Acta Psychiatr Scand 2002: 106: 27–34 Copyright ª Blackwell Munksgaard 2002

Printed in UK. All rights reserved ACTA PSYCHIATRICA

SCANDINAVICA
ISSN 0001-690X

An association between depression, anxiety

and thyroid function – a clinical fact
or an artefact?
Engum A, Bjøro T, Mykletun A, Dahl AA. An association between Anne Engum1, Trine Bjøro2,
depression, anxiety and thyroid function – a clinical fact or an artefact? Arnstein Mykletun3, Alv A. Dahl4
Acta Psychiatr Scand 2002: 106: 27–34. ª Blackwell Munksgaard 2002. 1
Department of Psychiatry, Innherred Hospital,
Levanger, Norway, 2The Norwegian Radium Hospital,
Objective: The aim of the study was to examine the association University of Oslo, Oslo, Norway, 3Department of
between depression, anxiety and thyroid dysfunction. Psychology, University of Bergen,
Method: The study is part of the HUNT-study. Individuals aged 40– Bergen, Norway and 4Department of Psychiatry,
89 years (n ¼ 30 589) with thyroid assays, and self-rating of depression Aker Hospital, University of Oslo, Norway
and anxiety – Hospital Anxiety and Depression Scale (HADS) – were
divided in six categories according to thyroid function. Relations were
investigated with logistic regression analysis.
Results: The group with biochemical hypothyroidism had significantly
lower risk for depression and anxiety compared with the reference
group with normal thyroid function. Subclinical hypothyroidism, and
latent and overt biochemical hyperthyroidism were not risk factors for
depression or anxiety. When individuals with former known thyroid Key words: thyroid function; depression; anxiety;
disease were excluded from the analyses, the results were essentially Hospital Anxiety and Depression Scale
identical, but this group had an increased risk of both anxiety and Anne Engum MD, Department of Psychiatry, Innherred
depression, independent of thyroid function. Hospital, N-7600 Levanger, Norway
Conclusion: In this large, unselected population, we found no E-mail: an-engum@online.no
statistical association between thyroid dysfunction, and the presence of
depression or anxiety disorder. Accepted for publication April 9, 2002

viewed as chemically euthyroid, have alterations in

Introduction
Both subclinical, mild, and overt hypothyroidism
have been associated with mood disorders. It has
been stated that abnormal thyroid functioning can
affect mood and influence the course of affective
disorders. Many hypotheses have been postulated
about mechanisms by which thyroid dysfunction
might alter the risk for development of depression.
Marangell et al. (1) hypothesized a relation
between thyroid hormone status and neurotrans-
mitter activity by postulating that thyrotropin
releasing hormone (TRH) itself is a neurotrans-
mitter that has significant antidepressant proper-
ties. Cleare et al. (2) found that depressed patients
had higher levels of thyroid stimulating hormone
(TSH), and suggested that hypothyroidism reduces
central 5-hydroxy tyramine(5-HT) activity in the
brain. They also indicated a threshold effect in that
higher TSH levels predicted both lower 5-HT
mediated endocrine responses and the presence of
clinical depression. Jackson (3) concluded that
most patients with depression, although generally
their thyroid function including slight elevation of
serum thyroxine, blunted thyrotropin response to
TRH stimulation, and loss of nocturnal TSH rise.
These changes were generally reversed following
alleviation of the depression. In the same review, it
was also postulated that the increased free thyrox-
ine (T4) and blunted TSH response to exogenous
TRH, was the result of glucocorticoid activation
that increased TRH secretion with down-regula-
tion of the TRH receptor as a consequence.
A review by Musselman et al. (4) stated that
patients with primary thyroid disease have high
rates of depression caused by alterations of the
hypothalamic–pituitary–thyroid (HPT) axis, and
that the alteration consists of changes in the TSH
response to TRH and elevated TRH concentra-
tions in the cerebrospinal fluid.
Most of the studies suggest an association
between hypothyroidism and depression, but
Ordas et al. (5) concluded that thyroid disease per
se rarely was an etiological factor of major depres-
sion. Even with no evidence for overt thyroid

