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Yayın Treatment and long-term outcome of mental disorders: The grim picture from a quasi-epidemiological investigation in 54,826 subjects from 40 countries(Elsevier Ireland Ltd, 2025-06) Fountoulakis, Konstantinos N.; Karakatsoulis, Gregory; Abraham, Seri; Adorjan, Kristina; Uddin Ahmed, Helal; Alarcòn, Renato Daniel; Arai, Kiyomi; Auwal, Sani Salihu; Berk, Michael; Levaj, Sarah; Yılmaz Kafalı, HelinIntroduction: This study registered rates of specific treatment options for mental disorders as well as their long-term outcome. Material and methods: The history of mental disorders was used as a proxy for diagnosis. The data came from the COMET-G study (40 countries; 54,826 subjects, 64.73 % females, 35.45±13.51 years old). The analysis included descriptive statistics, Risk Ratios, t-tests, and ANCOVA's. Results: 24.14 % reported a history of any mental disorder (depression >12 %, non-affective psychosis and Bipolar disorder 1 % each, >20 % self-injury, >10 % had attempted suicide, 7.17 % illegal substance abuse). Most patients were not under any kind of treatment (59.44 %) and most were not receiving treatment as recommended (e.g. 90 % of Bipolar and 2/3 of psychotic patients). No treatment at all and psychotherapy as monotherapy were consistently related to poorer outcomes. In anxiety or depression, only antidepressant monotherapy and benzodiazepines, in Bipolar disorder only antipsychotic monotherapy in males and antidepressant monotherapy in females and in non-affective psychosis antipsychotics and psychotherapy in females only, were related to good outcomes. No treatment modality was related to a good outcome in those with a history of self-harm, suicidal attempts, or illegal substance use. Only depression and treatment with antidepressants were related to metabolic syndrome. Discussion: In the community, the overwhelming majority of mental patients do not receive appropriate treatment or, even worse, no treatment at all. The outcome is unfavourable for the majority and only a few selective treatment options seem to make a difference.Yayın Analyzing language ability in first-episode psychosis and their unaffected siblings: a diffusion tensor imaging tract-based spatial statistics analysis study(Elsevier Ltd, 2024-11) Çabuk, Tuğçe; Şahin Çevik, Didenur; Çakmak, Işık Batuhan; Yılmaz Kafalı, Helin; Şenol, Bedirhan; Avcı, Hanife; Karlı Oğuz, Kader; Toulopoulou, TimotheaSchizophrenia (SZ) is a highly heritable mental disorder, and language dysfunctions play a crucial role in diagnosing it. Although language-related symptoms such as disorganized speech were predicted by the polygenic risk for SZ which emphasized the common genetic liability for the disease, few studies investigated possible white matter integrity abnormalities in the language-related tracts in those at familial high-risk for SZ. Also, their results are not consistent. In this current study, we examined possible aberrations in language-related white matter tracts in patients with first-episode psychosis (FEP, N = 20), their siblings (SIB, N = 20), and healthy controls (CON, N = 20) by applying whole-brain Tract-Based Spatial Statistics and region-of-interest analyses. We also assessed language ability by Thought and Language Index (TLI) using Thematic Apperception Test (TAT) pictures and verbal fluency to see whether the scores of these language tests would predict the differences in these tracts. We found significant alterations in language-related tracts such as inferior longitudinal fasciculus (ILF) and uncinate fasciculus (UF) among three groups and between SIB and CON. We also proved partly their relationship with the language test as indicated by the significant correlation detected between TLI Impoverished thought/language sub-scale and ILF. We could not find any difference between FEP and CON. These results showed that the abnormalities, especially in the ILF and UF, could be important pathophysiological vulnerability indexes of schizophrenia. Further studies are required to understand better the role of language as a possible endophenotype in schizophrenia with larger samples.Yayın Efficacy, all-cause discontinuation, and safety of serotonergic psychedelics and MDMA to treat mental disorders: a living systematic review with meta-analysis(Elsevier B.V., 2025-12) Højlund, Mikkel; Yılmaz Kafalı, Helin; Kırmızı, Begüm; Fusar-Poli, Paolo; Correll, Christoph U.; Cortese, Samuele; Sabé, Michel; Fiedorowicz, Jess; Saraf, Gayatri; Zein, Josephine; Berk, Michael; Husain, Muhammad I.; Rosenblat, Joshua D.; Rubaiyat, Ruby; Corace, Kim; Wong, Stanley; Hatcher, Simon; Kaluzienski, Mark; Yatham, Lakshmi N.; Cipriani, Andrea; Gosling, Corentin J.; Carhart-Harris, Robin; Tanuseputro, Peter; Myran, Daniel T.; Fabiano, Nicholas; Moher, David; Mayo, Leah M.; Nicholls, Stuart G.; White, Tracy; Prisco, Michele De; Radua, Joaquim; Vieta, Eduard; Ladha, Karim S.; Katz, Jay; Veroniki, Areti A.; Solmi, MarcoSerotonergic psychedelics and 3,4-methylendioxtmethamphetamine (MDMA) are promising treatments for mental disorders with a continuously evolving evidence base. We searched Pubmed/Scopus/clinical trial registries up to 08july2025 for double-blind randomized controlled trials (RCTs) testing MDMA or serotonergic psychedelics in patients with mental disorders. Primary outcomes were change in disease-specific symptoms and all-cause discontinuation. Standardized mean differences (SMD) and relative risk (RR) were estimated using random-effects meta-analysis. Risk of bias (RoB) was assessed with Cochrane’s RoB-tool version 2 and certainty of evidence with GRADE. The review is maintained as living systematic review ( https://ebipsyche-database.org/ ). We included 30 RCTs (1480 participants; female=45.8 %; with psychological support=83.3 %; high RoB=83.3 %). In post-traumatic stress disorder (PTSD), MDMA reduced PTSD symptoms compared to any control ( k = 11; SMD=-0.85 [-1.09; -0.60]; I2=0 %; GRADE=low). In major depressive disorder (MDD), psilocybin/ayahuasca/LSD reduced depressive symptoms ( k = 8; SMD=-0.62 [-0.97; -0.28]; I2=55 %; GRADE=very low). In anxiety disorders, both MDMA and serotonergic psychedelics reduced anxiety symptoms (SMDMDMA=-1.18 [-2.04; -0.32]; I2=0 %; k = 2; GRADE=low and SMDserotonergic=-0.88 [-1.70; -0.06]; I2=54 %; k = 5; GRADE=very low). In alcohol use disorder, neither psilocybin nor LSD reduced abstinence rates ( k = 6; RR=1.42 [0.89; 2.26]; I2=7 %; GRADE=very low). In attention-deficit hyperactivity disorder (ADHD), LSD did not reduce ADHD symptoms ( k = 1; SMD=0.22 [-0.32; 0.76]; GRADE=very low). Moderate certainty in evidence was only found for MDMA on PTSD symptoms when compared to placebo. MDMA/serotonergic psychedelics were not associated with higher risk of all-cause discontinuation (RRMDMA=0.74 [0.32; 1.72]; RRserotonergic=0.81 [0.56; 1.15]). Overall, MDMA/serotonergic psychedelics are promising for the treatment of PTSD, MDD, and anxiety disorders with moderate to large effect sizes. Pragmatic trials, long-term, head-to-head trials exploring the role of psychological support, aiming to identify predictors of response, and accounting for expectancy and functional unblinding are needed. Studies addressing these limitations will likely be required for regulatory approval of psychedelic drugs.
