Miriam Olivola, Filippo Mazzoni, Barbara Tarantino, Alessandro Guffanti, Matteo Marcatili, Federico Luigi Motta, Ranieri Domenico Cornaggia, Vassilis Martiadis, Tiziano Prodi, Pierluigi Politi, Natascia Brondino, Giovanni Martinotti, Massimo Clerici, Bernardo Dell'Osso
{"title":"精神化和情绪-认知僵化作为艾氯胺酮对难治性抑郁症影响的预测因素：一项前瞻性观察研究的结果。","authors":"Miriam Olivola, Filippo Mazzoni, Barbara Tarantino, Alessandro Guffanti, Matteo Marcatili, Federico Luigi Motta, Ranieri Domenico Cornaggia, Vassilis Martiadis, Tiziano Prodi, Pierluigi Politi, Natascia Brondino, Giovanni Martinotti, Massimo Clerici, Bernardo Dell'Osso","doi":"10.1016/j.jad.2025.120231","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Treatment-Resistant Depression (TRD) remains a major challenge in the management of Major Depressive Disorder (MDD). Esketamine, the S-enantiomer of ketamine and a glutamatergic modulator, has been approved by the FDA and EMA for TRD in 2019. Beyond its rapid antidepressant effects, esketamine may enhance neuroplasticity, facilitating the reconnection with emotional and cognitive processes, improving mentalization, social cognition and promoting resilience.</p><p><strong>Objective: </strong>This prospective multicenter observational study aimed to evaluate esketamine's therapeutic impact on depressive symptoms and explore whether psychological and clinical factors-including mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity-could predict treatment response, enabling a more personalized approach to TRD management.</p><p><strong>Methods: </strong>Thirty-six TRD patients treated with esketamine were assessed over a six-month follow-up period using psychometric measures of depression severity, suicidality, mentalization, social cognition, psychache, and cognitive-emotional rigidity.</p><p><strong>Results: </strong>A significant association emerged between mentalization deficits and depressive symptoms. Specifically, patients with poor baseline mentalization abilities exhibited higher Montgomery-Åsberg Depression Rating Scale (MADRS) scores both at baseline and throughout follow-up. In contrast, greater cognitive rigidity appeared to have a protective role, potentially mitigating negative thinking and providing emotional stability, which may enhance resilience to stressors.</p><p><strong>Conclusions: </strong>These findings highlight the importance of a personalized treatment approach in TRD. Esketamine may be particularly beneficial in reducing cognitive rigidity, improving mentalization, and breaking the cognitive inflexibility that contributes to sustained negative depressive thinking patterns. Further research is needed to refine patient stratification and optimize treatment strategies for individuals with TRD.</p>","PeriodicalId":14963,"journal":{"name":"Journal of affective disorders","volume":" ","pages":"120231"},"PeriodicalIF":4.9000,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Mentalization and Emotional-Cognitive Rigidity as predictors of esketamine's effects on Treatment-Resistant Depression: Findings from a prospective observational study.\",\"authors\":\"Miriam Olivola, Filippo Mazzoni, Barbara Tarantino, Alessandro Guffanti, Matteo Marcatili, Federico Luigi Motta, Ranieri Domenico Cornaggia, Vassilis Martiadis, Tiziano Prodi, Pierluigi Politi, Natascia Brondino, Giovanni Martinotti, Massimo Clerici, Bernardo Dell'Osso\",\"doi\":\"10.1016/j.jad.2025.120231\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Treatment-Resistant Depression (TRD) remains a major challenge in the management of Major Depressive Disorder (MDD). Esketamine, the S-enantiomer of ketamine and a glutamatergic modulator, has been approved by the FDA and EMA for TRD in 2019. Beyond its rapid antidepressant effects, esketamine may enhance neuroplasticity, facilitating the reconnection with emotional and cognitive processes, improving mentalization, social cognition and promoting resilience.</p><p><strong>Objective: </strong>This prospective multicenter observational study aimed to evaluate esketamine's therapeutic impact on depressive symptoms and explore whether psychological and clinical factors-including mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity-could predict treatment response, enabling a more personalized approach to TRD management.</p><p><strong>Methods: </strong>Thirty-six TRD patients treated with esketamine were assessed over a six-month follow-up period using psychometric measures of depression severity, suicidality, mentalization, social cognition, psychache, and cognitive-emotional rigidity.</p><p><strong>Results: </strong>A significant association emerged between mentalization deficits and depressive symptoms. Specifically, patients with poor baseline mentalization abilities exhibited higher Montgomery-Åsberg Depression Rating Scale (MADRS) scores both at baseline and throughout follow-up. In contrast, greater cognitive rigidity appeared to have a protective role, potentially mitigating negative thinking and providing emotional stability, which may enhance resilience to stressors.</p><p><strong>Conclusions: </strong>These findings highlight the importance of a personalized treatment approach in TRD. Esketamine may be particularly beneficial in reducing cognitive rigidity, improving mentalization, and breaking the cognitive inflexibility that contributes to sustained negative depressive thinking patterns. 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Mentalization and Emotional-Cognitive Rigidity as predictors of esketamine's effects on Treatment-Resistant Depression: Findings from a prospective observational study.
Introduction: Treatment-Resistant Depression (TRD) remains a major challenge in the management of Major Depressive Disorder (MDD). Esketamine, the S-enantiomer of ketamine and a glutamatergic modulator, has been approved by the FDA and EMA for TRD in 2019. Beyond its rapid antidepressant effects, esketamine may enhance neuroplasticity, facilitating the reconnection with emotional and cognitive processes, improving mentalization, social cognition and promoting resilience.
Objective: This prospective multicenter observational study aimed to evaluate esketamine's therapeutic impact on depressive symptoms and explore whether psychological and clinical factors-including mentalization, psychache, social cognition, suicidality, and cognitive-emotional rigidity-could predict treatment response, enabling a more personalized approach to TRD management.
Methods: Thirty-six TRD patients treated with esketamine were assessed over a six-month follow-up period using psychometric measures of depression severity, suicidality, mentalization, social cognition, psychache, and cognitive-emotional rigidity.
Results: A significant association emerged between mentalization deficits and depressive symptoms. Specifically, patients with poor baseline mentalization abilities exhibited higher Montgomery-Åsberg Depression Rating Scale (MADRS) scores both at baseline and throughout follow-up. In contrast, greater cognitive rigidity appeared to have a protective role, potentially mitigating negative thinking and providing emotional stability, which may enhance resilience to stressors.
Conclusions: These findings highlight the importance of a personalized treatment approach in TRD. Esketamine may be particularly beneficial in reducing cognitive rigidity, improving mentalization, and breaking the cognitive inflexibility that contributes to sustained negative depressive thinking patterns. Further research is needed to refine patient stratification and optimize treatment strategies for individuals with TRD.
期刊介绍：
The Journal of Affective Disorders publishes papers concerned with affective disorders in the widest sense: depression, mania, mood spectrum, emotions and personality, anxiety and stress. It is interdisciplinary and aims to bring together different approaches for a diverse readership. Top quality papers will be accepted dealing with any aspect of affective disorders, including neuroimaging, cognitive neurosciences, genetics, molecular biology, experimental and clinical neurosciences, pharmacology, neuroimmunoendocrinology, intervention and treatment trials.
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