However, at least one expert expressed concerns over the study’s conclusions.
Results from a study of 50 inpatients with schizophrenia showed significantly higher pro-inflammation, pro-oxidation, and leaky gut biomarkers in those with aggression vs. their peers who did not display aggression.
In addition, those with aggression showed less alpha diversity and evenness of the fecal bacterial community, lower levels of several beneficial gut bacteria, and higher levels of the fecal genera Prevotella.
Six short-chain fatty acids (SCFAs) and six neurotransmitters were also lower in the aggression vs. no-aggression groups.
“The present study was the first to compare the state of inflammation, oxidation, intestinal microbiota, and metabolites” in inpatients with schizophrenia and aggression, compared with those who did not show aggression, write the investigators, led by Hongxin Deng, department of psychiatry, Zhumadian (China) Psychiatric Hospital.
“Results indicate pro-inflammation, pro-oxidation and leaky gut phenotypes relating to enteric dysbacteriosis and microbial SCFAs feature the aggression in [individuals with schizophrenia], which provides clues for future microbial-based or anti-inflammatory/oxidative therapies on aggression,” they add.
The findings were published online in BMC Psychiatry.
Unknown pathogenesis
Although emerging evidence suggests that schizophrenia “may augment the propensity for aggression incidence about fourfold to sevenfold,” the pathogenesis of aggression “remains largely unknown,” the investigators note.
The same researchers previously found an association between the systemic pro-inflammation response and the onset or severity of aggression in schizophrenia, “possibly caused by leaky gut-induced bacterial translocation.”
The researchers suggest that peripheral cytokines “could cross the blood-brain barrier, thus precipitating changes in mood and behavior through hypothalamic-pituitary-adrenal axis.”
However, they note that the pro-inflammation phenotype is “often a synergistic effect of multiple causes.” Of these, chronic pro-oxidative stress has been shown to contribute to aggression onset in intermittent explosive disorder, but this association has rarely been confirmed in patients with schizophrenia.
In addition, increasing evidence points to enteric dysbacteriosis and dysbiosis of intestinal flora metabolites, including SCFAs or neurotransmitters, as potentially “integral parts of psychiatric disorders’ pathophysiology” by changing the state of both oxidative stress and inflammation.
The investigators hypothesized that the systemic pro-inflammation phenotype in aggression-affected schizophrenia cases “involves alterations to gut microbiota and its metabolites, leaky gut, and oxidative stress.” However, the profiles of these variables and their interrelationships have been “poorly investigated” in inpatients with schizophrenia and aggression.
To fill this gap, they assessed adult psychiatric inpatients with schizophrenia and aggressive behaviors and inpatients with schizophrenia but no aggressive behavior within 1 week before admission (n = 25 per group; mean age, 33.52 years, and 32.88 years, respectively; 68% and 64% women, respectively).
They collected stool samples from each patient and used enzyme-linked immunoassay (ELISA) to detect fecal calprotectin protein, an indicator of intestinal inflammation. They also collected fasting peripheral blood samples, using ELISA to detect several biomarkers.
The researchers also used the Modified Overt Aggression Scale (MOAS) to characterize aggressive behaviors and the Positive and Negative Syndrome Scale to characterize psychiatric symptoms.