BACKGROUND:Tobacco use is highly prevalent among individuals with schizophrenia and exacerbates craving, a key METHODS: Data were collected from 1769 patients within the FondaMental Expert Centers for Schizophrenia network. Sociodemographic, clinical, addictive, suicidal, and treatment-related variables were analyzed using both univariate and multivariate logistic regression models. Mediation analyses were performed to ensure robust statistical inference. RESULTS:The prevalence of tobacco smoking was 52.8% (n = 878). Higher tobacco craving scores were significantly correlated with increased suicidal ideation (p = 0.004), more frequent suicide attempts (p < 0.001), and higher suicide scores (p < 0.001). In the multivariable analysis, no significant associations were found between craving scores and all suicide outcomes. Regression models confirmed a strong association between tobacco craving and lifetime alcohol use disorder (AUD) (p < 0.001). Mediation analyses showed that AUD does not mediate the craving-suicide relationship (indirect effects p > 0.05). CONCLUSIONS:These findings highlight the complex interplay between clinical severity, substance use, and suicidality in shaping craving levels among patients with schizophrenia. Mediation analyses showed that AUD does not explain the craving-suicide relationship, indicating that these represent separate, parallel risk pathways. Assessment of tobacco craving and comorbid substance use, particularly AUD, is essential when assessing suicide risk. These findings have important implications for suicide prevention and treatment strategies in individuals with schizophrenia and co-occurring substance use disorders.

Background and Hypothesis First impressions are rapid judgments based on limited information, significantly influencing one’s willingness to interact. Social difficulties in schizophrenia may stem from negative first impressions formed by healthy individuals. We hypothesized that healthy individuals would quickly develop negative first impressions of those with schizophrenia, driven in part by reduced facial expressions and stigma. Study Design Twenty individuals with schizophrenia and 20 age- and sex-matched healthy controls were filmed responding to a question for 30 seconds. Three hundred participants from the general population rated their first impressions of the 40 video recordings. The diagnosis of individuals with schizophrenia was either retained, disclosed, or misrepresented as autistic. To isolate the effect of facial expressions, stimuli were presented without sound using a point light display. Study Results Individuals with schizophrenia received more negative first impression ratings than healthy controls, and higher negative symptoms were linked to poorer first impression ratings. OpenFace analysis confirmed that facial expressions significantly shaped impressions, particularly mouth movement. Additionally, ratings worsened when participants’ schizophrenia diagnosis was disclosed, highlighting the harmful impact of stigma. Conversely, when mislabeled as having autism, first impression ratings improved. Conclusions This study highlights the compounded negative effects of facial expressions and schizophrenia-related stigma on first impressions. Given their significant influence on social interactions, future research should explore strategies to mitigate these effects.

INTRODUCTION:The Praecox Feeling refers to clinicians' immediate sense of disturbed interpersonal contact when encountering individuals with schizophrenia. Although considered subjective, this experience persists in clinical practice through the PANSS Poor rapport item, used as an indirect operational proxy. The behavioral substrates underlying this judgment remain insufficiently specified. We examined whether objectively quantified gestural behavior during first contact relates to clinician-rated Poor rapport and whether interaction partners adapt their nonverbal behavior accordingly. METHODS:Naïve interaction partners (IP) engaged in two first-contact interactions, one with an individual with schizophrenia (ISZ) and one with a matched control (MAT), in an ecological setting. Gestural expansiveness was quantified using automatic motion tracking. Poor rapport was assessed independently during a subsequent standardized PANSS interview conducted by a trained psychiatrist not involved in the interaction. RESULTS:Within the schizophrenia group, reduced gestural expansiveness during first contact was associated with higher clinician-rated Poor rapport. No significant group difference in gestural expansiveness was observed between ISZ and MAT. However, interaction partners showed reduced gestural expansiveness when interacting with ISZ. CONCLUSIONS:Ecologically measured gesture kinematics were associated with independently assessed clinician-rated interpersonal disturbance. These findings suggest that Praecox Feeling may reflect clinicians' sensitivity to subtle, measurable alterations in embodied interpersonal dynamics that generalize across interactional settings. Disturbed social contact appears to emerge within a dyadic system rather than from individual behavior alone. Objective movement markers may contribute to operationalizing early interpersonal disturbance and may contribute to refining the phenomenological construct of Praecox Feeling.

