Table 4.
Results of population-based studies.
| Article | Main outcome measure | Results | Authors’ conclusion | Do results support the hypothesis? | ||
|---|---|---|---|---|---|---|
| PATIENTS FROM THE GENERAL POPULATION | ||||||
| KRYSIAK 2016 32 | Autoimmune SCH vs non-autoimmune SCH compared on multiple variables |
Non-autoimmune SCH N = 17 |
Autoimmune SCH N = 17 |
P-value | Both autoimmune thyroiditis and subclinical hypothyroidism are associated with a lower total FSFI score, lower scores in selected FSFI domains and higher BDI-II score. These disturbances are particularly pronounced in women whose secondary hypothyroidism results from autoimmune thyroiditis. The obtained results suggest that both thyroid autoimmunity and thyroid hypofunction disturb female sexual function and that their deteriorating effect on women's sexuality are additive. | Yes |
| BDI-II score (mean, SD) | 11.3 (3.9) | 15.6 (3.4) | < 0.05 | |||
| Depressive symptoms (n, %) | 6 (35) | 10 (59) | < 0.05 | |||
| Mild symptoms (n, %) | 6 (35) | 9 (53) | < 0.05 | |||
| Moderate symptoms (n, %) | 0 (0) | 1 (6) | – | |||
| Severe symptoms (n, %) | 0 (0) | 0 (0) | – | |||
| FSFI score (mean, SD) | 27.87 (3.62) | 23.74 (4.00) | – | |||
| Sexual desire (mean, SD) | 4.30 (0.48) | 3.38 (0.51) | < 0.01 | |||
| Sexual arousal (mean, SD) | 4.75 (0.67) | 4.25 (0.46) | – | |||
| Lubrication (mean, SD) | 4.70 (0.51) | 4.10 (0.48) | – | |||
| Orgasm (mean, SD) | 4.38 (0.60) | 3.95 (0.50) | – | |||
| Sexual satisfaction (mean, SD) | 4.92 (0.68) | 3.94 (0.47) | < 0.01 | |||
| Dyspareunia | 4.82 (0.65) | 4.12 (0.60) | – | |||
| DELITALA 2016 30 | Relation of TPO-abs and CES-D. Result of multiple regression analysis and logistic regression analysis, adjusted for age, sex, obesity (BMI≥30), smoking, and education. | CES-D Continuous: | Relation of TPO-abs + vs. TPO-abs – | β (se) −0.304 (0.394) P = 0.440 |
No support was found for an association between thyroid autoimmunity (TPO-abs) and depressive symptoms in a community-based cohort. | No |
| Relation of TPO-abs titer | 0.001 (0.001) P = 0.626 |
|||||
| CES-D > 16: | Relation of TPO-abs + vs. TPO-abs – | OR (95% CI) 1.20 (0.75–2.60) P = 0.126 |
||||
| Relation of TPO-abs titer | 1.00 (0.66–3.95) P = 0.300 |
|||||
| FJAELLEGAARD 2015 31 | Percentage of all euthyroid subjects with: | Anti-TPO – | Anti-TPO + | P-value | No significant differences were found in well-being or depression between euthyroid TPO-abs positive and TPO-abs negative individuals. | No |
| N = 7015 | N = 619 | |||||
| 1. Depression assessed with MDI questionnaire on depression categories: |
||||||
| - 0–3% “No” | 39 | 39 | – | |||
| - 4–19% “Low” | 56 | 56 | – | |||
| - 20–25% “Medium” | 3 | 2 | 0.8 | |||
| - >25% “High” | 2 | 3 | – | |||
| - DSM-IV MDD | 2 | 2 | 0.8 | |||
| 2. Well-being raw score ≥50% | 85 | 86 | 0.4 | |||
| ISEME 2015 34 | Change in CES-D from baseline to follow-up (5yr) |
TPO-abs – | TPO-abs + | Interaction term coefficient (r); 95% CI (P-value) | No significant association was found between change in CES-D score over time and TPO-abs. | No |
| Baseline | 4.47 | 3.95 | – | |||
| 5-year follow-up | 6.85 | 6.56 | – | |||
| Change | 2.38 | 2.61 | 0.23; −1.28-1.75 (0.76) | |||
| Adjusted for variables (gender, cholesterol, hypertension, medication, smoking, BMI). | ||||||
| Baseline | 4.16 | 3.06 | – | |||
| 5-year follow-up | 6.41 | 5.42 | – | |||
