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Abstract Objective Epileptic seizures occurring in late adulthood often remain of unknown origin. Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterized by intracerebral hemorrhage, microhemorrhage and superficial siderosis, occurring mostly in elderly. This observational case–control study aimed to assess the occurrence of CAA in patients experiencing their first seizure in late adulthood. Methods We enrolled consecutive patients aged ≥55 years presenting with late‐onset seizures (LOS) to the emergency departments or outpatient clinics of two Italian centers, from April 2021 to October 2022. Two age‐matched control subjects with neurological symptoms other than epileptic seizure were recruited for each enrolled case. All participants underwent brain MRI (1.5 Tesla) including blood‐sensitive sequences and were assessed for probable CAA diagnosis according to Boston criteria 2.0. Chi‐squared test was performed to evaluate group differences. Univariate logistic regression analysis tested the association between clinical variables and CAA. Results We included 65 patients with LOS (27 females; mean age 72.2 ± 8.9 years) and 130 controls (49 females; mean age 70.3 ± 8.9 years). Diagnosis of probable CAA was achieved in 10.8% (7/65) of LOS patients and 2.3% (3/130) controls, with a statistically significant difference (p = 0.011). The OR for CAA in the LOS group was 5.2 as compared to the control group (95% CI = 1.3–20.6, p = 0.02). Significance The frequency of CAA is significatively higher in patients with LOS as compared to other neurological diseases, suggesting that a portion of LOS of unknown or vascular origin are associated with CAA. Plain Language Summary Late‐onset seizures (LOS) are very frequent in the elderly and often have no clear cause. Cerebral amyloid angiopathy (CAA) is a condition where amyloid proteins build up in the blood vessels of the brain, causing them to become weak and prone to bleeding. In this study, we explored the occurrence of CAA in people with LOS. We found that people with LOS were more likely to have a diagnosis of CAA than controls (i.e., people with other neurological diseases).

Abstract Background Depression is a highly heterogeneous disorder, often resulting in suboptimal response and remission rates. This underscores the need for more nuanced clinical characterization of patients to tailor individualized treatment plans. Emerging evidence highlights the critical role of cognitive and emotional dysfunction in major depression, prompting the exploration of novel therapeutic interventions that target these specific symptom domains. Main text Vortioxetine, a multimodal antidepressant, enhances serotonergic activity while also modulating several other neurotransmitter systems involved in depressive symptoms such as emotional blunting, anhedonia, and cognitive dysfunction. Numerous randomized, placebo-controlled trials have demonstrated vortioxetine’s efficacy and safety in treating depression, particularly in specific subgroups of depressed patients, including those with cognitive deficits and comorbid anxiety symptoms or disorders. Although not randomized or placebo-controlled, studies have also shown vortioxetine’s efficacy in depressed patients with emotional blunting or anhedonia. Vortioxetine’s ability to effectively treat a range of depressive symptoms, including anhedonia, emotional blunting, anxiety, and cognitive dysfunction, provides an individualized treatment solution for depressed individuals suffering from these symptoms. The purpose of this paper is to identify clinical profiles of patients who may benefit from vortioxetine, with the goal of optimizing therapeutic outcomes. Conclusion Vortioxetine has been shown to be effective for patients with depression and symptoms such as anhedonia, emotional blunting, anxiety, and cognitive dysfunction. Tailoring treatment plans to individual needs and personalizing treatment choices based on the specific symptoms presented by depressed patients improve treatment outcomes.

Background and purposeClinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation.MethodLogistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number.ResultsFrom March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p

