Diagnostic Symptoms Of Autism Research Articles

Unusual repertoire of vocalizations in adult BTBR T+tf/J mice during three types of social encounters.

BTBR T+tf/J (BTBR) is an inbred mouse strain that displays social deficits and repetitive behaviors analogous to the first and third diagnostic symptoms of autism. We previously reported an unusual pattern of ultrasonic vocalizations in BTBR pups that may represent a behavioral homolog to the second diagnostic symptom of autism, impaired communication. This study investigated the social and vocal repertoire in adult BTBR mice, to evaluate the role of ultrasonic vocalizations in multiple social situations at the adult stage of development. Three different social contexts were considered: male-female, male-male (resident-intruder) and female-female interactions. Behavioral responses and ultrasonic vocalizations were recorded for BTBR and for the highly social control strain C57BL/6J (B6). No episodes of overt fighting or mating were observed during the short durations of the three different experimental encounters. BTBR displayed lower levels of vocalizations and social investigation in all three social contexts as compared with B6. In addition, the correlation analyses between social investigation and ultrasonic vocalization emission rate showed that in B6 mice, the two variables were positively correlated in all the three different social settings, whereas in BTBR mice, the positive correlation was significant only in the male-female interactions. These findings strongly support the value of simultaneously recording two aspects of the mouse social repertoire: social motivation and bioacoustic communication. Moreover, our findings in adults are consistent with previous results in pups, showing an unusual vocal repertoire in BTBR as compared with B6.

White matter fractional anisotrophy differences and correlates of diagnostic symptoms in autism

Individuals with autism have impairments in 3 domains: communication, social interaction and repetitive behaviours. Our previous work suggested early structural and connectivity abnormalities in prefrontal-striato-temporal-cerebellar networks but it is not clear how these are linked to diagnostic indices. Children with autism (IQ > 70) aged 6 to 14 years old and matched typically developing controls were studied using diffusion tensor imaging. Voxel-based methods were used to compare fractional anisotrophy (FA) measures in each group and to correlate FA measures in the autism group with the diagnostic phenotype described by the Autism Diagnostic Interview - Revised (ADI-R) algorithm for ICD-10. After controlling for the effects of age and white matter volume, we found that FA in the autism group was significantly lower than controls in bilateral prefrontal and temporal regions, especially in the right ventral temporal lobe adjacent to the fusiform gyrus. FA was greater in autism in the right inferior frontal gyrus and left occipital lobe. We observed a tight correlation between lower FA and higher ADI-R diagnostic algorithm scores across white matter tracts extending from these focal regions of group difference. Communication and social reciprocity impairments correlated with lower FA throughout fronto-striato-temporal pathways. Repetitive behaviours correlated with white matter indices in more posterior brain pathways, including splenium of the corpus callosum and cerebellum. Our data support the position that diagnostic symptoms of autism are associated with a core disruption of white matter development.

Mnesic imbalance: a cognitive theory about autism spectrum disorders

Autism is characterized by impairments in social interaction, communicative capacity and behavioral flexibility. Some cognitive theories can be useful for finding a relationship between these irregularities and the biological mechanisms that may give rise to this disorder. Among such theories are mentalizing deficit, weak central coherence and executive dysfunction, but none of them has been able to explain all three diagnostic symptoms of autism. These cognitive disorders may be related among themselves by faulty learning, since several research studies have shown that the brains of autistic individuals have abnormalities in the cerebellum, which plays a role in procedural learning. In keeping with this view, one may postulate the possibility that declarative memory replaces faulty procedural memory in some of its functions, which implies making conscious efforts in order to perform actions that are normally automatic. This may disturb cognitive development, resulting in autism symptoms. Furthermore, this mnesic imbalance is probably involved in all autism spectrum disorders. In the present work, this theory is expounded, including preliminary supporting evidence.

Unusual Repertoire of Vocalizations in the BTBR T+tf/J Mouse Model of Autism

BTBR T+ tf/J (BTBR) is an inbred mouse strain that displays social abnormalities and repetitive behaviors analogous to the first and third diagnostic symptoms of autism. Here we investigate ultrasonic vocalizations in BTBR, to address the second diagnostic symptom of autism, communication deficits. As compared to the commonly used C57BL/6J (B6) strain, BTBR pups called more loudly and more frequently when separated from their mothers and siblings. Detailed analysis of ten categories of calls revealed an unusual pattern in BTBR as compared to B6. BTBR emitted high levels of harmonics, two-syllable, and composite calls, but minimal numbers of chevron-shaped syllables, upward, downward, and short calls. Because body weights were higher in BTBR than B6 pups, one possible explanation was that larger thoracic size was responsible for the louder calls and different distribution of syllable categories. To test this possibility, we recorded separation calls from FVB/NJ, a strain with body weights similar to BTBR, and 129X1/SvJ, a strain with body weights similar to B6. BTBR remained the outlier on number of calls, displaying low numbers of complex, upward, chevron, short, and frequency steps calls, along with high harmonics and composites. Further, developmental milestones and growth rates were accelerated in BTBR, indicating an unusual neurodevelopmental trajectory. Overall, our findings demonstrate strain-specific patterns of ultrasonic calls that may represent different lexicons, or innate variations in complex vocal repertoires, in genetically distinct strains of mice. Particularly intriguing is the unusual pattern of vocalizations and the more frequent, loud harmonics evident in the BTBR mouse model of autism that may resemble the atypical vocalizations seen in some autistic infants.

