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Are Autoimmune Thyroid Dysfunction and Depression Related? 1
Abstract
The objective of this study was to examine the relationship between autoimmune thyroid disease and depression in perimenopausal women. Thyroid function [TSH, free T4, and thyroid peroxidase antibodies (TPO-Ab)] and depression (using the Edinburgh Depression Scale) were assessed cross-sectionally together with other determinants of depression. The subjects were 583 randomly selected perimenopausal women (aged 47-54 yr) from a community cohort of 6846 women. The main outcome measures were the occurrence of thyroid dysfunction (abnormal free T4 and/or TSH or elevated levels of TPO-Ab) and the concomitant presence of depression according to the Edinburgh Depression Scale. Neither biochemical thyroid dysfunction nor menopausal status was related to depression. Apart from several psycho-social determinants (the occurrence of a major life event, a previous episode of depression, or financial problems), an elevated level of TPO-Ab (> or = 100 U/mL) was significantly associated with depression (odds ratio, 3.0, 95% confidence interval, 1.3-6.8). We conclude that women with elevated TPO-Ab levels are especially vulnerable to depression, whereas postmenopausal status does not increase the risk of depression.
... After exclusion of duplicates, 3372 were screened and out of those, 62 were assessed for eligibility in full text. Fifteen studies [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] are included in this meta-analysis (PRISMA flowchart, Fig. 1). Three studies reported effects for overt, 7 for subclinical and 4 for both types of hyperthyroidism. ...
... In fourteen studies effects for both, hyper-and hypothyroidism were reported [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. Thomsen ...
Hyperthyroidism and clinical depression are common, and there is preliminary evidence of substantial comorbidity. The extent of the association in the general population, however, has not yet been estimated meta-analytically. Therefore we conducted this systematic review and meta-analysis (registered in PROSPERO: CRD42020164791). Until May 2020, Medline (via PubMed), PsycINFO, and Embase databases were systematically searched for studies on the association of hyperthyroidism and clinical depression, without language or date restrictions. Two reviewers independently selected epidemiological studies providing laboratory or ICD-based diagnoses of hyperthyroidism and diagnoses of depression according to operationalized criteria (e.g. DSM) or to cut-offs in established rating scales. All data, including study quality based on the Newcastle-Ottawa Scale, were independently extracted by two authors. Odds ratios for the association of clinical depression and hyperthyroidism were calculated in a DerSimonian-Laird random-effects meta-analysis. Out of 3372 papers screened we selected 15 studies on 239 608 subjects, with 61% women and a mean age of 50. Relative to euthyroid individuals, patients with hyperthyroidism had a higher chance of being diagnosed with clinical depression: OR 1.67 ([95% CI: 1.49; 1.87], I2: 6%; prediction interval: 1.40 to 1.99), a result supported in a number of sensitivity and subgroup analyses. The OR was slightly less pronounced for subclinical as opposed to overt hyperthyroidism (1.36 [1.06; 1.74] vs. 1.70 [1.49; 1.93]). This comorbidity calls for clinical awareness and its reasons need investigation and may include neurobiological mechanisms, common genetic vulnerability and a generally heightened risk for clinical depression in patients with chronic somatic disorders.
... Krysiak [32,36]. Seven out of these 12 general population studies showed a significant relation between symptoms and thyroid autoimmunity [34,35,37,38,40,42,44]. The other eleven studies were performed in populations from a primary care facility (n ¼ 3), postpartum women (n ¼ 3), pregnant women (n ¼ 2), perimenopausal Other BG N¼116 P-value Preoperatively, hypothyroid symptoms were significantly more expressed; sex life was significantly worse in HT patients than in BG patients (p¼0.025 and p¼0.007, respectively). ...
... 3 10 0.0302 -D2 total score II: number of correctly processed items minus errors. women (n ¼ 1), and patients with another autoimmune disease (n ¼ 2) [44][45][46][47][48][49][50][51][52][53][54]. In these studies, the following tests and questionnaires were used to evaluate symptoms: CIDI, Clinical Characteristics FM, EPDS, HADS-D, HADS-A, HRDS, MADS, MINI, POMS-D, POMS-A, Prevalence of FM/CWP. ...
Objective
Patients with hypothyroidism due to Hashimoto’s disease (HD) may experience persisting symptoms despite normal serum thyroid hormone (TH) levels. Several hypotheses have been postulated to explain these persisting symptoms. We hypothesized that thyroid autoimmunity may play a role.
Design
A systematic literature review.
Methods
A PubMed search was performed to find studies cross-sectional and cohort studies investigating the relation between the presence of thyroid autoimmunity and (persisting) symptoms. Included studies were critically appraised by the Newcastle – Ottawa Scale (NOS) and then subdivided into (A) disease-based studies, comparing biochemically euthyroid patients with HD, and euthyroid patients with non-autoimmune hypothyroidism or euthyroid benign goitre, and (B) (general) population-based studies. Due to different outcome measures among all studies, meta-analysis of data could not be performed.
Results
Thirty out of 1259 articles found in the PubMed search were included in this systematic review. Five out of seven disease-based studies found an association between thyroid autoimmunity and symptoms or lower quality of life (QoL). Sixteen of 23 population-based studies found a comparable positive association.. In total, the majority of included studies reported an association between thyroid autoimmunity and persisting symptoms or lower QoL in biochemically euthyroid patients.
Conclusion
(Thyroid) autoimmunity seems to be associated with persisting symptoms or lower QoL in biochemically euthyroid HD patients. As outcome measures differed among the included studies, we propose the use of similar outcome measures in future studies. To prove causality, a necessary next step is to design and conduct intervention studies, for example immunomodulation vs. placebo preferably in the form of a randomized controlled trial, with symptoms and QoL as main outcomes.
... Furthermore, their likelihood of acquiring a depressive condition in the subsequent years was notably elevated [29]. Upon reviewing the existing literature, it was determined that mood disturbances in thyroid diseases are primarily associated with thyroid autoantibodies rather than thyroid functions, as highlighted by Pop et al. [30]. ...
The aim of this study was to investigate the association between anxiety and depression among patients diagnosed with different thyroid disorders, as well as to identify the frequency of these comorbid conditions. A total of 181 (female/male; 142/39) patients with different thyroid diseases were assessed in this cross-sectional study. Patients were classified according to the type of thyroid disorder they were diagnosed with. The biochemical parameters were obtained from hospital database. The Beck Anxiety Inventory (BAI) and the Beck Depression Inventory (BDI) were utilized to evaluate the association between thyroid disorders and anxiety/depression among patients. Upon classifying patients according to their thyroid disease, it was found that 24 patients (13.2%) were diagnosed with non-autoimmune hypothyroidism, 40 (22.1%) with autoimmune hyperthyroidism, 85 (47%) with autoimmune hypothyroidism, and 32 (17.7%) with nodular thyroid disease. The average scores for BDI and BAI were 15.50±10.19 and 17.83±12.01 in the whole study group. Anxiety and depression were both quite common among patients, with respective rates of 75.7% and 66.7%. BDI scores were significantly correlated with the levels of anti-TPO and anti-TG in patient groups with autoimmune thyroid diseases. Additionally, there was a significant correlation between the BAI scores and anti-TG levels. Patients with thyroid disorders in this study frequently have high levels of anxiety and depression. There is a relationship between depression and anxiety and the levels of thyroid autoantibodies. The presence of thyroid autoantibodies may be a sign of susceptibility to depression and anxiety in thyroid patients.
... Similarly, patients diagnosed with Hashimoto's thyroiditis are more likely to develop depression, anxiety, or borderline personality disorder [29,30,33]. Hormone markers also predicted the development of unipolar and bipolar depression [34,35]. Hyperthyroidism was also associated with anxiety [31], bipolar disorder [36]. ...
Background
According to the 2010 European Health Interview Survey, 51% of women in Hungary have a chronic disease, and is among the poorest quartile in the EU countries. Thyroid diseases affected more than 650,000 women in 2021 based on a recent report by the Hungarian Central Statistical Office. Despite the high prevalence rates, quality of life in these patients is scarcely researched in Hungary. To fill this gap, this study aims to explore the associations of the quality of life of thyroid patients in Hungary with social support and adherence.
Methods
A cross-sectional study was conducted via an online questionnaire. Data from 885 female Hungarian thyroid patients with pharmacological treatment (M = 35.6 years, SD = 10.7, age range: 18–73 years) were analyzed. Participants were divided into two patient groups based on the type of thyroid disorder: hypothyroidism (n = 824; 93.1%) and hyperthyroidism (n = 61; 6.9%). Group comparisons, correlations, and a mediation model were performed to explore differences between thyroid patients.
Results
No differences were found between patients with different types of thyroid disorders in quality of life, adherence, and social support. Consistent, weak associations were found between quality of life and social support in both patient groups. Higher perceived social support partially explained the relationship between adherence and life quality in thyroid patients.
Conclusions
No substantial differences were found between patients with different types of thyroid disease in mental well-being indicators. These patients are psychologically more vulnerable and need a socially supportive environment to recover, because higher adherence is associated with a better quality of life, and social support can facilitate this process.
... While some previous studies investigating the relationship between thyroid autoimmunity and psychiatric disorders support this relationship, others do not. [21][22][23] Since there is no consensus on this issue, drawing a conclusion with our results seems complicated. More solid results can be obtained in future studies to be carried out with more participants. ...
Considering the possible adverse effects of thyroid autoantibodies on the brain, the present study aimed to investigate whether there was a difference in mental health difficulties and mindfulness awareness levels between subclinical Hashimoto’s thyroiditis patients with and without levothyroxine (LT4) use. A case-control study was conducted. The Strengths and Difficulties Questionnaire (SDQ) and the Mindful Attention Awareness Scale (MAAS) were used to screen mental health difficulties and mindfulness awareness. Scale scores were compared by performing correlation analysis between the groups with respect to LT4 use and thyroid autoantibodies. Levothyroxine alone does not affect scale results. Higher thyroid peroxidase antibody (TPOAb) titers were positively correlated with the behavioral problems subscale of the SDQ, while awareness level in patients was inversely correlated with higher thyroglobulin antibody (TgAb) levels.
... Similarly, patients diagnosed with Hashimoto's thyroiditis are more likely to develop depression, anxiety, or borderline personality disorder (19,20,23). Hormone markers also predicted the development of unipolar and bipolar depression (24,25). Hyperthyroidism was also associated with anxiety, bipolar disorder, attention de cit hyperactivity disorder, and suicidal tendencies (21). ...
Background
According to the 2010 European Health Interview Survey, 51% of women in Hungary have a chronic disease, and the overall health status of the Hungarian population is poorer than in other European countries. Thyroid diseases affected more than 650,000 women in 2021 based on a recent report by the Hungarian Central Statistical Office. Despite the high prevalence rates, quality of life in these patients is scarcely researched in Hungary. To fill this gap, this study aims to explore the associations of the quality of life of thyroid patients in Hungary with social support and adherence.
Methods
A cross-sectional study was conducted via an online questionnaire. Data from 1058 Hungarian women (M = 36.2 years, SD = 10.9, age range: 18–74 years) were analyzed. Participants were divided into four patient groups based on the type of thyroid disorder: hypothyroidism (n = 392; 37.1%), Hashimoto's thyroiditis (n = 588; 55.6%), hyperthyroidism (n = 36; 3.4%), and Graves’ disease (n = 42; 4.0%). Group comparisons, correlations, and mediation models were performed to explore differences between thyroid patients.
