Pub Date : 2022-01-01Epub Date: 2022-01-03DOI: 10.1159/000520457
Amir Keshavarzi, Aziz Sharifi, Leila Jahangard, Alireza Soltanian, Annette Beatrix Brühl, Mohammad Ahmadpanah, Serge Brand
Background: Levetiracetam is an anticonvulsant with a low side effect profile and favorable properties for individuals with bipolar I disorder during their manic phase. Despite initial promising results until about 2008, it appears that this track of research has not been followed-up. To counter this, we tested the influence of adjuvant levetiracetam on acute mania, compared to placebo. More specifically, we performed a randomized, double-blind, placebo-controlled clinical trial among inpatients with bipolar disorder I during their acute phase of mania.
Methods: A total of 72 inpatients (mean age: 33.98 years; 23.6% females) with diagnosed bipolar disorder I and during their acute manic phase were randomly assigned either to the adjuvant levetiracetam (250 mg to a maximum of 1,500 mg) or to the placebo condition. Standard medication was lithium at therapeutic dosages. At baseline, participants completed a series of self-rating questionnaires covering sociodemographic information and subjective sleep. Subjective sleep was re-assessed 24 days later at the end of the study. Experts rated participants' acute state of mania with the Young Mania Rating Scale at baseline and at day 12 and day 24. Participants' cognitive performance was assessed at baseline and at day 24 at the end of the study.
Results: Over time, mania scores significantly decreased (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (medium effect size). Likewise, over time, subjective sleep improved (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (large effect size). Over time, cognitive performance improved (large effect size), irrespective of the study condition.
Conclusions: Compared to placebo, adjuvant levetiracetam to lithium improved symptoms of mania, as rated by experts, and subjective sleep quality. Adjuvant levetiracetam had no further favorable (or detrimental) impact on cognitive performance.
背景介绍左乙拉西坦是一种抗惊厥药,副作用小,对处于躁狂期的躁狂 I 型双相情感障碍患者很有帮助。尽管直到 2008 年才取得了初步的可喜成果,但这一研究方向似乎并未得到跟进。为此,我们测试了与安慰剂相比,左乙拉西坦辅助药物对急性躁狂症的影响。更具体地说,我们在躁狂症急性期的躁狂症 I 型双相情感障碍住院患者中开展了一项随机、双盲、安慰剂对照临床试验:共有 72 名确诊为双相情感障碍 I 的住院患者(平均年龄:33.98 岁;23.6% 为女性)在急性躁狂期被随机分配到左乙拉西坦辅助药物(250 毫克至最高 1,500 毫克)或安慰剂治疗方案中。标准药物为治疗剂量的锂。在基线期,参与者填写了一系列自我评分问卷,内容包括社会人口学信息和主观睡眠情况。24 天后,在研究结束时再次对主观睡眠进行评估。专家们在基线期、第 12 天和第 24 天使用 Young 躁狂症评分量表对参与者的急性躁狂症状态进行评分。在基线和研究结束后的第24天,对参与者的认知能力进行评估:随着时间的推移,躁狂评分明显下降(大效应量),但与安慰剂相比,左乙拉西坦治疗条件下的躁狂评分下降更明显(中效应量)。同样,随着时间的推移,主观睡眠也有所改善(大效应量级),但与安慰剂相比,左乙拉西坦治疗组的主观睡眠改善程度更大(大效应量级)。随着时间的推移,认知能力得到改善(大效应量),与研究条件无关:与安慰剂相比,锂辅助左乙拉西坦能改善专家评定的躁狂症症状和主观睡眠质量。结论:与安慰剂相比,左乙拉西坦辅助锂剂可改善专家评定的躁狂症症状和主观睡眠质量,但对认知能力没有进一步的有利(或不利)影响。
{"title":"Levetiracetam as an Adjunctive Treatment for Mania: A Double-Blind, Randomized, Placebo-Controlled Trial.","authors":"Amir Keshavarzi, Aziz Sharifi, Leila Jahangard, Alireza Soltanian, Annette Beatrix Brühl, Mohammad Ahmadpanah, Serge Brand","doi":"10.1159/000520457","DOIUrl":"10.1159/000520457","url":null,"abstract":"<p><strong>Background: </strong>Levetiracetam is an anticonvulsant with a low side effect profile and favorable properties for individuals with bipolar I disorder during their manic phase. Despite initial promising results until about 2008, it appears that this track of research has not been followed-up. To counter this, we tested the influence of adjuvant levetiracetam on acute mania, compared to placebo. More specifically, we performed a randomized, double-blind, placebo-controlled clinical trial among inpatients with bipolar disorder I during their acute phase of mania.</p><p><strong>Methods: </strong>A total of 72 inpatients (mean age: 33.98 years; 23.6% females) with diagnosed bipolar disorder I and during their acute manic phase were randomly assigned either to the adjuvant levetiracetam (250 mg to a maximum of 1,500 mg) or to the placebo condition. Standard medication was lithium at therapeutic dosages. At baseline, participants completed a series of self-rating questionnaires covering sociodemographic information and subjective sleep. Subjective sleep was re-assessed 24 days later at the end of the study. Experts rated participants' acute state of mania with the Young Mania Rating Scale at baseline and at day 12 and day 24. Participants' cognitive performance was assessed at baseline and at day 24 at the end of the study.</p><p><strong>Results: </strong>Over time, mania scores significantly decreased (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (medium effect size). Likewise, over time, subjective sleep improved (large effect size), but more so in the levetiracetam condition, compared to the placebo condition (large effect size). Over time, cognitive performance improved (large effect size), irrespective of the study condition.</p><p><strong>Conclusions: </strong>Compared to placebo, adjuvant levetiracetam to lithium improved symptoms of mania, as rated by experts, and subjective sleep quality. Adjuvant levetiracetam had no further favorable (or detrimental) impact on cognitive performance.</p>","PeriodicalId":19239,"journal":{"name":"Neuropsychobiology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9227682/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39642816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2021-07-28DOI: 10.1159/000517859
