1. Chisholm K, Lin A, Abu-Akel A, Wood SJ. {{The association between autism and schizophrenia spectrum disorders: A review of eight alternate models of co-occurrence}}. {Neuroscience and biobehavioral reviews}. 2015 May 5.
Although now believed to be two distinct disorders, autism spectrum disorders (ASD) and schizophrenia spectrum disorders (SSD) share multiple phenotypic similarities and risk factors, and have been reported to co-occur at elevated rates. In this narrative review, we give a brief overview of the phenomenological, genetic, environmental, and imaging evidence for the overlap between ASD and SSD, highlighting similarities and areas of distinction. We examine eight possible alternate models of explanation for the association and comorbidity between the disorders, and set out a research agenda to test these models. Understanding how and why these disorders co-occur has important implications for diagnosis, treatment, and prognosis, as well as for developing fundamental aetiological models of the disorders.
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2. Frye RE, Rose S, Slattery J, MacFabe DF. {{Gastrointestinal dysfunction in autism spectrum disorder: the role of the mitochondria and the enteric microbiome}}. {Microbial ecology in health and disease}. 2015;26:27458.
Autism spectrum disorder (ASD) affects a significant number of individuals worldwide with the prevalence continuing to grow. It is becoming clear that a large subgroup of individuals with ASD demonstrate abnormalities in mitochondrial function as well as gastrointestinal (GI) symptoms. Interestingly, GI disturbances are common in individuals with mitochondrial disorders and have been reported to be highly prevalent in individuals with co-occurring ASD and mitochondrial disease. The majority of individuals with ASD and mitochondrial disorders do not manifest a primary genetic mutation, raising the possibility that their mitochondrial disorder is acquired or, at least, results from a combination of genetic susceptibility interacting with a wide range of environmental triggers. Mitochondria are very sensitive to both endogenous and exogenous environmental stressors such as toxicants, iatrogenic medications, immune activation, and metabolic disturbances. Many of these same environmental stressors have been associated with ASD, suggesting that the mitochondria could be the biological link between environmental stressors and neurometabolic abnormalities associated with ASD. This paper reviews the possible links between GI abnormalities, mitochondria, and ASD. First, we review the link between GI symptoms and abnormalities in mitochondrial function. Second, we review the evidence supporting the notion that environmental stressors linked to ASD can also adversely affect both mitochondria and GI function. Third, we review the evidence that enteric bacteria that are overrepresented in children with ASD, particularly Clostridia spp., produce short-chain fatty acid metabolites that are potentially toxic to the mitochondria. We provide an example of this gut-brain connection by highlighting the propionic acid rodent model of ASD and the clinical evidence that supports this animal model. Lastly, we discuss the potential therapeutic approaches that could be helpful for GI symptoms in ASD and mitochondrial disorders. To this end, this review aims to help better understand the underlying pathophysiology associated with ASD that may be related to concurrent mitochondrial and GI dysfunction.
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3. Frye RE, Slattery J, MacFabe DF, Allen-Vercoe E, Parker W, Rodakis J, Adams JB, Krajmalnik-Brown R, Bolte E, Kahler S, Jennings J, James J, Cerniglia CE, Midtvedt T. {{Approaches to studying and manipulating the enteric microbiome to improve autism symptoms}}. {Microbial ecology in health and disease}. 2015;26:26878.
