The sex ratio of full and half siblings of people diagnosed with an autism spectrum disorder: a Danish Nationwide Register Study.

In the extreme male brain theory of autism sex steroid hormones are hypothesized to influence brain development and to mediate sex differences in developmental psychopathology. Within this scope we examined the sex ratio (proportion of males) in siblings of individuals diagnosed with autism spectrum disorders (ASD). We did a nationwide, register based cohort study of the sex ratio in 17,380 siblings of the 10,297 patients diagnosed with ASD at age 17 years and younger and registered in the nationwide Danish Psychiatric Central Register between 1994 and 2012. Among the 17,380 siblings 8,828 were males and 8,552 females. This yields a sex ratio of 0.508, which is not different from the Danish live birth sex ratio of 0.513 during the relevant years (P = 0.18). Overall, our findings provide no support for the hypothesis that there are relatively more males among the siblings of people with ASD. Accordingly, our results do not give support to the extreme male brain theory of autism.

Epilepsy and other central nervous system diseases in atypical autism: a case control study.

There is an increased but variable risk of epilepsy in autism spectrum disorders. The objective of this study is to compare the prevalence and types of epilepsy and other central nervous system (CNS) diseases in a clinical sample of 89 individuals diagnosed as children with atypical autism (AA) with 258 matched controls from the general population. Diagnoses were based on data from the nationwide Danish National Hospital Register. The average observation time was 32.9 years, and mean age at follow-up was 48.5 years. Of the 89 individuals with AA, 20 (22.5%) were registered with at least one epilepsy diagnosis against 11 (4.3%) in the comparison group (P < 0.0001; OR 6.5; 95% CI 3.0-14.2). Other CNS diseases occurred with low frequency in both groups, and no single CNS disease (except epilepsy) was significantly more frequent among patients with AA. Low intelligence was a risk factor for epilepsy in AA.

Sibling sex ratio of individuals diagnosed with autism spectrum disorder as children.

AIM: To study the sex ratio (proportion of males) in siblings of individuals diagnosed with autism spectrum disorders (ASDs) as children. METHOD: In the current study, we extended previous studies dealing with the androgen theory of autism and examined sex ratios in the siblings of 326 individuals with ASD (245 males, 81 females) who had been consecutively assessed at two Danish university clinics of child psychiatry during the 25-year period from 1960 to 1985. RESULTS: Among the 513 siblings, 300 were males and 213 females. This yields a sex ratio of 0.585, which is significantly higher than the Danish live-birth sex ratio over the same period (0.514, p=0.001). The sibling sex ratio was not associated with the IQ in the autistic probands. INTERPRETATION: Our findings suggest a potential indirect confirmation of the androgen theory of autism.

Selected testosterone-related diseases in women who have given birth to a child with infantile autism.

AIM: The objective of the current study was to compare the prevalence of three testosterone-related cancer diseases in the mothers of 111 individuals diagnosed as children with infantile autism (IA) with a matched comparison group of mothers of 330 children from the general population. METHOD: All mothers were screened through the nationwide Danish National Hospital Register. We inquired about breast-, uterine-, and ovarian cancer diseases during an observation period of 27 years. RESULTS: At follow up a similar proportion of case and control mothers had a diagnosis of any cancer disease: 6.3% vs 8.5%. In addition, no single cancer disease was significantly more frequent among mothers of children with IA. CONCLUSION: Our study provides no support for an (eventually androgen-mediated) increased rate of cancer in mothers of persons with IA.

Psychiatric disorders in individuals diagnosed with infantile autism as children: a case control study.

The objective of this study was to compare the prevalence and types of psychiatric disorders in a clinical sample of 118 individuals diagnosed as children with infantile autism (IA) with psychiatric disorders in 336 matched controls from the general population using data from the nationwide Danish Psychiatric Central Register. The average observation time was 32.5 years, and mean age at follow-up was 40.6 years (range 25-55 years). Of the 118 individuals with IA, 57 (48.3%) had been in contact with psychiatric hospitals (inpatient hospitalization or outpatient visits) during the follow-up period, compared with 20/336 (6.0%) in the control group (p < 0.0001). This observation should alert general psychiatrists to the possibility of additional treatable psychiatric disorders occurring in individuals with IA. Of the 118 individuals in the IA group, 20 individuals (17%) had been given a comorbid psychiatric diagnosis during the observation period, compared with 9 individuals (2.7%) in the control group. Of the subjects with IA, 3.4% had received a diagnosis of schizophrenia (F20) at least once since the index admission in childhood, 0.8% had been diagnosed with delusional disorder (F22), 0.8% with acute psychotic disorder (F23), and 1.6% with unspecified non-organic psychosis (F29). In the control group, 0.9% had been diagnosed with schizophrenia (p = 0.08). In the group with IA, 3.4% had received a diagnosis in the broad category of affective disorders compared with 1.2% in the control group (p = 0.21). Issues associated with using registers in the ascertainment of co-occurring psychiatric disorders in IA are discussed.