27
Engum et al.
dysfunction, one could not conclude that the HPT
axis was without importance in depression. Fava
et al. (6) found that hypo- and hyper-thyroidism
were extremely uncommon in depressed patients,
and that the presence of subtle thyroid abnormal-
ities did not have an impact on treatment outcome.
The association between anxiety and thyroid
dysfunction has been less systematically researched,
but three studies indicate an association between
panic disorder and thyroid dysfunction (7–9).
Rogers et al. (7) found that patients with panic
disorder had more medical problems including
thyroid dysfunction than the population at large
and patients with other anxiety disorders.
Taken together, the literature suggests an
association between various degrees of thyroid
dysfunction and depressive disorder, although the
mechanism for this is unclear. There is a variety of
hypothesis considering biological causality. How-
ever, the studies are mainly based on clinical
samples with problems concerning bias and gener-
alizability.
Aims of the study
To test the hypothesis that, in a large unselected
population, there is no increased risk of anxiety
disorders or depression in individuals with thyroid
dysfunction.
Material and methods
Population
The study is part of the health study of Nord-
Trøndelag County of Norway (The HUNT Study,
www.hunt.folkehelsa.no) and it was conducted
from August 1995 to June 1997. All inhabitants
aged 20 years and above were invited to take part,
and 65 648 (71.3%) of a total of 92 100 individuals
participated in the study. The youngest and oldest
age groups had the lowest rates of attendance,
while the highest rates were found among women
and the middle aged. All inhabitants received a
letter with a questionnaire and an appointed date
for physical tests and blood samples. They were
asked to record their current status with respect to
personal and demographic characteristics, illnesses,
life style and health habits. The questionnaire
included eight thyroid-related questions about
known thyroid illness and treatment, and thyroid
stimulating hormone (TSH) blood tests were car-
ried out in the population above 40 years. Our
sample concerns individuals aged 40–89 years
(n ¼ 30 589) with thyroid assays and assessments
of depression and anxiety.
28
Measurements
Depression and anxiety. The level of anxiety and
depression was self-rated by Hospital Anxiety and
Depression Scale (HADS) (10). HADS consists of
seven items for depression (HADS-D) and seven
items for anxiety (HADS-A). A main characteristic
of HADS is that items covering somatic symptoms
of anxiety and depression have been eliminated. By
defining cut-off values, the HADS subscales can
give an indication of mental disorder: 0–7 normal,
8–10 mild, 11–14 moderate and 15–21 severe
disorder (11). In this study we have tested both
8+ and 11+ as cut-off levels for caseness of
anxiety disorder and depression.
HADS has been extensively tested and has well-
established psychometric properties (12). Several
studies have found good sensitivity, specificity and
correlation between HADS, other questionnaires,
and structured interviews used to diagnose depres-
sion and anxiety disorders (13, 14).
Thyroidea. The TSH blood tests were carried out in
50% of the men ‡40 years and in all women
‡40 years, and T4 was measured if TSH was <0.2
or >4.0 mU/l. Normal thyroid function in this
study considered TSH levels in the range from 0.2
to 4.0 mU/l. Latent and subclinical biochemical
hypothyroidism was considered with an elevation
of TSH with T4 in the normal range. Overt
biochemical hypothyroidism was defined by eleva-
ted TSH and a decrease of T4 levels. Biochemical
hyperthyroidism and latent biochemical hyperthy-
roidism was diagnosed in TSH levels below the
normal range with and without elevated T4.
Blood samples were drawn without any restric-
tion regarding eating or medication. The TSH
levels of serum samples were analysed at the
Hormone Laboratory, Aker University Hospital,
and was measured with DELFIA hTSH Ultra
(sensitivity 0.03 mU/l and total analytical variation
<5%) and fT4 with DELFIA freeT4 (total ana-
lytical variation <7%), both from Wallac Oy,
Turku, Finland. The laboratory’s reference values
were: TSH 0.2–4.5 mU/l and fT4 8–20 pmol/l.
Statistical analysis
The association between depression, anxiety, and
thyroid function was investigated with blockwise
multivariate logistic regression analysis with
HADS-D and HADS-A with cut off score 8 and
11 as dependent variables and TSH and T4
categories, age and gender, and interaction terms
between these as independent variables. Level of
significance was set at P < 0.05.
 An association between depression, anxiety and thyroid function

