Can studying autism also yield clues about addiction?
Drug addiction and autism may not seem to have much in common. However, Laura N. Smith, PhD, assistant professor in the Department of Neuroscience and Experimental Therapeutics at the Texas A&M College of Medicine, studies both. Her research into how brains are wired informs our understanding of both these conditions, but her original interest was in a third topic: learning and memory.
“I was originally interested in learning and memory, but I realized that studying the effects of drugs of abuse might represent a clearer path to understanding how experience is encoded in the brain,” Smith said. That’s because both learning and drug addiction are due to changes in the structure and function of synapses, which are the connections between neurons. The changes—which can include the addition or the removal of synapses—are similar for a number of types of “learning,” whether—through experience—it’s forming a new memory, revising an older memory or becoming dependent on an addictive substance.
Autism is also likely caused, at least in part, by connectivity issues. “The brain’s ineffective removal of synapses—called synaptic pruning—is observed in autism spectrum disorders and may contribute to symptoms such as sensory hypersensitivity, social overstimulation and problems with reward processing,” Smith said. That’s partly why she focused her attention on fragile X mental retardation protein, or FMRP, which is a developmental protein that helps traffic materials to synapses in the brain. FMRP is a major mediator of synapse changes, such as which synapses are stabilized and which ones are eliminated. Loss of FMRP results in fragile X syndrome, one of the most common known causes of autism.
Smith thinks FMRP is also involved in drug addiction, but it’s unclear how. “We’re still trying to figure out if FMRP is pro-addiction or anti-addiction,” she said, “and the answer may vary depending upon the type of cells in which it is functioning. To study this, we can knock out FMRP in specific cell types and measure addiction-relevant behaviors.”
Drugs of abuse are so addictive because they hijack the body’s natural reward system—the reason we feel happy when we level up in a video game, for example—by changing the synapses in these areas of the brain. “New evidence suggests that addiction-related synaptic and behavioral changes, similar to learning and memory, require the proper functioning of proteins like FMRP,” Smith said. “In my postdoctoral training, I led work showing that FMRP is critical for the development of multiple cocaine addiction-related behaviors.”
However, it’s still unclear exactly how FMRP is involved in addiction and reward function in the adult brain. “A better understanding could help us find new ways to prevent or reverse addiction and substance-use disorders, which would, of course, be incredibly valuable,” Smith said.
Smith and her team are also taking a somewhat unconventional approach to the study of autism: the role of autism-related proteins in a brain region called the striatum. There is emerging evidence that individuals with autism and fragile X syndrome are unable to interpret usual rewards ‘properly.’ In other words, while a typical brain may feel good after a hug from a loved one, the same stimulus doesn’t have the same effect for someone with autism and this gene mutation. Other behaviors common in autism, such as repetitive movements, also seem to stem from the same brain regions, perhaps offering a clue.
“By studying drugs of abuse, we can observe how plasticity, reward, motor function and other normal processes malfunction in autism,” Smith said.
Standing at the crossroads
“By studying both autism and addiction, we as a lab look down one road at reward-related dysfunction in autism and down the other at the roles of developmental and autism-related molecules in addiction. From this perspective, we see collateral benefits to each question that are not always intuitive,” Smith said. It’s through studying the synaptic changes of addiction that she hopes to approach autism in a new way—while still gaining valuable insights into how and why people become addicted to certain substances. In both, it all comes back to the neurons and their synapses.
“There’s nothing like looking under a microscope and seeing a neuron,” Smith added. “They’re just beautiful, and to spend time analyzing those connections and taking a closer look is just a lovely way to see the world.”