<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.181753.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Research Article</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Depression and Suicidal Ideation Among Men who have sex with men and Transgender Women in Chiang Mai, Thailand</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 1 approved with reservations]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Lynn</surname>
                        <given-names>Kyaw Sein</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Aurpibul</surname>
                        <given-names>Linda</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Project Administration</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Validation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0003-0246-8187</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Chotirosniramit</surname>
                        <given-names>Nuntisa</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Kosashunhanan</surname>
                        <given-names>Natthapol</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Srithanaviboonchai</surname>
                        <given-names>Kriengkrai</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Resources</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Oon-arom</surname>
                        <given-names>Awirut</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Visualization</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-5878-9620</uri>
                    <xref ref-type="aff" rid="a3">3</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>School of Health Sciences Research, Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Chiang Mai, 50200, Thailand</aff>
                <aff id="a2">
                    <label>2</label>Research Institute for Health Sciences, Chiang Mai University, Chiangmai, CHIANG MAI, 50200, Thailand</aff>
                <aff id="a3">
                    <label>3</label>Psychiatry, Chiang Mai University Faculty of Medicine, Chiang Mai, Chiang Mai, 50200, Thailand</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:linda.a@cmu.ac.th">linda.a@cmu.ac.th</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>21</day>
                <month>5</month>
                <year>2026</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2026</year>
            </pub-date>
            <volume>15</volume>
            <elocation-id>772</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>9</day>
                    <month>5</month>
                    <year>2026</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2026 Lynn KS et al.</copyright-statement>
                <copyright-year>2026</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/15-772/pdf"/>
            <abstract>
                <sec>
                    <title>Background</title>
                    <p>High burden of depression and suicidality were reported among men who have sex with men (MSM) and transgender women (TGW) globally. Currently, in Thailand, many of them can access to pre-exposure prophylaxis (PrEP) services for HIV prevention. We determined depression severity and suicidal ideation in PrEP users and non-users and associated factors.</p>
                </sec>
                <sec>
                    <title>Methods</title>
                    <p>A cross-sectional study was conducted at two HIV prevention clinics in Chiang Mai, Thailand. Inclusion criteria were: 1) aged &#x2265;20&#x00a0;years, 2) having sexual behaviours consistent with MSM or TGW; and 3) being a current PrEP user (using PrEP for &#x2265;6&#x00a0;months) or non-user (never used PrEP). Socio-demographic data was collected by face-to-face interview. Depression and suicidal ideation were assessed using the Patient Health Questionnaire-9 (PHQ-9), and the Columbia-Suicide Severity Rating Scale (C-SSRS), respectively. Group differences between PrEP users and non-users were examined and multiple linear regression was applied to identify associated factors.</p>
                </sec>
                <sec>
                    <title>Results</title>
                    <p>A total of 150 MSM and TGW (75 PrEP users; 75 non-users) were included. Clinically significant depression (PHQ-9 scores &#x2265;10) was observed in four PrEP users (5.3%) and 10 non-users (13.3%). PrEP users had significantly lower mean depression scores than non-users (3.80&#x00a0;&#x00b1;&#x00a0;3.46 vs. 5.96&#x00a0;&#x00b1;&#x00a0;3.76, 
                        <italic toggle="yes">p</italic>&#x00a0;&lt;&#x00a0;0.001). Suicidal ideation was uncommon, without difference between groups (
                        <italic toggle="yes">p</italic>&#x00a0;=&#x00a0;0.47). In adjusted models, PrEP use was associated with lower depression severity (
                        <italic toggle="yes">B</italic>&#x00a0;=&#x00a0;&#x2212;0.231, 
                        <italic toggle="yes">p</italic>&#x00a0;=&#x00a0;0.025), whereas higher education and high stress level were associated with depression. Depression severity was the only significant predictor of suicidal ideation (OR&#x00a0;=&#x00a0;2.82, 
                        <italic toggle="yes">p</italic>&#x00a0;=&#x00a0;0.028).</p>
                </sec>
                <sec>
                    <title>Conclusions</title>
                    <p>Lower depression frequency and severity among PrEP users suggesting that engagement with HIV-prevention services might positively affect the mental health well-being of the key populations. Incorporating depression and/or suicidal ideation screening into HIV-prevention packages would allow timely support or linkage to mental health services.</p>
                </sec>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Depression</kwd>