Executive deficits in schizophrenia are a major concern due to their strong impact on everyday functioning. Clinical neuropsychology offers several types of tools to assess executive functioning, including traditional, naturalistic, and self-rated measures. This study aimed to examine the predictive value of these different executive assessments on daily functional outcomes in schizophrenia patients. 40 individuals diagnosed with schizophrenia and 52 controls were included. All participants completed traditional executive tests (Digit Span, Trail Making Test, Color Word Interference Test, Verbal Fluency), naturalistic assessments (Paper version of the Errands Test and an alternate version of the Executive Function Performance Test [EFPT]), and a self-report measure (Behavior Rating Inventory of Executive Function-Adult Version [BRIEF-A]). Functional status was assessed using the Specific Level of Functioning Scale (SLOF). Results showed that, compared to controls, schizophrenia patients demonstrated lower executive performance and reported greater executive difficulties in daily life. After controlling for potential confounds, only the level of cueing required on the alternate EFPT and the BRIEF-A Global Executive Composite independently predicted functioning, explaining 36% of the variance in the SLOF Activities domain. These findings support the systematic inclusion of naturalistic and self-rated executive measures in neuropsychological assessments, alongside traditional tests, prior to implementing psycho-social interventions in schizophrenia.

BACKGROUND:Bipolar disorder (BD) and schizophrenia-spectrum disorders (SZ) are associated with high rates of suicidal ideation (SI) and suicide attempts (SA). Peripheral immune-vascular abnormalities may contribute to suicidal vulnerability in these disorders, but their specificity, temporal meaning, and diagnostic patterning remain unclear. METHODS:We quantified 28 peripheral immune-vascular variables (cytokines/chemokines, vascular-injury markers, blood counts, lipids) in 980 French FACE (FondaMental Advanced Centres of Expertise) outpatients with BD (n = 529) or SZ (n = 451). Elastic-net logistic regression and partial least-squares regression for binary outcomes examined associations with SA, baseline SI, and SI over 12 months in pooled and diagnosis-stratified samples. Models adjusted for age, sex, and body mass index, with sensitivity analyses for depression severity, medication classes, smoking, phenotype overlap, attrition, and missing data. RESULTS:In pooled analyses, SA was associated with higher vascular endothelial growth factor; stratified analyses suggested this signal was mainly driven by BD (OR = 1.33, 95% CI 1.08-1.64). In SZ, SA showed weaker platelet/SAA-related associations. Baseline SI showed more consistent multivariate signals than individual analytes; in BD, higher IL-7 and SAA remained associated with SI after adjustment, whereas SZ findings were more medication-sensitive. SI over 12 months showed the least stable associations; in BD, lower IL-7 was associated with follow-up SI (OR = 0.72, 95% CI 0.54-0.96). Internal validation indicated stronger performance for baseline SI than for SA or follow-up SI. CONCLUSIONS:We found modest, phenotype-dependent and partly diagnosis-specific peripheral immune-vascular correlates of SI and SA in BD and SZ. Replication and direct biological validation are needed.

