Association of Depression and Anxiety Disorders With Autoimmune Thyroiditis: A Systematic Review and Meta-analysis.

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.

Thyroid autoimmunity in bipolar disorder: A systematic review.

BACKGROUND: Accumulating evidence points to the pathophysiological relevance between immune dysfunction and mood disorders. High rates of thyroid dysfunction have been found in patients with bipolar disorder (BD), compared to the general population. A systematic review of the relationship between BD and thyroid autoimmunity was performed. METHODS: Pubmed, EMBASE and PsycINFO databases were searched up till January 28th, 2017. This review has been conducted according to the PRISMA statements. Observational studies clearly reporting data among BD patients and the frequency of autoimmune thyroid pathologies were included. RESULTS: 11 original studies met inclusion criteria out of 340 titles first returned from the global search. There is evidence of increased prevalence of circulating thyroid autoantibodies in depressed and mixed BD patients, while there is no evidence showing a positive relationship between BD and specific autoimmune thyroid diseases. There is a controversy about the influence of lithium exposure on circulating thyroid autoantibodies, even if most of studies seem not to support this association. A study conducted on bipolar twins suggests that autoimmune thyroiditis is related to the genetic vulnerability to develop BD rather than to the disease process itself. Females are more likely to develop thyroid autoimmunity. LIMITATIONS: The samples, study design and outcomes were heterogeneous. CONCLUSION: Thyroid autoimmunity has been suggested to be an independent risk factor for bipolar disorder with no clear association with lithium exposure and it might serve as an endophenotype for BD.

Sexual function and depressive symptoms in young women with thyroid autoimmunity and subclinical hypothyroidism.

OBJECTIVE: The results of few studies conducted to date suggest an increased prevalence of sexual dysfunction in patients with thyroid disorders. DESIGN: The aim of this study was to compare female sexual function and depressive symptoms between women with autoimmune thyroid disease and with mild thyroid failure. PATIENTS: The study included four groups of young women: euthyroid women with Hashimoto's thyroiditis (Group 1), women with nonautoimmune subclinical hypothyroidism (Group 2), women with autoimmune subclinical hypothyroidism (Group 3) and healthy euthyroid females without thyroid autoimmunity (Group 4). MEASUREMENTS: Beyond measuring serum hormone levels and thyroid antibody titres, all enrolled women completed questionnaires evaluating female sexual function (Female Sexual Function Index - FSFI) and the presence and severity of depressive symptoms (Beck Depression Inventory-Second Edition - BDI-II). RESULTS: The mean total FSFI score was lower in women with autoimmune hypothyroidism than in the remaining groups of women, as well as lower in Groups 1 and 2 than in Group 4. Compared to Group 4, three domains (sexual desire, lubrication and sexual satisfaction) were lower in Group 1, four domains (desire, arousal, lubrication and dyspareunia) in Group 2 and all FSFI domain scores in Group 3. The total BDI-II score was higher in Groups 1 and 2 than in Group 4, as well as higher in Group 3 than in the other groups of women. CONCLUSIONS: The obtained results suggest that both thyroid autoimmunity and mild thyroid failure, particularly if they occur together, may negatively affect female sexual function and depressive symptoms.

[The polyglandular autoimmune syndrome--quality of life and family clustering]. / Das polyglanduläre Autoimmunsyndrom--Lebensqualität und familiäre Beteiligung.

BACKGROUND AND AIM: For patients with polyglandular autoimmune syndrome (PGA), data pertaining to familial clustering and quality of life are missing. Therefore, we performed a prospective and controlled study to collect this information. PATIENTS AND METHODS: Clinical and serological evaluation of 75 consecutively recruited patients with PGA (mean age 47,5 ± 15,3 years; 65,3% women) and their 108 relatives (mean age 33,13 ± 20,08 years; 65,7% women) was performed. Three validated questionnaires for psychosocial evaluation (quality of life short form 36 [SF-36], hospital anxiety and depression scale [HADS] and the Gießener Beschwerdebogen [GBB]) were answered by patients and relatives. RESULTS: 47 (62%) patients with PGA had type 1 diabetes and autoimmune thyroid disease. 56 (52%) of their relatives had an autoimmune disease whereas Hashimoto's thyroiditis and type-A-gastritis were the most prevalent endocrine and non-endocrine components. Thyroid peroxidase autoantibodies were most prevalent in patients and involved relatives. Compared to a German reference group, all scales of the SF-36 were markedly decreased in patients and involved relatives (p < 0.001). Anxiety and depression scales were pathologically increased in patients and relatives (p < 0.001). Also, all GBB scales were elevated for patients and relatives (p < 0.001). Patients with both glandular and non-glandular autoimmune diseases showed the most pathological psychosocial results. CONCLUSION: Familial clustering is high in patients with PGA. Quality of life and psychosocial status are poor in patients and involved relatives. Multidisciplinary management of the multiplex families in specialized centers is warranted.

