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2023 - 20266
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  • Küçük Resim
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    The effect of SARS-CoV-2 virus on resting-state functional connectivity during adolescence: Investigating brain correlates of psychotic-like experiences and SARS-CoV-2 related inflammation response
    (Elsevier Ireland Ltd, 2023-12) Yılmaz Kafalı, Helin; Daşgın, Hacer; Şahin Çevik, Didenur; Sozan, Sara Sinem; Oğuz, Kader K.; Mutlu, Müge; Özkaya Parlakay, Aslınur; Toulopoulou, Timothea
    We first aimed to investigate resting-state functional connectivity (rs-FC) differences between adolescents exposed to SARS-CoV-2 and healthy controls. Secondly, the moderator effect of PLEs on group differences in rs-FC was examined. Thirdly, brain correlates of inflammation response during acute SARS-CoV-2 infection were investigated. Eighty-two participants aged between 14 and 24 years (SARS-CoV-2 (n = 35), controls (n = 47)) were examined using rs-fMRI. Seed-based rs-FC analysis was performed. The positive subscale of Community Assessment of Psychotic Experiences-42 (CAPE-Pos) was used to measure PLEs. The SARS-CoV-2 group had a lesser rs-FC within sensorimotor network (SMN), central executive network (CEN) and language network (LN), but an increased rs-FC within visual network (VN) compared to controls. No significant differences were detected between the groups regarding CAPE-Pos-score. However, including CAPE-Pos as a covariate, we found increased rs-FC within CEN and SN in SARS-CoV-2 compared to controls. Among the SARS-CoV-2 group, neutrophil/lymphocyte and thrombocyte*neutrophil/lymphocyte ratio was correlated with decreased/increased FC within DMN and SN, and increased FC within CEN. Our results showed rs-FC alterations within the SMN, CEN, LN, and VN among adolescents exposed to SARS-CoV-2. Moreover, changes in rs-FC associated with PLEs existed in these adolescents despite the absence of clinical changes. Furthermore, inflammation response was correlated with alterations in FC within the triple network system.
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    Attitudes of psychiatrists towards people with mental illness: a cross-sectional, multicentre study of stigma in 32 European countries
    (Elsevier Ltd, 2023-12) Őri, Dorottya; Szocsics, Péter; Molnár, Tamás; Bankovska Motlova, Lucie; Kazakova, Olga; Mörkl, Sabrina; Wallies, Michael; Abdulhakim, Mohamed; Boivin, Sylvie; Bruna, Krista; Cabaços, Carolina; Carbone, Elvira Anna; Dashi, Elona; Grech, Giovanni; Greguras, Stjepan; Ivanovic, Iva; Guevara, Kaloyan; Kakar, Selay; Kotsis, Konstantinos; Ingeholm Klinkby, Ida Maria; Maslak, Jovana; Matheiken, Shevonne; Mirkovic, Ana; Nechepurenko, Nikita; Panayi, Angelis; Pereira, Ana Telma Fernandes; Pomarol-Clotet, Edith; Raaj, Shaeraine; Prelog, Polona Rus; Soler-Vidal, Joan; Strumila, Robertas; Schuster, Florian; Kisand, Helena; Reim, Ann; Ahmadova, Gumru; Vircik, Matus; Yılmaz Kafalı, Helin; Grinko, Natalia; Győrffy, Zsuzsa; Rózsa,Sándor
    Background Mental health-related stigma occurs among the public and professionals alike. The lived experience of mental illness has been linked to less stigmatising attitudes. However, data on psychiatrists and the relationship between stigmatising attitudes and psychotherapeutic activity or case discussion groups remains scarce.Methods A cross-sectional multicentre study was performed in 32 European countries to investigate the lived experiences and attitudes of psychiatrists toward patients with mental illness as well as the relationship between stigma, psychosocial and professional factors. The self-reported, anonymous, internet-based Opening Minds Stigma Scale for Health Care Providers was used to measure the stigmatising attitudes. The survey was translated into the local language of each participating country. All participants were practising specialists and trainees in general adult or child and adolescent psychiatry. The study took place between 2nd October, 2019 and 9th July, 2021 and was preregistered at ClinicalTrial.gov (NCT04644978).Findings A total of 4245 psychiatrists completed the survey. The majority, 2797 (66%), had completed training in psychiatry, and 3320 (78%) worked in adult psychiatry. The final regression model showed that across European countries more favourable attitudes toward people with mental illness were statistically significantly associated with the lived experience of participants (including seeking help for their own mental health conditions (d = -0.92, 95% confidence interval (CI) = -1.68 to -0.15, p = 0.019), receiving medical treatment for a mental illness (d = -0.88, 95% CI = -1.71 to -0.04, p = 0.040), as well as having a friend or a family member similarly affected (d = -0.68, 95% CI = -1.14 to -0.22, p = 0.004)), being surrounded by colleagues who are less stigmatising (d = -0.98, 95% CI = -1.26 to -0.70, p < 0.001), providing psychotherapy to patients (d = -1.14, 95% CI = -1.63 to -0.65 p < 0.001), and being open to (d = -1.69, 95% CI = -2.53 to -0.85, p < 0.001) and actively participating in (d = -0.94, 95% CI = -1.45 to -0.42, p < 0.001) case discussion, supervision, or Balint groups.Interpretation Our study highlights the importance of psychotherapy training, supervision, case discussions and Balint groups in reducing the stigmatising attitudes of psychiatrists toward patients. As the findings represent cross -national predictors, Europe-wide policy interventions, national psychiatric education systems and the management of psychiatric institutions should take these findings into consideration.Funding National Youth Talent Award (Ministry of Human Resources, Hungary, (NTP-NFTo-20-B-0134). All authors received no funding for their contribution.
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    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, Helin
    Introduction: 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.
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    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, Timothea
    Schizophrenia (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.
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    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, Marco
    Serotonergic 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.
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    Formal thought disorder and familial risk in first-episode psychosis: A study of cortical thickness and neuroimaging-transcriptomic association analysis
    (Elsevier Ireland Ltd, 2026-01-16) Çabuk, Tuğçe; Zhang, Yuanchao; Palaniyappan, Lena; Şahin Çevik, Didenur; Avcı, Hanife; Çakmak, Işık Batuhan; Yılmaz Kafalı, Helin; Şenol, Bedirhan; Karlı Oğuz, Kader; Toulopoulou, Timothea
    Formal thought disorder (FTD), a prominent feature of schizophrenia, encompasses disruptions in thought, language, and communication. This study examines cortical thickness (CT) alterations in first-episode psychosis (FEP) patients (N = 24), their siblings (SIB) (N = 21), and healthy controls (CON) (N = 21) to explore potential neural correlates of FTD. Using structural MRI, we analyzed whole-brain CT and its relationship with positive and negative FTD measured by Thought and Language Index. Out-of-sample spatial correlations of gene expression with regional CT were also performed using a transcriptomic dataset. FEP had significant CT reductions in right middle frontal gyrus (MFG) compared with SIB and CON and in superior frontal gyrus (SFG) compared to CON; but SIB did not differ from CON. GLM analyses demonstrated that negative FTD exerted a significant main effect on CT in the MFG and SFG. By contrast, positive FTD showed no significant associations with CT. Neuroimaging-transcriptomic association analysis identified key biological pathways linked to cortical morphology. These findings emphasize the specific association between negative FTD and CT alterations in frontal brain regions, confirming prior reports. Future research should examine larger cohorts and investigate additional FTD subtypes to further elucidate neural correlates and potential familial risks of schizophrenia.