Auditory verbal hallucinations (AVHs) affect 60–80

BACKGROUND AND OBJECTIVES:Low-grade systemic inflammation contributes to the pathophysiology of severe mental illness (SMI) in a substantial subset of patients, who often experience greater disease burden and poorer treatment response. Elevated C-reactive protein (CRP), defined as CRP ≥ 3 mg/L, has been proposed to identify this group, but its non-specificity limits the biomarker's ability to guide targeted intervention. We aimed to determine the most consistent drivers of high CRP across bipolar disorder (BD), schizophrenia (SZ) and major depressive disorder (MDD), and to translate these into clinically actionable intervention targets using robust data-driven methods. METHODS:We pooled and harmonised data from three large French national SMI cohorts (n = 7149: 4797 bipolar disorder, 1958 schizophrenia and 394 resistant major depression) and classified participants by CRP ≥ 3 mg/L, as well as an alternative cut-off of 5 mg/L. We applied penalised logistic regression (PLR), random forests (RF) and unsupervised clustering, using 28 biopsychosocial variables to identify robust drivers of high-CRP status. We then grouped these into actionable targets and assessed relative dominance. RESULTS:In total, 30.16% of participants had CRP ≥ 3 mg/L. PLR identified female sex (OR [95% CI]: 1.60 [1.27, 1.93]), higher BMI (OR: 1.09 [1.07, 1.13]), current nicotine dependence (OR: 1.05 [1.02, 1.09]), lower HDL cholesterol (OR: 0.57 [0.44, 0.73]) and smoking (ex-smoker status OR: 0.84 [0.66, 0.98]) as consistent drivers. RF highlighted a similar set of key drivers, also including waist circumference, triglycerides and cardiovascular comorbidities. Clustering of the high-CRP group was almost entirely driven by smoking status and nicotine dependence. When grouped into actionable targets, the identified drivers accounted for 16% of variance in CRP status, with obesity emerging as most dominant contributor. This pattern was most pronounced in females; in males it was more diffuse, with a more prominent role for smoking. CONCLUSIONS:We propose a decision tree framework where CRP can serve as a first-line screening marker for inflammation in SMI, with subsequent steps focusing on the main contributing factors to guide targeted interventions. Priority should be given to targeting obesity and metabolic dysregulation. Among females, hyperuricemia represents the next most appropriate target, whereas in males, smoking warrants greater attention. This stepwise approach provides a route from a non-specific biomarker to targeted treatment strategies and should be validated in prospective studies.

Individuals with schizophrenia exhibit a range of verbal and nonverbal impairments during social interaction, which contribute to reduced interaction quality and broader social dysfunction. To optimize clinical interventions, it is essential to identify the mechanisms underlying these deficits. Building on previous findings demonstrating reduced emotional mimicry in schizophrenia, the present study examined whether gaze aversion is associated with instances of failed mimicry during naturalistic conversation. In a within-partner design, interacting partners (n = 20) each engaged in one conversation with an individual with schizophrenia (n = 20) and one with a matched healthy control (n = 20). Prior analyses using OpenFace-based video coding revealed diminished emotional mimicry in the schizophrenia group. In the present study, the same video recordings were reanalyzed using FaceReader to extract gaze direction. We specifically examined gaze aversion during the interaction and, more critically, during episodes of failed mimicry, defined as instances in which participants did not reciprocate their partner's smile. Results indicated that although individuals with schizophrenia did not display significantly greater overall gaze aversion across the entire interaction, they exhibited significantly greater gaze aversion when their partner was smiling. This pattern was associated with a higher proportion of failed mimicry accompanied by gaze aversion in the schizophrenia group compared to controls. These findings suggest that reduced visual attention may represent one mechanism contributing to emotional mimicry deficits in schizophrenia. Clinical implications are discussed, along with the potential role of stigma in exacerbating these processes.