The chronic autoimmune thyroiditis quality of life selenium trial (CATALYST): study protocol for a randomized controlled trial.

BACKGROUND: Patients with chronic autoimmune thyroiditis have impaired health-related quality of life. The thyroid gland has a high selenium concentration, and specific selenoprotein enzyme families are crucial to immune function, and catalyze thyroid hormone metabolism and redox processes in thyroid cells. Previous randomized controlled trials have found that selenium supplementation decreases thyroid-disease-specific antibody levels. We hypothesize that selenium might be beneficial in the treatment of chronic autoimmune thyroiditis. METHODS/DESIGN: The CATALYST trial is an investigator-initiated randomized, blinded, multicentre clinical trial of selenium supplementation versus placebo in patients with chronic autoimmune thyroiditis. INCLUSION CRITERIA: age ≥18 years; serum thyroid peroxidase antibody level ≥100 IU/ml within the previous 12 months; treatment with levothyroxine and written informed consent. EXCLUSION CRITERIA: previous diagnosis of toxic nodular goitre, Graves' hyperthyroidism, postpartum thyroiditis, Graves' orbitopathy; previous antithyroid drug treatment, radioiodine therapy or thyroid surgery; immune-modulatory or other medication affecting thyroid function; pregnancy, planned pregnancy or breastfeeding; allergy towards any intervention or placebo component; intake of selenium supplementation >55 µg/day; inability to read or understand Danish or lack of informed consent. The trial will include 2 × 236 participants. The experimental intervention and control groups will receive 200 µg selenium-enriched yeast or matching placebo tablets daily for 12 months. The experimental supplement will be SelenoPrecise®. The primary outcome is thyroid-related quality of life assessed by the Thyroid Patient-Reported Outcome (ThyPRO) questionnaire. Secondary outcomes include serum thyroid peroxidase antibody concentration; serum triiodothyronine/thyroxine ratio; levothyroxine dosage; adverse reactions and serious adverse reactions and events. DISCUSSION: In this pragmatic trial, participating patients follow their usual treatment at their usual hospitals. In order to collect high-quality data on the clinical course and quality of life, and to minimize missing data, an elaborate trial management system has been designed. 12 months intervention duration was selected in consideration of the primary outcome, thyroid-related quality of life. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02013479.

[Structural characteristics of asthenia in autoimmune thyroiditis].

An examination of 319 patients with hypertrophic form of autoimmune thyroiditis, including 157 patients with diffusive and 162 - with diffusive-nodule structure of the gland, has demonstrated the appearance of asthenic disorders during the euthyroid phase of the disease. Characteristics of these disorders relative to the thyroid gland structure and its diffusive or diffusive-nodule form were found. The association between changes in the immune homeostasis and characteristics of mental disorders was revealed.

Neuropsychological functioning, illness perception, mood and quality of life in chronic fatigue syndrome, autoimmune thyroid disease and healthy participants.

BACKGROUND: This study attempted to longitudinally investigate neuropsychological function, illness representations, self-esteem, mood and quality of life (QoL) in individuals with chronic fatigue syndrome (CFS) and compared them with both healthy participants and a clinical comparison group of individuals with autoimmune thyroid disease (AITD). METHOD: Neuropsychological evaluation was administered at two time points, five weeks apart. Twenty-one individuals with CFS, 20 individuals with AITD and 21 healthy participants were matched for age, pre-morbid intelligence, education level and socio-economic status (SES). All groups also completed measures of illness perceptions, mood, self-esteem and QoL at both time points. RESULTS: The CFS group showed significantly greater impairment on measures of immediate and delayed memory, attention and visuo-constructional ability, and reported significantly higher levels of anxiety and depression. After controlling for the effects of mood, the CFS group still demonstrated significant impairment in attention. The CFS group also reported significantly lower self-reported QoL than the AITD and healthy participants. In terms of illness perceptions, the AITD group believed that their condition would last longer, that they had more treatment control over their condition, and reported less concern than the CFS group. CONCLUSIONS: These results suggest that the primary cognitive impairment in CFS is attention and that this is not secondary to affective status. The lower treatment control perceptions and greater illness concerns that CFS patients report may be causally related to their affective status.