| Change | 2.25 | 2.36 | 0.11; −2.23-2.45 (0.93) | |||
| ITTERMANN 2015 35 | MDD, multivariable poisson regression models: |
Anti-TPO-increased (M ≥ 60, F ≥ 100 IU/mL) N = 115 (7.0%) |
P-value | This study detected significant associations between positive TPO-Abs and lifetime depression when excluding individuals with thyroid medication. Furthermore, no significant association was found between TPO-abs and recent depression in this study. A significant positive association between increased TPO-abs and MDD 12 months, but that finding was neither confirmed for positive TPO-abs nor for a BDI-II≥12. |
Yes | |
| RR (95% Confidence Interval) | ||||||
| - Global | 1.29 (0.78–2.11) | – | ||||
| - Recurrent | 1.18 (0.60–2.34) | – | ||||
| - Last 12 months | 2.88 (1.47–5.65) | – | ||||
| - Global lifetime | – | – | ||||
| - Global recurrent | – | – | ||||
| - BDI-II ≥12 | 0.93 (0.52–1.65) | – | ||||
| - Anxiety excl. specific phobias | 1.80 (0.96–3.38) | |||||
| MDD, multivariable poisson regression models: |
Anti-TPO positive (≥200 IU/mL) N = 54 (3.3%) RR (95% Confidence Interval) |
|||||
| - Global | 1.24 (0.54–2.84) | – | ||||
| - Recurrent | 1.47 (0.55–3.92) | – | ||||
| - Last 12 months | 1.78 (0.56–5.74) | – | ||||
| - Global lifetime | 2.14 (1.13–4.06) | 0.020 | ||||
| - Global recurrent | 3.30 (1.21–9.01) | 0.020 | ||||
| - BDI-II ≥12 | 0.42 (0.13–1.34) | – | ||||
| - Anxiety excl. specific phobias | 1.89 (0.75–4.81) | – | ||||
| VAN DE VEN 2012 36 | Self-reported fatigue and scores of RAND-36 vitality subscale and SFQ in euthyroid subjects free of known thyroid disorder (N = 5439): |
Euthyroid anti-TPO – N = 4870 |
Euthyroid anti-TPO + N = 569 |
RR or RC and [CI] | No association between the level of TPO-abs and fatigue was found. | No |
| - Self reported fatigue | 33.9% | 34.6% | RR 1.0 [0.8–1.1] | |||
| - RAND-36 vitality subscale | 66.3 | 66.3 | RC 0.7 [-0.9-2.2] | |||
| - SFQ | 11.1 | 11.4 | RC 0.1 [-0.5-0.7] | |||
| VAN DE VEN 2012 37 | Percentage of subjects with (number in brackets after % = number of patients that completed the specific questionnaire): | TPO-ab ≤12 kIU/l | TPO-ab >12 kIU/l | RR (95%CI), P-value | The presence of TPO-abs is associated with trait characteristics factors like neuroticism and lifetime diagnosis of depression, whereas thyroid function is not. | Yes |
| - Current depression | 15.3% (N = 791) | 19.1% (N = 115) | 1.2 (0.8–1.9) | The presence of TPO-abs may be a vulnerability marker for depression. | ||
| - Lifetime depression | 16.7% (N = 882) | 24.2% (N = 124) | 1.4 (1.0–2.1), < 0.05 | |||
| Scores: |
Difference from reference group (95% CI), P-value |
No significant relationship between the presence of TPO-abs and state markers of depression was found in the general population. | ||||
| - BDI | 5.1 (N = 791) | 6.0 (N = 115) | 0.74 (−0.2–1.7) | |||
| - EPQ-RSS neuroticism subscale | 3.2 (N = 879) | 4.1 (N = 121) | 0.7 (0.1–1.3), < 0.05 | |||
| GRIGOROVA 2012 38 | Significant correlations between scores on the executive function tests and thyroid hormone levels: Design fluency perseverative errors (corrected) Design fluency (total errors) Word fluency (total errors) Trails B errors. |