Body mass index in male and female children with pervasive developmental disorders.

BACKGROUND: The aim of the present study was to evaluate body mass index (BMI) of children with a pervasive developmental disorder (PDD) attending two university clinics during the 1960-84 period. METHODS: BMI derived from medical records of 83 consecutively admitted children with atypical autism and 115 children with Asperger syndrome were compared with the corresponding BMI percentiles in an age- and sex-matched reference population. RESULTS: The BMI distribution of the boys, but not the girls, in both diagnostic categories was significantly lower than those of the age-matched reference populations. Approximately 15% of the boys had a BMI below the fifth percentile. CONCLUSIONS: The present findings are comparable to the results of other studies. Particular attention is given to low BMI as a potential endophenotype in boys with PDD.

Mortality and causes of death in autism spectrum disorders: an update.

This study compared mortality among Danish citizens with autism spectrum disorders (ASDs) with that of the general population. A clinical cohort of 341 Danish individuals with variants of ASD, previously followed over the period 1960-93, now on average 43 years of age, were updated with respect to mortality and causes of death. Standardized mortality ratios (SMRs) were calculated for various times after diagnosis. In all, 26 persons with ASD had died, whereas the expected number of deaths was 13.5. Thus the mortality risk among those with ASD was nearly twice that of the general population. The SMR was particularly high in females. The excess mortality risk has remained unchanged since our first study in 1993. Eight of the 26 deaths were associated with epilepsy and four died from epilepsy. Future staff education should focus on better managing of the complex relationships between ASD and physical illness to prevent avoidable deaths.

Pervasive developmental disorders and criminal behaviour: a case control study.

The prevalence and pattern of criminal behaviour in a population of 313 former child psychiatric in-patients with pervasive developmental disorders were studied. The patients were divided into three subgroups and compared with 933 matched controls from the general population. Age at follow-up was between 25 years and 59 years. An account of convictions in the nationwide Danish Register of Criminality was used as a measure of criminal behaviour. Among 113 cases with childhood autism, .9% had been convicted. In atypical autism (n=86) and Asperger's syndrome (n=114) the percentages were 8.1% and 18.4%, respectively. The corresponding rate of convictions in the comparison groups was 18.9%, 14.7%, and 19.6% respectively. Particular attention is given to arson in Asperger's syndrome (p= .0009).

Eye Disorders among Adult People Diagnosed with Infantile Autism in Childhood: A Longitudinal Case Control Study.

PURPOSE: The objective of this study was to compare the prevalence and types of eye disorders in a clinical sample of 118 adult people diagnosed with infantile autism (IA) during childhood with 336 sex- and age-matched controls from the general population. METHODS: All participants were screened through the nationwide Danish National Hospital Register. The average observation time of both groups was 37.2 years, and mean age was 49.6 years, by the end of the observation period. RESULTS: The overall prevalence of any eye disorder was 15.3% (18/118) in cases with IA, compared to 10.1% (34/336) in controls (p = 0.18). Refraction and accommodation disorders were significantly associated with IA: 7.6% (9/118) vs 1.2% (4/336) (p = 0.001). The rate of eye disorder was particularly high (24.5%) in those with a co-occurring profound or severe learning disability (IQ < 50). CONCLUSIONS: Refraction and accommodation disorders were more frequently present in Danish adults with IA, particularly when a profound or severe learning disability was co-present. The increased prevalence of eye disorders in participants with a severe or profound learning disability, and the fact that people with IA do not necessarily realize the presence of a vision deficit, necessitates increased ophthalmological attention.

The Sex Ratio of Full and Half Siblings of People Diagnosed With ADHD in Childhood and Adolescence: A Danish Nationwide Register-Based Cohort Study.