                <kwd>Suicidal Ideation</kwd>
                <kwd>PrEP users</kwd>
                <kwd>men who have sex with men</kwd>
                <kwd>transgender women</kwd>
            </kwd-group>
            <funding-group>
                <award-group id="fund-1">
                    <funding-source>Research Institute for Health Sciences, Chiang Mai University</funding-source>
                </award-group>
                <funding-statement>This research was supported by the Research Institute for Health Sciences, Chiang Mai University and partially supported by Chiang Mai University.</funding-statement>
                <funding-statement>
                    <italic>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</italic>
                </funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec id="sec5" sec-type="intro">
            <title>Introduction</title>
            <p>Sexual and gender diversity populations, including men who have sex with men (MSM), transgender women (TGW), and other Lesbian, Gay, Bisexual, Transgender, Queer or Questioning, and other sexual and gender minority identities (LGBTQ+ groups), experience a substantially higher burden of mental health problems than the general population. A recent systematic review and meta-analysis estimated that the pooled global prevalence of depression among MSM is about 35%, which is roughly three times more common than in the general male population (
                <xref ref-type="bibr" rid="ref14">Nouri et al., 2022</xref>) International research consistently shows that MSM and transgender women experience substantially higher levels of depression and suicidal ideation compared with the general population, with studies from the United States and India highlighting especially elevated risk among these groups (
                <xref ref-type="bibr" rid="ref24">Tomori et al., 2016</xref>; 
                <xref ref-type="bibr" rid="ref28">Wilton et al., 2018</xref>). Across diverse cultural contexts, stigma, discrimination, and social exclusion remain consistent drivers of poor mental-health outcomes among sexual and gender diversity populations (
                <xref ref-type="bibr" rid="ref15">Operario et al., 2022</xref>; 
                <xref ref-type="bibr" rid="ref16">Pellicane &amp; Ciesla, 2022</xref>).</p>
            <p>In Thailand, emerging evidence indicates that LGBTQ+ populations continue to experience substantial mental-health challenges. Recent studies have highlighted high levels of psychological distress among sexual and gender minority individuals, with a survey of Thai medical students reporting notably elevated rates of depressive and anxiety symptoms among those identifying as LGBTQ+ (
                <xref ref-type="bibr" rid="ref26">Vadhanavikkit et al., 2025</xref>). Research among TGW in Bangkok has also documented a high prevalence of depressive symptoms, with low perceived social support identified as a significant contributing factor (
                <xref ref-type="bibr" rid="ref23">Tantirattanakulchai &amp; Hounnaklang, 2021</xref>). These findings reflect broader patterns observed across Southeast Asia, where stigma, discrimination, and social marginalization continue to shape mental-health disparities among MSM and TGW. Despite these concerns, systematic data on mental-health outcomes among key populations in northern Thailand remain limited, underscoring the need for focused research in this context.</p>
            <p>Pre-exposure prophylaxis (PrEP) has become a central component of HIV prevention for MSM and TGW, offering highly effective protection when taken consistently (
                <xref ref-type="bibr" rid="ref6">Davies et al., 2016</xref>; 
                <xref ref-type="bibr" rid="ref13">Naswa &amp; Marfatia, 2011</xref>; 
                <xref ref-type="bibr" rid="ref25">Turner et al., 2018</xref>). Beyond its biomedical benefits, the relationship between PrEP use and mental health is complex. Mental health concerns such as depression and anxiety are common among individuals at heightened risk for HIV and may hinder both PrEP uptake and adherence (
                <xref ref-type="bibr" rid="ref7">Hennessy et al., 2023</xref>; 
                <xref ref-type="bibr" rid="ref12">Miller et al., 2021</xref>). At the same time, PrEP-related stigma&#x2014;arising from misconceptions within and outside LGBTQ+ communities&#x2014;can influence willingness to initiate PrEP and contribute to psychological distress. Conversely, engagement with PrEP services may provide opportunities for social support and improved emotional well-being through regular contact with affirming healthcare settings. These intersecting dynamics highlight the importance of understanding mental-health profiles among PrEP users and non-users in Thailand (
                <xref ref-type="bibr" rid="ref19">Protiere et al., 2023</xref>; 
                <xref ref-type="bibr" rid="ref21">Sarah M. Wood, 2021</xref>; 
                <xref ref-type="bibr" rid="ref22">Sun et al., 2019</xref>; 
                <xref ref-type="bibr" rid="ref30">Yigit et al., 2022</xref>). In Thailand, PrEP delivery has expanded through the Key Population-Led Health Services (KPLHS) model, including in Chiang Mai, where community-based organizations provide HIV prevention services tailored to MSM, TGW, and other key populations. These settings aim to increase accessibility and reduce stigma related to HIV prevention. Although KPLHS clinics often offer more affirming environments compared with conventional healthcare facilities, stigma and limited service uptake remain challenges in several contexts.</p>
            <p>However, existing Thai research has focused largely on PrEP-related stigma, provider attitudes, and implementation issues (
