BJD

S Y S TE M A T IC R E V IE W British Journal of Dermatology

Vitiligo and depression: a systematic review and

meta-analysis of observational studies
Y.C. Lai,1 Y.W. Yew,2 C. Kennedy3 and R.A. Schwartz1,4
Rutgers New Jersey Medical School, Departments of 1Dermatology and 3Psychiatry, Newark, NJ, U.S.A.
2
National Skin Centre, Singapore
4
Rutgers University School of Public Affairs and Administration, Newark, NJ, U.S.A.

Linked Comment: Sharma and Bhatia. Br J Dermatol 2017; 177:612–613

Summary

Correspondence Vitiligo is a common depigmenting disorder with profound psychosocial

Robert A. Schwartz. impacts. Previous observational studies have suggested a link between vitiligo
E-mail: roschwar@cal.berkeley.edu
and psychiatric morbidity, such as depression. However, variability in study
Accepted for publication design makes it difficult to quantify accurately the relationship between vitiligo
9 November 2016 and depression. We aimed to investigate the underlying prevalence and risk of
depression among patients with vitiligo. A comprehensive search of MEDLINE,
Funding sources Embase and the Cochrane Library was conducted. Cross-sectional, case–control or
None. cohort studies that assessed the prevalence of depression among patients with
vitiligo or the relationship between vitiligo and depression were included.
Conflicts of interest
None declared.
DerSimonian and Laird random-effects models were utilized to calculate the
pooled prevalence and relative risks. Publication bias was evaluated by funnel
DOI 10.1111/bjd.15199 plots and Egger’s tests. Twenty-five studies with 2708 cases of vitiligo were
included. Based on diagnostic codes, the pooled prevalence of depression among
patients with vitiligo was 0
253 [95% confidence interval (CI) 0
16–0
34;
P < 0
001)]. Using self-reported questionnaires, the pooled prevalence of depres-
sive symptoms was 0
336 (95% CI 0
25–0
42; P < 0
001). The pooled odds
ratio of depression among patients with vitiligo was 5
05 vs. controls (95% CI
2
21–11
51; P < 0
001). Moderate-to-high heterogeneity was observed between
the studies. Patients with vitiligo were significantly more likely to suffer from
depression. Clinical depression or depressive symptoms can be prevalent, with
the actual prevalence differing depending on screening instruments or, possibly,
geographical regions. Clinicians should actively evaluate patients with vitiligo for
signs/symptoms of depression and provide appropriate referrals to manage their
psychiatric symptoms accordingly.

What’s already known about this topic?

• Vitiligo can have profound psychosocial impacts and impair patients’ quality of life.
• Studies have suggested a relationship between vitiligo and depression.

What does this study add?

• Patients with vitiligo were significantly more likely to suffer from depression than
controls.
• The pooled prevalence and risk of depression vary depending on screening instru-
ments or, possibly, geographical regions.

