Associations between executive functions, intelligence and adaptive behaviour in children and adolescents with mild intellectual disability.

Background: The purpose of this study was to explore the role of everyday executive functions in relation to intelligence and adaptive behaviour in children and adolescents with mild intellectual disability. Method: A group of children and adolescents, previously diagnosed with mild intellectual disability were assessed according to intelligence, everyday executive functions and adaptive behaviour. The association between everyday executive functions and intelligence was examined, and it was explored whether intelligence or everyday executive functions would best predict adaptive behaviour. Results: Adaptive behaviour was significantly predicted by executive functions, but not by intelligence. Nor was intelligence significantly related to everyday executive functions in this group. Conclusions: Although fundamental in diagnosing intellectual disability, intelligence cannot predict adaptive behaviour. Assessing everyday executive functions and adaptive behaviour, as well as acknowledging the strong association between them, provides valuable information in the process of optimizing developmental support for children and adolescents with mild intellectual disability.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with attention-deficit/hyperactivity disorder and autism spectrum disorder in children.

BACKGROUND: Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) may be a risk factor for neurodevelopmental deficits and disorders, but evidence is inconsistent. OBJECTIVES: We investigated whether prenatal exposure to PFAS were associated with childhood diagnosis of attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder (ASD). METHODS: This study was based on the Norwegian Mother, Father and Child Cohort Study and included n = 821 ADHD cases, n = 400 ASD cases and n = 980 controls. Diagnostic cases were identified by linkage with the Norwegian Patient Registry. In addition, we used data from the Medical Birth Registry of Norway. The study included the following PFAS measured in maternal plasma sampled mid-pregnancy: Perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorohexane sulfonate (PFHxS), perfluoroheptanesulfonic acid (PFHpS), and perfluorooctane sulfonate (PFOS). Relationships between individual PFAS and ADHD or ASD diagnoses were examined using multivariable adjusted logistic regression models. We also tested for possible non-linear exposure-outcome associations. Further, we investigated the PFAS mixture associations with ASD and ADHD diagnoses using a quantile-based g-computation approach. RESULTS: Odds of ASD was significantly elevated in PFOA quartile 2 [OR = 1.71 (95% CI: 1.20, 2.45)] compared to quartile 1, and PFOA appeared to have a non-linear, inverted U-shaped dose-response relationship with ASD. PFOA was also associated with increased odds of ADHD, mainly in quartile 2 [OR = 1.54 (95% CI: 1.16, 2.04)] compared to quartile 1, and displayed a non-linear relationship in the restricted cubic spline model. Several PFAS (PFUnDA, PFDA, and PFOS) were inversely associated with odds of ADHD and/or ASD. Some of the associations were modified by child sex and maternal education. The overall PFAS mixture was inversely associated with ASD [OR = 0.76 (95% CI: 0.64, 0.90)] as well as the carboxylate mixture [OR = 0.79 (95% CI: 0.68, 0.93)] and the sulfonate mixture [OR = 0.84 (95% CI: 0.73, 0.96)]. CONCLUSION: Prenatal exposure to PFOA was associated with increased risk of ASD and ADHD in children. For some PFAS, as well as their mixtures, there were inverse associations with ASD and/or ADHD. However, the inverse associations reported herein should not be interpreted as protective effects, but rather that there could be some unresolved confounding for these relationships. The epidemiologic literature linking PFAS exposures with neurodevelopmental outcomes is still inconclusive, suggesting the need for more research to elucidate the neurotoxicological potential of PFAS during early development.

A seven-year longitudinal study of the association between neurocognitive function and basic self-disorders in schizophrenia.

