Pub Date : 2025-01-10DOI: 10.1016/j.pnpbp.2025.111253
Thaís Pereira Mendes , Brunno Guimarães Pereira , Evandro Silva Freire Coutinho , Marina S. Melani , Thomas C. Neylan , William Berger
Posttraumatic stress disorder (PTSD) is a debilitating condition affecting 5.7 % of the global population in their lifetime. There is a strong association between trauma-related nightmares and insomnia with higher rates of physical illness, mental distress, and suicide among PTSD patients. Prazosin, an α1-adrenergic antagonist, has shown mixed results in treating these sleep disturbances. This study aims to evaluate the effect of prazosin compared to placebo on insomnia, nightmares, and global PTSD symptoms, and to examine variables that might influence this effect. We conducted a meta-analysis and a novel meta-regression analysis of randomized clinical trials (RCTs) comparing prazosin to placebo in samples of patients with PTSD. Data sources were MEDLINE, EMBASE, Scopus, ISI Web of Science, and PTSD Pubs. Examined variables were age, gender, military/civilian status, prazosin dose, treatment duration, baseline symptom severity, use of antidepressants, use of benzodiazepines (BDZ), prevalence of depression, and alcohol use disorder. Ten RCTs with 648 patients were included. Analysis revealed prazosin significantly improved insomnia (SMD = −0.654, p = 0.043) and nightmares (SMD = −0.641, p = 0.025), but not overall PTSD symptoms (SMD = −0.428, p = 0.077). Unexpectedly, higher BDZ use was associated with greater improvement in insomnia (β = −0.046; p = 0.01) and PTSD severity (β = −0.037; p = 0.004). These findings suggest that prazosin effectively reduces insomnia and nightmares in PTSD patients. Benzodiazepine co-administration seems to enhance prazosin's efficacy, suggesting that the addition of prazosin might allow for a reduction of BDZ doses in these patients. Further research should empirically test the efficacy of prazosin alone versus prazosin combined with BDZ to confirm these findings.
{"title":"Factors impacting prazosin efficacy for nightmares and insomnia in PTSD patients - a systematic review and meta-regression analysis","authors":"Thaís Pereira Mendes , Brunno Guimarães Pereira , Evandro Silva Freire Coutinho , Marina S. Melani , Thomas C. Neylan , William Berger","doi":"10.1016/j.pnpbp.2025.111253","DOIUrl":"10.1016/j.pnpbp.2025.111253","url":null,"abstract":"<div><div>Posttraumatic stress disorder (PTSD) is a debilitating condition affecting 5.7 % of the global population in their lifetime. There is a strong association between trauma-related nightmares and insomnia with higher rates of physical illness, mental distress, and suicide among PTSD patients. Prazosin, an α1-adrenergic antagonist, has shown mixed results in treating these sleep disturbances. This study aims to evaluate the effect of prazosin compared to placebo on insomnia, nightmares, and global PTSD symptoms, and to examine variables that might influence this effect. We conducted a meta-analysis and a novel meta-regression analysis of randomized clinical trials (RCTs) comparing prazosin to placebo in samples of patients with PTSD. Data sources were MEDLINE, EMBASE, Scopus, ISI Web of Science, and PTSD Pubs. Examined variables were age, gender, military/civilian status, prazosin dose, treatment duration, baseline symptom severity, use of antidepressants, use of benzodiazepines (BDZ), prevalence of depression, and alcohol use disorder. Ten RCTs with 648 patients were included. Analysis revealed prazosin significantly improved insomnia (SMD = −0.654, <em>p</em> = 0.043) and nightmares (SMD = −0.641, <em>p</em> = 0.025), but not overall PTSD symptoms (SMD = −0.428, <em>p</em> = 0.077). Unexpectedly, higher BDZ use was associated with greater improvement in insomnia (β = −0.046; <em>p</em> = 0.01) and PTSD severity (β = −0.037; <em>p</em> = 0.004). These findings suggest that prazosin effectively reduces insomnia and nightmares in PTSD patients. Benzodiazepine co-administration seems to enhance prazosin's efficacy, suggesting that the addition of prazosin might allow for a reduction of BDZ doses in these patients. Further research should empirically test the efficacy of prazosin alone versus prazosin combined with BDZ to confirm these findings.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111253"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143016525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10Epub Date: 2024-12-26DOI: 10.1016/j.pnpbp.2024.111238
Mustafa Munir Mustafa Dahleh, Sabrina Grendene Muller, Isabella Pregardier Klann, Luiza Souza Marques, Jéssica Leandra da Rosa, Murilo Barboza Fontoura, Marilise Escobar Burger, Cristina Wayne Nogueira, Marina Prigol, Silvana Peterini Boeira, Hecson Jesser Segat