708 British Journal of Dermatology (2017) 177, pp708–718 © 2017 British Association of Dermatologists

Vitiligo is a common depigmenting disorder that affects
approximately 0
5–2% of the population worldwide.1 It is
characterized by partial or complete absence of functioning
melanocytes,2,3 resulting in the development of white macules
or patches on various parts of the body. Owing to the cos-
metic disfigurement associated with it, vitiligo is known to
have profound psychosocial impacts.4 Vitiligo, as a result of
its visibility and chronicity, may cause a significant burden on
patients’ health-related quality of life.5 In addition, patients
with vitiligo may experience stigmatization and embarrass-
ment as a result of their physical appearance, leading to poor
body image, low self-esteem, social isolation and, ultimately,
depression.6,7
Multiple observational studies have suggested an epidemio-
logical link between vitiligo and psychiatric morbidity such as
depression.8–10 However, other studies have failed to establish
such a relationship.11,12 While most studies evaluated depres-
sive symptoms using validated psychometric tests, a few
defined depression clinically based on the criteria outlined in
the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition
(DSM-IV). Various screening inventory and rating scales for
depression were also utilized in different studies. In addition,
even among the studies that administered the same question-
naire, different cut-offs may sometimes be used. This variabil-
ity in study design makes it difficult to assess the relationship
between vitiligo and depression. Moreover, the prevalence of
depression among patients with vitiligo varies considerably
across studies, ranging from 10% to almost 60% depending
on study population, sample size and outcome measures.13,14
We therefore aimed to evaluate the underlying prevalence
and risk of depression among patients with vitiligo by con-
ducting a systematic review and meta-analysis of published
studies.
Materials and methods
The systematic review and meta-analysis was done in accor-
dance with the Preferred Reporting Items for Systematic
Reviews and Meta-Analyses (PRISMA) statement.15 A system-
atic and quantitative synthesis of all studies that evaluated the
relationship between vitiligo and depression was planned a
priori.
Search strategy
A comprehensive database search was performed indepen-
dently by using MEDLINE, Embase and the Cochrane Library.
The following search criteria were used: [“Vitiligo” (medical
subject heading; MeSH)] AND [“Depression” (MeSH) OR
“Depressive Disorder” (MeSH) OR Depress* (title/abstract;
TIAB) OR Antidepress* (TIAB)]. The search was limited to
English-language studies published from inception to 31
December 2015. All abstracts were evaluated based on the
inclusion criteria to determine eligibility for meta-analysis.
Additional studies were identified from manual searches of
references in retrieved articles.
© 2017 British Association of Dermatologists
Vitiligo and depression, Y.C. Lai et al. 709
Article selection
The following inclusion criteria were used to select original
studies for the analysis: cross-sectional, case–control or cohort
study design; analysis of the association between vitiligo and
depression or impaired general health; availability of a control
group (without vitiligo or other pigmentations disorders for
comparison). Prevalence of depression and total number of
cases needed to be reported from each study in order to
derive the standard errors (SEs). Studies needed to report suffi-
cient information, such as odds ratio (OR) and 95% confi-
dence interval (CI), so that the corresponding SEs could be
calculated. Where such information was not readily available,
crude data with the number of cases in exposed and unex-
posed groups should have been reported. Two reviewers
(Y.C.L and Y.W.Y) independently reviewed the titles and
abstracts of these articles. Based on the inclusion criteria and
information from abstract, articles were identified for full-text
review. Reviewers independently evaluated the full-text articles
to determine their eligibility for inclusion in our analysis. Any
disagreements were resolved by consensus.
Data extraction
Reviewers independently extracted the data from studies with
a standardized data extraction form. Relevant information
extracted included the study year, country of study, study
design, mean age, exposure and outcome assessment, number
of cases and controls, baseline proportions of subjects with
depression or mean values according to questionnaires. Cases
of vitiligo were identified via either a clinical diagnosis by a
physician or a self-report of a prior diagnosis. Depression was
assessed using different methods, including clinical diagnosis
by a physician, DSM-IV diagnostic criteria, and various vali-
dated screening inventory and rating scales for depressive
symptoms, such as Beck Depression Inventory (BDI), Center
for Epidemiologic Studies Depression Scale (CES-D), Emotional
State Questionnaire (ES-Q), Hospital Anxiety and Depression
Scale (HADS) and Hamilton Depression Rating Scale (HDRS),
Montgomery–
Asberg Depression Rating Scale (MADRS). Stud-
ies that used General Health Questionnaire (GHQ) were also
included to evaluate the general health of patients with viti-
ligo. Study quality was assessed according to the Newcastle–
Ottawa Scale (NOS), which was designed for nonrandomized
studies in meta-analysis.16 Studies that achieve ≥ 7 stars on
NOS were considered high quality, 4–6 stars indicated med-
ium-quality studies and < 4 stars indicated poor-quality stud-
ies.17
Meta-analysis
In both controlled and uncontrolled studies, pooled prevalence
of depression according to validated questionnaires or clinical
depression based on DSM-IV criteria was calculated. As few
studies provided 95% CIs for prevalence, the SE was calculated
by assuming prevalence as a Bernoulli random variable, p,
British Journal of Dermatology (2017) 177, pp708–718
710 Vitiligo and depression, Y.C. Lai et al.
Fig 1. Study selection flow diagram.
with variance equal to p(1–p).18 In controlled studies, mean
questionnaire values were compared between cases and con-
trols to calculate standardized mean difference (SMD) and cor-
responding 95% CI. ORs and 95% CIs of depression between
cases and controls were obtained from the crude data. To esti-
mate the summary prevalence, SMD and pooled OR, the ran-
dom-effects model of DerSimonian and Laird was used to
account for variance between and within the studies.19
Heterogeneity between studies was assessed using v2-test and
the I2 statistic, with values of 25%, 50% and 75% considered
as low, moderate and high heterogeneity, respectively.20 To
assess qualitatively publication bias, a funnel plot was con-
structed and visually inspected for any asymmetry. Egger’s
test, which evaluated small study effects, was utilized to assess
British Journal of Dermatology (2017) 177, pp708–718
quantitatively the asymmetry of the funnel plot.21 To explore
potential sources of study heterogeneity, meta-regression with
prespecified variables, including study country, study design
and study quality, was conducted. All analyses were performed
using STATA version 12
0 (Stata Corp., College Station, TX,
U.S.A.).
Results
Search results
A search using MEDLINE and Embase yielded a total of 270
articles (Fig. 1). No studies were identified from the Cochrane
Library database. A total of 129 duplicates were removed from
© 2017 British Association of Dermatologists

