The activation of extracellular signal-related kinase (ERK), a key enzyme in cellular signaling, may prove to be a useful biomarker in autism, as an aid in early diagnosis, a predictor of treatment response, and perhaps as a predictor of long-term outcomes. ERK is being used as a biomarker in fragile X syndrome because ERK activation is delayed in blood samples of people with the disorder, compared with controls.

Autism encompasses a range of cognitive and behavioral characteristics, and studies suggest that certain genetic abnormalities are common in individuals with autism. A major challenge is to link these genetic abnormalities with the behavioral features of autism, such as social deficits and anxiety. Gil Levkowitz and his colleagues are tackling basic questions concerning the development and function of the hypothalamus, an important yet understudied brain region.

Autism spectrum disorders share common features of impaired social relationships, impaired language and communication, repetitive behaviors and a limited range of interests. Although monogenic disorders collectively account for a minority of autism cases (10 to 15 percent), the molecular alterations in these disorders could reveal common pathways shared by disorders across the autism spectrum.

Abnormal brain wiring during early development may be a causal factor in autism spectrum disorders. Brain wiring requires the guidance of neuronal fibers (axons) to the appropriate brain regions, as well as the establishment of functional synapses — key points of communication between neurons.

Contactin-associated protein-like 2 (CASPR2, encoded by the gene CNTNAP2) is a cell adhesion molecule that is essential for proper neuronal function. Common and rare genetic variations in CNTNAP2 are associated with an increased risk of autism spectrum disorders. A recessive mutation in exon 22 of the gene causes a syndromic form of autism called cortical dysplasia-focal epilepsy syndrome (CDFE). CDFE is a common cause of intractable epilepsy in children, and the cerebral cortex of individuals with CDFE often shows a disorganized structure.

Stelios Smirnakis and his team at Baylor College of Medicine in Houston, Texas, worked to understand how genetic defects in autism lead to malfunction at the circuit level. Understanding the mechanism of circuit malfunction will help generate new hypotheses on how to intervene to promote recovery.

Autism spectrum disorders and fragile X syndrome have a remarkable clinical association and share biological ties to the molecular pathways critical for communication between brain cells, at synaptic junctions. Although a large number of genes have been implicated in autism, fragile X syndrome is caused by the loss of a single gene that encodes FMRP, a protein that regulates many messenger RNAs (mRNAs) before they are expressed as proteins.

J. David Sweatt and his colleagues at the University of Alabama at Birmingham carried out a set of mechanistic studies, using laboratory animals and cellular model systems, to understand the role of the TCF4 transcription factor in cognitive and central nervous system function. As a transcription factor, TCF4 directly regulates gene expression in the brain during development and in adulthood.

Some copy number variants associated with autism lead to measurable anatomical defects or exhibit ‘mirrored phenotypes,’ meaning that deletions and duplications of the chromosomal region have opposite anatomical effects. Nicholas Katsanis and his colleagues at Duke University in Durham, North Carolina, are using these observations to investigate which genes within certain copy number variants lead to neurodevelopmental traits.

Neurons are resident cells of our nervous system that are connected to one another through a structure called the synapse. These synaptic connections form the basis of nervous system function. Early in development, synapses form in excess and a subset must be eliminated during a process of synaptic remodeling to achieve the precise wiring diagram characteristic of the mature nervous system. If this process is disrupted, aberrant synaptic connections may lead to severe disruptions in behavior and overall function of the organism.