A 2026 brain-imaging study of university students in China found that people with subthreshold depression showed differences in several resting-brain connections and modestly higher levels of three inflammatory markers than healthy comparison students.
The findings may help researchers investigate how depressive symptoms, repetitive negative thinking and anxiety relate to brain activity and immune signals. They do not show that inflammation causes depression, that altered connectivity causes symptoms, or that the blood markers can predict who will develop major depression.
What the study examined
Researchers at Jinan University in Guangzhou compared 126 students with subthreshold depression with 104 healthy students. In the study, subthreshold depression meant having depressive symptoms that did not meet criteria for a major depression diagnosis.
Participants with subthreshold depression were 18 to 35 years old, right-handed Han Chinese university students. They met specified scores on the Center for Epidemiologic Studies Depression Scale and the 24-item Hamilton Depression Rating Scale, while healthy comparison students scored below both cutoffs.
The researchers excluded people with another psychiatric diagnosis, recent infection, allergy, autoimmune disease, obesity, current smoking or alcohol abuse. The groups were similar in age, sex and years of education.
Brain connections were stronger in three circuits
Resting MRI scans showed stronger connectivity in three cingulate-related circuits among students with subthreshold depression:
- the middle cingulate cortex and caudate;
- the left supracallosal anterior cingulate cortex and the front of the cerebellum; and
- the right supracallosal anterior cingulate cortex and superior frontal gyrus.
No cingulate circuit was weaker in the subthreshold-depression group.
In this context, functional connectivity describes how closely activity in two brain regions rises and falls together during a resting scan. It does not demonstrate physical wiring between the regions or show which area influences the other.
Stronger connectivity between the middle cingulate cortex and caudate was associated with higher depression scores and more rumination. Stronger connectivity between the right cingulate cortex and superior frontal gyrus was associated with higher anxiety scores. These symptom associations were small and were not adjusted for the number of statistical tests performed.
Inflammatory markers differed only modestly
Blood measurements were available for 125 of the 230 participants: 75 students with subthreshold depression and 50 healthy students. The researchers measured four cytokines in fasting morning blood samples.
Median levels of IL-1β, TNF-α and IL-17 were higher in the subthreshold-depression group:
- IL-1β: 5.83 versus 5.53 pg/ml;
- TNF-α: 130.25 versus 124.30 pg/ml; and
- IL-17: 18.95 versus 18.22 pg/ml.
IL-6 did not meaningfully differ between groups, with median levels of 12.27 versus 12.15 pg/ml and a reported p value of 0.559. The three reported cytokine differences were modest, and the middle half of values overlapped substantially between groups.
Within the subthreshold-depression group, higher IL-1β and IL-17 levels were associated with lower symptom scores in several analyses. The pattern was unexpected, and the researchers noted that it could reflect protective responses, a U-shaped relationship, chance, outliers or factors the study did not measure.
None of the cytokine levels directly correlated with any of the three altered brain connections. Statistical interaction models found that IL-1β combined with cingulate-frontal connectivity was associated with anxiety scores, while IL-17 combined with cingulate-frontal connectivity was associated with rumination. These are statistical patterns, not evidence that cytokines change brain connections.
Why the findings need cautious interpretation
The study measured brain activity, blood markers and symptoms at one point in time. Because it was cross-sectional and exploratory, it cannot establish what came first or determine whether the findings predict progression to major depression.
Blood samples were unavailable for 105 participants because of non-cooperation, insufficient serum, broken red blood cells or assay failure. That missing data could have influenced the results. The symptom correlations and interaction models also were not corrected for multiple comparisons.
The participants were a relatively narrow group of young university students. Exercise, caffeine, sleep and hormonal status were not assessed, and the study did not include a major-depression comparison group. Results may not apply to older adults, people with medical conditions or other populations.
For readers, the main practical message is that these cytokine differences are not a diagnostic blood test and cannot identify who will develop major depression. The study also provides no evidence that lowering inflammation would improve mood at the subthreshold stage.
Persistent low mood, anxiety or repetitive negative thinking still deserve attention, even when symptoms do not meet criteria for major depression. Discussing ongoing concerns with a doctor or mental-health professional can help determine what support may be appropriate. Longer-term studies are needed to learn whether the reported brain and immune signals mark rising risk over time.
AI tools were used to assist with the preparation of this article.
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