                <xref ref-type="bibr" rid="ref2">Chautrakarn et al., 2022</xref>; 
                <xref ref-type="bibr" rid="ref27">Vannakit et al., 2020</xref>), with limited attention to mental-health profiles of clients who used or did not use PrEP. Therefore, this study aimed to assess depression and suicidal ideation in MSM and TGW who were attending HIV prevention services in Chiang Mai, Thailand. We also looked for differences in mental health outcomes between PrEP users and non-users and identified potential associated factors. Understanding these patterns may support the development of integrated HIV prevention and mental-health services tailored to the needs of key populations.</p>
        </sec>
        <sec id="sec6">
            <title>Materials and methods</title>
            <sec id="sec7">
                <title>Study setting and participants</title>
                <p>Since 2016, PrEP has been firstly implemented in Thailand and become a part of the HIV prevention package a few years later (
                    <xref ref-type="bibr" rid="ref17">Phanuphak et al., 2018</xref>). Any hospital in the country can offer PrEP for those at risk for HIV acquisition, including the key populations. This cross-sectional study was conducted in Chiang Mai, Northern Thailand in 2025. At the time of this study, PrEP services are available at more than 20 government hospitals, more than 10 private hospitals, and several community-led clinics in Chiang Mai city also provide PrEP as a part of the campaign to minimize new HIV infection and achieve the HIV/AIDS elimination goal (
                    <xref ref-type="bibr" rid="ref5">

                        <italic toggle="yes">Data Center, Chiang Mai Provincial Health office.</italic>, 2025</xref>). Among these, two are the principal PrEP service providers for MSM and TGW in Chiang Mai City: PIMAN Clinic, a research-based clinic located in the main Chiang Mai University campus, and MPLUS Polyclinic, which is a Key Population-Led Health Service (KPLHS) operated by a community-based organization. Together, these two clinics, which are 7 kilometres apart, serve the majority of MSM and TGW PrEP clients in Chiang Mai (approximately 850 active clients) and represent the two dominant service delivery models in Thailand&#x2014;Healthcare facility and community-led. They were therefore selected purposively to maximize relevance, capture heterogeneity in service models, and ensure feasibility of participant recruitment. To align with programmatic definition of PrEP services target, the population of interest were biological males or transgender women who reported having sexual attraction and sexual activities with males.</p>
                <p>Recruitment was conducted through a purposive non-probability sampling strategy, aiming for a total sample size of 150 participants. A sample size of 150 participants was selected based on the commonly reported depression prevalence of approximately 35% among MSM (
                    <xref ref-type="bibr" rid="ref14">Nouri et al., 2022</xref>). With this sample, the 95% confidence interval around a 35% prevalence estimate would have a margin of error of about &#x00b1;8%, which was considered adequate for descriptive purposes. Thus, the final sample size was deemed sufficient to address the study&#x2019;s analytical aims and to explore associations between PrEP use, depression and suicidality among MSM and TGW in Chiang Mai. The study recruitment occurred from March to May 2025, with 75 participants enrolled from each clinic. Within each site, both MSM and TGW were included, ensuring balanced representation across service models. Inclusion criteria were: (1) aged &#x2265;20&#x00a0;years; (2) having sexual behaviours consistent with MSM or TGW; and (3) either a current PrEP user (&#x2265;6&#x00a0;months) or a non-user (never used PrEP). Recruitment was conducted by trained research assistants, who reviewed clinic appointment logs, approached eligible clients in waiting areas, obtained written informed consent, and administered structured questionnaires in private consultation rooms. The specific variables and measures used were as follows:</p>
            </sec>
            <sec id="sec8">
                <title>Data collection</title>
                <p>

                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Socio-demographic Factors</p>
                        </list-item>
                    </list>
                </p>
                <p>Participant data included age, self-identified gender identity (categorized as male, female, transgender woman, non-binary), education level, living arrangement, employment status and monthly income. Some participants self-identified as female or non-binary on the gender item; however, they were included because they met the study&#x2019;s behavioural eligibility criteria for MSM or TGW. This classification approach is consistent with programmatic definitions used in Thailand&#x2019;s PrEP services, which prioritize behavioural risk over identity labels. Behavioural classification was prioritized over gender label to ensure accurate inclusion of key populations relevant to HIV prevention services. Community safety was assessed with the item: &#x201c;Do you feel safe in your current living community?&#x201d; Participants selected one of two response options: Always safe or not always safe. Stress level was measured with a single-item indicator: &#x201c;How would you rate your current stress level?&#x201d; Responses were dichotomized into High stress and Low/no stress based on participants&#x2019; self-evaluation. LGBTQ+ community involvement was evaluated with the question: &#x201c;Are you actively involved in LGBTQ+ related community activities or groups?&#x201d; with binary response options: Yes or No.
