Association between bipolar affective disorder and thyroid dysfunction

Vinay Narasimha Krishna

a
, Ravish Thunga
b
, B. Unnikrishnan
c
, Tanuj Kanchan
d,
*, Mario Joseph Bukelo
e
,
Rajesh Kumar Mehta
f
, Anand Venugopal
g
a
Department of Internal Medicine, Mercy Catholic Medical Center, Philadelphia (Afliated to Drexel University College of Medicine), USA
b
Department of Psychiatry, Kasturba Medical College, Mangalore (Afliated to Manipal University), India
c
Department of Community Medicine, Kasturba Medical College, Mangalore (Afliated to Manipal University), India
d
Department of Forensic Medicine, Kasturba Medical College, Mangalore (Afliated to Manipal University), India
e
Department of Pediatrics, Fr Mullers Medical College, Mangalore, India
f
Department of Neurology and Psychiatry, Saint Louis University School of Medicine, St Louis, MO, USA
g
Department of Radiodiagnosis, Kasturba Medical College, Mangalore (Afliated to Manipal University), India
1. Introduction
The relationship between thyroid dysfunction and psychiatric
illness has interested clinicians since long. In 1888 the Committee
of the Clinical society of London reported on the mental changes
observed in over 100 cases of Myxoedema and noted the general
retardation, sluggishness and slowness of apprehension, which
was associated with insanity in the form of melancholia, chronic
mania and dementia (Asher, 1949). It is now clearer that the
thyroid hormones play a major role in the functioning and
regulation of the neural tissue activity. Hence, it follows that any
derangement in the synthesis, secretion, action and peripheral
metabolism of thyroid hormones affects the normal functioning of
neural tissue, the symptoms of which may manifest as psychiatric
syndromes (Bauer and Whybrow, 2001). Thyroid hormones have
profound effects on mood and behavior, and seem to be able to
modulate the phenotypic expression of major affective illness
(Bauer and Whybrow, 2001). Disturbances of affect and mood,
such as major depression and bipolar affective disorder, are
associated with disturbances of peripheral thyroid hormone
metabolism (Mu ller-Oerlinghausen et al., 2002). This is supported
by the fact that administration of adjunctive supraphysiological
doses of levothyroxine have been found to be an effective
Asian Journal of Psychiatry 6 (2013) 4245
A R T I C L E I N F O
Article history:
Received 16 March 2012
Received in revised form 5 July 2012
Accepted 6 August 2012
Keywords:
Bipolar affective disorder
Thyroid dysfunction
Cross-sectional study
Association
Bipolar Spectrum Diagnostic Scale
A B S T R A C T
Background: Bipolar affective disorder may be associated with alterations in thyroid function. A
comprehensive thyroid assessment is important for assessing clinical and sub-clinical imbalances linked
to a variety of mood disorders like bipolar affective disorder.
Aim: To nd out the association between bipolar affective disorder and thyroid dysfunction.
Materials and method: The present cross-sectional study was conducted at Government District Wenlock
Hospital, Mangalore (GDWH), India. Atotal of 50 newly diagnosed bipolar affective disorder patients and
50 age and sex matched controls without bipolar affective disorder as conrmed by the application of
Bipolar SpectrumDiagnostic Scale were included in the study. Thyroid function was assessed among the
patients and control group to study the association between bipolar affective disorder and thyroid
dysfunction. Odds ratio was calculated to nd out the strength of association between thyroid gland
dysfunction and bipolar affective disorder.
Results: The mean Bipolar Spectrum Diagnostic Scale score among patients diagnosed with bipolar
affective disorder was 20.84 and that of the control group was 1.98. The proportion of thyroid
dysfunction among bipolar affective disorder patients and among control group was 14% and 6%
respectively. The odds ratio was calculated to be 2.55. Mean T3 values were higher in the bipolar affective
disorder patients than the control group and this association was found to be statistically signicant
(p = 0.031). Mean T4 and TSH values were higher among the bipolar affective disorder patients but did
not show any signicant differences when compared with the control group.
Conclusion: The present study concludes that a statistically signicant association exists between
elevated T3 hormone and bipolar affective disorder and observes that the patients with bipolar affective
disorder are 2.55 times more commonly associated with thyroid dysfunction.
2012 Elsevier B.V. All rights reserved.
* Corresponding author. Tel.: +91 9448252394; fax: +91 824 2428183.
E-mail addresses: tanuj.kanchan@manipal.edu, tanujkanchan@yahoo.co.in
(T. Kanchan).