Amphetamine (AMPH) abuse represents a major global public health issue, highlighting the urgent need for effective therapeutic interventions to manage addiction caused by this psychostimulant. This study aimed to assess the potential of m-trifluoromethyl-diphenyldiselenide [(m-CF3-PhSe)2] in preventing the addictive effects induced by AMPH through targeting dopamine metabolism proteins. (m-CF3-PhSe)2 is of interest due to its demonstrated efficacy in mitigating opioid abuse, establishing it as a promising candidate for addiction treatment research. Initially, in silico studies examined the affinity of AMPH and (m-CF3-PhSe)2 for dopamine 1, 2, and 3 receptors (D1R, D2R, D3R), and dopamine transporter (DAT). In our experimental design, male Wistar rats were divided into four groups: I) Control; II) (m-CF3-PhSe)2; III) AMPH; IV) (m-CF3-PhSe)2 + AMPH. Animals were administered (m-CF3-PhSe)2 (0.1 mg/kg, by gavage) or canola oil (vehicle) 30 min before AMPH (4.0 mg/kg, i.p.) administration. Drug administration occurred for 8 days in the conditioned place preference (CPP) paradigm. Twenty-four hours after the last CPP conditioning section, preference for the drug-compartment was assessed, with anxiety-related effects and working memory were evaluated using the Y-maze test. Finally, animals were euthanized for striatal dissection to quantify D1R, D2R, D3R, and DAT levels in western blot. In silico findings suggest that (m-CF3-PhSe)2 may prevent AMPH activation in DAT, interacting with Asp46 and Phe319, preventing possible addictive effects of AMPH in DAT. In vivo results showed that (m-CF3-PhSe)2 attenuated AMPH effects, reducing preference for the drug-compartment in CPP test. Furthermore, (m-CF3-PhSe)2 prevented AMPH-induced anxiogenic effects in the elevated plus maze (EPM) test, similarly to light/dark test. No differences in locomotion or working memory were observed among the experimental groups in the Y-maze test. Ex vivo western blot analyses of the entire striatum indicates that (m-CF3-PhSe)2 prevented the AMPH-induced increase in D1R levels and decrease in D2R and DAT levels, with no changes in D3R levels. Overall, our study suggests that (m-CF3-PhSe)2 may interact with DAT sites similarly to AMPH, reducing drug-compartment preference and anxiogenic behaviors while maintaining dopaminergic metabolism proteins in the striatum, a key region involved in the onset and perpetuation of addiction.
{"title":"Chemistry to cognition: Therapeutic potential of (m-CF<sub>3</sub>-PhSe)<sub>2</sub> targeting rats' striatum dopamine proteins in amphetamine dependence.","authors":"Mustafa Munir Mustafa Dahleh, Sabrina Grendene Muller, Isabella Pregardier Klann, Luiza Souza Marques, Jéssica Leandra da Rosa, Murilo Barboza Fontoura, Marilise Escobar Burger, Cristina Wayne Nogueira, Marina Prigol, Silvana Peterini Boeira, Hecson Jesser Segat","doi":"10.1016/j.pnpbp.2024.111238","DOIUrl":"10.1016/j.pnpbp.2024.111238","url":null,"abstract":"<p><p>Amphetamine (AMPH) abuse represents a major global public health issue, highlighting the urgent need for effective therapeutic interventions to manage addiction caused by this psychostimulant. This study aimed to assess the potential of m-trifluoromethyl-diphenyldiselenide [(m-CF<sub>3</sub>-PhSe)<sub>2</sub>] in preventing the addictive effects induced by AMPH through targeting dopamine metabolism proteins. (m-CF<sub>3</sub>-PhSe)<sub>2</sub> is of interest due to its demonstrated efficacy in mitigating opioid abuse, establishing it as a promising candidate for addiction treatment research. Initially, in silico studies examined the affinity of AMPH and (m-CF<sub>3</sub>-PhSe)<sub>2</sub> for dopamine 1, 2, and 3 receptors (D1R, D2R, D3R), and dopamine transporter (DAT). In our experimental design, male Wistar rats were divided into four groups: I) Control; II) (m-CF<sub>3</sub>-PhSe)<sub>2</sub>; III) AMPH; IV) (m-CF<sub>3</sub>-PhSe)<sub>2</sub> + AMPH. Animals were administered (m-CF<sub>3</sub>-PhSe)<sub>2</sub> (0.1 mg/kg, by gavage) or canola oil (vehicle) 30 min before AMPH (4.0 mg/kg, i.p.) administration. Drug administration occurred for 8 days in the conditioned place preference (CPP) paradigm. Twenty-four hours after the last CPP conditioning section, preference for the drug-compartment was assessed, with anxiety-related effects and working memory were evaluated using the Y-maze test. Finally, animals were euthanized for striatal dissection to quantify D1R, D2R, D3R, and DAT levels in western blot. In silico findings suggest that (m-CF<sub>3</sub>-PhSe)<sub>2</sub> may prevent AMPH activation in DAT, interacting with Asp46 and Phe319, preventing possible addictive effects of AMPH in DAT. In vivo results showed that (m-CF<sub>3</sub>-PhSe)<sub>2</sub> attenuated AMPH effects, reducing preference for the drug-compartment in CPP test. Furthermore, (m-CF<sub>3</sub>-PhSe)<sub>2</sub> prevented AMPH-induced anxiogenic effects in the elevated plus maze (EPM) test, similarly to light/dark test. No differences in locomotion or working memory were observed among the experimental groups in the Y-maze test. Ex vivo western blot analyses of the entire striatum indicates that (m-CF<sub>3</sub>-PhSe)<sub>2</sub> prevented the AMPH-induced increase in D1R levels and decrease in D2R and DAT levels, with no changes in D3R levels. Overall, our study suggests that (m-CF<sub>3</sub>-PhSe)<sub>2</sub> may interact with DAT sites similarly to AMPH, reducing drug-compartment preference and anxiogenic behaviors while maintaining dopaminergic metabolism proteins in the striatum, a key region involved in the onset and perpetuation of addiction.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111238"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10Epub Date: 2025-01-06DOI: 10.1016/j.pnpbp.2025.111249
