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February 28, 2026BMC Psychiatry0 citationsOpen Access

The predictive value of niacin skin flushing response and inflammatory factors for the antidepressant efficacy

MYMeiyue YangLWLan WangMSMei Song

Key Result

The combined model of baseline niacin skin flushing response, COX-2, and PLA2 predicted early antidepressant efficacy with an AUC of 0.786 in adults with major depressive disorder.

Key Points

  • To examine the relationship between niacin skin flushing response and inflammation in predicting antidepressant efficacy in depressive disorder.
  • Compared niacin skin flushing response and inflammatory cytokines in responders and non-responders.
  • Measured baseline niacin skin flushing index and levels of COX-2 and PLA2.
  • Utilized Spearman’s correlation, binary logistic regression, and ROC curves for analysis.
  • Baseline niacin flushing response was inversely correlated with depression severity (HAMD score).
  • COX-2 levels predicted early treatment efficacy with AUC of 0.725.
  • The combined predictive model of NSFR, COX-2, and PLA2 showed optimal performance (AUC = 0.786).

Structured PICO

Do baseline niacin skin flushing response and inflammatory factors predict early antidepressant efficacy in patients with depressive disorder?

P
Population
50 patients aged 18-65 years with a diagnosis of major depressive disorder (MDD), HAMD-17 score ≥ 17, and no prior antidepressant treatment before study enrollment.
I
Intervention
Antidepressant treatment (observational assessment of baseline biomarkers: niacin skin flushing response [NSFR] and inflammatory cytokines)
C
Comparator
Non-responders (< 50% Hamilton Depression Rating Scale reduction at week 2)
O
Outcome
Early treatment response (≥ 50% Hamilton Depression Rating Scale reduction at week 2)surrogate

A combined model incorporating baseline niacin skin flushing response, COX-2, and PLA2 can effectively predict early antidepressant efficacy in patients with major depressive disorder.

Main Result

Effect estimate: AUC 0.786 for combined model (NSFR + COX-2 + PLA2)

Limitations

  • Small sample size with 50 patients initially, and loss to follow-up reducing some biomarker assessments to 32 patients at Week 2
  • No randomized control or placebo group, observational predictive modeling
  • Limited generalizability as single-center study in China
  • Inflammatory cytokines not measured at second assessment
  • Intervention details (antidepressant type/dose) not specified
  • absence of healthy controls
  • small sample size
  • short duration of trial

Abstract

Individual variations in depressive disorder (DD) treatment responses highlight the need for early efficacy prediction to optimize regimens. The niacin skin flushing response (NSFR) is a potential DD biomarker, and elevated inflammatory cytokines are linked to DD. This study explored the association between blunted NSFR and DD symptom severity, and evaluated the predictive value of NSFR and inflammatory cytokines for early antidepressant efficacy. Fifty DD patients were grouped as responders (≥ 50% Hamilton Depression Rating Scale reduction at week 2) or non-responders. Intergroup differences in NSFR index and inflammatory cytokines (Phospholipase A2 PLA2, Cyclooxygenase-2 COX-2) were compared. Spearman’s correlation, binary logistic regression, and receiver operating characteristic (ROC) curves analyzed associations and predictive performance. (1) Baseline NSFR index was significantly negatively correlated with baseline HAMD score (r = -0.736, p < 0.001), indicating that the degree of NSFR attenuation reflects depression severity. (2) Both baseline NSFR index (AUC = 0.615) and COX-2 level (AUC = 0.725) independently predicted early treatment efficacy, with patients exhibiting lower baseline NSFR index or higher baseline COX-2 levels showing superior early efficacy. (3) The combined predictive model incorporating baseline NSFR index, COX-2, and PLA2 demonstrated optimal predictive performance (AUC = 0.786). This study confirms that greater NSFR attenuation is associated with more severe depressive symptoms. Baseline NSFR and COX-2 hold promise as potential predictive biomarkers. Furthermore, the combined model based on NSFR and inflammatory cytokines exhibits superior predictive value, providing a potential basis for optimizing individualized DD treatment strategies and exploring anti-inflammatory therapeutic targets. Assessed NSFR and inflammatory cytokines for predicting early antidepressant efficacy. Confirmed that blunted NSFR reflects the severity of depressive disorder. Demonstrated combined NSFR + COX-2 + PLA2 model has optimal predictive performance. Offer basis for optimizing individualized DD treatment.

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Cite This Study

Yang et al. (2026) studied Adults aged 18-65 years with ICD-10 diagnosed major depressive disorder (first-onset or recurrent) and baseline HAMD-17 score ≥17, untreated with antidepressants prior to enrollment (n=50). Antidepressant pharmacotherapy vs. None (Responder vs Non-responder groups based on HAMD improvement) was evaluated on Early antidepressant treatment response defined as ≥50% reduction in HAMD-17 score at Week 2 (AUC 0.786 for combined model (NSFR + COX-2 + PLA2)). The combined model of baseline niacin skin flushing response, COX-2, and PLA2 predicted early antidepressant efficacy with an AUC of 0.786 in adults with major depressive disorder.

synapsesocial.com/papers/69a286850a974eb0d3c017afhttps://doi.org/10.1186/s12888-026-07921-5
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