Neuropsychiatric aspects of hypothyroidism and treatment reversibility. .

Thyroid hormone has important actions in the adult brain, and it is well accepted that hypothyroidism is associated with neuropsychiatric complaints and symptoms. Neuropsychiatric symptoms refer to a spectrum of emotional and cognitive problems that are directly related to changes in the brain secondary to multiple factors, including the direct effects of thyroid disease, as well as hormone deprivation in brain tissue. Hypothyroidism impacts aspects of cognitive functioning and mood. More severe hypothyroidism can mimic melancholic de-pression and dementia. Neuropsychiatric symptoms tend to improve with treatment and normalization to a euthyroid state, though the pattern is inconsistent and complete recovery is uncertain. The degree to which mild hypothyroidism, or subclinical hypothyroidism (SCH), impacts mood and cognitive functions and whether these symptoms respond to treatment, remains controversial. Most studies support a relationship between thyroid state and cognition, particularly slowed information processing speed, reduced efficiency in executive functions, and poor learning. Furthermore, hypo-thyroidism is associated with an increased susceptibility to depression and reductions in health-related quality of life. Controlled studies suggest that cognitive and mood symptoms improve with treatment, though the data are equivocal and limited by diverse methodologies. Functional neuroimaging data provide support for the mood and cognitive findings and treatment reversibility for both overt and SCH. These findings are not, however, without controversy. Recent investigations into the impact of SCH on cognition and mood, coupled epidemiological studies investigating the normal spectrum of thyroid stimulating hormone, have fueled significant debate regarding the appropriate, healthy range for TSH levels. This has led to concern over whether patients with overt hypothyroidism may be undertreated and whether SCH patients are truly out of the range of normal thyroid functioning and should be treated. The following is a review of the extant literature on the impact of hypothyroidism on cognition and mood, reversibility of symptoms, and treatment approaches. The spectrum of thyroid disease is reviewed, but mild, or subclinical, hypothyroidism is emphasized. The potential role of autoimmunity in neuropsychiatric symptoms and treatment resistance is addressed. Limitations of the current literature and future directions are discussed.

Familial autoimmune thyroid disease as a risk factor for regression in children with Autism Spectrum Disorder: a CPEA Study.

A multicenter study of 308 children with Autism Spectrum Disorder (ASD) was conducted through the Collaborative Programs of Excellence in Autism (CPEA), sponsored by the National Institute of Child Health and Human Development, to compare the family history of autoimmune disorders in children with ASD with and without a history of regression. A history of regression was determined from the results of the Autism Diagnostic Interview-Revised (ADI-R). Family history of autoimmune disorders was obtained by telephone interview. Regression was significantly associated with a family history of autoimmune disorders (adjusted OR=1.89; 95% CI: 1.17, 3.10). The only specific autoimmune disorder found to be associated with regression was autoimmune thyroid disease (adjusted OR=2.09; 95% CI: 1.28, 3.41).

Stress and autoimmune thyroid diseases.

Autoimmune thyroid diseases (AITD) are the far most common autoimmune disorders, their prevalence in Western countries exceeding 5% of the general population. In the large majority of individual cases the clinical impact of AITD is not severe, however, their widespread diffusion renders them a significant health problem. AITD are heterogeneous in their clinical presentation: the two main forms are autoimmune thyroiditis (AT) and Graves' disease (GD). Although they probably share, at least in part, a common genetic background and may occur in the same family as well as in the same individual, they are definitely two distinct diseases both in their clinical presentation and their pathophysiology. In fact, AT causes structural thyroid damage (mainly via cell-mediated immune destruction of thyroid follicular cells) which results, as a rule, in functional impairment (hypothyroidism); however, depending on clinical variants, evolution towards hypothyroidism may be very low, or thyroid function impairment occurs after an initial phase of mild thyrotoxicosis due to relatively rapid gland destruction. GD patients have hyperthyroidism, often severe, due to autoantibody-mediated thyrotropin receptor stimulation, with thyroid cell hyperplasia and hyperfunction. Such a functional heterogeneity is a key feature for the clinical management: as a matter of fact, therapy of AITD is mainly therapy of thyroid dysfunction. Moreover, since hyperthyroidism is quite early perceived by the patient as a cause of discomfort, the timing of the natural history of GD is relatively well defined; on the other hand, AT may be asymptomatic for a long time and defining its natural history in a single patient may be difficult. In some AITD patients (mainly, but not exclusively, with GD), clinical features not directly related to thyroid dysfunction, such as orbitopathy, are present. Graves' orbitopathy is probably related, at least in part, to autoantibodies directed to thyrotropin receptor; it may be, in a minority of patients, severe and sight-threatening, and represents an independent clinical problem.

