Understanding the substance use of autistic adolescents and adults: a mixed-methods approach.

BACKGROUND: Autistic individuals might be more likely to misuse substances than non-autistic individuals. Better understanding of these patterns can help clinicians identify strategies to reduce substance use, protecting physical and mental health. The aim of this study was to compare the experiences of substance use between autistic and non-autistic adolescents and adults. METHODS: This study is a mixed-methods study, including both quantitative (closed-ended questions) and qualitative (one open-ended question) online assessments. Data were collected as part of a larger study, the Autism and Physical Health Survey, in which we administered an anonymised, online questionnaire to autistic and non-autistic individuals aged 16-90 years. In the present study, we investigated data on substance use or misuse, using two overlapping but separate samples from the survey (one sample with complete quantitative responses and one sample with complete qualitative responses). Binary measures of substance use were investigated using unadjusted and adjusted binomial logistic regression models. Content analysis was used to compare experiences of autistic and non-autistic adolescents and adults. We used Fisher's exact tests to assess differences in frequency of reporting particular qualitative themes and subthemes. FINDINGS: Survey recruitment was done between Feb 7, 2018, and Aug 26, 2019. At the end of the recruitment, 3657 individuals had accessed the survey. After excluding duplicates as well as participants with missing or incomplete responses, we had data from 2386 participants (1183 autistic and 1203 non-autistic participants; 1571 female and 815 male participants) for the quantitative analyses and data from 919 participants (429 autistic and 490 non-autistic participants; 569 female and 350 male participants) in the qualitative analyses. The samples for the quantitative and qualitative analyses were predominantly composed of female individuals, White individuals, UK residents, and those without intellectual disability. Autistic individuals were less likely than non-autistic individuals to report consuming alcohol regularly (16·0% of autistic individuals vs 22·2% of non-autistic individuals; adjusted model: odds ratio [OR] 0·69, 95% CI 0·55-0·86; p=0·0022) or binge-drinking (3·8% vs 8·2%; adjusted model: OR 0·38, 0·26-0·56; p<0·0001). Autistic male participants were less likely than non-autistic male participants to report ever having smoked (50·8% of autistic male participants vs 64·6% of non-autistic male participants; adjusted OR 0·50; 0·32-0·76; p=0·0022) or ever using drugs (35·4% vs 52·7%; adjusted OR 0·53; 0·35-0·80; p=0·0022). Regarding our qualitative analyses, among participants who reported a specific motivation for drug use, compared with non-autistic individuals, autistic individuals were nearly nine times more likely to report using recreational substances to manage behaviour (OR 8·89, 2·05-81·12; p=0·0017) and more likely to report using recreational substances to manage mental health symptoms (OR 3·08, 1·18-9·08; p=0·032). Autistic individuals were also more likely to report vulnerability associated with substance use (OR 4·16, 1·90-10·05; p=0·00027), including childhood use of drugs and being forced or tricked into using drugs. INTERPRETATION: Autistic individuals might be less likely than non-autistic individuals to report engaging in substance misuse. They also report using drugs to self-medicate. Clinicians should be aware of vulnerability linked to substance use among autistic patients and should work cooperatively with patients to effectively manage autistic and comorbid symptoms. FUNDING: Autism Research Trust, Rosetrees Trust, Cambridge and Peterborough NHS Foundation Trust.Autism Research Trust, Cambridge and Peterborough NHS Foundation Trust, Rosetrees Trust, Corbin Charitable Trust, Autistica MRC, ARC-EoE, and Innovative Medicines Initiative 2 Joint Undertakin

An investigation of the diet, exercise, sleep, BMI, and health outcomes of autistic adults.

