Internalized stigma in patients with schizophrenia: A hospital-based cross-sectional study from Nepal.

INTRODUCTION: The aim of this study was to examine the internalized stigma of mental illness in patients with schizophrenia visiting psychiatry outpatient in a tertiary level hospital in Kathmandu, Nepal, and to explore the associated sociodemographic and clinical factors.
METHODS: This was a cross-sectional study, where participants were selected by purposive sampling from the outpatient department of psychiatry in Tribhuvan University Teaching Hospital, Kathmandu, Nepal. One hundred and fourteen patients were selected and given the Internalized Stigma of Mental Illness scale to complete to assess the level of stigma. A semi-structured sociodemographic form was used to get information on sociodemographic and clinical factors. Simple descriptive analysis was done followed by multivariate analysis to explore the sociodemographic and clinical correlates of stigma in these patients.
RESULTS: A total of 114 patients were included in the study. Moderate to high levels of internalized stigma was reported in almost 90% of patients with schizophrenia. The subscale with the highest mean score was stereotype endorsement and that with the lowest mean score was stigma resistance. Duration of illness was the only clinical variable associated with stigma while occupation was the only sociodemographic variable related to stigma.
CONCLUSION: Moderate to high levels of internalized stigma were reported across all subscales of stigma in patients with schizophrenia and the prevalence was high. Further, duration of illness was associated with stigma. Stigma reduction should therefore be a component of the overall management of patients diagnosed with schizophrenia.

Introduction

Stigma, first studied systemically by Goffman, is defined as a trait of any individual that sets him/ her apart from others with a negative connotation [1]. Stigma has been broadly divided into two types as public and self [2]. In the context of mental illness, public stigma is the cumulative response of the people against those with mental illness, while self-stigma is the prejudice that people with mental illnesses hold about themselves. Three components define both public and self-stigma: stereotypes, prejudice, and discrimination [3, 4].

Self-stigma is the end product of public stigma when individuals with mental illness start believing in the reactions of people around them and internalize the attributes and behave accordingly [5, 6].

Psychiatric disorders are considered untreatable, unpredictable, and evidence of personal failure despite many advances in medicine and psychiatry [7]. Stigma and discrimination associated with mental disorders lead to violation of human rights and lots of suffering, disability, and economic loss. Self-stigma and eventually internalized stigma lead to low self- esteem, depression, delayed treatment-seeking, long duration of untreated illness and poor quality of life [3, 7]. Additionally, compared to neurosis, psychotic illnesses like schizophrenia have high heritability, and are considered equivalent with insanity, and aggression [7] leading to more pervasive stigma [7-11].

The most consistent relation of stigma reported is with the duration of illness with both having positive correlation [12-14]. However, studies examining social and demographic factors have found inconsistent results with some studies reporting associations [2, 13], while others reporting no association at all [15, 16]. These inconsistencies could arise due to heterogeneity in terms of type of study, tools used, sample size, sample population characteristics, diagnostic categories, and setting.

In resource-poor countries like Nepal with limited facilities available for mental illnesses, patients with schizophrenia face higher stigma hindering their progress. To the best of our knowledge, very few studies have been conducted in examining internalized stigma in the mentally ill in Nepal [15, 17] and none in patients with schizophrenia. We, therefore, aimed to examine internalized stigma of patients with schizophrenia seeking help in the outpatient psychiatry department and to explore the sociodemographic and clinical factors associated with it.

Methods

Patients and procedure

This was a cross-sectional study. We recruited participants from psychiatry outpatient of Tribhuvan University Teaching Hospital, Kathmandu, Nepal, and included both old and new patients. This was a non-probability purposive sampling. All consecutive patients visiting psychiatry outpatient center with the diagnosis of schizophrenia were considered for the study. The exclusion criteria were other axis I psychiatric disorders, organic psychoses, intellectual disability, and high suicidality after clinical evaluation by psychiatrist. Those visiting psychiatry outpatient and with ICD-10 diagnosis of schizophrenia were invited to participate in the study and checked for eligibility. Those who were eligible and provided consent to participate were included. Eligibility criteria were those above 18 years of age, and who had a formal diagnosis. Schizophrenia diagnosis was made by the consultant psychiatrists on their respective outpatient days based on the diagnostic criteria given by ICD-10 Clinical description and diagnostic guidelines (CDDG). We had a total of 114 patients and the study was conducted for one year from July 2020 to July 2021. A proforma designed specifically for the project included all the relevant information to be completed. These were demographic variables as age, sex, permanent address, occupation, monthly family income along with disease-related variables such as duration of illness, substance dependence history, and medical comorbidities. The average time taken to collect information from one patient was forty minutes.

Sex was grouped into two categories as male and female, permanent address into two categories as urban and rural. Information on occupation was initially collected according to the national profession classification of Nepal [18, 19] and later grouped into four broad categories since there were very few numbers in some categories. Duration of illness was categorized into four groups as <1 year, 1–5 years, 5–10 years, and more than 10 years. Substance use history was categorized into two categories as presence or absence of dependence by inquiring with patients. In those with positive substance dependence history, they were further grouped based on the predominant substance of dependence. Stigma information was collected by using the Nepali translated Internalized stigma of Mental Illness (ISMI) scale for the patients. The patients filled in it themselves except for those who were not able to read and/ or write.