further evaluation. After examining the titles and abstracts of
the remaining 141 articles, 46 studies were selected, based on
the prescribed inclusion criteria. After reviewing the selected
articles in full, 21 studies were excluded for the following rea-
sons: review articles (n = 7); irrelevant outcome (n = 8);
insufficient information (n = 6). After these exclusions, 25
studies with 2708 cases of vitiligo were included in the meta-
analysis. The prevalence of depression was assessed based on
the following methods: self-reported questionnaires, and
International Classification of Diseases (ICD) and DSM-IV diag-
nosis. The prevalence of impaired general health was evaluated
using the GHQ. There were 14 cross-sectional studies that
reported prevalence of depression or impaired general health
and mean questionnaire values. Among 11 case–control stud-
ies that provided the aforementioned data, six also reported
on the odds of depression between patients with vitiligo and
healthy controls. Separate meta-analyses were performed for
ORs, SMD and prevalence of depression based on method of
diagnosis.
Description of included studies
Eleven studies utilized a case–control study design, while 14
studies employed a cross-sectional study design. There were
nine studies conducted in Europe, 13 in Asia and the remain-
ing three were from Africa. Table 1 summarizes the general
characteristics of each study.22–40 Most studies had cases of
vitiligo confirmed clinically by a dermatologist, whereas two
studies identified cases via self-reported diagnosis by a physi-
cian. Cases and controls were assessed for depression or
depressive symptoms based on either clinical diagnosis by a
psychiatrist (n = 1) or validated rating scales, including BDI
(n = 4), CES-D (n = 3), HADS (n = 2), HDRS (n = 5),
MADRS (n = 2) and ES-Q (n = 1), whereas their general
health was assessed by GHQ (n = 7). Based on NOS, only one
study was designated as high quality. Most studies (n = 13)
were designated as medium quality.
Prevalence of clinical depression
Among studies reporting the prevalence of depression based
on ICD codes, the pooled prevalence of depression among
patients with vitiligo was 0
25 (95% CI 0
16–0
34;
P < 0
001) (Fig. 2a). This amounted to 62 cases out of 236
patients with vitiligo. There was moderate heterogeneity
between the studies (I2 = 58
1%; P = 0
092). Using DSM-IV
criteria, the pooled prevalence decreased to 0
12 (95% CI
0
05–0
20; P = 0
002) with no heterogeneity between the
studies (Fig. 2b).
Prevalence of depressive symptoms
When the studies assessed the prevalence of depressive symp-
toms among patients with vitiligo based on self-reported ques-
tionnaires,12,25,30,32,34,35,37,38 the pooled prevalence of
depressive symptoms was 0
34 (95% CI 0
25–0
42;
© 2017 British Association of Dermatologists
Vitiligo and depression, Y.C. Lai et al. 711
P < 0
001) (Fig. 2c). This amounted to 350 cases out of
1080 patients with vitiligo. There was high heterogeneity
between the studies (I2 = 90
9%; P < 0
001). The pooled
prevalence of impaired general health among patients with
vitiligo based on GHQ was 0
34 (95% CI 0
29–0
38;
P < 0
001) (Fig. 2d).8–10,13,26,28,29 This amounted to 440
cases out of 1300 patients with vitiligo. There was moderate
heterogeneity between the studies (I2 = 52
5%; P = 0
049).
Table 2 summarizes the prevalence of depression and
impaired general health reported in each study.
Mean scores on depressive symptoms rating scales
The pooled estimate of GHQ, HADS, HDRS, MADRS and BDI
means among patients with vitiligo were 11
2 (95% CI
7
64–14
80), 8
48 (95% CI 6
31–10
66), 7
93 (95%
CI 6
90–8
96), 14
1 (95% CI 4
14–24
13) and 13
5 (95% CI
8
91–18
10), respectively. All subgroup meta-analyses had
high heterogeneity between the studies, with I2 statistics rang-
ing from 78
0% to 98
1%.
Odds ratio and standardized mean difference of
depression between patients with vitiligo and controls
The pooled OR of depression among patients with vitiligo
was 5
05 (95% CI 2
21–11
51; P < 0
001) (Fig. 3). There
was high heterogeneity between the studies (I2 = 74
2%;
P = 0
002). The funnel plot did not suggest any publication
bias (Fig. 4). Formal testing with Egger’s test also provided
no evidence for small-study effect (P = 0
896). After exclud-
ing the study that evaluated the risk of depression between
patients with vitiligo and oculocutaneous albinism (OCA)
from the analysis,37 the pooled OR became higher (5
64, 95%
CI 1
98–16
03; P = 0
001). Table 3 summarizes the ORs of
depression.
The pooled SMD for studies reporting mean questionnaire
values was 7
58 (95% CI 2
26–12
89; P = 0
005) (Fig. 5).
There was high heterogeneity between the studies
(I2 = 99
6%; P < 0
001). The funnel plot showed a lack of
small size studies with negative association, suggesting a prob-
able publication bias (Fig. 6). Formal testing with Egger’s test
failed to provide any evidence for small-study effect
(P = 0
079). Table 4 summarizes the mean questionnaire
score and standardized mean difference.
Meta-regression
Given the high heterogeneity between the studies, meta-
regression was performed to evaluate possible confounding
factors that may influence the prevalence of depressive
symptoms.
A meta-regression was performed on 17 prevalence studies
that reported a mean age to evaluate the pooled effect of age
on the prevalence of depressive symptoms. For every 10-year
increase in age, there was a slight decrease in the prevalence
of depressive symptoms (0
009); however, this was not
British Journal of Dermatology (2017) 177, pp708–718
 Table 1 Characteristics of included studies on vitiligo and depression