Ines Erkizia-Santamaría, Igor Horrillo, J Javier Meana, Jorge E Ortega
In the rapidly growing field of psychedelic research, psilocybin (and active metabolite psilocin) has been proposed as a promising candidate in the search for novel treatments for neuropsychiatric disorders. Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety. The safety profile is considered favourable, with low toxicity and good tolerance. Several preclinical studies have also been carried out to determine the long-term mechanism of action of this drug. In this sense, preclinical studies in naïve animals as well as in animal models of disease have shown somewhat discrepant results in conventional tests for assessment of depression- and anxiety-like phenotype in response to psilocybin, but overall suggest positive outcomes. Additionally, several valuable assays in rodent models have been developed over the years to elucidate the neurochemical correlates of serotonin 2A receptor (5HT2AR) activation in the brain, primary molecular target of psilocin. This review aims to provide a general overview of the current and most recent literature in the therapeutic potential of psilocybin through a description of clinical trials of psilocybin-assisted psychotherapy, and to showcase the scene in the up-to-date preclinical research. A detailed description of preclinical rodent models and experimental approaches that have been used to study the neurobiological and behavioural actions of psilocybin is provided, and potential therapeutic mechanisms of action are discussed.
{"title":"Clinical and preclinical evidence of psilocybin as antidepressant. A narrative review.","authors":"Ines Erkizia-Santamaría, Igor Horrillo, J Javier Meana, Jorge E Ortega","doi":"10.1016/j.pnpbp.2025.111249","DOIUrl":"10.1016/j.pnpbp.2025.111249","url":null,"abstract":"<p><p>In the rapidly growing field of psychedelic research, psilocybin (and active metabolite psilocin) has been proposed as a promising candidate in the search for novel treatments for neuropsychiatric disorders. Clinical trials have revealed that psilocybin has a large, rapid, and persistent effect in the improvement of symptoms of depression and anxiety. The safety profile is considered favourable, with low toxicity and good tolerance. Several preclinical studies have also been carried out to determine the long-term mechanism of action of this drug. In this sense, preclinical studies in naïve animals as well as in animal models of disease have shown somewhat discrepant results in conventional tests for assessment of depression- and anxiety-like phenotype in response to psilocybin, but overall suggest positive outcomes. Additionally, several valuable assays in rodent models have been developed over the years to elucidate the neurochemical correlates of serotonin 2A receptor (5HT2AR) activation in the brain, primary molecular target of psilocin. This review aims to provide a general overview of the current and most recent literature in the therapeutic potential of psilocybin through a description of clinical trials of psilocybin-assisted psychotherapy, and to showcase the scene in the up-to-date preclinical research. A detailed description of preclinical rodent models and experimental approaches that have been used to study the neurobiological and behavioural actions of psilocybin is provided, and potential therapeutic mechanisms of action are discussed.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111249"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111218
Kun Li , Liju Qian , Chenchen Zhang , Jiajia Zhang , Chuang Xue , Yuebing Zhang , Wei Deng
Schizophrenia, a severe mental illness characterized by cognitive impairment and olfactory dysfunction, remains an enigma with its pathological mechanism yet to be fully elucidated. The entorhinal cortex, a pivotal structure involved in numerous neural loop circuits related to olfaction, cognition, and emotion, has garnered significant attention due to its structural and functional abnormalities, which have been implicated in the pathogenesis of schizophrenia. This review focuses on the abnormal structural and functional changes in the entorhinal cortex in schizophrenia patients, as evidenced by neuroimaging, cellular biology, and genetic studies. These changes are posited to play a crucial role in the pathogenesis of cognitive impairment in schizophrenia. Furthermore, this review explores the various intervention strategies targeting the entorhinal cortex in current treatment modalities and proposes potential directions for future research endeavors, thereby providing a novel perspective on unraveling the complexity of neural mechanisms underlying schizophrenia and developing innovative therapeutic approaches for schizophrenia.
