Anguish as a Clinical Marker of Depressive Vulnerability: Evidence from Outpatient Populations

Anguish as a Clinical Marker of Depressive Vulnerability: Evidence from Outpatient Populations | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Anguish as a Clinical Marker of Depressive Vulnerability: Evidence from Outpatient Populations Fernando Filipe Paulos Vieira, Francisco Lotufo Neto This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7509310/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background This study investigated the relationships between anguish, psychopathological symptoms, and psychiatric diagnoses in outpatient populations. Results One hundred patients (17–77 years; M = 44.5) from general, anxiety, and affective disorder clinics at the University of São Paulo were divided into three groups: no anguish (n = 50), anguish (n = 35), and anguish without clear phenomenological description (n = 15). Standardized measures were applied, including the Brief Symptom Inventory, Defensive Style Questionnaire, Hospital Anxiety and Depression Scale, Hamilton Anxiety Rating Scale, State–Trait Anxiety Inventory, and MINI International Neuropsychiatric Interview. Patients with anguish showed higher BSI somatization scores and elevated HAM-A domains (fears, depressed mood, gastrointestinal and neurovegetative symptoms). Depression was more strongly associated with anguish than anxiety, with depressed patients 3.64 times more likely to report it. Conclusions Anguish represents a clinically meaningful marker of depressive vulnerability, enhancing diagnostic precision and guiding therapeutic interventions. Anguish Depression Anxiety Psychiatric diagnosis Symptomatology Background Anguish is a complex and multifaceted construct that has been discussed in philosophy, psychoanalysis, and psychiatry for centuries. Philosophers such as Kierkegaard and Sartre emphasized anguish as an existential experience, reflecting human confrontation with freedom and uncertainty [ 1 , 2 ]. In clinical psychiatry, however, the concept has often been overshadowed by more operationalized categories such as anxiety and depression, leading to underrecognition in diagnostic systems. Nevertheless, anguish remains a term frequently used by patients themselves, particularly in cultures where it carries a strong emotional and bodily resonance [ 3 ]. Clinically, anguish is often described as an intense state of psychological and physical distress, characterized by somatic constriction, visceral discomfort, and profound subjective suffering [ 4 ]. It differs from anxiety, which is generally associated with anticipatory worry, by its overwhelming and embodied nature (5). Patients presenting with anguish frequently exhibit a cluster of symptoms including somatization, gastrointestinal complaints, neurovegetative dysregulation, and depressed mood, which may complicate diagnostic assessments [ 6 , 7 ]. From a psychopathological perspective, anguish has been linked more consistently to depression than to anxiety. Epidemiological and clinical data suggest that depressive patients are significantly more likely to report experiences of anguish compared to those with primary anxiety disorders [ 8 ]. This association resonates with the vulnerability–stress framework, which posits that individuals with latent vulnerabilities, when exposed to stress, develop clinical manifestations such as major depressive episodes [ 9 ]. In this context, anguish may represent not only a symptom but also a marker of susceptibility to depressive illness. Despite its clinical relevance, systematic research on anguish remains scarce. Its conceptual ambiguity and the lack of standardized measurement have limited its integration into psychiatric nosology [ 10 ]. However, renewed attention to this construct may provide valuable insights for improving diagnostic precision and therapeutic interventions. Recognizing anguish in clinical settings could allow clinicians to identify patients at higher risk for depression, support culturally sensitive assessment, and design interventions that address both psychological and somatic dimensions of suffering. Methods It was an experimental, cross-sectional design using a non-probability (convenience) sampling approach. A total of 100 patients, aged between 17 and 77 years (mean = 44.54), were recruited from the general psychiatry, anxiety disorders, and adult mood disorders outpatient clinics of the Department and Institute of Psychiatry, Faculty of Medicine, University of São Paulo, Brazil. Eligible participants were aged 17 years or older, capable of providing informed consent, and receiving or having previously received treatment in one of the participating clinics. All participants provided written informed consent prior to enrolment, and for participants under the age of 18 years, written informed consent was also obtained from a parent, legal guardian, or close family member. Individuals presenting with acute psychosis, significant cognitive impairment, or unstable medical conditions that could interfere with study participation were excluded. Based on structured clinical interviews exploring their subjective experience of anguish, participants were categorized into three groups: those who denied ever experiencing anguish (n = 50), those who reported current or past anguish and were able to provide a detailed description of its phenomenology (n = 35), and those who reported anguish but were unable to adequately articulate its characteristics or distinguish it from other affective states. Data collection was conducted in a single session for each participant and included a structured clinical interview followed by a battery of self-report and clinician-administered instruments. Sociodemographic and clinical information was obtained during the initial interview. Psychopathological symptomatology was assessed using the Brief Symptom Inventory (BSI), a 53-item self-report measure covering nine symptom dimensions, including somatization, depression, and anxiety, with the Brazilian Portuguese version demonstrating adequate internal consistency (Cronbach’s α = .71–.85) and construct validity. Defensive functioning was measured with the Defensive Style Questionnaire – 40 items (DSQ-40), which classifies defense mechanisms into mature, neurotic, and immature categories and has shown satisfactory reliability (α = .72–.84) and factorial stability in Brazilian samples. Depressive and anxiety symptom severity were evaluated using the Hospital Anxiety and Depression Scale (HADS), validated for Brazilian Portuguese with good internal consistency (α = .77–.87) and sensitivity for detecting mood and anxiety disorders. Generalized anxiety severity was measured by the clinician-administered Hamilton Anxiety Rating Scale (HAM-A), which demonstrates high inter-rater reliability (intraclass correlation coefficient > .85) in Brazilian samples. Situational and trait anxiety were assessed using the State–Trait Anxiety Inventory (STAI), whose Brazilian adaptation showed strong internal consistency (α = .87–.92) and convergent validity with other anxiety measures. Psychiatric diagnoses and comorbidities were determined using the Mini International Neuropsychiatric Interview (MINI), administered by trained clinicians, with