OBJECTIVE: It has been suggested that high levels of prenatal testosterone exposure are implied in the etiology of male preponderance disorders such as autism spectrum disorder and ADHD. Within this scope, we studied the sex ratio (proportion of males) in siblings of individuals diagnosed with ADHD in childhood and adolescence. METHOD: We did a nationwide, register-based cohort study of the sex ratio in siblings of the 16,381 patients in Denmark diagnosed with ADHD at age 17 years and younger and registered in the nationwide Danish Psychiatric Central Register between January 1, 1994 and May 28, 2013. RESULTS: Among the 33,151 siblings, 17,041 were males and 16,110 females. This yields a sex ratio of 0.514, which is not statistically significant different from the Danish live birth sex ratio of 0.513 during the relevant years (p = .70). CONCLUSION: These findings provide no support for the hypothesis that the sex ratio is elevated among the siblings of people with ADHD.

Diseases of the circulatory system among adult people diagnosed with infantile autism as children: A longitudinal case control study.

BACKGROUND: Research dealing with adult people with autism spectrum disorders (ASD) noticeably lags behind studies of children and young individuals with ASD. AIMS: The objective of this study was to compare the prevalence and types of diseases of the circulatory system in a clinical sample of 118 adult people diagnosed with infantile autism (IA) as children with 336 sex and age matched controls from the general population. METHODS AND PROCEDURES: All participants were screened through the nationwide Danish National Hospital Register. The average observation time of both groups was 37.2 years, and mean age at follow-up was 49.6 years. OUTCOMES AND RESULTS: Of the 118 people with IA, 11 (9.3%) were registered with at least one disease of the circulatory system against 54 (16.1%) in the comparison group (p=0.09; OR=0.54; 95% CI 0.3-1.2). Ischemic heart diseases occurred significantly more frequently among people in the comparison group (p=0.02). CONCLUSIONS AND IMPLICATIONS: It is argued that diseases of the circulatory system may be underdiagnosed in people with IA because of the difficulties they face with respect to identifying and communicating symptoms of ill health. Bearing in mind that cardiovascular disease is the primary cause of death in most developed countries, it is suggested that to prevent disease and manage health conditions, health monitoring is essential in adult people with IA.

Body mass index in male and female children with infantile autism.

Morphometry, the measurement of forms, is an ancient practice. Recently, evidence has grown to support the notion that aberrant neurodevelopment may play a role in the pathophysiology of autism. Is the body, like the brain, affected by abnormal development in these patients? The aim of this study was to evaluate body mass index (BMI) of children with infantile autism, by comparing the BMI of 117 children with infantile autism with the corresponding BMI percentiles in an age- and sex-matched reference population. The BMI distribution of the male, but not female, children with infantile autism was significantly lower than that of the age-matched reference population. There was no evidence that BMI was associated with intelligence or socioeconomic status among children with infantile autism.

Diseases of the gastrointestinal tract in individuals diagnosed as children with atypical autism: a Danish register study based on hospital diagnoses.

The purpose of this study is to compare the prevalence and types of diseases (International classification of mental and behavioural disorders, 10th edition codes K20-K93) relating to the gastrointestinal tract in a clinical sample of 89 individuals diagnosed as children with atypical autism/pervasive developmental disorder not otherwise specified with 258 controls from the general population. All participants were screened through the nationwide Danish National Hospital Register. The average observation time was 32.9 years, and mean age at the end of the observation period was 48.5 years. Among the 89 cases with atypical autism, a total of 22 (24.7%) were registered with at least one diagnosis of any disease of the gastrointestinal tract, against 47 of 258 (18.2%) in the comparison group (p = 0.22; odds ratio = 1.5; 95% confidence interval = 0.8-2.6). Without reaching statistical significance, the rate of diseases of the gastrointestinal tract was particularly high (odds ratio = 1.2) in those with intelligence quotient < 70. Overall, people with atypical autism had about the same frequency of gastric, intestinal and hepatic diseases as had controls.

Epilepsy in individuals with a history of Asperger's syndrome: a Danish nationwide register-based cohort study.

