General Hospital Psychiatry 36 (2014) 95–98
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The prevalence of depression and anxiety disorders in patients with euthyroid Hashimoto’s thyroiditis: a comparative study Medine Giynas Ayhan, M.D. a,⁎, Faruk Uguz, M.D. b, Rustem Askin, M.D. c, Mehmet Sait Gonen, M.D. d a
Department of Psychiatry, Aksehir State Hospital, Konya, Turkey Department of Psychiatry, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey Department of Psychiatry, Sevket Yilmaz Education and Research Hospital, Bursa, Turkey d Department of Internal Medicine, Division of Endocrinology, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey b c
a r t i c l e
i n f o
Article history: Received 23 June 2013 Revised 28 September 2013 Accepted 1 October 2013 Keywords: Hashimoto's thyroiditis Goiter Depression Anxiety disorders Autoimmune thyroiditis
a b s t r a c t Objective: The aim of this study was to examine the current prevalence of major depression and anxiety disorders in patients with euthyroid Hashimoto’s thyroiditis (HT) and euthyroid goiter. Method: The study sample was formed by consecutive 51 and 45 patients who were admitted to the endocrinology outpatient clinic and diagnosed with euthyroid HT and endemic/nonendemic goiter, respectively, and 68 healthy controls. Current diagnoses of psychiatric disorders were determined using the Structured Clinical Interview for DSM-IV. Beck Depression Inventory and Beck Anxiety Inventory were applied to the participants. Results: There was a statistically significant difference among the three groups in terms of major depression (P=.001), any mood or anxiety disorder (P=.000), any depressive disorder (P=.020), any anxiety disorder (P=.016) and obsessive–compulsive disorder (OCD) (P=.013). In the HT group, the prevalence of depression (P=.000), OCD (P=.005) and panic disorder (P=.041) was significantly higher than that in the control group. In the goiter group, depression (P=.006), any depressive disorder (P=.03), and any mood or anxiety disorder (P=.000) were significantly common in comparison to the control group. No significant difference was found between the HT and goiter groups. Conclusions: Euthyroid HT and euthyroid goiter increase predisposition to major depression and anxiety disorders, and thyroid autoimmunity and other thyroid pathologies should be investigated in euthyroid patients with chronic and treatment-resistant complaints. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Hashimoto’s thyroid (HT) is the most frequent autoimmune thyroid disease, with a prevalence rate of 2%, which is caused by the autoimmune inflammation of the thyroid gland and has different clinical stages ranging from euthyroiditis to hypothyroiditis. It is the most frequent cause of adult hypothyroiditis in the world [1–3]. It is characterized by elevated levels of antithyroglobulin (Anti-Tg) antibody and antithyroid peroxidase (anti-TPO) and the thyroid gland’s typical hypoechogenic pattern in ultrasonography [4]. The disease is also known as chronic autoimmune thyroiditis and affects most commonly women [5,6]. The positivity of anti-TPO in individuals with euthyroid is between 12% and 26%. Anti-TPO positivity (silent autoimmune thyroid disease) is recognized to be a precursor of possible future thyroid deficiency in cases where serum thyroid hormones and thyroid stimulant hormone (TSH) levels are within normal bounds [7,8].
⁎ Corresponding author. E-mail address: [email protected] (M. Giynas Ayhan). 0163-8343/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.genhosppsych.2013.10.002
While there are studies that report that psychiatric disorders are seen more frequently in individuals with autoimmune thyroid diseases than the general population [9–15], others have reported that thyroid autoimmunity is not related to depression and anxiety [16–20]. However, previous studies are based on mostly psychiatric symptom scales rather than structured clinical interview, and the relationship between thyroid autoimmunity and anxiety disorders has been investigated only by a limited number of studies. In this study, we investigated the prevalence of major depression and anxiety disorders in patients with euthyroid endemic/nonendemic goiter and HT without having any thyroid hormone preparation and healthy subjects. Thereby, we aimed to examine whether HT specifically increases risk of depressive or anxiety disorders compared with endemic/nonendemic goiter or controls. 2. Method The study sample consisted of 51 patients with euthyroid HT and 45 patients with euthyroid endemic/nonendemic goiter who were admitted to the Endocrinology Outpatient Clinic, Meram Faculty of Medicine, Necmettin Erbakan University, in Konya, Turkey, between
