Low brain pH may play a role in autism, other conditions

This article also appeared in the 2017, volume 3 issue of ARI’s Autism Research Review International newsletter.

Autism spectrum disorders (ASD) and psychiatric conditions such as schizophrenia and bipolar disorder may involve an acid/ alkaline imbalance in the brain, according to a new study.

Hideo Hagihara and colleagues say that low brain pH (indicating greater acidity) has been reported in postmortem studies of individuals with bipolar disorder, schizophrenia, and ASD. However, they say, this was believed to be an artifact caused by secondary factors such as antipsychotic use.

To determine whether low brain pH might instead be a primary feature of a number of psychiatric disorders, the researchers first conducted a meta-analysis of datasets from ten postmortem studies of individuals with bipolar disorder or schizophrenia. They found that both groups of patients had low brain pH levels, even when the researchers factored in variables such as age at death, postmortem interval, and history of antipsychotic use.

Next, the researchers investigated brain pH levels using five mouse models of psychiatric disorders including schizophrenia, bipolar disorder, and ASD. In all five models, brain pH was significantly lower than in controls. In addition, the researchers detected elevated levels of lactate in the brains of the mice and found that the higher the lactate was, the lower the pH level was. They note that the increase in lactate may explain the decreased brain pH levels, because lactate acts as a strong acid.

The researchers comment that “brain acidosis influences a number of brain functions, such as anxiety, mood, and cognition.” In addition, they say, acidosis may affect the structure and function of several types of brain cells including GABAergic neurons and oligodendrocytes. “Alterations in these types of cells have been well-documented in the brains of patients with schizophrenia, bipolar disorder, and ASD,” they say, “and may underlie some of the cognitive deficits associated with these disorders.”

The researchers say that based on the assumption that low brain pH is an artifact, researchers have typically attempted to match postmortem samples based on tissue pH. In the process, they say, they may have obscured pathological features associated with changes in pH, such as neuronal hyper-excitation and inflammation.

“Decreased brain pH as a shared endophenotype of psychiatric disorders,” Hideo Hagihara, Vibeke S. Catts, Yuta Katayama, Hirotaka Shoji, Tsuyoshi Takagi, Freesia L. Huang, Akito Nakao, Yasuo Mori, Kuo-Ping Huang, Shunsuke Ishii, Isabella A. Graef, Keiichi I. Nakayama, Cynthia Shannon Weickert, and Tsuyoshi Miyakawa, Neuropsychopharmacology, August 4, 2017 (epub prior to print publication). Address: Tsuyoshi Miyakawa, Division of Systems Medical Science, Institute for Comprehensive Medical Science, Fujita Health University, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan, miyakawa@fujita-hu.ac.jp.


“Increased brain acidity in psychiatric disorders,” news release, Fujita Health University, August 7, 2017.127118310



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