Yuki Matsuda, Ryuichi Yamazaki, Taro Kishi, Nakao Iwata, Masahiro Shigeta, Shinsuke Kito
Introduction: Repetitive transcranial magnetic stimulation (rTMS) has been employed worldwide for therapy-resistant depression. The Food and Drug Administration has approved a number of therapeutic devices for treating major depressive disorder; however, no studies have examined the differences in efficacy and acceptability among commercially available stimulation devices. The aim of our study was to compare the efficacy and acceptability of 3 stimulation devices (NeuroStar, MagPro, and Magstim) for depressive disorders.
Methods: Our study included 31 randomized sham-controlled trials of high-frequency rTMS included in the network meta-analysis by Brunoni. We calculated the risk ratio and 95% confidence intervals, comparing each device with sham for the endpoints of response rate, remission rate, and all-cause discontinuation. We then analyzed the differences among the devices in effect size for those endpoints.
Results: After determining the effect sizes for the endpoints, we found no statistically significant subgroup differences in the response rates, all-cause discontinuation, or remission rates among the devices (p = 0.12, p = 0.84, and p = 0.07, respectively).
Conclusion: Our results suggest similar efficacy and acceptability for the 3 stimulation devices. Future studies need to perform head-to-head comparisons of the efficacy and acceptability of the stimulation devices for treating depression using the same stimulation protocols.
重复经颅磁刺激(rTMS)已在世界范围内用于治疗难治性抑郁症。美国食品和药物管理局(Food and Drug Administration)已经批准了一些用于治疗重度抑郁症的治疗设备;然而,目前还没有研究调查市面上可买到的刺激装置在功效和可接受性上的差异。本研究的目的是比较3种刺激装置(NeuroStar、MagPro和Magstim)治疗抑郁症的疗效和可接受性。方法:本研究纳入31项随机假对照高频rTMS试验,纳入Brunoni网络meta分析。我们计算了风险比和95%置信区间,将每个装置与假手术进行比较,以确定缓解率、缓解率和全因停药的终点。然后,我们分析了这些终点的效应大小在设备之间的差异。结果:在确定终点的效应大小后,我们发现在不同装置之间的反应率、全因停药率或缓解率没有统计学上显著的亚组差异(p = 0.12、p = 0.84和p = 0.07)。结论:3种刺激装置疗效相近,可接受性较好。未来的研究需要对使用相同的刺激方案治疗抑郁症的刺激装置的有效性和可接受性进行正面比较。
{"title":"Comparative Efficacy and Acceptability of 3 Repetitive Transcranial Magnetic Stimulation Devices for Depression: A Meta-Analysis of Randomized, Sham-Controlled Trials.","authors":"Yuki Matsuda, Ryuichi Yamazaki, Taro Kishi, Nakao Iwata, Masahiro Shigeta, Shinsuke Kito","doi":"10.1159/000517859","DOIUrl":"https://doi.org/10.1159/000517859","url":null,"abstract":"<p><strong>Introduction: </strong>Repetitive transcranial magnetic stimulation (rTMS) has been employed worldwide for therapy-resistant depression. The Food and Drug Administration has approved a number of therapeutic devices for treating major depressive disorder; however, no studies have examined the differences in efficacy and acceptability among commercially available stimulation devices. The aim of our study was to compare the efficacy and acceptability of 3 stimulation devices (NeuroStar, MagPro, and Magstim) for depressive disorders.</p><p><strong>Methods: </strong>Our study included 31 randomized sham-controlled trials of high-frequency rTMS included in the network meta-analysis by Brunoni. We calculated the risk ratio and 95% confidence intervals, comparing each device with sham for the endpoints of response rate, remission rate, and all-cause discontinuation. We then analyzed the differences among the devices in effect size for those endpoints.</p><p><strong>Results: </strong>After determining the effect sizes for the endpoints, we found no statistically significant subgroup differences in the response rates, all-cause discontinuation, or remission rates among the devices (p = 0.12, p = 0.84, and p = 0.07, respectively).</p><p><strong>Conclusion: </strong>Our results suggest similar efficacy and acceptability for the 3 stimulation devices. Future studies need to perform head-to-head comparisons of the efficacy and acceptability of the stimulation devices for treating depression using the same stimulation protocols.</p>","PeriodicalId":19239,"journal":{"name":"Neuropsychobiology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1159/000517859","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39252854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: The hippocampus is relevant to cognitive function in schizophrenia (SCZ) and mood disorder patients. Although not anatomically uniform, it is clearly divided into subfields. This study aimed to elucidate the relationship between hippocampal subfield volume and cognitive function in patients with SCZ, bipolar disorder (BP), and major depressive disorder (MDD).