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M. Giynas Ayhan et al. / General Hospital Psychiatry 36 (2014) 95–98
April 2010 and February 2012. The study sample also included a healthy control group consisting of 68 hospital personnels and their relatives who were matched for sociodemographic characteristics of the patients. All subjects underwent a complete thyroid evaluation including physical examination, thyroid ultrasonography and measure of serum free T4 (FT4), free T3 (FT3), TSH, anti-TPO and anti-Tg. The diagnosis of euthyroid HT was made on the basis of coexistence of high titers of anti-Tg (0–20 IU/ml) and anti-TPO (0– 10 IU/ml), diffuse hypoechogenic pattern in ultrasonography and normal serum levels of FT3 (2.0–4.4 pg/ml), FT4 (0.93–1.7 ng/dl) and TSH (0.27–4.0 mU/L). The diagnosis of endemic/nonendemic goiter was based on the presence of one or more multiple thyroid nodules in a normoechogenic gland in ultrasonography, with the absence of antithyroid autoantibodies and normal serum levels of free thyroid hormones and TSH. For the report that HT affects especially middle-aged women [21], patients between 20 and 45 years of age were included in the study. All participants were at least elementary school graduates. Cognitive incompetence and illiteracy, which make psychiatric interview difficult; having chronic medical illness (e.g., neurological, cardiovascular, pulmonary, rheumatological and endocrinological diseases); receiving thyroid hormone replacement treatment; using oral contraceptives; being in menopausal stage and having a history of schizophrenia or bipolar disorder were exclusion criteria. The study was approved by the Ethics Committee of Meram Faculty of Medicine of Necmettin Erbakan University. After the thyroid evaluation, relevant subjects were referred to psychiatry outpatient clinic. The subjects’ sociodemographic information was recorded in the information form. Current mood and anxiety disorders were ascertained by means of the Structured Clinical Interview for DSM-IV (SCID-I) [22]. The levels of anxiety and depression were screened using Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) [23–26]. Psychiatric examinations were conducted by psychiatrists with at least 4 years of experience about psychiatric disorders. In addition, the psychiatrists had a formal training about SCID-I. In the present study, we performed modules of affective and anxiety disorders of SCID-I. 2.1. Statistical analysis Data analysis was conducted using SPSS (version 15.0). The χ 2 test was used for categorical variants, and Fisher’s Exact χ 2 Test was used when necessary. One-way analysis of variance (ANOVA) was used for continuous variables among the groups. Tukey’s honestly significant difference test was used in the binary group comparisons of variables seen to be significant in ANOVA. Statistical significance was accepted as Pb.05. 3. Results The study included 164 participants aged 20–45 years. The mean age of the sample was 34.67±6.82 years. Fifty-one subjects of all the cases were in the HT group, 45 were in the goiter group, and 68 were in the control group. There was no significant difference among the groups with regard to sex, age, marital status, educational level and number of children (Table 1). While 27 (52.9%), 17 (37.8%) and 11 (16.2%) subjects were diagnosed with a current psychiatric disorder in the HT, goiter and control groups, 17 (33.3%), 11 (24.4%) and 4 (5.9%) subjects were diagnosed with a current depressive disorder in the HT, goiter and control groups, respectively. Moreover, 19 (37.3%), 11 (24.4%) and 10 (14.7%) people were diagnosed with an anxiety disorder in the HT, goiter and control groups, respectively. There was a statistically significant difference between three groups for these disorders (P= .000, P=.001 and P=.018, respectively). Twenty-eight subjects, 15 cases (29.4%) from the HT group, were diagnosed with major
Table 1 Sociodemographic characteristics of the HT, goiter and control groups
Sex (n, %) Female Male Marital status (n, %) Married Single Education (n, %) Elementary school High school College Occupation (n, %) Unemployed Employed Mean age (mean±SD)
Hashimoto's group (n=51)
Goiter group (n=45)
Control group (n=68)
49 (96.1) 2 (3.9)
41 (91.1) 4 (8.9)
64 (94.1) 4 (5.9)
38 (74.5) 13 (25.5)
37 (82.2) 8 (17.8)
52 (76.5) 16 (23.5)
25 (49.0) 15 (29.4) 11 (21.6)
26 (57.8) 11 (24.4) 8 (17.8)
40 (58.8) 19 (27.9) 9 (13.2)
35 (68.6) 16 (31.4)
29 (64.4) 16 (35.6)
46 (67.6) 22 (32.4)
35.10±7.75
35.47±6.74
33.82±6.07
1.61±1.328
1.91±1.164
1.78±1.208
P value .595⁎
Number of children (mean±SD)
.645⁎
.737⁎
.902⁎
.396⁎⁎
.482⁎⁎
⁎ χ2 test. ⁎⁎ ANOVA test.
