Psychological, behavioural and biological factors associated with gastrointestinal symptoms in autistic adults and adults with autistic traits.

LAY ABSTRACT: Little is known about factors related to the increased risk for gastrointestinal symptoms in adults with an autism spectrum disorder (ASD), while the negative impact of gastrointestinal symptoms is evident. Especially, the relationship between gastrointestinal symptoms and psychological, behavioural, and biological risk factors in adults with ASD (traits) is unclear. Autistic peer support workers and autism-advocates also emphasised the importance of identifying risk factors, because of the high prevalence of gastrointestinal problems in people with ASD. Therefore, our study investigated which psychological, behavioural, and biological factors are associated with gastrointestinal symptoms in adults with ASD or with autistic traits. We analysed data from 31,185 adults in the Dutch Lifelines Study. Questionnaires were used to evaluate the presence of an autism spectrum disorder diagnosis, autistic traits, gastrointestinal symptoms, psychological and behavioural factors. Biological factors were examined with body measurements. We found that not only adults with ASD but also adults with higher levels of autistic traits were at increased risk for gastrointestinal symptoms. Adults with ASD who experienced psychological problems (psychiatric problems, worse perceived health, chronic stress) had a higher risk for gastrointestinal symptoms than adults with ASD without these psychological problems. Moreover, adults with higher levels of autistic traits were less physically active, which was also associated with gastrointestinal symptoms. In conclusion, our study highlights the relevance of identifying psychological problems and evaluating physical activity when trying to help adults with ASD or autistic traits and gastrointestinal symptoms. This suggests that healthcare professionals should be more aware of behavioural and psychological risk factors when evaluating gastrointestinal symptoms in adults with ASD (traits).

Metabolic syndrome in adults with autistic traits: associated psychological, behavioral, and biological factors in females and males - a PharmLines initiative.

Background: While cardiovascular diseases is highly prevalent and an important cause of mortality in autistic adults, knowledge on their increased cardiovascular risk is limited. Hence, this study aimed to investigate psychological, behavioral, and physical factors associated with metabolic syndrome (MetS) in adults with autistic traits. Methods: In total, 17,705 adults from the Lifelines Cohort were included and categorized using Autism Spectrum Quotient-10 sum-scores. The quartiles with highest (HQ-traits-group females: n = 2,635; males: n = 1803) and lowest levels of autistic traits (LQ-traits-group, n = idem) were analyzed. Using multivariable logistic regression, the associations between MetS and (self-reported and interviewed) psychological, behavioral, and physically measured factors in these stratified groups were investigated. Results: Among females, MetS was more common in the HQ-traits-group than in the LQ-traits-group (10.0% versus 7.5%, p < 0.01), while this was not the case among males (HQ-traits-group 13.8% versus LQ-traits-group 13.1%, p = 0.52). In both the female and male HQ-traits-group, the presence of MetS was associated with poorer self-reported health, less daily physical activity, and altered leukocyte counts. Conclusion: These findings underline the relevance of adequate cardiovascular prevention in adults with higher levels of autistic traits. Future research could gain more insight into the relationship between cardiovascular risk and autistic traits in females, and into tailored cardiovascular prevention.

[Care for adolescents with an autism spectrum disorder and an intellectual disability]. / Zorg voor adolescenten met autisme en een verstandelijke beperking.

BACKGROUND: Due to an experienced gap in care for adolescents with an autism spectrum disorder (ASD) and an intellectual disability (ID), an interdisciplinary outpatient clinic was initiated by child- and adolescent psychiatry services together with intellectual disability physicians in the Rotterdam region in 2017. AIM: Evaluation of the ASD-ID outpatient clinic. METHOD: A retrospective chart review study of the first year of the ASD-ID outpatient clinic was performed. The care specific traits of the adolescents who visited the ASD-ID outpatient clinic, their health care costs and the effect of the ASD-ID outpatient clinic on both the health care costs and the patient outflow was compared to the traits of the adolescents of the autism outpatient clinic. RESULTS: 32 adolescents who were referred to the ASD-ID outpatient clinic were comparable to 204 adolescents of the autism outpatient clinic in age (mean 16.5 years) and gender (75% male). They had 39% more DSM-IV classifications, were in care 3.7 years longer and had 44% more health care costs. After visiting the ASD-ID outpatient clinic, 50% of the adolescents were transferred within a year and 100% within three years to a intellectual disability physician. CONCLUSION: Adolescents with ASD and ID are a group with a substantial demand for care who deserve specific attention. An integrated ASD-ID outpatient clinic contributes to this demand.