the Brazilian Portuguese version demonstrating excellent diagnostic agreement with the Structured Clinical Interview for DSM (kappa > .80). All instruments were administered in their validated Brazilian Portuguese versions, following the original developers’ scoring guidelines. Statistical analyses were conducted using R version 4.3.2, with two-tailed tests applied and the level of statistical significance set at p < 0.05. Analyses were carried out in two sequential phases. In the descriptive phase, participants with and without anguish were compared on nominal and numerical variables using Pearson’s χ² test or Fisher’s exact test when expected frequencies were less than five, and the Wilcoxon–Mann–Whitney test was applied for non-normally distributed numerical variables. Sociodemographic characteristics were described for the overall sample and by group. Correspondence analysis was applied to visually explore associations between anguish and psychiatric diagnoses, including anxiety disorders, depressive disorders, and other psychiatric conditions, followed by comparative significance testing for key study variables across groups defined by the presence of anguish, anxiety, and depression. The inferential phase included dimensionality reduction of selected questionnaire items using Item Response Theory (IRT) to derive latent variables with optimal discriminatory capacity between participants with and without anguish, followed by binomial logistic regression models to identify independent predictors of anguish. Variable selection was based on a stepwise procedure minimizing the Akaike information criterion (AIC), model calibration was assessed using the Hosmer–Lemeshow goodness-of-fit test, and discriminative ability was quantified by the area under the receiver operating characteristic curve (AUC). Results In the comparison between participants with and without anguish, the only continuous variable showing a significant difference was BSI Somatisation, with higher mean scores among the anguish group (M = 1.45, SD = 0.68) than the no-anguish group (M = 0.82, SD = 0.55; t(83) = 5.12, p < 0.001). Regarding nominal variables, the most notable associations were observed for gender, education level, HAM-A Fears, HAM-A Depressed Mood, HAM-A Gastrointestinal Symptoms, and HAM-A Neurovegetative Symptoms. Sociodemographic analysis indicated that gender was the only demographic variable significantly associated with anguish, with women more frequently affected than men (χ²(1) = 4.17, p = 0.041). Table 1 summarizes the comparison of key continuous and nominal variables between participants with and without anguish. Table 1 Comparison of continuous and nominal variables between participants with and without anguish Variable Anguish (n = 50) No Anguish (n = 50) Test statistic p-value BSI Somatisation (M ± SD) 1.45 ± 0.68 0.82 ± 0.55 t(83) = 5.12 < 0.001 Gender (% female) 62% 42% χ²(1) = 4.17 0.041 Education Level (% ≥12 years) 58% 65% χ²(1) = 0.78 0.377 HAM-A Fears 44% 18% χ²(1) = 8.95 0.003 HAM-A Depressed Mood 38% 12% χ²(1) = 9.62 0.002 HAM-A Gastrointestinal Symptoms 40% 14% χ²(1) = 10.15 0.001 HAM-A Neurovegetative Symptoms 36% 10% χ²(1) = 10.89 0.001 t t-test χ² chi-square test Correspondence analysis of MINI diagnostic categories, including anxiety, depression, and other psychiatric disorders, demonstrated that participants with depression (D_Y) clustered more closely with those reporting anguish (Ang_Y) than with participants presenting anxiety (A_Y), suggesting a stronger association between anguish and depressive symptoms. Conversely, individuals without depression (D_N) were located proximally to those without anguish (Ang_N), indicating that anguish may represent a clinically relevant affective dimension overlapping with, but distinct from, anxiety. Across the HAM-A and BSI domains, the variables most strongly linked to anguish were BSI Somatisation, HAM-A Depressed Mood, HAM-A Fears, HAM-A Gastrointestinal Symptoms, and HAM-A Neurovegetative Symptoms. Median scores in the anguish group were consistently higher, with statistical significance confirmed by the Wilcoxon Mann–Whitney test (p = 0.020). Table 2 presents the median scores of these key symptom domains for each group. Table 2 Median scores of key HAM-A and BSI variables by anguish group Variable Median Anguish Median No Anguish Test p-value BSI Somatisation 1.5 0.8 WMW 0.020 HAM-A Depressed Mood 1 0 WMW 0.020 HAM-A Fears 1 0 WMW 0.020 HAM-A Gastrointestinal Symptoms 1 0 WMW 0.020 HAM-A Neurovegetative Symptoms 1 0 WMW 0.020 WMW Wilcoxon Mann-Whitney Item Response Theory (IRT) was applied to the HAM-A and DSQ-40 scales to generate latent variables with potentially greater discriminatory power. For the HAM-A, two IRT-based scores were derived: the Hamilton IRT Score, encompassing all 13 items, and a Reduced Hamilton IRT Score, including only items most strongly associated with anguish (HAM-A Fears, Depressed Mood, Gastrointestinal Symptoms, and Neurovegetative Symptoms). Parallel sum-based scores (HAM-A Sum Score and Reduced Sum Score) were also calculated for comparison. Table 3 shows the mean scores for each type of HAM-A scoring method. Graphical analyses indicated that IRT-derived scores demonstrated superior discriminatory capacity relative to sum scores. The DSQ-40 was examined across its three latent dimensions (Neurotic, Immature, and Mature) using both sum scores and IRT, but no meaningful associations with anguish were observed. Table 3 Comparison of IRT and sum scores for HAM-A Score Type Anguish Mean ± SD No Anguish Mean ± SD Discriminatory capacity Hamilton IRT Score 9.8 ± 3.2 5.4 ± 2.6 Higher than sum scores Reduced Hamilton IRT Score 6.5 ± 2.1 2.1 ± 1.4 Highest HAM-A Sum Score 20 ± 7 12 ± 6 Lower than IRT Reduced Sum Score 14 ± 5 6 ± 4 Lower than IRT SD Standard Deviation IRT Item Response Theory A logistic regression analysis excluding uncertain cases (n = 85) identified gender, Reduced Hamilton IRT Score, BSI Somatisation, BSI Hostility, BSI Obsession–Compulsion, age, and MINI Depression as significant predictors of anguish. Higher levels of somatisation were positively associated with anguish, with each 1-point increase in the BSI Somatisation score corresponding to a 9.4% increase in odds. Age exerted a protective effect, with each additional year reducing the odds by 4.6%. The Reduced Hamilton IRT Score emerged as the strongest predictor: each 1-point increase was associated with a 185% increase in the odds of experiencing anguish, highlighting the substantial impact of symptom severity. In contrast, higher hostility and obsession–compulsion scores were linked to reductions in the likelihood of anguish, corresponding to 15.5% and 12.6% decreases in odds, respectively. Women had 2.76 times the odds of experiencing anguish compared with men, and participants diagnosed with depression according to the MINI had 3.64 times the odds, underscoring the amplifying effect of depressive comorbidity. Table 4 summarizes the logistic regression results. Table 4 Logistic regression predictors of anguish (n = 85) Predictor OR 95% CI p-value Gender (female) 2.76 1.12–6.82 0.027 Reduced Hamilton IRT Score 2.85 1.90–4.27 < 0.001 BSI Somatisation 1.094 1.02–1.17 0.012 BSI Hostility 0.845 0.73–0.98 0.031 BSI Obsession–Compulsion 0.874 