{"title":"The entorhinal cortex and cognitive impairment in schizophrenia: A comprehensive review","authors":"Kun Li , Liju Qian , Chenchen Zhang , Jiajia Zhang , Chuang Xue , Yuebing Zhang , Wei Deng","doi":"10.1016/j.pnpbp.2024.111218","DOIUrl":"10.1016/j.pnpbp.2024.111218","url":null,"abstract":"<div><div>Schizophrenia, a severe mental illness characterized by cognitive impairment and olfactory dysfunction, remains an enigma with its pathological mechanism yet to be fully elucidated. The entorhinal cortex, a pivotal structure involved in numerous neural loop circuits related to olfaction, cognition, and emotion, has garnered significant attention due to its structural and functional abnormalities, which have been implicated in the pathogenesis of schizophrenia. This review focuses on the abnormal structural and functional changes in the entorhinal cortex in schizophrenia patients, as evidenced by neuroimaging, cellular biology, and genetic studies. These changes are posited to play a crucial role in the pathogenesis of cognitive impairment in schizophrenia. Furthermore, this review explores the various intervention strategies targeting the entorhinal cortex in current treatment modalities and proposes potential directions for future research endeavors, thereby providing a novel perspective on unraveling the complexity of neural mechanisms underlying schizophrenia and developing innovative therapeutic approaches for schizophrenia.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111218"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111221
Andreas Karampas , George Leontaritis , Georgios Markozannes , Alexandros Asimakopoulos , Dimitra T. Archimandriti , Polyxeni Spyrou , Georgios Georgiou , Marios Plakoutsis , Konstantinos Kotsis , Paraskevi V. Voulgari , Petros Petrikis
Background
The aim of the present study was to measure adiponectin, resistin, interleukin-4 and TGF-β levels in first episode, treatment resistant patients with schizophrenia.
Methods
In total, fifty-three treatment-resistant patients were included in the study. In subgroups of these patients, we measured Interleukin-4 (IL-4), Tumor Growth Factor-β2 (TGF-β2), adiponectin and resistin levels at three different timepoints: in the drug-naïve state, after two rounds of treatment with different antipsychotic drugs for a total of 16 weeks and, after clozapine treatment for 12 weeks.
Results
TGF-β2 and adiponectin levels decreased after treatment with olanzapine and risperidone, while resistin and IL-4 levels did not differ significantly.Comparing the levels of the aforementioned cytokines before the initiation and after clozapine treatment, we found an even greater decrease in adiponectin levels while resistin and IL-4 levels significantly increased and TGF-β2 levels did not differ significantly.
Conclusions
We report elevated resistin and IL-4 levels and decreased adiponectin levels in first-episode, treatment resistant schizophrenia patients after clozapine treatment. These findings may be at least partly due to the anti-inflammatory action of clozapine, although sub-clinical metabolic disturbances may also have played a role as far as resistin and adiponectin are concerned. In a subgroup of these patients we report reduced TGF-β2 and adiponectin levels after two unsuccessful trials with risperidone and olanzapine comparing them with the ones of the same subgroup in the drug-naïve phase.