Sample size calculation

Sample size was calculated using the Cochran’s formula: n = (z1- α/2)2(p)(q)/(d)2, where p = 44% [8] and considering 10% drop out from the study, n = 95+10 = 105 was the minimum required sample size.

Ethical issues

Patients willing to participate were given detailed information about the project. Written informed consent form was completed for all participants before starting the interview process. For those who were not able to read and write, consent was taken with the help of the informant. Ethical approval was obtained from the Institutional Review Committee (IRC) at the Institute of Medicine (reference number 432/(6–11)E2/076/077) in Nepal.

The Internalized Stigma of Mental Illness (ISMI) scale

The ISMI scale was developed by Ritsher et al. [6]. It attempts to examine internalized stigma of people suffering from a mental illness. It is a self-report questionnaire and has five subscales: “Alienation” with 6 items, “Stereotype Endorsement” with 7 items, “Discrimination Experience” with 5 items, “Social Withdrawal” with 6 items, and “Stigma Resistance” with 5 items. All items are measured on a 4-point Likert-type scale from “strongly agree” to “strongly disagree” (4 = strongly agree to 1 = strongly disagree). All other subscales are positively worded except for the stigma resistance subscale. The Stigma Resistance subscale unlike other subscales, measures the degree of resistance towards being stigmatized.

Higher scores on the subscales, therefore, indicate higher stigma except for stigma resistance, which requires reverse coding. For our purpose, we reversed the mean stigma resistance score first. Thenafter, the overall mean stigma scores were calculated by summing up all the recorded scores and divided by the total number of items.

In terms of scoring, 4 categories were used. Minimal stigma for a score less than 2, low stigma for score of 2 to 2.5, moderate stigma for score of 2.5 to 3, and high stigma for score more than 3 [15].

The ISMI scale was translated in Nepali by psychiatrists and professional translators with strong command in both the languages and pretested in 15 patients at first to identify if the respondents had any problem comprehending the items [20]. These 15 were patients with diagnosis of any psychotic disorder and were not included in the final analysis.

Statistics

Data analysis was done by using software Stata 16 (Stata Corp LLC, TX, USA) and Statistical Package for Social Sciences (SPSS) version 26 (IBM SPSS Statistics for Windows, Armonk, NY: IBM Corp.). Descriptive statistics were used for the variables as appropriate. Means and standard deviations were reported for continuous variables and frequencies for categorical variables. Histograms and boxplots were used to check for the distribution of the continuous variables. There was no major violation of normality for the scores on the subscales of ISMI. Multivariate linear regression was done, where the five subscales of ISMI were kept as dependent variables and age as a continuous variable while sex, occupation, substance use, and duration of illness as categorical variables were kept as predictor variables. A p-value of .05 was taken as significant in all statistical tests.

Results

The total number of patients was 114. 56% of them were males, while 44% were females. The mean age was 36.9±11.5 years. 40% (n = 46) patients had comorbid substance dependence; of which alcohol was most common (20.2%, n = 23). The majority of patients had duration of illness ranging from 5–10 years (43.9%), followed by 1–5 years (34.2%), less than 1 year (15.8%), and more than 10 years (6.1%) (Table 1).

Table 1

Sociodemographic and clinical variables.

Variables (n = 114)		n	Percent
1. Age in years (Mean, SD)	36.98(11.48)
2. Income in local currency, Nepali Rupees (Mean, SD)	21684.21 (11706.83)
3. Sex	Male	64	56.14
	Female	50	43.86
4. Permanent address	Urban	45	39.47
	Rural	69	60.53
5. Occupation	Others	41	35.96
	Agricultural workers (Farming)	13	11.40
	Professionals/Legislators/managers	15	43.86
	Service workers	10	8.77
6. Physical comorbidities	Yes	17	14.9
	Diabetes	5
	Hypertension	4
	Others	8
	No	97	85.10
7. Substance dependence	Yes	46	40.35
	Alcohol	23
	Cannabis	4
	Nicotine	19
	No	68	59.65
8. Duration of illness	< 1 year	20	17.54
	1–5 years	41	35.96
	5–10 years	47	41.23
	>10 years	6	5.26

n = total number of patients, SD = standard deviation.

ISMI scores

Prevalence of moderate to high stigma was found in 102 (89.47%) patients and minimal to low stigma in 12 (10.53%) patients. As for the ISMI subscales, the results obtained are as follows. The highest score was obtained for stereotype endorsement subscale followed by alienation, social withdrawal, stigma discrimination experience and the lowest for resistance subscale. For the stigma resistance subscale, the average score calculation required subtraction from the total score to get its average score since it is different from other subscales.

The mean scores on total stigma and all the five subscales of ISMI have been presented in Table 2.