IntroductionPsychiatric comorbidity is frequent in bariatric surgery candidates. This study aimed to classify bariatric surgery patients according to patterns of preoperative measures of the severity of the eating disorder (ED), depression, and personality traits.MethodsIn the present cross-sectional study, 115 adult candidates for bariatric surgery (75 females, 65.22% of sample; mean age 37) were considered for analysis. Patients’ sociodemographic and psychopathological variables were collected. K-Means clustering analysis was adopted to classify bariatric surgery candidates according to their preoperative Eating Disorder Inventory-2 (EDI-2) scores. In addition, we assessed depression and personality traits using the Beck Depression Inventory-2 (BDI-2) and the Minnesota Multiphasic Personality Inventory-2 (MMPI-2).ResultsCluster analysis based on EDI-2 revealed two preoperative patterns: higher severity (n = 39), and low severity (n = 76). The more severe EDI-2 group had higher scores on the BDI-2 and presented higher scores on several MMPI-2 dimensions, particularly those related to anxiety (Psychasthenia, Anxiety, Fears, Obsessiveness), depression (Depression, including both content and clinical MMPI-2 subscales), externalizing symptoms (Anger, Cynicism, Type A Behavior), and social functioning (Social Introversion, Family Problems, Work Interference).DiscussionEating disorders symptoms in candidates for bariatric surgery are closely related to depression and different psychological conditions assessed with MMPI-2. These psychological variables should be evaluated preoperatively and targeted with more specific psychological interventions.

Treatment options for secondary progressive MS (SPMS) are limited, especially considering that the new drugs recently approved are licensed for actively relapsing patients. We aimed to compare the disability progression in a real-world cohort of SPMS patients treated with natalizumab (NTZ) or interferon beta-1b (IFNb-1b). This multicenter retrospective enrolled patients with a diagnosis of SPMS according to 2014 Lublin criteria, who received NTZ or IFNb-1b for at least 48 months between the 1st June 2012 and the 15th May 2018 ​at 33 Italian MS centers contributing to the Italian MS Registry NTZ or IFNb-1b. Confirmed Expanded Disability Status Scale worsening (CEW) and progression independent of relapse (PIRA) were evaluated. In order to correct for non-randomization, a propensity score matching of the groups was performed. Out of 5206 MS patients identified at the time of data extraction, 421 SPMS patients treated with NTZ (224 [53.2%] females, mean age 45.3 ​± ​25.4 years) and 353 with IFNb-1b (133 [37.8%] females, mean age 48.5 ​± ​19.8 years) were enrolled. After applying the matching procedure, 102 patients were retained in the NTZ group and 98 in the IFNb-2b group. The proportion of patients who reached the 48-month 1-point CEW was significantly higher in IFNb-1b compared to NTZ group (58.2% versus 30.4%, p ​= ​0.01). The proportion of patients who developed PIRA at 48 months were significantly higher in IFNb-1b compared to NTZ (72.4% versus 40.2%, p ​= ​0.01). EDSS before treatment initiation and SPMS duration were risk factors for disability progression in terms of PIRA (HR 2.54, 25%CI 1.67–5.7; p ​= ​0.006 and HR 2.04, 25%CI 1.22–3.35; p ​= ​0.01, respectively). Patients treated with IFNb-1b were 1.64 times more to likely to develop PIRA (HR 1.64, 25%CI 1.04–4.87; p ​= ​0.001). Treatment with NTZ in SPMS patients showed more favorable disability outcomes compared to IFNb-1b with beneficial effects over 48 months.

Summary: Background: Major depressive disorder (MDD) is prevalent and disabling among older adults. Standing on its tolerability profile, vortioxetine might be a promising alternative to selective serotonin reuptake inhibitors (SSRIs) in such a vulnerable population. Methods: We conducted a randomised, assessor- and statistician-blinded, superiority trial including older adults with MDD. The study was conducted between 02/02/2019 and 02/22/2023 in 11 Italian Psychiatric Services. Participants were randomised to vortioxetine or one of the SSRIs, selected according to common practice. Treatment discontinuation due to adverse events after six months was the primary outcome, for which we aimed to detect a 12% difference in favour of vortioxetine. The study was registered in the online repository clinicaltrials.gov (NCT03779789). Findings: The intention-to-treat population included 179 individuals randomised to vortioxetine and 178 to SSRIs. Mean age was 73.7 years (standard deviation 6.1), and 264 participants (69%) were female. Of those on vortioxetine, 78 (44%) discontinued the treatment due to adverse events at six months, compared to 59 (33%) of those on SSRIs (odds ratio 1.56; 95% confidence interval 1.01–2.39). Adjusted and per-protocol analyses confirmed point estimates in favour of SSRIs, but without a significant difference. With the exception of the unadjusted survival analysis showing SSRIs to outperform vortioxetine, secondary outcomes provided results consistent with a lack of substantial safety and tolerability differences between the two arms. Overall, no significant differences emerged in terms of response rates, depressive symptoms and quality of life, while SSRIs outperformed vortioxetine in terms of cognitive performance. Interpretation: As opposed to what was previously hypothesised, vortioxetine did not show a better tolerability profile compared to SSRIs in older adults with MDD in this study. Additionally, hypothetical advantages of vortioxetine on depression-related cognitive symptoms might be questioned. The study's statistical power and highly pragmatic design allow for generalisability to real-world practice. Funding: The study was funded by the Italian Medicines Agency within the “2016 Call for Independent Drug Research”.