Results
No differences were found between patients with different types of thyroid diseases in quality of life, adherence, and social support. Consistent, weak associations were found between these mental health indicators. Higher perceived social support partially explained the relationship between adherence and life quality in patients with hypothyroidism and Hashimoto’s thyroiditis.
Conclusions
No substantial differences were found between patients with different types of thyroid disease in mental well-being indicators. These patients are more psychologically vulnerable and need a socially supportive environment to recover, because higher adherence can lead to a better quality of life, and social support can facilitate this process.
... However, screening patients with depression for hypothyroidism is not widely supported 17 . Previous studies 18,19 have shown an association between immune thyroid diseases and depression, although in one study of subjects with normal thyroid function, there was no association between TPO antibodies and depression 20 . Our patient had markedly elevated thyroid antibodies, and it is not clear whether there was any association between the antibodies and depression. ...
We report a 54‐year‐old man with treatment‐resistant depression (TRD) and hypothyroidism who responded to LT3/LT4 combination, rather than LT4 alone. He was able to discontinue all antidepressant medications eventually. Interestingly, the patient has a DIO2 polymorphism.
... We present summarized characteristics of all included studies covering population with a simultaneous diagnosis of depression and autoimmune hypothyroidism in Table 2. This study showed that women with elevated levels of anti-TPO antibodies are more prone to developing depression, while postmenopausal [29] ...
Various autoimmune diseases, including autoimmune hypothyroidism (AHT), are associated with a higher risk of developing mood disorders throughout life. Depression is accompanied by the changes in the levels of inflammatory and trophic factors, including interleukins (IL-1beta, IL-2, IL-6), interferon alpha (IFN-alpha), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP), and brain derived neurotrophic factor (BDNF). Disclosure of the relationship between the coexistence of depression and AHT indicates that the pathomechanism of depression may be related to the changes in the immune system, it is also possible that both conditions may be caused by the same immune processes. The above hypothesis is indirectly supported by the observations that the treatment with both antidepressants and levothyroxine leads to a decrease in the levels of proinflammatory cytokines with an increase in BDNF concentrations, simultaneously correlating with an improvement in the clinical parameters. However, so far there are no long-term studies determining the causal relationship between depression, thyroid autoantibodies, and cytokine profile, which could bring us closer to understanding the interrelationships between them and facilitate the use of an adequate pharmacotherapy, not necessarily psychiatric. We consider the above issues to be insufficiently investigated but of great importance. This article is an overview of the available literature as well as an introduction to our research project.
... However, screening patients with depression for hypothyroidism is not widely supported (17). Previous studies (18,19) have shown an association between immune thyroid diseases and depression, although in one study of subjects with normal thyroid function there was no association between TPO antibodies and depression (20). Our patient had markedly elevated thyroid antibodies and it is not clear whether there was any association between the antibodies and depression. ...
We report a 54-year-old man with treatment-resistant depression (TRD) and hypothyroidism who responded to LT3/LT4 combination, rather than LT4 alone. He was able to discontinue all antidepressant medications eventually. Interestingly, the patient has a DIO2 polymorphism.
... A cross-sectional study also found that TPO Abs levels greater than 100 IU/mL significantly increased the risk of depression (odds ratio, 3.0, 95% confidence interval, 1.3-6.8) (160). Patients with hypothyroidism do appear to have more chronic medical conditions than other populations (161), but whether this accounts for their decreased quality of life is not clear. ...
Hypothyroidism is a common endocrinopathy and levothyroxine is frequently prescribed. Despite the basic tenets of initiating and adjusting levothyroxine being agreed upon, there are many nuances and complexities to consistently maintaining euthyroidism. Understanding the impact of patient weight and residual thyroid function on initial levothyroxine dosage and consideration of age, co-morbidities, TSH goal, life stage, and quality of life as levothyroxine is adjusted can be challenging and continually evolving. As levothyroxine is a life-long medication it is important to avoid risks from periods of overtreatment or undertreatment. For the subset of patients not restored to baseline health with levothyroxine, causes arising from all aspects of the patient’s life (co-existent medical conditions, stressors, lifestyle, psychosocial factors) should be broadly considered. If such factors do not appear to be contributing, and biochemical euthyroidism has been successfully maintained, there may be benefit to a trial of combination therapy with levothyroxine and liothyronine. This is not supported by the majority of randomized clinical trials, but may be supported by other studies providing lower quality evidence and by animal studies. Given this discrepancy, it is important that any trial of combination therapy only be continued as long as a patient benefit is being enjoyed. Monitoring for adverse effects, particularly in older or frail individuals, is necessary and combination therapy should not be utilized during pregnancy. A sustained release liothyronine preparation has completed phase 1 testing and may soon be available for better designed and powered studies assessing whether combination therapy provides superior therapy for hypothyroidism.
... 17,35 Considerando que boa parte dos pacientes hipotireoideos está acima do peso normal é possível que a presença de cefaleia seja mais provável quando há concomitância das duas doenças. Outro fator com possível implicação é a presença de anticorpos antitireoidianos circulantes que já foi associada a sintomas neuropsiquiátricos do hipotireoidismo em outros estudos, 30 embora o estudo de Moreau e colegas 26 não tenha mostrado essa relação particularmente com a cefaleia. ...
Cefaleia e hipotiroidismo são condições clínicas que causam grande impacto na qualidade de vida. Sabe-se que hipotiroidismo e cefaleia são ambos mais frequentes em mulheres. Hipotiroidismo é uma doença comum, clinicamente reconhecida como uma síndrome complexa com sinais e sintomas afetando todo o organismo. Cefaleia é um dos sintomas mais comuns no hipotiroidismo, estima-se que ocorra em aproximadamente um terço dos pacientes. Na ICHD-II (2ª edição, 2004), a cefaleia atribuída ao hipotiroidismo (CAH 10.4) foi incluída no grupo das cefaleias secundárias e foi descrita como bilateral, não pulsátil e/ou contínua e deve estar presente em pacientes com claro diagnóstico de hipotiroidismo. Além disso, o tratamento do hipotiroidismo deve aliviar ao levar à completa resolução deste tipo de cefaleia. Nós revisamos a literatura relacionada à prevalência de cefaleia em hipotireoideos, suas características considerando os critérios da ICHD-II e as possíveis diferenças entre o grupo com cefaleia e o grupo sem cefaleia.
... 13 Despite this, multiple studies have reported a high prevalence of depression in women with aTA. [21][22][23] Nonetheless, any degree of physical or psychological distress directly affects QoL. 12 Quality of life has been studied extensively in adult patients with chronic health conditions. However, it was not until recently that in-depth studies were conducted to measure the perceived life quality in individuals with HT. 24,25 A systematic review published in 2016 evaluated the efficacy of thyroid-specific QoL questionnaires. ...
Objective:
The aim of this review was to evaluate the association between anti-thyroid antibodies and quality of life in people with euthyroid Hashimoto's thyroiditis.
Introduction:
Patients with Hashimoto's report symptom distress more often than those with non-autoimmune thyroid disorders. Therefore, anti-thyroid antibodies may be related to decreased quality of life in persons with Hashimoto's. The etiology of lingering symptoms, even in euthyroidism, remains unknown. The relationship between anti-thyroid antibodies and quality of life for people with Hashimoto's has not been evaluated in a systematic review.
Inclusion criteria:
The participants were males and females at least 12 years old with Hashimoto's. Participants not in a euthyroid state were excluded from this review. In this review, the exposure was the presence of anti-thyroid antibodies and the primary outcome was quality of life.
Methods:
A three-step search strategy was implemented with an initial search of PubMed and CINAHL. A comprehensive database search using all identified keywords and index terms was undertaken in March 2019 for relevant published literature, gray literature, and clinical trial registries. The final updates to the search strategies were conducted in December 2019. The search was limited to studies published in English after 1956. Two independent reviewers completed screening for inclusion and utilized the recommended JBI approach to critical appraisal, study selection, data extraction, and data synthesis. The findings are presented in a meta-analysis and in a narrative synthesis, which includes tables and figures.
Results:
All 13 studies had high methodological quality. Four studies found a significant correlation (P < 0.05) between antibodies and quality of life. A fifth study found a significant correlation (P < 0.001) between higher antibody levels and quality of life. A meta-analysis was conducted using two cross-sectional studies, which revealed that the summative small effect size is statistically significant and suggests a lower quality of life in antibody-positive patients. Due to the heterogeneity of the studies, a narrative synthesis was conducted for the three secondary outcomes: symptom distress, executive function, and mental health. Three studies found a statistically significant (P < 0.05) correlation between symptom distress and antibodies, two studies found a statistically significant (P < 0.05) association between executive function and antibodies, and all but one study found a statistically significant (P < 0.05) relationship between mental health and antibodies.
Conclusions:
The findings in this review did not reveal a definitive relationship between antibodies and quality of life. However, our meta-analysis suggested a link between anti-thyroid antibodies and decreased quality of life in euthyroid children and adults. Though not conclusive, poor mental health and symptom distress may be associated with anti-thyroid antibodies. Therefore, it may be beneficial to periodically evaluate the quality of life and mental health in euthyroid patients with positive antibodies. It is unlikely that antibodies and executive functions are related. The studies and our review's limitations require replication of findings to confirm a connection between antibodies, quality of life, and the secondary outcomes. Future research should continue to evaluate the relationship between anti-thyroid antibodies and the quality of life in individuals with euthyroid Hashimoto's thyroiditis.
Systematic review registration number:
PROSPERO CRD42018084663.
... Production of antibodies to thyroid specific auto antigen i.e. thyroglobulin (TG), thyroperoxidase (TPO) and thyrotropin receptor (TSH-R) are the almost invariable feature of AITD. 3 Elevated TSH with TPO antibodies is the gold standard for diagnosis of chronic HT. 4 Various psychiatric syndromes have been associated with Hashimoto's thyroiditis, including depression, anxiety, mania, acute psychosis, dementia, loss of cognitive function. 1,[5][6][7][8] Most of these recover after treatment of Hashimoto's thyroiditis. There are few case reports published with obsessions and compulsions as a part of clinical picture in patients with Hashimoto's thyroiditis. ...
Hashimoto's thyroiditis (HT), can present with depression, anxiety, mania, acute psychosis, dementia, loss of cognitive function and other
symptoms. Case reports with obsessions and compulsions in patients with Hashimoto’s thyroiditis are few.1 We present a case report of
paediatric OCD with Hashimoto’s thyroiditis and Hypovitaminosis D3 in a 13 year old girl who was brought with complaints of fear of
contamination and washing rituals for last 2 years. Tetany and Hypothyroidism was diagnosed 3 months prior to the onset of illness.
Investigations revealed, low Vitamin D levels, Anti TPO antibodies and Anti Thyroglobulin antibodies (ATG) positive and normal anti
stroptolysin (ASO) titre. Till date no case of OCD was reported with comorbid autoimmune thyroid disorder and Vitamin D deficiency. This
case highlights the need to investigate for Hypothyroidism with OCD not just to rule out Pediatric autoimmune neuropsychiatric disorders
(PANDAS) but also to diagnose Hashimoto’s Thyroiditis. Vitamin D deficiency is common in patients with HT and its screening and
supplementation must be considered in all patients.