Ethics Table 2. Classification of thyroid dysfunction

The HUNT-II study has been recommended by the Label n TSH mU/l T4 pmol/l
National Data Inspectorate and the Board of I: Reference group 28 303 0.2–4.0 –
Medical Research Ethics in Health region IV of II: Latent biochemical hypothyreosis 1424 4.0–10.0 8–20
Norway. III: Subclinical biochemical hypothyreosis 137 >10.0 8–20
IV: Biochemical hypothyreosis 198 >4.0 <8
V: Latent biochemical hyper-thyreosis 346 <0.2 8–20
Results VI: Biochemical Hyperthyreosis 181 <0.2 >20

The prevalence of depression and anxiety defined

by cut-off level 8 on the HADS-D/A scale is 13.3
and 16.7%, respectively, in the total population
aged 40–89 years (Table 1). The prevalences are
significantly different (17.3% for depression and
21.7% for anxiety) in the group with previously
known thyroid disorder, and 10.9 and 14.5% in the
group with newly discovered thyroid dysfunction.
The demographic characteristics of the sample
concerning age and gender are shown in Table 3.
We did not find the expected association between
gender and depression, and this observation is
discussed in a study by Stordal et al. (15).
The 30 589 individuals, 40–89 years of age, with
measures of TSH, T4, and HADS were divided in
six groups according to their TSH and T4 levels, as
shown in Table 2.
The group with normal thyroid function (TSH
0.2–4.0 mU/l) was expected to have the lowest risk
of anxiety and depression, and was defined as the
reference group (group I).
Group IV with overt biochemical hypothyroid-
ism had significantly lower risk of depression
compared with group I. Group II and III with
latent and subclinical biochemical hypothyroidism,
and group V and VI with latent and overt
biochemical hyperthyroidism did not have any
significantly increased risk of depression (Table 3,
model 1), even when controlled for age and gender
(model 2). There was no statistically significant
difference in the effects of the groups on thyroid
function according to age and gender (model 3).
The analyses showed that none of the groups
had elevated risk of anxiety disorders compared
with the reference group (Table 4, model 1). When
age and gender were taken into account (Table 4,
model 2), the category with overt biochemical
hypothyroidism (group IV) had statistically lower
risk of anxiety, but group V and VI with latent and
overt biochemical hyperthyroidism had the same
risk compared with the reference group.
The same analyses carried out with cut-off score
11 on HADS-D and HADS-A, gave essentially
identical results (data not shown).
Of a total of 30 589 individuals, 2784 had a
recognized thyroid disease and 1526 were diag-
nosed with biochemical thyroid dysfunction. When
individuals with former known thyroid disease
were excluded from the analyses, the results
showed that the group with overt biochemical
hypothyroidism still had significantly lower risk of
depression and anxiety, and the groups with latent
and subclinical biochemical hypothyroidism, and
latent and overt biochemical hyperthyroidism did
not have any significantly increased risk of depres-
sion or anxiety (data not shown).
In our material, 2784 answered yes to at least
one of the thyroid-related questions in the ques-
tionnaire, indicating a history of thyroid disease. A
total of 1479 persons reported to have had hypo-
thyroidism, 785 had previously known hyperthy-
roidism and the remaining had goitre or other
thyroid diseases. However, 1635 were or had been
on thyroxine medication and 70 individuals were
or had been on carbimazole medication.
Seventy-three per cent (n ¼ 2021) of the group
with previously known thyroid disorder, had
normal thyroid function according to the thyroid

Table 1. Prevalence of anxiety and depression in thyroid disorder

HADS-D HADS-A

Cut-off ‡ 8 Cut-off ‡ 11 Cut-off ‡ 8 Cut-off ‡ 11

Total n n % n % n % n %

Total population 30 593 2674 13.3 818 4.0 3875 16.6 1377 5.8
Known thyroid disorder 2784 482*** 17.3 165*** 5.9 604*** 21.7 240*** 8.6
Newly discovered 1526 167* 10.9 47 3.1 222 14.5 61** 4.0
thyroid dysfunction

Chi-Square *P < 0.05, **P < 0.01, ***P < 0.001.