We performed a nationwide, register-based retrospective follow-up study of epilepsy in all people who were born between January 1, 1980 and June 29, 2006 and registered in the Danish Psychiatric Central Register with Asperger's syndrome on February 7, 2011. All 4,180 identified cases with AS (3,431 males and 749 females) were screened through the nationwide Danish National Hospital Register (DNHR) with respect to epilepsy. Mean age at follow-up was 18.1 years (range 4-31 years). Of the 4,180 individuals with AS, 164 (3.9%) were registered with at least one epilepsy diagnosis in the DNHR, which is significantly increased (p < 0.0001) relative to the same age group in the general population, where an estimate is about 2.0%.

Fractures in individuals with and without a history of infantile autism. A Danish register study based on hospital discharge diagnoses.

We compared the prevalence and types of fractures in a clinical sample of 118 individuals diagnosed as children with infantile autism (IA) with 336 matched controls from the general population. All participants were screened through the nationwide Danish National Hospital Register. The average observation time was 30.3 years (range 27.3-30.4 years), and mean age at follow-up was 42.7 years (range 27.3-57.3 years). Of the 118 individuals with IA, 14 (11.9%) were registered with at least one fracture diagnosis against 83 (24.7%) in the comparison group (p = 0.004; OR = 0.41; 95%CI 0.22-0.76), but the nature of their fractures seems somewhat different. Epilepsy was a risk factor, but only in the comparison group. Our results lend no support to the notion that fracture is a common comorbid condition in a population of people diagnosed with IA as children.

A longitudinal study of epilepsy and other central nervous system diseases in individuals with and without a history of infantile autism.

OBJECTIVE: To compare the prevalence and types of epilepsy and other central nervous system (CNS) diseases in a clinical sample of 118 individuals diagnosed as children with infantile autism (IA) with 336 matched controls from the general population. METHODS: All participants were screened through the nationwide Danish National Hospital Register (DNHR). The average observation time was 30.3years (range 27-30years), and mean age at follow-up was 42.7years (range 27-57years). RESULTS: Of the 118 individuals with IA, 29 (24.6%) were registered with at least one epilepsy diagnosis against 5 (1.5%) in the comparison group (p<0.0001; OR=21.6; 95% CI 8.1-57.3). Other CNS diseases occurred with low frequency in both groups and only cerebral palsy, unspecified (p=0.02) was significantly more frequent among participants with a history of IA. CONCLUSIONS: Our study lends further support to the notion that epilepsy, but not other CNS diseases, is a common comorbid condition in IA. Low intelligence, but not gender, was a risk factor for epilepsy in IA.

Epilepsy and other neurological diseases in the parents of children with infantile autism. A case control study.

In order to study the broader phenotype of infantile autism (IA) we compared the rates and types of epilepsy and other neurological diseases in the parents of 111 consecutively admitted patients with IA with a matched control group of parents of 330 children from the general population. All participants were screened through the nationwide Danish National Hospital Register (DNHR). We inquired about epilepsy and other neurological diseases during an observation period of 27 years. A similar proportion of case- and control mothers had a diagnosis of any neurological disease, 9.9% vs 10.6%. For case fathers the proportion was 5.7% vs 9.7%. No single neurological disease was significantly more frequent among parents of persons with IA. Our study lent support to the notion that epilepsy and other neurological diseases are not part of the broader IA phenotype.

Autoimmune diseases in parents of children with infantile autism: a case-control study.

This register study compared the rates and types of autoimmune disease in the parents of 111 patients (82 males, 29 females; mean age at diagnosis 5y 5mo [SD 2y 6mo]) with infantile autism (IA) with a matched control group of parents of 330 children from the general population. All parents were screened through the nationwide Danish National Hospital Register. We inquired about 35 autoimmune diseases during an observation period of 27 years. At follow-up the case and control mothers were identical in age (65y 7mo [SDs 9y 7mo and 9y respectively]). For case and control fathers the figures were 70 years 2 months (SD 10y 2mo) and 69 years 1 month (SD 10y 1mo) respectively. A similar proportion of case and control mothers had a diagnosis of any autoimmune disease: 10.8% versus 9.1%. For case fathers the proportion was 8.6% versus 4.6%. Two autoimmune conditions were associated with IA: ulcerative colitis in mothers (p=0.05) and type 1 diabetes in fathers (p=0.02). Additional studies are required to determine whether there is a true association between a parental history of autoimmune disease and pervasive developmental disorder in their offspring.