Methods: The study included 21 patients with SCZ, 22 with BP, and 21 with MDD and 25 healthy controls (HCs). Neurocognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. We obtained hippocampal subfield volumes using FreeSurfer 6.0. We compared the volumes of the hippocampal subfield between the 4 groups and ascertained correlation between the cognitive composite score and hippocampal subfield volume in each group.
Results: The SCZ group had significantly lower cognitive composite score than the BP, MDD, and HC groups. In the SCZ group, the left and right hippocampus-amygdala transition area and right subiculum and right presubiculum volumes were significantly reduced compared to those in the HC group. The left presubiculum volumes in the SCZ group were significantly reduced compared to those in the MDD group. Subfield volumes did not significantly differ between the BP, MDD, and HC groups. Interestingly, in the SCZ group, volumes of the right CA1, right molecular layer of the hippocampus, and right granule cell and molecular layer of the dentate gyrus were significantly correlated with the cognitive composite score.
Conclusion: Patients with SCZ had poorer cognitive function, which is related to their hippocampal pathology, than those with mood disorders.
{"title":"Hippocampal Subfield Volumes and Cognitive Function in Schizophrenia and Mood Disorders.","authors":"Kasumi Yasuda, Shinichi Yamada, Shinya Uenishi, Natsuko Ikeda, Atsushi Tamaki, Yuji Ohoshi, Tomikimi Tsuji, Shun Takahashi","doi":"10.1159/000521102","DOIUrl":"https://doi.org/10.1159/000521102","url":null,"abstract":"<p><strong>Introduction: </strong>The hippocampus is relevant to cognitive function in schizophrenia (SCZ) and mood disorder patients. Although not anatomically uniform, it is clearly divided into subfields. This study aimed to elucidate the relationship between hippocampal subfield volume and cognitive function in patients with SCZ, bipolar disorder (BP), and major depressive disorder (MDD).</p><p><strong>Methods: </strong>The study included 21 patients with SCZ, 22 with BP, and 21 with MDD and 25 healthy controls (HCs). Neurocognitive function was assessed using the Brief Assessment of Cognition in Schizophrenia. We obtained hippocampal subfield volumes using FreeSurfer 6.0. We compared the volumes of the hippocampal subfield between the 4 groups and ascertained correlation between the cognitive composite score and hippocampal subfield volume in each group.</p><p><strong>Results: </strong>The SCZ group had significantly lower cognitive composite score than the BP, MDD, and HC groups. In the SCZ group, the left and right hippocampus-amygdala transition area and right subiculum and right presubiculum volumes were significantly reduced compared to those in the HC group. The left presubiculum volumes in the SCZ group were significantly reduced compared to those in the MDD group. Subfield volumes did not significantly differ between the BP, MDD, and HC groups. Interestingly, in the SCZ group, volumes of the right CA1, right molecular layer of the hippocampus, and right granule cell and molecular layer of the dentate gyrus were significantly correlated with the cognitive composite score.</p><p><strong>Conclusion: </strong>Patients with SCZ had poorer cognitive function, which is related to their hippocampal pathology, than those with mood disorders.</p>","PeriodicalId":19239,"journal":{"name":"Neuropsychobiology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39700937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2021-08-30DOI: 10.1159/000518385
Vincenzo Nobile, Silvana Giardina, Francesco Puoci
Background: The gut-brain axis refers to the network of connections that involve multiple biologic systems, allowing bidirectional communication between the gut and the brain. This communication is mainly mediated by gut microbiota, thanks to its ability to modulate several processes like the production of neurotransmitters. As such, keeping a balanced gut microbiota through probiotic intake could be a valid solution in supporting the right gut-brain communications.
Methods: A two-step in vitro screening of five different probiotic strains was carried out to select the best performers in the modulation of stress markers. A first selection on SK-N-DZ neuronal cell lines was performed to evaluate the inhibition of the epigenetic enzyme LSD1, promotion of GABA, and expression of serotonin. Three out of five strains were tested for their ability to promote serotonin synthesis in the Caco2 cell line. As a result, Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 were selected as the best performing strains. To confirm their effects in humans, a proof-of-concept trial was carried out to evaluate stress-related parameters for 28 days of product intake in a group of 30 stressed students.
Results: A significant improvement of cognitive functions, in terms of short-term memory, attention, and executive performance, as well as of psychophysiological markers, such as salivary cortisol level, skin conductance, sleep quality, and anxiety, were observed.