Mean age Screening instruments

Reference Type of study Country Setting n (years) Diagnosis of vitiligo for depression (cut-off) NOS score
Ahmed et al. (2007)26 Cross-sectional Pakistan Tertiary outpatient dermatology clinic 100 24
6 Dermatologist GHQ-12 and ICD 3
Ajose et al. (2014)37 Prospective Nigeria Tertiary outpatient dermatology clinic 102 35
9 Dermatologist HADS (8) 6
case–control
Arycan et al. (2008)27 Cross-sectional Turkey Tertiary outpatient dermatology clinic 113 29
2 (male); Dermatologist ICD 3
33
4 (female)
Balaban et al. (2011)31 Case–control Turkey Tertiary outpatient dermatology clinic 42 39
7 Dermatologist DSM-IV and HADS (8) 4
Chan et al. (2013)34 Cross-sectional Singapore Tertiary outpatient dermatology clinic 222 48
4 Dermatologist CES-D (16) 4
712 Vitiligo and depression, Y.C. Lai et al.

Choi et al. (2010)30 Cross-sectional Korea Primary outpatient dermatology clinic 57 15
4 Dermatologist CES-D (16) 4
Esfandiar et al. (2003)23 Cross-sectional Iran Tertiary outpatient dermatology clinic 120 38
4 Dermatologist HDRS (7) 2
Ghajarzadeh et al. (2012)33 Cross-sectional Iran Tertiary outpatient dermatology clinic 100 28
9 Dermatologist BDI (10) 4