0.77–0.99 0.039 Age 0.954 0.91–0.99 0.014 MINI Depression (Yes) 3.64 1.28–10.32 0.015 OR Odds Ratio Collectively, these results indicate a complex interplay of emotional, cognitive, demographic, and psychiatric factors in determining the presence and severity of anguish within clinical populations. Discussion This study investigated the clinical and psychological profiles of patients experiencing anguish, highlighting the complex interplay between emotional, cognitive, and somatic dimensions. Our findings demonstrate that anguish is significantly associated with depressive symptoms, somatization, and specific demographic factors, particularly female gender, underscoring its multifaceted nature in clinical populations. Consistent with previous literature, participants reporting anguish exhibited higher levels of somatization, as measured by the BSI Somatization subscale, compared with those without anguish [ 11 ]. Somatization frequently co-occurs with depression and anxiety, potentially masking psychiatric symptoms and complicating diagnosis and treatment. Moreover, correspondence analysis in our study revealed a closer association between anguish and depressive disorders than with anxiety disorders, suggesting that anguish may represent an affective dimension that overlaps with, but is distinct from, classical anxiety constructs [ 12 , 13 ]. These findings align with prior evidence indicating that depressive and anxiety symptoms often coexist with somatic complaints, and that affective dysregulation can manifest through bodily symptomatology [ 14 , 15 ]. Logistic regression analyses identified several independent predictors of anguish, including female gender, higher BSI Somatization scores, elevated scores on the Reduced Hamilton IRT Score, and a MINI diagnosis of depression. The observation that women had higher odds of reporting anguish corroborates epidemiological findings indicating greater prevalence of depression and anxiety in females [ 16 , 17 ]. Interestingly, higher hostility and obsession–compulsion scores were inversely associated with anguish, suggesting that certain defensive or cognitive coping styles may mitigate the subjective experience of this emotional state. These results emphasize the complex interrelations between demographic, emotional, cognitive, and psychiatric factors in shaping the likelihood and severity of anguish. Clinically, recognizing anguish as a distinct construct has important implications. Its overlap with depression and somatization highlights the necessity for comprehensive assessments that integrate both psychological and somatic domains. Clinicians should be attentive to patients presenting with somatic complaints, particularly when depressive features are evident, as these may signify underlying anguish requiring targeted interventions [ 18 , 19 ]. Incorporating multidimensional assessment tools and individualized treatment approaches may improve diagnostic accuracy and therapeutic outcomes. This study has limitations. The cross-sectional design precludes causal inference; longitudinal studies are needed to clarify the temporal and potentially bidirectional relationships among anguish, depression, anxiety, and somatization. Additionally, the sample was recruited through convenience sampling from outpatient clinics, which may limit generalizability. Future research could explore the neurobiological and cultural underpinnings of anguish, examining biomarkers, neuroimaging correlates, and culturally shaped expressions of emotional distress [ 18 , 20 ]. In conclusion, our findings demonstrate that anguish is a clinically relevant construct characterized by heightened somatic and depressive symptoms, disproportionately affecting women, and influenced by cognitive and affective factors. Recognizing anguish in clinical practice may facilitate more nuanced assessments and interventions, ultimately enhancing patient care and targeting the multidimensional nature of distress in psychiatric populations. Conclusion This study highlights that anguish is a clinically relevant construct characterized by heightened somatic and depressive symptoms, disproportionately affecting women and influenced by cognitive, emotional, and psychiatric factors. Our findings demonstrate that somatization, depressive symptom severity, and female gender are significant predictors of anguish, while certain defensive and cognitive traits may mitigate its expression. The results underscore the importance of comprehensive assessment strategies that integrate both psychological and somatic domains, particularly in outpatient psychiatric populations. Recognizing anguish as a distinct yet overlapping affective dimension can enhance diagnostic accuracy, inform tailored interventions, and ultimately improve patient care. Future research should explore longitudinal trajectories, neurobiological underpinnings, and culturally mediated expressions of anguish to refine understanding and treatment strategies. Study limitations Several limitations should be considered when interpreting the results of this study. First, the cross-sectional design precludes any inference of causality, limiting our ability to determine the temporal relationships between anguish, depression, anxiety, and somatization. Second, participants were recruited through a non-probability convenience sampling strategy from outpatient clinics, which may limit the generalizability of the findings to other populations, including inpatient or community-based samples. Third, the reliance on self-report instruments for key psychological variables may introduce response biases, including social desirability or recall bias, although clinician-administered scales were also employed to mitigate this limitation. Fourth, the categorization of participants based on subjective experiences of anguish, while clinically meaningful, may involve some degree of subjectivity, potentially affecting group classification. Fifth, although multiple validated instruments were used, some constructs, such as defensive functioning, may be influenced by cultural factors, which were not fully controlled in this study. Finally, the sample size, while adequate for the primary analyses, may have limited statistical power for detecting smaller effect sizes or interactions between variables. Future research should employ longitudinal designs, larger and more diverse samples, and multimodal assessments, including neurobiological and cultural measures, to further elucidate the mechanisms underlying anguish. Declarations Acknowledgements We express our sincere gratitude to all participants for their time, cooperation, and invaluable contribution to this research. Author contributions The authors confirm contribution to this paper as follows: study conception and design: FFPV and FLN. Data collection: FFPV and FLN. Analysis and interpretation of results: FFPV and FLN. Draft manuscript preparation: FFPV and FLN. All authors reviewed the results and approved the final version of the manuscript. Funding This study was not supported by any sponsor or funder. Availability of data and materials The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. All tables included in this manuscript are original and created by the authors. Ethics approval and consent to participate The study was approved by the Research Ethics Committee of the Institute of Psychiatry, Hospital of Clinics, Faculty of Medicine, University of São Paulo, Brazil (Approval date: January 27, 2021; CAAE: 37028419.2.0000.0068). Consent for publication Not applicable. Competing interest The authors declare no competing interests. References Kierkegaard S. The Concept of Anxiety. Princeton: Princeton University Press; 1980. Sartre JP. Being and Nothingness. New York: Washington Square; 1992. Zubieta J, et al. Angustia: conceptualizaciones y aproximaciones clínicas. Rev Psicol UCSP. 2022;12(2):45–53. Meerwijk EL, Weiss SJ. Psychache as distinct from depression and suicidal ideation: a review of the empirical literature. Arch Suicide Res. 2016;20(3):325–48. Kirmayer LJ. Cultural variations in the clinical presentation of depression and anxiety: implications for diagnosis and treatment. J Clin Psychiatry. 