A recent study published in the journal Psychoneuroendocrinology suggests that physical signs of chronic stress, which are typically associated with depression, might actually be linked more closely to symptoms of anxiety. The findings provide evidence that biological markers like inflammation and altered stress hormone rhythms tend to associate with physical feelings of anxiousness rather than a loss of pleasure or general sadness.
Depression and anxiety often occur together in the same people. Because of this overlap, mental health professionals and researchers sometimes struggle to tell which condition is driving physical health problems.
“Depression and anxiety are highly comorbid, and anxiety is itself a symptom within the clinical definition of depression, so it’s unclear whether established links between these conditions and chronic stress biomarkers (e.g., cortisol, inflammation, heart-rate variability) reflect depression-specific, anxiety-specific, or nonspecific/shared symptoms,” said study author Peter B. Fitzgerald, who completed his master’s degree in psychology at American University and is an incoming doctoral student in the Social, Cognitive, and Affective Neuroscience program at Catholic University of America.
Fitzgerald noted that older data often failed to separate these interwoven feelings. “Prior research has been limited by diagnostic categories and measures that do not disentangle symptom dimensions,” he said. To understand how mental health affects the body, scientists rely on measuring physiological stress indicators.
One common indicator is the diurnal cortisol slope, which tracks how the stress hormone cortisol changes throughout the day. Typically, cortisol levels peak in the morning and gradually drop by bedtime, meaning a flatter slope reflects a disrupted rhythm and chronic stress. Researchers also look at systemic inflammation by measuring immune system proteins like C-reactive protein and interleukins in the blood. Low-frequency heart rate variability provides another window into bodily stress by tracking how the time between heartbeats changes, where lower variability indicates a poorer ability to handle stress.
Past studies have frequently connected depression to a flattened cortisol slope, high inflammation, and low heart rate variability. However, the surveys used to measure depression often include questions about anxiety and general distress. The authors of the current study wanted to separate overlapping symptoms to test which specific feelings actually predict biological stress.
“We used the MASQ, a measure designed to separate general distress from disorder-specific symptom dimensions, to test which biomarker associations are shared versus unique to anxious arousal or anhedonic depression—something few prior studies have done,” Fitzgerald said. To do this, the researchers analyzed data from two large, independent groups of American adults. The first group included 1,190 participants from the Midlife in the United States 2 project, and the second group included 806 participants from a related refresher project.
Participants completed a specialized questionnaire designed to separate mood and anxiety symptoms into three distinct categories. These categories included general distress, anhedonia, and anxious arousal. Anhedonia refers to a loss of interest and pleasure, which is specific to depression. The scientists then collected saliva and blood samples alongside resting heart rates, controlling for age, sex, and smoking status.
Across both groups of participants, anxious arousal emerged as the strongest and most consistent predictor of physiological stress. “Anxious arousal—the physical signs of a body in a state of alarm, like a racing heart, shortness of breath, trembling, or dizziness—appears to be the primary driver of the links between depression, anxiety, and the stress-related physical toll that predicts chronic health problems, rather than depression-specific anhedonic symptoms,” Fitzgerald told PsyPost.
“This only becomes visible with dimensional analysis; looking at depression and anxiety as separate diagnostic categories, as most prior research has, obscures the pattern.”
This stood out to the researchers, as they had initially made a different prediction. “The research linking depression to these biomarkers is extensive and well established, while the anxiety side of that literature is thinner and less consistent, so we expected anhedonic symptoms to show the stronger associations and anxious arousal to show weaker ones, if any,” Fitzgerald said. “The opposite happened. Anxious arousal’s associations were much more clear and consistent across stress biomarkers.”
Higher levels of anxious arousal predicted a flatter, unhealthier diurnal cortisol slope, as well as elevated levels of C-reactive protein and interleukin-6. In addition, participants with higher anxious arousal tended to have lower heart rate variability. When the researchers adjusted their statistical models to look at all three symptom categories simultaneously, the physical symptoms of anxiety remained the dominant predictor, while anhedonia showed much weaker and less consistent links.
The researchers then ran a second set of analyses using a different, traditional survey called the Center for Epidemiologic Studies Depression Scale, which blends general distress, anxiety, and depression into a single score. When using this traditional survey, higher depression scores successfully predicted a flatter cortisol slope, higher inflammation, and lower heart rate variability. This comparison suggests that older studies linking broad depression to physical stress might have accidentally been measuring the effects of hidden anxiety symptoms.
Still, the overall impact of a depression diagnosis remains a serious health concern. “This isn’t ‘depression doesn’t matter’ or ‘it’s really anxiety, not depression,'” Fitzgerald cautioned. “Depression is still genuinely linked to worse biomarker profiles—the point is about which symptoms are the mechanistic driver within that broader picture, not that the depression-biomarker link is spurious.”
In a third step, the scientists looked at a subset of participants who provided data roughly 10 years later to see if mood symptoms predicted changes in biology over time, or vice versa. The longitudinal results indicated a two-way relationship between anxious arousal and the stress biomarkers. Higher anxious arousal at the beginning predicted a flatter cortisol slope a decade later, while a flatter cortisol slope, higher inflammation, and lower heart rate variability at the start predicted increases in anxious arousal over the next 10 years.
It is incorrect to conclude from these findings that feeling anxious directly causes negative changes in the immune system and stress hormones. The biological relationship is highly complex and heavily influenced by outside factors like body weight and medical history. When the researchers factored in body mass index, diagnosed chronic health conditions, and anti-inflammatory medications, the statistical links between anxious arousal and the biomarkers weakened, with body weight playing a particularly large role in the inflammation data.
The study also relied on people from the general population reporting their own symptoms on a sliding scale. These findings might not apply to individuals diagnosed with severe, clinical depression or specific anxiety disorders in a hospital setting. The biological realities of psychiatric disorders can differ from everyday variations in mood.
Future research should investigate a wider range of biomarkers, such as metabolic profiles, to build a more complete picture of how the body handles psychological distress. Scientists also need to better understand exactly how body weight and chronic illnesses interact with anxiety symptoms to produce inflammation and alter cortisol levels.
The study, “Differential associations of depression and anxiety with stress-related biomarkers,” was authored by Peter B. Fitzgerald, Yiqing Alice Fan, Evelyn Behar, and Kathleen C. Gunthert.