... Production of antibodies to thyroid specific auto antigen i.e. thyroglobulin (TG), thyroperoxidase (TPO) and thyrotropin receptor (TSH-R) are the almost invariable feature of AITD. 3 Elevated TSH with TPO antibodies is the gold standard for diagnosis of chronic HT. 4 Various psychiatric syndromes have been associated with Hashimoto's thyroiditis, including depression, anxiety, mania, acute psychosis, dementia, loss of cognitive function. 1,[5][6][7][8] Most of these recover after treatment of Hashimoto's thyroiditis. There are few case reports published with obsessions and compulsions as a part of clinical picture in patients with Hashimoto's thyroiditis. ...
Hashimoto's thyroiditis (HT), can present with depression, anxiety, mania, acute psychosis, dementia, loss of cognitive function and other
symptoms. Case reports with obsessions and compulsions in patients with Hashimoto’s thyroiditis are few.1 We present a case report of
paediatric OCD with Hashimoto’s thyroiditis and Hypovitaminosis D3 in a 13 year old girl who was brought with complaints of fear of
contamination and washing rituals for last 2 years. Tetany and Hypothyroidism was diagnosed 3 months prior to the onset of illness.
Investigations revealed, low Vitamin D levels, Anti TPO antibodies and Anti Thyroglobulin antibodies (ATG) positive and normal anti
stroptolysin (ASO) titre. Till date no case of OCD was reported with comorbid autoimmune thyroid disorder and Vitamin D deficiency. This
case highlights the need to investigate for Hypothyroidism with OCD not just to rule out Pediatric autoimmune neuropsychiatric disorders
(PANDAS) but also to diagnose Hashimoto’s Thyroiditis. Vitamin D deficiency is common in patients with HT and its screening and
supplementation must be considered in all patients.
... At the same time, autoimmune diseases have a high risk factor for subsequent diagnosis of mental disorder (45% increase) (Benros et al., 2013). A subset of patients with mental disorders exhibit increased levels of circulating autoantibodies: patients with MDD and BD may present comorbidity with autoimmune thyroiditis, evident by the presence of thyroperoxidase antibodies (Pop et al., 1998;Kupka et al., 2002); patients with multiple sclerosis may experience neuropsychological alterations and chronic anxiety, as in MDD (Feinstein et al., 2014) or SCZ (Andreassen et al., 2015). ...
Innate and adaptive immune mechanisms have emerged as critical regulators of CNS homeostasis and mental health. A plethora of immunological factors have been reported to interact with emotion- and behavior-related neuronal circuits, modulating susceptibility and resilience to mental disorders. However, it remains unclear whether immune dysregulation is a cardinal causal factor, or an outcome of the pathologies associated with mental disorders. Emerging variations in immune regulatory pathways based on sex differences provide an additional framework for discussion in these psychiatric disorders. In this review, we present the current literature pertaining to the effects that disrupted immune pathways have in mental disorder pathophysiology, including immune dysregulation in CNS and periphery, microglial activation, and disturbances of the blood-brain barrier. In addition, we present the suggested origins of such immune dysregulation, and discuss the gender and sex influence of the neuroimmune substrates which contribute to mental disorders. The findings challenge the conventional view of these disorders and open the window to a diverse spectrum of innovative therapeutic targets, which focus on the immune-specific pathophenotypes in neuronal circuits and behavior. SIGNIFICANCE STATEMENT: The involvement of gender-dependent inflammatory mechanisms on the development of mental pathologies is gaining momentum. This review addresses these novel factors and presents the accumulating evidence introducing microglia and proinflammatory elements as critical components and potential targets, for the treatment of mental disorders.
... However, when examined more carefully, in general these earlier results are in line with the findings of this study. For instance, it has been suggested that the presence of elevated TPOAbs is related with an increased risk of depressive symptoms and depression, regardless of thyroid status (31)(32)(33)(34). However, these studies were performed in small, younger, or highly selected populations such as pregnant or perimenopausal women. ...
Background:
Elevated levels of antithyroperoxidase antibodies (TPOAbs) have been associated with progression of subclinical thyroid dysfunction, extrathyroidal diseases, and decrease in functional status. However, TPOAb as determinant of future thyroid dysfunction and other clinical outcomes has not been studied well for adults aged 85 years and over. This study aimed to assess associations of TPOAb levels with thyroid function, survival, physical function, disability in activities of daily living (ADL), cognitive function, and depressive symptoms in the oldest old.
Methods:
Data from a population-based cohort study (Leiden 85-plus Study) of residents of Leiden, the Netherlands, aged 85 and older were used. Baseline serum TPOAb levels were available for 488 participants (82% of the total cohort). We considered levels ≥35 IU/mL as elevated. Thyroid function (thyrotropin [TSH] and free thyroxine) was assessed at age 85 (baseline), 87, and 88 years. Survival, physical function, disability in ADL, cognitive function, and depressive symptoms were assessed from age 85 through 90 years.
Results:
At baseline, 64 of the 85-year old participants (13.1%) had elevated TPOAb levels. They were more often female, had higher TSH levels, and a higher prevalence of overt or subclinical hypothyroidism than participants with normal TPOAb levels. Over time, elevated TPOAb levels were independently associated with a lower mortality risk (hazard ratio 0.72, [95% confidence interval 0.53-0.99]), but were not associated with changes in thyroid function, nor with physical function, disability in ADL, cognitive function, or depressive symptoms.
Conclusions:
In community-dwelling oldest old, elevated TPOAb levels are cross-sectionally associated with higher TSH levels. Over time, elevated TPOAb levels are associated with a survival benefit but are not associated with changes in thyroid function, functional status, or depressive symptoms in old age. The added clinical value of TPOAb tests in oldest old persons with thyroid dysfunction is limited.
... However, the limitation of aforementioned study was that the participants primarily were middle-aged and generally healthy men and women from Korea, which may not be generalizable to other ethnic or age groups. An interesting finding in our review was that all studies from Korea (6,13,32), the Netherlands (15,19), and Norway (12,16) showed no association between SCH and depression, while studies from Brazil (22,25,33) did show significant associations, which suggests that regional differences, including economy, lifestyle, and diet, play key roles in these observational studies. ...
Background: Thyroid function is closely associated with neuropsychological functions, including mental state and cognitive functions. Although thyroid function is routinely examined in persons with depressive symptom, the association between subclinical hypothyroidism (SCH) and depression remains inconclusive. Objective: This systematic review and meta-analysis aimed to evaluate the risk of depression in persons with SCH. Methods: The PubMed, Embase, and Web of Science databases were searched up to August 2018. The primary outcome was the prevalence of depression, as evaluated by various types of self-reported depression scales. Odds ratios (ORs) were calculated to compare the risk of depression between persons with SCH and those with euthyroidism. Results: Twenty-one studies were included in the systematic review, with a total of 103,375 subjects from 7 studies being pooled for the meta-analysis to evaluate the risk of depression. The meta-analysis showed that persons with SCH had a significantly elevated risk of depression than persons with euthyroidism (OR = 1.78, 95% confidence interval [CI]: 1.11-2.86, P = 0.02). No publication bias was found, as indicated by Egger's test (t = -0.49, P = 0.647) and Begg's test (z = -0.15, P = 0.881). In addition, the funnel plot showed a symmetric distribution. Conclusions: This meta-analysis demonstrated that SCH was positively associated with the risk of depression, especially in persons above 50 years of age, suggesting it is necessary to pay close attention to depressive symptoms in persons with SCH.
... Unexpectedly, the decrease was persistent indicating an altered regulation of the hypothalamic-pituitary-thyroid axis. Similarly, other studies also reported that there was an association between thyroid autoimmunity with fibromyalgia and depression (Pop et al. 1998;Ribeiro and Proietti 2004). Interestingly, Pamuk and Cakir (2007) observed that thyroid autoimmunity in fibromyalgia was characteristic of older postmenopausal female patients, suggesting a possible role of estrogen. ...
The increasing number of individuals with comorbidities poses an urgent need to improve the management of patients with multiple co-existing diseases. Among these comorbidities, chronic pain and mood disorders, two long-lasting disabling conditions that significantly reduce the quality of life, could be cited first. The recent development of animal models accelerated the studies focusing on the underlying mechanisms of the chronic pain and depression/anxiety comorbidity. This review provides an overview of clinical and pre-clinical studies performed over the past two decades addressing the molecular aspects of the comorbid relationship of chronic pain and depression. We thus focused on the studies that investigated the molecular characteristics of the comorbid relationship between chronic pain and mood disorders, especially major depressive disorders, from the genetic and epigenetic point of view to key neuromodulators which have been shown to play an important role in this comorbidity.
... It is hypothesized that the dysfunction of the immune system may lead to the reduction of monoamine synaptic availability, which is considered a fundamental mechanism in the pathophysiology of depression [15]. One of the first studies to show the connection between autoimmune thyroid disorders and depression was conducted in 1998 and included 583 perimenopausal women; after adjustment for psychosocial factors it was concluded that women with elevated TPOAb levels (≥100 IU/ml) are at risk for depression [19]. Afterwards the association between MDD and thyroid autoimmunity was further examined in different studies; some of them aimed to reveal the link between HT and depression (see Table 1), while others focused on the connection between increased TPOAb levels and depressive symptoms among the general population (see Table 2). ...
Depression and bipolar disorder are two major psychiatric illnesses whose pathophysiology remains elusive. Newly emerging data support the hypothesis that the dysfunction of the immune system might be a potential factor contributing to the development of these mental disorders. The most common organ affected by autoimmunity is the thyroid; therefore, the link between autoimmune thyroid disorders and mental illnesses has been studied since the 1930s. The aim of this review is to discuss the associations between thyroid autoimmunity, depression and bipolar disorder.
... The ANA/RF positive TMD patients also showed higher scores of anxiety and depression. An intimate association between autoimmunity and depression has been demonstrated [24] and reports show that autoimmunity may be a crucial risk factor of anxiety disorder [25]. TMD is also a chronic pain disorder well known to be accompanied by psychological problems such as depression and anxiety [26]. ...
Background:
To investigate the differences in clinical characteristics and long-term treatment outcomes according to antinuclear antibody(ANA) and rheumatoid factor(RF) positivity and the correlation between pain-related and hematological indices in temporomandibular disorders(TMD) patients.
Methods:
Clinical examinations were done following the Research Diagnostic Criteria for TMD in 257 patients. Comprehensive screening along with psychological and hematological evaluations (ANA, RF, complete blood cell count, C-reactive protein[CRP] and erythrocyte sedimentation rate[ESR]) were conducted. Clinical characteristics and treatment outcomes were statistically compared between ANA/RF positive and negative groups.
Results:
Thirty-nine patients showed ANA/RF positivity. Male patients had smaller comfortable mouth opening(CMO)(p = 0.033) and maximum mouth opening(MMO)(p = 0.016) ranges with more painful neck muscles on palpation when RF/ANA positive. Pain duration, intensity, disability days and psychological distress levels were also higher in RF/ANA positive male patients. Significant correlation was shown in ESR with pain duration(p < 0.05) and numeric rating scale(NRS) before treatment(p < 0.05), CRP with NRS before treatment(p < 0.01), and red blood cell (RBC) with pain intensity(p < 0.05), NRS before treatment(p < 0.01), CMO(p < 0.01), pain on palpation of cervical muscles(p < 0.01), CMO(p < 0.05), and MMO(p < 0.05) 6 months after treatment.
Conclusions:
These results may point towards a nonspecific autoimmune disposition in a subgroup of TMD patients. RF and ANA could be considered as a screening test for the detection of autoimmune phenomena in TMD.