{"title":"Adiponectin, resistin, interleukin-4 and TGF-β2 levels in treatment resistant schizophrenia patients","authors":"Andreas Karampas , George Leontaritis , Georgios Markozannes , Alexandros Asimakopoulos , Dimitra T. Archimandriti , Polyxeni Spyrou , Georgios Georgiou , Marios Plakoutsis , Konstantinos Kotsis , Paraskevi V. Voulgari , Petros Petrikis","doi":"10.1016/j.pnpbp.2024.111221","DOIUrl":"10.1016/j.pnpbp.2024.111221","url":null,"abstract":"<div><h3>Background</h3><div>The aim of the present study was to measure adiponectin, resistin, interleukin-4 and TGF-β levels in first episode, treatment resistant patients with schizophrenia.</div></div><div><h3>Methods</h3><div>In total, fifty-three treatment-resistant patients were included in the study. In subgroups of these patients, we measured Interleukin-4 (IL-4), Tumor Growth Factor-β2 (TGF-β2), adiponectin and resistin levels at three different timepoints: in the drug-naïve state, after two rounds of treatment with different antipsychotic drugs for a total of 16 weeks and, after clozapine treatment for 12 weeks.</div></div><div><h3>Results</h3><div>TGF-β2 and adiponectin levels decreased after treatment with olanzapine and risperidone, while resistin and IL-4 levels did not differ significantly.Comparing the levels of the aforementioned cytokines before the initiation and after clozapine treatment, we found an even greater decrease in adiponectin levels while resistin and IL-4 levels significantly increased and TGF-β2 levels did not differ significantly.</div></div><div><h3>Conclusions</h3><div>We report elevated resistin and IL-4 levels and decreased adiponectin levels in first-episode, treatment resistant schizophrenia patients after clozapine treatment. These findings may be at least partly due to the anti-inflammatory action of clozapine, although sub-clinical metabolic disturbances may also have played a role as far as resistin and adiponectin are concerned. In a subgroup of these patients we report reduced TGF-β2 and adiponectin levels after two unsuccessful trials with risperidone and olanzapine comparing them with the ones of the same subgroup in the drug-naïve phase.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111221"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142866364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111224
Qiuyue Zhang , Xi Yang , Jianfeng Qiu , Weizhao Lu
Background and purpose
Autism spectrum disorder (ASD) is clinically heterogeneous, and resent neuroimaging studies have shown the presence of brain structural heterogeneity in ASD. However, there is currently a lack of evidence for systemic level brain structural heterogeneity. This study aimed to reveal the heterogeneity of brain structural changes at the systemic level in ASD patients through individual differential structural covariance network (IDSCN) analysis.
Materials and methods
We included 803 neurotypical controls (NCs) and 650 ASD patients from 24 sites and the corresponding structural magnetic resonance and clinical data. 516 ASD patients were used as training group, and 134 ASD patients were selected as an independent validation group. In the training group, we constructed IDSCN for each ASD patient, identified differentiated structural covariance edges, and resolved systemic heterogeneity using K-means clustering algorithm. We then conducted statistical analyses on the demographical and clinical data of the ASD subgroups, and performed correlation analyses between structural covariance edges and clinical profiles within each ASD subgroup. We also tested the reliability of the IDSCN in the validation group.
Results
The results of the training and validation groups were similar, revealing two subtypes of ASD, with 17 brain connections showing differences between the two subtypes. There were differences in clinical profiles between the two subgroups in restricted repetitive behavior score from autism diagnostic interview-revised (ADI_RRB_TOTAL), total score of autism diagnostic observation schedule (ADOS), social interaction score from ADOS and stereotyped behaviors score from ADOS. In both datasets, we also found a significant correlation between ADI_RRB_TOTAL scale and the Z-score for edges between the bilateral ventral tegmental area (VTA) and between the left VTA and right substantia nigra pars compacta.
Conclusion
ASD exhibited brain structural heterogeneity at the systemic level, mainly involving nucleus in the subcortical regions and brainstem, which can affect RRB in ASD patients. The two subtypes discovered in this study have the potential to be applied in precise diagnosis and treatment of the disorder.
{"title":"Systemic heterogeneity in autism spectrum disorder revealed by individualized structural covariance network analysis","authors":"Qiuyue Zhang , Xi Yang , Jianfeng Qiu , Weizhao Lu","doi":"10.1016/j.pnpbp.2024.111224","DOIUrl":"10.1016/j.pnpbp.2024.111224","url":null,"abstract":"<div><h3>Background and purpose</h3><div>Autism spectrum disorder (ASD) is clinically heterogeneous, and resent neuroimaging studies have shown the presence of brain structural heterogeneity in ASD. However, there is currently a lack of evidence for systemic level brain structural heterogeneity. This study aimed to reveal the heterogeneity of brain structural changes at the systemic level in ASD patients through individual differential structural covariance network (IDSCN) analysis.</div></div><div><h3>Materials and methods</h3><div>We included 803 neurotypical controls (NCs) and 650 ASD patients from 24 sites and the corresponding structural magnetic resonance and clinical data. 516 ASD patients were used as training group, and 134 ASD patients were selected as an independent validation group. In the training group, we constructed IDSCN for each ASD patient, identified differentiated structural covariance edges, and resolved systemic heterogeneity using K-means clustering algorithm. We then conducted statistical analyses on the demographical and clinical data of the ASD subgroups, and performed correlation analyses between structural covariance edges and clinical profiles within each ASD subgroup. We also tested the reliability of the IDSCN in the validation group.