BackgroundStudies of autistic children suggest that restricted eating, reduced physical activity, and sleep disorders are common; however, no studies attempt to broadly describe the diet, exercise, and sleep patterns of autistic adults or consider relationships between lifestyle behaviors and the widely reported increased risks of obesity and chronic conditions. To address this, the authors developed the largest study of lifestyle patterns of autistic adults and assessed their relationships to body mass index, health outcomes, and family history.MethodsWe administered an anonymized, online survey to n = 2386 adults (n = 1183 autistic) aged 16-90 years of age. We employed Fisher's exact tests and binomial logistic regression to describe diet, exercise, and sleep patterns; mediation of seizure disorders on sleep; body mass index (BMI); relationships of lifestyle factors to BMI, cardiovascular conditions, and diabetic conditions; and sex differences among autistic adults.ResultsAutistic adults, and particularly autistic females, exhibit unhealthy diet, exercise, and sleep patterns; they are also more likely to be underweight or obese. Limited sleep duration and high rates of sleep disturbances cannot be accounted for by epilepsy or seizure disorders. Lifestyle factors are positively related to higher risk of cardiovascular conditions among autistic males, even more than family history.LimitationsOur sample may not be representative of all autistic and non-autistic people, as it primarily comprised individuals who are white, female, have a high school education or higher, and reside in the UK. Our sampling methods may also exclude some individuals on the autism spectrum, and particularly those with moderate to severe intellectual disability. This is a cross-sectional sample that can test for relationships between factors (e.g., lifestyle factors and health outcomes) but cannot assess the direction of these relationships.ConclusionsAutistic adults are less likely to meet minimal health recommendations for diet, exercise, and sleep-and these unhealthy behaviors may relate to excess risk of cardiovascular conditions. Although the present study can only provide preliminary, correlational evidence, our findings suggest that diet, exercise, and sleep should be considered and further investigated as key targets for reducing the now widely reported and dramatically increased risks of health comorbidity and premature death among autistic individuals compared to others. Physicians should work cooperatively with patients to provide health education and develop individualized strategies for how to better manage challenges with diet, exercise, and sleep

An investigation of the diet, exercise, sleep, BMI, and health outcomes of autistic adults.

BackgroundStudies of autistic children suggest that restricted eating, reduced physical activity, and sleep disorders are common; however, no studies attempt to broadly describe the diet, exercise, and sleep patterns of autistic adults or consider relationships between lifestyle behaviors and the widely reported increased risks of obesity and chronic conditions. To address this, the authors developed the largest study of lifestyle patterns of autistic adults and assessed their relationships to body mass index, health outcomes, and family history.MethodsWe administered an anonymized, online survey to n = 2386 adults (n = 1183 autistic) aged 16-90 years of age. We employed Fisher's exact tests and binomial logistic regression to describe diet, exercise, and sleep patterns; mediation of seizure disorders on sleep; body mass index (BMI); relationships of lifestyle factors to BMI, cardiovascular conditions, and diabetic conditions; and sex differences among autistic adults.ResultsAutistic adults, and particularly autistic females, exhibit unhealthy diet, exercise, and sleep patterns; they are also more likely to be underweight or obese. Limited sleep duration and high rates of sleep disturbances cannot be accounted for by epilepsy or seizure disorders. Lifestyle factors are positively related to higher risk of cardiovascular conditions among autistic males, even more than family history.LimitationsOur sample may not be representative of all autistic and non-autistic people, as it primarily comprised individuals who are white, female, have a high school education or higher, and reside in the UK. Our sampling methods may also exclude some individuals on the autism spectrum, and particularly those with moderate to severe intellectual disability. This is a cross-sectional sample that can test for relationships between factors (e.g., lifestyle factors and health outcomes) but cannot assess the direction of these relationships.ConclusionsAutistic adults are less likely to meet minimal health recommendations for diet, exercise, and sleep-and these unhealthy behaviors may relate to excess risk of cardiovascular conditions. Although the present study can only provide preliminary, correlational evidence, our findings suggest that diet, exercise, and sleep should be considered and further investigated as key targets for reducing the now widely reported and dramatically increased risks of health comorbidity and premature death among autistic individuals compared to others. Physicians should work cooperatively with patients to provide health education and develop individualized strategies for how to better manage challenges with diet, exercise, and sleep

