U-Shaped Relationship Between Blood Pressure and Suicide Attempts in Untreated First-Episode Major Depressive Disorder with Anxiety Symptoms

Objective Although the regulatory role of autonomic-cardiovascular interaction pathways in the pathophysiology of affective disorders has been extensively studied, their dynamic interaction with suicide susceptibility in anxiety-depression comorbidity remains mechanistically undefined. The present study specifically investigated the nonlinear dose-response relationship between ambulatory blood pressure (BP) parameters - systolic blood pressure (SBP) and diastolic blood pressure (DBP)-and the risk of attempted suicide in first-onset, unmedicated major depressive disorder (MDD) patients with clinically significant anxiety (HAMA ≥14). Using standardized ambulatory BP monitoring and structured psychometric assessments, we aimed to characterize the threshold effect of hemodynamic indices on suicide risk. Methods This study utilized a cross-sectional design and included 1380 patients with first-onset major depressive disorder who had not received psychotropic medication and had significant anxiety symptoms (HAMA≥14). A history of suicide attempt was obtained through a structured interview and electronic medical record review, and resting seated blood pressure was measured using a standard mercury column sphygmomanometer (the mean of three measurements was recorded as systolic and diastolic blood pressure). Depression and anxiety severity were assessed by standardized 17-item Hamilton Depression Scale (HAMD-17) and 14-item Hamilton Anxiety Scale (HAMA), respectively. Statistical analyses included (1) univariate analyses to screen for potential confounders; (2) multivariate logistic regression modeling to assess the independent associations between blood pressure parameters and suicide attempts after correcting for age, sex, TSH, TC, and total scores of the HAMA and the HAMD; (3) smoothed curve fitting to identify the shape of dose-response curves for blood pressure parameters and suicide risk;(4) segmental regression modeling to to quantify the transitory effect of blood pressure thresholds (likelihood ratio test to identify optimal segmentation points). Results This study investigated 1,380 first-episode drug-naïve patients with major depressive disorder (FEDN-MDD) and clinically significant anxiety (HAMA ≥14), categorized by suicide attempt history: non-attempters (NSA, n=1045) and attempters (SA, n=335). Baseline characteristics revealed the SA group was marginally older than NSA counterparts (36.15±12.33 vs. 34.57±12.50 years, respectively), though gender distribution showed no significant difference (SA: 109M/226F vs NSA: 366M/679F).Multivariate logistic regression adjusted for age, sex, TSH, TC, and total HAMA/HAMD scores demonstrated that each 1 mmHg elevation in both systolic (SBP) and diastolic blood pressure (DBP) was associated with a 3% increased suicide attempt risk (SBP: OR=1.03, 95%CI 1.01-1.05, P=0.002; DBP: OR=1.03, 95%CI 1.01-1.05, P=0.012).Nonlinear smoothed curve fitting and threshold effect modeling revealed a U-shaped association between blood pressure parameters and suicide risk. Above critical thresholds, each 1 mmHg increase conferred substantially elevated risk: 18% greater risk for SBP ≥131mmHg (OR=1.18, 95%CI 1.11-1.24, P<0.001) and 9% increased risk for DBP ≥77mmHg (OR=1.09, 95%CI 1.05-1.13, P<0.001). Notably, a paradoxical inverse relationship emerged in hypotensive ranges, with lower DBP (<77mmHg) associated with elevated suicide risk (OR=0.96, 95%CI 0.92-1.00, P=0.047). While no significant association was observed for SBP <131mmHg (P=0.259), likelihood ratio testing confirmed overall model significance (P<0.001). Conclusion The present study identified a U-shaped dose-response relationship between blood pressure parameters and suicide attempt risk (SBP threshold: 131 mmHg; DBP threshold: 77 mmHg) in first-episode, drug-naïve major depressive disorder (FEDN MDD) patients with significant anxiety. This nonlinear association challenges the conventional stress-diathesis model's presumption of linear cumulative effects between physiological stress indicators and suicide risk.