A population study of risk factors for autism spectrum disorders in the Faroe Islands

Kočovská, Eva (2014) A population study of risk factors for autism spectrum disorders in the Faroe Islands. PhD thesis, University of Glasgow.

Abstract

Objectives: To study autism spectrum disorder (ASD) in the Faroe Islands, including prevalence, diagnostic stability and environmental factors that are potentially involved in the aetiology of autism.
Method: I. The target group was recruited from the entire population sample of participants with ASD during a two-phase screening and diagnostic process of the entire Faroe Islands population in the relevant school age group born between 1985-1994 (7-16 years, n=7,689) in 2002 and again in 2009 (15-24 years, n= 7,128) using an independent clinical diagnosis and standardised tools. II. The diagnostic stability of ASD from childhood to early adulthood over a period of 7 years compared diagnoses in 2002 and 2009. III. A literature search of vitamin D and ASD covering the period from January 1 1995 to October 31 2011 was carried out. IV. A pilot study involved questioning 20 mothers of young individuals from the target group and 13 mothers of healthy comparisons, regarding mothers’ diet habits, health, life-style and well-being during their pregnancy with an index child. V. 25-hydroxyvitamin D3 (25(OH)D3) levels were examined in a population based cross-sectional study that involved 219 individuals: 40 participants with a diagnosis of ASD from the target group (31 males/9 females), their 62 typically developing siblings (29 brothers/33 sisters), their 77 parents (40 mothers/37 fathers), and 40 healthy comparisons (28 males/12 females).
Results: I. The rate of ASD rose significantly from 0.56% (n=43) in 2002 to 0.93% (n=66) in 2009. Although these results were still within the range of typical findings from other studies, of the 24 newly discovered cases in 2009 nearly half were females thus altering the male/female ratio from 6/1 to 2.7/1. II. The stability of clinical ASD diagnosis was perfect for AD, good for “atypical autism”/PDD-NOS, and less than perfect for Asperger syndrome (AS). Stability of the diagnoses made by means of research tools were more variable but still good for AD. Both systems showed excellent stability over the seven-year period for “any ASD” diagnosis, although a number of clear cases (especially in females) had been missed in the original screening in 2002. These results support the notion that a single overarching diagnostic category, ‘autism’ or ASD, would better suit clinical realities as outlined in the new DSM-5. III. The systematic review (in 2010) provided some, albeit very limited, support for the possible role of vitamin D deficiency in the pathogenesis of ASD: there are three main areas of involvement of vitamin D in the human body that could potentially have direct impact on the development of ASD: (1) the brain, (2) gene regulation and (3) the immune system. The prevalence of ASD has been suggested to be raised at higher latitudes. IV. Mothers of individuals with ASD had had during their pregnancy significantly less positive “attitude to sun” (p=0.001), consumed fewer vegetables (p=0.026) and also less fruit (p=0.078). V. The ASD case group had significantly lower 25(OH)D3 levels (24.8 nmol/L) than their typically-developing siblings (42.6 nmol/L, p<0.001) and their parents (44.9 nmol/L, p<0.001), and also significantly lower than healthy age and gender matched comparisons (37.6 nmol/L, p=0.002). There was a trend for males having lower 25(OH)D3 levels than females. There was no association between vitamin D and age, month/season of birth, IQ or subcategories of ASD. Among the ASD group, 60% were severely deficient (<30 nmol/L) and 84.2% of the whole study sample (n=219) had deficient/insufficient levels (<50/<75 nmol/L).
Conclusions: I. ASD prevalence in the Faroe Islands increased from 0.56% in 2002 to 0.93% in 2009 mainly due to missed cases in 2002, nearly half of them females. II. There was diagnostic stability for the overall category of ASD over time in the group diagnosed in childhood (7—16) years, but considerable variability with regards to diagnostic sub-groupings. Diagnosing females require novel approach.
