recent large genome-wide association studies (GWAS). We analyzed independent GWAS summary statistics for ADHD (19,099 cases and 34,194 controls) and BD (20,352 cases and 31,358 controls) applying the conditional/conjunctional false discovery rate (condFDR/conjFDR) statistical framework that increases the power to detect novel phenotype-specific and shared loci by leveraging the combined power of two GWAS. We observed cross-trait polygenic enrichment for ADHD conditioned on associations with BD, and vice versa. Leveraging this enrichment, we identified 19 novel ADHD risk loci and 40 novel BD risk loci at condFDR <0.05. Further, we identified five loci jointly associated with ADHD and BD (conjFDR < 0.05). Interestingly, these five loci show concordant directions of effect for ADHD and BD. These results highlight a shared underlying genetic risk for ADHD and BD which may help to explain the high comorbidity rates and difficulties in differentiating between ADHD and BD in the clinic. Improving our understanding of the underlying genetic architecture of these disorders may aid in the development of novel stratification tools to help reduce these diagnostic difficulties.acceptedVersio

Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadAttention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5-BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10-21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.Innovative Medicines Initiative Joint Undertaking from the European Union's Seventh Framework Programme (EU-FP7/2007-2013) European Union (EU) EU-FP7-People-2011-IAPP grant Research Council of Norway KG Jebsen Stiftelsen South-East Norway Health Authorit

Attention-deficit hyperactivity disorder shares copy number variant risk with schizophrenia and autism spectrum disorder

Publisher's version (útgefin grein).Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable common childhood-onset neurodevelopmental disorder. Some rare copy number variations (CNVs) affect multiple neurodevelopmental disorders such as intellectual disability, autism spectrum disorders (ASD), schizophrenia and ADHD. The aim of this study is to determine to what extent ADHD shares high risk CNV alleles with schizophrenia and ASD. We compiled 19 neuropsychiatric CNVs and test 14, with sufficient power, for association with ADHD in Icelandic and Norwegian samples. Eight associate with ADHD; deletions at 2p16.3 (NRXN1), 15q11.2, 15q13.3 (BP4 & BP4.5–BP5) and 22q11.21, and duplications at 1q21.1 distal, 16p11.2 proximal, 16p13.11 and 22q11.21. Six of the CNVs have not been associated with ADHD before. As a group, the 19 CNVs associate with ADHD (OR = 2.43, P = 1.6 × 10−21), even when comorbid ASD and schizophrenia are excluded from the sample. These results highlight the pleiotropic effect of the neuropsychiatric CNVs and add evidence for ADHD, ASD and schizophrenia being related neurodevelopmental disorders rather than distinct entities.We are grateful to the participants and we thank the staff at the Research Recruitment Center. We also thank the staff at deCODE genetics core facilities and all our colleagues for their important contribution to this work. We are grateful to the Benefit Society for Children with Disabilities (Styrktarfélag Lamaðra og Fatlaðra; SLF) for their participation. The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreements’ no. 115008 (NEWMEDS) and no. 115300 (EUAIMS), of which resources are composed of EFPIA in-kind contribution and financial contribution from the European Union’s Seventh Framework Programme (EU-FP7/2007–2013), from EU-FP7 grants no. 602450 (IMAGEMEND) and no. 502805 (Aggressotype), EU-FP7-People-2011-IAPP grant no. 286213 (PsychDPC), and The Research Council of Norway (#226971, 229129, 223273, 213694, 248778), the KG Jebsen Stiftelsen (SKGJ-MED-002 and SKGJ-MED-008), and The South-East Norway Health Authority (#2012–132).Peer Reviewe

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