... The detection of anti-thyriod peroxidase (TPO-Ab), and anti-thyroglobulin (TG-Ab) antibodies an Table 1. Changes in thyroid function that the main mechanisms leading to changes in early pregnancy in the context of the clinical presentation of thyroid dysfunction, confirms the diagnosis of thyroid autoimmune disease [2]. ...
... Additionally, the effectiveness of thyroid hormone supplementation in the treatment of depression remains controversia, with some positive (4, 6, 7), but also some null studies (8). Studies of the association between subclinical hypothyroidism and depressive symptoms have been mostly cross-sectional and their findings were inconclusive, with some studies reporting a positive association (9,10) , while others found no association (11)(12)(13)(14) . Although some cohort studies have evaluated the association between subclinical hypothyroidism and depression (15,16) , most of these studies focused on elderly populations, and evidence on the association between subclinical hypothyroidism and depression in young and middle-aged populations is scarce. ...
Background
The role of subclinical hypothyroidism in the development of depression remains controversial. We examined the prospective association between subclinical hypothyroidism and incident depressive symptoms.
Methods
We conducted a prospective cohort study in 220,545 middle age adults without depression who underwent at least 2 comprehensive health exams between January 1, 2011 and December 31, 2014. Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxin (FT4) levels were measured by an electrochemiluminescent immunoassay. The study outcome was incident depressive symptom defined as a CES-D score >16.
Results
During a median follow-up of 2 years, incident depressive symptoms occurred in 7,323 participants. The multivariable-adjusted hazard ratio (HR) for incident depressive symptoms comparing subclinical hypothyroid to euthyroid participants was 0.97 (0.87 to 1.09). Similarly, among euthyroid participants (n = 87,822), there was no apparent association between thyroid hormone levels and increased risk of incident depressive symptoms.
Discussion
There was no apparent association between subclinical hypothyroidism and incident depressive symptoms in a large prospective cohort of middle-aged men and women.
... The question of whether thyroid autoimmunity itself can cause symptoms is a more complicated one. A large population study from Norway suggests not [56], however, two smaller studies suggest an association unrelated to thyroid hormone levels [57,58] giving it some plausibility. The answer is therefore not clear. ...
Background
Whilst trials of combination levothyroxine/liothyronine therapy versus levothyroxine monotherapy for thyroid hormone replacement have not shown any superiority, there remains a small subset of patients who do not feel well on monotherapy. Whilst current guidelines do not suggest routine use of combination therapy they do acknowledge a trial in such patients may be appropriate. It appears that use of combination therapy and dessicated thyroid extract is not uncommon but often being used by non-specialists and not adequately monitored. This review aims to provide practical advice on selecting patients, determining dose and monitoring of such a trial. Main bodyIt is important to select the correct patient for a trial so as to not delay diagnosis or potentially worsen an undiagnosed condition. An appropriate starting dose may be calculated but accuracy is limited by available formulations and cost. Monitoring of thyroid function, benefits and adverse effects are vital in the trial setting given lack of evidence of safe long term use. Also important is that patients understand set up of the trial, potential risks involved and give consent. Conclusion
Whilst evidence is lacking on whether a small group of patients may benefit from combination therapy a trial may be indicated in those who remain symptomatic despite adequate levothyroxine monotherapy. This should be undertaken by clinicians experienced in the field with appropriate monitoring for adverse outcomes in both short and long term.
... (Euesden et al., 2017) Autoimmune thyroid dysfunction has been an emerging area of research interest considering the inconclusive reports of increased titres of antithyroid autoantibodies (ATA) in patients with depression. (Pop et al., 1998) Autoimmune thyroid dysfunction, as an endophenotype of depression could clinically translate into a subset of patients with distinct clinical profile bearing differential prognostic implications. (Van de Ven et al., 2012) With this background a case of depression with elevated ATA is presented highlighting the diagnostic and treatment challenges. ...
... 13 Moreover, elevated concentrations of aTA was independently related to depression not related to thyroid dysfunction. 23 A recent study found that over half of patients with abnormally high levels of aTA showed a significant decrease in attention span and cognitive function. 19 Patients with higher aTA levels have scored worse in physical and psychological wellbeing categories compared to those with lower aTA levels. ...
Review question:
The objective of this systematic literature review is to identify the association between anti-thyroid antibodies and quality of life in patients with thyroid disorders.
... Another clinical consideration is the increased risk for women with increased TPO-ab titers for both thyroid dysfunction (particularly hypothyroidism) and depression later in life (Balucan et al., 2013;Pop et al., 1998;Vanderpump et al., 1995) The risk for hypothyroidism is especially high for women with both increased TPO-ab titers and TSH concentrations, even if TSH concentrations are still within the normal range (Prummel and Wiersinga, 2005;Vanderpump et al., 1995). ...
Background: During the postpartum period, women are at risk for the new onset of both auto-immune thyroid disorders and depression. The presence of thyroid peroxidase antibodies (TPO-ab) during early gestation is predictive for postpartum auto-immune thyroid dysfunction. The aim of this study was to investigate the association between TPO-ab status during early gestation and first-onset postpartum depression.
Methods: Prospective cohort study (n = 1075) with follow-up during pregnancy up to one year postpartum. Thyroid function and TPO-ab status were measured during early gestation. Depressive symptomatology was assessed during each trimester and at four time points postpartum with the Edinburgh Depression Scale (EDS). Women with antenatal depression were not eligible for inclusion. Self-reported postpartum depression was defined with an EDS cut-off of ≥ 13.
Results: The cumulative incidence of self-reported first-onset depression in the first postpartum year was 6.3%. A positive TPO-ab status was associated with an increased risk for self-reported first-onset depression at four months postpartum (adjusted OR 3.8; 95% CI 1.3–11.6), but not at other postpartum time points. Prevalence rates of self-reported postpartum depression declined after four months postpartum in the TPO-ab positive group, but remained constant in the TPO-ab negative group.
Limitations: Depression was defined with a self-rating questionnaire (EDS).
Conclusions: Women with an increased TPO-ab titer during early gestation are at increased risk for self-reported first-onset depression. The longitudinal pattern of self-reported postpartum depression in the TPO-ab positive group was similar to the typical course of postpartum TPO-ab titers changes. This suggests overlap in the etiology of first-onset postpartum depression and auto-immune thyroid dysfunction. Thyroid function should be evaluated in women with first-onset postpartum depression.
... On the other hand, it is possible that there is some aspect of the hypothyroid state, which is difficult to measure or capture in survey instruments, that is not adequately reversed with LT4 monotherapy. It is also possible that Hashimoto's hypothyroidism may cause morbidity that is specifically related to the underlying autoimmunity, rather than the thyroid status [51,52]. Finally, variations in genes associated with thyroid hormone metabolism and action could be associated with an inferior response to LT4 [43], or could be associated with other conditions that affect quality of life [42]. ...
Purpose of review:
A subset of patients being treated for hypothyroidism do not feel well while taking levothyroxine (LT4) replacement therapy, despite having a normal serum thyroid stimulating hormone level. Pursuing a relative triiodothyronine deficiency as a potential explanation for patient dissatisfaction, has led to trials of combination therapy with liothyronine (LT3), with largely negative outcomes. This review attempts to reconcile these diverse findings, consider potential explanations, and identify areas for future research.
Recent findings:
Patients being treated with LT4 often have lower triiodothyronine levels than patients with endogenous thyroid function. Linking patient dissatisfaction with low triiodothyronine levels has fueled multiple combination therapy trials that have generally not shown improvement in patient quality of life, mood, or cognitive performance. Some trials, however, suggest patient preference for combination therapy. There continues, moreover, to be anecdotal evidence that patients have fewer unresolved symptoms while taking combination therapy.
Summary:
The 14 trials completed to date have suffered from employing doses of LT3 that do not result in steady triiodothyronine levels, and having insufficient power to analyze results based on baseline dissatisfaction with therapy and patient genotype. Future trials that are able to incorporate such features may provide insight into what thyroid hormone preparations will most improve patient satisfaction with therapy.
... Our results are in agreement with Pop et al that women with elevated TPO antibody levels are especially vulnerable to depression, whereas postmenopausal status does not increase the risk of depression. 17 But our study results are in distinction to the above in the fact that when adjusted for TSH levels there was no significant association of depression with TPO antibody levels. Chopra et al 15 studied subtle abnormalities in the thyroid functions in depressive patients. ...
Background: There are limited studies on depression in medically ill using current diagnostic tools in India. The present study aims to find the prevalence of depression in patients with hypothyroidism and its association with clinical parameters and thyroid autoantibody levels. Materials and Methods: Patients fulfilling clinical and biochemical criteria suggesting hypothyroidism of either gender or age between18 and 65 years were included in the study. Clinical features and serum TSH were noted, Anti TPO antibody test was done. Patients were administered the validated local language version of the Hospital anxiety and depression score (HADS). Patients were classified as normal, those with borderline depression and those with depression. Results and Discussion: One hundred and forty four patients were included in the analysis. Eighteen out of 144 patients had depression and another 20 had borderline depression. Higher serum thyroid stimulating hormone, anti-thyroid peroxidase antibody levels and body mass index were found to have a significant relation to presence of depression. The independent association of TPO antibody to depression when adjusted for TSH could not be proven. Symptoms such as, cold intolerance, memory loss and clinical assessments like BMI as an association to depression in hypothyroid patients is a novel finding when compared to older studies. Conclusion: There is a high prevalence of depression in patients with hypothyroidism which can be diagnosed only if systematic screening using validated tools is used for the same. Depression needs to be actively screened and managed appropriately in hypothyroid patients so as to avoid the devastating consequences of untreated depression. Some clinical indicators like obesity, cold intolerance and memory loss may signal the presence of depression in hypothyroid patients.
Hypothyroidism is associated with a decreased health-related quality of life (HRQoL). We hypothesized that individuals with hypothyroidism (defined as use of thyroid hormone (TH)) and especially those having an impaired HRQoL are characterized by a high prevalence of comorbid disorders, and that the impact of hypothyroidism and comorbidity on HRQoL is synergistic. Presence of comorbidity was based on data obtained using structured questionnaires, physical examination, biochemical measurements and verified medication use. Single morbidities were clustered into 14 different disease domains. HRQoL was measured using the RAND-36. Logistic regression analyses were used to determine the effect of TH-use on the odds of having an affected disease domain and a lower score than an age- and sex-specific reference value for HRQoL. TH was used by 4537/147201 participants of the population-based Lifelines cohort with a mean(±SD) age of 51.0±12.8 years (88% females). 85% of the TH-users had ≥1 affected disease domain, in contrast to 71% of non-users. TH-use was associated with a higher odds of 13/14 affected disease domains, independent of age and sex. In a multivariable model, TH-use was associated with a decreased HRQoL across 6/8 dimensions. No significant interactions between TH-use and affected disease domains were observed. TH-users with an impaired HRQoL had significantly more comorbidity than those not having an impaired HRQoL. In this large, population-based study, we demonstrated that TH-users had more comorbidity than individuals not using TH. The co-existence of other chronic medical conditions in subjects with TH-use led to further lowering of HRQoL in an additive manner.