British Journal of Dermatology (2017) 177, pp708–718

Karelson et al. (2013)35 Case–control Estonia Tertiary outpatient dermatology clinic 54 36
6 Dermatologist ES-Q (12) 5
Kent and al-Abadie M (1996)6 Cross-sectional UK Questionnaire enclosed in the U.K. Vitiligo 614 46
6 Self-report of GHQ-12 4
Society’s newsletter physician diagnosis
Kr€
uger and Schallreuter (2015)12 Case–control Germany Specialized pigmentary disorder clinic 96 41
7 Dermatologist BDI (10) 5
Maleki et al. (2005)24 Case–control Iran Tertiary outpatient dermatology clinic 52 NR Dermatologist HDRS (7) 2
Mattoo et al. (2001)22 Case–control India Tertiary outpatient dermatology clinic 113 30
11 Dermatologist GHQ-12 and ICD 7
Mechri et al. (2006)25 Case–control Tunisia Tertiary outpatient dermatology clinic 60 38
9 Dermatologist MADRS (15) 5
Noh et al. (2013)36 Case–control Korea Tertiary outpatient dermatology clinic 60 35
1 Dermatologist BDI (10) 5
Osman et al. (2009)29 Cross-sectional Sudan Tertiary outpatient dermatology clinic 111 NR Dermatologist GHQ-12 3
Picardi et al. (2000)9 Cross-sectional Italy Tertiary outpatient dermatology clinic 32 NR Dermatologist GHQ-12 2
Ramakrishna and Rajni (2014)38 Cross-sectional India Tertiary outpatient dermatology clinic 53 NR Dermatologist HDRS (7) 2
Saleki and Yazdanfar (2015)40 Case–control Iran Tertiary outpatient dermatology clinic 110 43
8 Dermatologist HDRS (7) 6
Sampogna et al. (2008)28 Cross-sectional Italy Specialized vitiligo clinic 181 35 Dermatologist GHQ-12 3
Sangma et al. (2015)14 Case–control India Tertiary outpatient dermatology clinic 100 29
7 Dermatologist HDRS (7) 5
Shah et al. (2014)39 Cross-sectional U.K. Online questionnaire via U.K. Vitiligo 75 NR Self-report of HADS (8) 3
Society’s website and newsletter physician diagnosis
Sharma et al. (2001)13 Cross-sectional India Tertiary outpatient dermatology clinic 30 NR Dermatologist GHQ-H (score of 3
15 or more) and DSM-IV
Yamamoto et al. (2011)32 Cross-sectional Japan Tertiary outpatient dermatology clinic 54 NR Dermatologist CES-D (16) 2
Yanik et al. (2014)11 Case–control Turkey Tertiary outpatient dermatology clinic 57 43
63 Dermatologist BDI (10) 6

NOS, Newcastle–Ottawa Scale; GHQ-12, General Health Questionnaire; ICD, International Classification of Diseases; HADS, Hospital Anxiety and Depression Scale; DSM-IV, Diagnostic and Statistical Manual
of Mental Disorders, 4th Edition; CES-D, Center for Epidemiologic Studies Depression Scale; HDRS, Hamilton Depression Rating Scale; BDI, Beck Depression Inventory; ES-Q, Emotional State Questionnaires;
NR, not reported; MADRS, Montgomery–
Asberg Depression Rating Scale.

© 2017 British Association of Dermatologists

 Vitiligo and depression, Y.C. Lai et al. 713

(a) (b)

(c) (d)

Fig 2. Forest plots: prevalence of clinical depression among patients with vitiligo using: (a) International Classification of Diseases codes; and (b)
Diagnostic and Statistical Manual of Mental Disorders, 4th Edition criteria. (c) Prevalence of depressive symptoms among patients with vitiligo according to
questionnaires; and (d) prevalence of impaired general health among patients with vitiligo. The size of the square is proportional to study-specific
statistical weights, horizontal lines represent 95% confidence interval (CI) and diamonds represent summary measures of prevalence. SE, standard
error.