depression. There was a statistically significant difference among the three groups regarding the existence of major depression (P= .001) (Table 2). Among the anxiety disorders, the prevalence of panic disorder was found to be 11.8% in the HT group, 6.7% in the goiter group and 1.5% in the control group (P=.066). There was no significant difference among all groups regarding the prevalence of panic disorder according to the χ 2 test. The most frequent diagnosis concerning anxiety disorders was obsessive–compulsive disorder (OCD) (7.3%) in the general sample. Eight (15.7%) subjects were diagnosed with OCD in the HT group. There was a statistically significant difference among the three groups in terms of OCD (P=.013) (Table 2). Table 2 also shows scores of BDI and BAI in each study group. The average scores of the scales were consistent with the diagnoses of the subjects. When the HT and the control groups were compared, any psychiatric disorder (P=.000), any depressive disorder (P=.000), any anxiety disorder (P=.005), major depression (P=.000), OCD (P= .005) and panic disorder (P=.041) cases were found to be more common in the HT group than the control group. There was no significant difference between the HT and control groups in terms of dysthymic disorder (P=.576), generalized anxiety disorder (GAD) (P=.650) and phobic disorder (P=1.000) (Table 2). Major depression (P=.006), any depressive disorder (P=.009) and any disorder (P=.014) cases were significantly more common in the goiter group than the control group. However, there was no significant difference regarding dysthymic disorder (P=.081), OCD (P=.299), panic disorder (P=.299), GAD (P=1.000) and phobic disorder (P=.681). There was no significant difference between the HT and goiter groups regarding all the depressive and anxiety disorders evaluated [major depression (P=.489), dysthymic disorder (P=.414), OCD (P=.209), panic disorder (P=.495), GAD (P=.620), phobic disorder (P=.663), any anxiety disorder (P=.194), any depressive disorder (P=.375), any psychiatric disorder (P=.155)] (Table 2). 4. Discussion In this study, we found the current prevalence of any depressive disorder to be 29.4% and 33.3% in the HT group and 22.2% and 24.4% in the goiter group, respectively. This percentage was only 5.9% in the control subjects. The rates seem to be very high in patients with HT and goiter compared to healthy subjects.
M. Giynas Ayhan et al. / General Hospital Psychiatry 36 (2014) 95–98 Table 2 The comparison of the HT, goiter and control groups for the prevalence of psychiatric diagnoses Hashimoto’s group (n=51) Major depressiona,b (n, %) Existent 15 (29.4) None 36 (70.6) Dysthymic disorder (n, %) Existent 2 (3.9) None 49 (96.1) c OCD (n, %) Existent 8 (15.7) None 43 (84.3) PDd (n, %) Existent 6 (11.8) None 45 (88.2) GAD (n, %) Existent 3 (5.9) None 48 (94.1) Phobic disorder (n, %) Existent 2 (3.9) None 49 (96.1) An anxiety disordere (n, %) Existent 19 (37.3) None 32 (62.7) Any depressive disorderf,g (n, %) Existent 17 (33.3) None 34 (66.7) Any disorderh,i (n, %) Existent 27 (52.9) None 24 (47.1) BDI score 13.06±8.69 (min: 1, max: 32) BAI 12.59±9.88 (min: 2, max: 41)
Goiter group (n=45)
Control group (n=68)
10 (22.2) 35 (77.8)
3 (4.4) 65 (95.6)
4 (8.9) 41 (91.1)
1 (1.5) 67 (98.5)
3 (6.7) 42 (93.3)
1 (1.5) 67 (98.5)
3 (6.70) 42 (93.3)
1 (1.5) 67 (98.5)
1 (2.2) 44 (97.8)
2 (2.90) 66 (97.10)
3 (6.7) 42 (93.3)
3 (4.4) 65 (95.6)
11 (24.4) 34 (75.6)
10 (14.7) 58 (85.3)
11 (24.4) 34 (75.6)
4 (5.9) 64 (94.1)
17(37.8) 28 (62.2) 12.09±10.80 (min:1, max: 55) 10.62 ±12.49 (min:1, max: 49)
11 (16.2) 57 (83.8) 4.32±4.65 (min:0, max: 19) 4.07±3.24 (min:0, max: 16)
P value
.001⁎
.160⁎
.013 ⁎
.066 ⁎
.583⁎
.801⁎
.018 ⁎
.001⁎
.000⁎
.000⁎⁎ .000⁎⁎
a P=.000 between the HT and control groups, bP=.006 between the goiter and control groups, cP=.005 between the HT and control groups, dP=.041 between the HT and control groups, eP=.005 between the HT and control groups, fP=.000 between the HT and control groups, gP=.009 between the goiter and control groups, hP=.000 between the HT and control groups, iP=.014 between the goiter and control groups. ⁎ χ 2. ⁎⁎ ANOVA test.