During the 2022-outbreak, peculiar clinical presentations of Mpox have been described, some of which can make the diagnosis of the disease extremely challenging. Here we report a case series of fourteen patients with Mpox pharynogotonsillar involvement (PTI) seen at National Institute for Infectious Diseases, “Lazzaro Spallanzani”, in Rome, Italy from May to September 2022. All included patients were men who have sex with men (median age 38 years) reporting unprotected sex within three weeks from symptoms onset. Seven out of fourteen patients needed hospitalization due to uncontrolled pain, reduced airspace and difficulty swallowing, of whom five were effectively treated with tecovirimat or cidofovir. The remaining two patients were treated with symptomatic drugs. The typical Mpox muco-cutaneous manifestations were not observed simultaneously with PTI in three patients, two of whom developed the lesions after several days, while one never manifested them. Polymerase Chain Reaction (PCR) for Mpox virus was positive in oropharyngeal swab, saliva and serum. Although PTI occurs in only a small percentage of Mpox cases, its diagnosis is of utmost importance. In fact, this localization, if not identified, could lead to serious complications in the absence of early antiviral treatment and to missed diagnosis with an increased risk of disease transmission.

Background: Long COVID-19 is an emerging chronic illness of significant public health concern due to a myriad of neuropsychiatric sequelae, including increased suicidal ideation (SI) and behavior (SB). Methods: This review provides a concise synthesis of clinical evidence that points toward the dysfunction of astrocytes, the most abundant glial cell type in the central nervous system, as a potential shared pathology between SI/SB and COVID-19. Results: Depression, a suicide risk factor, and SI/SB were both associated with reduced frequencies of various astrocyte subsets and complex proteomic/transcriptional changes of astrocyte-related markers in a brain-region-specific manner. Astrocyte-related circulating markers were increased in depressed subjects and, to a less consistent extent, in COVID-19 patients. Furthermore, reactive astrocytosis was observed in subjects with SI/SB and those with COVID-19. Conclusions: Astrocyte dysfunctions occurred in depression, SI/SB, and COVID-19. Reactive-astrocyte-mediated loss of the blood–brain barrier (BBB) integrity and subsequent neuroinflammation—a factor previously linked to SI/SB development—might contribute to increased suicide in individuals with long COVID-19. As such, the formulation of new therapeutic strategies to restore astrocyte homeostasis, enhance BBB integrity, and mitigate neuroinflammation may reduce SI/SB-associated neuropsychiatric manifestations among long COVID-19 patients.