[Hyperprolactinemia and antipsychotics: it's not always what it seems to be]. / Jongeren met hyperprolactinemie bij antipsychoticagebruik: denk aan macroprolactine.

Hyperprolactinemia is a relatively frequent laboratory abnormality (30-80%) as a result of antipsychotics and a reason to reduce or stop them. We describe two youngsters with autism spectrum disorder whose hyperprolactinemia was based on a false-positive laboratory finding due to macroprolactin. The consequences were: unnecessary endocrinological evaluation including a brain MRI, and undesirable antipsychotic dose reduction. Thus, hyperprolactinemia can be due to a falsely elevated prolactin concentration. There should be an addition to the current guidelines in which a work-up for macroprolactin screening is included.

Maternal weight gain in excess of pregnancy guidelines is related to daughters being overweight 40 years later.

BACKGROUND: Exceeding the Institute of Medicine guidelines for pregnancy weight gain increases childhood and adolescent obesity. However, it is unknown if these effects extend to midlife. OBJECTIVE: We sought to determine if exceeding the Institute of Medicine guidelines for pregnancy weight gain increases risk of overweight/obesity in daughters 40 years later. STUDY DESIGN: This cohort study is based on adult offspring in the Child Health and Development Studies and the Collaborative Perinatal Project pregnancy cohorts originally enrolled in the 1960s. In 2005 through 2008, 1035 daughters in their 40s were recruited to the Early Determinants of Mammographic Density study. We classified maternal pregnancy weight gain as greater than vs less than or equal to the 2009 clinical guidelines. We used logistic regression to compare the odds ratios of daughters being overweight/obese (body mass index [BMI] ≥25) at a mean age of 44 years between mothers who did not gain or gained more than pregnancy weight gain guidelines, accounting for maternal prepregnant BMI, and daughter body size at birth and childhood. We also examined potential family related confounding through a comparison of sisters using generalized estimating equations, clustered on sibling units and adjusted for maternal age and race. RESULTS: Mothers who exceeded guidelines for weight gain in pregnancy were more likely to have daughters who were overweight/obese in their 40s (odds ratio [OR], 3.4; 95% confidence interval {CI}, 2.0-5.7). This magnitude of association translates to a relative risk (RR) increase of 50% (RR = 1.5; 95% CI, 1.3-1.6). The association was of the same magnitude when examining only the siblings whose mother exceeded guidelines in 1 pregnancy and did not exceed the guidelines in the other pregnancy. The association was stronger with increasing maternal prepregnancy BMI (P trend < .001). Compared to mothers with BMI <25 who did not exceed guidelines, the relative risks (RR) for having an overweight/obese adult daughter were 1.3 (95% CI, 1.1-1.7), 1.7 (95% CI, 1.4-2.1) and 1.8 (95% CI, 1.5-2.1), respectively, if mothers exceeded guidelines and their prepregnancy BMI was <25, overweight (BMI 25-<30), or obese (BMI >30). This pattern held irrespective of daughters' weight status at birth, at age 4 years, or at age 20 years. CONCLUSION: Our findings support that obesity prevention before pregnancy and strategies to maintain weight gain during pregnancy within the IOM guidelines might reduce the risk of being overweight in midlife for the offspring.

Glucocorticoid receptor gene haplotypes are not associated with birth anthropometry, blood pressure, glucose and insulin concentrations, and body composition in subjects born small for gestational age.

