Depression and Diastolic Hypertension: A Female-specific role of thyroid dysfunction in NHANES and LEMON Studies

Q: What are the key findings of this study?

Depression in NHANES women doubled the odds of comorbid diastolic hypertension and hypothyroidism compared to non-depressed women (OR 2.22, 95% CI 1.46-3.36, p=0.0002), mediated by T4 suppression.

Q: What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Depression, psychological stress, thyroid dysfunction, and diastolic hypertension (n=8537). Intervention: Depression (PHQ-9 score 10-27) and thyroid dysfunction (hypothyroidism/elevated TSH) vs. Non-depressed (PHQ-9 score 0) and euthyroid/normal-TSH individuals. Primary outcome: Co-occurrence of diastolic hypertension (>80 mmHg) and hypothyroidism (free T4 <0.8 ng/dL) in NHANES women (OR 2.22, 95% CI 1.46-3.36, p=0.0002).

Q: What does this research mean for the field?

Thyroid dysfunction mediates and moderates the relationship between psychological distress and elevated diastolic blood pressure specifically in women. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

Keerthana Choudari; Swapnali Chaudhari; Pramod Somvanshi

doi:10.21203/rs.3.rs-10847373/v2

October 6, 2026Open Access

Depression and Diastolic Hypertension: A Female-specific role of thyroid dysfunction in NHANES and LEMON Studies

View Full Paper

Ask AI

Bookmark

Share

Key result

Depression in women linked to ~2.2-fold higher odds of comorbid diastolic hypertension and hypothyroidism.

OR 2.22
95% CI 1.46-3.36
P=0.0002
n=8,537

Why the study?

The role of stress-induced thyroid dysfunction in the development of hypertension and whether thyroid status modifies or mediates the relationship between psychological distress and blood pressure by sex remain unclear.

Does thyroid dysfunction modify or mediate the association between depression/psychological distress and diastolic blood pressure in men and women?

Key Points

To test whether thyroid status mediates or modifies the relationship between psychological distress and blood pressure across two sex-stratified independent cohorts.
Analyzed cross-sectional data from the US NHANES thyroid module (2007-2012; N = 8,310; 4,177 men, 4,133 women) assessing depression via PHQ-9, thyroid hormones (free and total T4, free T3), and blood pressure.
Analyzed data from the German LEMON study (N = 227; 145 men, 82 women) evaluating psychological distress (Hamilton depression, TICS chronic stress subscales), TSH levels, and blood pressure.
Performed sex-stratified moderation, causal mediation, and subgroup analyses to evaluate whether thyroid parameters altered or transmitted the effect of psychological distress on blood pressure.
In NHANES women, depression was associated with co-occurring diastolic hypertension and hypothyroidism (OR = 2.22, 95% CI: 1.46-3.36, p = 0.0002); depression inversely predicted free T4 (β = -0.027, p = 0.017) and total T4 (β = -0.028, p = 0.029), which in turn inversely predicted diastolic BP (β = -0.081 and -0.062 respectively, p < 0.001), showing significant mediation (ACME = 0.00215 and 0.00174 respectively, p < 0.05).
In LEMON women, TSH positively moderated the effect on diastolic BP of Hamilton depression (β interaction = 0.213, p = 0.037, 95% CI: 0.014 to 0.412) and chronic worrying (β interaction = 0.207, p = 0.043, 95% CI: 0.006 to 0.407), with both independently predicting diastolic BP in the high-TSH subgroup (β = 0.248, p = 0.018 and β = 0.307, p = 0.010, respectively, N = 13).
No significant moderation or mediation effects of thyroid variables linking psychological distress to blood pressure were observed in men in either cohort.

Study Design

Type

Cross-Sectional (n=8,537)

Multicenter

Yes

Structured PICO

Does thyroid dysfunction modify or mediate the association between depression/psychological distress and diastolic blood pressure in men and women?

P

Population

8,537 adults (49.4% female) across two cross-sectional cohorts in the United States (NHANES, n=8,310) and Germany (LEMON, n=227) evaluated for psychological distress, thyroid function, and blood pressure.

E

Exposure

Exposure to psychological distress, including depression (assessed via PHQ-9 in NHANES and Hamilton depression scale in LEMON), trait anxiety (State-Trait Anxiety Inventory), perceived stress (Perceived Stress Questionnaire), and chronic stress (Trier Inventory for Chronic Stress [TICS] subscales), analyzed for moderation and mediation by thyroid function markers (TSH, free T4, total T4, free T3, total T3).