Table 2

Means and standard deviations of total stigma and 5 subscales of ISMI.

Variables (n = 114)	M	SD
1. Total stigma score	2.89	.23
2. Stigma Alienation score	3.01	.39
3. Stereotype endorsement	3.05	.39
4. Stigma experience score	2.88	.53
5. Stigma withdrawal	2.99	.41
6. Stigma Resistance	2.49	.68

n = total number of patients, M = mean, SD = standard deviation.

Sociodemographic and clinical factors related to ISMI

A multivariate linear regression model was built where the mean scores on five items of ISMI were kept as dependent variables, while age, sex, occupation, duration of illness, and substance dependence were kept as predictor variables. Among the sociodemographic variables, occupation was the only factor reported to have statistically significant association with stigma scores. However, the stigma subscales were different for different occupational categories. Farmers experienced more discrimination experience while managers/ professionals/ legislators had more social withdrawal stigma. For the clinical variables, the only factor reported to be statistically significant in predicting the stigma score in subscales of social withdrawal stigma was duration of illness 1 to 5 years and 5 to 10 years (Table 3).

Table 3

Multivariate linear regressions for five domains of Internalized stigma of mental illness (ISMI) as dependent variables and age, sex, occupation, duration of illness and substance dependence as predictor variables, where sex, occupation, duration of illness and substance dependence are categorized.

Variables (n = 114)	Alienation			Stereotype endorsement			Discrimination experience			Social withdrawal			Resistance score
	β	95% CI		β	95% CI		β	95% CI		β	95% CI		β	95%CI
		LB	UB		LB	UB		LB	UB		LB	UB		LB	UB
Age	-.0005	-.0113	.0023	-.0013	-.008	.0053	-.0047	-.0141	.0047	-.0061	-.0129	.0006	.0005	-.01	.01
Sex
Male
Female	-.12	-.27	.03	-.06	-.22	.10	-.05	-.26	.16	-.08	-.23	.07	.05	-.22	.32
Occupation
Others
Agricultural workers	-.08	-.33	-.31	-.07	-.33	.19	.35*	.0077	.6935	-.08	-.32	.17	.43	-.02	.87
Professionals/ Legislators	-.13	.17	.04	-.0069	-.18	.19	-.07	-.31	.17	-.22*	-.39	-.64	.08	-.23	.40
Elementary occupations	-.13	-.44	.18	.21	-.09	.56	.21	-.21	.64	.06	-.25	.37	-.13	-.69	.42
Duration of illness
< 1 year
1–5 years	.14	-.09	.37	.05	-.19	.29	.13	-.18	.45	.23*	.0012	.4553	-.10	-.50	.30
-10 years	.23	-.006	.46	.13	-.12	.38	.17	-.15	.49	.29*	.0543	.52	.20	-.21	.63
>10 years	.19	-.23	.61	-.14	-.57	.30	-.08	-.65	.49	-.03	-.45	.38	-.10	-.84	.64
Substance dependence
No
Yes	.1	-.06	.25	.05	-.11	.22	.17	-.04	.39	.15	-.0071	.307	-.10	-.84	.64
F value	1.32			0.72			0.18			0.0053			0.31
R square	10.3			5.54			11.14			19.61			9.34%

*p < .05. ISMI = Internalized stigma of mental illness, n = number of participants, β = unstandardized regression coefficient, CI = confidence interval, LB = lower bound, UB = upper bound.

Discussion

Males outnumbered females in our study accounting to 56%, as opposed to another study from Nepal where almost 60% of the respondents were females [17]. This could be because males are said to have higher incidence of schizophrenia, while if all mental illnesses are taken into consideration females are at higher risk. In line with this, a study from Poland reported almost 55% of respondents to be females [14]. The mean age of the patients in our study was 37 years, which is supported by another study from Nepal reporting mean age of 35 years in mentally ill patients [15]. In our study, almost 40% had comorbid substance dependence, most common being alcohol (20%). This finding is in agreement with results from a systemic review and metanalysis on any substance use disorder comorbidity in schizophrenia where prevalence rate of any substance comorbidity was 42% [21], with alcohol use disorder being around 24%.

Our main finding is the presence of moderate to high level of internalized stigma in all subscales in patients with schizophrenia. This finding is comparable to studies published elsewhere as in Africa [2, 12, 22, 23], Europe [9] and Asia [24-26]. A study from Nepal also reported similar findings [27] though this was among mentally ill patients and not only schizophrenia. Studies on stigma in Nepal have mostly been carried out in mentally ill patients, not distinguishing between neurotic and psychotic disorders, making it difficult to compare and contrast the findings.