OBJECTIVE: Smaller size at birth has been associated with an increased risk of metabolic and cardiovascular disorders in adult life. Fetal programming of the hypothalamic-pituitary-adrenal axis has been suggested as a possible explanation. Fetal glucocorticoid (GC) overexposure has effects that suggest a role of GCs in this programming. The effects of GCs are mediated through the GC receptor (GR or NR3C1). Several functional polymorphisms have been described, which are associated with relative GC resistance or hypersensitivity. Our aim is to compare frequencies of GR haplotypes, characterized by the R23K, N363S, Bcl1, or 9ß polymorphisms, in subjects born small for gestational age (SGA) and associate birth anthropometry data, response to GH treatment, blood pressure, glucose and insulin concentrations, and body composition with these haplotypes. DESIGN: In total, 418 SGA subjects and 697 healthy controls were enrolled in this study. Methods Anthropometry data were obtained, as well as blood samples to determine fasting glucose and insulin concentrations. Dual energy X-ray absorptiometry scans were used to measure the amount of fat and lean mass. RESULTS: No differences were found between GR haplotype frequencies in SGA children compared with healthy controls. No associations were found between GR haplotypes and birth length and birth weight, growth response during GH treatment, blood pressure, glucose and insulin concentrations, and body composition. CONCLUSION: GR haplotypes and their effect on GC sensitivity do not seem to play a significant role in GH-induced catch-up growth and the risk factors of developing metabolic and cardiovascular disorders in adult life of SGA children.

Genetic and epigenetic variability in the gene for IGFBP-3 (IGFBP3): correlation with serum IGFBP-3 levels and growth in short children born small for gestational age.

CONTEXT: IGF-I and IGFBP-3 play a central role in fetal and postnatal growth and levels are low in short SGA children. The -202 A/C and -185 C/T SNPs are located near elements involved in directing IGFBP3 promoter activity and expression. Changes in promoter CpG methylation status affect transcription factor binding and transcriptional activation of IGFBP3 in vitro. OBJECTIVE: To assess the relationship between IGFBP3 promoter SNPs, IGFBP-3 levels, spontaneous growth and growth response to GH treatment in short prepubertal SGA children. To assess promoter methylation status in a subgroup of short SGA subjects and controls. PATIENTS: 292 Short prepubertal SGA children, 39 short young SGA adults and 85 young adults with normal stature. INTERVENTION: Short prepubertal SGA children received GH 1mg/m(2)/day. OUTCOME MEASURES: Fasting levels of IGF-I and IGFBP-3, baseline and delta height SDS. RESULTS: At baseline, IGFBP-3 levels were highest in SGA children with -202 AA genotype and lower in children with 1 or 2 copies of the C-allele (P<0.001). Children with C(-202)/C(-185) haplotype, compared to children with A(-202)/C(-185) haplotype, had lower IGFBP-3 levels (P=0.003) and were shorter (P=0.03). During GH treatment, children with C(-202)/C(-185) haplotype showed a significantly greater increase in IGFBP-3 SDS and in height SDS than children with A(-202)/C(-185) haplotype, resulting in similar IGFBP-3 levels and similar height SDS after 12 months of GH treatment. CpG methylation patterns showed a trend towards more methylation of CpGs involved in transcription factor binding in short young SGA adults compared to controls. CONCLUSION: Polymorphic variation in the IGFBP3 promoter region is correlated with IGFBP-3 levels, spontaneous growth and response to GH treatment in short SGA children.

Polymorphisms in the IGF1 and IGF1R genes and children born small for gestational age: results of large population studies.

Small for gestational age (SGA) is the term used to describe a group of children born with a birth weight and/or birth length below the normal range of a reference population, corrected for their gestational age. Although animal models have shown that insulin-like growth factor 1 (IGF1) and insulin-like growth factor 1 receptor (IGF1R) genes are important candidates for reduced pre- and postnatal growth, only limited case reports have been published describing mutations. This might suggest that IGF1 and IGF1R are such crucial growth factors that only common genetic polymorphisms are allowed to survive. Common IGF1 and IGF1R gene polymorphisms, such as single nucleotide polymorphisms and variable number of tandem repeats, have been investigated with conflicting results with respect to SGA-related outcomes. The exact contribution of these polymorphisms to clinical practice remains to be elucidated.