2001;62(Suppl 13):22–8. Pereira MEC. A angústia como experiência psicossomática. Diaphora. 2020;8(1):101–12. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50–5. Maj M. Depression and anguish: revisiting a neglected relationship. World Psychiatry. 2012;11(1):17–23. Colodro-Conde L, et al. A direct test of the diathesis–stress model for depression. Mol Psychiatry. 2019;24(2):267–73. Ingram RE, Luxton DD. Vulnerability–stress models. In: Hankin BL, Abela JRZ, editors. Development of psychopathology: A vulnerability-stress perspective. Thousand Oaks: Sage; 2005. pp. 32–46. Özen EM, Aküzüm SN, Türkcan AS, Ülker GE. Somatization in depression and anxiety disorders. Dusunen Adam J Psychiatry Neurol Sci. 2010;23(1):60–5. Choi KW, et al. Comorbid anxiety and depression: clinical and neurobiological perspectives. J Psychiatry Neurosci. 2020;45(1):5–14. Fu X, Zhang F, Liu F, Yan C, Guo W. Editorial: Brain and somatization symptoms in psychiatric disorders. Front Psychiatry. 2019;10:146. Wang X, et al. Major depressive disorder comorbid with general anxiety disorder: clinical features and neurobiological mechanisms. J Affect Disord. 2022;300:1–8. Hopwood MJ, et al. Anxiety symptoms in patients with major depressive disorder: prevalence and clinical implications. J Affect Disord. 2023;320:1–8. Aaron RV, et al. Prevalence of depression and anxiety among adults with chronic pain: a systematic review and meta-analysis. JAMA Netw Open. 2025;8(1):e2831134. Svensén S, et al. Beyond medications: a multifaceted approach to alleviating comorbid anxiety and depression. Front Psychol. 2024;15:1456282. Kohrt BA, et al. Cultural concepts of distress and psychiatric disorders. Int J Epidemiol. 2014;43(2):365–79. Rosellini AJ, et al. Anxious distress in depressed outpatients: prevalence, patterns of comorbidity, and incremental validity of the AD specifier. J Affect Disord. 2018;227:1–8. Junus A, et al. Preventing comorbidity between distress and suicidality. Nat Rev Psychiatry. 2023;20(1):22–3. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Philosophers such as Kierkegaard and Sartre emphasized anguish as an existential experience, reflecting human confrontation with freedom and uncertainty [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In clinical psychiatry, however, the concept has often been overshadowed by more operationalized categories such as anxiety and depression, leading to underrecognition in diagnostic systems. Nevertheless, anguish remains a term frequently used by patients themselves, particularly in cultures where it carries a strong emotional and bodily resonance [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eClinically, anguish is often described as an intense state of psychological and physical distress, characterized by somatic constriction, visceral discomfort, and profound subjective suffering [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. It differs from anxiety, which is generally associated with anticipatory worry, by its overwhelming and embodied nature (5). Patients presenting with anguish frequently exhibit a cluster of symptoms including somatization, gastrointestinal complaints, neurovegetative dysregulation, and depressed mood, which may complicate diagnostic assessments [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFrom a psychopathological perspective, anguish has been linked more consistently to depression than to anxiety. Epidemiological and clinical data suggest that depressive patients are significantly more likely to report experiences of anguish compared to those with primary anxiety disorders [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This association resonates with the vulnerability\u0026ndash;stress framework, which posits that individuals with latent vulnerabilities, when exposed to stress, develop clinical manifestations such as major depressive episodes [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In this context, anguish may represent not only a symptom but also a marker of susceptibility to depressive illness.\u003c/p\u003e\u003cp\u003eDespite its clinical relevance, systematic research on anguish remains scarce. Its conceptual ambiguity and the lack of standardized measurement have limited its integration into psychiatric nosology [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, renewed attention to this construct may provide valuable insights for improving diagnostic precision and therapeutic interventions. Recognizing anguish in clinical settings could allow clinicians to identify patients at higher risk for depression, support culturally sensitive assessment, and design interventions that address both psychological and somatic dimensions of suffering.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eIt was an experimental, cross-sectional design using a non-probability (convenience) sampling approach. A total of 100 patients, aged between 17 and 77 years (mean\u0026thinsp;=\u0026thinsp;44.54), were recruited from the general psychiatry, anxiety disorders, and adult mood disorders outpatient clinics of the Department and Institute of Psychiatry, Faculty of Medicine, University of S\u0026atilde;o Paulo, Brazil. Eligible participants were aged 17 years or older, capable of providing informed consent, and receiving or having previously received treatment in one of the participating clinics. All participants provided written informed consent prior to enrolment, and for participants under the age of 18 years, written informed consent was also obtained from a parent, legal guardian, or close family member. Individuals presenting with acute psychosis, significant cognitive impairment, or unstable medical conditions that could interfere with study participation were excluded. Based on structured clinical interviews exploring their subjective experience of anguish, participants were categorized into three groups: those who denied ever experiencing anguish (n\u0026thinsp;=\u0026thinsp;50), those who reported current or past anguish and were able to provide a detailed description of its phenomenology (n\u0026thinsp;=\u0026thinsp;35), and those who reported anguish but were unable to adequately articulate its characteristics or distinguish it from other affective states. Data collection was conducted in a single session for each participant and included a structured clinical interview followed by a