Autism spectrum and obsessive-compulsive disorders: OC behaviors, phenotypes and genetics
ABSTRACT Autism spectrum disorders (ASDs) are a phenotypically and etiologically heterogeneous set of disorders that include obsessive-compulsive behaviors (OCB) that partially overlap with symptoms associated with obsessive-compulsive disorder (OCD). The OCB seen in ASD vary depending on the individual's mental and chronological age as well as the etiology of their ASD. Although progress has been made in the measurement of the OCB associated with ASD, more work is needed including the potential identification of heritable endophenotypes. Likewise, important progress toward the understanding of genetic influences in ASD has been made by greater refinement of relevant phenotypes using a broad range of study designs, including twin and family-genetic studies, parametric and nonparametric linkage analyses, as well as candidate gene studies and the study of rare genetic variants. These genetic analyses could lead to the refinement of the OCB phenotypes as larger samples are studied and specific associations are replicated. Like ASD, OCB are likely to prove to be multidimensional and polygenic. Some of the vulnerability genes may prove to be generalist genes influencing the phenotypic expression of both ASD and OCD while others will be specific to subcomponents of the ASD phenotype. In order to discover molecular and genetic mechanisms, collaborative approaches need to generate shared samples, resources, novel genomic technologies, as well as more refined phenotypes and innovative statistical approaches. There is a growing need to identify the range of molecular pathways involved in OCB related to ASD in order to develop novel treatment interventions.
- SourceAvailable from: Paolo Brambilla
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- "The concepts of 'character immaturity' and 'obsessive temperament' derived from the TCI literature may bear some resemblance with autistic traits. Indeed, the links between and the partial overlap of ASD and obsessive–compulsive disorder (OCD) have recently received increasing attention in the literature . In both disorders a preoccupation with routine, ritualised patterns of verbal and nonverbal behaviour , and fixed, highly restrictive interests may appear, sometimes making it difficult to differentiate between the rituals, stereotypes, and adherence to routines inherent to ASD and the obsessions and compulsions typical of OCD . "
ABSTRACT: Background: In recent years, several twin studies adopted a dimensional approach to Autism Spectrum Disorders (ASD) and estimated the contribution of genetic and environmental influences to variation in autistic traits. However, no study was performed on adults over 18 years of age and all but two studies were based on parent or teacher ratings. Also, the genetic and environmental contributions to the interplay between autistic traits and adult personality dimensions have not been investigated. Methods: A sample of 266 complete twin pairs (30% males, mean age 40 ± 12 years) drawn from the population-based Italian Twin Register was administered the Autism-Spectrum Quotient, Temperament and Character Inventory (TCI-125), and General Health Questionnaire (GHQ-12). Genetic structural equation modelling was performed with the Mx program. Estimates were adjusted for gender, age, and GHQ-12 score. Results: Genetic factors accounted for 44% and 20%-49% of individual differences in autistic traits and TCI dimensions, respectively. Unshared environmental factors explained the remaining proportion of variance. Consistently with the notion of a personality profile in ASD characterised by obsessive temperament, autistic traits showed significant phenotypic correlations with several TCI dimensions (positive: HA; negative: NS, RD, SD, C). Genetic and unshared environmental correlations between AQ and these TCI dimensions were significant. The degree of genetic overlap was generally greater than the degree of environmental overlap. Conclusions: Despite some limitations, this study suggests that genetic factors contribute substantially to individual differences in autistic traits in adults, with unshared environmental influences also playing an important role. It also suggests that autistic traits and the majority of temperament and character dimensions share common genetic and environmental aetiological factors.Comprehensive Psychiatry 12/2014; 58. DOI:10.1016/j.comppsych.2014.12.018 · 2.25 Impact Factor