Conclusions: According to the results, L. reuteri PBS072 and B. breve BB077 are potential probiotic candidates for improving stress resilience, cognitive functions, and sleep quality.
{"title":"The Effect of a Probiotic Complex on the Gut-Brain Axis: A Translational Study.","authors":"Vincenzo Nobile, Silvana Giardina, Francesco Puoci","doi":"10.1159/000518385","DOIUrl":"https://doi.org/10.1159/000518385","url":null,"abstract":"<p><strong>Background: </strong>The gut-brain axis refers to the network of connections that involve multiple biologic systems, allowing bidirectional communication between the gut and the brain. This communication is mainly mediated by gut microbiota, thanks to its ability to modulate several processes like the production of neurotransmitters. As such, keeping a balanced gut microbiota through probiotic intake could be a valid solution in supporting the right gut-brain communications.</p><p><strong>Methods: </strong>A two-step in vitro screening of five different probiotic strains was carried out to select the best performers in the modulation of stress markers. A first selection on SK-N-DZ neuronal cell lines was performed to evaluate the inhibition of the epigenetic enzyme LSD1, promotion of GABA, and expression of serotonin. Three out of five strains were tested for their ability to promote serotonin synthesis in the Caco2 cell line. As a result, Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 were selected as the best performing strains. To confirm their effects in humans, a proof-of-concept trial was carried out to evaluate stress-related parameters for 28 days of product intake in a group of 30 stressed students.</p><p><strong>Results: </strong>A significant improvement of cognitive functions, in terms of short-term memory, attention, and executive performance, as well as of psychophysiological markers, such as salivary cortisol level, skin conductance, sleep quality, and anxiety, were observed.</p><p><strong>Conclusions: </strong>According to the results, L. reuteri PBS072 and B. breve BB077 are potential probiotic candidates for improving stress resilience, cognitive functions, and sleep quality.</p>","PeriodicalId":19239,"journal":{"name":"Neuropsychobiology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39413533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hayley Riel, Erica Rudolph, Catrina MacPhee, Philip G Tibbo, Derek J Fisher
Introduction: The present study compared the mismatch negativity (MMN) and P3a waveforms among early-phase psychosis (EPP; n = 13) individuals and healthy controls (n = 30) to contribute to the research on these waveforms as potential biomarkers for schizophrenia.
Methods: MMN and P3a were elicited with a novelty paradigm using complex stimuli with electrophysiological technology.
Results: No significant group differences of amplitude were observed with either waveform. Increased asociality and blunted affect were associated with a reduction in both MMN and P3a waveforms indicating a relationship between these negative symptoms and cognitive deficits. Good social and occupational functioning correlated with improved MMN and P3a waveforms in the EPP group.
Conclusions: This study suggests that MMN and P3a may be more appropriately used as an indicator of illness progression and symptomology rather than a biomarker in the early phase of the illness.
{"title":"MMN and P3a Elicited by a Novelty Oddball Paradigm Are Not Reduced in Early-Phase Psychosis.","authors":"Hayley Riel, Erica Rudolph, Catrina MacPhee, Philip G Tibbo, Derek J Fisher","doi":"10.1159/000526745","DOIUrl":"https://doi.org/10.1159/000526745","url":null,"abstract":"<p><strong>Introduction: </strong>The present study compared the mismatch negativity (MMN) and P3a waveforms among early-phase psychosis (EPP; n = 13) individuals and healthy controls (n = 30) to contribute to the research on these waveforms as potential biomarkers for schizophrenia.</p><p><strong>Methods: </strong>MMN and P3a were elicited with a novelty paradigm using complex stimuli with electrophysiological technology.</p><p><strong>Results: </strong>No significant group differences of amplitude were observed with either waveform. Increased asociality and blunted affect were associated with a reduction in both MMN and P3a waveforms indicating a relationship between these negative symptoms and cognitive deficits. Good social and occupational functioning correlated with improved MMN and P3a waveforms in the EPP group.</p><p><strong>Conclusions: </strong>This study suggests that MMN and P3a may be more appropriately used as an indicator of illness progression and symptomology rather than a biomarker in the early phase of the illness.</p>","PeriodicalId":19239,"journal":{"name":"Neuropsychobiology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10351956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Functional connectivity is attracting increasing attention for understanding the pathophysiology of depression and predicting the therapeutic efficacy of antidepressants. In this study, we evaluated effective connectivity using isolated effective coherence (iCoh), an effective functional connectivity analysis method developed from low-resolution brain electromagnetic tomography (LORETA) and estimated its practical usefulness for predicting the reaction to antidepressants in theta and alpha band iCoh values.
Methods: We enrolled 25 participants from a depression treatment randomized study (the GUNDAM study) in which electroencephalography was performed before treatment. We conducted iCoh between the rostral anterior cingulate cortex (rACC) and anterior insula (AI), which are associated with the salience network. The patients were divided into responder and nonresponder groups at 4 weeks after the start of treatment, and iCoh values were compared between the two groups. Additionally, the sensitivity and specificity of iCoh were calculated using the receiver-operating characteristic (ROC) curve.