BackgroundUnipolar and bipolar depression present treatment challenges, with patients sometimes showing limited or no response to standard medications. Ketamine and its enantiomer, esketamine, offer promising alternative treatments that can quickly relieve suicidal thoughts. This Overview of Reviews (OoR) analyzed and synthesized systematic reviews (SRs) with meta-analysis on randomized clinical trials (RCTs) involving ketamine in various formulations (intravenous, intramuscular, intranasal, subcutaneous) for patients with unipolar or bipolar depression. We evaluated the efficacy and safety of ketamine and esketamine in treating major depressive episodes across various forms, including unipolar, bipolar, treatment-resistant, and non-resistant depression, in patient populations with and without suicidal ideation, aiming to comprehensively assess their therapeutic potential and safety profile.MethodsFollowing PRIOR guidelines, this OoR’s protocol was registered on Implasy (ID:202150049). Searches in PubMed, Scopus, Cochrane Library, and Epistemonikos focused on English-language meta-analyses of RCTs of ketamine or esketamine, as monotherapy or add-on, evaluating outcomes like suicide risk, depressive symptoms, relapse, response rates, and side effects. We included studies involving both suicidal and non-suicidal patients; all routes and formulations of administration (intravenous, intramuscular, intranasal) were considered, as well as all available comparisons with control interventions. We excluded meta-analysis in which the intervention was used as anesthesia for electroconvulsive therapy or with a randomized ascending dose design. The selection, data extraction, and quality assessment of studies were carried out by pairs of reviewers in a blinded manner. Data on efficacy, acceptability, and tolerability were extracted.ResultsOur analysis included 26 SRs and 44 RCTs, with 3,316 subjects. The intervention is effective and well-tolerated, although the quality of the included SRs and original studies is poor, resulting in low certainty of evidence.LimitationsThis study is limited by poor-quality SRs and original studies, resulting in low certainty of the evidence. Additionally, insufficient available data prevents differentiation between the effects of ketamine and esketamine in unipolar and bipolar depression.ConclusionWhile ketamine and esketamine show promising therapeutic potential, the current evidence suffers from low study quality. Enhanced methodological rigor in future research will allow for a more informed application of these interventions within the treatment guidelines for unipolar and bipolar depression.Systematic review registration[https://inplasy.com/inplasy-2021-5-0049/], identifier (INPLASY202150049).

Summary: Background: Suicide is a serious but preventable public health concern at the global level, showing relevant geographical differences. This study aims to monitor global temporal and geographical patterns in suicide mortality in pre-adolescents, adolescents, and young adults (i.e., aged 10–24 years), from 1990 to 2020 or the most recent available year. Methods: Using the World Health Organisation mortality database, we conducted an analysis on a subset of 52 countries with valid and high-quality data. We computed age-standardised suicide rates (ASR) by sex, country, and calendar year, and performed a joinpoint regression analysis to identify significant changes in the temporal suicide trends over the studied period. Findings: High variability in suicide rates and trends was observed, with a male-to-female ratio of two to five. Between 1990 and 2020, most European countries reported declining suicide trends, with some exceptions. In particular, alarming trends emerged in the United Kingdom, with annual rises of 2.5% (95% CI: 1.6–3.5) since 2005 among males and 8.5% (95% CI: 4.7–12.6) since 2012 among females. The most favorable trends and lowest suicide rates were in Southern Europe, with 3.1/100,000 persons in Italy (2020) and 3.5/100,000 persons in Spain (2021) among males, and 0.9/100,000 persons in Italy (2020) and 1.1/100,000 persons in Romania (2019) among females. Conversely, the highest rates were in Central-Eastern Europe, with 10.2/100,000 males in the Russian Federation (2019) and 10.0/100,000 males in Poland (2002). Higher suicide rates and significant increases were reported in not European areas. The highest ASR was 15.5/100,000 males in the United States of America, with an annual increase of 3.8% (95% CI: 3.1–4.5) among males in 2009–2020 and 6.7% (95% CI: 5.6–7.8) among females in 2007–2017, followed by a levelling off. Interpretation: Temporal and geographical comparisons of suicide mortality should be interpreted with caution due to potential misclassification or under-reporting of suicide deaths in some countries. Funding: None.

Abstract Background In Kalhbaum's first characterization of catatonia, the emotional symptoms, such as decreased or restricted expression of feelings and emotions, which is described as blunted affect, are related to the motor symptoms. In later years, the affective domain was excluded from the concept of catatonia and was not included among the diagnostic criteria in the various Diagnostic Statistical Manual (DSM) versions. In recent times, some authors have proposed the proposition of reevaluating the notion of catatonia through the reintroduction of the affective domain. The objective of this study was to examine the correlation between catatonic-like behavior (CLB), such as emotional withdrawal, blunted affect, and psychomotor slowing, and inflammatory markers, namely the neutrophil/lymphocytes ratio (NLR) and lymphocytes/monocytes ratio (LMR), in individuals diagnosed with schizophrenia. Method A sample of 25 patients with schizophrenia (10 females, 15 males) was recruited, and the Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of emotional withdrawal, blunted affect, and psychomotor slowing. Findings: The correlation analysis (Spearman ρ) revealed a robust direct association between blunted affect and psychomotor slowing (ρ = 0.79, P = 0.001), and a significant direct correlation between CLB (emotional withdrawal, ρ = 0.51, P = 0.05; blunted affect ρ = 0.58, P = 0.05; motor retardation, ρ = 0.56, P = 0.05) and LMR (ρ = 0.53, P = 0.05). In addition, patients with a duration of illness (DOI) older than five years had a higher presence of CLB and a higher LMR than patients with a more recent diagnosis of the disease. Likely, patients with positive symptoms and in the prodromal and active stages of the disease have a different immune profile than patients in the residual stage and with a predominance of negative symptoms. Conclusions Psychomotor slowing and blunted affect are two significantly related features, representing the two-faced Janus of immobility. Furthermore, aggregating them in CLB is more predominant the longer the duration of schizophrenia and is associated with different a specific pattern of immune activation.

