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708 British Journal of Dermatology (2017) 177, pp708–718 © 2017 British Association of Dermatologists
Vitiligo and depression, Y.C. Lai et al. 709
© 2017 British Association of Dermatologists British Journal of Dermatology (2017) 177, pp708–718
710 Vitiligo and depression, Y.C. Lai et al.
with variance equal to p(1–p).18 In controlled studies, mean quantitatively the asymmetry of the funnel plot.21 To explore
questionnaire values were compared between cases and con- potential sources of study heterogeneity, meta-regression with
trols to calculate standardized mean difference (SMD) and cor- prespecified variables, including study country, study design
responding 95% CI. ORs and 95% CIs of depression between and study quality, was conducted. All analyses were performed
cases and controls were obtained from the crude data. To esti- using STATA version 120 (Stata Corp., College Station, TX,
mate the summary prevalence, SMD and pooled OR, the ran- U.S.A.).
dom-effects model of DerSimonian and Laird was used to
account for variance between and within the studies.19
Results
Heterogeneity between studies was assessed using v2-test and
the I2 statistic, with values of 25%, 50% and 75% considered
Search results
as low, moderate and high heterogeneity, respectively.20 To
assess qualitatively publication bias, a funnel plot was con- A search using MEDLINE and Embase yielded a total of 270
structed and visually inspected for any asymmetry. Egger’s articles (Fig. 1). No studies were identified from the Cochrane
test, which evaluated small study effects, was utilized to assess Library database. A total of 129 duplicates were removed from
British Journal of Dermatology (2017) 177, pp708–718 © 2017 British Association of Dermatologists
Vitiligo and depression, Y.C. Lai et al. 711
further evaluation. After examining the titles and abstracts of P < 0001) (Fig. 2c). This amounted to 350 cases out of
the remaining 141 articles, 46 studies were selected, based on 1080 patients with vitiligo. There was high heterogeneity
the prescribed inclusion criteria. After reviewing the selected between the studies (I2 = 909%; P < 0001). The pooled
articles in full, 21 studies were excluded for the following rea- prevalence of impaired general health among patients with
sons: review articles (n = 7); irrelevant outcome (n = 8); vitiligo based on GHQ was 034 (95% CI 029–038;
insufficient information (n = 6). After these exclusions, 25 P < 0001) (Fig. 2d).8–10,13,26,28,29 This amounted to 440
studies with 2708 cases of vitiligo were included in the meta- cases out of 1300 patients with vitiligo. There was moderate
analysis. The prevalence of depression was assessed based on heterogeneity between the studies (I2 = 525%; P = 0049).
the following methods: self-reported questionnaires, and Table 2 summarizes the prevalence of depression and
International Classification of Diseases (ICD) and DSM-IV diag- impaired general health reported in each study.
nosis. The prevalence of impaired general health was evaluated
using the GHQ. There were 14 cross-sectional studies that
Mean scores on depressive symptoms rating scales
reported prevalence of depression or impaired general health
and mean questionnaire values. Among 11 case–control stud- The pooled estimate of GHQ, HADS, HDRS, MADRS and BDI
ies that provided the aforementioned data, six also reported means among patients with vitiligo were 112 (95% CI
on the odds of depression between patients with vitiligo and 764–1480), 848 (95% CI 631–1066), 793 (95%
healthy controls. Separate meta-analyses were performed for CI 690–896), 141 (95% CI 414–2413) and 135 (95% CI
ORs, SMD and prevalence of depression based on method of 891–1810), respectively. All subgroup meta-analyses had
diagnosis. high heterogeneity between the studies, with I2 statistics rang-
ing from 780% to 981%.
© 2017 British Association of Dermatologists British Journal of Dermatology (2017) 177, pp708–718
Table 1 Characteristics of included studies on vitiligo and depression
Choi et al. (2010)30 Cross-sectional Korea Primary outpatient dermatology clinic 57 154 Dermatologist CES-D (16) 4
Esfandiar et al. (2003)23 Cross-sectional Iran Tertiary outpatient dermatology clinic 120 384 Dermatologist HDRS (7) 2
Ghajarzadeh et al. (2012)33 Cross-sectional Iran Tertiary outpatient dermatology clinic 100 289 Dermatologist BDI (10) 4
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.