There is a growing body of scientific evidence that the health of the microbiome (the trillions of microbes that inhabit the human host) plays an important role in maintaining the health of the host and that disruptions in the microbiome may play a role in certain disease processes. An increasing number of research studies have provided evidence that the composition of the gut (enteric) microbiome (GM) in at least a subset of individuals with autism spectrum disorder (ASD) deviates from what is usually observed in typically developing individuals. There are several lines of research that suggest that specific changes in the GM could be causative or highly associated with driving core and associated ASD symptoms, pathology, and comorbidities which include gastrointestinal symptoms, although it is also a possibility that these changes, in whole or in part, could be a consequence of underlying pathophysiological features associated with ASD. However, if the GM truly plays a causative role in ASD, then the manipulation of the GM could potentially be leveraged as a therapeutic approach to improve ASD symptoms and/or comorbidities, including gastrointestinal symptoms. One approach to investigating this possibility in greater detail includes a highly controlled clinical trial in which the GM is systematically manipulated to determine its significance in individuals with ASD. To outline the important issues that would be required to design such a study, a group of clinicians, research scientists, and parents of children with ASD participated in an interdisciplinary daylong workshop as an extension of the 1st International Symposium on the Microbiome in Health and Disease with a Special Focus on Autism (www.microbiome-autism.com). The group considered several aspects of designing clinical studies, including clinical trial design, treatments that could potentially be used in a clinical trial, appropriate ASD participants for the clinical trial, behavioral and cognitive assessments, important biomarkers, safety concerns, and ethical considerations. Overall, the group not only felt that this was a promising area of research for the ASD population and a promising avenue for potential treatment but also felt that further basic and translational research was needed to clarify the clinical utility of such treatments and to elucidate possible mechanisms responsible for a clinical response, so that new treatments and approaches may be discovered and/or fostered in the future.
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4. Pozo P, Sarria E. {{Still stressed but feeling better: Well-being in autism spectrum disorder families as children become adults}}. {Autism : the international journal of research and practice}. 2015 May 8.
The transition to adulthood and adulthood itself have been identified as times of stress for parents of individuals with autism spectrum disorder. Longitudinal studies, however, show improvements in the well-being of mothers of adolescents and young adults with autism spectrum disorder. This article presents a cross-sectional study of 102 Spanish parents (51 mothers and 51 fathers) of 102 individuals with autism spectrum disorder. The aim was to examine parental well-being (evaluated based on stress, anxiety, depression and psychological well-being) in three groups of parents of adults, adolescents and young children with autism spectrum disorder. In addition, the relationships between parental well-being and the characteristics of their children, social support, parental age and sense of coherence were analysed. The results showed that although parental stress and psychological well-being levels were similar across the groups, depression and anxiety were lower in parents of adolescents or adults compared with parents of young children. Different factors predicted different measures of parental well-being, but sense of coherence emerged as the main predictive factor for all parental well-being measures. These findings are discussed in relation to parental adaptation over the lifespan and the implications for interventions in autism spectrum disorder families.
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5. Roberts AL, Koenen KC, Lyall K, Robinson EB, Weisskopf MG. {{Association of autistic traits in adulthood with childhood abuse, interpersonal victimization, and posttraumatic stress}}. {Child abuse & neglect}. 2015 May 5.
Persons with autistic traits may be at elevated risk for interpersonal victimization across the life course. Children with high levels of autistic traits may be targeted for abuse, and deficits in social awareness may increase risk of interpersonal victimization. Additionally, persons with autistic traits may be at elevated risk of posttraumatic stress disorder (PTSD) symptoms subsequent to trauma. We examined retrospectively reported prevalence of childhood abuse, trauma victimization and PTSD symptoms by autistic traits among adult women in a population-based longitudinal cohort, the Nurses’ Health Study II (N=1,077). Autistic traits were measured by the 65-item Social Responsiveness Scale. We estimated odds ratios (OR) for childhood sexual and physical/emotional abuse and PTSD symptoms by quintiles of autistic traits. We examined possible mediation of PTSD risk by abuse and trauma type. Women in the highest versus lowest quintile of autistic traits were more likely to have been sexually abused (40.1% versus 26.7%), physically/emotionally abused (23.9% versus 14.3%), mugged (17.1% versus 10.1%), pressured into sexual contact (25.4% versus 15.6%) and have high PTSD symptoms (10.7% versus 4.5%). Odds of PTSD were elevated in women in the top three quintiles of autistic traits compared with the reference group (OR range=1.4 to 1.9). Childhood abuse exposure partly accounted for elevated risk of PTSD in women with autistic traits. We identify for the first time an association between autistic traits, childhood abuse, trauma victimization, and PTSD. Levels of autistic traits that are highly prevalent in the general population are associated with abuse, trauma and PTSD.