29
Engum et al.

Table 3. Logistic regression analysis of HADS-D, age, and gender in relation to thyroid function

Model 1 Model 2 Model 3

Covariate n OR 95% CI OR 95% CI OR 95% CI

I: TSH 0.2–4 28 303 1.00 1.00 1.00

II: TSH 4–10 and T4 8–20 1424 0.99 0.85–1.16 0.93 0.80–1.09 0.90 0.66–1.21
III: TSH > 10 and T4 8–20 137 0.86 0.51–1.45 0.84 0.50–1.42 1.78 0.76–4.19
IV: TSH > 4 and T4 < 8 198 0.53 0.31–0.91 0.51 0.30–0.86 0.65 0.19–2.13
V: TSH < 0.2 and T4 8–20 346 1.07 0.79–1.46 1.01 0.75–1.38 0.82 0.35–1.94
VI: TSH < 0.2 and T4 > 20 181 1.09 0.72–1.66 1.05 0.69–1.59 0.83 0.25–2.80
Gender male1 10 030 1.00 1.00
Gender female 20 559 0.94 0.87–1.01 0.94 0.88–1.01
Age 40–44 years1 4161 1.00 1.00
Age 45–54 years 9829 1.29 1.14–1.46 1.29 1.14–1.46
Age 55–69 years 9885 1.62 1.43–1.82 1.62 1.44–1.83
Age 70–84 years 6714 2.12 1.87–2.40 2.12 1.87–2.40
TSH 0.2–4 in females1 18 778 1.00
TSH 4–10 and T4 8–20 in females 1051 1.06 0.74–1.51
TSH > 10 and T4 8–20 in females 105 0.33
TSH > 4 and T4 < 8 in females 168 0.75
TSH < 0.2 and T4 8–20 in females 299 1.28
TSH < 0.2 and T4 > 20 in females 158 1.31
)2 log likelihood mod 0: 23923.833 23721.542 23717.088
Block significance 0.207 0.000 0.486
1
Reference category.

Table 4. Logistic regression analysis of HADS-A, age, and gender in relation to thyroid function

Model 1 Model 2 Model 3

Covariate n OR 95% CI OR 95% CI OR 95% CI

I: TSH 0.2–4 28 303 1.00 1.00 1.00

II: TSH 4–10 and T4 8–20 1424 1.03 0.90–1.19 1.02 0.89–1.17 1.10 0.81–1.50
III: TSH > 10 and T4 8–20 137 1.17 0.76–1.79 1.13 0.74–1.74 1.02 0.36–2.91
IV: TSH > 4 and T4 < 8 198 0.63 0.40–0.98 0.58 0.37–0.91 0.52 0.12–2.20
V: TSH < 0.2 and T4 8–20 346 1.14 0.86–1.49 1.06 0.80–1.39 0.33 0.08–1.36
VI: TSH < 0.2 and T4 > 20 181 1.03 0.70–1.52 0.96 0.65–1.41 0.71 0.17–3.04
Gender male1 10 030 1.00 1.00
Gender female 20 559 1.67 1.56–1.79 1.67 1.55–1.79
Age 40–44 ys1 4161 1.00 1.00
Age 45–54 ys 9829 1.04 0.95–1.15 1.04 0.94–1.15
Age 55–69 ys 9885 0.96 0.87–1.06 0.96 0.87–1.06
Age 70–84 ys 6714 0.81 0.73–0.90 0.81 0.72–0.90
TSH 0.2–4 and T4 8–20 in females1 18 778 1.00
TSH 4–10 and T4 8–20 in females 1051 0.91 0.64–1.29
TSH > 10 and T4 8–20 in females 105 1.14 0.36–3.59
TSH > 4 and T4 < 8 in females 168 1.13 0.25–5.10
TSH < 0.2 and T4 8–20 in females 299 3.49 0.82–14.7
TSH < 0.2 and T4 > 20 in females 158 1.39 0.31–6.26
)2 log likelihood mod 0: 27567.104 27307.542 27302.867
Block significance 0.265 0.000 0.457
1
Reference category.