The sexual health, orientation, and activity of autistic adolescents and adults

Funder: Applied Health Research and Care (ARC‐EoE); Id: http://dx.doi.org/10.13039/501100012358Funder: Corbin Charitable TrustFunder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100000265Funder: National Institute of Health Research (NIHR)Funder: Templeton World Charity Foundation; Id: http://dx.doi.org/10.13039/501100011730Funder: University of Cambridge; Id: http://dx.doi.org/10.13039/501100000735Funder: Department of Health; Id: http://dx.doi.org/10.13039/501100003921Funder: Health Research; Id: http://dx.doi.org/10.13039/100005622Funder: National Institute for Health Research; Id: http://dx.doi.org/10.13039/501100000272Funder: Biomedical Research Centre; Id: http://dx.doi.org/10.13039/100014461Funder: AUTISM SPEAKS; Id: http://dx.doi.org/10.13039/100000073Funder: Horizon 2020; Id: http://dx.doi.org/10.13039/100010661Funder: European Union; Id: http://dx.doi.org/10.13039/501100000780Funder: Innovative Medicines Initiative; Id: http://dx.doi.org/10.13039/501100010767Funder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100010269Abstract: Small studies suggest significant differences between autistic and nonautistic individuals regarding sexual orientation and behavior. We administered an anonymized, online survey to n = 2386 adults (n = 1183 autistic) aged 16–90 years to describe sexual activity, risk of sexually transmitted infections (STIs), and sexual orientation. Autistic individuals are less likely to report sexually activity or heterosexuality compared to nonautistic individuals, but more likely to self‐report asexuality or an ‘other’ sexuality. Overall, autistic, and nonautistic groups did not differ in age of sexual activity onset or contraction of STIs. When evaluating sex differences, autistic males are uniquely more likely to be bisexual (compared to nonautistic males); conversely, autistic females are uniquely more likely to be homosexual (compared to nonautistic females). Thus, both autistic males and females may express a wider range of sexual orientations in different sex‐specific patterns than general population peers. When comparing autistic males and females directly, females are more likely to have diverse sexual orientations (except for homosexuality) and engage in sexual activity, are less likely to identify as heterosexual, and have a lower mean age at which they first begin engaging in sexual activity. This is the largest study of sexual orientation of autistic adults. Sexual education and sexual health screenings of all children, adolescents, and adults (including autistic individuals) must remain priorities; healthcare professionals should use language that affirms a diversity of sexual orientations and supports autistic individuals who may have increased risks (affecting mental health, physical health, and healthcare quality) due to stress and discrimination from this intersectionality

Investigating the effectiveness of the Mediterranean diet in pregnant women for the primary prevention of asthma and allergy in high-risk infants: protocol for a pilot randomised controlled trial

This research is funded by the Chief Scientist Office of The Scottish Government/Chief Medical Officer Directorate (Grant CZG/2/558). The authors would like to acknowledge the staff involved in the NHS ethical and research and development review processes, and staff at the Health Records Department of the Edinburgh Royal Infirmary for their help in getting the recruitment material to potential participants. The staff at the ultrasound/X-ray clinics at the two NHS Lothian sites where the participants are met by the researcher are most helpful and accommodating. The authors thank Anne Galloway (dietitian) who, when available, is delivering the intervention at one of the sites. They would also like to thank the participants for volunteering to take part, Dr Rob Elton the independent statistician, and Julia Clark (dietitian), Dr Ulugbek Nurmatov (researcher), and our Consumer Involvement Group for their input.Peer reviewedPublisher PD

Increased prevalence of non-communicable physical health conditions among autistic adults