The prevalence of moderate to high stigma was reported in almost 90% of patients in this study. This finding is in line with a study from China conducted among severe mental disorders in rural communities using the same tool for measuring stigma [25]. However, this estimate is higher compared to most other studies within Nepal [15, 17] and other parts [8, 28] of the world. Studies comparing stigma scores within diagnostic categories have persistently reported higher self-stigma scores for schizophrenia and psychosis compared to affective disorders and this could be the main reason behind the discrepancy reported [25, 29]. Additionally, we included both new and old patients in our study regardless of the symptomatology severity. Furthermore, scales used to assess stigma could have been different in these studies with varying cut-offs. In studies from Nepal, all mentally ill patients were included not limiting to schizophrenia which could have led to decreased estimates of stigma prevalence in patients.

The mean ISMI scores among the patients with schizophrenia in this study were higher compared to studies from Ethiopia and Europe [2, 9]. Going to the individual domains in ISMI, patients seemed to have high levels of stigma in alienation and stereotype endorsement while moderate level was seen in other domains, namely discrimination experience, social withdrawal, and resistance. This is in line with another study from Nepal where stereotype endorsement subscale was the one with highest level of internalized stigma attached [15], though this study included all mentally ill patients and not only schizophrenia. Studies conducted elsewhere have reported inconsistent results with some studies reporting highest scores for alienation [14] and least for endorsement subscale [9, 14, 30], and other studies reporting highest scores for discrimination experience [28, 30] with the same assessment tool. There could be multiple explanations for this. Firstly, mentally ill in Nepal seem to endorse the stereotypes without questioning because of the low mental health literacy, which might not hold true in other parts of the world. However, when it comes to alienation and discrimination experience, this is the actual experience these people go through, which might not be very different in most parts of the world. Secondly, stigma experience might differ based on the study setting as hospital or community setting.

Duration of illness was the only clinical variable associated with the stigma scores in social withdrawal category in our study. Duration of illness in 2 categories as 1 to 5 years and 5 to 10 years had significant associations with social withdrawal subscale. Less than one year of duration of illness in schizophrenia could mean too short a period to fully understand the course and prognosis leading to low stigma scores. On the other hand, too long duration as more than 10 years could mean patients have adjusted somehow to their diagnosis leading to less stigma as reported in this study. Results reporting positive correlations of duration of illness with ISMI scores have been reported in a number of studies [8, 12–14]. These differences could be because the first study was conducted among all outpatients with mental illness and not only schizophrenia, the second study among severe mental illnesses, including schizophrenia, schizoaffective disorder, and bipolar disorder while the third study was conducted among psychosis in community setting, rather than in hospital setting. Furthermore, we did not take into consideration other variables of interest in measuring stigma scores such as self-esteem, social and community support, level of symptomatology, and insight. A systematic review published in 2013 on the self-stigma in schizophrenia spectrum disorders, however, did not report any association between stigma severity and duration of psychosis [31]. In terms of sociodemographic factors, occupation was the only variable associated with discrimination and withdrawal subscales, where being farmer was associated with experience of discrimination and another occupational category of managers and professional and legislators was associated with social withdrawal scale. Contrary to this, a study from Nepal had no association with any of the demographic variables [15] but this study included all mentally ill patients and was not limited to schizophrenia. Studies from India [16], Poland [14], and China [24, 25] in severe mental illness, including schizophrenia also reported no association of stigma with demographic variables. On the other hand, there were studies which reported demographic factors such as age [13, 28], education level [13], employment status [28] to have positive correlations with ISMI scores [13] in severe mental illnesses. Coming from rural background and being single were associated with high stigma scores in a study from Ethiopia in schizophrenia in a hospital-based study [2]. In a recently published review and meta-analysis of studies assessing stigma using ISMI in patients with severe mental illness, Rosal et al. reported weak and inconsistent relationship of stigma with sociodemographic variables such as gender, age, occupation, education and marital status [32]. Similar weak associations with sociodemographic variables were reported in another systemic review of stigma in schizophrenia spectrum disorders [31].

Limitations

There are several limitations in this study. This has cross-sectional design, so it is difficult to infer causality. Since this was conducted in an outpatient setting; it is difficult to generalize the findings to inpatients who might have more severity and might have different levels of internalized stigma. More important factors that affect stigma in people with schizophrenia like social support, and self-esteem and severity of psychopathology along with insight level were not considered in this study that could have led to biased estimates. Despite these limitations, this is one of the very few studies that has attempted to explore the level of internalized stigma in outpatients with schizophrenia in Nepali context. The diagnoses were made based on standard ICD-10 classification by psychiatrists adding on to the evidence reporting high levels of stigma in most subscales in patients with schizophrenia from perspective of Nepal, a low- and middle-income country.

Conclusions and recommendations

The findings suggest that patients with diagnosis of schizophrenia have a moderate to high level of internalized stigma in Nepal. Literature suggests that stigma affects many aspects of treatment in patients from treatment seeking to opening up about symptoms, adhering to treatment and follow-up procedures. This ultimately leads to poor prognosis leading to increased disability and the cycle continues. Stigma therefore needs to be addressed within the broader perspective and be included in the treatment packages of patients with schizophrenia. This study will serve as reference for future studies exploring stigma in patients with schizophrenia in Nepal and will add to the evidence gap in this field. Future studies should focus on studying stigma in schizophrenia with more robust methodology and with larger samples for the results to generalize in context of Asia.

