CNS SpectrumsPub Date : 2025-08-26DOI: 10.1017/S1092852925100515
Álex Escolà-Gascón, Neil Dagnall, Kenneth Drinkwater, Abdrew Denovan, Julián Benito-León
{"title":"Placebo effects in alternative medical treatments for anxiety: false hope or healing potential?","authors":"Álex Escolà-Gascón, Neil Dagnall, Kenneth Drinkwater, Abdrew Denovan, Julián Benito-León","doi":"10.1017/S1092852925100515","DOIUrl":"10.1017/S1092852925100515","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether anxiety reductions attributed to healing crystals reflect placebo responses driven by conditioning and belief-related biases rather than specific therapeutic effects.</p><p><strong>Methods: </strong>In a randomized, controlled study, 138 adults were classified as believers or nonbelievers in crystal efficacy and assigned to rose quartz (experimental) or a visually matched placebo. Participants followed a standardized 14-day protocol. Anxiety was assessed pre- and post-intervention with the Beck Anxiety Inventory and the Spanish Kuwait University Anxiety Scale. Multilevel <i>analyses of variance</i> (ANOVA) and Bayesian models were used to evaluate main effects, interactions, and evidence for treatment specificity.</p><p><strong>Results: </strong>Anxiety reductions occurred only among believers, regardless of crystal assignment. No differences were detected between groups in primary outcomes, and improvements did not exceed the magnitudes typically associated with placebo responses. Bayesian estimates favored the null hypothesis for specific treatment effects. Preexisting belief strongly predicted perceived efficacy and symptom change, consistent with causal illusions plausibly shaped by conditioning mechanisms. Nonbelievers showed no reliable improvement.</p><p><strong>Conclusion: </strong>Healing crystals did not demonstrate anxiolytic effects beyond those of the placebo. Symptom change was mediated by expectancy and conditioning, particularly in individuals inclined toward intuitive or magical thinking. Although nonspecific, context-dependent factors-such as elements of the therapeutic alliance-may amplify placebo responsiveness in clinical settings, these findings do not support attributing inherent therapeutic value to crystals. Future work should delineate how expectations, clinician-patient rapport, and related variables interact to shape placebo response and how such mechanisms might be ethically leveraged to enhance evidence-based care without promoting pseudoscientific practices.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e70"},"PeriodicalIF":4.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CNS SpectrumsPub Date : 2025-08-26DOI: 10.1017/S1092852925100382
Sean E Evans
{"title":"When do psychiatric interventions work? An argument for using functional outcomes when evaluating the effectiveness of treating schizophrenia.","authors":"Sean E Evans","doi":"10.1017/S1092852925100382","DOIUrl":"10.1017/S1092852925100382","url":null,"abstract":"<p><p>Schizophrenia is known to be a disabling psychiatric condition with wide reaching impact on everyday functioning and outcomes. These functional outcomes include increases in all-cause mortality (especially suicide and injury), cognitive and functional capacity deficits, lower reported levels of quality of life (QoL), increased incarceration, higher risk for violence and victimization, and homelessness. Studies have shown that medications and outpatient services can improve each of these functional outcomes in individuals with schizophrenia. However, most studies of pharmacological treatment utilize rating scales that do not reflect these real-world outcomes. This review looks at available studies focused on real-world outcomes and argues for an expansion of this body of research.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e71"},"PeriodicalIF":4.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CNS SpectrumsPub Date : 2025-08-26DOI: 10.1017/S1092852925100527
Vishal Kumar Gautam, Tapas Kumar Aich, Amil Hayat Khan, Sujita Kumar Kar, Ajeet Chaudhury, Umashankar Kushwaha
{"title":"The short-term efficacy of low-frequency rTMS versus continuous theta burst stimulation as early augmentation, targeting right DLPFC in the management of obsessive-compulsive disorder: a randomized clinical study.","authors":"Vishal Kumar Gautam, Tapas Kumar Aich, Amil Hayat Khan, Sujita Kumar Kar, Ajeet Chaudhury, Umashankar Kushwaha","doi":"10.1017/S1092852925100527","DOIUrl":"https://doi.org/10.1017/S1092852925100527","url":null,"abstract":"<p><strong>Background: </strong>Obsessive-compulsive disorder (OCD) is a significantly disabling and difficult-to-treat psychiatric disorder. Non-invasive neuromodulation techniques like repetitive transcranial magnetic stimulation (rTMS) have been increasingly used in the management of OCD. This study aimed to compare the efficacy of early augmentation with low-frequency rTMS (LF-rTMS) and continuous theta burst stimulation (cTBS) in improving psychopathology in OCD patients.</p><p><strong>Methods: </strong>The study design was a parallel-group, double-blind, randomized clinical trial. The study recruited 46 OCD patients who were randomly allocated to receive either LF-rTMS or cTBS (23 patients in each group) following the computer-generated random table method. All participants were rated on YBOCS, HAM-A, and HAM-D at baseline and third week and sixth weeks. These patients received a total of 15 sessions of LF-rTMS or cTBS stimulation once daily for 5 consecutive days in a week for 3 consecutive weeks over the right dorso-lateral pre-frontal cortex (DLPFC) area.</p><p><strong>Results: </strong>There was a statistically significant improvement in the total YBOCS score for both the LF-rTMS group and the cTBS group at the end of the third and sixth week when compared with their baseline scores. However, there was no statistically significant difference between the 2 groups in terms of the improvement in the total YBOCS score, as well as the total scores for the HAM-A and HAM-D during the follow-up periods.</p><p><strong>Conclusion: </strong>The study results suggest that both LF-rTMS and cTBS were equally effective in managing OCD patients as an early augmentation strategy.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":"30 1","pages":"e67"},"PeriodicalIF":4.1,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CNS SpectrumsPub Date : 2025-08-19DOI: 10.1017/S1092852925100503