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Depression</p>
                        </list-item>
                    </list>
                </p>
                <p>Depression severity was measured using the Patient Health Questionnaire-9 (PHQ-9).(
                    <xref ref-type="bibr" rid="ref8">Kroenke et al., 2001</xref>) This is a 9-item self-report scale assessing the frequency of depressive symptoms over the past two weeks on a 4-point scale (0&#x00a0;=&#x00a0;&#x2018;Not at all&#x2019; to 3&#x00a0;=&#x00a0;&#x2018;Nearly every day&#x2019;). A total score was calculated by summing the responses, ranging from 0 to 27. The continuous PHQ-9 total score (`Depression Score`) was categorized into `Depression Severity` levels (Non-Minimal, Mild, Moderate, Moderately Severe, Severe) based on standard clinical cut-offs (0&#x2013;4, 5&#x2013;9, 10&#x2013;14, 15&#x2013;19, 20&#x2013;27), and clinically significant depression was defined as PHQ-9&#x00a0;&#x2265;&#x00a0;10.The Thai version of the PHQ-9 has demonstrated good reliability and validity for screening major depression, with a Cronbach&#x2019;s alpha of 0.79 yielding 84% sensitivity and 77% specificity. (
                    <xref ref-type="bibr" rid="ref9">Lotrakul et al., 2008</xref>)
                    <list list-type="bullet">
                        <list-item>
                            <label>&#x2022;</label>
                            <p>Suicidal Ideation/Risk</p>
                        </list-item>
                    </list>
                </p>
                <p>Suicidal ideation and risk were assessed using the Columbia-Suicide Severity Rating Scale (C-SSRS) Screen Version. (
                    <xref ref-type="bibr" rid="ref18">Posner et al., 2011</xref>) It demonstrated good convergent and divergent validity with high sensitivity and specificity. The Thai version is also validated and accessible from the Columbia Lighthouse Project Website. (
                    <xref ref-type="bibr" rid="ref4">

                        <italic toggle="yes">The Columbia Lighthouse Project</italic>, 2016</xref>) Individual Yes/No responses to items covering wished dead, thoughts of killing self, method, intent, plan, and behaviour (Items 1&#x2013;6) were collected. These responses were summarized into a single multi-categorical variable (`Suicidal Thoughts`) representing different levels of suicidal ideation and risk.</p>
            </sec>
            <sec id="sec9">
                <title>Data analysis</title>
                <p>All data were entered and analyzed using the Statistical Package for the Social Sciences (SPSS), version 25. Data cleaning included verifying entries, checking for out-of-range values, and correcting entry errors.</p>
                <p>Descriptive analyses were used to summarize sociodemographic, psychosocial, and outcome variables, presented as frequencies, percentages, means, and standard deviations. Group comparisons between PrEP users and non-users were conducted using &#x03c7;
                    <sup>2</sup> tests for categorical variables and independent-samples 
                    <italic toggle="yes">t</italic> tests (or Mann&#x2013;Whitney U tests for non-normal distributions) for continuous variables.</p>
                <p>Regression analyses were conducted to identify predictors of key outcomes. Multivariable linear regression models were used for the continuous outcomes of depression severity (PHQ-9 total score) and a binary logistic regression model was used for suicidal ideation. Covariates entered into all multivariable models included age, education, employment status, monthly income, community safety, stress level, social support, PrEP use, and LGBTQ+ community involvement. All reported findings therefore represent adjusted associations. Model assumptions were examined: residuals were inspected for linearity and homoscedasticity, and variance inflation factors (VIFs &lt;2.0) indicated no problematic multicollinearity.</p>
            </sec>
        </sec>
        <sec id="sec10" sec-type="results">
            <title>Results</title>
            <sec id="sec11">
                <title>Participant characteristics</title>
                <p>A total of 150 participants were included in the analysis, comprising 75 PrEP users and 75 non-users. Sociodemographic and psychosocial characteristics by PrEP use status are presented in 
                    <xref ref-type="table" rid="T1">
Table 1</xref>. Of the 150 participants, the majority self-identified as MSM (76.0%), followed by transgender women (16.0%), non-binary individuals (5.3%), and a small proportion biological males who identified themselves as female (2.7%).</p>
                <table-wrap id="T1" orientation="portrait" position="float">
                    <label>
Table 1. </label>
                    <caption>
                        <title>Comparison of sociodemographic and psychosocial characteristics by PrEP use status.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Characteristics</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Those who use PrEP (n&#x00a0;=&#x00a0;75)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Those who do not use PrEP (n&#x00a0;=&#x00a0;75)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">p value</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="bottom">
                                    <bold>Age group (years)</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">0.03</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">20&#x2013;40&#x00a0;years</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">65 (47.1%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">73 (52.9%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">After 40&#x00a0;years</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">10 (83.3%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">2 (16.7%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="bottom">
                                    <bold>Education level</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">0.54</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">High/Vocational school or lower</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">13 (43.3%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">62 (51.7%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Undergraduate or higher</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">62 (51.7%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">58 (48.3%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="bottom">
                                    <bold>Living arrangement</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">0.25</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Living alone</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">39 (55.7%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">31 (44.3%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Living with others (Family or friends)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">36 (45.0%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">44 (55.0%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="bottom">
                                    <bold>Employment Status</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">0.02</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Unemployed/student</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">13 (33.3%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">26 (66.7%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Employed</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">62 (55.9%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">49 (44.1%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="bottom">