statistically significant (P = 0
804). Another meta-regression
was performed on five case–control studies that reported ORs
to evaluate the pooled effect of age on the risk of depressive
symptoms. For every 10-year increase in age, there was some
reduction in the risk of depressive symptoms (0
297); how-
ever, this was not statistically significant (P = 0
304).
Although two studies reported that females are more likely
to be associated with depression than males,4,24 most studies
did not report any significant effect of sex on depression in
vitiligo.
The pooled prevalence of impaired general health was inde-
pendent of the study design (P = 0
975), study quality
(P = 0
450) and region where the study was conducted
(P = 0
706). The pooled prevalence of depressive symptoms
according to questionnaire scales was independent of study
design (case–control vs. cross-sectional; P = 0
959). Although
the prevalence from the European studies was 0
24 (95% CI
0
17–0
31) vs. 0
33 (95% CI 0
20–0
46) from studies con-
ducted in regions such as Asia, Africa and the Middle East, this
difference was not statistically significant (P = 0
520).
The pooled OR of depression was 1
35 (95% CI 0
56–
3
25) for European studies vs. 7
93 (95% CI 3
62–17
37) for
studies conducted in other countries; however, the result was
not statistically significant (P = 0
088).
The pooled prevalence of depression was 0
30 (95% CI
0
24–0
37) for low-quality studies, whereas the pooled
prevalence of depression was 0
30 (95% CI 0
25–0
35) for
moderate-to-high-quality studies. Study quality did not signifi-
cantly affect the prevalence of depression. The pooled OR of
depression was also not significantly affected by the study
quality (P = 0
403).
Discussion
To our knowledge, the present study is the first meta-analysis
to evaluate the association between vitiligo and depression.
This study demonstrated that patients with vitiligo were at a
significantly higher risk of clinical depression or depressive
symptoms compared with those without a depigmenting dis-
ease. Approximately one-third of patients with vitiligo
reported depressive symptoms or impaired general health, and
up to one-quarter of them had clinical depression. The pooled
mean values for all validated depression questionnaires evalu-
ated in this study, including HADS, MADRS, HDRS and BDI,
exceeded the cut-off values for depressive symptoms. More-
over, the pooled SMD of questionnaire values between patients
with vitiligo and healthy controls was statistically significant,
suggesting that patients with vitiligo were, indeed, more likely
to show symptoms of depression.
The pooled prevalence of clinical depression differed con-
siderably, ranging from 12
2% to 25
3%, depending on
whether the diagnosis was made using DSM-IV criteria or ICD

© 2017 British Association of Dermatologists British Journal of Dermatology (2017) 177, pp708–718
714 Vitiligo and depression, Y.C. Lai et al.

Table 2 Prevalence of depression and general health in patients with vitiligo

Reference Country Groups compared Study design Prevalence Total cases (n)
Depression questionnaires
Ajose et al. (2014)37 Nigeria Vitiligo vs. OCA types 1 and 2 Case–control 0
294 102
Chan et al. (2013)34 Singapore Vitiligo only Cross-sectional 0
162 222
Choi et al. (2010)30 Korea Vitiligo only Cross-sectional 0
228 57
Esfandiar et al. (2003)23 Iran Vitiligo only Cross-sectional 0
308 120
Karelson et al. (2013)35 Estonia Vitiligo vs. benign skin tumour Case–control 0
200 54
uger and Schallreuter (2015)12
Kr€ Germany Vitiligo vs. healthy control Case–control 0
271 96
Maleki et al. (2005)24 Iran Vitiligo vs. healthy control Case–control 0
462 52
Mechri et al. (2016)25 Tunisia Vitiligo vs. healthy control Case–control 0
183 60
Ramakrishna and Rajni (2014)38 India Vitiligo only Cross-sectional 0
566 53
Saleki and Yazdanfar (2015)40 Iran Vitiligo vs. healthy control Case–control 0
527 110
Sangma et al. (2015)14 India Vitiligo vs. healthy control Case–control 0
590 100
Yamamoto et al. (2011)32 Japan Vitiligo only Cross-sectional 0
278 54
DSM-IV
Balaban et al. (2011)31 Turkey Vitiligo vs. healthy control Case–control 0
143 42
Sharma et al. (2001)13 India Vitiligo only Cross-sectional 0
1 30
ICD
Ahmed et al. (2007)26 Pakistan Vitiligo only Cross-sectional 0
2 100
Arycan et al. (2008)27 Turkey Vitiligo only Cross-sectional 0
327 113
Mattoo et al. (2002)10 India Vitiligo vs. healthy control Case–control 0
217 23
GHQ
Ahmed et al. (2007)26 Pakistan Vitiligo only Cross-sectional 0
420 100
Kent and al-Abadie (1996)6 UK Vitiligo only Cross-sectional 0
354 614
Mattoo et al. (2001)10 India Vitiligo vs. healthy control Case–control 0
336 113
Osman et al. (2009)29 Sudan Vitiligo only Cross-sectional 0
324 111
Picardi et al. (2000)9 Italy Vitiligo only Cross-sectional 0
250 32
Sampogna et al. (2008)28 Italy Vitiligo only Cross-sectional 0
390 177
Sharma et al. (2001)13 India Vitiligo only Cross-sectional 0
167 30

OCA, oculocutaneous albinism; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; ICD, International Classification of Diseases;
GHQ, General Health Questionnaire.