Contents lists available at SciVerse ScienceDirect
Asian Journal of Psychiatry
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1876-2018/$ see front matter 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ajp.2012.08.003
treatment option for refractory bipolar affective disorder (Bauer
et al., 1998; Baumgartner et al., 1994). Sub-clinical hypothyroid-
ism has also been suspected of being a risk factor for depression
(Haggerty et al., 1993; Kraus et al., 1997; Oomen et al., 1996). A
number of studies have investigated the association between
thyroid dysfunction and mood disorders. The investigators in these
studies had observed an altered thyroid function in mood disorder
(Baumgartner et al., 1988; Kraus et al., 1997; Maes et al., 1993;
Poirier et al., 1995). It is evident from earlier studies that there
exists an association between thyroid gland dysfunction and
psychiatric disorders. To the best of our knowledge no previous
study had investigated such an association in the bipolar disorder
psychiatric group.
The manifestations in patients with bipolar affective disorder
are exceptionally diverse ranging from mild hypomania or mild
depression to severe forms of mania or depression accompanied
by profound psychosis. The lifetime prevalence of bipolar
affective disorder is 1.31.6% with mortality rates being 23
times higher than that of the general population. Equally
prevalent among bothsexes (except rapid cycling bipolar disorder
which is more common in females), nearly one third of the
affected patients admit to at least one suicide attempt (Mu ller-
Oerlinghausen et al., 2002). Bipolar affective disorder has been
eating into the vitals of mankind leading to obesity, loss of work
efciency, impairment of mental functions, deteriorating social
relationships and nally deliberate self-harm (Elmslie et al.,
2001). Lewnsohn et al. (2003) found that the onset of bipolar
affective disorder occurred mostly during adolescence and also
pointed out that relatives of bipolar affective disorder adolescents
have elevated rates of sub threshold bipolar disorder and major
depressive disorder. Preventing bipolar affective disorder, thus,
becomes a highpublic healthpriority. It has beensuggestedthat of
all the endocrine systems thought to be linked to the pathophysi-
ology of bipolar affective disorder, the hypothalamicpituitary
thyroid axis is the prime candidate (Mu ller-Oerlinghausen et al.,
2002). Thus, it has been assumed that bipolar affective disorder
may be associated with alterations in thyroid function and hence
the need for a comprehensive thyroid assessment is important for
assessing clinical and sub-clinical imbalances linked to a variety
of mood disorders like bipolar affective disorder (Nath and Sagar,
2001).
The present cross-sectional study is intended to test the
association between thyroid dysfunction and bipolar disorder
spectrum in patients with newly diagnosed bipolar affective
disorder (ICD-10). In the present investigation, the strength
of association would be dened using odds ratio. The degree of
association between the two might help in a better prognosis of
patients with bipolar affective disorder as appropriate treatment
can be administered to both the problems without undermining
the importance of this association.
2. Materials and methods
The present cross-sectional study was conducted at Govern-
ment District Wenlock Hospital, Mangalore (GDWH) which is a
550 bed tertiary care hospital providing comprehensive health
care to the patients of Dakshina Kannada district in Karnataka.
GDWH is also a teaching hospital for Kasturba Medical College
(KMC), Mangalore. The present research included 50 newly
diagnosed bipolar affective disorder patients and 50 age and sex
matched controls without bipolar affective disorder. Institutional
ethical committee approval was taken prior to the study. Informed
consent was obtained from each participant before undertaking
the research.
Bipolar affective disorder patients for this study were
taken from amongst those who attended the psychiatric
outpatient department of GDWH. The clinical diagnosis was
reached by the consultant psychiatrist. The diagnosis was
conrmed by the application of Bipolar Spectrum Diagnostic
Scale (Nassir Ghaemi et al., 2005). The Bipolar Spectrum
Diagnostic Scale (BSDS) developed by Dr. Ronald Pies is a self-
report questionnaire that is found to be highly sensitive and
specic for bipolar spectrum illness (Nassir Ghaemi et al.,
2005) in its original format and even when the local versions of
the BSDS are used (Zaratiegui et al., 2011). With regards to
BSDS score, a total score of 2025 indicates that bipolar
spectrum disorder is highly likely; a score from 13 to 19
indicates moderate probability; a score from 7 to 12 indicates
low probability; and a score from 0 to 6 indicates that bipolar
disorder is highly unlikely. The severity of symptoms in the
present study was measured using Hamilton rating scale for
depression (Hamilton, 1967) and Young mania rating scale
(Young et al., 1978).