Higher Tg-ab levels were positively correlated with more errors on: - Trail Making Test Part B (r = 0.470; P = 0.000) - Word Fluency Test (r = 0.284; P = 0.023) - Design Fluency (r = 0.28; P = 0.045) test. The demographic, mood, and neuropsychological test data of all participants with Tg-Ab levels lower than 20mU/L were merged into a low (<20mU/L) Tg-ab group (N = 96) and compared to that of the women whose Tg-ab levels were >20mU/L (high Tg-ab group; N = 29). There were no significant differences between the groups on any of the demographic or mood scores. However, the women in the high Tg-ab group made significantly more perseverative errors on the Design Fluency test (P = 0.003) compared to women in the log Tg-ab group. |
The hypothesis that higher levels of Tg-ab would be associated with worse performance on all of the neuropsychological tests was partially supported. Only on the Trails Making Test-Part B, the Design Fluency and the Word Fluency tests, higher levels of Tg-abs were associated with more errors. These findings suggest that higher levels of Tg-abs antibodies are related to poorer performance on tasks of executive functions. | Yes | ||
| ENGUM 2005 39 | Prevalence (%) in TPO-abs positive subjects (cut-off 200U/mL) compared to general population: |
TPO-abs – (reference category): N = 29,180 (General population) |
TPO-abs + N = 995 |
P-value | The presence of TPO-abs was not associated with depression or anxiety. | No |
| - HADS-D (≥8) | 13.2% | 11.6% | 0.125 | |||
| - HADS-A (≥8) | 16.7% | 16.3% | 0.709 | |||
| Logistic regression analysis of depression or anxiety as dependent variables in relation to thyroid antibodies, when controlling for age, gender and thyroid function | OR adj. (95%) | |||||
| 1 | 0.92 (0.69–1.22) P = 0.557 | HADS-D ≥8 | ||||
| 1 | 0.76 (0.45–1.26) P = 0.285 | HADS-D ≥11 | ||||
| 1 | 0.93 (0.72–1.20) P = 0.584 | HADS-A ≥8 | ||||
| 1 | 1.18 (0.77–1.81) P = 0.447 | HADS-A ≥11 | ||||
| GRABE 2005 40 | Explorative comparison of symptoms between women, MANOVA (adjusted mean [SE]): |
Euthyroid without goiter N = 961 |
Euthyroid Autoimmune thyroiditis N = 30 |
MANOVA | There is some preliminary evidence, that AIT, even without pathologic changes in thyroid hormones, could alter mental well-being at least in females. Therefore, AIT could be associated with negative well-being independently from the current thyroid function. | Yes |
| - Tachycardia | 1.6 [0.02] | F = 4.8; df = 1990; P = 0.03 | ||||
| - Anxiety | 1.5 [0.02] | F = 7.1; df = 1990; P = 0.008 | ||||
| - Globus sensation | 1.3 [0.02] | F = 1.7; df = 1990; P = 0.19 | ||||
| - Nausea |
1.3 [0.02] | F = 2.5; df = 1, 990; P = 0.11 | ||||
| Adjusted for age, gender, education and marital status | ||||||
| STRIEDER 2005 41 | Experienced stress in TPO-abs positive and TPO-abs negative euthyroid subjects. (Mean [SD]) |
TPO-abs – N = 576 |
TPO-abs + N = 183 |
P-value, observed [corrected for age] | No association between recently experienced stressful life events, daily hassles or mood and the presence or absence of TPO antibodies was found in euthyroid women. | No |
| Recent life events - Total life events |
11.2 [6.2] |
10.3 [6.1] |
0.09 [0.97] |
|||
| - Unpleasant events | 4.7 [3.4] | 4.6 [3.5] | 0.68 [0.68] | |||
| - Pleasant events | 5.2 [3.5] | 4.5 [3.5] | 0.02 [0.66] | |||
| - Total unpleasantness | 16.7 [12.4] | 15.1 [11.0] | 0.13 [0.68] | |||
| - Total pleasantness | 18.9 [12.6] | 15.9 [11.4] | 0.01 [0.38] | |||
| Daily Hassles - Total number |
25.2 [14.1] |
23.8 [13.6] |
0.24 [0.83] |
|||
| - Intensity per hassle | 1.3 [0.4] | 1.3 [0.4] | 0.52 [0.38] | |||