Background and Aims Individuals with schizophrenia exhibit markedly low levels of physical activity and prolonged inactivity, contributing to increased cardiometabolic risk and reduced life expectancy. Fatigue is highly prevalent in schizophrenia and frequently reported as a major barrier to physical activity; however, its relationship with objectively measured activity remains poorly understood. In particular, the role of maladaptive cognitive appraisals of fatigue has not been examined. This exploratory study investigated associations between self-reported fatigue, fatigue catastrophizing, and objectively measured physical activity in individuals with schizophrenia compared with non-clinical controls. Methods Sixty participants (27 individuals with schizophrenia and 33 non-clinical controls), matched on age, sex, and body mass index, wore a tri-axial wrist accelerometer continuously for seven days. Physical activity and inactivity were derived using standardized processing pipelines. Fatigue was assessed with the Multidimensional Fatigue Inventory and fatigue catastrophizing with the Fatigue Catastrophizing Scale. Associations between fatigue measures, physical activity, and clinical symptoms were examined. Results Compared with controls, individuals with schizophrenia showed significantly lower levels of light, moderate, and vigorous physical activity, alongside higher fatigue, fatigue catastrophizing, and depressive symptoms. In the schizophrenia group, fatigue severity was not associated with objectively measured physical activity. In contrast, higher fatigue catastrophizing was associated with lower moderate physical activity and reduced step count. Fatigue severity was associated with depressive and negative symptoms, but not with physical activity. Conclusion These findings suggest a dissociation between fatigue severity and actual physical activity behavior in schizophrenia and highlight fatigue catastrophizing as a key cognitive factor linked to reduced activity.

Individuals with schizophrenia generally engage in significantly less physical activities in comparison with the general population, partly due to motivation deficits, but also structural barriers such as lack of available qualified health professionals. One solution is to use social robots to facilitate engagement in exercise. This research has a dual focus: first, comparing attitudes, self-efficacy, and behavioral intentions towards engaging in exercise with NAO between individuals with schizophrenia and healthy controls; second, assessing the impact of interpersonal coordination between the robot and human on intention to engage in exercise in both groups. In this study based on health Behaviour Change Theories, 22 participants with schizophrenia were matched with 24 nonclinical participants. Physical activities were conducted with NAO under two conditions: Synchronizing (NAO is adaptive to the participant’s rhythm) and Not-Synchronizing (non-adaptive). Participants completed questionnaires measuring attitudes, self-efficacy, and intention to engage in exercise with NAO after each condition. Results indicated that both groups held generally positive attitudes towards exercise with NAO. However, individuals with schizophrenia reported lower self-efficacy compared to control participants but similar behavioral intention to engage in exercise with NAO than control participants. Behavioral intention subscales were positively correlated with positive attitudes and self-efficacy. This study contributes to the increased efforts to develop new technologies for use in mental health care interventions for adults with severe mental disorders. Finally, we will discuss the potentials and limitations of using social robots to promote exercise in individuals with schizophrenia.

Individuals with schizophrenia often experience social skill deficits, leading to reduced social interaction quality. Emotional mimicry, the automatic imitation of a counterpart’s expression, plays a crucial role in social interactions. This study introduces a novel methodology for assessing positive emotional mimicry during a naturalistic conversation. We recruited interacting partners (n = 20), each engaging in two interactions: one with an individual diagnosed with schizophrenia (n = 20) and one with a matched healthy control (n = 20). Participants were video recorded while taking turns sharing happy personal memories during six minutes. Using OpenFace, we detected participants’ emotional expressions and computed mimicry scores based on their temporal alignment. Consistent with our hypotheses, individuals with schizophrenia exhibited reduced smiling and positive emotion mimicry. Furthermore, interacting partners reported lower willingness to continue interacting with individuals with schizophrenia compared to healthy controls. This study stands out for its innovative methodology, assessing a key social skill in an ecological setting. Our findings highlight the potential of emotional mimicry training as an important intervention to improve social interaction in schizophrenia.