All the newly diagnosed bipolar affective disorder (ICD-10)
patients aged between 18 and 50 years without any thyroid
dysfunction clinically and without any prior history of lithium or
thyroid hormone treatment were included in the study and
constituted the bipolar affective disorder group. Control group
consisted of participants aged between 18 and 50 years who
were employed in various industries and did not suffer from
bipolar affective disorder as conrmed by the application of
BSDS. While recruiting participants in the control group
individual matching was done for age and sex, i.e. once the
bipolar affective disorder patients were included in the study,
the corresponding age and sex matched participants were
included in the control group. Thus, a total of 24 males and 26
females were included in each group. Mean age of participants in
both groups was 36.9 years. All participants had at least
completed their high school education and were able to
understand and comprehend English language well. It was
ensured that the participants had no thyroid dysfunction
clinically or any prior history of lithium or thyroid hormone
treatment. Participants who were on steroid treatment, amio-
darone and antihypertensive drug therapy or had taken cough
medicines within last two weeks, or had any contrast medium
during the previous eight months for any investigation were
excluded from the study.
For assessment of thyroid function, blood samples were
collected fromthe cases and controls and analyzed for T3, T4 and
TSH levels using ECLIA electrochemiluminescence immunoas-
say. The normal ranges for thyroid hormones as indicated in the
assessment kit was were 0.62.02 ng/mL, 5.1314.06 mg/dL, and
0.275.5 mIU/mL for T3, T4 and TSH respectively. Presence of a
genuine thyroid dysfunction was in accordance with dened
biochemical parameters. Participants having T3 > 2.02 ng/mL,
T4 > 14.06 mg/dL and TSH < 0.27 mIU/mL were considered
hyperthyroid while participants with T3 < 0.6 ng/mL,
T4 < 5.13 mg/dL and TSH > 5.5 mIU/mL were considered hypo-
thyroid.
The details of all participants in both groups were collected
using a pretested proforma that was lled by interviewing the
participants. The proforma contained patients individual infor-
mation, personal history, family history, childhood experiences,
investigation reports, BSDS score, Young mania rating scale score
and Hamilton rating scale for depression score.
The data collected was analyzed statistically using SPSS
(Statistical Package for Social Sciences) computer software version
11.0. Students t-test was done to compare mean values of thyroid
hormone levels among cases and controls. A p-value of <0.05 was
considered as signicant. Odds ratio was calculated to nd out the
strength of association between thyroid gland dysfunction and
bipolar affective disorder.
V.N. Krishna et al. / Asian Journal of Psychiatry 6 (2013) 4245 43
3. Results
The mean BSDS score among patients diagnosed with
bipolar affective disorder was 20.84 3.15 (high probability
of having bipolar affective disorder) while the score among the
control group was 1.98 2.14 (highly unlikely to have bipolar
affective disorder).
Among the 50 patients diagnosed with bipolar affective
disorder, seven cases had genuine thyroid dysfunction (six
hyperthyroid and one hypothyroid) while the others (n = 43)
had a normal thyroid function status. Three participants in the
control group had thyroid dysfunction (all hyperthyroid status)
while others (n = 47) had a normally functioning thyroid gland.
Thus the proportion of thyroid dysfunction among bipolar affective
disorder patients and among controls was 14% and 6% respectively.
The odds ratio was calculated to be 2.55.
It is observed that the mean T3 values were higher in the bipolar
affective disorder patients when compared to the control group.
This association was found to be statistically signicant (p = 0.031).
Mean T4 and TSH values were higher among the patients
diagnosed with bipolar affective disorder than the control group.
The difference between the two groups however, was not
statistically signicant. Thyroid status among bipolar affective
disorder and control group is shown in Table 1.
All the six bipolar affective disorder patients with hyperthy-
roidism were diagnosed as having a current episode of mania. This
diagnosis was associated with high Youngs mania rating scale
score and low scores on Hamiltons rating scale for depression.
The other patient with hypothyroidism was associated with the
diagnosis of a current episode of depression. The severity of the
patients depressive symptoms was reected by a high Hamilton
rating scale for depression score.