In a study by Carta et al. [15], it was reported that there is an increased risk of depressive disorder in patients with HT independent of thyroid dysfunction measured by routine serum tests, but there is no increased risk of depressive disorders between the euthyroid goiter group and the control group. In another study, the researchers observed that the rates of anxiety, depression and panic disorder in patients with euthyroid cold nodules decreased dramatically following surgery [27]. In this study, we found an increased risk of depressive disorders in both the euthyroid HT group and the euthyroid goiter group compared to the control group. This result suggests that thyroid autoimmunity and goiter have an effect on depressive disorders by different mechanisms or similar changes in the thyroid gland tissue. It is reported that hypothalamic–pituitary–thyroid (HPT) axis disorder and 5-hydroxytryptamine dysregulation on the HT base have a role in the etiopathogenesis and neurobiology of depressive disorders. Some studies concluded that antithyroid antibodies might be elevated, the TSH response to thyrotropin-releasing hormone (TRH) might be decreased, TRH concentration might be elevated in cerebrospinal fluid and triiodothyronine enhances the efficiency of antidepressants in depressive disorders [28–34]. It is thought that there is a defect in TSH’s circadian rhythm in some depressive disorder and that a slight disorder in TSH and thyroid hormone levels within normal serum levels affects the mood [35]. Fountoulakis et al. [36] called this condition as “low-thyroid function syndrome.” Some studies reported that the brain might be affected before the other
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organs in euthyroid conditions and that this situation can be considered to be “brain hypothyroidism” [29,37–39]. Haggerty et al. [16] concluded that the positivity of antithyroid antibodies and the elevated TSH level were correlated. According to some authors, serotonergic dysfunction is much more pronounced in depressive patients with normal HPT axis. It is suggested that HPT dysregulation in depressive disorders develops through a compensatory mechanism against decreased central serotonin activity [40]. On the other hand, Hardoy et al. found significant cerebral perfusion anomalies in major depressive disorder with HT [41]. Further, changes in the hypothalamic–pituitary–adrenal (HPA) axis affected by proinflammatory and anti-inflammatory agents might also cause depression by triggering thyroid autoimmunity [4,42,43]. The prevalence of an anxiety disorder in general population is between 6.8% and 9.7% [44]. The results of this study show that the prevalence of an anxiety disorder in the HT and goiter groups is much higher than that in the general population. OCD (15.7%) is the most frequently seen anxiety disorder in the HT group. The lifetime prevalence of OCD in general population is between 0.8% and 3.2% [44–46]. To our knowledge, the present study is the first that points out the possible relationship between HT and OCD. Autoimmunity in HT may be a possible mechanism underlying this result, but it is still unclear. Some studies [47–52] that have investigated the relationship between autoimmunity and OCD have different results. Morer et al. [53] reported that OCD was a heterogeneous disorder and early phase OCD might be related to autoimmune etiology. On the other hand, although OCD has a higher prevalence in the HT group than the control group, there is no significant difference between the HT and goiter groups in the current study. Therefore, to explain that OCD and autoimmunity have a relationship seems to be difficult. This hypothesis needs further studies. Although there is no significant difference between the HT and goiter groups regarding panic disorder, the HT group has a higher prevalence rate of panic disorder compared to healthy subjects. Similar to the outcomes of the present study, some authors concluded that anti-TPO positivity was significantly higher in people with panic disorder than the control group, and anti-TPO positivity might be related to panic attacks [54,55]. Stein et al. [56] found no significant difference between panic disorder and the control group regarding the autoimmune thyroiditis. Carta et al. [15] found a high rate of GAD and social phobia in autoimmune thyroiditis, while they found a significant relationship between not-otherwise-specified anxiety disorder and thyroid autoimmunity in another study [10]. Engum et al. [17], on the other hand, found no relationship between thyroid autoimmunity and anxiety. In line with the results of our study, a study found no association between social phobia and the control group regarding anti-TPO positivity [57]. These heterogeneous results may be due to methodological variations including study sample, sample sizes, interview or assessment instruments, and diagnostic criteria. Our study has some limitations. First of all, our sample is relatively small and is composed of patients presenting to the endocrinology clinic, who may not represent all the people with silent thyroid disease. Thus, studies covering the general population need to be conducted. The second point is that our study has a crosssectional characteristic and does not take the psychiatric history of participants into consideration. Formative studies conducted through the determination of individuals’ serum autoantibody levels and the imaging of their thyroid glands will reveal more dependable information on the effect of thyroid autoimmunity. We did not correct for multiple testing for the number of diagnoses. Also, another limitation of the study is that the interviewers who carried out clinical assessments were not blind to group membership. Finally, some of the patients probably had high-normal TSH levels. It would be difficult to discern the symptoms of anxiety or depression from the effects of subclinical hypothyroidism.
