Do Biological Subtypes of Schizophrenia Exist?
How finding different subtypes might lead to new ways of treating schizophrenia.
Posted July 2, 2025 | Reviewed by Monica Vilhauer Ph.D.
Schizophrenia is largely known to be a “heterogeneous” disorder, which means that few patients who have the diagnosis exhibit the same symptoms.
Some patients can have more positive symptoms, like hallucinations and delusions. Others might have more cognitive impairments, like the inability to speak coherently or think linearly and logically. Others might have more depression , and then again, others might have a blunted affect altogether.
Researchers who develop drug treatments for schizophrenia operate on the assumption that all cases of schizophrenia are the same, which is why the drug options focus on similar neurotransmitters.
But what if schizophrenia is organized into subtypes, with different causes and symptom clusters that include more recent interests, like gut bacteria?
Researchers of a new study released this year in 2025 found that there were brain subtypes (BSs), gut subtypes (GSs), and gut-brain subtypes (B-GSs) with potential biomarkers , which are physical indicators that can potentially be used for diagnosing psychiatric disorders. Psychiatry and neuroscience aim to identify biomarkers so that clinicians may eventually use them to diagnose conditions, instead of using behavioral markers, which are more difficult to distinguish between each person.
Researchers in China decided to investigate further, and here is what they found.
The researchers sought to find any association between positive and negative symptoms, gut microbacteria, and cognitive impairments. To gather these initial variables, they screened 768 individuals for psychotic symptoms, which include positive symptoms like hallucinations and delusions, as well as cognitive functioning on psychological tests to verify their diagnosis. They tested for memory , verbal learning, processing speed, and attention , to name a few.
Then they took stool samples from the participants and removed 176 genera (biological family categories) of bacteria in the participants’ stool samples to gauge the levels present in each subject.
To observe the activity in the participants’ brains, the subjects were instructed to undergo MRI scans to investigate if there was an association between individuals’ brain structures and the gut bacteria extracted from stool samples.
By using a novel fusion method to link specific gut microbacteria to MRI brain imaging results, the researchers were able to identify seven biological subtypes of patients with schizophrenia who have distinct differences between their gut-brain health, biological brain structure, and symptom expressions.
By looking at brain structure, researchers can break down different subtypes of a disorder like schizophrenia, which they successfully did in this paper. Some of the things they looked for in the brain subtypes were the extent of white matter volume loss (which is linked to social withdrawal and cognitive deficits) and functional connectivity (the degree to which brain regions have activity between each other). In the literature, there is already evidence to show that differences in these biological expressions present differences in cognitive and clinical symptoms.
One subtype, called BS1, showed increased white matter volume in the frontal and temporal lobes (the front forward lobe and the lobes on the side of the head by the ears), with other structural indicators of cognitive impairment within the brain itself. BS1 also showed weak functional connectivity in brain regions related to the default mode network (the brain network involved with self processes), the somatomotor network, the visual network, and attentional networks.
Subtype BS2 showed the opposite in white matter volume and also weak default mode network, visual network, and attentional networks.
Subtype BS1 also happened to score higher on clinical scales, which assessed positive and negative symptoms that include hallucinations and delusions, lack of affect, and disorganized thinking.
There were three gut subtypes with distinct differences between each other. GS1 had higher levels of the bacteria Collinsella (which is associated with inflammation, leading to gut health issues), and GS2 showed decreased Gemmiger and increased Prevotella (which is associated with weight loss and higher clinical symptoms). Since this study was done in China, which has a different diet , more Prevotella was found in this sample than in other samples from Western cultures.
Researchers also took note that a lower BMI was associated with worse symptom severity. GS3 was similar to GS2 but with a greater increase in Streptococcus , which is more known to have an effect on neurotransmitters that affect behavior.
Of these findings, group GS1 showed correlated scores on the symptom assessments with the amount of Prevotella-Streptococcus and Biophilia -Gemmiger . Group GS2 had correlations between the presence of hallucinations, delusions, and cognitive impairments and Ruminococcus-Anaerostipes . GS3 showed negative correlations between the bacteria Bifidobacterium-Veillonella with positive and negative symptoms. These results might imply that specific gut bacteria may be a potential treatment method for symptoms, if the connection is truly an influential one.
More results showed that the brain-gut subtypes B-GS1 and B-GS2 overlapped significantly with BS2. GS1 was widely distributed across BSs and B-GSs, and GS3 was present in BS2 and B-GS1.
What Does It All Mean?
Brain subtypes might benefit more from targeted treatment. For example, BS1, which has more structural abnormalities and negative symptoms, might do better with structural interventions like transcranial magnetic stimulation (TMS).
Patients with BS2 might do better with antipsychotics , specifically those that work on dopamine D2 antagonists (a fancy term for targeted neurotransmitter treatment) like risperidone and cognitive behavioral therapy (CBT).
The finding that gut bacteria are directly related to the presence of certain symptom clusters in schizophrenia might indicate that bacterial treatments could be considered in future treatment development.
While the study is novel in its methods, statistical analysis, and design, there were some limitations. The sample size and demographics might affect these results, considering certain bacteria like Prevotella might not necessarily be present in all cultures across the world to the degree that it was present in this sample.
The study also did not account for current treatments and lifestyle habits being used, which could affect the gut microbiome . Things like antipsychotics, diet, and drug interventions were not screened for during the study. The study primarily focused on the presence of each bacteria in the subject sample, but it might not be possible to separate the baseline presence of one’s gut bacteria versus the effect of smoking on gut health, for example, which many patients with schizophrenia do.
Although the study had limitations, studies that traverse new territory are emerging from the dark. To have a study that explores alternative associations to a very mysterious and puzzling disorder further adds evidence to the idea that schizophrenia is truly a biological disorder that can be treated with biological remedies.
Wang, Y., Feng, S., Huang, Y., Peng, R., Liang, L., Wang, W., ... & Wu, K. (2025). Revealing multiple biological subtypes of schizophrenia through a data-driven approach. Journal of Translational Medicine, 23(1), 505.
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Sarah An Myers is a writer with a Master of Arts in psychology and behavioral neuroscience from the University of Missouri-St. Louis. She researches novel computational and therapeutic methods for treating and diagnosing mental disorders.
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