4. Discussion
Spratt et al. (1982) reported hyperthyroxinemia in acute
psychiatric disorders like schizophrenia, functional psychosis,
major affective disorder and personality disorders. Variations in
thyroid hormone have been reported in the depressive
psychiatric group by various authors (Bauer et al., 1994;
Baumgartner et al., 1992; Bottai et al., 1991; Garbutt et al.,
1986; Saxena et al., 2000; Wahby et al., 1989). All these studies
have shown a variable T4 and TSH levels but consistently low
levels of T3 in patients of depression. Baumgartner et al. (1992)
observed slightly higher levels of T4 and lower T3 and TSH
levels, while Bauer et al. (1994) and Saxena et al. (2000) found
lower T3, T4 and TSH levels in patients of depression. Garbutt et
al. (1986) reported higher levels of T4, Bottai et al. (1991) lower
levels of T3 and Wahby et al. (1989) found lower levels of T3
and raised TSH levels in patients of depression. Boral et al.
studied T3, T4 and TSH levels in cases of depression, mania and
schizophrenia individually and compared the thyroid levels with
corresponding values estimated in normal control group that
were matched for age, sex and socio economic status. The results
showed that depressives and schizophrenics had sub clinical
hypothyroidism while the maniacs showed slightly higher
values for T3 and T4 when compared to control group (Boral
et al., 1980). Most of all the studies report variations in the
thyroid prole levels within the normal biochemical range when
comparisons were made between psychiatric diagnostic groups
and control groups. These variations are only relative and do not
signify a clinically established thyroid dysfunction as reected
by the biochemical parameters.
The present study observes that the patients with bipolar
affective disorder are at 2.55 times more risk of having an
associated thyroid dysfunction when compared to the general
population as represented by the control group. The proportion
of thyroid dysfunction among patients with bipolar affective
disorder (14%) was more than double of that observed in the
control group (6%). It is observed that six out of the seven bipolar
disorder patients who suffered from thyroid dysfunction had
elevated T3 levels and normal T4, and TSH levels. It is noteworthy
that the hyperthyroid state had resulted due to elevated T3
hormones in the background of normal T4 and TSH. This probably
suggests an increased rate of peripheral generation of T3 from T4
or an increase in the primary synthesis and release of T3 from the
thyroid gland. The other thyroid dysfunction patient had
elevated TSH levels and normal T3, T4 levels. All the six bipolar
affective disorder patients with elevated T3 levels were diag-
nosed of having a current episode of mania while the other
patient with elevated TSH levels was associated with the
diagnosis of a current episode of depression. The results are in
coherence with the peripheral actions of T3 and T4. It is well
documented that an increase in peripheral T3 hormone levels is
associated with elevated mood and/or irritability, distractibility,
increased physical activity and such other symptoms which are
constituent symptoms of maniac phase of bipolar disorder.
Hence, it can be inferred here that the symptoms demonstrated
by bipolar affective disorder patients in their manic phase could
have resulted due to elevated T3 hormone levels. This was
conrmed when an association between elevated T3 levels and
diagnosis of bipolar affective disorder was found to be statisti-
cally signicant (p = 0.031). The same could not be demonstrated
with levels of T4 and TSH. A similar association between mania
and hyperthyroid state was reported by Boral et al. (1980) who
observed elevated T3 levels in mania patients. It is possible that
the symptoms in the bipolar affective disorder patient with a
current episode of depression could have been due to elevated
TSH serum levels but such an association was not found to be
statistically signicant. The T3 and T4 hormone levels in this
patient were within normal ranges. Saxena et al. (2000) and
Boral et al. (1980) in their studies had found a signicant
association between depressive psychiatric groups and biochem-
ical hypothyroidism as demonstrated by low T3 and T4 with
normal TSH levels. The observation that can be drawn here is that
a statistically signicant association exists between psychiatric
diagnostic groups and thyroid dysfunction whenever the
dysfunction is due to variations in T3 and T4 hormones, and
that the same ceases to exist when the dysfunction is due to
variations in TSH. This indicates that T3 and T4 (mainly T3 which
is the most active form) plays an important role in psychiatric
disorders.
Table 1
Thyroid prole among bipolar affective disorder and control group.
Thyroid prole BAD group (n = 50) (Mean S.D.) Control group (n = 50) (Mean S.D.) t-Value p-Value
T3 (ng/dL) 138.84 26.43 121.30 30.86 2.182 0.031
*
T4 (mg/dL) 7.36 1.56 7.34 1.62 0.083 0.934
TSH (mIU/mL) 3.11 2.11 2.75 2.34 0.659 0.512
BAD, bipolar affective disorder; S.D., standard deviation.
*
p < 0.05.