</div></div><div><h3>Results</h3><div>The results of the training and validation groups were similar, revealing two subtypes of ASD, with 17 brain connections showing differences between the two subtypes. There were differences in clinical profiles between the two subgroups in restricted repetitive behavior score from autism diagnostic interview-revised (ADI_RRB_TOTAL), total score of autism diagnostic observation schedule (ADOS), social interaction score from ADOS and stereotyped behaviors score from ADOS. In both datasets, we also found a significant correlation between ADI_RRB_TOTAL scale and the <em>Z</em>-score for edges between the bilateral ventral tegmental area (VTA) and between the left VTA and right substantia nigra pars compacta.</div></div><div><h3>Conclusion</h3><div>ASD exhibited brain structural heterogeneity at the systemic level, mainly involving nucleus in the subcortical regions and brainstem, which can affect RRB in ASD patients. The two subtypes discovered in this study have the potential to be applied in precise diagnosis and treatment of the disorder.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111224"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142873524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111230
Payman Raise-Abdullahi , Mehrnaz Rezvani , Fatemeh Yousefi , Sadaf Rahmani , Morvarid Meamar , Ehsan Raeis-Abdollahi , Abbas Ali Vafaei , Hamed Rashidipour , Ali Rashidy-Pour
Post-traumatic stress disorder (PTSD) is a challenging mental health condition that affects millions of people worldwide after they experience traumatic events. The current medications often do not fully address the wide range of PTSD symptoms or the underlying brain mechanisms, prompting the need to explore new treatments. Polyphenols, which are natural compounds found in many plant-based foods, have gained interest due to their brain-protective, anti-inflammatory, and antioxidant benefits. This review looks at how polyphenols might help treat PTSD by influencing important brain pathways related to the disorder. We explored how polyphenols affect the stress-response system, fear-related memories, brain chemicals, and inflammation. Specifically, we discuss how compounds like resveratrol, curcumin, green tea extract, and quercetin can balance stress hormones, help reduce fear memories, regulate brain chemicals, and decrease brain inflammation. Studies with animals have provided insights into how these compounds might work to ease PTSD symptoms. Based on the preclinical studies, the present review suggests that polyphenols could be a valuable addition or alternative to current PTSD treatments. However, more research is needed to confirm these findings and to determine the best ways to use polyphenols in treating PTSD.
{"title":"Natural polyphenols as therapeutic candidates for mitigating neuropsychiatric symptoms in post-traumatic stress disorder: Evidence from preclinical studies","authors":"Payman Raise-Abdullahi , Mehrnaz Rezvani , Fatemeh Yousefi , Sadaf Rahmani , Morvarid Meamar , Ehsan Raeis-Abdollahi , Abbas Ali Vafaei , Hamed Rashidipour , Ali Rashidy-Pour","doi":"10.1016/j.pnpbp.2024.111230","DOIUrl":"10.1016/j.pnpbp.2024.111230","url":null,"abstract":"<div><div>Post-traumatic stress disorder (PTSD) is a challenging mental health condition that affects millions of people worldwide after they experience traumatic events. The current medications often do not fully address the wide range of PTSD symptoms or the underlying brain mechanisms, prompting the need to explore new treatments. Polyphenols, which are natural compounds found in many plant-based foods, have gained interest due to their brain-protective, anti-inflammatory, and antioxidant benefits. This review looks at how polyphenols might help treat PTSD by influencing important brain pathways related to the disorder. We explored how polyphenols affect the stress-response system, fear-related memories, brain chemicals, and inflammation. Specifically, we discuss how compounds like resveratrol, curcumin, green tea extract, and quercetin can balance stress hormones, help reduce fear memories, regulate brain chemicals, and decrease brain inflammation. Studies with animals have provided insights into how these compounds might work to ease PTSD symptoms. Based on the preclinical studies, the present review suggests that polyphenols could be a valuable addition or alternative to current PTSD treatments. However, more research is needed to confirm these findings and to determine the best ways to use polyphenols in treating PTSD.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111230"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111229
Xiuli Wang , Xipeng Long , Bochao Cheng , Yuan Cao , Di Kong , Baolin Wu , Hongsheng Xie , Ziru Zhao , Neil Roberts , Nenghan Zhang , Zhiyun Jia
Objective
The overlap of affective disturbance and psychosis considerably makes it complex to determine the etiology of bipolar disorder (BD) and develop targeted interventions. The present study aimed to determine the white matter microstructural alterations that distinguish between BD with psychosis (BDP) and BD with no psychosis (BDNP) to identify patients who may specifically benefit from appropriately effective treatments.
Methods
Diffusion-weighted magnetic resonance images were acquired from 38 participants with BDP, 52 participants with BDNP and 70 healthy controls (HCs). The indices of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were computed and compared among the three groups via tract-based spatial statistics (TBSS).
Results
Analysis of covariance (ANCOVA) revealed the main effects of group on the FA, MD and RD values of the forceps minor (FMI) of the corpus callosum, right anterior thalamic radiation (ATR), and left corticospinal tract (CST). Post hoc analysis revealed that BDP patients had lower FA value in the FMI than HCs did, as well as lower FA and higher RD values in the FMI than BDNP patients did, whereas BDNP patients had lower FA and MD values in the right ATR, as well as higher FA and lower RD values in the left CST than HCs did.