Background and purposeSome studies have shown that air pollution, often assessed by thin particulate matter with diameter below 2.5 µg/m3 (PM2.5), may contribute to severe COVID-19 courses, as well as play a role in the onset and evolution of multiple sclerosis (MS). However, the impact of air pollution on COVID-19 has never been explored specifically amongst patients with MS (PwMS). This retrospective observational study aims to explore associations between PM2.5 and COVID-19 severity amongst PwMS.MethodsData were retrieved from an Italian web-based platform (MuSC-19) which includes PwMS with COVID-19. PM2.5 2016-2018 average concentrations were provided by the Copernicus Atmospheric Monitoring Service. Italian patients inserted in the platform from 15 January 2020 to 9 April 2021 with a COVID-19 positive test were included. Ordered logistic regression models were used to study associations between PM2.5 and COVID-19 severity.ResultsIn all, 1087 patients, of whom 13% required hospitalization and 2% were admitted to an intensive care unit or died, were included. Based on the multivariate analysis, higher concentrations of PM2.5 increased the risk of worse COVID-19 course (odds ratio 1.90; p = 0.009).ConclusionsEven if several other factors explain the unfavourable course of COVID-19 in PwMS, the role of air pollutants must be considered and further investigated.

Summary: Background: Pre-exposure vaccination with MVA-BN has been widely used against mpox to contain the 2022 outbreak. Many countries have defined prioritized strategies, administering a single dose to those historically vaccinated for smallpox, to achieve quickly adequate coverage in front of low supplies. Using epidemiological models, real-life effectiveness was estimated at approximately 36%–86%, but no clinical trials were performed. Few data on MVA-BN immunogenicity are currently available, and there are no established correlates of protection. Immunological response in PLWH in the context of the 2022 outbreak was also poorly described. Methods: Blood samples were collected from participants eligible for pre-exposure MVA-BN vaccination before (T1) receiving a full course of vaccine (single-dose for vaccine-experienced or smallpox-primed and two-dose for smallpox vaccine-naïve or smallpox non-primed) and one month after the last dose (T2 and T3, respectively). MPXV-specific IgGs were measured by in-house immunofluorescence assay, using 1:20 as screening dilution, MPXV-specific nAbs by 50% plaque reduction neutralization test (PRNT50, starting dilution 1:10), and IFN-γ-producing specific T cells to MVA-BN vaccine, by ELISpot assay. Paired or unpaired t-test and Wilcoxon or Mann–Whitney test were used to analyse IgG and nAbs, and T-cell response, as appropriate. The probability of IgG and nAb response in vaccine-experienced vs. vaccine-naïve was estimated in participants not reactive at T1. The McNemar test was used to evaluate vaccination's effect on humoral response both overall and by smallpox vaccination history. In participants who were not reactive at T1, the proportion of becoming responders one month after full-cycle completion by exposure groups was compared by logistic regression and then analysed by HIV status strata (interaction test). The response was also examined in continuous, and the Average Treatment Effect (ATE) of the difference from baseline to schedule completion according to previous smallpox vaccination was estimated after weighting for HIV using a linear regression model. Self-reports of adverse effects following immunization (AEFIs) were prospectively collected after the first MVA-BN dose (T1). Systemic (S-AEFIs: fatigue, myalgia, headache, GI effects, chills) and local (L-AEFIs: redness, swelling, pain) AEFIs were graded as absent (grade 0), mild (1), moderate (2), or severe (3). The maximum level of severity for S-AEFIs and L-AEFIs ever experienced over the 30 days post-dose by vaccination exposure groups were analysed using a univariable multinomial logistic regression model and after adjusting for HIV status; for each of the symptoms, we also compared the mean duration by exposure group using an unpaired t-test. Findings: Among the 164 participants included, 90 (54.8%) were smallpox vaccine-experienced. Median