Importance:Neuropsychiatric disorders impose a substantial burden on individuals and societies worldwide. Despite significant advances in the understanding of the brain, only a handful of mechanism-based treatments for psychiatric disorders have been discovered and validated in the past 50 years. Observations:After discussing the reasons for poor progress in drug discovery in mental disorders, this article outlines recommendations for a paradigm shift toward precision psychiatry, emphasizing the need for biomarker discovery and suggesting a reform of clinical trial methodology. To drive this transformation, increased public and private investment must be aligned with the societal impact of mental disorders, while regulatory agencies should adopt more flexible and biomarker-informed trials, as seen in oncology and other medical fields. Conclusion and Relevance:Promoting cross-sector collaboration between academia, biotech, industry, and health care systems will be critical to support high-risk, high-reward innovations. This article reflects the broad consensus of experts from academia, industry, regulatory agencies, and patient representatives to advance the agenda for precision psychiatry.
This viewpoint highlights the indispensable role of informal caregivers in mental health recovery. The authors note that mental disorders affect around one in eight people worldwide, with major impacts on family quality of life and substantial health system costs. Informal caregivers are advocated not as peripheral supporters, but as key partners in care pathways, to be recognized in public policies and clinical practice. Scientific evidence shows their involvement reduces relapses, isolation, and hospitalization rates. This viewpoint identifies significant psychosocial risks facing informal caregivers and stresses the need for tailored support measures. The authors underscore the need for comprehensive support measures, clearer institutional recognition, ethically balanced information-sharing practices, structured educational initiatives, and more rigorous research and evaluation frameworks. Five priority areas are proposed for transforming care models: recognition, support, ethics, education, and research. Neglecting informal caregivers weakens mental health systems, whereas including them helps build more humane, effective, and resilient approaches.
BACKGROUND:Epigenetic age accelerations have been associated with the clinical expression of BD; however, with few available studies. METHOD:We calculated Horvath, Hannum, EN, GrimAge, and PhenoAge epigenetic ages in a sample of 139 individuals with BD. We used a latent profile analysis to identify subgroups of individuals based on their profile of epigenetic age accelerations. We compared these profiles for socio-demographic characteristics, course of BD, associated psychiatric conditions, current medication use, telomere length, mitochondrial DNA copy number (mtDNAcn), markers of metabolic syndrome, and of systemic inflammation. RESULTS:The latent profile analysis identified two subgroups, one with accelerated and one with decelerated epigenetic aging (respectively 58% and 42%). Subgroups did not differ for socio-demographic characteristics, course of BD, associated psychiatric conditions, nor current medication use. The accelerated aging subgroup was characterized by higher depressive symptoms (p < 0.001), lower mtDNAcn (p < 0.001), higher levels of systemic inflammation (platelet/neutrophil ratio, neutrophil/lymphocyte ratio, systemic inflammation index, p < 0.001) that remained significant after correction for multiple testing. Some associations with anxiety symptoms, social functioning, blood pressure, and waist circumference did not remain significant after correction for multiple testing. CONCLUSIONS:Most individuals with BD were characterized by an accelerated epigenetic age profile. This study suggests a link between epigenetic age acceleration, systemic inflammation, and mtDNAcn. This subgroup might represent a target for personalized prevention and treatment.
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.
Studies examining the effect of mania on cognition in Bipolar Disorders (BD) have yielded contradictory results. Koenders and collaborators showed in 2014 that, among 189 adults with BD, adults with subclinical manic symptoms perform a task measuring divided attention significantly better than adults with less or more severe manic symptoms. We aimed to replicate this finding in a larger sample. We included adults from the FACE-BD cohort with a BD diagnosis based on the DSM-IV-R criteria. We excluded adults with a current characterized depressive or manic episode or with other possible sources of cognitive impairment. We assessed the associations between the YMRS score and cognitive functions involved in divided attention using linear regression models, adjusting for the same covariates as the original study. We found no significant linear or quadratic associations between the YMRS total score and attention, working memory, and executive performance in the bivariable models nor after adjusting for covariates in 2,739 adults with BD. We were unable to replicate the findings reported by Koenders and collaborators. The low variance and mean severity of manic symptoms in our sample may partly explain the absence of significant associations. Our results suggest that subclinical hypomanic symptoms neither enhance nor impair cognitive performance in adults with BD, calling into question the benefit of residual hypomanic symptoms on patients’ cognitive functioning.