III. Vitamin D deficiency–either during pregnancy or early childhood–may be an environmental trigger for ASD in individuals genetically predisposed to the broad phenotype of autism. IV. There are some interesting differences in the diet and life-style habits between mothers with a child with ASD and mothers with a healthy child. The ASD-group’s negative “attitude to sun” may indicate some life-style/health differences which may play a role in pathogenesis of ASD, especially in combination with other environmental risk factors.
V. The present study, demonstrating an association between low levels of 25(OH)D3 and ASD, is the first to be based in a total population and to use siblings, parents and general population control groups. It adds to similar findings from other regions of the world, indicating vitamin D deficiency in the population and especially in individuals with ASD. As all groups were exposed to low levels of sunlight, the very low 25(OH)D3 in the ASD group suggests that some other underlying pathogenic mechanism may be involved.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Published articles: I. Kočovská, E., Biskupstø, R., Gillberg, I. C., Ellefsen, Á., Kampmann, H., Stórá, T., Billstedt, E., and Gillberg, C. (2012) The rising prevalence of autism: A prospective longitudinal study in the Faroe Islands. Journal of Autism and Developmental Disorders, 42, 1959-1966. II. Kočovská, E., Fernell, E., Billstedt, E., Minnis, H., and Gillberg, C. (2012). Vitamin D and Autism: Clinical Review. Journal of Research in Developmental Disabilities, 33, 1541-1550. III. Kočovská, E., Billstedt, E., Ellefsen, Á., Kampmann, H., Gillberg, I. C., Biskupstø, R. Andorsdóttir, G., Stórá, T., and Gillberg, C. (2013). Autism in the Faroe Islands: Diagnostic stability from childhood to early adult life. The Scientific World Journal, Special Issue on ESSENCE, Article ID 592371, http://dx.doi.org/10.1155/2013/592371. IV. Kočovská, E., Andorsdóttir, G., Weihe, P., Halling, J., Fernell, E., Stórá, T., Biskupstø, R., Gillberg, I.C., Shea, R., Billstedt, E., Bourgeron, T., Minnis, H., and Gillberg, C. (2014). Vitamin D in the General Population of Young Adults with Autism in the Faroe Islands. Journal of Autism and Developmental Disorders. E-published June 2014 DOI : 10.1007/s10803-014-2155-1 V. Kočovská, E., Weihe, P., Fossadal, E., Andorsdóttir, G., Biskupstø, R., Halling, J., Minnis, H. and Gillberg, C. (2014). Dietary and lifestyle habits in pregnancy in the Faroe Islands. Brief Report. Manuscript in preparation.
• Keywords: Autism, autism spectrum disorder, ASD, Asperger syndrome, atypical autism, DSM-IV, DSM-5, Diagnostic Interview for Social and Communication Disorders, DISCO, Autism Diagnostic Observation Schedule, ADOS, Autism Spectrum Screening Questionnaire, ASSQ, psychological aspects, neuropsychological aspects, IQ, autism prevalence, aetiology of autism, gene-environment interaction, neurodevelopment, population, diagnosis of autism, diagnostic stability, gender aspects of ASD, the Faroe Islands, genetic isolate, vitamin D, 25(OH)D3, maternal/neonatal vitamin D deficiency, calcitriol, 1,25(OH)2D3, diet, mercury, Hg, MeHg, MeHgX, CH3HgX, pilot whale, Globicephala melas, mercury toxicity, genetic susceptibility, environmental risk factors, maternal lifestyle during pregnancy, attitude to sun, siblings, parents, typically developing children, adolescents, young adults.
• Subjects: B Philosophy. Psychology. Religion > BF Psychology; R Medicine > R Medicine (General); R Medicine > RJ Pediatrics
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
• Supervisor's Name: Minnis, Professor Helen, Gillberg, Professor Christopher and Billstedt, Dr. Eva
• Date of Award: 2014
• Depositing User: Dr Eva Marie Kočovská
• Unique ID: glathesis:2014-5555
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 09 Oct 2014 10:57
• Last Modified: 23 Nov 2015 14:44
• URI: https://theses.gla.ac.uk/id/eprint/5555