Pain is strongly influenced by expectations and learning from previous experience, such as in classical conditioning. Conditioned responses and expectations can generalize to perceptually and conceptually related cues, but how generalization influences pain experience and the neurobiological processing of pain remains unclear. We used fMRI and multilevel mediation analyses to address this question. Thirty-six human participants first learned to associate two visual cues from distinct conceptual categories (e.g., animals vs. vehicles) with high or low levels of heat pain. In a subsequent phase, they were presented novel cues (images, drawings, or words) not previously paired with pain, but which shared the conceptual category of the initial pain-predictive cues. Participants who developed explicit expectations during learning reported greater pain in response to stimuli conceptually related to high-vs. low-pain cues ('generalization stimuli'), demonstrating generalization of cue influences on pain. This effect was mediated by increased pain-related activity to generalization stimuli in the hippocampus, which correlated with individual differences in cue-evoked expectations. A broader network, including areas of the default mode network and striatum, also contributed to conceptual generalization of pain modulation, while threat-related regions such as the amygdala responded to generalization stimuli but did not mediate effects on pain ratings. These findings extend our understanding of expectancy-driven pain modulation by showing how conceptual processes can influence pain and its neurobiological substrates, offering new insight into placebo effects and maladaptive learning in chronic pain.
INTRODUCTION:Parkinsonian syndromes are increasingly recognized in aging populations, but data from the Caribbean remain limited. In the French West Indies, atypical forms may be particularly prevalent, potentially linked to environmental exposures. This study assessed the prevalence, clinical features, and one-year mortality of parkinsonian syndromes in institutionalized older adults. METHODS:We analyzed two observational cohorts: KASEHPAD (n = 332 nursing home residents) and KASAF (n = 107 professional foster family residents). Parkinsonian syndromes were defined by clinical diagnosis and/or antiparkinsonian medication use. Data collected included demographics, comorbidities, cognitive function (MMSE), functional dependence (ADL), physical performance (SPPB), quality of life (EQ-5D-3L), and neuropsychiatric symptoms (NPI-Q). Cox model identified predictors of one-year mortality. RESULTS:Among 439 residents, 51 (11.7%; 95% CI: 8.7-14.7) presented with a parkinsonian syndrome. Compared with non-parkinsonian residents, they had greater functional dependence (ADL score: 1.6 ± 1.9 vs. 2.2 ± 2.1), more depressive symptoms, lower quality of life (EQ-5D score: 0.11 ± 0.36 vs. 0.24 ± 0.42; p = 0.035), and higher anxiety prevalence (66.7% vs. 43.3%; p = 0.002). One-year mortality did not differ (22.5% vs. 22.2%; p = 0.975), and parkinsonian status was not independently associated with mortality. CONCLUSION:Parkinsonian syndromes are common and clinically severe in French Caribbean long-term care facilities, with substantial functional and neuropsychiatric burden, but without increased short-term mortality. Mortality may be mainly influenced by frailty, comorbidities, and functional impairment, underscoring the need for tailored care strategies. TRIAL REGISTRY:NCT04545775 and NCT04587466.
Background Social cognition is a core impairment in psychotic disorders and is strongly associated with functional outcomes. Although social cognitive training is effective, challenges remain regarding skill generalization and accessibility. This study aimed to develop culturally adapted French- and English-Canadian versions of RC2S and to assess the feasibility and acceptability of remote delivery. Methods Fourteen individuals with a psychotic disorder were assessed at baseline, offered 24 twice-weekly RC2S sessions with a therapist over 12 weeks, and reassessed post-intervention. Motivation and therapeutic alliance were assessed through intra-session questionnaires. RC2S uses a personalized approach targeting social cognition and combines pen-and-paper exercises with digital relational simulations using avatars to promote skill transfer. Feasibility and acceptability were examined descriptively and paired-samples t-tests assessed exploratory pre–post changes. Results All participants who initiated RC2S met the predefined completion criterion (≥50% of sessions), and all completed at least 75% of planned sessions (mean = 20.9). Acceptability was high for cultural adaptation, ease of use, and remote interaction (all>4.1/5), although ratings were lower for the RC2S interface (mean = 3.75/5). Motivation and therapeutic alliance remained high throughout the intervention (MUSIC>5.1;WAI > 4.3). Therapist support, perceived benefits, and remote accessibility were key facilitators. The largest exploratory pre–post changes occurred in therapist-administered goal attainment and functional impact measures. Findings from independently administered measures were more mixed, although a large change was observed for theory of mind. Conclusions Findings support the feasibility and acceptability of remotely delivered, culturally adapted RC2S. Exploratory outcomes were mixed, requiring confirmation in a randomized trial with independent, blinded outcome assessment.