                                    <bold>Monthly income</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">1</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Low income (&lt;20,000 THB or no income)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">48 (49.5%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">49 (50.5%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Higher income (&gt;20,000 THB)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">27 (50.9%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">26 (49.1%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="bottom">
                                    <bold>Experience of discrimination</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">0.5</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Experienced discrimination</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">47 (52.8%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">42 (47.2%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">No discrimination</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">28 (45.9%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">33 (54.1%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="bottom">
                                    <bold>Family/Society pressure</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">0.14</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">High pressure</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">16 (39.0%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">25 (61.0%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Low/No pressure</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">59 (54.1%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">50 (45.9%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="bottom">
                                    <bold>Community safety</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">0.04</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Always safe</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">48 (57.8%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">35 (42.2%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Not always safe</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">27 (40.3%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">40 (59.7%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="bottom">
                                    <bold>Current stress level</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">0.01</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">High stress</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">0 (0.00%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">7 (100%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Low stress</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">75 (52.4%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">68 (47.6%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="bottom">
                                    <bold>Social support</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">0.12</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Has support</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">75 (51.4%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">71 (48.6%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">No support</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">0 (0.00%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">4 (100%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="3" rowspan="1" valign="bottom">
                                    <bold>LGBTQ+ Community involvement</bold>
</td>
                                <td align="left" colspan="1" rowspan="1" valign="middle">&lt;0.01</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">Yes</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">66 (55.9%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">52 (44.1%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">No</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">9 (28.1%)</td>
                                <td align="left" colspan="1" rowspan="1" valign="bottom">23 (71.9%)</td>
                                <td colspan="1" rowspan="1"/>
                            </tr>
                        </tbody>
                    </table>
                    <table-wrap-foot>
                        <p>PrEP pre-exposure prophylaxis; THB Thai baht; LGBTQ Lesbian, gay, bisexual, transgender, queers plus.</p>
                    </table-wrap-foot>
                </table-wrap>
                <p>The 
PrEP users were more likely to be in the older age group (after 40&#x00a0;years) compared with non-users (83.3% vs. 16.7%, 
                    <italic toggle="yes">p</italic>&#x00a0;=&#x00a0;0.03), with a higher proportion being employed than non-users (55.9% vs. 44.1%, 
                    <italic toggle="yes">p</italic>&#x00a0;=&#x00a0;0.02). Perceived community safety was higher among PrEP users, with 57.8% reporting always feeling safe compared with 42.2% of non-users (
                    <italic toggle="yes">p</italic>&#x00a0;=&#x00a0;0.04). Stress levels differed significantly between groups; none of the PrEP users reported high stress level, whereas 100% of the non-users did (
                    <italic toggle="yes">p</italic>&#x00a0;=&#x00a0;0.01). PrEP users were more likely involved in LGBTQ+ community than non-users (55.9% vs. 44.1%, 
                    <italic toggle="yes">p</italic>&#x00a0;&lt;&#x00a0;0.01). Other characteristics, including education, living arrangement, income, discrimination, family pressure, and social support, did not differ significantly between the two groups (
                    <italic toggle="yes">p</italic>&#x00a0;&gt;&#x00a0;0.05).</p>
            </sec>
            <sec id="sec12">
                <title>Depression and suicidal ideation</title>
                <p>Mental-health outcomes by PrEP use status are summarized in 
                    <xref ref-type="table" rid="T2">
Table 2</xref>. The mean depression score was significantly lower among PrEP users (mean&#x00a0;=&#x00a0;3.80, SD&#x00a0;=&#x00a0;3.46) compared with non-users (mean&#x00a0;=&#x00a0;5.96, SD&#x00a0;=&#x00a0;3.76), with a mean difference of 2.16 (95% CI: 0.99&#x2013;3.33; 
                    <italic toggle="yes">p</italic>&#x00a0;&lt;&#x00a0;0.001). Clinically significant depression (PHQ-9&#x00a0;&#x2265;&#x00a0;10) was observed in 4 PrEP users (5.3%) and 10 non-users (13.3%), indicating a higher proportion of moderate-to-severe depressive symptoms among those not using PrEP.</p>
                <table-wrap id="T2" orientation="portrait" position="float">
                    <label>
Table 2. </label>
                    <caption>
                        <title>Mental health outcomes among PrEP users and non-users.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Variables</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Those who use PrEP (mean, SD)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Those who do not use PrEP (mean, SD)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Mean difference (95% CI)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">p-value