Introduction: Basic self-disorders (SDs) and neurocognitive impairments are fundamental trait-like aspects of schizophrenia spectrum disorders. There has been little research on the association between SDs and neurocognitive impairments in schizophrenia, and no longitudinal studies have investigated if they are related. The aim of this study was to investigate the association between SDs and neurocognitive function in a follow-up study of patients with schizophrenia. Methods: SDs and neurocognition were examined in 35 patients with schizophrenia during their first treatment and 7 years later (mean 7.1, SD 0.42). SDs were examined with the Examination of Anomalous Self-Experience (EASE) instrument. The neurocognitive examination included assessments of psychomotor speed, executive- and memory functions. Results: Poorer executive functions at baseline were significantly associated with more SDs 7 years later and smaller reductions in SDs over time. There were no significant associations between other neurocognitive functions and SDs. Discussion: Executive functions are important for self-regulation, and impairments in these functions in everyday life may have an impact on the development and/or persistence of SDs.

Sex as a Moderator Between Parent Ratings of Executive Dysfunction and Social Difficulties in Children and Adolescents with Autism Spectrum Disorder.

Girls and boys might differ in autistic symptoms and associated cognitive difficulties such as executive function (EF). We investigated sex differences in the relationship between parent rated EF and autistic symptoms in 116 children and adolescents (25 girls) aged 5-19 years with an intelligence quotient above 70 and an autism spectrum disorder (ASD) diagnosis. They were rated with the behavior rating inventory of executive function (BRIEF) and the autism diagnostic interview revised (ADI-R). We found a positive association between EF and the ADI-R domains of reciprocal social interaction (p < 0.001) and communication (p = 0.001) in girls, while these relationships were small and non-significant in boys. Our results provide a greater understanding of the sex-specific characteristics of children and adolescents with ASD.

Metal and essential element concentrations during pregnancy and associations with autism spectrum disorder and attention-deficit/hyperactivity disorder in children.

BACKGROUND: Prenatal exposure to toxic metals or variations in maternal levels of essential elements during pregnancy may be a risk factor for neurodevelopmental disorders such as attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in offspring. OBJECTIVES: We investigated whether maternal levels of toxic metals and essential elements measured in mid-pregnancy, individually and as mixtures, were associated with childhood diagnosis of ADHD or ASD. METHODS: This study is based on the Norwegian Mother, Father and Child Cohort Study and included 705 ADHD cases, 397 ASD cases and 1034 controls. Cases were identified through linkage with the Norwegian Patient Registry. Maternal concentrations of 11 metals/elements were measured in blood at week 17 of gestation; cadmium; cesium; cobalt; copper; lead; magnesium; manganese; selenium; zinc; total arsenic; and total mercury. Multivariable adjusted logistic regression models were used to examine associations between quartile levels of individual metals/elements and outcomes. We also investigated non-linear associations using restricted cubic spline models. The joint effects of the metal/element mixture on ASD and ADHD diagnoses were estimated using a quantile-based g-computation approach. RESULTS: For ASD, we identified positive associations (increased risks) in the second quartile of arsenic [OR = 1.77 (CI: 1.26, 2.49)] and the fourth quartiles of cadmium and manganese [OR = 1.57 (CI: 1.07 2.31); OR = 1.84 (CI: 1.30, 2.59)], respectively. In addition, there were negative associations between cesium, copper, mercury, and zinc and ASD. For ADHD, we found increased risk in the fourth quartiles of cadmium and magnesium [OR = 1.59 (CI: 1.15, 2.18); [OR = 1.42 (CI: 1.06, 1.91)]. There were also some negative associations, among others with mercury. In addition, we identified non-linear associations between ASD and arsenic, mercury, magnesium, and lead, and between ADHD and arsenic, copper, manganese, and mercury. There were no significant findings in the mixture approach analyses. CONCLUSION: Results from the present study show several associations between levels of metals and elements during gestation and ASD and ADHD in children. The most notable ones involved arsenic, cadmium, copper, mercury, manganese, magnesium, and lead. Our results suggest that even population levels of these compounds may have negative impacts on neurodevelopment. As we observed mainly similarities among the metals' and elements' impact on ASD and ADHD, it could be that the two disorders share some neurochemical and neurodevelopmental pathways. The results warrant further investigation and replication, as well as studies of combined effects of metals/elements and mechanistic underpinnings.