Individuals diagnosed with schizophrenia often experience social interaction deficits, and these difficulties may arise as early as the first encounter. First impressions, formed during initial interactions, are crucial in shaping relationship outcomes. This study explored how first impressions formed during initial encounters influence the quality of social interactions between healthy individuals and those with schizophrenia. We recruited 60 participants, including 20 healthy individuals to serve as interacting partners, 20 individuals diagnosed with schizophrenia, and 20 age and sex-matched healthy controls. Each interacting partner interacted once with an individual diagnosed with schizophrenia and once with a sex- and age-matched healthy control, without knowledge of any diagnosis. Upon arrival at the experiment location, participants were briefly introduced to each other and then asked to rate their first impressions independently. Then, they engaged in four conversational tasks, after which they assessed their willingness to continue interacting-a measure of social interaction quality. Results showed that interacting partners rated individuals with schizophrenia more negatively than healthy controls in both first impressions and willingness to continue interacting. While first impression ratings across all participants significantly predicted willingness to continue interacting, they did not mediate the group differences in willingness scores, suggesting the involvement of additional underlying factors. This study is the first to assess first impressions of individuals with schizophrenia in ecological settings, marking an important step toward understanding the factors contributing to altered first impressions of individuals diagnosed with schizophrenia.

AIMS:Recent studies on Metabolic dysfunction-associated fatty liver (MAFLD) in schizophrenia show inconsistent findings, often based on small or specific samples. This study aims to assess the prevalence of MAFLD and its sociodemographic, clinical, and treatment-related risk factors in a large cohort of chronic patients with schizophrenia. A secondary goal is to identify an immuno-inflammatory signature associated with MAFLD. METHODS:1009 stable outpatients with schizophrenia were included in the cross-sectional analysis. Individuals with liver disease, hepatitis B/C, or current alcohol use disorder were excluded. MAFLD was screened using the Fatty Liver Index (FLI), with FLI > 60 indicating MAFLD. Risk factors were assessed using multivariate logistic regression, and inflammatory markers were analysed with penalized logistic regression. RESULTS:In a sample of 1009 individuals with schizophrenia, MAFLD prevalence was 36.6 %, higher in men than in women (38.3 % vs 32.0 %, p < 0.0001). Multivariate analysis identified male gender, older age, current smokers, mood stabilizers, antidepressant, clozapine, olanzapine and quetiapine as risk factors for MAFLD. The use of risperidone was associated with a lower risk of MAFLD (0.63 (0.42-0.94). Elevated levels of inflammatory markers such as TNF-α, CRP, and IL-12/IL-23p40 were also linked to a higher likelihood of MAFLD. CONCLUSION:Although not generalizable to all patients with schizophrenia, this study confirms the high prevalence of MAFLD in individuals with schizophrenia. Psychiatrists should promote healthy lifestyle changes, such as weight control, improved diet, better sleep, and increased physical activity, to improve both physical health and quality of life in these patients.

Disruptions in language processing observed in Individuals diagnosed with schizophrenia (ISZ) are likely to impair turn-taking fluency and social functioning. While turn-taking research in ISZ is limited and mostly interview-based, this study examines fluency differences between ISZ and controls in free conversations and their links to social outcomes and symptoms. We recruited 20 ISZ, 20 healthy interacting partners (IP), and 20 matched controls (MAT). Each IP, unaware of the ISZ diagnosis, had a 6-min conversation with an ISZ and a MAT, and then rated their willingness to interact again. Voice recordings were analyzed for pauses, gaps, and overlaps. Results revealed that conversations with ISZ featured fewer overlaps, more and longer gaps, and extended pauses. Additionally, the gap duration influenced participants’ willingness to engage in future interactions. ISZ symptoms disrupted their speech and were linked to longer gaps and pauses in their partner’s speech. This study extends fluency research in ISZ by shedding light on natural conversational dynamics.