Results: The Mann-Whitney U test showed significantly weaker connectivity flow from the rACC to the left AI in the alpha band in the responder group. The ROC curve for the connectivity flow from the rACC to the left AI in the alpha band showed 82% sensitivity and 86% specificity.
Discussion/conclusion: These findings suggest the pathological importance of effective connectivity flow from the rACC to the left AI in the alpha and theta bands and suggest its usefulness as a biomarker to distinguish responders to antidepressants.
{"title":"Association between the Rostral Anterior Cingulate Cortex and Anterior Insula in the Salience Network on Response to Antidepressants in Major Depressive Disorder as Revealed by Isolated Effective Coherence.","authors":"Shota Minami, Masaki Kato, Shunichiro Ikeda, Masafumi Yoshimura, Satsuki Ueda, Yosuke Koshikawa, Yoshiteru Takekita, Toshihiko Kinoshita, Keiichiro Nishida","doi":"10.1159/000525338","DOIUrl":"https://doi.org/10.1159/000525338","url":null,"abstract":"<p><strong>Introduction: </strong>Functional connectivity is attracting increasing attention for understanding the pathophysiology of depression and predicting the therapeutic efficacy of antidepressants. In this study, we evaluated effective connectivity using isolated effective coherence (iCoh), an effective functional connectivity analysis method developed from low-resolution brain electromagnetic tomography (LORETA) and estimated its practical usefulness for predicting the reaction to antidepressants in theta and alpha band iCoh values.</p><p><strong>Methods: </strong>We enrolled 25 participants from a depression treatment randomized study (the GUNDAM study) in which electroencephalography was performed before treatment. We conducted iCoh between the rostral anterior cingulate cortex (rACC) and anterior insula (AI), which are associated with the salience network. The patients were divided into responder and nonresponder groups at 4 weeks after the start of treatment, and iCoh values were compared between the two groups. Additionally, the sensitivity and specificity of iCoh were calculated using the receiver-operating characteristic (ROC) curve.</p><p><strong>Results: </strong>The Mann-Whitney U test showed significantly weaker connectivity flow from the rACC to the left AI in the alpha band in the responder group. The ROC curve for the connectivity flow from the rACC to the left AI in the alpha band showed 82% sensitivity and 86% specificity.</p><p><strong>Discussion/conclusion: </strong>These findings suggest the pathological importance of effective connectivity flow from the rACC to the left AI in the alpha and theta bands and suggest its usefulness as a biomarker to distinguish responders to antidepressants.</p>","PeriodicalId":19239,"journal":{"name":"Neuropsychobiology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10348425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-02-14DOI: 10.1159/000522003
Antonio Del Casale, Stefano Ferracuti, Andrea Steven Barbetti, Paride Bargagna, Paolo Zega, Alessia Iannuccelli, Federico Caggese, Teodolinda Zoppi, Gabriele Pasquale De Luca, Giovanna Parmigiani, Isabella Berardelli, Maurizio Pompili
Introduction: In recent years, research on posttraumatic stress disorder (PTSD) focused on the description of different biological correlates of illness. Morphological changes of different brain regions were involved in PTSD neurophysiopathology, being related to trauma or considered a resilience biomarker. In this meta-analysis, we aimed to investigate the grey matter changes reported in magnetic resonance imaging (MRI) studies on patients who have developed PTSD compared to exposed subjects who did not show a clinical PTSD onset.
Methods: We meta-analysed eight peer-reviewed MRI studies conducted on trauma-exposed patients and reported results corrected for false positives. We then conducted global and intergroup comparisons from neuroimaging data of two cohorts of included subjects. The included studies were conducted on 250 subjects, including 122 patients with PTSD and 128 non-PTSD subjects exposed to trauma.
Results: Applying a family-wise error correction, PTSD subjects compared to trauma-exposed non-PTSD individuals showed a significant volume reduction of a large left-sided grey matter cluster extended from the parahippocampal gyrus to the uncus, including the amygdala.
Conclusions: These volumetric reductions are a major structural correlate of PTSD and can be related to the expression of symptoms. Future studies might consider these and other neural PTSD correlates, which may lead to the development of clinical applications for affected patients.