| - Total intensity of all | 35.4 [25.5] | 32.2 [22.9] | 0.15 [0.57] | |||
| Positive and Negative affect schedule scale - Report negative feelings |
22.2 [7.3] |
22.1 [7.4] |
0.89 [0.88] |
|||
| - Report positive feelings | 38.3 [5.3] | 38.2 [5.1] | 0.91 [0.91] | |||
| CARTA 2004 33 | Association between anti-TPO+, mood and anxiety disorders: | OR anti-TPO + vs anti-TPO – | P-value (95% CI) | Anti-TPO positivity is associated with a higher lifetime risk of a diagnosis of one mood or anxiety disorder. | Yes | |
| - One anxiety diagnosis (GAD + PD + SP + ADNOS) | 4.2 | 0.001 (1.9–38.8) | ||||
| - One mood diagnosis (MDE + DD + DDNOS) |
2.9 | 0.011 (1.4–6.6) | ||||
| - GAD | 2.7 | 0.058 (0.97–7.5) | ||||
| - PD | 5.4 | 0.096 (0.7–37.3) | ||||
| - SP | 3.6 | 0.111 (0.7–7.6) | ||||
| - ADNOS | 4.0 | 0.045 (1.1–15.5) | ||||
| - MDE | 2.7 | 0.033 (1.1–6.7) | ||||
| - DD | 5.2 | 0.250 (0.3–16.8) | ||||
| - DDNOS | 4.4 | 0.049 (1–19.3) | ||||
| PATIENTS FROM A PRIMARY CARE FACILITY | ||||||
| BUNEVICIUS 2007 50 | Number of pre-menopausal women (N = 153) with: |
Normo-echoic thyroid N = 137 |
Hypo-echoic thyroid (AITD) N = 16 | P-value | Thyroid autoimmunity, evaluated by a relatively simple, cost effective but reliable technique, ultrasonographic imaging of the thyroid gland, is associated with mood symptoms in primary health care patients, especially in pre-menopausal women. | Yes |
| - HADS depression >10 | 4 (3%) | 3 (19%) | 0.02 | |||
| - HADS anxiety >10 | 27 (20%) | 6 (38%) | 0.2 | |||
| - MINI diagnoses major depression | 21 (15%) | 3 (19%) | 0.7 | |||
| - MINI diagnoses AD: | ||||||
| Panic disorder | 6 (4%) | 2 (13%) | 0.2 | |||
| Social phobia | 8 (6%) | 2 (13%) | 0.3 | |||
| Generalized anxiety | 30 (33%) | 5 (31%) | 0.4 | |||
| - Depression or anxiety disorder | 40 (29%) | 8 (50%) | 0.09 | |||
| KIRIM 2012 51 | Number of subjects HRDS levels positive for thyroid autoantibodies vs. negative. |
Thyroid auto- antibodies – N = 107 |
Thyroid auto- antibodies + N = 94 |
P value | Patients with euthyroid chronic autoimmune thyroiditis showed an elevated frequency of depression and a higher rate of severe depression. HDRS scores were correlated to age only in the control group and not in patients with euthyroid chronic AIT, suggesting a possible link between depression and euthyroid Hashimoto's Disease. | Yes |
| - Normal (0–7) | 94 (87.9%) | 8 (8.5%) | – | |||
| - Mild-medium (8-23) | 13 (12.1%) | 51 (54.3%) | – | |||
| - Severe-very severe (19–53) | 0 (0%) | 35 (37.2%) | – | |||
| Average HDRS value: | 3.65 (±3.17) | 16.05 (±6.05) | <0.001 | |||
| BAZZICHI 2007 52 | Percentage of FM patients with clinical characteristics: |
Anti-TPO – N = 70 |
Anti-TPO + N = 50 |
P-value | The results suggest a relationship between thyroid autoimmunity and FM, and highlight the association between thyroid autoimmunity and some typical symptoms such as: dysuria, allodynia, sore throat, blurred vision and dry eyes. Thyroid autoimmunity is a marker of the severity of FM, especially if patients are in post-menopausal status. |
Yes |
| - Dry eyes | 36.5% | 56.0% | <0.05 | |||
| - Burning/pain with urination | 10.0% | 36.0% | <0.01 | |||
| - Allodynia | 32.4% | 73.5% | <0.01 | |||
| - Blurred vision | 22.5% | 48.9% | <0.01 | |||
| - Sore throat | 16.9% | 43.7% | <0.01 | |||
| POSTPARTUM WOMEN | ||||||
| GROER 2013 43 | POMS-D and POMS-A at the time of pregnancy measurement. |
Anti-TPO – N = 72 |