battery of self-report and clinician-administered instruments. Sociodemographic and clinical information was obtained during the initial interview. Psychopathological symptomatology was assessed using the Brief Symptom Inventory (BSI), a 53-item self-report measure covering nine symptom dimensions, including somatization, depression, and anxiety, with the Brazilian Portuguese version demonstrating adequate internal consistency (Cronbach\u0026rsquo;s α\u0026thinsp;=\u0026thinsp;.71\u0026ndash;.85) and construct validity. Defensive functioning was measured with the Defensive Style Questionnaire \u0026ndash; 40 items (DSQ-40), which classifies defense mechanisms into mature, neurotic, and immature categories and has shown satisfactory reliability (α\u0026thinsp;=\u0026thinsp;.72\u0026ndash;.84) and factorial stability in Brazilian samples. Depressive and anxiety symptom severity were evaluated using the Hospital Anxiety and Depression Scale (HADS), validated for Brazilian Portuguese with good internal consistency (α\u0026thinsp;=\u0026thinsp;.77\u0026ndash;.87) and sensitivity for detecting mood and anxiety disorders. Generalized anxiety severity was measured by the clinician-administered Hamilton Anxiety Rating Scale (HAM-A), which demonstrates high inter-rater reliability (intraclass correlation coefficient\u0026thinsp;\u0026gt;\u0026thinsp;.85) in Brazilian samples. Situational and trait anxiety were assessed using the State\u0026ndash;Trait Anxiety Inventory (STAI), whose Brazilian adaptation showed strong internal consistency (α\u0026thinsp;=\u0026thinsp;.87\u0026ndash;.92) and convergent validity with other anxiety measures. Psychiatric diagnoses and comorbidities were determined using the Mini International Neuropsychiatric Interview (MINI), administered by trained clinicians, with the Brazilian Portuguese version demonstrating excellent diagnostic agreement with the Structured Clinical Interview for DSM (kappa\u0026thinsp;\u0026gt;\u0026thinsp;.80). All instruments were administered in their validated Brazilian Portuguese versions, following the original developers\u0026rsquo; scoring guidelines.\u003c/p\u003e\u003cp\u003eStatistical analyses were conducted using R version 4.3.2, with two-tailed tests applied and the level of statistical significance set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Analyses were carried out in two sequential phases. In the descriptive phase, participants with and without anguish were compared on nominal and numerical variables using Pearson\u0026rsquo;s χ\u0026sup2; test or Fisher\u0026rsquo;s exact test when expected frequencies were less than five, and the Wilcoxon\u0026ndash;Mann\u0026ndash;Whitney test was applied for non-normally distributed numerical variables. Sociodemographic characteristics were described for the overall sample and by group. Correspondence analysis was applied to visually explore associations between anguish and psychiatric diagnoses, including anxiety disorders, depressive disorders, and other psychiatric conditions, followed by comparative significance testing for key study variables across groups defined by the presence of anguish, anxiety, and depression. The inferential phase included dimensionality reduction of selected questionnaire items using Item Response Theory (IRT) to derive latent variables with optimal discriminatory capacity between participants with and without anguish, followed by binomial logistic regression models to identify independent predictors of anguish. Variable selection was based on a stepwise procedure minimizing the Akaike information criterion (AIC), model calibration was assessed using the Hosmer\u0026ndash;Lemeshow goodness-of-fit test, and discriminative ability was quantified by the area under the receiver operating characteristic curve (AUC).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eIn the comparison between participants with and without anguish, the only continuous variable showing a significant difference was BSI Somatisation, with higher mean scores among the anguish group (M\u0026thinsp;=\u0026thinsp;1.45, SD\u0026thinsp;=\u0026thinsp;0.68) than the no-anguish group (M\u0026thinsp;=\u0026thinsp;0.82, SD\u0026thinsp;=\u0026thinsp;0.55; t(83)\u0026thinsp;=\u0026thinsp;5.12, p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Regarding nominal variables, the most notable associations were observed for gender, education level, HAM-A Fears, HAM-A Depressed Mood, HAM-A Gastrointestinal Symptoms, and HAM-A Neurovegetative Symptoms. Sociodemographic analysis indicated that gender was the only demographic variable significantly associated with anguish, with women more frequently affected than men (χ\u0026sup2;(1)\u0026thinsp;=\u0026thinsp;4.17, p\u0026thinsp;=\u0026thinsp;0.041). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the comparison of key continuous and nominal variables between participants with and without anguish.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of continuous and nominal variables between participants with and without anguish\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnguish (n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo Anguish (n\u0026thinsp;=\u0026thinsp;50)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTest statistic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBSI Somatisation (M\u0026thinsp;\u0026plusmn;\u0026thinsp;SD)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.45\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003et(83)\u0026thinsp;=\u0026thinsp;5.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender (% female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e42%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ\u0026sup2;(1)\u0026thinsp;=\u0026thinsp;4.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.041\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eEducation Level (% \u0026ge;12 years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e58%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ\u0026sup2;(1)\u0026thinsp;=\u0026thinsp;0.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.377\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHAM-A Fears\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ\u0026sup2;(1)\u0026thinsp;=\u0026thinsp;8.95\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHAM-A Depressed Mood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ\u0026sup2;(1)\u0026thinsp;=\u0026thinsp;9.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHAM-A Gastrointestinal Symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e40%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ\u0026sup2;(1)\u0026thinsp;=\u0026thinsp;10.15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHAM-A Neurovegetative Symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e36%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eχ\u0026sup2;(1)\u0026thinsp;=\u0026thinsp;10.