Background
The morbidity of thyroid cancer has been increasing in the last decades all over the world. In addition to the more sensitive thyroid nodule screening technology, several social and environmental factors might represent credible candidates for this increase. They include psychological stress, lifestyle-associated risk factors, nutritional deficiencies, and environmental pollutants. Foremost, psychological stress had gained high interest as a possible promoter and a modifiable risk factor for thyroid nodules in recent years. The present study was to investigate the clinical characteristics and psychological status of the population during the peak of coronavirus disease 2019 (COVID-19) and assessed the association of psychosocial determinants and the ultrasonic characteristics of thyroid nodules.
Methods
In this cross-sectional study, 490 adult subjects who had received at least two doses of COVID-19 vaccine and were not infected with COVID-19, and did not know whether they had thyroid nodules, received thyroid color ultrasound examination and psychological questionnaire survey. Depression, anxiety, and stress were assessed using Depression Anxiety Stress Scales-21 (DASS-21). Sleep quality was rated using the Pittsburgh sleep quality index (PQSI). The characteristics of 243 subjects with thyroid nodules were described and recorded in detail by thyroid color ultrasound, and the correlations between anxiety, depression, sleep quality, clinical indicators, and thyroid nodule ultrasound characteristics were analyzed. Associations between psychological status (mutually adjusted predictors) and ultrasonic characteristics of thyroid nodules (outcome) were modeled using binary logistic regression controlling for sex, age, BMI, TSH, FT3, and FT4.
Results
Depression was positively correlated with thyroid hypoechoic nodule (OR = 3.720, 95%CI 1.615–8.570), microcalcification of thyroid nodule (OR = 3.638, 95%CI 1.476–8.966), the aspect ratio of thyroid nodule>1 (OR = 3.860, 95%CI 1.052–14.161), the unclear boundary of thyroid nodule (OR = 4.254, 95%CI 1.359–13.312), and the irregular edge of thyroid nodule (OR = 4.134, 95%CI 1.810–9.439). Anxiety was positively correlated with microcalcification of thyroid nodules (OR = 4.319, 95%CI 1.487–11.409). Stress was positively correlated with thyroid hypoechoic nodules (OR = 4.319, 95%CI 1.487–11.409), microcalcification of thyroid nodules (OR = 2.724, 95%CI 1.038–7.151), and the irregular edge of thyroid nodules (OR = 2.478, 95%CI 1.077–5.705).
Conclusion
This study demonstrates that depression, anxiety, and stress were associated with the morbidity of thyroid nodules and thyroid ultrasound characteristics. During COVID-19, people’s negative emotions increased significantly compared to before. Negative emotions might be harmful to thyroid health. Therefore, during periods of high stress, strategies to prevent psychological problems should be implemented to improve thyroid health.
Objective: To investigate the association between thyroid-stimulating hormone (TSH) and clinically relevant depression (CRD) in a population-based study.
Patients and Methods: Adult patients (≥18 years of age) who received care at Mayo Clinic in Rochester, Minnesota, and completed a TSH and Patient Health Questionnaire - 9 (PHQ-9) within 6 months of each other, between July 8, 2017, and August 31, 2021, were included. Demographics, medical comorbidities, thyroid function laboratory data, psychotropic medications, presence of primary thyroid disorder, thyroid hormone replacement (T4 and/or T3), and mood disorder diagnoses (using International Classification of Diseases, 10th version, Clinical Modifications codes) were extracted electronically. The primary outcome, CRD, was defined as a PHQ-9 score greater than or equal to 10. Logistic regression analysis was conducted to assess the association between TSH categories (low ≤0.3 mIU/L; normal >0.3-4.2 mIU/L; high >4.2 mIU/L) and CRD.
Results: The cohort included 29,034 patients, mean age 51.4 years, 65% females, 89.9% White, and a mean body mass index of 29.9 kg/m2. The mean ± standard deviation for TSH was 3.0±8.5 mIU/L, and the mean PHQ-9 score was 6.3±6.2. After adjustment, the odds of CRD were significantly higher among the low TSH category (odds ratio, 1.37; 95% CI, 1.18-1.57; P<.001) compared with the normal TSH category, especially in people 70 years of age or younger compared with people older than 70 years of age. Subgroup analysis did not show an increase in odds of CRD among patients with subclinical/overt hypothyroidism/hyperthyroidism (after adjustment).
Conclusion: In this large population-based cross-sectional study, we report that low TSH was associated with higher odds of depression. Future longitudinal cohort studies are needed to investigate the relationship between thyroid dysfunction and depression as well as sex differences.
Thyroid autoimmunity (TAI) triggered by genetic and epigenetic variation occurs mostly in women of reproductive age. TAI is described mainly by positivity of anti-thyroid peroxidase antibody (TPO-Ab) and/or thyroglobulin antibody (TG-Ab). TPO-Ab, but not TG-Ab, was suggested to be associated with pregnancy outcome in euthyroid women undergoing assisted reproductive technology (ART), but their results are conflicting. This meta-analysis was performed to decide whether the presence of TPO-Ab-in a concentration dependent manner-correlates with the success of ART. A systematic literature search was performed in the PubMed, Web of Science, and EMBASE databases for relevant articles published from January 1999 to April 2022, and these studies focused on the effect of TAI on pregnancy outcomes of women who underwent in vitro fertilization, intracytoplasmic sperm injection and intrauterine insemination and met the inclusion criteria: (i) the studies were prospective or retrospective study; (ii) all patients undergoing ART were tested for thyroid-related antibodies; (iii) the assessed ART outcomes included miscarriage rate (MR) or delivery rate (DR). The exclusion criteria were: (i) female congenital uterine malformation, chromosomal diseases and other infectious diseases; (ii) overt hypothyroidism or pre-existing thyroid disease; (iii) thrombus tendency. We divided the included patients into three groups according to the TPO-Ab threshold they defined: (i) TPO-Ab (-), threshold <34 IU/mL; (ii) TPO-Ab-34, threshold >34 IU/mL; (iii) TPO-Ab-100, threshold >100 IU/mL. We then extracted necessary relevant data, including MR and DR. Egger's test was used to evaluate the risk of publication bias. This meta-analysis included a total of 7 literatures involving 7466 patients with TAI (-) and 965 patients with TAI (+) and revealed that there was no significant difference between group TPO-Ab-34 and group TPO-Ab (-) in MR [risk ratio (RR): 0.61 (0.35, 1.08), p = 0.09] and DR [RR: 0.97 (0.83, 1.13), p = 0.69]. By contrast, compared to TPO-Ab (-) group, TPO-Ab-100 patients showed markedly higher MR [RR: 2.12 (1.52, 2.96), p = 0.0046], and lower DR [RR: 0.66 (0.49, 0.88), p < 0.0001] with high degree of statistical significance. This meta-analysis suggests that, for euthyroid patients, high level of TPO-Ab (>100 IU/mL) could adversely influence the pregnancy outcome of ART.
Background:
Subjects receiving levothyroxine (L-T4) treatment have increased prevalence of depression, anxiety, and antidepressant use, but whether the underlying mechanism relates to thyroid autoimmunity is still unclarified.
Methods:
This is a population-based longitudinal study. Baseline biochemical and questionnaire data from the Danish General Suburban Population Study (GESUS) in 2010-2013 were linked with individual-level longitudinal data in national health registries. The aim was to investigate the associations between thyroid peroxidase antibodies (TPOAb) and L-T4 treatment, separately and through interaction, and at least one redeemed prescription for antidepressants. Logistic and Cox regression were used to evaluate initiation of antidepressant use before and after the baseline examination in GESUS, respectively. All exposures and covariates were fixed at the date of baseline examination. Thyroid autoimmunity was defined as serum thyroid peroxidase antibodies (TPOAbs)>60 U/mL. Adjustments included sex, age, education, income, Charlson comorbidity index, smoking and alcohol. Sensitivity analyses were performed for missing variables, exclusion of lithium use, exclusion of thyroid surgery, and conservative definitions for L-T4 treatment and antidepressant use requiring at least 2 prescriptions.
Results:
We included 12,894 individuals, of whom 2,353 (18%) had "past or current" antidepressant use at baseline, leaving 10,541 individuals at risk for incident antidepressant use after baseline. Median follow-up was 7.8 years during which 783 individuals (7.4% of 10,541 individuals) had incident antidepressant use. TPOAb positivity was not associated with "past or current" (OR 0.90, 95% CI[0.78-1.03], p=0.13) nor incident antidepressant use (HR 1.02, 95% CI[0.83-1.25], p=0.88). L-T4 treatment was associated with increased "past or current" antidepressant use (OR 1.33, 95% CI[1.10-1.62], p=0.004) and increased incident antidepressant use (HR 1.38, 95% CI[1.03-1.85], p=0.03). There were no interactions between effects of TPOAb positivity and L-T4 treatment on use of antidepressants in logistic (p=0.87) or Cox regression models (p=0.82). Sensitivity analyses were robust, except that incident use of least 2 redeemed antidepressant prescriptions was not statistically significant.
Conclusions:
Levothyroxine treatment, but not TPOAb positivity, was associated with increased prevalent or incident antidepressant use with at least one prescription. Our findings do not support that thyroid autoimmunity is an important factor for antidepressant use in patients receiving L-T4 treatment.
There are many thyroid-related factors that combine with non-thyroid-related factors in order to affect the patient response to treatment of hypothyroidism, in terms of their satisfaction with therapy. Some of the thyroid-derived factors include the etiology of the hypothyroidism and the amount of residual thyroid function that the patient retains. These two factors may be intertwined and affected by a third influence, the presence of thyroid peroxidase antibodies. The downstream consequences of the interactions between these three factors may influence both free thyroxine and free triiodothyronine levels, TSH concentrations, and various thyroid biomarkers. Evidence of the widespread importance of thyroid hormones can be inferred from the multiple genes that are regulated, with their regulation affecting multiple serum biomarkers. Thyroid biomarkers may extend from various well-known serum markers such as lipids and sex hormone-binding globulin to serum levels of thyroid hormone metabolites. Moreover, the interplay between thyroid hormones and biomarkers and their relative ratios may be different depending on the hypothyroidism etiology and degree of residual thyroid function. The ultimate significance of these relationships and their effect on determining patient-reported outcomes, quality of life, and patient satisfaction is, as yet, poorly understood. However, identification of better biomarkers of thyroid function would advance the field. These biomarkers could be studied and correlated with patient-reported outcomes in future prospective studies comparing the impact of various thyroid hormone therapies.
The majority of patients with hypothyroidism feel better when levothyroxine treatment restores thyroid-stimulating hormone (TSH) concentrations to normal. Increasingly, a significant minority of patients remain symptomatic and are dissatisfied with their treatment. Overzealous treatment of symptomatic patients with subclinical hypothyroidism may contribute to dissatisfaction among hypothyroidism patients, as potential hypothyroid symptoms in patients with minimal hypothyroidism rarely respond to treatment. Thyroid hormone prescriptions have increased by 30% in the United States in the last decade. The diagnosis of subclinical hypothyroidism should be confirmed by repeat thyroid function tests ideally obtained at least 2 months later, as 62% of elevated TSH levels may revert to normal spontaneously. Generally, treatment is not necessary unless the TSH exceeds 7.0–10 mIU/L. In double-blinded randomized controlled trials, treatment does not improve symptoms or cognitive function if the TSH is less than 10 mIU/L. While cardiovascular events may be reduced in patients under age 65 with subclinical hypothyroidism who are treated with levothyroxine, treatment may be harmful in elderly patients with subclinical hypothyroidism. TSH goals are age dependent, with a 97.5 percentile (upper limit of normal) of 3.6 mIU/L for patients under age 40, and 7.5 mIU/L for patients over age 80. In some hypothyroid patients who are dissatisfied with treatment, especially those with a polymorphism in type 2 deiodinase, combined treatment with levothyroxine and liothyronine may be preferred.
