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Cytokine Profiles in Major Depression (Low IL-17C) & Comorbid Anxiety (2024 Study)

Recent studies have shed light on the intricate relationship between cytokines—proteins crucial for cell signaling in the immune system—depression, and anxiety.

This exploration is pivotal in unveiling the potential biomarkers and therapeutic targets for major depressive disorder (MDD), particularly in patients experiencing their first episode and those untreated with drugs, with or without comorbid anxiety.

The focus on cytokine levels in such patients provides a nuanced understanding of the biological underpinnings of these mental health conditions, offering hope for more tailored and effective treatments.


  1. Cytokines & Mental Health: Cytokines play a critical role in both the development and severity of depression and anxiety, influencing the brain’s neurotransmitter systems and neuroinflammatory pathways.
  2. Study Insights: A recent study found no significant differences in the levels of 37 cytokines between drug-naive MDD patients with and without anxiety, challenging the hypothesis that cytokine levels could differentiate between these patient groups.
  3. Correlation with Severity: The study noted a negative correlation between the severity of depression, as measured by the Hamilton Depression Rating Scale (HAMD), and levels of IL-17C, a specific cytokine.
  4. Diagnostic Potential: Despite initial findings, cytokines such as IL-17C and CCL17 showed limited diagnostic performance in distinguishing between MDD patients with and without anxiety, suggesting that while cytokines are involved in MDD, their role in comorbid anxiety remains unclear.

Source: BMC Psychiatry (2024)

The Link Between Cytokines & Depression: Rationale for Research

The exploration of the relationship between cytokines and depression is grounded in the growing evidence of the immune system’s pivotal role in mental health.

Cytokines, as key mediators of immune responses, have been shown to influence brain function and mood regulation, making them a subject of interest in psychiatric research.

This interest is further justified by observations of altered cytokine levels in individuals with major depressive disorder (MDD), suggesting an inflammatory component to the disorder.

The immune system communicates with the central nervous system through various pathways, including cytokines, which can cross the blood-brain barrier and interact with the brain’s immune cells, neurons, and neurotransmitter systems.

These interactions can lead to changes in brain function and behavior, contributing to the development and maintenance of depression.

For instance, pro-inflammatory cytokines can enhance the reuptake and reduce the production of serotonin, a neurotransmitter closely linked to mood regulation.

Additionally, cytokines can activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated cortisol levels, which have been associated with depression.

Given these mechanisms, researching the link between cytokines and depression offers potential insights into understanding the pathophysiology of the disorder.

It also opens up the possibility of identifying novel biomarkers for depression, which could aid in diagnosis and in monitoring treatment response.

Furthermore, understanding this link could lead to new therapeutic targets, offering hope for more effective treatments for those suffering from depression, particularly in cases where traditional antidepressant therapies are ineffective.

Findings: Cytokine Levels in Major Depression & Anxiety (2024 Study)

1. Cytokine Levels in MDD with vs. without Anxiety

Initially, the study found significant differences in the levels of IL-17 C and CCL17 between MDD patients with and without anxiety, suggesting a potential role of these cytokines in mediating the effects of anxiety within the context of MDD.

Specifically, IL-17 C and CCL17 levels were lower in MDD patients with anxiety compared to those without.

This finding could indicate that these cytokines are involved in the neuroinflammatory pathways that underpin anxiety symptoms in depressed patients.

However, after applying the Benjamini-Hochberg corrections to account for multiple comparisons, these differences did not remain statistically significant.

This adjustment is crucial in studies with multiple endpoints to reduce the risk of type I error (false positives), ensuring that the findings are not simply due to chance.

2. Multiple Linear Regression Analysis

The use of multiple linear regression models further explored the relationship between cytokine levels and the presence of anxiety in MDD patients.

These models considered various independent variables, including demographic and clinical characteristics.

The analysis revealed that the grouping based on the presence or absence of anxiety was not a significant predictor of IL-17 C or CCL17 levels.

This outcome underscores the complexity of the relationship between cytokines and mood disorders, suggesting that the presence of anxiety symptoms does not independently influence the levels of these cytokines in MDD patients.

3. Diagnostic Performance of IL-17 C & CCL17

The ROC curve analysis assessed the utility of IL-17 C and CCL17 levels in distinguishing between MDD patients with and without anxiety.

With AUC values of 0.643 and 0.637, respectively, these cytokines demonstrated inadequate diagnostic accuracy.