</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Depression score</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">3.80, 3.46</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">5.96, 3.76</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2.16 (0.99, 3.33)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&lt;0.001</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Suicidal ideation</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.07, 0.25</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.04, 0.19</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2212;0.027 (&#x2212;0.10, 0.05)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.47</td>
                            </tr>
                        </tbody>
                    </table>
                    <table-wrap-foot>
                        <p>PrEP pre-exposure prophylaxis; SD standard deviation; CI confident interval</p>
                    </table-wrap-foot>
                </table-wrap>
                <p>The 
frequencies of suicidal ideation were 7% among PrEP users and 4% among non-users, without difference between group.</p>
            </sec>
            <sec id="sec13">
                <title>Factors associated with depression</title>
                <p>A multiple linear regression model was conducted to examine predictors of depression severity 
                    <bold>

                        <italic toggle="yes">(</italic>
</bold>
                    <xref ref-type="table" rid="T3">
Table 3</xref>
                    <bold>

                        <italic toggle="yes">).</italic>
</bold> Education level was a significant predictor, with higher education associated with higher depression scores (
                    <italic toggle="yes">B</italic>&#x00a0;=&#x00a0;0.125, 
                    <italic toggle="yes">p</italic>&#x00a0;=&#x00a0;0.024). Current stress level was also positively associated with depression severity (
                    <italic toggle="yes">B</italic>&#x00a0;=&#x00a0;0.234, 
                    <italic toggle="yes">p</italic>&#x00a0;=&#x00a0;0.01).</p>
                <table-wrap id="T3" orientation="portrait" position="float">
                    <label>
Table 3. </label>
                    <caption>
                        <title>Linear Regression for Depression Severity.</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Predictors</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">B</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">SE</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">&#x03b2; (Beta)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">t</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">p-value
</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">95% CI for B</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">VIF</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">(Constant)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1.532</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.723</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2014;</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2.119</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.036</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">[0.103, 2.962]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2014;</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Age in years</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.007</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2212;0.002</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2212;0.027</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.979</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">[&#x2212;0.014, 0.013]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1.077</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Education level</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.125</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.055</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.133</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2.289</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.024</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">[0.017, 0.233]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1.036</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Current stress frequency</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.234</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.089</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.161</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">2.617</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.01</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">[0.057, 0.410]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1.177</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">PrEP Adherence</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2212;1.078</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.595</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2212;0.104</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2212;1.81</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.072</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">[&#x2212;2.254, 0.099]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1.013</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">PHQ-9 Diagnosis (Cut-off &#x2265;10)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1.694</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.165</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.618</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">10.289</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&lt;.001</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">[1.368, 2.019]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1.115</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">PrEP Use</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2212;0.231</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.102</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2212;0.136</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2212;2.261</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">0.025</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">[&#x2212;0.433, &#x2212;0.029]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1.124</td>
                            </tr>
                        </tbody>
                    </table>
                    <table-wrap-foot>
                        <p>PrEP pre-exposure prophylaxis; SE standard error; VIF Variance Inflation Factor</p>
                    </table-wrap-foot>
                </table-wrap>
                <p>PrEP use was independently negatively associated with lower depression scores (B&#x00a0;=&#x00a0;&#x2212;0.231, p&#x00a0;=&#x00a0;0.025) after adjusting for covariates. Other covariates, including age and PrEP adherence, were found as insignificant predictors. No multicollinearity concerns were identified (all VIF values &lt;2).</p>
            </sec>
            <sec id="sec14">
                <title>Factors associated with suicidal ideation</title>
                <p>A logistic regression model was performed to identify predictors of suicidal ideation. PHQ-9 depression severity was the only significant predictor, with higher depressive symptoms associated with increased odds of suicidal ideation (
                    <italic toggle="yes">OR</italic>&#x00a0;=&#x00a0;2.822, 95% CI: 1.120&#x2013;7.110; 
                    <italic toggle="yes">p</italic>&#x00a0;=&#x00a0;0.028). PrEP use and other sociodemographic or psychosocial factors were not significantly associated with suicidal ideation.</p>
            </sec>
        </sec>
        <sec id="sec15" sec-type="discussion">
            <title>Discussion</title>