Fig 3. Forest plots: association between

vitiligo and depression. The size of the square
is proportional to study-specific statistical
weights, horizontal lines represent 95%
confidence interval (CI) and diamonds
represent summary measures of association.
SE, standard error.

codes. This discrepancy in the prevalence suggested that there
might be inherent differences between DSM-IV criteria and
ICD codes in terms of the severity of mental disorders cap-
tured. The ICD codes are more sensitive in identifying milder
depressive symptoms, while the DSM-IV criteria are more sen-
sitive in identifying moderate-to-severe ones.41 The diagnosis
of depression as defined by the DSM-IV classification requires
several criteria to be met.42 Therefore, a smaller group of viti-
ligo patients with more severe depressive symptoms sufficient
to meet the DSM-IV criteria would be diagnosed with major
depression. However, it is important to recognize the entire
spectrum of psychiatric problems among patients with vitiligo.
A significant number of patients with vitiligo may have sub-
clinical depression or depressive symptoms severe enough to

British Journal of Dermatology (2017) 177, pp708–718 © 2017 British Association of Dermatologists

Fig 4. Funnel plots of studies evaluating the relationship between
vitiligo and depression. SE, standard error; OR, odds ratio.
affect their quality of life. Our study demonstrated, via vali-
dated questionnaires, which may capture milder somatic
symptoms that have yet to meet the full criteria for clinical
depression, that more than one-third of patients with vitiligo
had experienced such symptoms.
All but one study evaluated the odds of depression between
patients with vitiligo and healthy controls. Ajose et al. used
patients with OCA,37 instead of healthy subjects, as controls.
Patients with OCA, as it is also a depigmenting disorder, are
expected to be at a higher risk for depressive symptoms.
Using patients with OCA as controls would, therefore, bias
the pooled risk toward the null. To examine the magnitude of
this effect, we re-performed the meta-analysis by excluding
the study by Ajose et al.37 The pooled OR increased slightly
from 5
05 in the original analysis to 5
64, which suggested
potential negative confounding.
The results of meta-regression showed that the pooled
prevalence of depressive symptoms was independent of study
design. The pooled prevalence of depressive symptoms
increased from 24% for studies conducted in Europe to 33%
for studies conducted in Asia, Africa or the Middle East. Simi-
larly, the pooled OR of depression also varied according to
the study region, ranging from 1
35 for European studies to
7
93 for studies conducted in other countries. However, none
of the aforementioned results achieved statistical significance.
Table 3 Odds of depression: patients with vitiligo vs. controls
Reference Country
37
Ajose et al. (2014) Nigeria
Balaban et al. (2011)31 Turkey
uger and Schallreuter (2015)12
Kr€ Germany
Maleki et al. (2005)24 Iran
Saleki and Yazdanfar (2015)40 Iran
Sangma et al. (2015)14 India
OR, odds ratio; CI, confidence interval; OCA, oculocutaneous albinism.
© 2017 British Association of Dermatologists
Vitiligo and depression, Y.C. Lai et al. 715
Although some European studies did not report the composi-
tion of their study populations, among those that did,6,12,28,35
the study population mainly consisted of white people
(at least 80%) with Fitzpatrick skin types I–III/IV. As ethnicity
correlated with skin colour, we postulate that depigmented
vitiligo patches have a greater adverse psychological effect on
study participants of ethnicities with darker Fitzpatrick skin
types, as well as on those that recognize depigmented spots as
possible signs of leprosy.43 The pooled prevalence and OR of
depression were not affected by the study quality. This might
be partly owing to the fact that most studies were of medium
quality.
Neuroendocrine dysregulation, which is responsible for the
development of depression, has been implicated as one of the
potential mechanisms for the depigmentation observed in viti-
ligo. In particular, increased levels of norepinephrine and
acetylcholine have been postulated to play important roles.44
The onset of pigment loss was triggered by psychological
stress in up to 62
5% of cases of vitiligo.45 In response to
mental stress, the hypothalamic–pituitary–adrenal axis secretes
catecholamines, which bind and activate a-receptors of skin
arterioles, causing vasoconstriction, hypoxia, overproduction
of oxygen radicals and, ultimately, destruction of melano-
cytes.46,47 The activity of acetylcholinesterase in vitiliginous
skin is also decreased during depigmentation, leading to a
greater inhibition of dopa oxidase activity in melanocytes by
acetylcholine.48 Namazi proposed that an antidepressant agent
such as amitriptyline, which has a strong anticholinergic effect
and weak norepinephrine reuptake blockade, may be benefi-
cial in patients suffering from both vitiligo and depression.44
The Vitiligo Impact Scale-22, a vitiligo-specific quality-of-life
instrument, would be useful in identifying patients who suffer
from significant psychological stress.49 These patients can
potentially benefit from cognitive behavioural therapy for
stress reduction, which may be helpful in repigmentation.50
The major strength of this study was the large sample size,
and the inclusion of studies using various screening instru-
ments for depression and subjects from various geographical
regions. The accumulation of multiple studies increases the
statistical power and leads to more precise quantification of
the prevalence and risk of depression among patients with
vitiligo. In addition, it facilitates evaluation of the effect of
screening tools on the prevalence of depression.
Groups compared OR 95% CI
Vitiligo vs. OCA types 1 and 2 3
21 1
46–7
03
Vitiligo vs. healthy control 2
58 0
49–13
73
Vitiligo vs. healthy control 1
05 0
37–2
96
Vitiligo vs. healthy control 14
00 3
87–50
70
Vitiligo vs. healthy control 6
55 3
42–12
54
Vitiligo vs. healthy control 22
54 6
57–77
39
British Journal of Dermatology (2017) 177, pp708–718
716 Vitiligo and depression, Y.C. Lai et al.

