Serotonin Imbalance May Contribute to Autistic Behavior

A deficiency in the levels of serotonin, a key brain chemical, may lead to the development of certain symptoms of autism, suggests a new animal study.

In particular, low serotonin levels may contribute to a lack of sociability, which is one of the hallmarks of autism spectrum disorder (ASD), reports a group of researchers from the Riken Brain Science Institute in Japan.

In the current study, the researchers discovered that giving young mice with low levels of the brain chemical a serotonin boost during the first three weeks of life led to improved social behavior in adulthood.

They also found that administering serotonin via medicinal means — that is, treating the mice with a selective serotonin reuptake inhibitor (SSRI), a drug commonly used to treat depression — improved the balance of the mice’s response to external stimulus.

“Our work shows that early serotonergic intervention rescues regional excitatory/inhibitory abnormalities in the brain as well as behavioral abnormalities,” said corresponding author Toru Takumi with the Riken Brain Science Institute in Japan.

Building on Past Research

An emerging body of research has linked serotonin levels to symptoms of autism. For example, a 2016 study from Vanderbilt University found an association between serotonin levels and sensory dysfunction, or “unusually strong reactions to touch, sound or visual stimuli, or diminished or absent reactions to stimuli.”

While the Vanderbilt study focused on hyperserotonemia, or elevated levels of the chemical neurotransmitter, the new Japanese study adds an important new layer of understanding of the role and resultant behavior of serotonin deficiency.

“Although abnormalities in the serotonin system have been thought to be part of the pathophysiology in patients with ASD, the functional impact of serotonin deficiency in ASD was totally unknown,” said Takumi.

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As many as one in 68 children is affected by an autism disorder, according to the Centers for Disease Control and Prevention (CDC), and prevalence has been rising in recent years.

Low serotonin levels are tied to mood disorders, such as anxiety and depression, and the neurotransmitter also plays a key role in bodily functions that encompass digestion, sleep, blood clotting and sexual health.

In the current study, the researchers used brain-mapping techniques among the mice to identify abnormal neural activity, leading them to focus on serotonin.

“Because the sensory region was receiving abnormally low serotonin input, we reasoned that giving infant mice serotonin therapy might reduce the imbalance and also rescue some of the behavioral abnormalities,” said first author Nobuhiro Sakai, a fellow researcher at the Riken Brain Science Institute.

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To test the sociability of mice that had received SSRI therapy, the researchers exposed them to a cage with an unknown mouse and, alternatively, a cage with no mouse. After receiving SSRI therapy, the ASD-linked mice were more likely to spend time with the unknown mouse, which mirrors behavior of non-ASD mice.

The new study leaves the researchers optimistic about a future serotonin-related therapy. However, they caution that additional studies are needed.

“Our genetic model for ASD is one of many and because the number of genetic mutations associated with ASD is so high, we need to investigate differences and common mechanisms among multiple genetic ASD models,” said Takumi.

“Additionally, before we can administrate SSRIs to patients with ASD, we must study the effects of SSRIs in more detail, especially because adverse effects have been reported in some animal studies,” Takumi added.

The study appeared in the journal Science Advances.