Schizophrenia (SZ) is characterized by a variable clinical expression and course peppered/hampered by severe complications. In particular, resistance to treatment (overall-TRS, treatment resistant SZ including UTRS, ultra-TRS) and metabolic syndrome (MetS) are highly prevalent, and both demonstrated to be underpinned, at least partly, by pro-inflammatory processes. Given that such processes also underlie SZ per se, we hypothesized that potential inter-twinning between SZ- and MetS-related inflammatory processes may exert a combined effect on the risk of having overall-TRS/UTRS. A total of 419 outpatients with SZ underwent clinical assessments and blood sample collection. Using the values of circulating levels of eleven cytokines, we built a ratio between pro- and anti-inflammatory components respectively corresponding to the immunoinflammatory response system (IRS) and the compensatory immunoregulatory reflex system (CIRS) which overall reflect the underlying inflammatory status. Such ratios allowed to categorize the patients according to Inflammation and MetS on four categories as follow: Inflammation(+)MetS(+), Inflammation(+)MetS(-), Inflammation(-)MetS(+) and Inflammation(-)MetS(-). Multivariate logistic regression analysis showed that the combination of inflammation and MetS modulate the risk of having the overall-TRS [Inflammation(+)MetS(-): OR=2.28, 95 %CI [1.04-5.00], p = 0.039 and Inflammation(+)MetS(+): OR=4.59, 95 % CI [1.76-11.97], p = 0.002 overall in comparison to Inflammation(-)MetS(-)]. Moreover, we observed that individuals with UTRS are those associated with both inflammation and/or MetS. Our results demonstrated the potential combined effect of MetS and inflammation towards resistance to treatment. Given that overall-TRS/UTRS are unpredictable while both inflammation and MetS can be early detected and managed, our findings shed new light on the possibility to better prevent treatment resistance in SZ.

OBJECTIVES:Psychiatric patients are frequently exposed to factors that increase their risk of developing chronic liver diseases. These factors include the presence of metabolic syndrome, high rates of current or past alcohol and illicit substance use, and the direct liver toxicity of certain psychiatric medications. Despite this, systematic screening for chronic liver diseases in this population is not routine. Transient elastography (FibroScan®), a non-invasive method to assess liver stiffness, could facilitate early detection of advanced hepatic fibrosis. This study aimed to assess the acceptability of non-invasive liver fibrosis evaluation using FibroScan® among psychiatric inpatients and to evaluate the prevalence of alcohol and illicit drug use, viral hepatitis, significant liver fibrosis, and linkage to somatic care. METHODS:This prospective, interventional cohort study was conducted in a tertiary psychiatric hospital from March 2023 to January 2024. Liver stiffness measurement (LSM) by transient elastography (FibroScan®) screening for the detection of significant liver fibrosis was proposed to all hospitalized patients after providing informed consent. Patients responded to a structured interview that included the AUDIT-C questionnaire to assess alcohol use disorders, along with items on illicit drug use and other liver disease risk factors like metabolic syndrome or viral hepatitis. Significant fibrosis was defined as liver stiffness measurement (LSM) ≥10kPa. Demographic, clinical, biological and virological data was collected from patients' medical files. RESULTS:A total of 180 patients were included in the study, with 122 (67.8%) consenting to FibroScan® screening. The cohort's mean age was 44.4±15.5 years, with 61% male. The seroprevalence of HCV antibodies was 2.5%, with a higher prevalence among men (6.5%). Chronic HBV infection prevalence was 0.81%. Metabolic syndrome was present in 28.7% of patients. Alcohol use disorders were identified in 45.9% of patients, with men showing higher AUDIT-C scores than women (P=0.04). Drug use was reported by 37.7% of patients, with recent use in 20%. Significant fibrosis was detected in 0.8% of patients and linkage to care was provided in this case. CONCLUSIONS:Transient elastography is an acceptable method for screening hepatic fibrosis in psychiatric settings. It represents an excellent option to assess other associated comorbidities in this underserved population and improve linkage to somatic care.