(DTA)

Click here for additional data file.

22 Dec 2021

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Soumitra Das

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: I Don't Know

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: The aim of the study is not clear, the introduction in abstract can be reframed.

Line 77- 78 need reframing

The inclusion criteria does not mention about presence or stance on other axis 1 psychiatric disorders, also how was the diagnosis of schizophrenia confirmed.

From line 125 line 141 is it desired to put this under the ethical issues section or rather the methodology section.

Line 164 - were these 15 participants included in the final analysis

In the results section either use numerical to describe percentages or words, kindly maintain uniformity for better readability.

In table 1 please mention units for relevant variables.

For patients of duration of illness how was the diagnosis of Schizophrenia made considering time stipulations.

Line 214 -217 need to be rearranged talk about categorization either in methodology or describe it before the sub scale scores.

How is the score of stigma resistance interpreted as in if the scores are coded in reverse - a low score means less resistance if so then has that been take care of during calculating the mean score of the scale?

Have all other studies done with the ISMI scale compared to the current findings in the discussion?

Reviewer #2: Thank-you for the opportunity to review your article ‘Internalized stigma in patients with schizophrenia: a hospital-based cross-sectional study from Nepal’. The article is on a critical area, being stigma in patients with schizophrenia as stigma impacts upon other outcomes for patients with schizophrenia. As stigma erodes the patient’s self-esteem and thus has broad impacts on the patient's quality of life and wellbeing. Please see revisions below.

Abstract:

Line 33 – English phrasing ‘to fill up’ please revise

Introduction:

The introduction provides a good concise summary of stigma and the associated impacts on individuals with schizophrenia. The inconsistency in previous research pertaining to the relationship between stigma and sociodemographic variables is noted. However, the introduction may benefit from the addition of more information pertaining to the inconsistent results. Further the introduction would benefit from a thorough proofread with particular attention to English phrasing, please see below.

Line 54 - ‘stigma’ is missing after the comma

Line 57 - English phrasing ‘people around persons’ please revise

Line 59 - English phrasing ‘constitute in defining’ please revise

Line 77 - ‘being’ is omitted

Line 79/80 - English phrasing

Line 81 – results not ‘relations’

Methods:

The authors provided enough detail in the methods section for the study to be replicated. Further the authors provided a good summary of the measure used. Please address the issues noted below.

Line 94/95 - English phrasing ‘and took’ please revise possibly recruiting

Line 95 - English phrasing

Line 96/99 – Clinic or centre omitted from sentence

Line 120/126 – Completed not filled

Line 129 – Revise sentence

Line 140/141 - in omitted

Line 143 – The internalized stigma of mental illness scale (re-state title)

Line 159 – revise

Line 166/167 - Remove

Line 176 – revise ‘were done’

Results:

The results are well presented and summarized. Please see points below.

Line 182 – Percent not percentage

Line 216 – please clarify “Considering scoring, 4 categories were used”.

Line 242 – revise ‘seen’

Line 242-245 – Please revise

Discussion:

The discussion requires a thorough proofread and revision to enhance the clarity of the points being made especially in the section comparing the current research to previous research as well as the limitations section.

Line 252/253 - revise start of sentence

Line 257 – add disorders after psychotic and remove and before therefore

Line 264/265 - Revise

Line 268 – studies

Line 277 – change taken

Line 285 – 287 – please revise

Reviewer #3: Presence of stigmas and their negative effects on the clinical outcome in schizophrenia is an established matter. But, this study tried to explore it from a perspective of an Asian and developing country. And that is the rationality of this study.

The study overall highlighted some new findings from Nepal's perspective.

But, I have some minor suggestions-

1) Introduction section can be rewritten in more concise manner.

2) Sample size determination process is not necessary in details, it can be omitted or can be written in a single sentence mentioning the p = 44%

3) Ethical issue section and The Internalized Stigma of Mental Illness (ISMI) scale section should be more concise.

4) Result section should be more concise excluding the repetition of not so important findings described in description as well as shown in table

5) Discussion section should include the socio-demographic sections to highlight the similarities and differences with other studies, which is necessary for comparison

6) Limitation section includes several limitations, which is good. But, should include clarification how they were resolved, or why this study is yet important with these limitations.

7) Conclusion section revealed as there is nothing new in this study. This section should be re-written highlighting the importance and inference of this study.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Dr. Prateek Varshney

Reviewer #2: Yes: Nagesh Brahmavar Pai

Reviewer #3: No

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

14 Jan 2022

Dear Soumitra Das

Academic Editor

PLOS ONE

Thank you for reviewing our manuscript and giving us the opportunity to revise it. Your suggestions and comments from the reviewers have been very valuable and thought provoking while revising our manuscript. We believe this has improved the standard of our manuscript. We have incorporated all the comments and suggestions as far as possible. For those comments we have not done, we have explained why. We have thoroughly made changes from abstract to the conclusion and references have been added accordingly. We have also rewritten introduction section and revised other sections, especially results sections as appropriate.

