Simplex and multiplex stratification in ASD and ADHD families: a promising approach for identifying overlapping and unique underpinnings of ASD and ADHD?

Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) are highly heterogeneous neuropsychiatric disorders, that frequently co-occur. This study examined whether stratification into single-incidence (SPX) and multi-incidence (MPX) is helpful in (a) parsing heterogeneity and (b) detecting overlapping and unique underpinnings of the disorders. ASD and ADHD traits were measured in 56 ASD/31 ADHD SPX families, 59 ASD/171 ADHD MPX families and 203 control families. In ASD but not ADHD, behavioral traits were less elevated in SPX than MPX unaffected relatives, suggesting that SPX-MPX stratification may thus help parse ASD, but not ADHD heterogeneity. Particularly unaffected relatives from MPX ASD/ADHD families displayed elevated trait levels of both disorders, indicating shared (multifactorial) underpinnings underlying ASD and ADHD in these families. Cross-disorder traits were highest in MPX ASD unaffected siblings.

The reciprocal relationship of ASD, ADHD, depressive symptoms and stress in parents of children with ASD and/or ADHD.

This study investigated the role of parental Autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and depressive symptoms on parenting stress in 174 families with children with ASD and/or ADHD, using generalized linear models and structural equation models. Fathers and mothers reported more stress when parenting with their child with ASD and/or ADHD than when parenting with the unaffected sibling; they also experienced more stress than a norm population. Depressive symptoms were most pronounced in the parents of children with ASD and ASD+ADHD. Spouse correlations were found for ASD, depression, and parenting stress. Paternal ASD and maternal ADHD symptoms were related to increased parenting stress, and parental ADHD symptoms with depressive symptoms and parenting stress. The results highlight the increased burden of raising a child with ASD and/or ADHD and the reciprocal relationship this has with parents' ASD, ADHD, and depressive symptoms, and levels of stress.

Recognition of facial emotion and affective prosody in children with ASD (+ADHD) and their unaffected siblings.

Autism is a highly heritable and clinically heterogeneous neuropsychiatric disorder that frequently co-occurs with other psychopathologies, such as attention-deficit/hyperactivity disorder (ADHD). An approach to parse heterogeneity is by forming more homogeneous subgroups of autism spectrum disorder (ASD) patients based on their underlying, heritable cognitive vulnerabilities (endophenotypes). Emotion recognition is a likely endophenotypic candidate for ASD and possibly for ADHD. Therefore, this study aimed to examine whether emotion recognition is a viable endophenotypic candidate for ASD and to assess the impact of comorbid ADHD in this context. A total of 90 children with ASD (43 with and 47 without ADHD), 79 ASD unaffected siblings, and 139 controls aged 6-13 years, were included to test recognition of facial emotion and affective prosody. Our results revealed that the recognition of both facial emotion and affective prosody was impaired in children with ASD and aggravated by the presence of ADHD. The latter could only be partly explained by typical ADHD cognitive deficits, such as inhibitory and attentional problems. The performance of unaffected siblings could overall be considered at an intermediate level, performing somewhat worse than the controls and better than the ASD probands. Our findings suggest that emotion recognition might be a viable endophenotype in ASD and a fruitful target in future family studies of the genetic contribution to ASD and comorbid ADHD. Furthermore, our results suggest that children with comorbid ASD and ADHD are at highest risk for emotion recognition problems.

Are parental autism spectrum disorder and/or attention-deficit/Hyperactivity disorder symptoms related to parenting styles in families with ASD (+ADHD) affected children?

An understudied and sensitive topic nowadays is that even subthreshold symptoms of autism spectrum disorder (ASD) and attention-deficit/Hyperactivity disorder (ADHD) in parents may relate to their parenting styles. The aim of this study was to explore the influence of (the combined) effect of child diagnosis (ASD or ASD + ADHD affected/unaffected children) and parental ASD and/or ADHD on parenting styles. Ninety-six families were recruited with one child with a clinical ASD (+ADHD) diagnosis, and one unaffected sibling. Parental ASD and ADHD symptoms were assessed using self-report. The Parenting Styles Dimensions Questionnaire (PSDQ) self- and spouse-report were used to measure the authoritative, authoritarian, and permissive parenting styles. Fathers and mothers scored significantly higher than the norm data of the PSDQ on the permissive style regarding affected children, and lower on the authoritative and authoritarian parenting style for affected and unaffected children. Self- and spouse-report correlated modestly too strongly. Higher levels of paternal (not maternal) ADHD symptoms were suboptimally related to the three parenting styles. Further, two parent-child pathology interaction effects were found, indicating that fathers with high ADHD symptoms and mothers with high ASD symptoms reported to use a more permissive parenting style only towards their unaffected child. The results highlight the negative effects of paternal ADHD symptoms on parenting styles within families with ASD (+ADHD) affected offspring and the higher permissiveness towards unaffected offspring specifically when paternal ADHD and/or maternal ASD symptoms are high. Parenting training in these families may be beneficial for the well-being of all family members.