Christoph U Correll
{"title":"Long-acting injectable antipsychotics for patients with first-episode and early-phase schizophrenia: still not considered often enough.","authors":"Christoph U Correll","doi":"10.1017/S1092852925100503","DOIUrl":"10.1017/S1092852925100503","url":null,"abstract":"<p><p>Schizophrenia is a severe mental disorder with heterogeneous outcomes that depend heavily on symptom stability as a prerequisite for psychosocial rehabilitation and reintegration. Long-acting injectable antipsychotics (LAIs) are a relevant treatment tools that can help advance meaningful outcomes through improved antipsychotic adherence and relapse prevention, deliver pharmacokinetic advantages less achievable with oral formulations, improve patient autonomy, increase functioning, and reduce the risk of premature mortality even more than oral antipsychotics. However, LAIs remain largely underutilized. Non-modifiable and modifiable risk factors for relapse are summarized, potential advantages and disadvantages of LAIs are reviewed, and myths and misconceptions regarding LAIs are outlined and contrasted with evidence. This information is crucial when engaging in shared decision-making and motivational interviewing to educate patients and caregivers about the treatment option of LAIs, including in early illness stages. Since the first episode and early phases of schizophrenia are a defining time, choosing treatments with the greatest potential for improved outcomes is key. In adults with multi-episode schizophrenia, LAIs have shown superiority over oral antipsychotics for relapse/hospitalization and a variety of multiple other efficacy, effectiveness, functionality, and survival metrics. Additionally, LAIs have shown superiority over oral antipsychotics in patients with first-episode/ or early-phase illness, at least in meaningful subgroups of studies and patients that point toward superiority in settings, individuals, and treatment paradigms that more closely match clinical care. Based on this evidence, hesitancies to discuss and offer LAIs in clinical care need to be overcome, framing LAIs not as a last resort but a viable first-line/earlyphase treatment option that can meaningfully transform the long-term course of schizophrenia.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e66"},"PeriodicalIF":4.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"SLC6A3 gene methylation may be associated with alcohol use disorder, but personality and life stress may not influence methylation.","authors":"Te-En Chyou, Shin-Chang Kuo, Yi-Wei Yeh, Chun-Yen Chen, Chun-Long Lin, Chih-Yun Huang, Shin-Min Lee, San-Yuan Huang","doi":"10.1017/S1092852925100473","DOIUrl":"10.1017/S1092852925100473","url":null,"abstract":"<p><strong>Background: </strong>DNA methylation plays a crucial role in gene regulation and has been implicated in various neuropsychiatric disorders, including alcohol use disorder (AUD). The rs27072 polymorphism within the SLC6A3 gene has been studied in addictive disorders; however, its role in epigenetic modifications remains unclear. This study investigates the methylation levels of CpG sites near rs27072 and their potential associations with AUD, personality traits, and environmental stressors.</p><p><strong>Materials and methods: </strong>One hundred twenty-four male participants (66 patients with AUD and 58 controls) were analyzed for DNA methylation at CpG islands proximal to the rs27072 locus. The personality traits and life stress events were assessed in all participants.</p><p><strong>Results: </strong>AUD patients had a lower methylation level than healthy controls (p = 0.003 for total average). However, the results changed to borderline significance after adjusting for clinical covariates in the analysis (p = 0.042), and the genotype at rs27072 did not modulate the methylation levels. There is high novelty seeking (p < 0.001), and more bad life events in patients with AUD than healthy controls (p < 0.001). Additionally, no significant correlations were found between methylation levels and personality traits or life stress scores (p > 0.05).</p><p><strong>Conclusions: </strong>The methylation of the SLC6A3 gene may be marginally associated with AUD; however, the rs27072 genotype, personality, and life stress may not be directly linked to epigenetic modifications. Cross-sectional epigenetic studies may not establish causality; future studies with larger, more diverse cohorts and longitudinal designs are warranted to elucidate the complex interplay in AUD pathophysiology.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e62"},"PeriodicalIF":4.1,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CNS SpectrumsPub Date : 2025-08-12DOI: 10.1017/S109285292510045X
Gia Han Le, Sabrina Wong, Stavroula Bargiota, Swainson Jennifer, Heidi K Y Lo, Diana Orsini, Kayla Teopiz, Hernan F Guillen-Burgos, Poh Khuen Lim, Roger S McIntyre
