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Relationship of CYP3A4*1B Single Nucleotide Polymorphism to the Efficiency and Safety Profiles of Haloperidol in Patients Enduring Acute Alcoholic Hallucinosis. CYP3A4*1B 单核苷酸多态性与急性酒精性幻觉病患者服用氟哌啶醇的效率和安全性之间的关系
Pub Date : 2023-12-04
A A Parkhomenko, M S Zastrozhin, VYu Skryabin, A E Petukhov, S A Pozdniakov, V A Ivanchenko, I A Zaytsev, I V Bure, P O Bochkov, K A Akmalova, V V Smirnov, E A Bryun, D A Sychev

To date, haloperidol has been widely used to treat patients with acute alcoholic hallucinosis. There is strong evidence that haloperidol therapy is commonly associated with adverse drug reactions (ADRs). The 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) is known to affect the metabolism rates of haloperidol; hence it correlates with both therapy efficacy and safety parameters.

Objective: The study objective was to investigate the effect of 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) on the efficacy and safety profiles of haloperidol in patients with acute alcoholic hallucinosis.

Methods: This study enrolled 100 male patients suffering from acute alcoholic hallucinosis (mean age 41.4 ± 14.4 years). The efficacy profile of haloperidol was assessed using the PANSS (Positive and Negative Syndrome Scale) validated psychometric scale. The safety profile of therapy was assessed with the UKU Side-Effect Rating Scale and the SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scale. Genotyping was performed using the real-time polymerase chain reaction (Real-time PCR).

Results: There were no statistically significant results for the efficacy rates (dynamics of the PANSS score: AA genotype -14.00 [-16.00; -12.00], AG genotype -13.00 [-14.00; -10.50], p = 0.306). Similarly, there was no statistically significant difference in the safety profiles (dynamics of the UKU score: AA genotype - 9.00 [7.00; 13.00], AG genotype - 8.50 [7.25; 10.50], p = 0.620; dynamics of the SAS score: AA genotype -12.00 [10.00; 16.75], AG genotype - 10.00 [10.00; 12.25], p = 0.321).

Conclusion: The study demonstrated that the 392A > G polymorphism of the CYP3A4*1B gene (rs2740574) in patients with acute alcoholic hallucinosis does not affect the efficacy and safety rates of haloperidol therapy.

迄今为止,氟哌啶醇已被广泛用于治疗急性酒精性幻觉症患者。有确凿证据表明,氟哌啶醇治疗通常与药物不良反应(ADRs)有关。已知 CYP3A4*1B 基因的 392A > G 多态性(rs2740574)会影响氟哌啶醇的代谢率,因此它与疗效和安全性参数都有关联:研究目的:探讨 CYP3A4*1B 基因 392A > G 多态性(rs2740574)对急性酒精性幻觉症患者氟哌啶醇疗效和安全性的影响:本研究招募了 100 名患有急性酒精性幻觉的男性患者(平均年龄为 41.4 ± 14.4 岁)。使用PANSS(阳性和阴性综合征量表)有效心理测量量表评估氟哌啶醇的疗效。治疗的安全性采用UKU副作用评定量表和SAS(辛普森-安格斯锥体外系症状量表)量表进行评估。基因分型采用实时聚合酶链反应(Real-time PCR)进行:结果:疗效率(PANSS评分的动态变化)无统计学意义:AA基因型-14.00 [-16.00; -12.00],AG基因型-13.00 [-14.00; -10.50],P = 0.306)。同样,在安全性方面也没有统计学意义上的显著差异(UKU 评分的动态变化:AA基因型 - 9.00 [7.00; 13.00],AG基因型 - 8.50 [7.25; 10.50],p = 0.620;SAS评分的动态变化:AA基因型-12.00 [10.00; 16.75],AG基因型-10.00 [10.00; 12.25],p = 0.321):该研究表明,急性酒精性幻觉患者的 CYP3A4*1B 基因 392A > G 多态性(rs2740574)不会影响氟哌啶醇治疗的疗效和安全性。
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引用次数: 0
Consequences of 1,4-Butanediol Misuse: A Review. 滥用 1,4-丁二醇的后果:综述。
Pub Date : 2023-12-04
VYu Skryabin, YuB Shevtsova, E A Novoselova

Gamma-hydroxybutyrate (GHB), along with its precursors, 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL), are potent central depressant agents widely illicitly used for their euphoric and relaxant effects. The article presents a review of the literature on the 1,4-BD misuse, the clinical picture of intoxication, development of addiction and delirium. The available evidence shows that 1,4-BD is a substance with its own psychoactive effects, a high addiction potential and potentially severe withdrawal symptoms.