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The prevalence of depression and anxiety disorders in patients with euthyroid Hashimoto’s thyroiditis: a comparative study Medine Giynas Ayhan, M.D. a,⁎, Faruk Uguz, M.D. b, Rustem Askin, M.D. c, Mehmet Sait Gonen, M.D. d a
Department of Psychiatry, Aksehir State Hospital, Konya, Turkey Department of Psychiatry, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey Department of Psychiatry, Sevket Yilmaz Education and Research Hospital, Bursa, Turkey d Department of Internal Medicine, Division of Endocrinology, University of Necmettin Erbakan, Meram Faculty of Medicine, Konya, Turkey b c
a r t i c l e
i n f o
Article history: Received 23 June 2013 Revised 28 September 2013 Accepted 1 October 2013 Keywords: Hashimoto's thyroiditis Goiter Depression Anxiety disorders Autoimmune thyroiditis
a b s t r a c t Objective: The aim of this study was to examine the current prevalence of major depression and anxiety disorders in patients with euthyroid Hashimoto’s thyroiditis (HT) and euthyroid goiter. Method: The study sample was formed by consecutive 51 and 45 patients who were admitted to the endocrinology outpatient clinic and diagnosed with euthyroid HT and endemic/nonendemic goiter, respectively, and 68 healthy controls. Current diagnoses of psychiatric disorders were determined using the Structured Clinical Interview for DSM-IV. Beck Depression Inventory and Beck Anxiety Inventory were applied to the participants. Results: There was a statistically significant difference among the three groups in terms of major depression (P=.001), any mood or anxiety disorder (P=.000), any depressive disorder (P=.020), any anxiety disorder (P=.016) and obsessive–compulsive disorder (OCD) (P=.013). In the HT group, the prevalence of depression (P=.000), OCD (P=.005) and panic disorder (P=.041) was significantly higher than that in the control group. In the goiter group, depression (P=.006), any depressive disorder (P=.03), and any mood or anxiety disorder (P=.000) were significantly common in comparison to the control group. No significant difference was found between the HT and goiter groups. Conclusions: Euthyroid HT and euthyroid goiter increase predisposition to major depression and anxiety disorders, and thyroid autoimmunity and other thyroid pathologies should be investigated in euthyroid patients with chronic and treatment-resistant complaints. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Hashimoto’s thyroid (HT) is the most frequent autoimmune thyroid disease, with a prevalence rate of 2%, which is caused by the autoimmune inflammation of the thyroid gland and has different clinical stages ranging from euthyroiditis to hypothyroiditis. It is the most frequent cause of adult hypothyroiditis in the world [1–3]. It is characterized by elevated levels of antithyroglobulin (Anti-Tg) antibody and antithyroid peroxidase (anti-TPO) and the thyroid gland’s typical hypoechogenic pattern in ultrasonography [4]. The disease is also known as chronic autoimmune thyroiditis and affects most commonly women [5,6]. The positivity of anti-TPO in individuals with euthyroid is between 12% and 26%. Anti-TPO positivity (silent autoimmune thyroid disease) is recognized to be a precursor of possible future thyroid deficiency in cases where serum thyroid hormones and thyroid stimulant hormone (TSH) levels are within normal bounds [7,8].
⁎ Corresponding author. E-mail address: [email protected] (M. Giynas Ayhan). 0163-8343/$ – see front matter © 2014 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.genhosppsych.2013.10.002
While there are studies that report that psychiatric disorders are seen more frequently in individuals with autoimmune thyroid diseases than the general population [9–15], others have reported that thyroid autoimmunity is not related to depression and anxiety [16–20]. However, previous studies are based on mostly psychiatric symptom scales rather than structured clinical interview, and the relationship between thyroid autoimmunity and anxiety disorders has been investigated only by a limited number of studies. In this study, we investigated the prevalence of major depression and anxiety disorders in patients with euthyroid endemic/nonendemic goiter and HT without having any thyroid hormone preparation and healthy subjects. Thereby, we aimed to examine whether HT specifically increases risk of depressive or anxiety disorders compared with endemic/nonendemic goiter or controls. 2. Method The study sample consisted of 51 patients with euthyroid HT and 45 patients with euthyroid endemic/nonendemic goiter who were admitted to the Endocrinology Outpatient Clinic, Meram Faculty of Medicine, Necmettin Erbakan University, in Konya, Turkey, between
