Elevated maternal interleukin 6 (IL-6) during pregnancy has been associated with adverse fetal brain development and neurodevelopmental disorders, which often involve executive functioning (EF) impairments. However, the association between maternal IL-6 levels during pregnancy and EF remains largely unexplored.

The COPSYCH study is based on the prospective COPSAC2010 birth cohort of 700 mother-child pairs, recruited during pregnancy. The children’s executive functioning was assessed at age 10 using: (i) the Behavior Rating Inventory of Executive Function, Second Edition (BRIEF-2) parental questionnaire, and (ii) a comprehensive neuropsychological test battery. Maternal blood levels of IL-6 and hs-CRP were measured at gestational week 24. Associations between IL-6 (main analysis) and hs-CRP (secondary analysis) and EF in children at age 10 were investigated with regression models with extensive confounder adjustment.

Six hundred and four children (86% of the cohort) completed the 10-year follow-up. Higher maternal IL-6 levels were significantly associated with less efficient parental-rated executive functioning in the children: BRIEF-2 Global Executive Composite score (p = 0.003), Behavior Regulation Index (p = 0.005), Emotion Regulation Index (p=0.04), and Cognitive Regulation Index (p=0.007). Interaction analysis with sex was significant (p-value=0.01) and exploratory analyses showed that IL-6 associations to BRIEF-2 were solely driven by boys. Associations between IL-6 and neuropsychological tests, as well as associations between hs-CRP and EF outcomes, were non-significant.

IL-6 during pregnancy was associated with less efficient everyday EF in children at age 10. If replicated, preventive strategies targeting inflammation in pregnancy may ameliorate adverse cognitive outcomes in offspring.

While several risk factors for schizophrenia have been identified, their individual impacts are rather small. The relative independent and cumulative impacts of multiple risk factors on disease risk and age of onset warrant further investigation.

We conducted a register-based case–control study including all individuals receiving a schizophrenia spectrum disorder in Denmark from 1973 to 2018 (N = 29,142), and a healthy control sample matched 5:1 on age, sex, and parental socioeconomic status (N = 136,387). Register data included parental history of psychiatric illness, birth weight, gestational age, season of birth, population density of birthplace, immigration, paternal age, and Apgar scores. Data were analysed using logistic regression and machine learning.

Parental history of psychiatric illness (OR = 2.32 [95%CI 2.21–2.43]), high paternal age (OR = 1.30 [1.16–1.45]), and low birth weight (OR = 1.28 [1.16–1.41]) increased the odds of belonging to the patient group. In contrast, being a second-generation immigrant (OR = 0.65 [0.61–0.69]) and high population density of the birthplace (OR = 0.92 [0.89–0.96]) decreased the odds. The findings were supported by a decision tree analysis where parental history, paternal age, and birth weight contributed most to diagnostic classification (ACCtest = 0.69, AUCtest = 0.59, p < 0.001). Twenty percent of patients were child-onset cases. Here, female sex (OR = 1.82 [1.69–1.97]) and parental psychiatric illness (OR = 1.62 [1.49–1.77]) increased the odds of receiving the diagnosis <18 years.

Multiple early factors contribute independently to a higher psychosis risk, suggesting cumulative effects leading to symptom onset. Routine assessments of the most influential risk factors could be incorporated into clinical practise. Being female increased the risk of diagnosis during childhood, suggesting sex differences in the developmental trajectories of the disorder.

Few studies have explored associations between adaptive functioning and cognition in adolescents with early-onset schizophrenia spectrum disorders (EOS).

Adaptive functioning, cognition, positive, negative, and general symptoms were characterized in adolescents with EOS and healthy controls. A modified scale of negative, respectively, general symptoms was used. Bivariate analyses identified correlates of adaptive functioning to be included in multivariate analysis.

Adolescents with EOS showed significant impairments of social- and neurocognitive functions (−0.86 < Cohen´s ds < −0.58) and adaptive functioning (Cohen´s d = −2.23). Visual memory, verbal working memory, processing speed, reaction time, social cognition, and modified negative and general symptoms correlated significantly with adaptive functioning. The multiple regression analysis revealed only verbal working memory as uniquely associated with adaptive functioning (explaining 22.7 % of its variance). Verbal working memory also associated significantly with adaptive functioning in the context of the nonsignificant modified negative and the significant modified general symptoms dimension.

Adolescents with first-episode EOS had large impairments in adaptive functioning and moderate to large cognitive deficits. Verbal working memory was an important associate to concurrent adaptive functioning and may be a treatment target for trials to improve cognitive and adaptive functioning in adolescents with EOS.

Many cognitive functions are under strong genetic control and twin studies have demonstrated genetic overlap between some aspects of cognition and schizophrenia. How the genetic relationship between specific cognitive functions and schizophrenia is influenced by IQ is currently unknown.

We applied selected tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to examine the heritability of specific cognitive functions and associations with schizophrenia liability. Verbal and performance IQ were estimated using The Wechsler Adult Intelligence Scale-III and the Danish Adult Reading Test. In total, 214 twins including monozygotic (MZ = 32) and dizygotic (DZ = 22) pairs concordant or discordant for a schizophrenia spectrum disorder, and healthy control pairs (MZ = 29, DZ = 20) were recruited through the Danish national registers. Additionally, eight twins from affected pairs participated without their sibling.

Significant heritability was observed for planning/spatial span (h2 = 25%), self-ordered spatial working memory (h2 = 64%), sustained attention (h2 = 56%), and movement time (h2 = 47%), whereas only unique environmental factors contributed to set-shifting, reflection impulsivity, and thinking time. Schizophrenia liability was associated with planning/spatial span (rph = −0.34), self-ordered spatial working memory (rph = −0.24), sustained attention (rph = −0.23), and set-shifting (rph = −0.21). The association with planning/spatial span was not driven by either performance or verbal IQ. The remaining associations were shared with performance, but not verbal IQ.

This study provides further evidence that some cognitive functions are heritable and associated with schizophrenia, suggesting a partially shared genetic etiology. These functions may constitute endophenotypes for the disorder and provide a basis to explore genes common to cognition and schizophrenia.