In the result section, we found an error in line 248 of the original submission as duration of illness less than 1 to 5 years while we meant 1 to 5 years, so we corrected this in the revised manuscript. We have rewritten our discussion section citing more studies to compare and contrast our results. Besides, we have made correction at few places where we could find some errors during the review process from abstract to results and discussion and added few texts in limitation in light of the revised discussion. The manuscript has also been proofread by a native English speaker.

Please find our point-by-point responses to the comments from the reviewers. We have responded each comment in bold blue fonts. As per your guidance, we are submitting the revised manuscript with track changes, clean copy as manuscript and Response to the reviewers. If there are further queries and comments from you and the reviewers, we would be glad to address them.

Thank you

Regards,

Saraswati Dhungana, MD (on behalf of coauthors)

Point by point Responses to reviewers' comments:

Reviewer #1: The aim of the study is not clear, the introduction in abstract can be reframed.

Response: Thank you for your comment. The introduction part has been reframed as “The aim of this study was to examine the internalized stigma of mental illness in patients with schizophrenia visiting psychiatry outpatient in a tertiary level hospital in Kathmandu, Nepal, and to explore the associated sociodemographic and clinical factors.”

Line 77- 78 need reframing

Response: Thank you for your comment. The line has been reframed as “Additionally, compared to neurosis, psychotic illnesses like schizophrenia have high heritability, and are considered equivalent with insanity, and aggression leading to more pervasive stigma.”

The inclusion criteria does not mention about presence or stance on other axis 1 psychiatric disorders, also how was the diagnosis of schizophrenia confirmed.

Response: Thank you for your thoughtful observation. We have added about the exclusion of other axis I disorders as “The exclusion criteria were other axis 1 psychiatric disorders, organic psychoses, intellectual disability, and high suicidality after clinical evaluation by psychiatrist.” in the Patients and procedure subsection of Methods section. Also, we have clarified the diagnosis of schizophrenia by adding the following statement in the Patients and procedure subsection of Methods section: “Schizophrenia diagnosis was made by the consultant psychiatrists on their respective outpatient days based on the diagnostic criteria given by ICD-10 Clinical description and diagnostic guidelines (CDDG).”

From line 125 line 141 is it desired to put this under the ethical issues section or rather the methodology section.

Response: Thank you for your thoughtful comment. We have included line 125 to line 141 in the methodology patients and procedure section, rather than the ethical issues section.

Line 164 - were these 15 participants included in the final analysis

Response: Thank you for this important question. These 15 participants mentioned in line 164 were patients with diagnosis of any psychotic disorder and were not included in the final analysis and this statement has been added to the manuscript as: “These 15 were patients with diagnosis of any psychotic disorder and were not included in the final analysis.”

In the results section either use numerical to describe percentages or words, kindly maintain uniformity for better readability.

Response: Thank you for your comment. We have maintained uniformity by using percent at all places in the results section as applicable.

In table 1 please mention units for relevant variables.

Response: Thank you for your comment. We have mentioned units for age in years and income in local currency (Nepali Rupees) in table 1.

For patients of duration of illness how was the diagnosis of Schizophrenia made considering time stipulations.

Response: Thank you for your comment. The diagnosis of schizophrenia was made based on the ICD-10 criteria as mentioned in the methodology section. Considering time stipulations, the total duration of illness was categorized into four and it was the total illness period, rather than the presence of florid psychotic symptoms during interview. We have addressed this issue by the following statement: “Schizophrenia diagnosis was made by the consultant psychiatrists on their respective outpatient days based on the diagnostic criteria given by ICD-10 Clinical description and diagnostic guidelines (CDDG). Considering time stipulations, the total duration of illness was categorized into four and it was the total illness period, rather than the presence of florid psychotic symptoms during interview.”

Line 214 -217 need to be rearranged talk about categorization either in methodology or describe it before the sub scale scores.

Response: Thank you for the suggestion. Line 214-217 about the categorization of ISMI scores has been rearranged and moved to the methodology section in the ISMI subsection as you have advised.

How is the score of stigma resistance interpreted as in if the scores are coded in reverse - a low score means less resistance if so then has that been take care of during calculating the mean score of the scale?

Response: Thank you for your comment. Mean stigma resistance scores were reverse coded first, so that low scores meant more resistance as equivalent with other subscale scores and therefore, the mean total score made sense in interpretation. This has been made clearer in the ISMI section by adding the following statement: “For our purpose, we reversed the mean stigma resistance score first. Thenafter, the overall mean stigma scores were calculated by summing up all the recorded scores and divided by the total number of items.”

Have all other studies done with the ISMI scale compared to the current findings in the discussion?

Response: Thank you for the question. To the best of our knowledge, we have included all other studies using ISMI scale in discussion section. We have added few more studies in the discussion section (Reference number 25, 27, 28, 31-33).