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April 2010 and February 2012. The study sample also included a healthy control group consisting of 68 hospital personnels and their relatives who were matched for sociodemographic characteristics of the patients. All subjects underwent a complete thyroid evaluation including physical examination, thyroid ultrasonography and measure of serum free T4 (FT4), free T3 (FT3), TSH, anti-TPO and anti-Tg. The diagnosis of euthyroid HT was made on the basis of coexistence of high titers of anti-Tg (0–20 IU/ml) and anti-TPO (0– 10 IU/ml), diffuse hypoechogenic pattern in ultrasonography and normal serum levels of FT3 (2.0–4.4 pg/ml), FT4 (0.93–1.7 ng/dl) and TSH (0.27–4.0 mU/L). The diagnosis of endemic/nonendemic goiter was based on the presence of one or more multiple thyroid nodules in a normoechogenic gland in ultrasonography, with the absence of antithyroid autoantibodies and normal serum levels of free thyroid hormones and TSH. For the report that HT affects especially middle-aged women [21], patients between 20 and 45 years of age were included in the study. All participants were at least elementary school graduates. Cognitive incompetence and illiteracy, which make psychiatric interview difficult; having chronic medical illness (e.g., neurological, cardiovascular, pulmonary, rheumatological and endocrinological diseases); receiving thyroid hormone replacement treatment; using oral contraceptives; being in menopausal stage and having a history of schizophrenia or bipolar disorder were exclusion criteria. The study was approved by the Ethics Committee of Meram Faculty of Medicine of Necmettin Erbakan University. After the thyroid evaluation, relevant subjects were referred to psychiatry outpatient clinic. The subjects’ sociodemographic information was recorded in the information form. Current mood and anxiety disorders were ascertained by means of the Structured Clinical Interview for DSM-IV (SCID-I) [22]. The levels of anxiety and depression were screened using Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) [23–26]. Psychiatric examinations were conducted by psychiatrists with at least 4 years of experience about psychiatric disorders. In addition, the psychiatrists had a formal training about SCID-I. In the present study, we performed modules of affective and anxiety disorders of SCID-I. 2.1. Statistical analysis Data analysis was conducted using SPSS (version 15.0). The χ 2 test was used for categorical variants, and Fisher’s Exact χ 2 Test was used when necessary. One-way analysis of variance (ANOVA) was used for continuous variables among the groups. Tukey’s honestly significant difference test was used in the binary group comparisons of variables seen to be significant in ANOVA. Statistical significance was accepted as Pb.05. 3. Results The study included 164 participants aged 20–45 years. The mean age of the sample was 34.67±6.82 years. Fifty-one subjects of all the cases were in the HT group, 45 were in the goiter group, and 68 were in the control group. There was no significant difference among the groups with regard to sex, age, marital status, educational level and number of children (Table 1). While 27 (52.9%), 17 (37.8%) and 11 (16.2%) subjects were diagnosed with a current psychiatric disorder in the HT, goiter and control groups, 17 (33.3%), 11 (24.4%) and 4 (5.9%) subjects were diagnosed with a current depressive disorder in the HT, goiter and control groups, respectively. Moreover, 19 (37.3%), 11 (24.4%) and 10 (14.7%) people were diagnosed with an anxiety disorder in the HT, goiter and control groups, respectively. There was a statistically significant difference between three groups for these disorders (P= .000, P=.001 and P=.018, respectively). Twenty-eight subjects, 15 cases (29.4%) from the HT group, were diagnosed with major
Table 1 Sociodemographic characteristics of the HT, goiter and control groups
Sex (n, %) Female Male Marital status (n, %) Married Single Education (n, %) Elementary school High school College Occupation (n, %) Unemployed Employed Mean age (mean±SD)
Hashimoto's group (n=51)
Goiter group (n=45)
Control group (n=68)
49 (96.1) 2 (3.9)
41 (91.1) 4 (8.9)
64 (94.1) 4 (5.9)
38 (74.5) 13 (25.5)
37 (82.2) 8 (17.8)
52 (76.5) 16 (23.5)
25 (49.0) 15 (29.4) 11 (21.6)
26 (57.8) 11 (24.4) 8 (17.8)
40 (58.8) 19 (27.9) 9 (13.2)
35 (68.6) 16 (31.4)
29 (64.4) 16 (35.6)
46 (67.6) 22 (32.4)
35.10±7.75
35.47±6.74
33.82±6.07
1.61±1.328
1.91±1.164
1.78±1.208
P value .595⁎
Number of children (mean±SD)
.645⁎
.737⁎
.902⁎
.396⁎⁎
.482⁎⁎
⁎ χ2 test. ⁎⁎ ANOVA test.
