Neuroimaging studies have described altered structural and functional connectivity across brain regions of individuals with autism spectrum disorder (ASD). These findings have led to the hypothesis that altered brain connectivity may provide a key pathophysiological contribution in ASD. However the neurobiological determinants and significance of these findings remain unclear.

The gene encoding the transcription factor FOXP1 is strongly implicated in the etiology of individuals with autism spectrum disorder (ASD) and of those with intellectual disability. FOXP1 is among the 40 highest-ranked candidate ASD risk genes (according to SFARI Gene). Brain-wide deletion of FOXP1 in mice results in altered behaviors relevant to ASD.

Autism spectrum disorders (ASDs) represent a group of neurodevelopmental disorders for which the underlying etiologies are heterogeneous. Risk factors range from environmental insults to single gene mutations. A unifying model explaining how this array of risk factors leads to deficits in communication, social interactions, and sensory and repetitive behavior is lacking.

The diagnostic dyad defining autism spectrum disorder (ASD) belies a tremendous phenotypic heterogeneity that remains a key challenge to diagnosis and treatment. The strong genetic component of ASD suggests that heterogeneity in underlying genetic mutations may contribute to phenotypic heterogeneity. However, the germline genetics of ASD has thus far proven insufficient to explain the clinical heterogeneity of the disorder.

Components of the mammalian target of rapamycin (mTOR) signaling pathway are key players in the pathogenesis of autism spectrum disorder (ASD). The mTOR pathway regulates protein homeostasis by promoting protein synthesis and inhibiting autophagy, a lysosomal degradation process that maintains protein quality control by breaking down cellular proteins and organelles to generate amino acids. Guomei Tang, David Sulzer and their colleagues at Columbia University Medical Center recently analyzed postmortem brain samples from individuals with ASD and discovered that, in response to hyperactive mTOR, autophagy was impaired in excitatory neurons. In animal models, autophagy deficiency causes ASD-like synapse pathology and social behaviors.

Autism spectrum disorder (ASD) is diagnosed in boys 4-5 times more frequently than in girls. Many factors contribute to this gender bias, but the origins of the biological factors remain largely unknown. Sex differences in the expression of candidate risk genes may underlie at least some of this bias, but these differences have not been explored.

In contrast to rare copy number variants (CNVs) causing classical syndromes such as Smith-Magenis syndrome and Williams syndrome, recent studies have identified a class of rare CNVs associated with the risk of developing a wide variety of neurodevelopmental and neuropsychiatric features. Individuals affected by these variants often have carrier parents who are apparently unaffected or manifest only subclinical neuropsychiatric features. This makes genetic diagnosis, counseling and management of individuals affected by such CNVs difficult. Several identified CNVs of this category, including 16p11.2 deletion, 1q21.1 deletion, 15q13.3 deletion and 16p12.1 deletion, collectively account for about 20 percent of individuals with neurodevelopmental disorders. Although these CNVs confer higher risk for a disorder, alone they are not sufficient for the manifestation of the disorder. It is therefore essential to consider additional genetic factors that may account for the observed variability in manifestation of these disorders.

A large number of autism risk genes encode proteins that play critical roles in regulating the formation, maturation and function of synaptic connections in the brain, yet the underlying molecular mechanisms of autism are poorly understood. Synaptic connections in the brain consist of the presynaptic axon, the postsynaptic dendrite and the ensheathing astrocytic process. Astrocytes are morphologically complex, non-neuronal cells that play critical roles in synapse assembly, maturation and function.

Autism spectrum disorders (ASDs) are heterogeneous neurodevelopmental syndromes characterized by repetitive behaviors and deficits in the core domains of language development and social interactions. Although the clinical criteria used to define ASDs are entirely behavioral, a wealth of research suggests that mechanisms underlying sensory processing and sensorimotor coupling are altered in individuals with ASDs, and that these differences significantly contribute to ASD pathology. However, the neural basis for these sensory and sensorimotor phenotypes are not completely understood.