Abstract
Importance
Hypothyroidism is considered a cause of or a strong risk factor for depression, but recent studies provide conflicting evidence regarding the existence and the extent of the association. It is also unclear whether the link is largely due to subsyndromal depression or holds true for clinical depression.
Objective
To estimate the association of hypothyroidism and clinical depression in the general population.
Data Sources
PubMed, PsycINFO, and Embase databases were searched from inception until May 2020 for studies on the association of hypothyroidism and clinical depression.
Study Selection
Two reviewers independently selected epidemiologic and population-based studies that provided laboratory or International Statistical Classification of Diseases and Related Health Problems diagnoses of hypothyroidism and diagnoses of depression according to operationalized criteria (eg, Diagnostic and Statistical Manual of Mental Disorders or International Statistical Classification of Diseases and Related Health Problems) or cutoffs in established rating scales.
Data Extraction and Synthesis
Two reviewers independently extracted data and evaluated studies based on the Newcastle-Ottawa Scale. Summary odds ratios (OR) were calculated in random-effects meta-analyses.
Main Outcomes and Measures
Prespecified coprimary outcomes were the association of clinical depression with either hypothyroidism or autoimmunity.
Results
Of 4350 articles screened, 25 studies were selected for meta-analysis, including 348 014 participants. Hypothyroidism and clinical depression were associated (OR, 1.30 [95% CI, 1.08-1.57]), while the OR for autoimmunity was inconclusive (1.24 [95% CI, 0.89-1.74]). Subgroup analyses revealed a stronger association with overt than with subclinical hypothyroidism, with ORs of 1.77 (95% CI, 1.13-2.77) and 1.13 (95% CI, 1.01-1.28), respectively. Sensitivity analyses resulted in more conservative estimates. In a post hoc analysis, the association was confirmed in female individuals (OR, 1.48 [95% CI, 1.18-1.85]) but not in male individuals (OR, 0.71 [95% CI, 0.40-1.25]).
Conclusions and Relevance
In this systematic review and meta-analysis, the effect size for the association between hypothyroidism and clinical depression was considerably lower than previously assumed, and the modest association was possibly restricted to overt hypothyroidism and female individuals. Autoimmunity alone may not be the driving factor in this comorbidity.
Introduction: Studies have found greater experiences of stigma among persons with schizophrenia than other mental disorders. Caregiver’s knowledge and perception of schizophrenia might affect the perceived stigma by the patients. However, this relationship between knowledge of schizophrenia among caregivers and stigma faced by the persons with schizophrenia has not been explored.
Aim and Objective: To assess the relationship between caregivers’ knowledge of schizophrenia and the stigma faced by the persons with schizophrenia.
Materials and Methods: A cross-sectional observational study was conducted on 70 persons with schizophrenia of minimum one-year duration and living with their primary caregivers’ for at least 6-months. Subjects of both genders with age range of 18 to 60 years were assessed with ‘internalized stigma of mental illness’ (ISMI) scale and ‘knowledge about schizophrenia interview’ (KASI) scale, along with their primary caregivers.
Results: We found a negative co-relation between primary caregivers’ knowledge and the stigma faced by the persons with schizophrenia. Caregivers knowledge about ‘etiology’ (p=0.01), ‘course & prognosis’ (p=0.03) and overall knowledge about ‘schizophrenia’ (p=0.03) was significantly associated with reduced ‘perceived discrimination’ faced by the persons with schizophrenia.
Conclusion: The study concludes that primary caregivers’ awareness and knowledge about different aspects of schizophrenia shows significant negative correlation with perceived discrimination among persons with schizophrenia. However, knowledge assessed was based on the biomedical model. Therefore, development of assessment tools for knowledge about schizophrenia based on culture specific beliefs is highly recommended.
The important prevalence of autoimmune thyroid disease (AITD) in the general population was the main motivation for conducting the present study. The present paper aims to estimate the possible comorbidities related to female sexual dysfunction (FSD) and depression related to AITD. The study group consisted of 320 patients: 250 cases known with untreated AITD, divided into subgroups (euthyroid subgroup, subclinical hypothyroidism subgroup and clinical hypothyroidism subgroup); respectively 70 healthy females in the control group. Patients underwent thyroid evaluation, ovarian evaluation and laboratory assays. At the time of the diagnosis of autoimmune thyroid disease, psychometric scales were filled in by the patients: the Female Sexual Function Index 6 (FSFI-6) and the Beck’s Depression Inventory-II (BDI-II). It was observed that healthy patients had significantly higher FSFI scores than patients with AITD (28 vs. 27; p = 0.006). In the AITD group, the risk of FSD increases with the severity of thyroid disease. The most affected areas were: sexual desire (p < 0.001), lubrication (p = 0.001) and orgasm (p = 0.008), followed by excitability and sexual satisfaction. The severity of hypothyroidism influences the degree of decrease in libido, central and peripheral excitability. Sexual satisfaction and orgasm were less influenced. The field related to pain seems uninfluenced by the presence of thyroid disease. The concomitant presence of depression and the value of thyroid-stimulating hormone (TSH) are risk factors in the development of FSD. Higher TSH value and BDI-II score increase the risk of female sexual dysfunction by 1.083 and 1.295 times, respectively. Our findings are significant and promising; they may help professionals dealing with sexual and reproductive health. Despite the importance of female sexual dysfunction and its prevalence, clinicians and patients often ignore it. In fact, only a small percentage of patients consult their doctors about sexual health, and their doctors do not often ask them questions related to this aspect.
The role of gonadal steroids in human behavior is both more complex and more poorly delineated. This chapter examines the role of gonadal steroids in behavior in women by employing two strategies: it suggests that findings from both molecular biological and animal in vivo studies illustrate the exquisite context dependency of responses to gonadal steroid signals; and it reviews the role of both gonadal steroids and context in several reproductive endocrine-related mood disorders in women (menstrual cycle-related mood disorders, perimenopausal depression, postpartum depression, and hormone replacement therapy-related dysphoria). Steroid receptors are members of a large family of intracellular proteins that serve as transcription factors when activated by their cognate hormone. By influencing the transcription of cellular proteins, steroid hormones could potentially regulate all aspects of cellular function.
Objective:
Dissatisfaction with treatment and impaired quality of life (QOL) are reported amongst people with treated hypothyroidism. We aimed to gain insight into this.
Design and patients:
We conducted an online survey of individuals with self-reported hypothyroidism.
Results:
969 responses were analysed. Dissatisfaction with treatment was common (77.6%) and overall QOL scores were low. Patient satisfaction did not correlate with type of thyroid hormone treatment, but treatment with combination levothyroxine (L-T4) and liothyronine (L-T3) or with desiccated thyroid extract (DTE) was associated with significantly better reported QOL than L-T4 or L-T3 monotherapies (p<0.001), however, multivariate analysis inclusive of other clinical parameters failed to confirm an association between type of thyroid hormone treatment and QOL or satisfaction. Multivariate analysis showed positive correlations between satisfaction and age (p=0.026), male gender (p=0.011), being under the care of a thyroid specialist (p<0.001), family doctor (GP) prescribing DTE or L-T4+L-T3 or L-T3 (p<0.001), and being well informed about hypothyroidism (p<0.001); negative correlations were observed between satisfaction and negative experiences with L-T4 (p<0.001) and expectations for more support from the GP (p<0.001), for L-T4 to resolve all symptoms (p=0.004), and to be referred to a thyroid specialist (p<0.001). For QOL, positive correlations were with male gender (p=0.011) and duration of hypothyroidism (p=0.002); negative correlations were with age (p=0.027), visiting the GP more than 3 times before diagnosis (p<0.001), sourcing DTE or L-T3 independently (p=0.014), negative experiences with L-T4 (p=0.013), having expectations for L-T4 to resolve all symptoms (p<0.001) and of more support from the GP (p=0.006).
Conclusions:
Multiple parameters including prior healthcare experiences and expectations influence satisfaction with hypothyroidism treatment and QOL. Focusing on enhancing the patient experience and clarifying expectations at diagnosis may improve satisfaction and QOL.
Importance
With a prevalence of 4% to 13% in the United States, autoimmune thyroiditis (AIT) is a major health problem. Besides somatic complications, patients with AIT can also experience psychiatric disorders. The extent of these organic psychiatric diseases in patients with AIT, however, is so far not commonly known.
Objective
To provide meta-analytic data on the association of depression and anxiety with AIT.
Data Sources
Google Scholar, the EBSCO Host databases, the Web of Knowledge, and PubMed were searched from inception through December 5, 2017. Articles identified were reviewed and reference lists were searched manually.
Study Selection
Case-control studies that reported the association between AIT and either depression or anxiety disorders or both were included.
Data Extraction and Synthesis
Data extraction was performed by multiple observers following the PRISMA guidelines. Two univariate random-effects meta-analyses were performed, and moderators were tested with Bonferroni-corrected meta-regression analysis. Heterogeneity was assessed with the I² statistic. Sensitivity analyses tested the robustness of the results. Small study effects were assessed with funnel plots and the Egger test.
Main Outcomes and Measures
The odds ratio of patients with AIT and depression compared with a healthy control group, as well as the odds ratio of patients with AIT and anxiety disorders compared with a healthy control group.
Results
Nineteen studies comprising 21 independent samples were included, with a total of 36 174 participants (35 168 for depression and 34 094 for anxiety). Patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had significantly higher scores on standardized depression instruments, with an odds ratio of 3.56 (95% CI, 2.14-5.94; I² = 92.1%). For anxiety disorders, patients with AIT, Hashimoto thyroiditis, or subclinical or overt hypothyroidism had an odds ratio of 2.32 (95% CI, 1.40-3.85; I² = 89.8%). Funnel plot asymmetry was detected for studies of depression. Study quality assessed with the Newcastle-Ottawa Scale for case-control studies (mean [SD] score: anxiety, 5.77 [1.17]; depression, 5.65 [1.14]; of a possible maximum score of 9) and proportion of females did not modulate the meta-analytic estimate, whereas mean age did.
Conclusions and Relevance
This meta-analysis establishes the association between AIT and depression and anxiety disorders. Patients with AIT exhibit an increased chance of developing symptoms of depression and anxiety or of receiving a diagnosis of depression and anxiety disorders. This finding has important implications for patients and could lead to the choice of early treatment—and not only psychotherapeutic treatment—of the organic disorder.
Objective: Even mild hypothyroidism in premenopausal women is accompanied by impaired sexual functioning. The study was aimed at comparing the effect of levothyroxine, administered alone or in combination with liothyronine, on sexual function and depressive symptoms in premenopausal women treated because of hypothyroidism.
Methods: This quasi-randomized, single-blind study included 39 young women receiving levothyroxine treatment who, despite thyrotropin and thyroid hormone levels within normal limits, still experienced clinical symptoms of hypothyroidism. These patients were divided into two groups: group A (n = 20) continued levothyroxine treatment, while group B (n = 19) received levothyroxine/liothyronine combination therapy. At the beginning of the study and six months later, all participants of the study filled in questionnaires evaluating female sexual functioning (Female Sexual Function Index - FSFI) and the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition - BDI-II).