Conclusion
These findings provide further insights into the specific neurobiological mechanisms that underlie the presence of psychosis in BD patients and represent potential objective biomarkers for differentiating between BDP and BDNP.
{"title":"Alterations in white matter microstructure in bipolar disorder patients with and without psychosis","authors":"Xiuli Wang , Xipeng Long , Bochao Cheng , Yuan Cao , Di Kong , Baolin Wu , Hongsheng Xie , Ziru Zhao , Neil Roberts , Nenghan Zhang , Zhiyun Jia","doi":"10.1016/j.pnpbp.2024.111229","DOIUrl":"10.1016/j.pnpbp.2024.111229","url":null,"abstract":"<div><h3>Objective</h3><div>The overlap of affective disturbance and psychosis considerably makes it complex to determine the etiology of bipolar disorder (BD) and develop targeted interventions. The present study aimed to determine the white matter microstructural alterations that distinguish between BD with psychosis (BDP) and BD with no psychosis (BDNP) to identify patients who may specifically benefit from appropriately effective treatments.</div></div><div><h3>Methods</h3><div>Diffusion-weighted magnetic resonance images were acquired from 38 participants with BDP, 52 participants with BDNP and 70 healthy controls (HCs). The indices of fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were computed and compared among the three groups via tract-based spatial statistics (TBSS).</div></div><div><h3>Results</h3><div>Analysis of covariance (ANCOVA) revealed the main effects of group on the FA, MD and RD values of the forceps minor (FMI) of the corpus callosum, right anterior thalamic radiation (ATR), and left corticospinal tract (CST). Post hoc analysis revealed that BDP patients had lower FA value in the FMI than HCs did, as well as lower FA and higher RD values in the FMI than BDNP patients did, whereas BDNP patients had lower FA and MD values in the right ATR, as well as higher FA and lower RD values in the left CST than HCs did.</div></div><div><h3>Conclusion</h3><div>These findings provide further insights into the specific neurobiological mechanisms that underlie the presence of psychosis in BD patients and represent potential objective biomarkers for differentiating between BDP and BDNP.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111229"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142883652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10DOI: 10.1016/j.pnpbp.2024.111210
Guowei Luo , Jian Zhou , Luyu Liu , Xinran Song , Min Peng , Xiangyang Zhang , the REST-meta-MDD Consortium
Background
The assessment of suicide risk in patients with major depressive disorder (MDD) is somewhat subjective in clinical diagnosis and may lead to diagnostic bias and serious consequences. Therefore, the aim of this study was to determine whether MDD patients with suicidal ideation or suicide attempts exhibited local brain functional synchrony and spontaneous activity intensity, thus providing certain imaging basis for suicide assessment.
Methods
This study was conducted using ReHo and ALFF analyses on 213 first episode drug-naïve MDD patients from the REST-meta-MDD consortium. All patients were categorized into MDD with SI or SA group and MDD without SI and SA. A voxel-based two-sample t-test was then used to identify brain regions with significant differences in ReHo or ALFF values. Finally, Reho or ALFF values of those brain regions in MDD with SI or SA group were extracted for correlation analysis with suicide severity.
Results
Compared with MDD patients without SI or SA, MDD patients with SI or SA had increased ReHo in the triangular part of left inferior frontal gyrus, orbital part of right inferior frontal gyrus and right precuneus gyrus, and increased ALFF in the middle occipital gyrus. All of these brain region characteristics were positively correlated with suicide severity on the HAMD 3th item score and HAMD 9th item score.
Conclusion
Our findings suggest that abnormalities of regional spontaneous brain activity were found in IFG, precuneus gyrus, and MOG among MDD patients with suicidal thoughts or attempts, which provides a reliable imaging basis for identifying and preventing suicide.