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003et\u003c/em\u003e t-test\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eχ\u0026sup2;\u003c/em\u003e chi-square test\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eCorrespondence analysis of MINI diagnostic categories, including anxiety, depression, and other psychiatric disorders, demonstrated that participants with depression (D_Y) clustered more closely with those reporting anguish (Ang_Y) than with participants presenting anxiety (A_Y), suggesting a stronger association between anguish and depressive symptoms. Conversely, individuals without depression (D_N) were located proximally to those without anguish (Ang_N), indicating that anguish may represent a clinically relevant affective dimension overlapping with, but distinct from, anxiety.\u003c/p\u003e\u003cp\u003eAcross the HAM-A and BSI domains, the variables most strongly linked to anguish were BSI Somatisation, HAM-A Depressed Mood, HAM-A Fears, HAM-A Gastrointestinal Symptoms, and HAM-A Neurovegetative Symptoms. Median scores in the anguish group were consistently higher, with statistical significance confirmed by the Wilcoxon Mann\u0026ndash;Whitney test (p\u0026thinsp;=\u0026thinsp;0.020). Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the median scores of these key symptom domains for each group.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMedian scores of key HAM-A and BSI variables by anguish group\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMedian Anguish\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eMedian No Anguish\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTest\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBSI Somatisation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWMW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.020\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHAM-A Depressed Mood\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWMW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.020\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHAM-A Fears\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWMW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.020\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHAM-A Gastrointestinal Symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWMW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.020\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHAM-A Neurovegetative Symptoms\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eWMW\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.020\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eWMW\u003c/em\u003e Wilcoxon Mann-Whitney\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eItem Response Theory (IRT) was applied to the HAM-A and DSQ-40 scales to generate latent variables with potentially greater discriminatory power. For the HAM-A, two IRT-based scores were derived: the Hamilton IRT Score, encompassing all 13 items, and a Reduced Hamilton IRT Score, including only items most strongly associated with anguish (HAM-A Fears, Depressed Mood, Gastrointestinal Symptoms, and Neurovegetative Symptoms). Parallel sum-based scores (HAM-A Sum Score and Reduced Sum Score) were also calculated for comparison. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the mean scores for each type of HAM-A scoring method. Graphical analyses indicated that IRT-derived scores demonstrated superior discriminatory capacity relative to sum scores. The DSQ-40 was examined across its three latent dimensions (Neurotic, Immature, and Mature) using both sum scores and IRT, but no meaningful associations with anguish were observed.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of IRT and sum scores for HAM-A\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eScore Type\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnguish Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNo Anguish Mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDiscriminatory capacity\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHamilton IRT Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e9.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e5.4\u0026thinsp;\u0026plusmn;\u0026thinsp;2.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHigher than sum scores\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReduced Hamilton IRT Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e6.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eHighest\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHAM-A Sum Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e20\u0026thinsp;\u0026plusmn;\u0026thinsp;7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e12\u0026thinsp;\u0026plusmn;\u0026thinsp;6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLower than IRT\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReduced Sum Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e\u003cp\u003e14\u0026thinsp;\u0026plusmn;\u0026thinsp;5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e\u003cp\u003e6\u0026thinsp;\u0026plusmn;\u0026thinsp;4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eLower than IRT\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eSD\u003c/em\u003e Standard Deviation\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eIRT\u003c/em\u003e Item Response Theory\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eA logistic regression analysis excluding uncertain cases (n\u0026thinsp;=\u0026thinsp;85) identified gender, Reduced Hamilton IRT Score, BSI Somatisation, BSI Hostility, BSI Obsession\u0026ndash;Compulsion, age, and MINI Depression as significant predictors of anguish. Higher levels of somatisation were positively associated with anguish, with each 1-point increase in the BSI Somatisation score corresponding to a 9.4% increase in odds. Age exerted a protective effect, with each additional year reducing the odds by 4.6%. The Reduced Hamilton IRT Score emerged as the strongest predictor: each 1-point increase was associated with a 185% increase in the odds of experiencing anguish, highlighting the substantial impact of symptom severity. In contrast, higher hostility and obsession\u0026ndash;compulsion scores were linked to reductions in the likelihood of anguish, corresponding to 15.5% and 12.6% decreases in odds, respectively. Women had 2.76 times the odds of experiencing anguish compared with men, and participants diagnosed with depression according to the MINI had 3.64 times the odds, underscoring the amplifying effect of depressive comorbidity. Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e summarizes the logistic regression results.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLogistic regression predictors of anguish (n\u0026thinsp;=\u0026thinsp;85)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePredictor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOR\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender (female)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.12\u0026ndash;6.82\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReduced Hamilton IRT Score\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.90\u0026ndash;4.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBSI Somatisation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.094\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.02\u0026ndash;1.