function tests (TSH and T4), 13% (n ¼ 360) had
subclinical biochemical hypothyroidism, 1%
(n ¼ 29) had biochemical hypothyroidism, 8.5%
(n ¼ 237) had subclinical biochemical hyperthy-
roidism and 4.8% (n ¼ 134) had biochemical
hyperthyroidism. The mean levels of depression
and anxiety were the same, with and without
thyroid dysfunction [mean HADS-D of 4.3 and 4.2
(P ¼ 0.48) and mean HADS-A of 4.9 and 4.7
(P ¼ 0.35), respectively].
The individuals with previously known hypo-
thyroidism and hyperthyroidism, or a history of
present or earlier thyroxine medication, were
associated with significantly increased risk of

30
 An association between depression, anxiety and thyroid function

depression and anxiety, even when controlled for lower risk(40 of 70) for mental symptoms in
age and gender (Table 5). groups with thyroid dysfunction (II–VI) compared
The number of statistical significantly associa- with the healthy reference group (I). These differ-
tions between the 14 items of HADS and the six ences were not statistically significant, however
categories of thyroid function did not exceed the (Table 7).
number expected by chance, with significance level
of 0.05 (Table 6). The significant associations goes
Discussion
in both positive and negative directions. The non-
significant differences observed showed mainly The prevalence of depression is significantly higher
in the group with previously known thyroid
disorder, and lower in those with newly discovered
Table 5. Thyroid disorder in relation to depression and anxiety thyroid dysfunction, compared with the general
HADS-D8 HADS-A8 population. However, the relation between thyroid
disorder and symptoms of anxiety and depression
OR1 CI 95% OR1 CI 95% is relatively weak: Depression (HADS-D ‡ 8) is
Hypothyroidism ref.gr. 2
1.000 1.000 reported by 17.3% in the group with previously
Hypothyroidism 1.402 1.220–1.612 1.358 1.195–1.542 known thyroid disorder, as compared with 13.3%
Hyperthyroidism ref.gr.2 1.000 1.000 in the general population, aged 40–89 years. The
Hyperthyroidism 1.526 1.271–1.831 1.589 1.346–1.876
Thyroxin ref.gr.2 1.000 1.000
result for anxiety is equivalent.
Thyroxin medication 1.347 1.178–1.540 1.338 1.184–1.513 In our study, logistic regression analyses with
Neo-Mercazole ref.gr.2 1.000 1.000 HADS-A and HADS-D at well established cut-off
Neo-Mercazole medication 1.295 0.678–2.474 1.278 0.720–2.269 values for caseness (14, 16) showed that the
1
OR, controlled for age and gender. groups with latent and subclinical biochemical
2
The reference group is individuals without the actual condition or medication. hypothyroidism, and the groups with latent and

Table 6. Thyroid function in relation to items in HADS

Latent biochemical Subclinical biochemical Bio-chemical Latent Biochemical Bio-chemical

Healthy hyper-thyreosis hypo-thyreosis hypo-thyreosis hyper-thyreosis hyper-thyreosis
References II III IV V VI
I n = 1424 n = 137 n = 198 n = 346 n = 181
n = 28 303 TSH 4–10 and TSH > 10 and TSH > 4 and TSH < 0.2 and TSH < 0.2 and
HADS-items TSH 0.2–4 T4 8–20 T4 8–20 T4 < 8 T4 8–20 T4 > 20 Model significance