BACKGROUND:Aging is often accompanied by increasing difficulties in daily living that may compromise aging in place. In France, three main housing types can be distinguished: ordinary home (OH), intermediate housing (IH) and nursing home (NH). This study aimed to explore the relationship between functional disability, cognition, and residential transitions in older adults. METHODS:Participants aged 65 years and older living in OH at baseline were drawn from three French population-based cohorts (PAQUID, Three-City and AMI), followed for up to 30 years. A hierarchical indicator of functional disability was derived from mobility, IADL and ADL disabilities, while cognitive function was assessed using the Mini Mental State Examination (MMSE). A multi-state model was applied to investigate the associations between functional disability and cognition (as time-dependent variables) with housing transitions, adjusting for sex, cohort, marital status and education. We also examined the involvement of IADL disabilities on transitions from OH to IH or NH in sex-stratified models. Sensitivity analyses were performed using lagged measures. RESULTS:Among 5264 included participants (mean age 74.7 ± 6.0 years; 56.9% women), 832 relocated from OH during a median follow-up of 10.2 years, including 216 to IH and 616 to NH. Mild and moderate disability, as lower MMSE scores, were independently associated with higher risks of transitioning to IH or NH, while severe disability and cognitive impairment were only associated with NH transitions. In sex-stratified analyses, transportation difficulties were associated with IH and NH transitions among women, whereas only with NH admission in men. Difficulties with handling finances in women, with medications management in men, and difficulties with shopping in both sexes were also associated with transition to NH. DISCUSSION:Intermediate housing was more frequently associated with mild or moderate disability, whereas transitions to long-term care were more often observed in participants with severe cognitive decline.
Abstract Background Schizophrenia is a neurodevelopmental disorder shaped by immune-related mechanisms, particularly dysregulated complement-mediated synaptic pruning. Genome-wide association studies have identified CSMD1 as a major schizophrenia risk gene, an association robustly replicated across populations of diverse ancestries. As a complement regulator, CSMD1 further links genetic vulnerability to synaptic refinement processes. However, the transcriptional status of CSMD1 and its homolog CSMD2 in individuals with schizophrenia (SZ individuals) remains poorly characterized. We conducted a meta-analysis of gene-expression datasets to determine whether CSMD1 and CSMD2 are differentially expressed in brain and peripheral tissues, and to assess the concordance between central and peripheral transcriptional signals. Methods Transcriptional data were obtained from gene expression omnibus. Random-effects meta-analyses were performed on CSMD1 and CSMD2 expression data from 854 postmortem brain samples derived from 348 SZ individuals and 346 healthy controls (HC), and 295 peripheral blood samples from 162 SZ individuals and 133 HC. Sex-stratified analyses and meta-regressions evaluated potential moderators. Results In brain tissues, CSMD2 expression was significantly increased in SZ individuals vs. HC (SMD: 0.22 [0.05; 0.39], adj-p=0.026), whereas CSMD1 showed no differential expression. The female-only meta-analysis revealed nominal CSMD2 overexpression (p=0.037) in brain tissues, not surviving correction. No significant transcriptional differences were detected in peripheral blood. Conclusion In schizophrenia, our findings point to a dissociation between genetic vulnerability and transcriptional activity within the CSMD gene family. Schizophrenia is associated with selective brain CSMD2 overexpression, contrasting with unchanged CSMD1 transcription and absent peripheral blood alterations. These findings support complement-related dysregulation as a central pathway in schizophrenia.