Cognitive Performance in Early-Onset Schizophrenia and Attention-Deficit/Hyperactivity Disorder: A 25-Year Follow-Up Study.

Early-Onset Schizophrenia (EOS) and Attention Deficit-Hyperactivity Disorder (ADHD) are early- onset neurodevelopmental disorders associated with cognitive deficits. The current study represents the first attempt to compare these groups on a comprehensive cognitive test battery in a longitudinal design over 25 years in order to enhance our knowledge of particular patterns resulting from the interaction between normal maturational processes and different illness processes of these disorders. In the baseline study, 19 adolescents with schizophrenia were compared to 20 adolescents with ADHD and 30 healthy controls (HC), all between 12 and 18 years of age. After 13 years (T2) and after 25 years (T3) they were re-evaluated with the cognitive test battery. A cognitive Composite Score was used in a linear mixed model. The EOS group had a significant cognitive stagnation or deterioration from T1 to T2 compared to HC. However, the EOS group had the most positive change from T2 to T3, supporting a stable level of cognitive performance over the 25 year span. The ADHD group improved or had similar development as the HC group from T1 to T2. They continued to improve significantly compared to the HC group from T2 to T3. Individuals in the EOS group performed more impaired on the cognitive composite score compared to the HC group and the ADHD group at all three time points. Results might indicate a neurodevelopmental pathway of EOS with subnormal cognitive development specific in adolescence. In comparison, the ADHD group had a more consistent cognitive maturation supporting a maturational delay hypothesis of ADHD.

Prenatal exposure to perfluoroalkyl substances and associations with symptoms of attention-deficit/hyperactivity disorder and cognitive functions in preschool children.

BACKGROUND: Perfluoroalkyl substances (PFASs) are persistent organic pollutants that are suspected to be neurodevelopmental toxicants, but epidemiological evidence on neurodevelopmental effects of PFAS exposure is inconsistent. We investigated the associations between prenatal exposure to PFASs and symptoms of attention-deficit/hyperactivity disorder (ADHD) and cognitive functioning (language skills, estimated IQ and working memory) in preschool children, as well as effect modification by child sex. MATERIAL AND METHODS: This study included 944 mother-child pairs enrolled in a longitudinal prospective study of ADHD symptoms (the ADHD Study), with participants recruited from The Norwegian Mother, Father and Child Cohort Study (MoBa). Boys and girls aged three and a half years, participated in extensive clinical assessments using well-validated tools; The Preschool Age Psychiatric Assessment interview, Child Development Inventory and Stanford-Binet (5th revision). Prenatal levels of 19 PFASs were measured in maternal blood at week 17 of gestation. Multivariable adjusted regression models were used to examine exposure-outcome associations with two principal components extracted from the seven detected PFASs. Based on these results, we performed regression analyses of individual PFASs categorized into quintiles. RESULTS: PFAS component 1 was mainly explained by perfluoroheptane sulfonate (PFHpS), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorooctanoic acid (PFOA). PFAS component 2 was mainly explained by perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA) and perfluorononanoic acid (PFNA). Regression models showed a negative association between PFAS component 1 and nonverbal working memory [ß = -0.08 (CI: -0.12, -0.03)] and a positive association between PFAS component 2 and verbal working memory [ß = 0.07 (CI: 0.01, 0.12)]. There were no associations with ADHD symptoms, language skills or IQ. For verbal working memory and PFAS component 2, we found evidence for effect modification by child sex, with associations only for boys. The results of quintile models with individual PFASs, showed the same pattern for working memory as the results in the component regression analyses. There were negative associations between nonverbal working memory and quintiles of PFOA, PFNA, PFHxS, PFHpS and PFOS and positive associations between verbal working memory and quintiles of PFOA, PFNA, PFDA and PFUnDA, with significant relationships mainly in the highest concentration groups. CONCLUSIONS: Based on our results, we did not find consistent evidence to conclude that prenatal exposure to PFASs are associated with ADHD symptoms or cognitive dysfunctions in preschool children aged three and a half years, which is in line with the majority of studies in this area. Our results showed some associations between PFASs and working memory, particularly negative relationships with nonverbal working memory, but also positive relationships with verbal working memory. The relationships were weak, as well as both positive and negative, which suggest no clear association - and need for replication.