Thyroid autoimmunity, depression and anxiety; are there any connections? An epidemiological study of a large population.

OBJECTIVE: The aim of the study was to examine the relationship between antithyroid antibodies, depression, and anxiety in a large population. METHODS: In a population of 30,175 individuals aged 40-84 years, thyroid-stimulating hormone (TSH) was assessed in all women and in 50% of the men. Thyroid peroxidase autoantibodies (TPOAb) were measured in almost all samples with TSH > or = 4.0 mU/L (n = 1700) and in randomly selected samples without thyroid disease or biochemical dysfunction (n = 745). The levels of anxiety and depression were screened using the Hospital Anxiety and Depression Scale (HADS). Relations were investigated with multiple logistic regression analyses. RESULTS: In individuals with normal TSH and without known thyroid disorder, the prevalence of TPOAb was 14.2% in women and 4.3% in men. The prevalence of TPOAb in participants with biochemical thyroid dysfunction was 59.0% in women and 38.9% in men. No associations were found between thyroid autoimmunity and depression or anxiety, neither crude nor adjusted for age, gender, TSH, and thyroxine (T4). CONCLUSION: Thyroid autoimmunity is a common disorder in the population, mainly affecting females. In a population-based study, no associations were found between antithyroid antibodies and depression or anxiety.

Hashimoto's encephalopathy with selective involvement of the nucleus accumbens: a case report.

Hashimoto's encephalopathy (HE) is an acute or subacute relapsing disorder usually affecting euthyroid patients with evidence of autoimmune thyroiditis. The neurological manifestations are non-specific, with subacute cognitive impairment, movement disorders, generalized seizures, focal neurological symptoms such as stroke-like episodes, or psychiatric disturbances. Autoimmune phenomena are likely to play an etiological role. Magnetic resonance imaging (MRI) findings are usually normal or show non-specific changes. We report the case of an 11-year-old girl with autoimmune thyroiditis who presented acutely with a complex neuropsychiatric disorder in association with MRI evidence of focal involvement of the nucleus accumbens (NA). The NA, a ventral striate nucleus, is part of a complex dopaminergic network. Lesions to the NA result in several psychiatric symptoms, such as attention-deficit hyperactivity disorders. In this patient, we observed alternating phases of stupor and hyperkinetic-anxious behavior, with marked instability. The pathogenetic mechanism and the anatomic and functional correlations are briefly discussed.

Stress is not associated with thyroid peroxidase autoantibodies in euthyroid women.

OBJECTIVE: Multiple genes and environmental factors play a role in the etiology of autoimmune thyroid disease (AITD). In Graves' hyperthyroidism, stress is such an environmental factor, but whether it plays a role in Hashimoto's hypothyroidism is unknown. We used validated questionnaires to evaluate an association between TPO antibodies, an early marker for AITD, and self-reported stress. SUBJECTS AND METHODS: Recently Experienced Stressful Life Events, Daily Hassles, and mood (tendency to report positive and negative affects) were assessed in 759 euthyroid subjects. RESULTS: TPO antibodies were found in 183/759 (24%) of subjects. The TPO-Ab positive subjects were older (39.7+/-12 vs. 34.2+/-12 years; p<.001) than the TPO-Ab negative subjects, but the number of daily hassles (24+/-14 vs. 25+/-14; p=.24), the number of stressful life events (10+/-6 vs. 11+/-6; p=.09), and the scores on the affect scales (22.1+/-7.4 vs. 22.2+/-7.3; p=.89 for negative affect and 38.2+/-5.1 vs. 38.3+/-5.3; p=.91 for positive affect) were similar in TPO-Ab positive and TPO- Ab negative subjects. CONCLUSIONS: We found no association between recently experienced stressful life events, daily hassles or mood and the presence of TPO antibodies in these euthyroid women.

Styles of adaptation in autoimmune thyroiditis and bipolar disorder: a pilot study.

