J Korean Med Sci.  2025 May;40(18):e66. 10.3346/jkms.2025.40.e66.

Association Between Childhood Trauma and Anhedonia-Related Symptoms: The Mediation Role of Trait Anhedonia and Circulating Proteins

• Rhee SJ
• Shin D
• Shin D
• Song Y
• Joo EJ
• Jung HY
• Roh S
• Lee SH
• Kim H
• Bang M
• Lee KY
• Lee J
• Kim Y
• Kim Y
• Ahn YM

• KMID: 2568098
• DOI: http://doi.org/10.3346/jkms.2025.40.e66

Abstract

Background
Though accumulating evidence suggests an association between childhood trauma and anhedonia, further analysis is needed to consider specific traumatic dimensions, both traits and state anhedonia, and the role of circulating proteins. Therefore, this study investigated the association between different types of childhood traumas and their influence on anhedonia-related symptoms, and to evaluate the influence of anhedonia traits and plasma proteins as mediators.
Methods
This study included 170 patients with schizophrenia, bipolar disorder, major depressive disorder, and healthy controls aged 19–65 years. Multiple reaction monitoring was performed to quantify plasma proteins, and 464 proteins were analyzed. The association between childhood trauma dimensions, anhedonic traits, and related symptoms was analyzed with linear regression. A series of mediation analyses was performed to determine whether anhedonic traits and plasma proteins mediated the association between childhood trauma and anhedonia-related symptoms.
Results
Childhood emotional neglect was significantly associated with anhedonic traits and anhedonia-related symptoms. Mediation analysis revealed that the indirect effect of anhedonic traits for childhood emotional neglect on anhedonia-related symptoms (effect = 0.037; bias-corrected CI, 0.009 to 0.070) was statistically significant. The indirect effect of plasma TNR5 for anhedonic traits on anhedonia-related symptoms was statistically significant (effect = −0.011; bias-corrected CI, −0.026 to −0.002). Serial mediation analysis revealed that the indirect effect of childhood emotional neglect on anhedonia-related symptoms via anhedonic traits and TNR5 was statistically significant (effect = 0.007; biascorrected CI, 0.001 to 0.017).
Conclusion
Anhedonic traits and plasma TNR5 protein levels serially mediated the association between childhood emotional neglect and anhedonia-related symptoms. The study highlights the importance of considering both psychopathological traits and biological correlates when investigating the association between childhood trauma and psychopathological symptoms.

Keyword

Childhood Emotional Neglect; Anhedonia; Proteomics; Serial Mediation; TNR5

Figure

• 

  Fig. 1 Mediation analysis for childhood emotional neglect on anhedonia-related symptoms via anhedonic traits. The analysis was controlled for age, sex, body mass index, diagnosis, non-anhedonic depressive symptoms, alcohol consumption, exercise, and smoking. For the indirect effect, the bias-corrected 95% CI was calculated with 5,000 bootstrapping resamples. The lines in red are statistically significant paths.β = standardized coefficients, B = unstandardized coefficients, SE = unstandardized coefficients standard error, CI = confidence interval.

• 

  Fig. 2 Mediation analysis for anhedonic traits on anhedonia-related symptoms via plasma TNR5. The analysis was controlled for age, sex, body mass index, diagnosis, non-anhedonic depressive symptoms, alcohol consumption, exercise, smoking, blood collection time, and fasting time. For the indirect effect, the bias-corrected 95% CI was calculated with 5,000 bootstrapping resamples. The lines in red are statistically significant paths.β = standardized coefficients, B = unstandardized coefficients, SE = unstandardized coefficients standard error, CI = confidence interval.

• 

  Fig. 3 Serial mediation for childhood emotional neglect on anhedonia-related symptoms via anhedonic traits and plasma TNR5. The analysis was controlled for age, sex, body mass index, diagnosis, non-anhedonic depressive symptoms, alcohol consumption, exercise, smoking, blood collection time, and fasting time. For the indirect effect, the bias-corrected 95% CI was calculated with 5,000 bootstrapping resamples. The lines in red are statistically significant paths and lines in blue are non-significant paths.β = standardized coefficients, B = unstandardized coefficients, SE = unstandardized coefficients standard error, CI = confidence interval.

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