Mouse Behavioral Assays Relevant to the Symptoms of Autism*

While the cause of autism remains unknown, the high concordance between monozygotic twins supports a strong genetic component. The importance of genetic factors in autism encourages the development of mutant mouse models, to advance our understanding of biological mechanisms underlying autistic behaviors. Mouse models of human neuropsychiatric diseases are designed to optimize (i) face validity (resemblance to the human symptoms) (ii) construct validity (similarity to the underlying causes of the disease) and (iii) predictive validity (expected responses to treatments that are effective in the human disease). There is a growing need for mouse behavioral tasks with all three types of validity, to define robust phenotypes in mouse models of autism. Ideal mouse models will incorporate analogies to the three diagnostic symptoms of autism: abnormal social interactions, deficits in communication and high levels of repetitive behaviors. Social approach is tested in an automated three chambered apparatus that offers the subject a choice between spending time with another mouse, with a novel object, or remaining in an empty familiar environment. Reciprocal social interaction is scored from videotapes of interactions between pairs of unfamiliar mice. Communication is evaluated by measuring emission and responses to vocalizations and olfactory cues. Repetitive behaviors are scored for measures of grooming, jumping, or stereotyped sniffing of one location or object. Insistence on sameness is modeled by scoring a change in habit, for example, reversal of the spatial location of a reinforcer in the Morris water maze or T-maze. Associated features of autism, for example, mouse phenotypes relevant to anxiety, seizures, sleep disturbances and sensory hypersensitivity, may be useful to include in a mouse model that meets some of the core diagnostic criteria. Applications of these assays include (i) behavioral phenotyping of transgenic and knockout mice with mutations in genes relevant to autism; (ii) characterization of inbred strains of mice; (iii) evaluation of environmental toxins; (iv) comparison of behavioral phenotypes with genetic factors, such as unusual expression patterns of genes or unusual single nucleotide polymorphisms; and (v) evaluation of proposed therapeutics for the treatment of autism.

Autism‐like behavioral phenotypes in BTBR T+tf/J mice

Autism is a behaviorally defined neurodevelopmental disorder of unknown etiology. Mouse models with face validity to the core symptoms offer an experimental approach to test hypotheses about the causes of autism and translational tools to evaluate potential treatments. We discovered that the inbred mouse strain BTBR T+tf/J (BTBR) incorporates multiple behavioral phenotypes relevant to all three diagnostic symptoms of autism. BTBR displayed selectively reduced social approach, low reciprocal social interactions and impaired juvenile play, as compared with C57BL/6J (B6) controls. Impaired social transmission of food preference in BTBR suggests communication deficits. Repetitive behaviors appeared as high levels of self-grooming by juvenile and adult BTBR mice. Comprehensive analyses of procedural abilities confirmed that social recognition and olfactory abilities were normal in BTBR, with no evidence for high anxiety-like traits or motor impairments, supporting an interpretation of highly specific social deficits. Database comparisons between BTBR and B6 on 124 putative autism candidate genes showed several interesting single nucleotide polymorphisms (SNPs) in the BTBR genetic background, including a nonsynonymous coding region polymorphism in Kmo. The Kmo gene encodes kynurenine 3-hydroxylase, an enzyme-regulating metabolism of kynurenic acid, a glutamate antagonist with neuroprotective actions. Sequencing confirmed this coding SNP in Kmo, supporting further investigation into the contribution of this polymorphism to autism-like behavioral phenotypes. Robust and selective social deficits, repetitive self-grooming, genetic stability and commercial availability of the BTBR inbred strain encourage its use as a research tool to search for background genes relevant to the etiology of autism, and to explore therapeutics to treat the core symptoms.

Food faddism causing vision loss in an autistic child

Eating disorders are common in autism, a neurodevelopmental disorder that is characterized by social interaction deficiency, communication problems and stereotypic behaviours. The spectrum of eating problems includes pica, particular food refusal, food fads, overeating and various degrees of anorectic behaviours. Although eating behaviours are not diagnostic symptoms of autism, they may be quite troubling in the management of the child and sometimes giving rise to some serious complications. We report a case of vitamin A deficiency with secondary xerophthalmia in an autistic and epileptic child.