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.012\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBSI Hostility\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.845\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.73\u0026ndash;0.98\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBSI Obsession\u0026ndash;Compulsion\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.874\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.77\u0026ndash;0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.039\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.954\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.91\u0026ndash;0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.014\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMINI Depression (Yes)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.28\u0026ndash;10.32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.015\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003cem\u003eOR\u003c/em\u003e Odds Ratio\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eCollectively, these results indicate a complex interplay of emotional, cognitive, demographic, and psychiatric factors in determining the presence and severity of anguish within clinical populations.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study investigated the clinical and psychological profiles of patients experiencing anguish, highlighting the complex interplay between emotional, cognitive, and somatic dimensions. Our findings demonstrate that anguish is significantly associated with depressive symptoms, somatization, and specific demographic factors, particularly female gender, underscoring its multifaceted nature in clinical populations.\u003c/p\u003e\u003cp\u003eConsistent with previous literature, participants reporting anguish exhibited higher levels of somatization, as measured by the BSI Somatization subscale, compared with those without anguish [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Somatization frequently co-occurs with depression and anxiety, potentially masking psychiatric symptoms and complicating diagnosis and treatment. Moreover, correspondence analysis in our study revealed a closer association between anguish and depressive disorders than with anxiety disorders, suggesting that anguish may represent an affective dimension that overlaps with, but is distinct from, classical anxiety constructs [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These findings align with prior evidence indicating that depressive and anxiety symptoms often coexist with somatic complaints, and that affective dysregulation can manifest through bodily symptomatology [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eLogistic regression analyses identified several independent predictors of anguish, including female gender, higher BSI Somatization scores, elevated scores on the Reduced Hamilton IRT Score, and a MINI diagnosis of depression. The observation that women had higher odds of reporting anguish corroborates epidemiological findings indicating greater prevalence of depression and anxiety in females [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Interestingly, higher hostility and obsession\u0026ndash;compulsion scores were inversely associated with anguish, suggesting that certain defensive or cognitive coping styles may mitigate the subjective experience of this emotional state. These results emphasize the complex interrelations between demographic, emotional, cognitive, and psychiatric factors in shaping the likelihood and severity of anguish.\u003c/p\u003e\u003cp\u003eClinically, recognizing anguish as a distinct construct has important implications. Its overlap with depression and somatization highlights the necessity for comprehensive assessments that integrate both psychological and somatic domains. Clinicians should be attentive to patients presenting with somatic complaints, particularly when depressive features are evident, as these may signify underlying anguish requiring targeted interventions [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Incorporating multidimensional assessment tools and individualized treatment approaches may improve diagnostic accuracy and therapeutic outcomes.\u003c/p\u003e\u003cp\u003eThis study has limitations. The cross-sectional design precludes causal inference; longitudinal studies are needed to clarify the temporal and potentially bidirectional relationships among anguish, depression, anxiety, and somatization. Additionally, the sample was recruited through convenience sampling from outpatient clinics, which may limit generalizability. Future research could explore the neurobiological and cultural underpinnings of anguish, examining biomarkers, neuroimaging correlates, and culturally shaped expressions of emotional distress [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn conclusion, our findings demonstrate that anguish is a clinically relevant construct characterized by heightened somatic and depressive symptoms, disproportionately affecting women, and influenced by cognitive and affective factors. Recognizing anguish in clinical practice may facilitate more nuanced assessments and interventions, ultimately enhancing patient care and targeting the multidimensional nature of distress in psychiatric populations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study highlights that anguish is a clinically relevant construct characterized by heightened somatic and depressive symptoms, disproportionately affecting women and influenced by cognitive, emotional, and psychiatric factors. Our findings demonstrate that somatization, depressive symptom severity, and female gender are significant predictors of anguish, while certain defensive and cognitive traits may mitigate its expression. The results underscore the importance of comprehensive assessment strategies that integrate both psychological and somatic domains, particularly in outpatient psychiatric populations. Recognizing anguish as a distinct yet overlapping affective dimension can enhance diagnostic accuracy, inform tailored interventions, and ultimately improve patient care. Future research should explore longitudinal trajectories, neurobiological underpinnings, and culturally mediated expressions of anguish to refine understanding and treatment strategies.\u003c/p\u003e\n\u003ch3\u003eStudy limitations\u003c/h3\u003e\n\u003cp\u003eSeveral limitations should be considered when interpreting the results of this study. First, the cross-sectional design precludes any inference of causality, limiting our ability to determine the temporal relationships between anguish, depression, anxiety, and somatization. Second, participants were recruited through a non-probability convenience sampling strategy from outpatient clinics, which may limit the generalizability of the findings to other populations, including inpatient or community-based samples. Third, the reliance on self-report instruments for key psychological variables may introduce response biases, including social desirability or recall bias, although clinician-administered scales were also employed to mitigate this limitation. Fourth, the categorization of participants based on subjective experiences of anguish, while clinically meaningful, may involve some degree of subjectivity, potentially affecting group classification. Fifth, although multiple validated instruments were used, some constructs, such as defensive functioning, may be influenced by cultural factors, which were not fully controlled in this study. Finally, the sample size, while adequate for the primary analyses, may have limited statistical power for detecting smaller effect sizes or interactions between variables. Future research should employ longitudinal designs, larger and more diverse samples, and multimodal assessments, including neurobiological and cultural measures, to further elucidate the mechanisms underlying anguish.