Background Schizophrenia (SZ) commonly manifests through multiple relapses, each impeding the path to recovery and incurring personal and societal costs. Despite the identification of various risk factors associated to the risk of relapse, the development of accurate algorithms predictive of relapse has been limited, partly due to inadequate statistical methods. Additionally, despite the wealth of data showing strong associations between inflammation and schizophrenia, the two existing studies failed to demonstrate whether inflammatory parameters could predict relapse. Our goal is then to identify clinical and inflammatory parameters associated with relapse in schizophrenia and to develop model to predict relapse in each patient. Methods We have used classical Cox regression, survival penalized regression, as well as survival random forests to analyze clinical and inflammatory biological data collected in the network of the Schizophrenia Expert Centers in France in which individuals with SZ are clinically assessed and followed up annually for 3 years. Results Among 247 individuals with SZ, 71 (29 %) experienced a psychotic relapse during the 3-year follow-up period. The variables most consistently associated with relapses were smoking status, severity of positive symptoms and low global functioning. From a panel of inflammatory parameters, only IL-8 serum levels were associated with time to relapse. The predictive performance, assessed using C-index, was 0.54 using both penalized regression and random forests. Conclusions We found several clinical and biological variables consistently associated with relapses across three distinct statistical methods. However, despite these associations, the predictive capacity of these models remained low, highlighting that association does not necessarily mean prediction.

BACKGROUND AND HYPOTHESIS:We examined the association between metacognitive performance, functioning, and quality of life (QoL) in schizophrenia using structural equation model analyses. STUDY DESIGN:A sample of 249 participants was assessed for symptoms, functioning, QoL, and both objective and subjective cognitive performance. Metacognitive performance was defined as the adequation between objective and subjective measures of cognitive performance. STUDY RESULTS:Our model showed an excellent fit (CFI = 0.981; RMSEA = 0.014-0.081) and explained 53.3 % of the variance in functioning and 50.3 % in QoL. Metacognitive performance was not significantly associated with functioning but showed a negative association with QoL (β = -0.383, p < 0.001). Thus, a greater underestimation of one's cognitive abilities was linked with lower QoL, potentially reflecting heightened awareness of deficits that affect well-being. Depression, also negatively associated with QoL (β = -0.359, p < 0.001), was linked to the underestimation of cognitive abilities, whereas symptom severity was associated with their overestimation (β = -0.296, p < 0.001). Complementary analyses suggest that the subjective cognition model closely mirrors that of metacognitive performance, questioning the distinctiveness of metacognition as an explanatory factor in schizophrenia outcomes. CONCLUSION:Our findings imply that interventions that boost confidence in cognitive abilities, such as cognitive remediation, may improve QoL. Future research should investigate the causal pathways between these factors and explore the role of social cognition, often impaired in schizophrenia, as another mediator. Comprehensive treatment that addresses clinical symptoms, depression, and subjective cognition challenges appear essential to improve outcomes in schizophrenia.

Introduction:It has been postulated that immune dysregulations may establish a link between early risk factors, such as childhood trauma (CT), and the later development of schizophrenia. Schizophrenia and experience of childhood trauma (CT) have independently been associated with increased circulating levels of inflammatory biomarkers, while CT and inflammation have also been linked to particular clinical features of the disorder. We investigated whether increased levels of inflammatory biomarkers were underpinned by CT among subjects with schizophrenia, and whether this inflammation mediated the relationship between CT and symptom dimensions. Methods:451 subjects from the FACE-SZ ("FondaMental Academic Centres of Expertise for Schizophrenia") cohort were included. Path-analysis was used to evaluate direct and indirect relationships between Childhood Trauma Questionnaire (CTQ) scores, serum concentrations of C-reactive protein (CRP), interleukin (IL)-6 and tumour necrosis factor (TNF)-α, and Positive And Negative Syndrome Scale of Schizophrenia (PANSS) scales. Results:Significant associations between CTQ and PANSS scales and between the former and inflammatory biomarkers were found. Notably, CRP was positively predicted by emotional abuse (β = 0.10) and physical neglect (β = 0.12), and negatively by emotional neglect while IL-6 (β = -0.18) was negatively predicted by sexual abuse (β = -0.05). No indirect associations between CT on PANSS through effects on the inflammatory biomarkers were found. Conclusions:Our study confirmed the association between CT and PANSS dimensions and identified novel links between CT and inflammation among patients with schizophrenia, highlighting the need for further elucidation of the complex relationships between early stress and chronic inflammation in psychiatry.