V.N. Krishna et al. / Asian Journal of Psychiatry 6 (2013) 4245 44
5. Limitations of the study
Co-morbid conditions in patients as well as in controls have not
been ruled out using a standardized instrument such as the MINI.
6. Conclusion
The present study that was taken up to nd out the association
between bipolar affective disorder and thyroid dysfunction reveals
that:
1. A statistically signicant association exists between levels of T3
hormone and bipolar affective disorder.
2. An odds ratio of 2.55 signies that patients with bipolar affective
disorder are 2.55 times more commonly associated with thyroid
dysfunction than the control group.
3. A proportion of thyroid dysfunction in bipolar affective disorder
patients was 14% against 6% observed in the control group.
The present research suggests that the bipolar affective disorder
patients do have a demonstrable change in their thyroid function.
Therefore, evaluation of thyroid status prior to beginning
treatment using mood stabilizing drugs in thyroid dysfunction is
suggested. Correction of the underlying thyroid dysfunction may
probably lead to the remission of signs and symptoms observed in
bipolar affective disorder patients, and a better prognosis. A
positive response to an adjunct thyroid hormone replacement
therapy would further suggest that bipolar affective disorder is to a
large extent affected by thyroid hormone dysfunction.
It needs to be emphasized that elevated T3/T4 serum values
does not necessarily mean that free T4/free T3 is also high.
Measurements of free T3 and free T4 have always been better
indicators of thyroid function. It is free T3 and free T4 that nally
execute the peripheral actions and not the bound forms. Hence, it is
felt that the association be veried by measuring free T3 and free
T4 serum levels in future studies. The results obtained here suggest
new scope for the use of thyroid hormones in the treatment of
bipolar affective disorder patients. The potential of such treatment
options needs to be explored.
Funding source
The present research was taken up as an Indian Council of
Medical Research (ICMR) (STS-2006) project. The project was
approved and supported by the ICMR in the year 2006 as a
Short Term Student (STS) project. The ICMR provided the
nancial support required for the investigations conducted in
the project.
Authors contributions
VNK conceived and designed the study, collected data and
drafted the paper. He will act as the guarantor of the study. RT
conceived the study and helped in manuscript writing. TK
analyzed and interpreted the data. TK revised the manuscript for
important intellectual content. BU also designed the study, and
helped in analysis of the results. MJB, RKM and AV assisted in
manuscript writing. The nal manuscript was approved by all
authors.
Conict of interest
The authors have no conict of interest to declare.
Acknowledgments
We wish to acknowledge ICMR for their support and thank the
participants of the study without whom the study would not have
been accomplished.
References
Asher, R., 1949. Myxoedematous madness. British Medical Journal 2, 555562.
Bauer, M., Priebe, S., Ku rten, I., Gra f, K.J., Baumgartner, A., 1994. Psychological and
endocrine abnormalities in refugees from East Germany: Part I. Prolonged
stress, psychopathology, and hypothalamicpituitarythyroid axis activity.
Psychiatry Research 51, 6173.
Bauer, M., Hellweg, R., Gra f, K.J., Baumgartner, A., 1998. Treatment of refractory
depression with high-dose thyroxine. Neuropsychopharmacology 18, 444455.
Bauer, M., Whybrow, P.C., 2001. Thyroid hormone, neural tissue and mood modu-
lation. World Journal of Biological Psychiatry 2, 5969.
Baumgartner, A., Gra f, K.J., Ku rten, I., Meinhold, H., 1988. The hypothalamic
pituitarythyroid axis in psychiatric patients and healthy subjects: parts 1
4. Psychiatry Research 24, 271332.
Baumgartner, A., Campos-Barros, A., Meinhold, H., 1992. Thyroid hormones and
depressive illness: implications for clinical and basic research. Acta Medica
Austriaca 19, 98102.
Baumgartner, A., Bauer, M., Hellweg, R., 1994. Treatment of intractable non-rapid
cycling bipolar affective disorder with high-dose thyroxine: an open clinical
trial. Neuropsychopharmacology 10, 183189.
Boral, G.C., Gosh, A.B., Pal, S.K., Gosh, K.K., Nandi, D.N., 1980. Thyroid function in
different psychiatric disorders. Indian Journal of Psychiatry 22, 200202.
Bottai, T., Levy, C., Lancon, C., Azorin, J.M., Grignon, S., Valli, M., Jadot, G., Tissot, R.,
1991. Plasma MHPG, peripheral noradrenergic marker and hormonal plasma
levels of cortisol-T3-T4-TSH in depressive syndromes. Encephale 17, 203221
(Abstract).