Basic self-disturbances independently predict recovery in psychotic disorders: A seven year follow-up study.

BACKGROUND: Recovery is the ultimate goal of psychosis treatment. Basic self-disturbances (BSDs) are non-psychotic phenomena associated with clinical outcome, present in prodromal, psychotic and residual phases of psychotic disorders. AIM: To investigate the relationship between BSDs and recovery seven years after first treatment in patients with psychotic disorders. METHOD: Prospective longitudinal study of 56 patients recruited during first adequate treatment for schizophrenia (n = 35) and other psychotic disorders (n = 21) (psychotic bipolar disorder, delusional disorder, psychotic disorder NOS). At baseline and follow-up BSDs were assessed using the Examination of Anomalous Self-Experience (EASE) manual, while standard clinical instruments were used to ascertained diagnosis, clinical symptom severity, and functioning. Recovery was defined as absence of psychotic symptoms and regaining of functioning that persisted the last two years before follow-up. RESULTS: At follow up, 34% achieved recovery (5 (14%) with schizophrenia and 14 (67%) with other psychoses at baseline). Recovery was predicted by an absence of a schizophrenia diagnosis, low baseline level of BSDs and further reductions in BSDs from baseline to follow-up. Change in BSDs was the strongest predictor, also after adjusting for premorbid adjustment and duration of untreated psychosis, and was not confounded by diagnosis. CONCLUSION: Low baseline levels of basic self-disturbances and further reductions over time independently predict recovery seven years later in first treated psychosis patients.

Stability in basic self-disturbances and diagnosis in a first treated psychosis: A seven year follow-up study.

BACKGROUND: Basic self-disturbances (BSDs) are considered core features of schizophrenia spectrum disorders, and are present in the prodromal, early psychotic and chronic phases. Considerable levels of BSDs are also present at first treatment in some patients with psychotic disorders outside the schizophrenia spectrum. There is limited knowledge about the stability of self-disturbances over time. AIM: To explore the stability of BSDs in a seven-year follow-up of first treatment patients, and the association between baseline levels and changes in BSDs and diagnostic changes at follow-up. METHOD: Longitudinal study of 56 patients (35 schizophrenia and 21 non-schizophrenia) recruited at their first treatment for a psychotic disorder. BSDs were assessed using the Examination of Anomalous Self-Experience (EASE), while diagnostic categories, clinical symptom severity, and functioning were assessed with standard clinical instruments. RESULTS: The schizophrenia group had significantly lower levels of BSDs at follow-up compared to baseline. The EASE domain "Cognition and stream of consciousness" was the most stable. There were no diagnostic changes into or out of schizophrenia spectrum. Patients with schizophrenia had significantly higher levels of BSDs both at baseline and at follow up than patients with psychotic disorders outside the schizophrenia spectrum, who showed stable low levels. CONCLUSION: We found a decrease and thus less stability in BSDs in schizophrenia than expected. This might indicate that BSDs tent to weaken over time, and that unknown individual characteristics may influence the development of BSDs. Diagnostic stability from baseline to follow-up may be due to long DUP before service entry.

Severity of Autism Symptoms and Degree of Attentional Difficulties Predicts Emotional and Behavioral Problems in Children with High-Functioning Autism; a Two-Year Follow-up Study.

Children with autism often struggle with emotional and behavioral problems (EBP). This study investigated whether level of autism symptoms, attention problems or verbal IQ at baseline can predict EBP 2 years later in children with High-Functioning Autism (HFA). Thirty-four participants with HFA and 45 typically developing children (TD) (ages 9-16) were assessed with parent ratings of EBP, autism symptoms, attention problems, and a test of verbal IQ. The amount of autism symptoms and degree of attention problems at baseline significantly predicted EBP at follow-up, whereas verbal IQ did not. The findings from this study emphasize the importance of assessing and understanding the consequences of autism symptoms and attention problems when treating EBP in children with HFA. Furthermore, interventions aimed at improving ASD symptoms may positively affect the prevalence of EBP in children with HFA.