Fig 5. Forest plots: standardized mean

difference (SMD) for depressive symptoms
between patients with vitiligo and controls.
The size of the square is proportional to
study-specific statistical weights, horizontal
lines represent 95% confidence interval (CI)
and diamonds represent summary SMD.

A major limitation of this study was the moderate-to-high
heterogeneity between the included studies. This effect can be
partly due to the broad inclusion criteria used in conducting
this meta-analysis. Meta-regression results revealed study
region as a possible major contributor to the considerable
Fig 6. Funnel plots of studies evaluating the standardized mean
difference for depressive symptoms between patients with vitiligo and
controls. SE, standard error; SMD, standardized mean difference.
heterogeneity observed. We have attempted to address study
heterogeneity by employing a random-effects model. How-
ever, owing to substantial heterogeneity, the results may be
difficult to interpret and not generalizable to all patients with
vitiligo. It is important to note that evaluation of the preva-
lence or risk of depression was not the primary goal of the
most studies included. A large number of studies identified
patients with vitiligo from tertiary referral centres, which can
result in potential referral and selection bias. Information on
the type and severity of vitiligo, which can be potential
sources of heterogeneity, were also not readily available in
most studies. Among studies that evaluated the association of
depression with the severity and type of vitiligo, depression
scores were found to correlate more closely with the location
and extent of vitiligo than the type of vitiligo per se.26,28,30,37
Depigmented patches over an exposed area or genitalia often
have a more significant impact on depression scores.26,28,30,37
In addition, more than half of the included studies did not
have adequate controls, making the results susceptible to the
effect of various confounding factors. Finally, few studies
included in this meta-analysis were assigned a high-quality
rating according to the NOS classification. However, the qual-
ity of the studies did not significantly affect the pooled results.
Another limitation is that the ratings scale or inventory used

Table 4 Mean questionnaire score and standardized difference in mean: patients with vitiligo vs. controls

Total Total Case Control

Reference Country cases (n) controls (n) score score SMD
37
Ajose et al. (2014) Nigeria 102 87 6
18 3
52 8
70
Balaban et al. (2011)31 Turkey 42 33 4
4 6
8 3
60
Mechri et al. (2006)25 Tunisia 60 60 9
1 1
6 12
93
Saleki and Yazdanfar (2015)40 Iran 110 110 7
4 3
9 11
77
Sangma et al. (2015)14 India 100 50 8
45 3
2 15
27
Yanik et al. (2014)11 Turkey 57 58 11
21 10
62 0
60

SMD, standardized mean difference.

British Journal of Dermatology (2017) 177, pp708–718 © 2017 British Association of Dermatologists
 Vitiligo and depression, Y.C. Lai et al. 717

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