Autism phenotype versus registered diagnosis in Swedish children: prevalence trends over 10 years in general population samples

Objective: To compare the annual prevalence of the autism symptom phenotype and of registered diagnoses for autism spectrum disorder during a 10 year period in children. Design: Population based study. Setting: Child and Adolescent Twin Study and national patient register, Sweden. Participants: 19 993 twins (190 with autism spectrum disorder) and all children (n=1 078 975; 4620 with autism spectrum disorder) born in Sweden over a 10 year period from 1993 to 2002. Main outcome measures: Annual prevalence of the autism symptom phenotype (that is, symptoms on which the diagnostic criteria are based) assessed by a validated parental telephone interview (the Autism-Tics, ADHD and other Comorbidities inventory), and annual prevalence of reported diagnoses of autism spectrum disorder in the national patient register. Results: The annual prevalence of the autism symptom phenotype was stable during the 10 year period (P=0.87 for linear time trend). In contrast, there was a monotonic significant increase in prevalence of registered diagnoses of autism spectrum disorder in the national patient register (P<0.001 for linear trend). Conclusions: The prevalence of the autism symptom phenotype has remained stable in children in Sweden while the official prevalence for registered, clinically diagnosed, autism spectrum disorder has increased substantially. This suggests that administrative changes, affecting the registered prevalence, rather than secular factors affecting the pathogenesis, are important for the increase in reported prevalence of autism spectrum disorder

Genome-wide analysis of adolescent psychotic-like experiences shows genetic overlap with psychiatric disorders

This study aimed to test for overlap in genetic influences between psychotic-like experience traits shown by adolescents in the community, and clinically-recognized psychiatric disorders in adulthood, specifically schizophrenia, bipolar disorder, and major depression. The full spectra of psychotic-like experience domains, both in terms of their severity and type (positive, cognitive, and negative), were assessed using self- and parent-ratings in three European community samples aged 15-19 years (Final N incl. siblings = 6,297-10,098). A mega-genome-wide association study (mega-GWAS) for each psychotic-like experience domain was performed. SNP-heritability of each psychotic-like experience domain was estimated using genomic-relatedness-based restricted maximum-likelihood (GREML) and linkage disequilibrium- (LD-) score regression. Genetic overlap between specific psychotic-like experience domains and schizophrenia, bipolar disorder, and major depression was assessed using polygenic risk scoring (PRS) and LD-score regression. GREML returned SNP-heritability estimates of 3-9% for psychotic-like experience trait domains, with higher estimates for less skewed traits (Anhedonia, Cognitive Disorganization) than for more skewed traits (Paranoia and Hallucinations, Parent-rated Negative Symptoms). Mega-GWAS analysis identified one genome-wide significant association for Anhedonia within IDO2 but which did not replicate in an independent sample. PRS analysis revealed that the schizophrenia PRS significantly predicted all adolescent psychotic-like experience trait domains (Paranoia and Hallucinations only in non-zero scorers). The major depression PRS significantly predicted Anhedonia and Parent-rated Negative Symptoms in adolescence. Psychotic-like experiences during adolescence in the community show additive genetic effects and partly share genetic influences with clinically-recognized psychiatric disorders, specifically schizophrenia and major depression

Do psychopathic personality traits in childhood predict subsequent criminality and psychiatric outcomes over and above childhood behavioral problems?

Peer reviewe

Soluble angiotensin-converting enzyme 2 is transiently elevated in COVID-19 and correlates with specific inflammatory and endothelial markers

The main entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is angiotensin-converting enzyme 2 (ACE2). SARS-CoV-2 interactions with ACE2 may increase ectodomain shedding but consequences for the renin-angiotensin system and pathology in Coronavirus disease 2019 (COVID-19) remain unclear. We measured soluble ACE2 (sACE2) and sACE levels by enzyme-linked immunosorbent assay in 114 hospital-treated COVID-19 patients compared with 10 healthy controls; follow-up samples after four months were analyzed for 58 patients. Associations between sACE2 respectively sACE and risk factors for severe COVID-19, outcome, and inflammatory markers were investigated. Levels of sACE2 were higher in COVID-19 patients than in healthy controls, median 5.0 (interquartile range 2.8-11.8) ng/ml versus 1.4 (1.1-1.6) ng/ml, p < .0001. sACE2 was higher in men than women but was not affected by other risk factors for severe COVID-19. sACE2 decreased to 2.3 (1.6-3.9) ng/ml at follow-up, p < .0001, but remained higher than in healthy controls, p = .012. sACE was marginally lower during COVID-19 compared with at follow-up, 57 (45-70) ng/ml versus 72 (52-87) ng/ml, p = .008. Levels of sACE2 and sACE did not differ depending on survival or disease severity. sACE2 during COVID-19 correlated with von Willebrand factor, factor VIII and D-dimer, while sACE correlated with interleukin 6, tumor necrosis factor alpha, and plasminogen activator inhibitor 1. Conclusions: sACE2 was transiently elevated in COVID-19, likely due to increased shedding from infected cells. sACE2 and sACE during COVID-19 differed in correlations with markers of inflammation and endothelial dysfunction, suggesting release from different cell types and/or vascular beds

Prothrombotic changes in patients with COVID-19 are associated with disease severity and mortality