Co-segregation of social cognition, executive function and local processing style in children with ASD, their siblings and normal controls.

Cognitive research proposes that social cognition (SC), executive functions (EF) and local processing style (weak CC) may be fruitful areas for research into the familial-genetic underpinnings of Autism Spectrum Disorders (ASD). The performance of 140 children with ASD, 172 siblings and 127 controls on tasks measuring SC (face recognition, affective prosody, and facial emotion recognition), EF (inhibition, cognitive flexibility, and verbal working memory) and local processing style was assessed. Compelling evidence was found for the interrelatedness of SC and EF, but not local processing style, within individuals and within families, suggesting that these domains tend to co-segregate in ASD. Using the underlying shared variance of these constructs in genetic research may increase the power for detecting susceptibility genes for ASD.

How to use the ADI-R for classifying autism spectrum disorders? Psychometric properties of criteria from the literature in 1,204 Dutch children.

The algorithm of the Autism Diagnostic Interview-Revised provides criteria for autism versus non-autism according to DSM-IV. Criteria for the broader autism spectrum disorders are needed. This study investigated the validity of seven sets of criteria from the literature, in 1,204 Dutch children (aged 3-18 years) with and without mental retardation. The original criteria (Rutter et al. in ADI-R Autism Diagnostic Interview Revised. Manual. Western Psychological Services, Los Angeles, 2003) well discriminated ASD from non-ASD in MR. All other criteria (IMGSAC in Am Soc Hum Genet 69:570-581 2001; Sung et al. in Am J Hum Genet 76: 68-81, 2005; Risi et al. in J Am Acad Child Adolesc Psychiatry 45: 1094-1103, 2006) were sensitive at the cost of specificity, bearing the risk of overinclusiveness. In the group without MR, clinicians should decide whether sensitivity or specificity is aimed for, to choose the appropriate criteria. Including the Autism Diagnostic Observation Schedule revised algorithms in the classification, the specificity increases, at the cost of sensitivity. This study adds to a more valid judgment on which criteria to use for specific objectives.

Match or mismatch? Influence of parental and offspring ASD and ADHD symptoms on the parent-child relationship.

Few studies have examined the influence of parental ASD and ADHD symptoms in combination with child pathology on the parent- child relationship as perceived by the child. A sample of 132 families was recruited with one child with ASD (with/without ADHD), and one unaffected sibling. Affected children (regardless of diagnosis) reported lower acceptance and conflict resolution scores than their unaffected siblings, with conflict resolution scores (but not acceptance) being lower than the norm according to both affected and unaffected children in both fathers and mothers. Higher paternal, but not maternal, ASD and ADHD symptoms were related to poorer scores regarding acceptance and conflict resolution, respectively. Treatment targeting conflict resolution skills of parents and the feeling of being less accepted in children with ASD/ADHD may be beneficial.

Head circumference and height abnormalities in autism revisited: the role of pre- and perinatal risk factors.

Pre/perinatal risk factors and body growth abnormalities have been studied frequently as early risk markers in autism spectrum disorder (ASD), yet their interrelatedness in ASD has received very little research attention. This is surprising, given that pre/perinatal risk factors can have a substantial impact on growth trajectories in the first years of life. We aimed to determine which pre/perinatal factors were more prevalent in ASD children and if these factors differentially influenced body growth in ASD and control children. A total of 96 ASD and 163 control children matched for gender participated. Data of growth of head size and body length during the first 13 months of life were collected. Data on pre/perinatal risk factors were retrospectively collected through standardized questionnaires. Results indicated that after matching for SES, prematurity/low birth weight and being first born were more prevalent in the ASD versus the control group. In addition, with increasing age children with ASD tended to have a proportionally smaller head circumference compared to their height. However, the effect of prematurity/low birth weight on head growth corrected for height was significantly different in ASD and control children: premature/low birth weight control children showed a disproportionate larger head circumference in relation to height during their first year of life, whereas this effect was absent in premature/low birth weight ASD children. This may suggest that the etiology of abnormal growth is potentially different in ASD and control children: where abnormal growth in control children is related to suboptimal conditions in the uterus, abnormal growth in ASD may be more strongly related to the causal factors that also increase the risk for ASD. However, prospective studies measuring growth and ASD characteristics in both premature/low birth weight and a terme children are necessary to support this conclusion.

A randomized controlled pilot study into the effects of a restricted elimination diet on family structure in families with ADHD and ODD.