{"title":"Abnormal ReHo and ALFF values in drug-naïve depressed patients with suicidal ideation or attempts: Evidence from the REST-meta-MDD consortium","authors":"Guowei Luo , Jian Zhou , Luyu Liu , Xinran Song , Min Peng , Xiangyang Zhang , the REST-meta-MDD Consortium","doi":"10.1016/j.pnpbp.2024.111210","DOIUrl":"10.1016/j.pnpbp.2024.111210","url":null,"abstract":"<div><h3>Background</h3><div>The assessment of suicide risk in patients with major depressive disorder (MDD) is somewhat subjective in clinical diagnosis and may lead to diagnostic bias and serious consequences. Therefore, the aim of this study was to determine whether MDD patients with suicidal ideation or suicide attempts exhibited local brain functional synchrony and spontaneous activity intensity, thus providing certain imaging basis for suicide assessment.</div></div><div><h3>Methods</h3><div>This study was conducted using ReHo and ALFF analyses on 213 first episode drug-naïve MDD patients from the REST-meta-MDD consortium. All patients were categorized into MDD with SI or SA group and MDD without SI and SA. A voxel-based two-sample <em>t</em>-test was then used to identify brain regions with significant differences in ReHo or ALFF values. Finally, Reho or ALFF values of those brain regions in MDD with SI or SA group were extracted for correlation analysis with suicide severity.</div></div><div><h3>Results</h3><div>Compared with MDD patients without SI or SA, MDD patients with SI or SA had increased ReHo in the triangular part of left inferior frontal gyrus, orbital part of right inferior frontal gyrus and right precuneus gyrus, and increased ALFF in the middle occipital gyrus. All of these brain region characteristics were positively correlated with suicide severity on the HAMD 3th item score and HAMD 9th item score.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that abnormalities of regional spontaneous brain activity were found in IFG, precuneus gyrus, and MOG among MDD patients with suicidal thoughts or attempts, which provides a reliable imaging basis for identifying and preventing suicide.</div></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":"136 ","pages":"Article 111210"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142781676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-10Epub Date: 2024-09-30DOI: 10.1016/j.pnpbp.2024.111155
Randall D Ordovich-Clarkson, Maurice Jabbour, Daniel Arteaga Pelayo, Daniel Lara, Sebastian La Croix, Macie Mumman, Shoshanah Stukas, Reagan Anderson, David Meraz, Anthony Bangura, Brooklyn Anderson, Luke Bamrud, Caleb Blake
Background & aim: Treatment of Parkinson's disease (PD) has remained largely unchanged and focuses primarily on symptomatic relief through activation of dopaminergic pathways. Currently, there are no proven prophylactic approaches to the prevention of PD. This systematic review seeks to compare two separate compounds, metformin (MTF) and psilocybin, as potential prophylactic therapeutics against the development of PD.
Methods: The authors conducted a systematic review focusing on primary studies that test these compounds on cell and animal models to determine if they might have any neuroprotective or neuroplastic effects.
Results: The results of this review found that MTF may halt the progression of diseases such as PD through multiple mechanisms including reduced oxidative stress at the level of the mitochondria, thereby reducing α-synuclein related damage. Psilocybin, on the other hand, may increase repair of damaged neurons through psychoplastogenic activation of serotonergic pathways, particularly 5-HT2A receptor activation, ultimately increasing the release of brain derived neurotropic factor (BDNF) and the reduction of α-synuclein accumulation.
Conclusion: Implications of this study include a need for further research in off-label use of MTF as well as further research into serotonergic compounds such as psilocybin for the treatment and prevention of neurodegenerative diseases.
{"title":"Comparing psilocybin to metformin as neuroprotective agents against Parkinson's dementia: A systematic review of evidence and efficacy.","authors":"Randall D Ordovich-Clarkson, Maurice Jabbour, Daniel Arteaga Pelayo, Daniel Lara, Sebastian La Croix, Macie Mumman, Shoshanah Stukas, Reagan Anderson, David Meraz, Anthony Bangura, Brooklyn Anderson, Luke Bamrud, Caleb Blake","doi":"10.1016/j.pnpbp.2024.111155","DOIUrl":"10.1016/j.pnpbp.2024.111155","url":null,"abstract":"<p><strong>Background & aim: </strong>Treatment of Parkinson's disease (PD) has remained largely unchanged and focuses primarily on symptomatic relief through activation of dopaminergic pathways. Currently, there are no proven prophylactic approaches to the prevention of PD. This systematic review seeks to compare two separate compounds, metformin (MTF) and psilocybin, as potential prophylactic therapeutics against the development of PD.</p><p><strong>Methods: </strong>The authors conducted a systematic review focusing on primary studies that test these compounds on cell and animal models to determine if they might have any neuroprotective or neuroplastic effects.</p><p><strong>Results: </strong>The results of this review found that MTF may halt the progression of diseases such as PD through multiple mechanisms including reduced oxidative stress at the level of the mitochondria, thereby reducing α-synuclein related damage. Psilocybin, on the other hand, may increase repair of damaged neurons through psychoplastogenic activation of serotonergic pathways, particularly 5-HT<sub>2A</sub> receptor activation, ultimately increasing the release of brain derived neurotropic factor (BDNF) and the reduction of α-synuclein accumulation.</p><p><strong>Conclusion: </strong>Implications of this study include a need for further research in off-label use of MTF as well as further research into serotonergic compounds such as psilocybin for the treatment and prevention of neurodegenerative diseases.</p>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":" ","pages":"111155"},"PeriodicalIF":5.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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