(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 = 0804). Another meta-regression prevalence of depression was 030 (95% CI 025–035) for
was performed on five case–control studies that reported ORs moderate-to-high-quality studies. Study quality did not signifi-
to evaluate the pooled effect of age on the risk of depressive cantly affect the prevalence of depression. The pooled OR of
symptoms. For every 10-year increase in age, there was some depression was also not significantly affected by the study
reduction in the risk of depressive symptoms (0297); how- quality (P = 0403).
ever, this was not statistically significant (P = 0304).
Although two studies reported that females are more likely
Discussion
to be associated with depression than males,4,24 most studies
did not report any significant effect of sex on depression in To our knowledge, the present study is the first meta-analysis
vitiligo. to evaluate the association between vitiligo and depression.
The pooled prevalence of impaired general health was inde- This study demonstrated that patients with vitiligo were at a
pendent of the study design (P = 0975), study quality significantly higher risk of clinical depression or depressive
(P = 0450) and region where the study was conducted symptoms compared with those without a depigmenting dis-
(P = 0706). The pooled prevalence of depressive symptoms ease. Approximately one-third of patients with vitiligo
according to questionnaire scales was independent of study reported depressive symptoms or impaired general health, and
design (case–control vs. cross-sectional; P = 0959). Although up to one-quarter of them had clinical depression. The pooled
the prevalence from the European studies was 024 (95% CI mean values for all validated depression questionnaires evalu-
017–031) vs. 033 (95% CI 020–046) from studies con- ated in this study, including HADS, MADRS, HDRS and BDI,
ducted in regions such as Asia, Africa and the Middle East, this exceeded the cut-off values for depressive symptoms. More-
difference was not statistically significant (P = 0520). over, the pooled SMD of questionnaire values between patients
The pooled OR of depression was 135 (95% CI 056– with vitiligo and healthy controls was statistically significant,
325) for European studies vs. 793 (95% CI 362–1737) for suggesting that patients with vitiligo were, indeed, more likely
studies conducted in other countries; however, the result was to show symptoms of depression.
not statistically significant (P = 0088). The pooled prevalence of clinical depression differed con-
The pooled prevalence of depression was 030 (95% CI siderably, ranging from 122% to 253%, depending on
024–037) for low-quality studies, whereas the pooled 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.
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 0294 102
Chan et al. (2013)34 Singapore Vitiligo only Cross-sectional 0162 222
Choi et al. (2010)30 Korea Vitiligo only Cross-sectional 0228 57
Esfandiar et al. (2003)23 Iran Vitiligo only Cross-sectional 0308 120
Karelson et al. (2013)35 Estonia Vitiligo vs. benign skin tumour Case–control 0200 54
uger and Schallreuter (2015)12
Kr€ Germany Vitiligo vs. healthy control Case–control 0271 96
Maleki et al. (2005)24 Iran Vitiligo vs. healthy control Case–control 0462 52
Mechri et al. (2016)25 Tunisia Vitiligo vs. healthy control Case–control 0183 60
Ramakrishna and Rajni (2014)38 India Vitiligo only Cross-sectional 0566 53
Saleki and Yazdanfar (2015)40 Iran Vitiligo vs. healthy control Case–control 0527 110
Sangma et al. (2015)14 India Vitiligo vs. healthy control Case–control 0590 100
Yamamoto et al. (2011)32 Japan Vitiligo only Cross-sectional 0278 54
DSM-IV
Balaban et al. (2011)31 Turkey Vitiligo vs. healthy control Case–control 0143 42
Sharma et al. (2001)13 India Vitiligo only Cross-sectional 01 30
ICD
Ahmed et al. (2007)26 Pakistan Vitiligo only Cross-sectional 02 100
Arycan et al. (2008)27 Turkey Vitiligo only Cross-sectional 0327 113
Mattoo et al. (2002)10 India Vitiligo vs. healthy control Case–control 0217 23
GHQ
Ahmed et al. (2007)26 Pakistan Vitiligo only Cross-sectional 0420 100
Kent and al-Abadie (1996)6 UK Vitiligo only Cross-sectional 0354 614
Mattoo et al. (2001)10 India Vitiligo vs. healthy control Case–control 0336 113
Osman et al. (2009)29 Sudan Vitiligo only Cross-sectional 0324 111
Picardi et al. (2000)9 Italy Vitiligo only Cross-sectional 0250 32
Sampogna et al. (2008)28 Italy Vitiligo only Cross-sectional 0390 177
Sharma et al. (2001)13 India Vitiligo only Cross-sectional 0167 30
OCA, oculocutaneous albinism; DSM-IV, Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; ICD, International Classification of Diseases;
GHQ, General Health Questionnaire.