HAD A1 1.00 0.98 0.38 0.42 1.16 2.21 0.002

(0.77–1.23) (0.12–1.19) (0.17–1.03) (0.75–1.80) (1.39–3.51)
HAD A2 1.00 1.07 1.45 0.70 1.15 1.11 0.253
(0.92–1.25) (0.94–2.24) (0.44–1.13) (0.85–1.55) (0.55–1.65)
HAD A3 1.00 0.96 0.87 0.47 1.30 1.16 0.034
(0.81–1.13) (0.51–1.49) (0.26–0.84) (0.97–1.74) (0.77–1.77
HAD A4 1.00 1.05 0.52 0.56 1.07 0.91 0.073
(0.89–1.23) (0.26–1.02) (0.33–0.97) (0.78–1.48) (0.57–1.46)
HAD A5 1.00 0.87 0.99 0.88 1.18 1.08 0.851
(0.67–1.12) (0.46–2.13) (0.45–1.72) (0.76–1.85) (0.57–2.05)
HAD A6 1.00 0.93 1.17 0.65 0.95 0.93 0.251
(0.82–1.07) (0.78–1.75) (0.44–0.97) (0.72–1.24) (0.64–1.35)
HAD A7 1.00 0.91 0.48 0.55 1.38 1.52 0.144
(0.70–1.19) (0.15–1.52) (0.23–1.34) (0.88–2.15) (0.85–2.74)
HAD D1 1.00 1.01 0.81 0.80 1.12 1.24 0.893
(0.82–1.26) (0.38–1.74) (0.42–1.51) (0.74–1.70) (0.72–2.15)
HAD D2 1.00 0.82 0.78 0.91 0.88 1.42 0.447
(0.63–1.05) (0.34–1.78) (0.48–1.73) (0.54–1.43) (0.82–2.45)
HAD D3 1.00 0.89 0.67 0.46 0.95 1.30 0.034
(0.74–1.06) (0.35–1.28) (0.24–0.86) (0.67–1.35) (0.84–2.00)
HAD D4 1.00 1.21 0.88 1.23 1.59 1.54 0.001
(1.04–1.41) (0.52–1.48) (0.83–1.82) (1.21–2.10) (1.05–2.25)
HAD D5 1.00 1.11 0.97 0.71 0.95 0.77 0.577
(0.92–1.32) (0.53–1.75) (0.40–1.24) (0.65–1.39) (0.44–1.36)
HAD D6 1.00 0.94 1.02 1.04 1.24 1.41 0.328
(0.80–1.10) (0.63–1.66) (0.70–1.55) (0.93–1.65 (0.96–2.06)
HAD D7 1.00 1.03 0.85 0.97 0.96 0.77 0.957
(0.84–1.25) (0.43–1.68) (0.57–1.65) (0.64–1.44) (0.42–1.42)

Numbers are odds ratio with 95% CI.

31
Engum et al.

Table 7. Items of Hospital Anxiety and Depression

percentage with Scale (HADS)
high score1 Item label

HAD-A1 7 I feel tense or `wound up'

HAD-A2 14 I get a sort of frightened feeling as if something awful is about to happen
HAD-A3 13 Worrying thoughts go through my mind
HAD-A4 12 I can sit at ease and feel relaxed
HAD-A5 5 I get a sort of frightened feeling like `butterflies' in the stomach
HAD-A6 20 I feel restless as I have to be on the move
HAD-A7 4 I get sudden feelings of panic
HAD-D1 6 I still enjoy the things I used to enjoy
HAD-D2 6 I can laugh and see the funny side of things
HAD-D3 11 I feel cheerful
HAD-D4 14 I feel as if I am slowed down
HAD-D5 9 I have lost interest in my appearance
HAD-D6 14 I look forward with enjoyment to things
HAD-D7 8 I can enjoy a good book or radio or TV program
1
Four responses (0–3) for each item, high score is estimated response 2 and 3.