{"title":"Grey Matter Volume Reductions of the Left Hippocampus and Amygdala in PTSD: A Coordinate-Based Meta-Analysis of Magnetic Resonance Imaging Studies.","authors":"Antonio Del Casale, Stefano Ferracuti, Andrea Steven Barbetti, Paride Bargagna, Paolo Zega, Alessia Iannuccelli, Federico Caggese, Teodolinda Zoppi, Gabriele Pasquale De Luca, Giovanna Parmigiani, Isabella Berardelli, Maurizio Pompili","doi":"10.1159/000522003","DOIUrl":"https://doi.org/10.1159/000522003","url":null,"abstract":"<p><strong>Introduction: </strong>In recent years, research on posttraumatic stress disorder (PTSD) focused on the description of different biological correlates of illness. Morphological changes of different brain regions were involved in PTSD neurophysiopathology, being related to trauma or considered a resilience biomarker. In this meta-analysis, we aimed to investigate the grey matter changes reported in magnetic resonance imaging (MRI) studies on patients who have developed PTSD compared to exposed subjects who did not show a clinical PTSD onset.</p><p><strong>Methods: </strong>We meta-analysed eight peer-reviewed MRI studies conducted on trauma-exposed patients and reported results corrected for false positives. We then conducted global and intergroup comparisons from neuroimaging data of two cohorts of included subjects. The included studies were conducted on 250 subjects, including 122 patients with PTSD and 128 non-PTSD subjects exposed to trauma.</p><p><strong>Results: </strong>Applying a family-wise error correction, PTSD subjects compared to trauma-exposed non-PTSD individuals showed a significant volume reduction of a large left-sided grey matter cluster extended from the parahippocampal gyrus to the uncus, including the amygdala.</p><p><strong>Conclusions: </strong>These volumetric reductions are a major structural correlate of PTSD and can be related to the expression of symptoms. Future studies might consider these and other neural PTSD correlates, which may lead to the development of clinical applications for affected patients.</p>","PeriodicalId":19239,"journal":{"name":"Neuropsychobiology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39614689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-01-11DOI: 10.1159/000521185
Qi Wang, Hongsheng Bi, Hongfei Huang, Yitong Wang, Lili Gong, Na Qi, Dongdong Li, Xin Jin, Tianchao Xu, Baoguang Shi
Background: The precise physiological mechanisms of acupuncture in the treatment of depression are still unknown. This study aimed to observe the effects of electroacupuncture (EA) on depression-like behavior of mouse in chronic mild stress (CMS) model and explore the underlying mechanism.
Methods: The depression model was established by using CMS method for 6 weeks. After the third week of the CMS paradigm, EA treatment was performed daily for 15 min over a period of 3 weeks. The antidepressant-like effects of EA were evaluated using the sucrose preference test and the forced swimming test (FST). The protein levels of the nuclear factor-kappa B (NF-κB), p-NF-κB, inhibitor of NF-κB, p-IκBα, NOD-like receptor protein 3, interleukin (IL)-6, IL-1β, IL-18, and tumor necrosis factor-α (TNF-α) in hippocampus of mice were detected.
Results: Sucrose preference was decreased after 6 weeks of CMS and the effects of CMS was reversed by EA. CMS increased immobility time and decreased latency to the first immobility in the FST test, but these effects were reversed by EA. CMS-induced nuclear entry of NF-κB (nuclear/cytoplasmic ratio of NF-κB) with an increase in protein levels of p-NF-κB and p-IκBα in the hippocampus. The CMS also increased NLRP3 levels in the hippocampus. However, these effects were reversed by EA. In addition, the levels of IL-6, IL-1β, IL-18, and TNF-α in the hippocampus were increased by CMS, and these effects of stress were reversed by EA.
Conclusion: EA prevented CMS-induced depressive-like behaviors by inhibiting NF-κB/NLRP3 inflammatory pathway.
背景:针刺治疗抑郁症的确切生理机制尚不清楚。本研究旨在观察电针(EA)对慢性轻度应激(CMS)模型小鼠抑郁样行为的影响,并探讨其机制。方法:采用CMS方法建立抑郁模型,持续6周。在CMS模式的第三周后,在3周的时间内每天进行15分钟的EA治疗。采用蔗糖偏好试验和强迫游泳试验(FST)评价EA的抗抑郁样作用。检测小鼠海马组织核因子κB (NF-κB)、p-NF-κB、NF-κB抑制剂、p -κB α、nod样受体蛋白3、白细胞介素(IL)-6、IL-1β、IL-18、肿瘤坏死因子-α (TNF-α)的蛋白水平。结果:CMS治疗6周后,蔗糖偏好降低,EA可逆转CMS的作用。在FST试验中,CMS增加了固定时间,减少了第一次固定的潜伏期,但这些作用被EA逆转。CMS诱导NF-κB (NF-κB核/质比)进入核,海马中p-NF-κB和p- i -κB α蛋白水平升高。CMS还增加了海马中NLRP3的水平。此外,CMS可使海马组织中IL-6、IL-1β、IL-18、TNF-α水平升高,并可逆转应激作用。结论:EA可通过抑制NF-κB/NLRP3炎症通路抑制CMS诱导的抑郁样行为。
{"title":"Electroacupuncture Prevents the Depression-Like Behavior by Inhibiting the NF-κB/NLRP3 Inflammatory Pathway in Hippocampus of Mice Subjected to Chronic Mild Stress.","authors":"Qi Wang, Hongsheng Bi, Hongfei Huang, Yitong Wang, Lili Gong, Na Qi, Dongdong Li, Xin Jin, Tianchao Xu, Baoguang Shi","doi":"10.1159/000521185","DOIUrl":"https://doi.org/10.1159/000521185","url":null,"abstract":"<p><strong>Background: </strong>The precise physiological mechanisms of acupuncture in the treatment of depression are still unknown. This study aimed to observe the effects of electroacupuncture (EA) on depression-like behavior of mouse in chronic mild stress (CMS) model and explore the underlying mechanism.</p><p><strong>Methods: </strong>The depression model was established by using CMS method for 6 weeks. After the third week of the CMS paradigm, EA treatment was performed daily for 15 min over a period of 3 weeks. The antidepressant-like effects of EA were evaluated using the sucrose preference test and the forced swimming test (FST). The protein levels of the nuclear factor-kappa B (NF-κB), p-NF-κB, inhibitor of NF-κB, p-IκBα, NOD-like receptor protein 3, interleukin (IL)-6, IL-1β, IL-18, and tumor necrosis factor-α (TNF-α) in hippocampus of mice were detected.