γ-羟丁酸(GHB)及其前体1,4-丁二醇(1,4-BD)和γ-丁内酯(GBL)都是强效的中枢抑制剂,因具有兴奋和松弛作用而被广泛非法使用。文章回顾了有关 1,4-BD 滥用、中毒临床表现、成瘾发展和谵妄的文献。现有证据表明,1,4-丁二酸是一种具有自身精神活性作用的物质,成瘾可能性很高,并可能出现严重的戒断症状。
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引用次数: 0
Relationship of the 1846G > A Polymorphism of the CYP2D6 Gene to the Equilibrium Concentration Levels of Haloperidol in Patients with Acute Alcoholic Hallucinosis. CYP2D6 基因 1846G > A 多态性与急性酒精性幻觉症患者氟哌啶醇平衡浓度水平的关系。
Pub Date : 2023-12-04
A A Parkhomenko, M S Zastrozhin, VYu Skryabin, A E Petukhov, S A Pozdniakov, V A Ivanchenko, I A Zaytsev, I V Bure, P O Bochkov, K A Akmalova, V V Smirnov, E A Bryun, D A Sychev

Haloperidol is currently used in addictology for the treatment of acute psychotic disorders, including acute alcoholic hallucinosis. The use of haloperidol is often accompanied by the occurrence of adverse drug reactions (ADRs). There is evidence that CYP2D6 isoenzyme is involved in the biotransformation of haloperidol.

Aim: The study aimed to evaluate the relationship of 1846G > A polymorphism of the CYP2D6 gene to the equilibrium concentration levels of haloperidol in patients with acute alcoholic hallucinosis.

Material and methods: The study was conducted on 100 male patients with acute alcoholic hallucinosis (mean age 41.4 ± 14.4 years). The efficacy profile was evaluated using the PANSS (Positive and Negative Syndrome Scale) scale. The safety of therapy was assessed using the UKU Side-Effect Rating Scale and the SAS (Simpson-Angus Scale for Extrapyramidal Symptoms) scale. Genotyping was performed using the real-time polymerase chain reaction (Real-time PCR). Equilibrium plasma concentration levels of haloperidol were investigated using the high-performance liquid chromatography with mass spectrometry (HPLC with MS/MS).

Results: No statistically significant results were obtained during the therapy efficacy assessment (dynamics of the PANSS score: GG genotype (-13.00 [-16.00; -16.00; -11.00]), GA genotype (-15.00 [-16.75; -13.00], p = 0.728). There was a statistically significant difference in safety assessment scores (dynamics of the UKU score: GG genotype (8.00 [7.00; 10.00]), GA genotype (15.00 [9.25; 18.00], p < 0.001); dynamics of the SAS score: GG genotype (11.00 [9.00; 14.00]), GA genotype (14.50 [12.00; 18.00], p < 0.001). The pharmacokinetic study results showed a statistically significant difference: GG (3.13 [2.32; 3.95]), GA (3.89 [2.92; 5.26], p = 0.010). Thus, a study conducted on a group of 100 patients with acute alcoholic hallucinosis demonstrated an association between the 1846G > A polymorphism of the CYP2D6 gene (rs3892097) and the safety profile of haloperidol therapy. We also revealed the presence of statistically significant difference in the equilibrium concentration levels of haloperidol in patients with the GG and AG genotypes.

Conclusion: It can be concluded that patients with the GA genotype have a higher risk of ADRs compared to patients carrying the GG genotype. It is shown that 1846G > A polymorphism of the CYP2D6 gene (rs3892097) has a statistically significant effect on the equilibrium concentration levels of haloperidol.