Results: The study completed 37 women. Baseline sexual functioning and depressive symptoms did not differ between the study groups. Neither the total FSFI score nor the domain scores changed throughout the study in women who continued levothyroxine treatment. Compared to levothyroxine administered alone, levothyroxine/liothyronine combination therapy increased scores for two domains: sexual desire and arousal, tended to increase the total FSFI score, as well as tended to decrease the overall BDI-II score. The effect of the combination therapy on sexual function correlated with a treatment-induced increase in serum levels of free triiodothyronine and testosterone.
Conclusions: The obtained results suggest that levothyroxine administered together with liothyronine is superior to levothyroxine administered alone in affecting female sexual functioning.
http://journal.frontiersin.org/article/10.3389/fendo.2017.00091/full
To define the relation between mood and autoimmune thyroid dysfunction during the eight months after delivery.
Double blind comparison of the psychiatric status of women positive and negative for thyroid antibodies. Clinical examination and blood sampling for free triiodothyronine and thyroxine, thyroid stimulating hormone, and thyroid antibody concentrations at four weekly intervals. Psychiatric assessment at six, eight, 12, 20, and 28 weeks post partum.
Outpatient department of district hospital.
145 antibody positive women and 229 antibody negative women delivering between August 1987 and December 1989.
Thyroid status. Number of cases of mental ill health by the general health questionnaire, research diagnostic criteria, Hamilton 17 item depression scale, hospital anxiety and depression scale, and Edinburgh postnatal depression scale.
Six weeks after delivery the general health questionnaire showed 62 (43%) antibody positive women and 65 (28%) antibody negative women had mental ill health (chi 2 = 8.18, p less than 0.005). Follow up of 110 antibody positive and 132 antibody negative women showed significantly greater depression by research diagnostic criteria in antibody positive women (47%) than antibody negative women (32%) regardless of thyroid dysfunction. Antibody positive women showed higher mean scores for depression on the Hamilton (6.01 v 3.89, p = 0.0002), Edinburgh (7.45 v 5.92, p = 0.031), and hospital depression scales (4.95 v 3.79, p = 0.003).
Depressive symptoms are associated with positive thyroid antibody status in the postpartum period.
This study presents estimates of lifetime and 12-month prevalence of 14 DSM-III-R psychiatric disorders from the National Comorbidity Survey, the first survey to administer a structured psychiatric interview to a national probability sample in the United States.
The DSM-III-R psychiatric disorders among persons aged 15 to 54 years in the noninstitutionalized civilian population of the United States were assessed with data collected by lay interviewers using a revised version of the Composite International Diagnostic Interview.
Nearly 50% of respondents reported at least one lifetime disorder, and close to 30% reported at least one 12-month disorder. The most common disorders were major depressive episode, alcohol dependence, social phobia, and simple phobia. More than half of all lifetime disorders occurred in the 14% of the population who had a history of three or more comorbid disorders. These highly comorbid people also included the vast majority of people with severe disorders. Less than 40% of those with a lifetime disorder had ever received professional treatment, and less than 20% of those with a recent disorder had been in treatment during the past 12 months. Consistent with previous risk factor research, it was found that women had elevated rates of affective disorders and anxiety disorders, that men had elevated rates of substance use disorders and antisocial personality disorder, and that most disorders declined with age and with higher socioeconomic status.
The prevalence of psychiatric disorders is greater than previously thought to be the case. Furthermore, this morbidity is more highly concentrated than previously recognized in roughly one sixth of the population who have a history of three or more comorbid disorders. This suggests that the causes and consequences of high comorbidity should be the focus of research attention. The majority of people with psychiatric disorders fail to obtain professional treatment. Even among people with a lifetime history of three or more comorbid disorders, the proportion who ever obtain specialty sector mental health treatment is less than 50%. These results argue for the importance of more outreach and more research on barriers to professional help-seeking.
Microsomal antibodies have been related to postpartum thyroid dysfunction and postpartum depression.
To detect the value of microsomal antibodies during gestation in a random population, as a risk factor for thyroid dysfunction and depression during the postpartum period.
The presence of microsomal antibodies was investigated in a random population of 293 women at 32 weeks' gestation. At the same time, postpartum thyroid function was assessed repeatedly in all women every six weeks up to 34 weeks' postpartum. Postpartum thyroid dysfunction, defined as the presence of abnormal TSH, in combination with abnormal fT4 and/or fT3 values, occurred in 21 women (7.2%) during the postpartum period. Depression was assessed using the Research Diagnostic Criteria without knowing the results of biochemical thyroid function tests. At 32 weeks' gestation there were 27 (9.2%) women with elevated microsomal antibody titres. Compared with microsomal-antibody negative women at 32 weeks' gestation, these women had an RR of 20 for developing postpartum thyroid dysfunction and an RR of 1.7 for developing postpartum depression.
Women with elevated microsomal antibody titres during gestation are particularly at risk for postpartum thyroid dysfunction, but only have a slightly increased risk for postpartum depression.
Introduction
At first sight there could hardly be a more simple disorder to diagnose and treat than hypothyroidism. Now that we have robust hormone assays and reliable preparations of thyroxine in tablet sizes sufficiently small to tailor doses to an individual's requirement, what issues remain? The purpose of this review is to flesh out some of the recently published consensus views on hypothyroidism,1 2 in particular regarding the role of screening for hypothyroidism and the need for treatment in subclinical hypothyroidism. Table 1) gives the definitions of hypothyroidism.
View this table:In this windowIn a new windowTable 1 Definitions of hypothyroidism
Methods
I have conducted a monthly Medline search for all articles on hypothyroidism for five years. For this review I scanned these papers and background papers for a recent consensus statement,2 together with their references, for those focusing on screening and subclinical hypothyroidism. In addition, as part of my 15 years of thyroid related research I have continuously reviewed the literature.
Frequency of hypothyroidism
New information on the frequency of hypothyroidism has been provided by a survey of a randomly selected population of 2779 adults living in Whickham, Tyne and Wear, who had baseline thyroid function tests and were then reexamined after 20 years.3 Remarkably, 96% of the 1877 survivors participated in a follow up survey and 91% had further tests. The mean incidence of spontaneous overt hypothyroidism in women was 3.5 survivors/1000/year and in men 0.6/1000/year. There was no apparent excess of hypothyroidism in those who had died. The mean average at diagnosis was 58-59, but the probability of developing hypothyroidism increased steadily with age, reaching 14 cases/1000/year for women aged 75-80.
This survey also clarified the predictive value of detecting thyroid antibodies (against thyroid peroxidase/microsomal antigen) and measuring thyroid stimulating hormone concentrations. For women with subclinical hypothyroidism but without thyroid antibodies the relative risk of developing overt hypothyroidism over …
To determine the prevalence of psychiatric disorders in non-institutionalised Dutch adults.
Cross-sectional.
Trimbos Institute, Utrecht, the Netherlands.
A representative sample of 7076 adults (18-64 years) in the Netherlands' population were interviewed in 1996 to determine the prevalence of mental disorders ever, in the previous 12 months and in the previous month. Objectives and study design are described in the previous article (1997: 2448-52). The 'Composite international diagnostic interview' (CIDI) was used to assess the following mental disorders according to Diagnostic and statistical manual of mental disorders, 3rd revised edition (DSM-III-R): affective disorders, anxiety disorders, eating disorders, schizophrenia and other non-affective psychoses, substance dependence and substance abuse.
Mental disorders were common in the general population: the prevalence 'ever' of all disorders was 41.2%, the 12-month prevalence 23.5%, without sex differences. Depression, anxiety disorders and alcohol abuse and dependence showed high prevalence and comorbidity. The prevalence 'ever' of schizophrenia and other non-affective psychoses was low (0.4%).
The authors identify the differences in formal inclusion and exclusion criteria used to classify patient data into diagnoses as the largest source of diagnostic unreliability in psychiatry. They describe the efforts that have been made to reduce these differences, particularly the specified criteria approach to defining diagnostic categories, which was developed for research purposes. On the basis of studies showing that the use of specified criteria increases the reliability of diagnostic judgments, they suggest that including such criteria in the next edition of APA's Diagnostic and Statistical Manual of Mental Disorders (DSM-III) would improve the reliability and validity of routine psychiatric diagnosis.
The Edinburgh Post Natal Depression Scale (EPDS), a 10-item self-rating depression scale, was translated into Dutch and compared in 293 postpartum women with other self-rating scales commonly in use in The Netherlands. In addition the structure of EPDS was analyzed by various factor analyses to reveal some of its dimensional aspects. The Dutch version of EPDS was found to be a self-rating scale with good psychometric characteristics which measures what it claims to measure: the strength of depressive symptoms. With LISREL a 2-factor model could be distinguished which contained subscales reflecting depressive symptoms and cognitive anxiety.
The role of stressful life events in the onset of Graves' disease (toxic diffuse goitre) is controversial. However, the numerous early clinical reports that supported such an association were not adequately controlled and specificity of the diagnosis could be questioned. Later studies have not shown a causal relation, but these studies were small, did not have proper controls, or epidemiological methods were inappropriate. To assess possible associations between life events, heredity, social support, and Graves' disease, we have done a population-based case-control study in a defined area with about 1 million inhabitants. Over 2 years, 208 (95%) of 219 eligible patients with newly-diagnosed Graves' disease and 372 (80%) of all selected matched controls answered an identical mailed questionnaire about marital status, occupation, drinking and smoking habits, physical activity, familial occurrence of thyroid disease, life events, social support, and personality. Compared with controls, patients claimed to have had more negative life events in the 12 months preceding the diagnosis, and negative life-event scores were also significantly higher (odds ratio 6.3, 95% confidence interval 2.7-14.7, for the category with the highest negative score). Individuals who had relatives with thyroid disease (especially first-degree and second-degree relatives) were more likely to have Graves' disease (3.6, 2.2-5.9). Slightly more patients than controls were divorced (1.8, 1.0-3.3) and reported a less frequent intake of alcohol (0.4, 0.2-0.8). When results were adjusted for possible confounding factors in multivariate analyses, risk estimates were almost unchanged. These findings indicate that negative life events and hereditary factors may be risk factors for Graves' disease.
One hundred and forty-seven mothers were screened for major depression at six to eight weeks post-partum. Using predetermined cut-off points, the Edinburgh Postnatal Depression Scale and the Beck scale were compared in their abilities to identify the 15% of subjects who had major depression according to DSM-III criteria. The sensitivity of the Edinburgh scale was 95% and its specificity 93%. The performance of the Beck scale was markedly inferior, with a sensitivity of 68% and specificity of 88%.
The development of a 10-item self-report scale (EPDS) to screen for Postnatal Depression in the community is described. After extensive pilot interviews a validation study was carried out on 84 mothers using the Research Diagnostic Criteria for depressive illness obtained from Goldberg's Standardised Psychiatric Interview. The EPDS was found to have satisfactory sensitivity and specificity, and was also sensitive to change in the severity of depression over time. The scale can be completed in about 5 minutes and has a simple method of scoring. The use of the EPDS in the secondary prevention of Postnatal Depression is discussed.
The original Whickham Survey documented the prevalence of thyroid disorders in a randomly selected sample of 2779 adults which matched the population of Great Britain in age, sex and social class. The aim of the twenty-year follow-up survey was to determine the incidence and natural history of thyroid disease in this cohort.