BACKGROUND: A growing body of evidence suggests that styles of adaptation, assessed with the Serial Color-Word Test (S-CWT, a 5-trials Stroop task), are able to differentiate several mental and psychosomatic disorders. Recent findings have confirmed a very high rate of cases of autoimmune thyroiditis (so called Hashimoto disease) among bipolar patients, suggesting an etio-pathogenetic relatedness between the two ailments. Based on the latter relatedness, it was hypothesized that the same styles of adaptation, which are known to differentiate bipolar and control subjects are also characteristic of patients with autoimmune thyroiditis. METHODS: Three groups (autoimmune thyroiditis, fully remitted bipolar I, and nonclinical) of 40 women, matched on age and schooling, were administered the S-CWT. The following variables were considered: (a) early discontinuity (i.e. the summed nonlinear change of the first three trials), (b) late discontinuity (i.e. the summed nonlinear change of the last two trials), (c) across-trials discontinuity (i.e. the nonlinear change of the five measures of nonlinear change). RESULTS: The thyroiditis group had (1) higher values of early discontinuity (P=0.006) and of late discontinuity (P=0.004) compared with nonclinical controls, (2) lower values of early discontinuity (P=0.005) and of across-trials discontinuity (P=0.008) compared with the bipolar group. LIMITATIONS: The study did not include men patients and lacked a quantification of affective symptoms among clinical and nonclinical participants. CONCLUSION: A discontinuous style of adaptation is more marked among remitted bipolar than among thyroiditis patients, and more marked among the latter ones than among nonclinical controls, thus delineating a sort of adaptive continuum.

Increased prevalence of sublinical brain perfusion abnormalities in patients with autoimmune thyroiditis: evidence of Hashimoto's encephalitis?

OBJECTIVES: Hashimoto's encephalitis is a term which describes encephalopathy associated with autoimmune thyroiditis, but it is not based on evidence, whether Hashimoto's encephalitis is a distinct clinical entity by itself. In previously reported cases of Hashimoto's encephalitis, abnormal brain perfusion studies have been reported. The aim of this study was to evaluate the prevalence of brain perfusion abnormalities in euthyroid patients with autoimmune thyroiditis. METHODS: 99mTc Ethyl cystein dimer (ECD) single photon emission computed tomography (SPECT) studies were performed in a study group of 41 euthyroid patients with autoimmune thyroiditis and a matched control group of 35 healthy individuals. All study participants had a normal neurological investigation and a detailed neurological history taking. Individuals with known or suspected morphological brain abnormalities were excluded from the study. Zung's Self-Rating Anxiety Scale (SAS) and Zung's Self-Rating Depression Scale (SDS) were used to detect depression and mood disorders. Automatic quantification of perfusion was performed with both a voxel-based analysis as well as a volume-of-interest (VOI) based analysis of 46 predefined cortical and subcortical regions. The findings from both groups were compared to a reference template. RESULTS: In the voxel-based analysis, there was a significant difference between patients and controls in the mean volume of perfusion defects deviating 2SD below the normal values (21.8 ml vs. 10.4 ml; P = 0.02). Hyperperfused areas, however, did not differ significantly between study patients and controls. A significant correlation of the perfusion defects with time since diagnosis of autoimmune thyroiditis was seen (r = 0.42). In the VOI-based analysis, abnormal regions were more frequent in the study group when compared to controls (P < 0.01) However, no topographic pattern was apparent. Regarding neurological findings, no significant difference was found between study patients and controls. However, both the SAS and SDS scores differed significantly between the two groups, but there was neither a correlation between the two scores and perfusion abnormalities nor an association with depression in our study group. CONCLUSIONS: These findings of impaired brain perfusion in patients with autoimmune thyroiditis further strengthen the hypothesis of a possible cerebral involvement in autoimmune thyroiditis in individual cases. The presence of cerebral hypoperfusion suggests a cerebral vasculitis as the most likely pathogenetic model.

[Acute schizophreniform disorder in Hashimoto disease]. / Akute schizophreniforme Störung bei M. Hashimoto.

While for some diseases with hyperthyreosis psychotic developments are well known, for a rare autoimmune thyroiditis, Hashimoto's thyroiditis, only one case of development of psychotic symptoms is known. In this case-study we present a 42-year-old white female who was admitted to hospital showing symptoms of acute psychosis. The results of the laboratory examinations showed the constellation of beginning Hashimoto's thyroiditis in hyperthyreotic state with high level of antithyroid peroxidase antibodies and comparatively low level of anti-TSH receptor antibodies. The patient recovered well in 4-weeks time under therapy with neuroleptics and benzodiazepines.