depression. There was a statistically significant difference among the three groups regarding the existence of major depression (P= .001) (Table 2). Among the anxiety disorders, the prevalence of panic disorder was found to be 11.8% in the HT group, 6.7% in the goiter group and 1.5% in the control group (P=.066). There was no significant difference among all groups regarding the prevalence of panic disorder according to the χ 2 test. The most frequent diagnosis concerning anxiety disorders was obsessive–compulsive disorder (OCD) (7.3%) in the general sample. Eight (15.7%) subjects were diagnosed with OCD in the HT group. There was a statistically significant difference among the three groups in terms of OCD (P=.013) (Table 2). Table 2 also shows scores of BDI and BAI in each study group. The average scores of the scales were consistent with the diagnoses of the subjects. When the HT and the control groups were compared, any psychiatric disorder (P=.000), any depressive disorder (P=.000), any anxiety disorder (P=.005), major depression (P=.000), OCD (P= .005) and panic disorder (P=.041) cases were found to be more common in the HT group than the control group. There was no significant difference between the HT and control groups in terms of dysthymic disorder (P=.576), generalized anxiety disorder (GAD) (P=.650) and phobic disorder (P=1.000) (Table 2). Major depression (P=.006), any depressive disorder (P=.009) and any disorder (P=.014) cases were significantly more common in the goiter group than the control group. However, there was no significant difference regarding dysthymic disorder (P=.081), OCD (P=.299), panic disorder (P=.299), GAD (P=1.000) and phobic disorder (P=.681). There was no significant difference between the HT and goiter groups regarding all the depressive and anxiety disorders evaluated [major depression (P=.489), dysthymic disorder (P=.414), OCD (P=.209), panic disorder (P=.495), GAD (P=.620), phobic disorder (P=.663), any anxiety disorder (P=.194), any depressive disorder (P=.375), any psychiatric disorder (P=.155)] (Table 2). 4. Discussion In this study, we found the current prevalence of any depressive disorder to be 29.4% and 33.3% in the HT group and 22.2% and 24.4% in the goiter group, respectively. This percentage was only 5.9% in the control subjects. The rates seem to be very high in patients with HT and goiter compared to healthy subjects.
M. Giynas Ayhan et al. / General Hospital Psychiatry 36 (2014) 95–98 Table 2 The comparison of the HT, goiter and control groups for the prevalence of psychiatric diagnoses Hashimoto’s group (n=51) Major depressiona,b (n, %) Existent 15 (29.4) None 36 (70.6) Dysthymic disorder (n, %) Existent 2 (3.9) None 49 (96.1) c OCD (n, %) Existent 8 (15.7) None 43 (84.3) PDd (n, %) Existent 6 (11.8) None 45 (88.2) GAD (n, %) Existent 3 (5.9) None 48 (94.1) Phobic disorder (n, %) Existent 2 (3.9) None 49 (96.1) An anxiety disordere (n, %) Existent 19 (37.3) None 32 (62.7) Any depressive disorderf,g (n, %) Existent 17 (33.3) None 34 (66.7) Any disorderh,i (n, %) Existent 27 (52.9) None 24 (47.1) BDI score 13.06±8.69 (min: 1, max: 32) BAI 12.59±9.88 (min: 2, max: 41)
Goiter group (n=45)
Control group (n=68)
10 (22.2) 35 (77.8)
3 (4.4) 65 (95.6)
4 (8.9) 41 (91.1)
1 (1.5) 67 (98.5)
3 (6.7) 42 (93.3)
1 (1.5) 67 (98.5)
3 (6.70) 42 (93.3)
1 (1.5) 67 (98.5)
1 (2.2) 44 (97.8)
2 (2.90) 66 (97.10)
3 (6.7) 42 (93.3)
3 (4.4) 65 (95.6)
11 (24.4) 34 (75.6)
10 (14.7) 58 (85.3)
11 (24.4) 34 (75.6)
4 (5.9) 64 (94.1)
17(37.8) 28 (62.2) 12.09±10.80 (min:1, max: 55) 10.62 ±12.49 (min:1, max: 49)
11 (16.2) 57 (83.8) 4.32±4.65 (min:0, max: 19) 4.07±3.24 (min:0, max: 16)
P value
.001⁎
.160⁎
.013 ⁎
.066 ⁎
.583⁎
.801⁎
.018 ⁎
.001⁎
.000⁎
.000⁎⁎ .000⁎⁎
a P=.000 between the HT and control groups, bP=.006 between the goiter and control groups, cP=.005 between the HT and control groups, dP=.041 between the HT and control groups, eP=.005 between the HT and control groups, fP=.000 between the HT and control groups, gP=.009 between the goiter and control groups, hP=.000 between the HT and control groups, iP=.014 between the goiter and control groups. ⁎ χ 2. ⁎⁎ ANOVA test.