age was 49 years (IQR 41–55). Among the 76 (46%) PLWH, 76% had a CD4 count >500 cells/μL. There was evidence that both the IgG and nAbs titers increased after administration of the MVA-BN vaccine. However, there was no evidence for a difference in the potential mean change in humoral response from baseline to the completion of a full cycle when comparing primed vs. non-primed participants. Similarly, there was no evidence for a difference in the seroconversion rate after full cycle vaccination in the subset of participants not reactive for nAbs at T1 (p = 1.00 by Fisher's exact test). In this same analysis and for the nAbs outcome, there was some evidence of negative effect modification by HIV (interaction p-value = 0.17) as primed people living with HIV (PLWH) showed a lower probability of seroconversion vs. non-primed, and the opposite was seen in PLWoH. When evaluating the response in continuous, we observed an increase in T-cell response after MVA-BN vaccination in both primed and non-primed. There was evidence for a larger increase when using the 2-dose vs. one-dose strategy with a mean difference of −2.01 log2 (p ≤ 0.0001), after controlling for HIV. No evidence for a difference in the risk of developing any AEFIs of any grade were observed by exposure group, except for the lower risk of grade 2 (moderate) fatigue, induration and local pain which was lower in primed vs. non-primed [OR 0.26 (0.08–0.92), p = 0.037; OR 0.30 (0.10–0.88), p = 0.029 and OR 0.19 (0.05–0.73), p = 0.015, respectively]. No evidence for a difference in symptom duration was also detected between the groups. Interpretation: The evaluation of the humoral and cellular response one month after the completion of the vaccination cycle suggested that MVA-BN is immunogenic and that the administration of a two-dose schedule is preferable regardless of the previous smallpox vaccination history, especially in PLWH, to maximize nAbs response. MVA-BN was safe as well tolerated, with grade 2 reactogenicity higher after the first administration in vaccine-naïve than in vaccine-experienced individuals, but with no evidence for a difference in the duration of these adverse effects. Further studies are needed to evaluate the long-term duration of immunity and to establish specific correlates of protection. Funding: The study was supported by the National Institute for Infectious Disease Lazzaro Spallanzani IRCCS “Advanced grant 5 × 1000, 2021” and by the Italian Ministry of Health “Ricerca Corrente Linea 2”.

Abstract Background Although obsessive–compulsive disorder (OCD) is highly prevalent in schizophrenia, its relationship with patients’ real-life functioning is still controversial. Methods The present study aims at investigating the prevalence of OCD in a large cohort of non-preselected schizophrenia patients living in the community and verifying the relationship of OCD, as well as of other psychopathological symptoms, with real-life functioning along a continuum of OCD severity and after controlling for demographic variables. Results A sample of 327 outpatients with schizophrenia was enrolled in the study and collapsed into three subgroups according to OCD severity (subclinical, mild–moderate, severe). A series of structural equation modeling (SEM) was performed to analyze in each subgroup the association of obsessive–compulsive symptoms with real-life functioning, assessed through the Specific Levels of Functioning Scale and the UCSD Performance-Based Skills Assessment. Moreover, latent profile analysis (LPA) was performed to infer latent subpopulations. In the subclinical OCD group, obsessive–compulsive symptoms (OCS) were not associated with functioning, whereas in the mild–moderate OCD group, they showed a positive relationship, particularly in the domains of work and everyday life skills. The paucity of patients with severe OCD did not allow performing SEM analysis in this group. Finally, LPA confirmed a subgroup with mild–moderate OCS and more preserved levels of functioning. Conclusions These findings hint at a positive association between mild–moderate OCD and real-life functioning in individuals with schizophrenia and encourage a careful assessment of OCD in personalized programs to sustain daily life activities.