This suggests that, despite their initial promise, IL-17C and CCL17 levels cannot reliably differentiate between MDD patients based on the presence of anxiety symptoms.

4. Cytokine Levels & Depression Severity

A significant negative correlation was observed between the HAMD scores and IL-17 C levels, indicating that as the severity of depression increases, the levels of IL-17C decrease.

This relationship points to a potential role of IL-17C in the pathophysiology of MDD, potentially reflecting its involvement in neuroinflammatory processes that exacerbate depressive symptoms.

However, no significant correlations were found between the HAMA scores and cytokine levels after adjusting for sex, highlighting the complex interplay between cytokines, depression, and anxiety that cannot be fully explained by these biomarkers alone.

Cytokine Levels in Major Depression with vs. without Anxiety (2024 Study)

Jun Liang et al. examined the levels of various cytokines in patients diagnosed with first-episode, drug-naive major depressive disorder (MDD), with a particular focus on comparing those with and without comorbid anxiety.

It aimed to analyze the correlation between the severity of depression or anxiety and the serum levels of these cytokines, potentially identifying biomarkers for MDD with comorbid anxiety.


  • The study enrolled 55 patients diagnosed with first-episode, drug-naive MDD, classified based on the presence or absence of anxiety symptoms assessed using the 14-item Hamilton Anxiety Rating Scale (HAMA).
  • These patients were divided into two groups: 23 MDD patients without anxiety and 32 MDD patients with anxiety.
  • The researchers measured 37 different cytokines in the serum of these patients. Multiple linear regression models were used to explore the relationship between the presence of anxiety and abnormal cytokine levels.
  • Additionally, receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of serum cytokines in discriminating between MDD patients with and without anxiety.
  • The correlation between the severity of depression or anxiety (as measured by the HAMD and HAMA scores) and cytokine levels was also assessed.


  • The study found that, initially, IL-17 C and CCL17 levels were significantly lower in MDD patients with anxiety compared to those without anxiety.
  • However, after correcting for multiple comparisons using Benjamini-Hochberg corrections, these differences were not statistically significant.
  • Multiple linear regression models indicated that the group (with or without anxiety) was not a significant independent predictor of serum IL-17 C or CCL17 levels.
  • The ROC curve analysis showed that IL-17 C and CCL17 had inadequate accuracy (AUC values of 0.643 and 0.637, respectively) for distinguishing between MDD patients with and without anxiety.
  • A notable correlation was found between HAMD scores and IL-17 C levels, indicating that higher depression severity was associated with lower IL-17 C levels, but no significant correlation was observed between HAMA scores and cytokine levels after adjusting for sex as a covariate.


  • The study’s limitations include its relatively small sample size and its cross-sectional design, which restricts the ability to infer causal relationships between cytokine levels and the presence of anxiety in MDD patients.
  • Additionally, the lack of a healthy control group makes it challenging to determine whether the observed cytokine levels are specific to MDD or represent a more generalized response to stress or illness.
  • Furthermore, the study was conducted in a single center, limiting the generalizability of the findings.
  • The researchers also acknowledged the potential influence of other unmeasured factors, such as lifestyle or genetic predispositions, which could affect cytokine levels and their association with MDD and anxiety.

Low IL-17C Cytokines & Depression Severity (Correlation)

The study highlighted an intriguing aspect of the relationship between cytokine levels and the severity of depression, particularly noting a significant negative correlation between IL-17 C levels and the severity of depressive symptoms as measured by the Hamilton Depression Rating Scale (HAMD).

This finding suggests that individuals with more severe depression may exhibit lower levels of IL-17 C, a cytokine that is part of the interleukin-17 family known for its role in inflammation and immune response.

Function of IL-17 C

IL-17 C is a member of the IL-17 cytokine family, which plays a crucial role in the immune system, particularly in the response to bacterial and fungal infections.

IL-17 cytokines, including IL-17 C, are primarily known for their involvement in promoting inflammatory responses.

They help in recruiting neutrophils and other immune cells to the site of infection or inflammation, thereby playing a critical role in host defense mechanisms.

However, beyond their well-established functions in immunity, IL-17 cytokines have also been implicated in various autoimmune and inflammatory diseases, where their dysregulation contributes to pathological inflammation.

IL-17 C Levels in Depression

The specific mechanisms through which IL-17 C levels might influence depression severity are not fully elucidated within the study.

However, the negative correlation observed suggests that reduced levels of IL-17 C may be associated with an increased severity of depressive symptoms.