</p><p><strong>Results: </strong>Sucrose preference was decreased after 6 weeks of CMS and the effects of CMS was reversed by EA. CMS increased immobility time and decreased latency to the first immobility in the FST test, but these effects were reversed by EA. CMS-induced nuclear entry of NF-κB (nuclear/cytoplasmic ratio of NF-κB) with an increase in protein levels of p-NF-κB and p-IκBα in the hippocampus. The CMS also increased NLRP3 levels in the hippocampus. However, these effects were reversed by EA. In addition, the levels of IL-6, IL-1β, IL-18, and TNF-α in the hippocampus were increased by CMS, and these effects of stress were reversed by EA.</p><p><strong>Conclusion: </strong>EA prevented CMS-induced depressive-like behaviors by inhibiting NF-κB/NLRP3 inflammatory pathway.</p>","PeriodicalId":19239,"journal":{"name":"Neuropsychobiology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39810967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-01-11DOI: 10.1159/000521103
Gianna Spitta, Tobias Gleich, Kristin Zacharias, Oisin Butler, Ralph Buchert, Jürgen Gallinat
Introduction: Reduced striatal dopamine D2/3 receptor availability in alcohol use disorder (AUD) has been demonstrated in recent clinical studies and meta-analyses. However, only a limited number of studies investigated extrastriatal D2/3 availability in AUD or in at-risk populations. In line with a dimensional understanding of addiction, extrastriatal dopaminergic neuroadaptations have been suggested to be relevant from a pathobiological perspective.
Methods: We investigated D2/3 receptor availability via 18F-fallypride positron emission tomography applying a region of interest (ROI) approach. We selected ROIs for the prefrontal cortex (PFC) and the anterior cingulate cortex (ACC). Our sample included 19 healthy controls (low risk [LR]), 19 individuals at high risk (HR) to develop addiction, and 20 recently detoxified AUD patients.
Results: We found significantly higher D2/3 receptor availability of HR compared to AUD in the left and right rostral ACC (rACC), as well as in the left ventrolateral PFC (vlPFC). We did not observe a significant difference between AUD and LR. After corrections for multiple comparisons none of the ROIs reached significance throughout the group comparison. The D2/3 receptor availability in the left rACC was inversely correlated with symptom severity assessed with the Alcohol Dependency Scale.
Discussion: To our knowledge, the present work is the first study investigating extrastriatal D2/3 receptor availabilities in individuals at HR and patients with AUD. The observation that D2/3 receptor availabilities are highest in HR might suggest that their pathobiology differs from subjects with AUD. Future studies are necessary to clarify the intraindividual course of this biomarker over different disease stages and its possible role as a risk or protective factor.
{"title":"Extrastriatal Dopamine D2/3 Receptor Availability in Alcohol Use Disorder and Individuals at High Risk.","authors":"Gianna Spitta, Tobias Gleich, Kristin Zacharias, Oisin Butler, Ralph Buchert, Jürgen Gallinat","doi":"10.1159/000521103","DOIUrl":"https://doi.org/10.1159/000521103","url":null,"abstract":"<p><strong>Introduction: </strong>Reduced striatal dopamine D2/3 receptor availability in alcohol use disorder (AUD) has been demonstrated in recent clinical studies and meta-analyses. However, only a limited number of studies investigated extrastriatal D2/3 availability in AUD or in at-risk populations. In line with a dimensional understanding of addiction, extrastriatal dopaminergic neuroadaptations have been suggested to be relevant from a pathobiological perspective.</p><p><strong>Methods: </strong>We investigated D2/3 receptor availability via 18F-fallypride positron emission tomography applying a region of interest (ROI) approach. We selected ROIs for the prefrontal cortex (PFC) and the anterior cingulate cortex (ACC). Our sample included 19 healthy controls (low risk [LR]), 19 individuals at high risk (HR) to develop addiction, and 20 recently detoxified AUD patients.</p><p><strong>Results: </strong>We found significantly higher D2/3 receptor availability of HR compared to AUD in the left and right rostral ACC (rACC), as well as in the left ventrolateral PFC (vlPFC). We did not observe a significant difference between AUD and LR. After corrections for multiple comparisons none of the ROIs reached significance throughout the group comparison. The D2/3 receptor availability in the left rACC was inversely correlated with symptom severity assessed with the Alcohol Dependency Scale.</p><p><strong>Discussion: </strong>To our knowledge, the present work is the first study investigating extrastriatal D2/3 receptor availabilities in individuals at HR and patients with AUD. The observation that D2/3 receptor availabilities are highest in HR might suggest that their pathobiology differs from subjects with AUD. Future studies are necessary to clarify the intraindividual course of this biomarker over different disease stages and its possible role as a risk or protective factor.</p>","PeriodicalId":19239,"journal":{"name":"Neuropsychobiology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39811091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-01-01Epub Date: 2022-01-28DOI: 10.1159/000521104
Teresa Massardo, Juan C Quintana, Luis Risco, Sebastian Corral, Jane Spuler, Daniel Vicentini, Gabriel Castro-Muñoz, Byron Riedel, Carolina Villa, Jaime I Pereira
Introduction: Major depressive disorder (MDD) is a prevalent condition which has a well-known association with ischemic cardiomyopathy, probably explained by an inflammatory mediator mechanism. Statins, besides reducing cholesterol production, have pleiotropic effects including anti-inflammatory activity. The goal was to evaluate the effect of statins as an addition to standard therapy on mood status, brain perfusion, and neurocognitive performance in MDD.