Anti-TPO + N = 63 (pregnant) N = 47 (post-partum) |
The 63 TPO-positive pregnant women had statistically significantly higher scores on the POMS depression-dejection (POMS-D) subscale (8.5) compared to TPO-negative women (5.9) at the time of pregnancy measurement (P = 0.028). Depression symptom reports were higher postpartum for TPO-positive than PPT-negative mothers, F(1.129) = 9.1, P = 0.003. POMS-A subscale scores, F(1.131) = 6.4, P = 0.013, and total mood disturbance scores, F(1.130) = 5.3, P = 0.023, were also higher in the TPO-positive group than in the TPO-negative group. |
In pregnant women, more clinical depression and higher depressive symptom scores were found when TPO positive, and the same pattern continued postpartum. The findings support a relationship between dysphoric moods and TPO antibody status across the peripartum period. |
Yes |
| MCCOY 2008 45 | Score on 10-item EPDS score 4 weeks postpartum. |
TPO-abs – N = 44 |
TPO-abs + N = 7 Seven subjects had positive antibody tests at 4 weeks postpartum. |
P-value The 7 participants with positive antibody tests were more likely than their counterparts to have higher EPDS scores. P = 0.0428 |
TPO-abs + women tended to have higher scores on the EPDS at 4 weeks post-partum than TPO-abs – women, even when PPD was not present. | Yes |
| HARRIS 1989 46 | Psychiatric assessment according to DSM-III criteria for depressed mood by a psychiatrist on three questionnaires: The Rasking 3-area scale for depression, The MADS and The Edinburgh Postnatal depression scale. |
Anti-TPO – N = 82 (56%) |
Anti-TPO + N = 65 (44%) The frequency of cases of postnatal depression at the time of assessment was not significantly different in Ab + compared with Ab- women (x2 test). This was true for both microsomal and thyroglobulin antibody status. |
P-value Not mentioned. |
The presence of autoantibodies showed little association with depressed mood. | No |
| PREGNANT WOMEN | ||||||
| WESSELOO 2018 47 | Risk of self-reported first-onset postpartum depression: |
Anti-TPO + 121 (11.3%) |
Anti-TPO – 954 |
Adjusted OR, P-value (95% CI) | Women with a positive TPO-ab status during early gestation are at increased risk for self-reported first-onset depression at four months postpartum, but not at other time points. This period coincides with the typical postpartum rebound phenomena of the maternal immune system, which suggest an overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. | Yes |
| - 6 weeks | 1.7% | 2.1% | – | |||
| - 4 months | 5.8% (7/121) | 2.1% | 3.8, 0.017 (1.3–11.6)∗ |
|||
| - 8 months | 1.7% | 3.0% | – | |||
| - 12 months | 0.8% | 2.2% | – | |||
| POP 2006 48 | Assessment of depression by CIDI: Multiple logistic regression analysis in 1017 women at two different assessments during gestation |
OR Increased TPO-abs titers (>35) N = 1017 |
95% CI | At 12 and 24 weeks gestation, an elevated titre of TPO-abs was significantly related to depression as well as other confounders. | Yes | |
| - 12 weeks gestation | 2.1 | 1.1–5.8 | ||||
| - 24 weeks gestation | 2.8 | 1.9–7.1 | ||||
| PERIMENOPAUSAL WOMAN | ||||||
| POP 1998 42 | Multiple logistic regression analysis with depression (score ≥12 on the Edinburgh Depression Scale) as dependent variable. |
Low TPO-ab levels (<100 U/mL) N = 525 (90%) |
High TPO-ab levels (≥100 U/mL) N = 58 (10%) |
95% CI |