氟哌啶醇目前在成瘾学中用于治疗急性精神病,包括急性酒精性幻觉。在使用氟哌啶醇的同时,经常会出现药物不良反应(ADRs)。目的:该研究旨在评估 CYP2D6 基因 1846G > A 多态性与急性酒精性幻觉症患者氟哌啶醇平衡浓度水平的关系:研究对象为 100 名急性酒精性幻觉症男性患者(平均年龄为 41.4 ± 14.4 岁)。疗效采用 PANSS(阳性和阴性综合征量表)量表进行评估。治疗的安全性采用 UKU 副作用评定量表和 SAS(辛普森-安格斯锥体外系症状量表)量表进行评估。基因分型采用实时聚合酶链反应(Real-time PCR)进行。使用高效液相色谱-质谱法(HPLC-MS/MS)检测氟哌啶醇的平衡血浆浓度水平:结果:在疗效评估(PANSS评分的动态变化、GG基因型(-13.00%)、PANSS评分的动态变化、PANSS评分的动态变化)中没有发现有统计学意义的结果:GG基因型(-13.00 [-16.00; -16.00; -11.00]),GA基因型(-15.00 [-16.75; -13.00],P = 0.728)。安全性评估得分(UKU 评分动态变化)差异有统计学意义:GG基因型(8.00 [7.00; 10.00]),GA基因型(15.00 [9.25; 18.00],p < 0.001);SAS评分动态:GG基因型(11.00 [9.00; 14.00]),GA基因型(14.50 [12.00; 18.00],P <0.001)。药代动力学研究结果显示,两者之间存在显著的统计学差异:GG(3.13 [2.32; 3.95]),GA(3.89 [2.92; 5.26],p = 0.010)。因此,一项针对 100 名急性酒精性幻觉症患者的研究表明,CYP2D6 基因的 1846G > A 多态性(rs3892097)与氟哌啶醇治疗的安全性之间存在关联。我们还发现,GG 和 AG 基因型患者的氟哌啶醇平衡浓度水平存在显著的统计学差异:结论:与 GG 基因型患者相比,GA 基因型患者发生不良反应的风险更高。研究表明,CYP2D6 基因的 1846G > A 多态性(rs3892097)对氟哌啶醇的平衡浓度水平有显著的统计学影响。
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引用次数: 0
Association of Psychopharmacological Medication Preference with Autistic Traits and Emotion Regulation in ADHD. 精神药理学用药偏好与自闭症特质和多动症情绪调节的关系。
Pub Date : 2023-12-04
Burcu Ozbaran, Ipek Inal-Kaleli, Nurhak Dogan, Halil Ibrahim Colak, Anil Altunkaya, Beyza Ozbaran, Sezen Kose

Background: This study intends to evaluate the relationship between medication switching and autistic traits, emotion dysregulation, and methylphenidate side effects in children with attention deficit hyperactivity disorder (ADHD).

Methods: Children with ADHD, ages 9-18, treated with methylphenidate (MTP) (n = 23), and switched to atomoxetine (ATX) (n = 20) were included. All participants were interviewed with K-SADS-PL to confirm ADHD diagnosis and exclude comorbid psychiatric disorders. The participants then completed Difficulty in Emotion Regulation Scale (DERS) and Autism-Spectrum Quotient (AQ) and their parents completed Autism Spectrum Screening Questionnaire (ASSQ) and Barkley Stimulant Side Effect Rating Scale(BSSERS).

Results: The MTP group scored higher than the ATX group in ASSQ, AQ, and the lack of emotional clarity subscale of DERS, while the ATX group had higher scores in the emotional non-acceptance subscale of DERS. No differences were found between the MTP and ATX groups in methylphenidate side-effect severity. Multiple regression analyses revealed that non-acceptance of emotions predicted the switch to ATX while lack of emotional clarity predicted the maintenance of MTP therapy, rather than autistic traits.

Conclusions: This study highlights emotion regulation difficulties and how different emotional profiles may influence medication selection in children with ADHD.

研究背景本研究旨在评估注意力缺陷多动障碍(ADHD)儿童换药与自闭症特征、情绪失调和哌醋甲酯副作用之间的关系:方法:研究对象包括9-18岁的ADHD儿童,他们曾接受过哌醋甲酯(MTP)治疗(23人),后改用阿托西汀(ATX)治疗(20人)。所有参与者都接受了 K-SADS-PL 问诊,以确认多动症诊断并排除合并精神病。然后,参与者填写了情绪调节困难量表(DERS)和自闭症谱系商数(AQ),其家长填写了自闭症谱系筛查问卷(ASSQ)和巴克利兴奋剂副作用评定量表(BSSERS):自闭症谱系筛查问卷(ASSQ)和巴克利刺激剂副作用评定量表(BSSERS)的得分,MTP组均高于ATX组,而ATX组在自闭症谱系筛查问卷(ASSQ)和巴克利刺激剂副作用评定量表(BSSERS)中的得分则高于MTP组。在哌醋甲酯副作用严重程度方面,MTP 组和 ATX 组之间没有差异。多元回归分析显示,不接受情绪预示着患者会转用ATX疗法,而缺乏情绪清晰度则预示着患者会继续接受MTP疗法,而不是自闭症特质:本研究强调了情绪调节方面的困难,以及不同的情绪特征如何影响多动症儿童的药物选择。
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引用次数: 0
Rhabdomyolysis Complicated with Hyponatremia Due to Water Intoxication and Severe Aspiration Pneumonia: Description of a Patient with Chronic Schizophrenia and Literature Review. 因水中毒和严重吸入性肺炎导致的横纹肌溶解并发低钠血症:一名慢性精神分裂症患者的描述和文献综述。
Pub Date : 2023-12-04
Shintaro Watanabe, Yoshio Sato, Junya Miyaki, Takefumi Suzuki