Background and Aims: Patients with severe coronavirus disease 2019 (COVID-19) are at significant risk of thrombotic complications. However, their prothrombotic state is incompletely understood. Therefore, we measured in vivo activation markers of hemostasis, plasma levels of hemostatic proteins, and functional assays of coagulation and fibrinolysis in plasma from patients with COVID-19 and determined their association with disease severity and 30-day mortality. Methods: We included 102 patients with COVID-19 receiving various levels of respiratory support admitted to general wards, intermediate units, or intensive care units and collected plasma samples shortly after hospital admission. Results: Patients with COVID-19 with higher respiratory support had increased in vivo activation of coagulation and fibrinolysis, as reflected by higher plasma levels of d-dimer, thrombin-antithrombin, and plasmin-antiplasmin complexes as compared to patients with no to minimal respiratory support and healthy controls. Moreover, the patients with COVID-19 with higher respiratory support exhibited substantial ex vivo thrombin generation and lower ex vivo fibrinolytic capacity, despite higher doses of anticoagulant therapy compared to less severely ill patients. Fibrinogen, factor VIII, and von Willebrand factor levels increased, and ADAMTS13 levels decreased with increasing respiratory support in patients with COVID-19. Low platelet count; low levels of prothrombin, antithrombin, and ADAMTS13; and high levels of von Willebrand factor were associated with short-term mortality. Conclusions: Severe COVID-19 is associated with prothrombotic changes with increased in vivo activation of coagulation and fibrinolysis, despite anticoagulant therapy

Neural gain control measured through cortical gamma oscillations is associated with sensory sensitivity

Gamma oscillations facilitate information processing by shaping the excitatory input/output of neuronal populations. Recent studies in humans and nonhuman primates have shown that strong excitatory drive to the visual cortex leads to suppression of induced gamma oscillations, which may reflect inhibitory-based gain control of network excitation. The efficiency of the gain control measured through gamma oscillations may in turn affect sensory sensitivity in everyday life. To test this prediction, we assessed the link between self-reported sensitivity and changes in magneto-encephalographic gamma oscillations as a function of motion velocity of high-contrast visual gratings. The induced gamma oscillations increased in frequency and decreased in power with increasing stimulation intensity. As expected, weaker suppression of the gamma response correlated with sensory hypersensitivity. Robustness of this result was confirmed by its replication in the two samples: neurotypical subjects and people with autism, who had generally elevated sensory sensitivity. We conclude that intensity-related suppression of gamma response is a promising biomarker of homeostatic control of the excitation-inhibition balance in the visual cortex

Association of genetic risk factors for psychiatric disorders and traits of these disorders in a Swedish population twin sample

Importance Psychiatric traits associated with categorically defined psychiatric disorders are heritable and present to varying degrees in the general population. It is commonly assumed that diagnoses represent the extreme end of continuously distributed traits in the population, but this assumption has yet to be robustly tested for many psychiatric phenotypes. Objective To assess whether genetic risk factors associated with psychiatric disorders are also associated with continuous variation in milder population traits. Design, Setting, and Participants This study combined a novel twin analytic approach with polygenic risk score (PRS) analyses in a large population-based twin sample.Phenotypic and genetic data were available from the Child and Adolescent Twin Study in Sweden. Inpatient data were available for January 1, 1987, to December 31, 2014, and outpatient data for January 1, 2001, to December 31, 2013. The last day of follow-up was December 31, 2014. Data analysis was performed from January 1, 2017, to September 30, 2017. Main Outcomes and Measures Questionnaires that assessed traits of autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), learning difficulties, tic disorders (TDs), obsessive-compulsive disorder (OCD), anxiety, major depressive disorder (MDD), mania, and psychotic experiences were administered to a large Swedish twin sample. Individuals with clinical psychiatric diagnoses were identified using the Swedish National Patient Register. Joint categorical/continuous twin modeling was used to estimate genetic correlations between psychiatric diagnoses and continuous traits. The PRSs for psychiatric disorders were calculated based on independent discovery genetic data. The association between PRSs for each disorder and associated continuous traits was tested. Results Phenotype data were available for 13 923 twin pairs (35.1% opposite sex and 31.7% same-sex females) at 9 years of age, 5165 pairs (36.9% opposite sex and 34.0% same-sex females) at 15 years of age, and 4273 pairs (36.5% opposite sex and 34.4% same-sex females) at 18 years of age. Genetic data were available for 13 412 individuals (50.2% females). Twin genetic correlations between numerous psychiatric diagnoses and corresponding traits ranged from 0.31 to 0.69. Disorder PRSs were associated with related population traits for ASD (β [SE] = 0.04 [0.01] at 9 years of age), ADHD (β [SE] = 0.27 [0.03] at 9 years of age), TDs (β [SE] = 0.02 [0.004] at 9 years of age), OCD (β [SE] = 0.13 [0.05] at 18 years of age), anxiety (β [SE] = 0.18 [0.08] at 9 years of age; β [SE] = 0.07 [0.02] at 15 years of age; and β [SE] = 0.40 [0.17] at 18 years of age), MDD (β [SE] = 0.10 [0.03] at 9 years of age; β [SE] = 0.11 [0.02] at 15 years of age; and β [SE] = 0.41 [0.10] at 18 years of age), and schizophrenia (β [SE] = 0.02 [0.01] at 18 years of age). Polygenic risk scores for depressive symptoms were associated with MDD diagnoses (odds ratio, 1.16; 95% CI, 1.02-1.32). Conclusions and Relevance These results suggest that genetic factors associated with psychiatric disorders are also associated with milder variation in characteristic traits throughout the general population for many psychiatric phenotypes. This study suggests that many psychiatric disorders are likely to be continuous phenotypes rather than the categorical entities currently defined in diagnostic manuals, which has strong implications for genetic research in particular