C

Comparator

Non-depressed participants (PHQ-9 score = 0 in NHANES) and lower stress/normal or low thyroid hormone strata (e.g., normal-TSH [µ±1SD, n=52] and low-TSH [<µ-1SD, n=15] subgroups in LEMON).

O

Outcome

Systolic and diastolic blood pressure (mean of three consecutive seated measurements in NHANES; pre-MRI [BP1] and post-MRI [BP2] readings in LEMON) and prevalence of diastolic hypertension (defined as diastolic BP > 80 mmHg) comorbid with hypothyroidism (defined as free T4 < 0.8 ng/dL).surrogate

Main Result

Odds Ratio: 2.22 (95% CI 1.46–3.36)

Absolute Event Rate: 9.3% vs 4.2%

p-value: p=0.0002

Across two independent cohorts, thyroid dysfunction (suppressed T4 or elevated TSH) uniquely mediated and moderated the association between depression/chronic stress and elevated diastolic blood pressure in women, but not in men.

Limitations

Cross-sectional design requiring prospective confirmation
NHANES used self-reported PHQ-9 for depression and neither cohort measured cortisol or CRH directly
Genetic background, early-life adversity, and chronic-versus-acute stress distinctions were not captured
Small female sample size in the LEMON cohort (N=82) and exclusion of ages 40-55 spanning perimenopause
Healthy volunteer recruitment in LEMON likely attenuated effect sizes
Evaluation of the proportion of mediated effect in NHANES women remains unstable as the direct and total effects were not statistically significant
Thyroid hormone levels (T3, T4) were not reported in LEMON data, so only TSH was used for the mediation and moderation analysis in that cohort

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Supports female-specific thyroid pathway from depression to diastolic hypertension; leaves open whether screening improves outcomes.

Abstract

The role of stress-induced thyroid dysfunction in the development of hypertension remains unclear. We tested whether thyroid status modifies or mediates the relationship between psychological distress and blood pressure in sex-stratified two independent cohorts. The NHANES thyroid module (N = 8,310; 4,177 men, 4,133 women; United States, 2007-2012) provided depression (PHQ-9), T3, T4, and blood pressure. The LEMON study (N = 227; 145 men, 82 women; Germany) provided trait anxiety, perceived stress, Hamilton depression, TICS chronic-stress subscales, TSH, and blood pressure. We tested sex-stratified moderation and mediation hypotheses for the effect of thyroid variables on the association between psychological distress and blood pressure, followed by the subgroup analysis. The odds of diastolic hypertension comorbid with hypothyroidism in NHANES women with depression was OR=2.22 (95% CI: 1.46-3.36, p=0.0002). Depression was inversely associated with free T4 (β = -0.027, p = 0.017) and total T4 (β = -0.028, p = 0.029), each predicted diastolic BP (β = -0.081 and -0.062, both p<0.001), with a significant mediation effect (ACME = 0.00215 & 0.00174 respectively, p<0.05). In LEMON women, TSH positively moderated the effect of Hamilton depression and chronic worrying on diastolic BP (β interaction = 0.213 and 0.207, p<0.05); within the high-TSH subgroup, both independently predicted diastolic BP (β = 0.307 and 0.248, p<0.05). However, there were neither moderated nor mediated effects of thyroid variables in men. Analysis reveals a potential Female-specific role of thyroid function in linking depression to elevated diastolic blood pressure, indicating a thyroid-vascular axis in women.

Discussion

No takes yet. Share an insight, caveat, or question.

Cite This Study

Choudari et al. (2026) conducted a cross-sectional in Depression, psychological stress, thyroid dysfunction, and diastolic hypertension (n=8,537). Depression (PHQ-9 score 10-27) and thyroid dysfunction (hypothyroidism/elevated TSH) vs. Non-depressed (PHQ-9 score 0) and euthyroid/normal-TSH individuals was evaluated on Co-occurrence of diastolic hypertension (>80 mmHg) and hypothyroidism (free T4 <0.8 ng/dL) in NHANES women (OR 2.22, 95% CI 1.46-3.36, p=0.0002). Depression in NHANES women doubled the odds of comorbid diastolic hypertension and hypothyroidism compared to non-depressed women (OR 2.22, 95% CI 1.46-3.36, p=0.0002), mediated by T4 suppression.

synapsesocial.com/papers/6ae682a3e432e7a5c4ef35ca https://doi.org/10.21203/rs.3.rs-10847373/v2

View Full Paper

Ask AI

Bookmark

Share

Depression and Diastolic Hypertension: A Female-specific role of thyroid dysfunction in NHANES and LEMON Studies

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Depression and Diastolic Hypertension: A Female-specific role of thyroid dysfunction in NHANES and LEMON Studies

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Keep reading

Keep reading