Funder: National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation TrustFunder: NIHR Biomedical Research Centre, CambridgeFunder: The Rosetrees TrustFunder: Corbin Charitable TrustFunder: Templeton World Charity Foundation; FundRef: https://doi.org/10.13039/501100011730Funder: Wellcome Trust; FundRef: https://doi.org/10.13039/100004440Funder: Cambridgeshire and Peterborough NHS Foundation TrustFunder: Medical Research Council; FundRef: https://doi.org/10.13039/501100000265Funder: Autism Research TrustFunder: university of cambridge; FundRef: https://doi.org/10.13039/501100000735Autistic individuals may be at risk of premature mortality, and physical health comorbidity increases this risk; however, most studies fail to include older autistic adults or consider lifestyle-related factors that affect health. We developed an anonymous, online physical health survey. The final sample included n = 2368 individuals (mean age = 41.42), and of these, n = 1156 were autistic individuals (mean age = 40.98). We utilized three sex-stratified statistical models to determine the prevalence of cancer, cardiovascular conditions, respiratory conditions, and diabetes. All three models indicate that autistic females are more likely to have cardiovascular conditions, respiratory conditions, asthma, low blood pressure, arrhythmias, and prediabetes than non-autistic females, and autistic males are more likely to have arrhythmias than non-autistic males; these results suggest that autistic individuals carry increased risks for these conditions when compared to the general population, even after controlling for age, ethnicity, education level, body mass index, smoking, and alcohol use. Further, these risks may differ depending on biological sex for autistic individuals. Autistic adults, and particularly autistic females, have greater and wider-ranging risks than previously thought, even after controlling for demographic and lifestyle-related factors. Although this is a large sample of autistic adults across the lifespan, future research should employ larger, population-based samples to confirm these findings. Lay abstract: Previous research indicates autistic individuals die at a younger age than others and that this is possibly due in part to chronic physical health conditions. The present study used an anonymous, online survey to determine how common certain physical health conditions are among autistic adults, compared with non-autistic adults. We found autistic adults are more likely to develop heart conditions, lung conditions, and diabetes than non-autistic adults. Autistic females may be at higher risk of developing certain conditions (including respiratory conditions, asthma, and prediabetes) than autistic males. Finally, autistic individuals have increased health risks even when considering lifestyle factors (such as smoking, alcohol, and body mass index). This is still a relatively small study, and future research needs to confirm these findings and identify why these risks exist

Elevated rates of autism, other neurodevelopmental and psychiatric diagnoses, and autistic traits in transgender and gender-diverse individuals

Abstract: It is unclear whether transgender and gender-diverse individuals have elevated rates of autism diagnosis or traits related to autism compared to cisgender individuals in large non-clinic-based cohorts. To investigate this, we use five independently recruited cross-sectional datasets consisting of 641,860 individuals who completed information on gender, neurodevelopmental and psychiatric diagnoses including autism, and measures of traits related to autism (self-report measures of autistic traits, empathy, systemizing, and sensory sensitivity). Compared to cisgender individuals, transgender and gender-diverse individuals have, on average, higher rates of autism, other neurodevelopmental and psychiatric diagnoses. For both autistic and non-autistic individuals, transgender and gender-diverse individuals score, on average, higher on self-report measures of autistic traits, systemizing, and sensory sensitivity, and, on average, lower on self-report measures of empathy. The results may have clinical implications for improving access to mental health care and tailoring adequate support for transgender and gender-diverse individuals

AMPK is essential for energy homeostasis regulation and glucose sensing by POMC and AgRP neurons