Reviewer #2: Thank-you for the opportunity to review your article ‘Internalized stigma in patients with schizophrenia: a hospital-based cross-sectional study from Nepal’. The article is on a critical area, being stigma in patients with schizophrenia as stigma impacts upon other outcomes for patients with schizophrenia. As stigma erodes the patient’s self-esteem and thus has broad impacts on the patient's quality of life and wellbeing. Please see revisions below.

Response: Thank you for your encouraging remarks. We have attempted to respond to all your comments as much as possible.

Abstract:

Line 33 – English phrasing ‘to fill up’ please revise

Response: Thank you for your comment. We have replaced it by “to complete”.

Introduction:

The introduction provides a good concise summary of stigma and the associated impacts on individuals with schizophrenia. The inconsistency in previous research pertaining to the relationship between stigma and sociodemographic variables is noted. However, the introduction may benefit from the addition of more information pertaining to the inconsistent results. Further the introduction would benefit from a thorough proofread with particular attention to English phrasing, please see below.

Response: Thank you for your comment. We have revised the introduction section according to your suggestions. We have added a statement explaining the reason for inconsistencies as: “These inconsistencies could arise due to heterogeneity in terms of type of study, tools used, sample size, sample population characteristics, diagnostic categories, and setting.” Additionally, we have done thorough proof reading and have rephrased English phrases deemed not appropriate.

Line 54 - ‘stigma’ is missing after the comma

Response: We did not understand the comment, However, we added comma after stigma in line 54 as “Stigma, first studied systemically by Goffman, is defined as a trait of any individual that sets him/ her apart from others with a negative connotation.”

Line 57 - English phrasing ‘people around persons’ please revise

Response: We have replaced it with “people against those with mental illness.”

Line 59 - English phrasing ‘constitute in defining’ please revise

Response: We have replaced “constitute in defining” by “define”.

Line 77 - ‘being’ is omitted

Response: Thank you for pointing this out. We have rephrased the entire sentence for more clarity.

Line 79/80 - English phrasing

Response: We have rephrased the entire sentence as: “The most consistent relation of stigma reported is with the duration of illness with both having positive correlation.”

Line 81 – results not ‘relations’

Response: Thank you for the comment. We have replaced “relations” with “results”.

Methods:

The authors provided enough detail in the methods section for the study to be replicated. Further the authors provided a good summary of the measure used. Please address the issues noted below.

Line 94/95 - English phrasing ‘and took’ please revise possibly recruiting

Response: We have replaced “took” with “included”. “Recruiting” was not used because this has been used in the same sentence at the beginning.

Line 95 - English phrasing

Response: We have replaced “took” with “included”.

Line 96/99 – Clinic or centre omitted from sentence

Response: We have added “center” after psychiatry outpatient.

Line 120/126 – Completed not filled

Response: We have replaced “filled” with “completed” at both the places in line 120/ 126 as suggested.

Line 129 – Revise sentence

Response: We have revised the sentence as: “The average time taken to collect information from one patient was forty minutes.”

Line 140/141 - in omitted

Response: Thank you for the comment, “In” has been inserted in the line 140/141.

Line 143 – The internalized stigma of mental illness scale (re-state title)

Response: We have restated the title as: “The ISMI scale” in the beginning of the sentence in line 143.

Line 159 – revise

Response: Thank you for the comment. We have rewritten the whole paragraph to comply with the other reviewer’s comment as well. In doing so, we have rephrased this as “All other subscales are positively worded except for the stigma resistance subscale. The Stigma Resistance subscale unlike other subscales, measures the degree of resistance towards being stigmatized.”

Line 166/167 – Remove

Response: Thank you for your comment. We have removed the statement “Overall, the items were well understood. So, we adapted the Nepali translation as it was” in line 166/167.

Line 176 – revise ‘were done’

Response: Thank you for pointing out this error. This has been revised with “was done” and “s” has been deleted from regressions in line 176.

Results:

The results are well presented and summarized. Please see points below.

Line 182 – Percent not percentage

Response: We have corrected this.

Line 216 – please clarify “Considering scoring, 4 categories were used”.

Response: Thank you for this important comment. This categorization of scores statement has been taken above in the methodology section under ISMI subsection and further clarification has been made.

Line 242 – revise ‘seen’

Response: Thank you for the comment. In revising line 242-245 as your another suggestion, the whole statement has been rephrased for more clarity as stated in the response to the following comment.

Line 242-245 – Please revise

Response: Thank you for the comment. The line 242-245 has been rephrased as “Among the sociodemographic variables, occupation was the only factor reported to have statistically significant association with stigma scores. However, the stigma subscales were different for different occupational categories. Farmers experienced more discrimination experience while managers/ professionals/ legislators had more social withdrawal stigma.”

Discussion:

The discussion requires a thorough proofread and revision to enhance the clarity of the points being made especially in the section comparing the current research to previous research as well as the limitations section.

Response: Thank you for the comment. We have revised the discussion section, especially in comparing our results to findings from previous studies along with the limitations. We have added 9 more references (25-33) in doing so. We have also proofread this thoroughly and revised the lines as follows.

