Thinking Problems in Schizophrenia Patients Stem from Brain Rhythms

Abnormal rhythms in the brain may be to blame for thinking problems in schizophrenia patients, according to findings published in Neuron.

Researchers from the University of California, San Francisco used mice which were carriers of the Dlx5 and Dlx6 genes, which mediate the building of fast spiking (FS) interneuron circuitry as the brain develops. In these mice, FS interneurons only become abnormal, which mirrors human schizophrenia, in a stage which corresponds to human post adolescence. The researchers noted when these mice performed a “rule shift” task, which they designed to imitate the Wisconsin Card Sorting Test (WSCT) in humans, which are typically done at a young age.

When the mice were young, their performance on the task were similar to that or normal mice. However, the mice which carried the Dlx5 and Dlx6 genes showed deficits in the WSCT tasks as they aged into young adulthood.

The researchers disrupted gamma oscillations in the brains of normal adult mice in order to establish that interneuron abnormalities were responsible for the declining WSCT task performance. The researchers were able to light up the mice’s brains to inhibit the activity of the interneurons in the front of the brains, including FS interneurons. The normal mice with the gamma oscillations disrupted performed just as poorly on the rule shift task as the mice who lacked the Dlx5 and Dlx6 genes did. Once these gamma oscillation disrupted mice were restored to normal, they performed the WSCT tasks as well as the normal mice did.

The researchers didn’t stop there, though; they administered clonazepam (brand name Klonopin) to the mice lacking Dlx5 and Dlx6 genes in order to modulate the GABA neurotransmitter system used by the FS interneurons. The mice still performed the WSCT task normally. Typically, clonazepam is used in humans to treat anxiety in schizophrenia patients at high levels. The lower doses of clonazepam may be useful, the researchers said, because they or better designed compounds can specifically target FS interneuron in the prefrontal cortex.

“Meditation has been shown to potently increase gamma oscillations, and you may be able to teach patients to increase gamma oscillations by themselves,” senior author Vikaas Sohal, MD, PhD, explained in a press release. “Now that we know that gamma oscillations are directly related to cognitive performance, it’s certainly an interesting idea to pursue.”

The thinking problems schizophrenia patients may have, the researchers said, included learning, attention, and decision making. This is in addition to other burdens of schizophrenia, which are positive symptoms (like delusions and hallucinations) and negative symptoms (like social withdrawal and lack of motivation). These thinking problems can create challenges in places like educational and work environments, and strain interpersonal relationships, the University’s statement continued.