Hypothalamic AMP-activated protein kinase (AMPK) has been suggested to act as a key sensing mechanism, responding to hormones and nutrients in the regulation of energy homeostasis. However, the precise neuronal populations and cellular mechanisms involved are unclear. The effects of long-term manipulation of hypothalamic AMPK on energy balance are also unknown. To directly address such issues, we generated POMC alpha 2KO and AgRP alpha 2KO mice lacking AMPK alpha 2 in proopiomelanocortin- (POMC-) and agouti-related protein-expressing (AgRP-expressing) neurons, key regulators of energy homeostasis. POMC alpha 2KO mice developed obesity due to reduced energy expenditure and dysregulated food intake but remained sensitive to leptin. in contrast, AgRPa2KO mice developed an age-dependent lean phenotype with increased sensitivity to a melanocortin agonist. Electrophysiological studies in AMPK alpha 2-deficient POMC or AgRP neurons revealed normal leptin or insulin action but absent responses to alterations in extracellular glucose levels, showing that glucose-sensing signaling mechanisms in these neurons are distinct from those pathways utilized by leptin or insulin. Taken together with the divergent phenotypes of POMC alpha 2KO and AgRP alpha 2KO mice, our findings suggest that while AMPK plays a key role in hypothalamic function, it does not act as a general sensor and integrator of energy homeostasis in the mediobasal hypothalamus

Glucose Induces Pancreatic Islet Cell Apoptosis That Requires the BH3-Only Proteins Bim and Puma and Multi-BH Domain Protein Bax

OBJECTIVE: High concentrations of circulating glucose are believed to contribute to defective insulin secretion and beta-cell function in diabetes and at least some of this effect appears to be caused by glucose-induced beta-cell apoptosis. In mammalian cells, apoptotic cell death is controlled by the interplay of proapoptotic and antiapoptotic members of the Bcl-2 family. We investigated the apoptotic pathway induced in mouse pancreatic islet cells after exposure to high concentrations of the reducing sugars ribose and glucose as a model of beta-cell death due to long-term metabolic stress. RESEARCH DESIGN AND METHODS: Islets isolated from mice lacking molecules implicated in cell death pathways were exposed to high concentrations of glucose or ribose. Apoptosis was measured by analysis of DNA fragmentation and release of mitochondrial cytochrome c. RESULTS: Deficiency of interleukin-1 receptors or Fas did not diminish apoptosis, making involvement of inflammatory cytokine receptor or death receptor signaling in glucose-induced apoptosis unlikely. In contrast, overexpression of the prosurvival protein Bcl-2 or deficiency of the apoptosis initiating BH3-only proteins Bim or Puma, or the downstream apoptosis effector Bax, markedly reduced glucose- or ribose-induced killing of islets. Loss of other BH3-only proteins Bid or Noxa, or the Bax-related effector Bak, had no impact on glucose-induced apoptosis. CONCLUSIONS: These results implicate the Bcl-2 regulated apoptotic pathway in glucose-induced islet cell killing and indicate points in the pathway at which interventional strategies can be designed

Protective Unfolded Protein Response in Human Pancreatic Beta Cells Transplanted into Mice

Background: There is great interest about the possible contribution of ER stress to the apoptosis of pancreatic beta cells in the diabetic state and with islet transplantation. Methods and Findings: Expression of genes involved in ER stress were examined in beta cell enriched tissue obtained with laser capture microdissection (LCM) from frozen sections of pancreases obtained from non-diabetic subjects at surgery and from human islets transplanted into ICR-SCID mice for 4 wk. Because mice have higher glucose levels than humans, the transplanted beta cells were exposed to mild hyperglycemia and the abnormal environment of the transplant site. RNA was extracted from the LCM specimens, amplified and then subjected to microarray analysis. The transplanted beta cells showed an unfolded protein response (UPR). There was activation of many genes of the IRE-1 pathway that provide protection against the deleterious effects of ER stress, increased expression of ER chaperones and ERAD (ER-associated protein degradation) proteins. The other two arms of ER stress, PERK and ATF-6, had many down regulated genes. Downregulation of EIF2A could protect by inhibiting protein synthesis. Two genes known to contribute to apoptosis, CHOP and JNK, were downregulated. Conclusions: Human beta cells in a transplant site had UPR changes in gene expression that protect against the proapoptotic effects of unfolded proteins