Line 252/253 - revise start of sentence

Response: Thank you for the comment. This has been revised by omitting few words in the statement as “This finding is comparable to studies published elsewhere as in Africa (2, 12, 21, 22), Europe (9) and Asia (27, 28).”

Line 257 – add disorders after psychotic and remove and before therefore

Response: Thank you for the comment. We have added disorders after psychotic and removed and before therefore as suggested. Additionally, we have rephrased the statement for more clarity as “Studies on stigma in Nepal have mostly been carried out in mentally ill patients, not distinguishing between neurotic and psychotic disorders, making it difficult to compare and contrast the findings.”

Line 264/265 – Revise

Response: Thank you for the comment. This has been rephrased as “In studies from Nepal, all mentally ill patients were included not limiting to schizophrenia which could have led to decreased estimates of stigma prevalence in patients”.

Line 268 – studies

Response: Thank you for pointing this out. This has been corrected and “study” has been replaced with “studies”.

Line 277 – change taken

Response: Thank you for the comment. In rewriting the discussion as suggested by you and other reviewers for clarity, we have rephrased this line as well.

Line 285 – 287 – please revise

Response: Thank you for the thoughtful comment and pointing out the discrepancy. We have revised the statement as “Less than one year of duration of illness in schizophrenia could mean too short a period to fully understand the course and prognosis leading to low stigma scores”.

Reviewer #3: Presence of stigmas and their negative effects on the clinical outcome in schizophrenia is an established matter. But, this study tried to explore it from a perspective of an Asian and developing country. And that is the rationality of this study.

The study overall highlighted some new findings from Nepal's perspective.

Response: Thank you so much for highlighting the rationality in simple words. We have incorporated all your suggestions as follows in the respective sections.

But, I have some minor suggestions-

1) Introduction section can be rewritten in more concise manner.

Response: We have rewritten it and made it more concise and omitted some statements deemed not necessary.

2) Sample size determination process is not necessary in details, it can be omitted or can be written in a single sentence mentioning the p = 44%

Response: Thank you for the comment. We have summarized sample size determination in single sentence as suggested and have omitted the rest.

3) Ethical issue section and The Internalized Stigma of Mental Illness (ISMI) scale section should be more concise.

Response: We agree. We have made it more concise and omitted the unnecessary statements.

4) Result section should be more concise excluding the repetition of not so important findings described in description as well as shown in table.

Response: Thank you for the suggestion. We have omitted some texts in the results section as suggested and have made it more concise.

5) Discussion section should include the socio-demographic sections to highlight the similarities and differences with other studies, which is necessary for comparison.

Response: Thank you for the thoughtful comment. We have included pertinent sociodemographic and clinical findings in the first paragraph of discussion section as “Males outnumbered females in our study accounting to 56%, as opposed to another study from Nepal where almost 60% of the respondents were females (17). This could be because males are said to have higher incidence of schizophrenia, while if all mental illnesses are taken into consideration females are at higher risk. In line with this, a study from Poland reported almost 55% of respondents to be females (25). The mean age of the patients in our study was 37 years, which is supported by another study from Nepal reporting mean age of 35 years in mentally ill patients (15). In our study, almost 40% had comorbid substance dependence, most common being alcohol (20%). This finding is in agreement with results from a systemic review and metanalysis on any substance use disorder comorbidity in schizophrenia where prevalence rate of any substance comorbidity was 42% (26), with alcohol use disorder being around 24%”.

We have also cited more studies (reference number 25-33) while comparing and contrasting the findings with other studies.

6) Limitation section includes several limitations, which is good. But, should include clarification how they were resolved, or why this study is yet important with these limitations.

Response: Thank you for the important observation. We have rewritten the limitation section and clarified on why this study is important despite the limitations by adding the following statement: “Despite these limitations, this is one of the very few studies that has attempted to explore the level of internalized stigma in outpatients with schizophrenia in Nepali context. The diagnoses were made based on standard ICD-10 classification by psychiatrists adding on to the evidence reporting high levels of stigma in most subscales in patients with schizophrenia from perspective of Nepal, a low- and middle-income country.”

7) Conclusion section revealed as there is nothing new in this study. This section should be re-written highlighting the importance and inference of this study.

Response: Thank you for the comment. We have also rewritten the conclusion section.

Submitted filename: Responses to Reviewers.docx

Click here for additional data file.

11 Feb 2022

Internalized stigma in patients with schizophrenia: a hospital-based cross-sectional study from Nepal

PONE-D-21-32070R1

Dear Dr. Dhungana,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Soumitra Das

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #3: The authors covered up all the queries made before. If other reviewers are agreed, this study could be accepted.

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Dr Prateek Varshney

Reviewer #3: Yes: Panchanan Acharjee

3 Mar 2022

PONE-D-21-32070R1

Internalized stigma in patients with schizophrenia: a hospital-based cross-sectional study from Nepal

Dear Dr. Dhungana:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Soumitra Das

Academic Editor

PLOS ONE