overt biochemical hyperthyroidism did not have
any significantly increased risk of depression or
anxiety (OR < 1.00). The group with overt bio-
chemical hypothyroidism actually had a signifi-
cantly lower risk of depression and anxiety,
compared with the reference group with normal
thyroid function. Both cut-off values gave the
same findings.
We have primarily examined the association
between thyroid dysfunction and depression and
anxiety, but we have also examined individuals
with self-reported thyroid disease. In this group,
73% had normal thyroid function tests, and the
rest had elevated or low TSH. We also looked
upon subgroups with present or earlier use of
thyroxine or carbimazole medication. Both a
history of earlier diagnosed hypothyroidism,
hyperthyroidism and present or earlier use of
thyroxine was associated with increased risk of
both depression and anxiety.
These results are not in accordance with previ-
ous research, because several studies have shown a
high prevalence of psychological disturbances in
individuals with thyroid dysfunction. The preval-
ence of dysfunction reported by different authors is
difficult to compare due to the use of different
assays, lack of international standardization of the
assays, and different cut-off values for laboratory
measures. Few of the studies have included control
groups, or used other means of addressing major
causes of bias, such as gender and age. An
objection to previous influential research is the
use of clinical samples. Studies on thyroid disease
and mood disorder have been based on clinical
samples which inevitably suffer from some lack of
generalizability as a result of selection and recruit-
ment biases (17). This study is designed with
special attention toward this problem, thus resol-
ving the main source of bias.
Another major problem in clinical samples is
that the more homogeneous the sample is concern-
ing outcome, the more difficult it is to show that
the factor under study actually is a potent risk
factor. Large samples are needed for the statistical
power to detect differences (18, 19).
The dilemma when diagnosing depression or
anxiety disorders in concurrent illness, is the
distinction between symptoms due to psychiatric
or physical diseases. Depressed mood or anhedonia
must be present to diagnose depressive disorder,
and symptoms that are clearly caused by physical
illness should not be counted as diagnostic criteria.
A main characteristic of HADS is that items that
could be caused by physical illness have been
omitted, and the emphasis is on psychological
symptoms of depression and anxiety.
Three issues have been of special interest in the
literature concerning the relation between depres-
sion and thyroid function. One issue is the sig-
nificance of a blunted TSH response to the
thyrotropin-releasing hormone (TRH). Another is
the disturbances of the HPT axis rhythm. A third
issue is the relation between varying grades of
subclinical hypothyroidism and depression. The
literature suggests a relation between thyroid hor-
mone status and neurotransmitter activity (1) and
that thyroid hormones may have important central
nervous system effects, even when euthyroid (3).
A review by Sullivan et al. (20) concluded that
TSH response to TRH was not an impressive
discriminator between depressed and control sub-
jects, and the TSH variable was mainly associated
with treatment response in depressed individuals.
Our study shows that earlier diagnosed thyroid
disorder is associated with both anxiety and depres-
sion, independent of thyroid function, but this
association is weak. The causal relation between
thyroid disease and anxiety and depression remains

32
 An association between depression, anxiety and thyroid function
unclear. The association can be because of specific
conditions in the HPT axis regulation (1, 3, 4). It
can also be part of coping with a chronic medical
condition (21, 22).
Limitations
In former studies on the association between
thyroid dysfunction and mental disorders, both
questionnaires and structured interviews have been
used to measure anxiety and depression. Although
the terms depression and anxiety disorder are used
in this study, they does not refer to clinically
diagnosed disorders, but rather to a range of
symptoms, measured by the use of the HADS.
However, the association between HADS and
clinical diagnosis of anxiety and depression is
strong (14, 16).
We have classified subjects on the basis of a
single basal TSH and T4 assay without the benefit
of repetitive thyroid function tests or knowledge of
clinical course. Abnormal test results alone are not
indicative of a thyroid disorder. In a study by
Lederbogen et al. (23), genuine thyroid disease was
found in slightly less than half of the psychiatric
in-patients with an abnormal value of T4 or TSH.
Both thyroid dysfunction, and anxiety and
depression are defined merely upon screening,
and although sensitivity and specificity of such
techniques are good, the ‘case-finding’ abilities are
not perfect. The result is usually a weakening of the
association, i.e. strengthening of the zero hypothe-
sis. However, because of the large sample size, this
cannot explain the finding. Secondly, the alternat-
ive to screening in populations is usually analysis
from clinical materials, which implies other and
more severe limitations.
Conclusion
In these population-based data, using multivariate
logistic regression analyses, we found no associ-
ation between thyroid dysfunction, including all
degrees of biochemical hypothyroidism and hyper-
thyroidism defined by thyroid blood tests, and the
presence of depression or anxiety disorder defined
by the HADS self-rating scale. The model is
adjusted for age and gender and the analysis is
done both with and without individuals with
former known thyroid disease or dysfunction.
Present biochemical thyroid dysfunction was not
associated with anxiety or depression, but a history
of previously known hypothyroidism and hyper-
thyroidism was significantly associated.
The clinical implication of the findings is that
when depression or anxiety disorders are diagnosed
in patients with thyroid dysfunction, the disorders
must be diagnosed and treated separately. The
relation between thyroid disorder and depression
and anxiety is still unclear, and we also have to
consider that common disorders can coexist by
chance without really influencing each other, or
without any causal or pathogenic effects on each
other.
Acknowledgements
The Nord-Trøndelag Health Study (The HUNT Study) is a
collaboration between the HUNT Research Centre, Faculty of
Medicine, Norwegian University of Science and Technology
(NTNU), Verdal, The National Institute of Public Health, The
National Health Screening Service of Norway and Nord-
Trøndelag County Council.
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