{"title":"Biased agonism in psychopharmacology: an opportunity to improve efficacy and safety of treatments.","authors":"Gia Han Le, Sabrina Wong, Stavroula Bargiota, Swainson Jennifer, Heidi K Y Lo, Diana Orsini, Kayla Teopiz, Hernan F Guillen-Burgos, Poh Khuen Lim, Roger S McIntyre","doi":"10.1017/S109285292510045X","DOIUrl":"10.1017/S109285292510045X","url":null,"abstract":"<p><p>G protein-coupled receptors (GPCRs) are involved in many physiological and pathophysiological processes. Conventional pharmacological models categorize the typology of pharmacologic ligands as agonists or antagonists. Biased agonism is a relatively newer pharmacodynamic characteristic that has potential to optimize therapeutic efficacy while minimizing adverse effects in psychiatric and neurological treatments. We conducted a narrative literature review of articles obtained from PubMed, Embase, and MEDLINE from inception to April 2025, focusing on pharmacologic antagonism (i.e., competitive, noncompetitive, uncompetitive) and agonism (i.e., full, partial, inverse, superagonism, biased). Primary and secondary articles defining these concepts were included, provided they addressed pharmacologic (rather than chemical) antagonism and agonism. Distinct mechanisms of antagonism and agonism were identified, each contributing nuanced receptor modulation beyond the conventional models. Notably, biased agonism facilitates targeted intracellular signaling (e.g., G protein- versus β-arrestin-mediated). Use cases demonstrate relatively greater efficacy (e.g., incretin receptor agonist, tirzepatide) and improved safety (e.g., serotonergic psychedelics, opioids). Biased agonism provides a potential avenue for future drug development, with emerging preclinical evidence suggesting potential to differentially activate intracellular pathways and thereby improve efficacy and safety profiles of psychopharmacologic agents-pending clinical validation. Future research vistas should aim to rigorously assess the long-term outcomes of biased agonism, explicitly addressing individual variability in receptor signaling and therapeutic response.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e63"},"PeriodicalIF":4.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CNS SpectrumsPub Date : 2025-08-11DOI: 10.1017/S1092852925100485
Richard Skaff
{"title":"Neurosteroids as a prospective treatment for Social Anxiety Disorder.","authors":"Richard Skaff","doi":"10.1017/S1092852925100485","DOIUrl":"https://doi.org/10.1017/S1092852925100485","url":null,"abstract":"","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"1-4"},"PeriodicalIF":4.1,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CNS SpectrumsPub Date : 2025-07-31DOI: 10.1017/S1092852925100461
Christoph U Correll
{"title":"Do antipsychotics work in people with schizophrenia? A review of outcomes and effect sizes.","authors":"Christoph U Correll","doi":"10.1017/S1092852925100461","DOIUrl":"10.1017/S1092852925100461","url":null,"abstract":"<p><strong>Background: </strong>The origins and treatment-target-related mechanisms of schizophrenia remain to be fully understood. Pharmacological and non-pharmacological treatments require expansion and improvements to meet peoples' needs and goals. Nevertheless, antipsychotics are a cornerstone when managing schizophrenia, being essential for reducing symptom severity, preventing relapse, improving long-term functional outcomes, and reducing premature mortality risk.</p><p><strong>Methods: </strong>This narrative review synthesizes key evidence on the efficacy and risks associated with antipsychotic medications. The concept of effect sizes is introduced, allowing to compare antipsychotics across trials with different rating instruments and across different conditions.</p><p><strong>Results: </strong>The available evidence in schizophrenia and comparison with medications used for medical conditions counters the sometimes-voiced criticism that antipsychotics \"do not work.\" Instead, for a substantial group of people with schizophrenia, positive psychotic symptoms and global psychopathology improve witha small-medium effect size of about 0.4 versus placebo. These results are comparable to median effect sizes across commonly used medications for somatic disorders. When patients with initial response are continued on antipsychotics, the effect size increases to 0.9 for relapse prevention, translating into a number needed to treat (NNT) of about 3 to prevent one more relapse versus no treatment. This NNT is 10-20 times higher than that for the prevention of poor outcomes in some common medical conditions.</p><p><strong>Conclusions: </strong>Despite general efficacy and effectiveness of antipsychotics for schizophrenia, further development is needed regarding preventive interventions and medications with mechanisms other than postsynaptic dopamine receptor blockade, with broader efficacy for positive, negative, cognitive, suicidality, and/or reward dysregulation symptomatology, and the identification of illness mechanism/biomarker-targeting treatments to enhance treatment personalization.</p>","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"e59"},"PeriodicalIF":4.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144752622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
CNS SpectrumsPub Date : 2025-07-25DOI: 10.1017/S1092852925100448
Ambarin Faizi, Stephen M Stahl
{"title":"Drugs for Psychosis in People with Schizophrenia: What happens if you take them and what happens if you don't?","authors":"Ambarin Faizi, Stephen M Stahl","doi":"10.1017/S1092852925100448","DOIUrl":"https://doi.org/10.1017/S1092852925100448","url":null,"abstract":"","PeriodicalId":10505,"journal":{"name":"CNS Spectrums","volume":" ","pages":"1-26"},"PeriodicalIF":3.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}