Women with a high concentration of TPO-abs are at risk for depression, a relationship that still exists after adjustment for other (psycho-social) determinants of depression. | Yes |
| OR | 1 | 3.0 | 1.3–6.8 | |||
| The occurrence of financial problems, caring for parents, a previous episode of depression in the woman's life, the occurrence of a major life event, and an elevated concentration of TPO-Ab (≥100 U/mL) were all significantly and independently related to depression. | ||||||
| PATIENTS WITH AUTOIMMUNE DISEASE | ||||||
| AHMAD 2015 44 |
No Autoimmune Thyroid Disease N = 130 |
Autoimmune Thyroid Disease N = 74 |
P-value |
This study shows a positive association between AIT and the presence of TPO-abs, and FM or CWP in patients with established RA. | Yes | |
| FM or CWP | 17% | 40% | <0.01 | |||
| OR | OR (95%CI) | |||||
| TPO-abs adjusted OR for FM (adjusted for age, sex, DM, BMI and spinal Degenerative Disc Disorder) |
1 | 4.458 (1.950–10.191) | < 0.001 | |||
| CARTA 2002 49 |
Anti-TPO – N = 25 |
Anti TPO+ N = 11 |
P-value |
Celiac patients with positive anti-TPO were more frequently affected by lifetime MDD than celiac patients without anti-TPO. A similar significant association between PD and TPO + among celiac patients was found. | Yes | |
| Number of celiac patients effected with lifetime MDD | 6 (24%) | 9 (81.8%) | <0.01 | |||
| Number of celiac patients effected with PD | 1 (4%) | 4 (36.4%) | <0.01 | |||
ab = antibody, Adj. = adjusted, ADNOS = anxiety disorder not otherwise specified, AIT = autoimmune thyroiditis, AITD(s) = autoimmune thyroid disease(s), anti-TPO = anti thyroid peroxidase, anti-TPO+/- = anti-TPO positive/negative, BDI = Beck depression inventory, BMI = body mass index, CES-D = centre for epidemiological studies-depression scale, CI = confidence interval, CIDI = the composite international diagnostic interview, CWP = chronic widespread pain, DD = dysthymic disorder, DDNOS = depressive disorder not otherwise specified, df = degrees of freedom, DM = Diabetes Mellitus, DSM = diagnostic and statistical manual of mental disorders, EPDS = Edinburgh postnatal depression subscale, EPQ-RSS = Eysenck personality questionnaire revised short scale, F = female, FSFI = female sexual function index, GAD = generalized anxiety disorder, HADS = hospital anxiety and depression scale, HADS-A = HADS-anxiety, HADS-D = HADS-depression, HDRS = Hamilton depression rating scale, M = male, MADS = Montgomery-Asberg depression rating scale, MANOVA = multivariate analysis of variance, MDE = major depressive episode, MDI = WHO major (ICD-10) depression inventory, MDD = major depression diagnosis, MINI = mini international neuropsychiatric interview, N = number, OR = odds ratio, PD = panic disorder, POMS-A = profile of mood states checklists for anxiety, POMS-D = profile of mood states checklists for depression, PPD = post-partum depression, PPT = post-partum thyroiditis, RA = rheumatoid arthritis, RAND-36 = research and development-36, RC = regression coefficient, RR = relative risk, SCH = subclinical hypothyroidism, SD = standard deviation, SE = standard error, SFQ = shortened fatigue questionnaire, SP = social phobia, Tg-ab(s) = thyroglobulin antibody(-ies), TPO = thyroid peroxidase, TPO-ab(s) = thyroid peroxidase antibody(-ies), TPO-ab+/- = TPO-ab positive/negative, yr = year.
∗
Different sample: anti-TPO + (n = 119), anti-TPO–(n = 934). Self-reported first-onset depression rates 5.0% and 1.5% resp.