Methods: We studied 20 MDD patients with brain single-photon emission tomography and Cambridge Neuropsychological Test Automated Battery (CANTAB), half randomized to 10 mg of Rosuvastatin or placebo, in addition to selective serotonin reuptake inhibitors (SSRIs) therapy and being reevaluated 3 months later. The images were compared using Statistical Parametric Mapping; clinical scores (Hamilton Depression Score with 17 items and Beck's Depression Inventory) as well as neurocognitive parameters were applied as covariances (CoV) to estimate regional cerebral blood flow (rCBF) changes with both therapies.
Results: Clinical scores decreased in both groups (p = 0.0001); Beck's presented a larger decrease with statins. We observed significantly rCBF changes expressed as significant larger clusters of voxels (p < 0.05) in the pre/subgenual anterior cingulate plus orbitofrontal cortex and a small area in the posterior cingulate gyrus in the statins group, whereas it was not observed with placebo, when using clinical scores as CoV. A similar pattern of rCBF changes was present with emotions recognition, attentional, paired associates learning, spatial planning, and working memory tasks.
Conclusion: Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance. These findings, even though demonstrated in a small sample, could open a new therapeutic tool in the comprehensive management of this disorder.
{"title":"Effect of Low-Dose Statins in Addition to Standard Therapy on Brain Perfusion and Neurocognitive Performance in Patients with Major Depressive Disorder.","authors":"Teresa Massardo, Juan C Quintana, Luis Risco, Sebastian Corral, Jane Spuler, Daniel Vicentini, Gabriel Castro-Muñoz, Byron Riedel, Carolina Villa, Jaime I Pereira","doi":"10.1159/000521104","DOIUrl":"https://doi.org/10.1159/000521104","url":null,"abstract":"<p><strong>Introduction: </strong>Major depressive disorder (MDD) is a prevalent condition which has a well-known association with ischemic cardiomyopathy, probably explained by an inflammatory mediator mechanism. Statins, besides reducing cholesterol production, have pleiotropic effects including anti-inflammatory activity. The goal was to evaluate the effect of statins as an addition to standard therapy on mood status, brain perfusion, and neurocognitive performance in MDD.</p><p><strong>Methods: </strong>We studied 20 MDD patients with brain single-photon emission tomography and Cambridge Neuropsychological Test Automated Battery (CANTAB), half randomized to 10 mg of Rosuvastatin or placebo, in addition to selective serotonin reuptake inhibitors (SSRIs) therapy and being reevaluated 3 months later. The images were compared using Statistical Parametric Mapping; clinical scores (Hamilton Depression Score with 17 items and Beck's Depression Inventory) as well as neurocognitive parameters were applied as covariances (CoV) to estimate regional cerebral blood flow (rCBF) changes with both therapies.</p><p><strong>Results: </strong>Clinical scores decreased in both groups (p = 0.0001); Beck's presented a larger decrease with statins. We observed significantly rCBF changes expressed as significant larger clusters of voxels (p < 0.05) in the pre/subgenual anterior cingulate plus orbitofrontal cortex and a small area in the posterior cingulate gyrus in the statins group, whereas it was not observed with placebo, when using clinical scores as CoV. A similar pattern of rCBF changes was present with emotions recognition, attentional, paired associates learning, spatial planning, and working memory tasks.</p><p><strong>Conclusion: </strong>Short-term use of low-dose statins in MDD patients under SSRIs results in important rCBF changes in key mood associated areas to improvement in neurocognitive performance. These findings, even though demonstrated in a small sample, could open a new therapeutic tool in the comprehensive management of this disorder.</p>","PeriodicalId":19239,"journal":{"name":"Neuropsychobiology","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39870356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}