Elmslie, J.L., Mann, J.I., Silverstone, J.T., Williams, S.M., Romans, S.E., 2001. Deter-
minants of overweight and obesity in patients with bipolar disorder. Journal of
Clinical Psychiatry 62, 486491.
Garbutt, J.C., Loosen, P.T., Blacharsh, J., Prange Jr., A.J., 1986. The prolactin response
to thyrotropin-releasing hormone in depressed patients and normal subjects.
Psyhoneuroendocrinology 11, 213219.
Haggerty Jr., J.J., Stern, R.A., Mason, G.A., Beckwith, J., Morey, C.E., Prange Jr., A.J.,
1993. Subclinical hypothyroidism: a modiable risk factor for depression?
American Journal of Psychiatry 150, 508510.
Hamilton, M., 1967. Development of a rating scale for primary depressive illness.
British Journal of Social and Clinical Psychology 6, 278296.
Kraus, R.P., Phoenix, E., Edmonds, M.W., Nicholson, I.R., Chandarana, P.C., Tokma-
kejian, S., 1997. Exaggerated TSH responses to TRH in depressed patients with
normal baseline TSH. Journal of Clinical Psychiatry 58, 266270.
Lewnsohn, P.M., Seeley, J.R., Klein, D.N., 2003. Bipolar disorders during adolescence.
Acta Psychiatrica Scandinavica. Supplementum 418, 4750.
Maes, M., Meltzer, H.Y., Cosyns, P., Suy, E., Schotte, C., 1993. An evaluation of basal
hypothalamicpituitarythyroid axis function in depression: results of large-
scaled and controlled study. Psyconeuroendocrinology 18, 607620.
Mu ller-Oerlinghausen, B., Bergho fer, A., Bauer, M., 2002. Bipolar disorder. Lancet
359, 241247.
Nassir Ghaemi, S., Miller, C.J., Berv, D.A., Klugman, J., Rosenquist, K.J., Pies, R.W.,
2005. Sensitivity and specicity of a new bipolar spectrum diagnostic scale.
Journal of Affective Disorders 84, 273277.
Nath, J., Sagar, R., 2001. Late-onset bipolar disorder due to hyperthyroidism. Acta
Psychiatrica Scandinavica 104, 7275.
Oomen, H.A., Schipperijn, A.J., Drexhage, H.A., 1996. The prevalence of affective
disorder and in particular of a rapid cycling of bipolar disorder in patients with
abnormal thyroid function tests. Clinical Endocrinology 45, 215223.
Poirier, M.F., Loo, H., Galinowski, A., Bourdel, M.C., Re mi-Bouissie` re, P., Piketty, M.L.,
Vanelle, J.M., 1995. Sensitive assay of thyroid stimulating hormone in depressed
patients. Psychiatry Research 57, 4148.
Saxena, J., Singh, P.N., Srivastava, U., Siddiqui, A.Q., 2000. A study of thyroid
hormones (T
3
, T
4
& TSH) in patients of depression. Indian Journal of Psychiatry
42, 243246.
Spratt, D.I., Pont, A., Miller, M.B., McDougall, I.R., Bayer, M.F., McLaughlin, W.T.,
1982. Hyperthyroxinemia in patients with acute psychiatric disorders. Ameri-
can Journal of Medicine 73, 4148.
Wahby, V., Ibrahim, G., Friedenthal, S., Giller, E., Kosten, T., Mason, J., 1989. Serum
concentrations of circulating thyroid hormones in a group of depressed men.
Neuropsychobiology 22, 810.
Young, R.C., Biggs, J.T., Ziegler, V.E., Meyer, D.A., 1978. A rating scale for mania:
reliability, validity and sensitivity. British Journal of Psychiatry 133, 429435.
Zaratiegui, R.M., Va zquez, G.H., Lorenzo, L.S., Marinelli, M., Aguayo, S., Strejilevich,
S.A., Padilla, E., Goldchluk, A., Herbst, L., Vilaprino, J.J., Bonetto, G.G., Cetkovich-
Bakmas, M.G., Abraham, E., Kahn, C., Whitham, E.A., Holtzman, N.S., Ghaemi, N.,
2011. Sensitivity and specicity of the mood disorder questionnaire and the
bipolar spectrum diagnostic scale in Argentinean patients with mood disorders.
Journal of Affective Disorders 132, 445449.
V.N. Krishna et al. / Asian Journal of Psychiatry 6 (2013) 4245 45