            <p>This study compared depression severity and suicidal ideation between PrEP users and non-users among MSM and TGW in Chiang Mai and examined sociodemographic and psychosocial correlates of these mental-health outcomes. PrEP users had significantly lower depression scores than non-users, while suicidal ideation was infrequent overall and did not differ by PrEP status. In multivariable models, PrEP use remained associated with lower depression, whereas depression severity, but not PrEP use, was associated with suicidal ideation.</p>
            <p>This study has several limitations. Its cross-sectional design prevents causal inference; thus, we cannot determine whether PrEP use leads to lower depression or whether individuals with lower depression are more likely to access and adhere to PrEP. The sample was recruited from two community-based sites in a single province, which may limit generalizability to MSM and TGW in other regions or those not connected to services. Self-reported measures of depression and suicidal ideation are subject to underreporting, especially given stigma around mental-health disclosure. Finally, the low number of participants with suicidal ideation reduced the power to detect associations beyond depression.</p>
            <p>Despite these limitations, the study provides important insights into mental-health differences between PrEP users and non-users in a key-population setting in northern Thailand. The results support calls for integrating mental-health screening and support into PrEP programs, particularly within community-led models that already serve MSM and TGW. Incorporating routine assessment of depressive symptoms, stress, and suicidality, along with referral pathways and brief psychosocial interventions, could enhance both mental health and HIV-prevention outcomes.</p>
            <p>Our finding of a substantial burden of depressive symptoms among MSM and TGW is consistent with global evidence showing elevated depression in this population. A 2022 meta-analysis estimated that depression among MSM was nearly three times more common than in the general male population, highlighting the persistent mental-health inequality faced by this group (
                <xref ref-type="bibr" rid="ref14">Nouri et al., 2022</xref>). Longitudinal research among MSM without HIV in China has also shown that anxiety and depression are highly prevalent and remain elevated over time, underscoring the chronic nature of psychological distress in MSM communities (
                <xref ref-type="bibr" rid="ref29">Wu et al., 2022</xref>). Among transgender women, high levels of depression have been reported in several Asian settings. A study of trans women in Bangkok found that more than half met criteria for depression, and low perceived social support was strongly associated with depressive symptoms, which is similar to the pattern of stress and support observed in our data (
                <xref ref-type="bibr" rid="ref23">Tantirattanakulchai &amp; Hounnaklang, 2021</xref>).</p>
            <p>The lower depression scores among PrEP users in our study are in line with emerging literature on the mental-health dimensions of PrEP. A 2023 study examining PrEP, anxiety, and depression among MSM found that mental-health concerns such as depression and anxiety were closely related to PrEP use patterns and impacted broader quality of life and sexual satisfaction, suggesting that PrEP is embedded within a wider psychosocial context rather than being a purely biomedical intervention (
                <xref ref-type="bibr" rid="ref20">Reiriz et al., 2023</xref>). More recently, a 2024 study of Chinese MSM initiating PrEP showed distinct trajectories of anxiety and depression during PrEP use and concluded that mental-health support should be integrated into PrEP programs to sustain adherence and well-being (
                <xref ref-type="bibr" rid="ref3">Chen et al., 2024</xref>). Together, these findings support our interpretation that engagement in PrEP services, particularly in community-based settings, may be associated with more favourable mental-health profiles, while also highlighting that PrEP users remain vulnerable to stress and require ongoing psychosocial support.</p>
            <p>Although suicidal ideation was relatively rare in our sample and did not differ by PrEP status, the strong association between depression and suicidal thoughts in our regression analysis is consistent with the broader literature on sexual and gender minority mental health. A 2024 analysis of adults with sexual and gender diversity from multiple cohorts found that they were at substantially higher risk of suicidal thoughts and behaviors compared with cisgender heterosexual peers, and that depression and discrimination were key correlates of suicide risk (
                <xref ref-type="bibr" rid="ref11">Manges et al., 2024</xref>).</p>
            <p>The patterns observed in this study mirror broader Southeast Asian evidence showing substantial mental-health challenges among LGBTQ+ communities. A recent paper on Thai TGW highlighted that depression prevalence was many times higher than in the general population and that perceived low social support dramatically increased the odds of depression, reinforcing the importance of social and structural determinants (
                <xref ref-type="bibr" rid="ref23">Tantirattanakulchai &amp; Hounnaklang, 2021</xref>). Regional work has similarly emphasized that stigma, discrimination, and limited access to affirming mental-health care remain key drivers of poor outcomes, underscoring the need for integrated HIV and mental-health services tailored to MSM and TGW (
                <xref ref-type="bibr" rid="ref1">Chaovanalikit et al., 2022</xref>).</p>
            <p>Our findings from Chiang Mai are consistent with these national patterns and suggest that MSM and TGW engaging in HIV prevention services still face substantial mental-health needs that are not routinely addressed in clinical care. A strength of this work is the use of validated measures and multivariable models to explore multiple psychosocial outcomes within a key population.</p>
        </sec>
        <sec id="sec16" sec-type="conclusion">
            <title>Conclusion</title>
            <p>These findings support the benefit of integrating mental-health support within HIV prevention settings in Thailand, which could be a valuable entry point for routine screening and early identification of depression, alongside referral pathways for individuals requiring additional care. Strengthening mental-health services within PrEP delivery models may improve both psychological well-being and HIV-prevention outcomes for MSM and TGW.</p>
            <p>Future research should use longitudinal designs to clarify the temporal relationships between PrEP engagement, psychosocial stressors, and mental-health trajectories. Additional studies across diverse regions of Thailand are also needed to inform more inclusive and comprehensive mental-health strategies for key populations.</p>
        </sec>
        <sec id="sec17">
            <title>Ethical considerations</title>
            <p>The study protocol was reviewed and approved by the Institutional Review Board of Chiang Mai University (certificate no.41/67). Written informed consent was obtained from all participants before data collection.</p>
        </sec>
    </body>
    <back>
        <sec id="sec20" sec-type="data-availability">
            <title>Data availability statement</title>
            <p>The data that support the findings of this study can be accessed from Zenodo repository. Dataset_depression and suicidal ideation in Thai MSM [Data set]. Zenodo. 