BACKGROUND: Behavioural improvements of children with attention-deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) following a restricted elimination diet (RED), may be due to concurrent changes in family environment. METHODS: Twenty-four children with ADHD, were randomized to either a 5-week RED intervention, or a control intervention consisting of healthy food advices in a pilot study. RESULTS: No differences in family environment were found, neither at baseline nor when comparing the start and end measurements of both groups. CONCLUSIONS: In this pilot study, the effects of an RED on ADHD and ODD are not mediated by improvement of family environment in families motivated to follow an RED. Replication of this preliminary study in larger groups of children is advised.

Are autism spectrum disorder and attention-deficit/hyperactivity disorder different manifestations of one overarching disorder? Cognitive and symptom evidence from a clinical and population-based sample.

OBJECTIVE: Autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD) frequently co-occur. Given the heterogeneity of both disorders, several more homogeneous ASD-ADHD comorbidity subgroups may exist. The current study examined whether such subgroups exist, and whether their overlap or distinctiveness in associated comorbid symptoms and cognitive profiles gives support for a gradient overarching disorder hypothesis or a separate disorders hypothesis. METHOD: Latent class analysis was performed on Social Communication Questionnaire (SCQ) and Conners' Parent Rating Scale (CPRS-R:L) data for 644 children and adolescents (5 through 17 years of age). Classes were compared for comorbid symptoms and cognitive profiles of motor speed and variability, executive functioning, attention, emotion recognition, and detail-focused processing style. RESULTS: Latent class analysis revealed five classes: two without behavioral problems, one with only ADHD behavior, and two with both clinical symptom levels of ASD and ADHD but with one domain more prominent than the other (ADHD[+ASD] and ASD[+ADHD]). In accordance with the gradient overarching disorder hypothesis were the presence of an ADHD class without ASD symptoms and the absence of an ASD class without ADHD symptoms, as well as cognitive functioning of the simple ADHD class being less impaired than that of both comorbid classes. In conflict with this hypothesis was that there was some specificity of cognitive deficits across classes. CONCLUSIONS: The overlapping cognitive deficits may be used to further unravel the shared etiological underpinnings of ASD and ADHD, and the nonoverlapping deficits may indicate why some children develop ADHD despite their enhanced risk for ASD. The two subtypes of children with both ASD and ADHD behavior will most likely benefit from different clinical approaches.

The co-occurrence of autism spectrum disorder and attention-deficit/hyperactivity disorder symptoms in parents of children with ASD or ASD with ADHD.

BACKGROUND: Autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) share about 50-72% of their genetic factors, which is the most likely explanation for their frequent co-occurrence within the same patient or family. An additional or alternative explanation for the co-occurrence may be (cross-)assortative mating, e.g., the tendency to choose a partner that is similar or dissimilar to oneself. Another issue is that of parent-of-origin effect which refers to the possibility of parents differing in the relative quantity of risk factors they transmit to the offspring. The current study sets out to examine (cross-)assortative mating and (cross-)parent-of-origin effects of ASD and ADHD in parents of children with either ASD or ASD with ADHD diagnosis. METHODS: In total, 121 families were recruited in an ongoing autism-ADHD family genetics project. Participating families consisted of parents and at least one child aged between 2 and 20 years, with either autistic disorder, Asperger disorder or PDD-NOS, and one or more biological siblings. All children and parents were carefully screened for the presence of ASD and ADHD. RESULTS: No correlations were found between maternal and paternal ASD and ADHD symptoms. Parental ASD and ADHD symptoms were predictive for similar symptoms in the offspring, but with maternal hyperactive-impulsive symptoms, but not paternal symptoms, predicting similar symptoms in daughters. ASD pathology in the parents was not predictive for ADHD pathology in the offspring, but mother's ADHD pathology was predictive for offspring ASD pathology even when corrected for maternal ASD pathology. CONCLUSIONS: Cross-assortative mating for ASD and ADHD does not form an explanation for the frequent co-occurrence of these disorders within families. Given that parental ADHD is predictive of offspring' ASD but not vice versa, risk factors underlying ASD may overlap to a larger degree with risk factors underlying ADHD than vice versa. However, future research is needed to clarify this issue.

A pilot study of abnormal growth in autism spectrum disorders and other childhood psychiatric disorders.

The aims of the current study were to examine whether early growth abnormalities are (a) comparable in autism spectrum disorders (ASD) and other childhood psychiatric disorders, and (b) specific to the brain or generalized to the whole body. Head circumference, height, and weight were measured during the first 19 months of life in 129 children with ASD and 59 children with non-ASD psychiatric disorders. Both groups showed comparable abnormal patterns of growth compared to population norms, especially regarding height and head circumference in relation to height. Thus abnormal growth appears to be related to psychiatric disorders in general and is mainly expressed as an accelerated growth of height not matched by an increase in weight or head circumference.