Schizophrenia: when following your gut leads to aggression

Schizophrenia is a psychiatric illness counted among the psychotic disorders and is often unjustly reduced to the aggressive behavior of affected patients. What causes this propensity to aggressiveness? According to a team of Chinese researchers¹, the gut microbiota may be involved.

From inflammation to dysbiosis

The starting point for their hypothesis is that the bodies of schizophrenic patients with aggressive tendencies are rich in inflammatory molecules. According to the authors, this state of generalized inflammation may impact patients’ gut microbiota (although this causal relationship has yet to be confirmed). They note that the gut flora of schizophrenic patients with aggressive tendencies varies significantly from that of schizophrenic patients with no such tendencies: it is less diverse, with some species dominating, while others have been depleted. The gut bacteria are involved in the production of certain molecules, notably short-chain fatty acids (sidenote: Short chain fatty acids (SCFA) Short chain fatty acids (SCFA) are a source of energy (fuel) for an individual’s cells. They interact with the immune system and are involved in communication between the intestine and the brain. Silva YP, Bernardi A, Frozza RL. The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. ) (SCFAs) and neurotransmitters (sidenote: Neurotransmitters Specific molecules that enable communication between the neurons (the nerve cells in the brain), as well as with the bacteria in the microbiota. They are produced by the individual’s cells and by the bacteria in the microbiota.    Baj A, Moro E, Bistoletti M, Orlandi V, Crema F, Giaroni C. Glutamatergic Signaling Along The Microbiota-Gut-Brain Axis. Int J Mol Sci. 2019;20(6):1482. ) . In the schizophrenic patients with aggressive tendencies, six SCFAs and six neurotransmitters were significantly depleted.

From dysbiosis to oxidation and aggressiveness?

According to the researchers’ theory, a direct consequence of this imbalance (or dysbiosis) is that the gut is more permeable. Usually the gut wall, made up of a layer of tightly joined cells, acts as a barrier between the contents of the digestive tract and the bloodstream. When the gut microbiota is unbalanced (as with schizophrenic patients with aggressive tendencies), the gut barrier becomes permeable and porous, allowing gut bacteria to reach the bloodstream. The researchers suspect that this mechanism generates a specific reaction known as oxidative stress (sidenote: Oxidative stress Oxidative stress is where the cell no longer controls the excessive presence of toxic molecules (free radicals) that can damage cells and DNA. Pizzino G, Irrera N, Cucinotta M, et al. Oxidative Stress: Harms and Benefits for Human Health. Oxid Med Cell Longev. 2017;2017:8416763.  ) , where molecules harmful to the body (pro-oxidant molecules called free radicals) and known to damage cells are produced in excess. They also showed that the level of oxidative stress in patients is associated with the severity of aggressiveness. The circuit is thus completed: hyper-inflammation leads, via the gut microbiota, to hyper-oxidation, and ultimately to aggressiveness.

Breaking the vicious circle

The study also suggests a possible solution: using probiotics to rebalance the gut flora of schizophrenia patients, or anti-inflammatories to block the harmful mechanism referred to above, thus reducing patients’ aggressiveness. The gut microbiota thus presents a promising line of research.