In a study by Carta et al. [15], it was reported that there is an increased risk of depressive disorder in patients with HT independent of thyroid dysfunction measured by routine serum tests, but there is no increased risk of depressive disorders between the euthyroid goiter group and the control group. In another study, the researchers observed that the rates of anxiety, depression and panic disorder in patients with euthyroid cold nodules decreased dramatically following surgery [27]. In this study, we found an increased risk of depressive disorders in both the euthyroid HT group and the euthyroid goiter group compared to the control group. This result suggests that thyroid autoimmunity and goiter have an effect on depressive disorders by different mechanisms or similar changes in the thyroid gland tissue. It is reported that hypothalamic–pituitary–thyroid (HPT) axis disorder and 5-hydroxytryptamine dysregulation on the HT base have a role in the etiopathogenesis and neurobiology of depressive disorders. Some studies concluded that antithyroid antibodies might be elevated, the TSH response to thyrotropin-releasing hormone (TRH) might be decreased, TRH concentration might be elevated in cerebrospinal fluid and triiodothyronine enhances the efficiency of antidepressants in depressive disorders [28–34]. It is thought that there is a defect in TSH’s circadian rhythm in some depressive disorder and that a slight disorder in TSH and thyroid hormone levels within normal serum levels affects the mood [35]. Fountoulakis et al. [36] called this condition as “low-thyroid function syndrome.” Some studies reported that the brain might be affected before the other
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organs in euthyroid conditions and that this situation can be considered to be “brain hypothyroidism” [29,37–39]. Haggerty et al. [16] concluded that the positivity of antithyroid antibodies and the elevated TSH level were correlated. According to some authors, serotonergic dysfunction is much more pronounced in depressive patients with normal HPT axis. It is suggested that HPT dysregulation in depressive disorders develops through a compensatory mechanism against decreased central serotonin activity [40]. On the other hand, Hardoy et al. found significant cerebral perfusion anomalies in major depressive disorder with HT [41]. Further, changes in the hypothalamic–pituitary–adrenal (HPA) axis affected by proinflammatory and anti-inflammatory agents might also cause depression by triggering thyroid autoimmunity [4,42,43]. The prevalence of an anxiety disorder in general population is between 6.8% and 9.7% [44]. The results of this study show that the prevalence of an anxiety disorder in the HT and goiter groups is much higher than that in the general population. OCD (15.7%) is the most frequently seen anxiety disorder in the HT group. The lifetime prevalence of OCD in general population is between 0.8% and 3.2% [44–46]. To our knowledge, the present study is the first that points out the possible relationship between HT and OCD. Autoimmunity in HT may be a possible mechanism underlying this result, but it is still unclear. Some studies [47–52] that have investigated the relationship between autoimmunity and OCD have different results. Morer et al. [53] reported that OCD was a heterogeneous disorder and early phase OCD might be related to autoimmune etiology. On the other hand, although OCD has a higher prevalence in the HT group than the control group, there is no significant difference between the HT and goiter groups in the current study. Therefore, to explain that OCD and autoimmunity have a relationship seems to be difficult. This hypothesis needs further studies. Although there is no significant difference between the HT and goiter groups regarding panic disorder, the HT group has a higher prevalence rate of panic disorder compared to healthy subjects. Similar to the outcomes of the present study, some authors concluded that anti-TPO positivity was significantly higher in people with panic disorder than the control group, and anti-TPO positivity might be related to panic attacks [54,55]. Stein et al. [56] found no significant difference between panic disorder and the control group regarding the autoimmune thyroiditis. Carta et al. [15] found a high rate of GAD and social phobia in autoimmune thyroiditis, while they found a significant relationship between not-otherwise-specified anxiety disorder and thyroid autoimmunity in another study [10]. Engum et al. [17], on the other hand, found no relationship between thyroid autoimmunity and anxiety. In line with the results of our study, a study found no association between social phobia and the control group regarding anti-TPO positivity [57]. These heterogeneous results may be due to methodological variations including study sample, sample sizes, interview or assessment instruments, and diagnostic criteria. Our study has some limitations. First of all, our sample is relatively small and is composed of patients presenting to the endocrinology clinic, who may not represent all the people with silent thyroid disease. Thus, studies covering the general population need to be conducted. The second point is that our study has a crosssectional characteristic and does not take the psychiatric history of participants into consideration. Formative studies conducted through the determination of individuals’ serum autoantibody levels and the imaging of their thyroid glands will reveal more dependable information on the effect of thyroid autoimmunity. We did not correct for multiple testing for the number of diagnoses. Also, another limitation of the study is that the interviewers who carried out clinical assessments were not blind to group membership. Finally, some of the patients probably had high-normal TSH levels. It would be difficult to discern the symptoms of anxiety or depression from the effects of subclinical hypothyroidism.
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