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- "Consistent with the objectives of NIMHs Research Domain Criteria project ('RDoC', see http://www.nimh.nih. gov/research-funding/rdoc.shtml) to identify endophenotypes that potentially cut across traditional diagnostic boundaries (Insel and Cuthbert, 2009; Miller, 2010), in the present study we addressed common and unique patterns of brain activity during different aspects of social and non-social reward processing in SAD and ASD, with the ultimate long-term goal to help refine classification and aid in the development of empirically derived approaches to treatment for these conditions (Hasler et al., 2004; Carter, 2005; Jacob et al., 2009). There is emerging consensus that ASDs are characterized by altered function of frontostriatal brain circuitry in response to rewards (Scott-Van Zeeland et al., 2010; Demurie et al., 2011; Kohls et al., 2011; Larson et al., 2011; Dichter et al., 2012b). "
ABSTRACT: Autism spectrum disorders (ASDs) and social anxiety disorder (SAD) are both characterized by social dysfunction, but no study to date has compared neural responses to social rewards in ASDs and SAD. Neural responses during social and nonsocial reward anticipation and outcomes were examined in individuals with ASD (n=16), SAD (n=15), and a control group (n=19) via functional magnetic resonance imaging. Analyses modeling all three groups revealed increased nucleus accumbens (NAc) activation in SAD relative to ASD during monetary reward anticipation, whereas both the SAD and ASD group demonstrated decreased bilateral NAc activation relative to the control group during social reward anticipation. During reward outcomes, the SAD group did not differ significantly from the other two groups in ventromedial prefrontal cortex activation to either reward type. Analyses comparing only the ASD and SAD groups revealed greater bilateral amygdala activation to social rewards in SAD relative to ASD during both anticipation and outcome phases, and the magnitude of left amygdala hyperactivation in the SAD group during social reward anticipation was significantly correlated with the severity of trait anxiety symptoms. Results suggest reward network dysfunction to both monetary and social rewards in SAD and ASD during reward anticipation and outcomes, but that NAc hypoactivation during monetary reward anticipation differentiates ASD from SAD.Social Cognitive and Affective Neuroscience 12/2012; 9(3). DOI:10.1093/scan/nss146 · 7.37 Impact Factor
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- "Our observations that TPH2−/− mice showed high levels of compulsive and impulsive behaviors is completely consistent with current behavioral analyses relating to ASD-like behaviors. In fact, OCD-like behaviors are common in children with ASDs , . The present behavioral phenotyping of TPH2−/− mice focused on social behaviors and extended characterization of these mice as neonates, pre-weanlings (1–21 days of age), weanlings (23–28 days of age) and adults. "
ABSTRACT: Autism is a complex neurodevelopmental disorder characterized by impaired reciprocal social interaction, communication deficits and repetitive behaviors. A very large number of genes have been linked to autism, many of which encode proteins involved in the development and function of synaptic circuitry. However, the manner in which these mutated genes might participate, either individually or together, to cause autism is not understood. One factor known to exert extremely broad influence on brain development and network formation, and which has been linked to autism, is the neurotransmitter serotonin. Unfortunately, very little is known about how alterations in serotonin neuronal function might contribute to autism. To test the hypothesis that serotonin dysfunction can contribute to the core symptoms of autism, we analyzed mice lacking brain serotonin (via a null mutation in the gene for tryptophan hydroxylase 2 (TPH2)) for behaviors that are relevant to this disorder. Mice lacking brain serotonin (TPH2-/-) showed substantial deficits in numerous validated tests of social interaction and communication. These mice also display highly repetitive and compulsive behaviors. Newborn TPH2-/- mutant mice show delays in the expression of key developmental milestones and their diminished preference for maternal scents over the scent of an unrelated female is a forerunner of more severe socialization deficits that emerge in weanlings and persist into adulthood. Taken together, these results indicate that a hypo-serotonin condition can lead to behavioral traits that are highly characteristic of autism. Our findings should stimulate new studies that focus on determining how brain hyposerotonemia during critical neurodevelopmental periods can alter the maturation of synaptic circuits known to be mis-wired in autism and how prevention of such deficits might prevent this disorder.PLoS ONE 11/2012; 7(11):e48975. DOI:10.1371/journal.pone.0048975 · 3.23 Impact Factor