Metacognitive Aspects of Executive Function Are Highly Associated with Social Functioning on Parent-Rated Measures in Children with Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is characterized by social dysfunction. Even though executive dysfunction has been recognized as important in understanding ASD, the findings are inconsistent. This might be due to different definitions of executive function (EF), which part of EF that has been studied, structured vs. unstructured tasks, inclusion of different moderators (age, IQ, sex) and different diagnostic categories within the spectrum. The main finding is that people with ASD have more EF difficulties than normal controls and more difficulties on open-end tasks than on structured cognitive tasks. Since some EF difficulties may not be observable in a laboratory setting, informant measures might have higher ecological validity than neuropsychological tests. Evidence suggests that executive dysfunctions are associated with social impairments, but few studies have investigated the details of this relationship, and it remains unclear what types of EF deficits are relevant for the social problems of individuals with ASD. Here we investigated which EF domains were associated with various domains of social function on parent-rated measures. A total of 86 children and adolescents with a diagnosis of ASD were included and tested for general cognitive abilities. Parents completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Social Responsiveness Scale (SRS). Multiple regression analysis revealed significant associations between SRS scores and age, sex, total IQ and the BRIEF indexes. The Metacognition Index from the BRIEF added significantly to the prediction of the SRS total score and the subscales Social Communication, Social Motivation and Autistic Mannerisms. The findings suggest that metacognitive aspects of EF are of particular importance for social abilities in children and adolescents with ASD. Earlier research has shown that typically developing (TD) children have a different relationship between EF and social function than children with ASD. They found that in TD children the EF domain related to behavioral regulation was most important to social function. The results from the current study may have implications for understanding the cognitive components of the social problems that define ASD, and may be relevant in developing more targeted clinical EF interventions related to core ASD dysfunctions.

The Association between Anomalous Self-experiences, Self-esteem and Depressive Symptoms in First Episode Schizophrenia.

Background: Anomalous self-experiences (ASEs) aggregate in schizophrenia spectrum disorders, but the relationship between ASEs, and depression has been studied to a limited extent. Lower self-esteem has been shown to be associated with depression in early psychosis. Our hypothesis is that ASEs in early phases of schizophrenia are linked to lower levels of self-esteem, which in turn is associated with depression. Aim: The aim is to examine the relationship between ASEs, self-esteem and depression in first-episode schizophrenia spectrum disorders. Method: ASEs were assessed in 55 patients with first-episode schizophrenia by means of the Examination of anomalous Self-Experience (EASE) instrument. Assessment of depression was based on the Calgary Depression Scale for Schizophrenia (CDSS). Self-esteem was measured using the Rosenberg Self-Esteem Scale (RSES). Symptom severity was assessed using the Structured Clinical Interview for the Positive and Negative Syndrome Scale (SCI-PANSS). Substance misuse was measured with the Drug Use Disorder Identification Test (DUDIT), and alcohol use was measured with the Alcohol Use Disorder Identification Test (AUDIT). Data on childhood adjustment were collected using the Premorbid Adjustment Scale (PAS). Data on childhood trauma were collected using the Norwegian version of the Childhood Trauma Questionnaire, short form (CTQ-SF). Results: Analyses detected a significant association between current depression and ASEs as measured by the EASE in women, but not in men. The effect of ASEs on depression appeared to be mediated by self-esteem. No other characteristics associated with depression influenced the relationship between depression, self-esteem and ASEs. Conclusion: Evaluating ASEs can assist clinicians in understanding patients' experience of self-esteem and depressive symptoms. The complex interaction between ASEs, self-esteem, depression and suicidality could be a clinical target for the prevention of suicidality in this patient group.