codes. This discrepancy in the prevalence suggested that there several criteria to be met.42 Therefore, a smaller group of viti-
might be inherent differences between DSM-IV criteria and ligo patients with more severe depressive symptoms sufficient
ICD codes in terms of the severity of mental disorders cap- to meet the DSM-IV criteria would be diagnosed with major
tured. The ICD codes are more sensitive in identifying milder depression. However, it is important to recognize the entire
depressive symptoms, while the DSM-IV criteria are more sen- spectrum of psychiatric problems among patients with vitiligo.
sitive in identifying moderate-to-severe ones.41 The diagnosis A significant number of patients with vitiligo may have sub-
of depression as defined by the DSM-IV classification requires clinical depression or depressive symptoms severe enough to
British Journal of Dermatology (2017) 177, pp708–718 © 2017 British Association of Dermatologists
Vitiligo and depression, Y.C. Lai et al. 715
© 2017 British Association of Dermatologists British Journal of Dermatology (2017) 177, pp708–718
716 Vitiligo and depression, Y.C. Lai et al.
A major limitation of this study was the moderate-to-high heterogeneity observed. We have attempted to address study
heterogeneity between the included studies. This effect can be heterogeneity by employing a random-effects model. How-
partly due to the broad inclusion criteria used in conducting ever, owing to substantial heterogeneity, the results may be
this meta-analysis. Meta-regression results revealed study difficult to interpret and not generalizable to all patients with
region as a possible major contributor to the considerable 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
Fig 6. Funnel plots of studies evaluating the standardized mean rating according to the NOS classification. However, the qual-
difference for depressive symptoms between patients with vitiligo and ity of the studies did not significantly affect the pooled results.
controls. SE, standard error; SMD, standardized mean difference. 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
British Journal of Dermatology (2017) 177, pp708–718 © 2017 British Association of Dermatologists
Vitiligo and depression, Y.C. Lai et al. 717
to detect depression have not been validated in patients with 16 Wells GA, Shea B, O’Connell D et al. The Newcastle-Ottawa Scale
vitiligo. Validation studies should be conducted in the future (NOS) for assessing the quality of nonrandomised studies in meta-
to evaluate the utility of these depression-screening instru- analyses. Available at: http://www.ohri.ca/programs/clinical_epi
demiology/oxford.asp (last accessed 1 June 2017).
ments in dermatological diseases.
17 McPheeters ML, Kripalani S, Peterson NB et al. Closing the quality
This meta-analysis provides evidence that patients with viti- gap: revisiting the state of the science (vol. 3: quality improve-
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19 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin
needed to validate and identify the most appropriate depres-
Trials 1986; 7:177–88.
sion-screening instruments for patients with dermatological 20 Higgins JP, Thompson SG, Deeks JJ et al. Measuring inconsistency
disorders. All clinicians should be cognizant of this association in meta-analyses. BMJ 2003; 327:557–60.
and actively evaluate patients with vitiligo for signs/symptoms 21 Egger M, Davey Smith G, Schneider M et al. Bias in meta-analysis
of depression and provide appropriate referrals to manage detected by a simple, graphical test. BMJ 1997; 315:629–34.
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British Journal of Dermatology (2017) 177, pp708–718 © 2017 British Association of Dermatologists