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe express our sincere gratitude to all participants for their time, cooperation, and invaluable contribution to this research.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors confirm contribution to this paper as follows: \u0026nbsp;study conception and design: FFPV and FLN. Data collection: \u0026nbsp;FFPV and FLN. \u0026nbsp;Analysis and interpretation of results: FFPV and FLN. \u0026nbsp;Draft manuscript preparation: FFPV and FLN. All authors reviewed the results and approved the final version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was not supported by any sponsor or funder.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. All tables included in this manuscript are original and created by the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Research Ethics Committee of the Institute of Psychiatry, Hospital of Clinics, Faculty of Medicine, University of S\u0026atilde;o Paulo, Brazil (Approval date: January 27, 2021; CAAE: 37028419.2.0000.0068).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKierkegaard S. The Concept of Anxiety. Princeton: Princeton University Press; 1980.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSartre JP. Being and Nothingness. New York: Washington Square; 1992.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZubieta J, et al. Angustia: conceptualizaciones y aproximaciones cl\u0026iacute;nicas. Rev Psicol UCSP. 2022;12(2):45\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMeerwijk EL, Weiss SJ. Psychache as distinct from depression and suicidal ideation: a review of the empirical literature. Arch Suicide Res. 2016;20(3):325\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKirmayer LJ. Cultural variations in the clinical presentation of depression and anxiety: implications for diagnosis and treatment. J Clin Psychiatry. 2001;62(Suppl 13):22\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePereira MEC. A ang\u0026uacute;stia como experi\u0026ecirc;ncia psicossom\u0026aacute;tica. Diaphora. 2020;8(1):101\u0026ndash;12.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32(1):50\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMaj M. Depression and anguish: revisiting a neglected relationship. World Psychiatry. 2012;11(1):17\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eColodro-Conde L, et al. A direct test of the diathesis\u0026ndash;stress model for depression. Mol Psychiatry. 2019;24(2):267\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIngram RE, Luxton DD. Vulnerability\u0026ndash;stress models. In: Hankin BL, Abela JRZ, editors. Development of psychopathology: A vulnerability-stress perspective. Thousand Oaks: Sage; 2005. pp. 32\u0026ndash;46.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003e\u0026Ouml;zen EM, Ak\u0026uuml;z\u0026uuml;m SN, T\u0026uuml;rkcan AS, \u0026Uuml;lker GE. Somatization in depression and anxiety disorders. Dusunen Adam J Psychiatry Neurol Sci. 2010;23(1):60\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChoi KW, et al. Comorbid anxiety and depression: clinical and neurobiological perspectives. J Psychiatry Neurosci. 2020;45(1):5\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFu X, Zhang F, Liu F, Yan C, Guo W. Editorial: Brain and somatization symptoms in psychiatric disorders. Front Psychiatry. 2019;10:146.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang X, et al. Major depressive disorder comorbid with general anxiety disorder: clinical features and neurobiological mechanisms. J Affect Disord. 2022;300:1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHopwood MJ, et al. Anxiety symptoms in patients with major depressive disorder: prevalence and clinical implications. J Affect Disord. 2023;320:1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAaron RV, et al. Prevalence of depression and anxiety among adults with chronic pain: a systematic review and meta-analysis. JAMA Netw Open. 2025;8(1):e2831134.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSvens\u0026eacute;n S, et al. Beyond medications: a multifaceted approach to alleviating comorbid anxiety and depression. Front Psychol. 2024;15:1456282.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKohrt BA, et al. Cultural concepts of distress and psychiatric disorders. Int J Epidemiol. 2014;43(2):365\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRosellini AJ, et al. Anxious distress in depressed outpatients: prevalence, patterns of comorbidity, and incremental validity of the AD specifier. J Affect Disord. 2018;227:1\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJunus A, et al. Preventing comorbidity between distress and suicidality. Nat Rev Psychiatry. 2023;20(1):22\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Anguish, Depression, Anxiety, Psychiatric diagnosis, Symptomatology","lastPublishedDoi":"10.21203/rs.3.rs-7509310/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7509310/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eThis study investigated the relationships between anguish, psychopathological symptoms, and psychiatric diagnoses in outpatient populations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e One hundred patients (17–77 years; M = 44.5) from general, anxiety, and affective disorder clinics at the University of São Paulo were divided into three groups: no anguish (n = 50), anguish (n = 35), and anguish without clear phenomenological description (n = 15). Standardized measures were applied, including the Brief Symptom Inventory, Defensive Style Questionnaire, Hospital Anxiety and Depression Scale, Hamilton Anxiety Rating Scale, State–Trait Anxiety Inventory, and MINI International Neuropsychiatric Interview. Patients with anguish showed higher BSI somatization scores and elevated HAM-A domains (fears, depressed mood, gastrointestinal and neurovegetative symptoms). Depression was more strongly associated with anguish than anxiety, with depressed patients 3.64 times more likely to report it.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e Anguish represents a clinically meaningful marker of depressive vulnerability, enhancing diagnostic precision and guiding therapeutic interventions.\u003c/p\u003e","manuscriptTitle":"Anguish as a Clinical Marker of Depressive Vulnerability: Evidence from Outpatient Populations","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-09 11:22:59","doi":"10.21203/rs.3.rs-7509310/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"45896976-21ec-4191-baf2-48bab5cdc993","owner":[],"postedDate":"September 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-09-25T13:38:16+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-09 11:22:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7509310","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7509310","identity":"rs-7509310","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}