Subjects were traced at follow-up via the Electoral Register, General Practice registers, Gateshead Family Health Services Authority register and Office of Population Censuses and Surveys. Eight hundred and twenty-five subjects (30% of the sample) had died and, in addition to death certificates, two-thirds had information from either hospital/General Practitioner notes or post-mortem reports to document morbidity prior to death. Of the 1877 known survivors, 96% participated in the follow-up study and 91% were tested for clinical, biochemical and immunological evidence of thyroid dysfunction.
Outcomes in terms of morbidity and mortality were determined for over 97% of the original sample. The mean incidence (with 95% confidence intervals) of spontaneous hypothyroidism in women was 3.5/1000 survivors/year (2.8-4.5) rising to 4.1/1000 survivors/year (3.3-5.0) for all causes of hypothyroidism and in men was 0.6/1000 survivors/year (0.3-1.2). The mean incidence of hyperthyroidism in women was 0.8/1000 survivors/year (0.5-1.4) and was negligible in men. Similar incidence rates were calculated for the deceased subjects. An estimate of the probability of the development of hypothyroidism and hyperthyroidism at a particular time, i.e. the hazard rate, showed an increase with age in hypothyroidism but no age relation in hyperthyroidism. The frequency of goitre decreased with age with 10% of women and 2% of men having a goitre at follow-up, as compared to 23% and 5% in the same subjects respectively at the first survey. The presence of a goitre at either survey was not associated with any clinical or biochemical evidence of thyroid dysfunction. In women, an association was found between the development of a goitre and thyroid-antibody status at follow-up, but not initially. The risk of having developed hypothyroidism at follow-up was examined with respect to risk factors identified at first survey. The odds ratios (with 95% confidence intervals) of developing hypothyroidism with (a) raised serum TSH alone were 8 (3-20) for women and 44 (19-104) for men; (b) positive anti-thyroid antibodies alone were 8 (5-15) for women and 25 (10-63) for men; (c) both raised serum TSH and positive anti-thyroid antibodies were 38 (22-65) for women and 173 (81-370) for men. A logit model indicated that increasing values of serum TSH above 2mU/l at first survey increased the probability of developing hypothyroidism which was further increased in the presence of anti-thyroid antibodies. Neither a positive family history of any form of thyroid disease nor parity of women at first survey was associated with increased risk of developing hypothyroidism. Fasting cholesterol and triglyceride levels at first survey when corrected for age showed no association with the development of hypothyroidism in women.
This historical cohort study has provided incidence data for thyroid disease over a twenty-year period for a representative cross-sectional sample of the population, and has allowed the determination of the importance of prognostic risk factors for thyroid disease identified twenty years earlier.
The contribution of stress to the aetiology of Graves' disease (GD) remains controversial. We have therefore examined life events, daily stress and coping in patients with this disease. We wished to determine whether the clinical presentation of Graves' hyperthyroidism is associated with preceding stressful events.
A prospective controlled study. Ninety-five patients with newly diagnosed GD were compared to matched controls.
A self-reporting questionnaire recalling life events, daily stress and coping in the twelve months preceding the diagnosis.
More Graves' disease patients than controls reported negative events (P < 0.0005), whereas the number of subjects reporting positive events and neutral events were similar in both groups. Graves' disease patients also experienced more negative events (P < 0.0001) and perceived them with higher ratings (P < 0.0001). Each group had similar coping ability in terms of the number of coping methods and magnitude of utilization of these methods. Similarly, Graves' disease patients reported more daily hassle (P < 0.001) and had higher hassle scores (P < 0.001).
Patients with Graves' disease experienced greater psychological stress and adverse events prior to the onset of the disease. As stress may alter the immune system, it could play an important role in precipitating the disease in subjects predisposed to autoimmune thyroid disorders.
All new attenders at the Menopause Clinic in Edinburgh over six months were interviewed to detect current depressive disorder (MADRS) and past psychiatric disorders (SADS-L), to find out whether women who were depressed at the time of clinic attendance had a history of depression. Of the 95 subjects who entered the study, 78 had gone through a natural menopause and 17 had undergone hysterectomy with or without oophorectomy. Of the 78 who had experienced a natural menopause, 35 were found to be depressed at the time of clinic attendance and 43 were not. A strong association was found between current and past depressive illness, 29 of the patients depressed at the time of clinic attendance having had depression previously. However, a clear peak of illness was seen in the perimenopausal period (four years either side of the last menstrual period): 35% of all patients with past or current depressive illness experienced their first episode of illness in this period.
Hypothyroidism is associated with both reduced central 5-HT function and an increased incidence of depression. This study tested the hypothesis that the reduced 5-HT function returns to normal with thyroxine replacement therapy. Seven hypothyroid patients were tested before and after adequate thyroxine replacement. Cortisol and prolactin responses to d-fenfluramine, a centrally acting 5-HT-releasing agent, were used as an index of central (hypothalamic) 5-HT responsiveness. 5-HT-mediated cortisol responses were significantly higher after thyroxine replacement. Basal prolactin levels were reduced, but 5-HT-mediated prolactin responses were not significantly higher after treatment, perhaps due to the pre-treatment responses being elevated by the direct stimulatory effects of hypothyroidism itself on pituitary prolactin secretion. Depressive symptomatology improved with thyroxine. TSH levels were positively related to depressive symptomatology, and inversely to cortisol responses. Depressive symptomatology was inversely related to cortisol responses. These findings thus provide further support that central 5-HT neurotransmission is affected by hypothyroidism. They also suggest that the reduction in 5-HT responsiveness is reversible with thyroxine replacement therapy.
This paper reports the validation of the EPDS against a Research Diagnostic Criteria diagnosis of Major and Minor depression. The EPDS was administered to non-postnatal women with older children (mean age of youngest child 3 years 9 months) and to postnatal women (baby aged 6 months). All who scored 9 or above and one third of low scorers were interviewed, using Goldberg's Clinical Interview Schedule. The study confirmed good user acceptability of the EPDS when administered as a postal questionnaire (92% response rate). The EPDS was found to have satisfactory sensitivity (79%) and specificity (85%). Our findings suggest that the EPDS take a place alongside other screening scales for depression in Community samples. It is proposed that when used in these settings it is referred to as the Edinburgh Depression Scale.
Cognitive and affective functioning is sensitive to changes in thyroid hormones. We have sought to determine: (1) the prevalence of thyroid function abnormalities in a psychiatric population on admission (as compared to the prevalence in a normal population), and (2) whether such thyroid function abnormalities are associated with the occurrence or development of cognitive and affective disorders.
Serum was collected 2-3 weeks after hospitalization in 3 major clinics from 3756 psychiatric patients in 1987-1990, stored, and assayed in 1993 for the presence of antibodies against the TSH-receptor and thyroperoxidase (TPO-Ab) and for TSH levels. The psychiatric cohort was matched with a control population of healthy individuals living in the same area (n = 1877). The prevalence study was followed by a case-control study involving patients from one clinic that had routinely assigned a DSM-IIIR classification to its patients. Cases were those admissions with thyroid abnormalities and three subgroups of cases were randomly formed demonstrating either TSH less than 0.4 mU/l (n = 44) or over 4.0 mU/l (n = 44), or TPO-Ab positivity (n = 50). Cases were compared to random controls from the same psychiatric population, viz patients without thyroid abnormalities (n = 83). Comparison was with respect to their psychiatric follow-up diagnosis (the investigator was blinded to the thyroid test results).
Prevalence study. The percentage of patients positive for TSH-receptor-Ab was 0.26 (9/3504), for TPO-Ab was 10.0 (331/3316) and outside the TSH range of 0.4-4.0 mU/l was 10.0 ((332/3316): 5.9% (198/3316) > 4.0 mU/l and 4.1% (134/3316) < 0.4 mU/l). Abnormal total thyroxine levels were found in only 9.8% of subjects with abnormal TSH, indicating the predominantly subclinical character of the thyroid alteration. In comparison, the healthy area controls over 55 years of age showed the same prevalence of positive TPO-antibodies and TSH under 0.4 mU/l, but a higher prevalence of TSH over 4.0 mU/l. CASE-CONTROL STUDY: In the case control analysis differences could not be noticed with regard to prevalences of dementia, schizophrenia or other psychiatric illnesses apart from the prevalence of affective disorders which were more prevalent in TPO-Ab positive patients and patients with a low serum TSH. Since prior use of lithium, carbamezapine, carbimazole and/or thyroxine could be a factor of importance in this association, analyses were also carried out excluding patients with such prior drug use. In these analyses affective disorders were still more prevalent in patients with a low serum TSH (particularly in males, 40% in cases vs 9% in controls, P < 0.05). The most significant association was however between TPO-antibody positivity (and in particular with high titre and/or with TSH > 4.0 mU/l) and a subgroup of the affective disorders, viz with a rapid cycling of bipolar disorder (18% in cases vs 0% in controls, P < 0.001).
Though causal relations cannot be determined from this cross-sectional study, this admission survey found early forms of autoimmune thyroid disease, sometimes characterized only by TPO-Abs, highly significantly associated with rapid cycles of a bipolar disorder. It also found a weak association between subclinical hyperthyroidism (low serum TSH without TPO-Ab positivity) and affective disorder.
To assess whether causal criteria can be used to find out whether there is support in published research for maintaining that menopause causes depression.
Ninety four articles from 30 years of research examining the relation of natural menopause to depression were traced by using Medline and systematic follow up of reference lists. Specified exclusion and inclusion criteria were applied, and the resulting 43 epidemiological primary research articles were classified and tabulated according to sample and measures used and the researchers' own conclusion as to whether or not an association had been established. This material was qualitatively evaluated with Hill's nine criteria for causality.
There is insufficient evidence at present to maintain that menopause causes depression. In addition to methodological and statistical problems, a temporal problem in the menopause concept hinders research in this area.
Causal criteria can usefully be used to structure a literature review. Further theoretical work is required to integrate standard clinical epidemiological concepts.
For over 200 years, the relationships between neuroendocrine systems and mental illness have been studied. Research has focused in substantial part on mood disorders and thyroid axis function. This review presents a brief examination of the history and the progress in this area of investigation. Consideration is given to mood states in thyroid disorders, as well as to thyroid function in mood disorders. Thyroid hormones, usually in conjunction with standard medications, can be used to treat both manic and depressed phases of mood disorders. The review with a presentation of some of the many issues that merit further investigation.
We examined the prevalence of antimicrosomal and antithyroglobulin antibodies in psychiatric inpatients with unipolar depression (N = 218), bipolar disorder manic (N = 51), bipolar disorder depressed (N = 19), and bipolar disorder mixed (N = 26) in comparison with two control groups: psychiatric inpatients with adjustment disorder (N = 80) and family medicine outpatients without current psychiatric illness (N = 144). A statistical analysis that controlled for age and sex revealed the frequency of positive antibody titers not to be increased in patients with a diagnosis of unipolar depression (6.9%) or bipolar disorder manic (3.9%), when compared with patients with adjustment disorder (2.5%) and non-psychiatric subjects (6.9%). There was a weak trend toward an increased prevalence of antithyroid antibodies in patients with bipolar disorder, mixed (19%) or depressed subtype (16%). The excess occurrence of antibodies in patients with either mixed or depressed bipolar disorder did not appear to be related to lithium exposure, which was similar in all bipolar subgroups. When the intervening influences of age and sex are taken into account, unipolar depression does not appear to be associated with an excessive rate of antithyroid antibodies; however thyroid autoimmunity may be weakly associated with subtypes of bipolar disorder in which depressive symptoms are prominent.
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