                <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5281/zenodo.20061760">https://doi.org/10.5281/zenodo.20061760</ext-link> (
                <xref ref-type="bibr" rid="ref10">Lynn, K. S., 2026</xref>).</p>
        </sec>
        <ack>
            <title>Acknowledgments</title>
            <p>The author thanks the staff and participants at PIMAN Clinic and MPLUS Polyclinic for their support and cooperation.</p>
            <p>An earlier version of this work was posted as a preprint on 
                <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.21203/rs.3.rs-7176096/v1;">https://doi.org/10.21203/rs.3.rs-7176096/v1;</ext-link>
            </p>
            <p>However, the current manuscript has undergone substantial revision including updated analyses and interpretation of findings.</p>
        </ack>
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    <sub-article article-type="reviewer-report" id="report489296">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.200630.r489296</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Vedovo</surname>
                        <given-names>Francesca</given-names>
                    </name>
                    <xref ref-type="aff" rid="r489296a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-9791-6888</uri>
                </contrib>
                <aff id="r489296a1">
                    <label>1</label>University of Trieste, Trieste, Italy</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>1</day>
                <month>6</month>
                <year>2026</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2026 Vedovo F</copyright-statement>
                <copyright-year>2026</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport489296" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.181753.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This manuscript addresses an important and clinically relevant topic: depression and suicidal ideation among MSM and transgender women attending HIV prevention services in Chiang Mai. The use of validated tools such as PHQ-9 and C-SSRS is a strength, and the integration of mental-health screening into PrEP services is a valuable public-health message. However, several major issues should be addressed before approval. 
                <list list-type="order">
                    <list-item>
                        <p>
                            <bold>The causal interpretation should be toned down.</bold>
                        </p>
                        <p> The study is cross-sectional, so it cannot establish whether PrEP use leads to lower depression. The authors should consistently state that PrEP use was &#x201c;associated with&#x201d; lower depression scores, without implying a protective effect.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>PrEP users and non-users differ in several baseline characteristics.</bold>
                        </p>
                        <p> The two groups differ in age, employment, perceived community safety, stress level, and LGBTQ+ community involvement. These factors may confound the association between PrEP use and depression and should be discussed more clearly.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>The regression model for depression needs revision.</bold>
                        </p>
                        <p> Table 3 includes &#x201c;PHQ-9 diagnosis/cut-off &#x2265;10&#x201d; as a predictor of PHQ-9 depression score. This is circular, because the predictor is derived from the same scale used as the outcome. This variable should be removed and the model should be repeated.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>The analysis of suicidal ideation is likely underpowered.</bold>
                        </p>
                        <p> Suicidal ideation was rare in the sample. A multivariable logistic regression with several predictors may therefore be unstable. The authors should simplify this analysis or clearly present it as exploratory.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Tables need careful checking.</bold>
                        </p>
                        <p> Some percentages and counts, especially in Table 1, are difficult to interpret and may be inconsistent. The authors should clarify whether percentages are row-based or column-based and correct any discrepancies.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>The discussion and conclusion should be more cautious.</bold>
                        </p>
                        <p> The findings support mental-health screening within HIV prevention services, but they do not prove that PrEP itself improves mental health. Alternative explanations, such as better healthcare engagement or stronger social support among PrEP users, should be emphasized.</p>
                    </list-item>
                </list> </p>
            <p> I recommend 
                <bold>major revision</bold>. The topic is relevant and potentially useful, but the statistical analysis and interpretation need important corrections before the manuscript can be approved.</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Partly</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>Partly</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Yes</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Partly</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Partly</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Partly</p>
            <p>Reviewer Expertise:</p>
            <p>I am a urologist and andrologist with clinical and research experience in sexual medicine, gender dysphoria, and transgender health. I have been involved in the assessment of sexual function in transgender women and served as the ideator and coordinator of the study group that developed the oMtFSFI questionnaire. My expertise allows me to evaluate this manuscript from the perspective of urology, andrology, sexual health, gender-affirming care, and the methodological assessment of patient-reported outcomes in transgender populations.</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
    </sub-article>
</article>