This could be interpreted in the context of the cytokine’s role in inflammation and immune regulation.

One hypothesis could be that lower levels of IL-17 C reflect an imbalance in the immune system’s ability to respond to stress or inflammation, which could exacerbate or contribute to the pathophysiology of depression.

Inflammation has been proposed as a key contributor to the development of depression in some individuals, with pro-inflammatory cytokines influencing neurotransmitter systems, brain neuroplasticity, and neuroendocrine function.

Therefore, abnormal levels of cytokines like IL-17 C could potentially disrupt these delicate balances, leading to or worsening depressive symptoms.

What are the potential implications of lower IL-17C levels in severe depression?

The observed correlation between IL-17 C levels and depression severity could have several clinical implications.

It suggests that IL-17 C might serve as a biomarker for identifying individuals with more severe forms of depression, potentially guiding treatment decisions.

For example, treatments that modulate the immune response or specifically target the IL-17 cytokine pathway might be beneficial for patients with severe depression linked to immune dysregulation.

However, it’s important to note that the relationship between cytokines and depression is complex and influenced by numerous factors.

Therefore, IL-17 C levels should not be considered in isolation but as part of a broader assessment of inflammatory markers and immune function in individuals with depression.

Limitations of Examining Cytokines in Depression

While the study of cytokines in the context of depression is scientifically valuable, translating these findings into clinical practice presents several challenges.

One of the primary reasons cytokines may be clinically less useful in diagnosing or treating depression is the considerable variability and lack of specificity in their levels due to multiple influencing factors.

This variability can obscure the relationship between cytokine levels and depression, making it difficult to establish clear diagnostic criteria or treatment protocols based on cytokine profiles.

Lack of Specificity

Cytokines are involved in a wide range of bodily functions and responses, not just those related to mental health. Elevated levels of certain cytokines can be indicative of various conditions, including infections, autoimmune diseases, chronic stress, and more. This lack of specificity means that abnormal cytokine levels cannot be directly attributed to depression without ruling out other potential causes, complicating their use as biomarkers for the disorder.

Influence of External Factors

The expression of cytokines is sensitive to a myriad of external factors, further complicating their clinical utility in depression. Factors such as genetics, lifestyle choices, environmental stressors, and comorbid medical conditions can all influence cytokine levels, making it challenging to discern whether abnormalities are related to depression or other variables.

Potential Reasons for Abnormal Cytokine Levels in Depression


Genetic predispositions can influence an individual’s cytokine response, leading to variations in cytokine production and regulation.

These genetic differences can affect susceptibility to depression and the severity of symptoms, making it difficult to establish a one-size-fits-all approach to diagnosis and treatment based on cytokine levels.

Lifestyle Factors

Diet, exercise, and obesity are all closely linked to cytokine levels.

Poor diet choices and lack of exercise can lead to chronic inflammation, marked by elevated cytokine levels, which have been associated with an increased risk of depression.

Conversely, regular physical activity and a healthy diet can modulate cytokine levels and potentially mitigate depressive symptoms.


Obesity is a well-known contributor to systemic inflammation, characterized by elevated levels of pro-inflammatory cytokines.

This chronic inflammatory state can influence brain function and mood, contributing to the development of depression.

The relationship between obesity, inflammation, and depression exemplifies the complex interplay between physical health and mental well-being.

Environmental & Social Factors

Stressful life events, socioeconomic status, and other environmental and social factors can also influence cytokine levels.

Chronic stress, for example, can lead to prolonged activation of the immune system, altering cytokine production and signaling pathways involved in mood regulation.

Conclusion: Cytokine Levels in MDD with & without Anxiety (2024)

This study embarked on an important investigation into the cytokine profiles of MDD patients with and without comorbid anxiety, revealing intricate details about the potential role of cytokines in the pathophysiology of depression and anxiety.

Despite initial findings suggesting differences in IL-17 C and CCL17 levels between patient groups, these did not withstand correction for multiple comparisons, nor did they show significant diagnostic utility.

The negative correlation between HAMD scores and IL-17 C levels, however, opens avenues for further research into the role of cytokines in depression severity.

The study’s limitations, including its small sample size and cross-sectional design, highlight the need for larger, longitudinal studies to elucidate the complex relationships between cytokines, MDD, and anxiety.

Ultimately, this research underscores the complexity of the immune system’s involvement in psychiatric disorders and the challenges in identifying biomarkers for mood disorders and their comorbidities.


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