Hyponatremia due to water intoxication is frequently observed in patients with chronic schizophrenia. We herein present a 49-year-old man who developed schizophrenia at the age of 23 and had been admitted to the closed ward of our hospital for 7 years. He was found by a round nurse standing at the bedside, covering both ears with his hands and making groaning noises. He was disoriented and immediately after being returned to bed, a general tonic-clonic seizure occurred. Severe hyponatremia (Na 104 mEq/L) was noted and intravenous sodium correction was started. A few hours later, due to glossoptosis and massive vomiting, ventilation got worse to the point where he had to be put on a ventilator. On the following day, he developed aspiration pneumonia and antimicrobial treatment was started. In addition, a blood sample taken 36 hours later revealed an extensive elevation of creatine kinase (41,286 U/L), pointing to a possibility of rhabdomyolysis as a complication. Subsequently, the general condition gradually improved with antimicrobial therapy and sodium correction. He eventually recovered without any complications including central pontine myelinolysis. He had no history of polydipsia before this event but it was later found that esophageal stricture triggered complusive fluid intake, resulting in acute hyponatremia, seizure, aspiration pneumonia and rhabdomyolysis. A brief discussion will be provided on the issues surrounding hyponatremia, rhabdomyolysis and schizophrenia.

慢性精神分裂症患者经常会出现因水中毒导致的低钠血症。我们在此介绍一名 49 岁的男性患者,他在 23 岁时患上精神分裂症,在本医院的封闭病房住院已有 7 年之久。查房护士发现他站在床边,双手捂住双耳,发出呻吟声。他神志不清,被送回病床后立即出现全身强直-阵挛发作。发现严重低钠血症(Na 104 mEq/L),开始静脉补钠。几小时后,由于出现舌苔黄腻和大量呕吐,通气情况恶化,不得不使用呼吸机。第二天,他患上了吸入性肺炎,并开始接受抗菌治疗。此外,36 小时后采集的血样显示肌酸激酶广泛升高(41,286 U/L),这表明并发症可能是横纹肌溶解症。随后,经过抗菌治疗和钠纠正,他的总体情况逐渐好转。他最终康复,没有出现任何并发症,包括中枢神经髓鞘溶解症。在此之前,他没有多尿史,但后来发现食道狭窄引发了并发症性液体摄入,导致急性低钠血症、癫痫发作、吸入性肺炎和横纹肌溶解症。我们将简要讨论与低钠血症、横纹肌溶解症和精神分裂症有关的问题。
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引用次数: 0
β-Blockers for Autism-Help or Hindrance? β-受体阻滞剂治疗自闭症--帮助还是阻碍?
Pub Date : 2023-12-04
Ahmed Naguy, Seshni Gourika Moodliar-Rensburg, Bibi Alamiri

A renewed interest in the use of β-blockers for neurodevelopmental disorders has recently resurfaced, notably as an addition to the limited psychopharmacological armamentarium of autism spectrum disorders (ASD). In this clinical perspective, authors decently argue this use could be advantageous and multi-folded for this population.

最近,人们再次对使用β受体阻滞剂治疗神经发育障碍产生了兴趣,尤其是将其作为自闭症谱系障碍(ASD)有限的精神药物治疗手段的补充。从这一临床角度来看,作者认为这种使用对自闭症患者具有多重优势。
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引用次数: 0
Treatment-Resistant Juvenile Depression-A Quicksand? 难治性青少年抑郁症--流沙?
Pub Date : 2023-12-04
Ahmed Naguy, Saxby Pridmore, Hessa Alhazeem, Bibi Alamiri

Though research in juvenile depression is advancing, evidence examining effective treatments for Treatment-resistant juvenile depression remains at large limited. There is a dire need for more studies to help guide clinicians navigating these challenging cases.

尽管对青少年抑郁症的研究在不断进步,但对治疗耐药青少年抑郁症的有效治疗方法进行研究的证据仍然十分有限。我们迫切需要更多的研究来帮助指导临床医生处理这些具有挑战性的病例。
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引用次数: 0
Probable Olanzapine-Related Idiopathic Intracranial Hypertension in an Adolescent With First-Episode Psychosis. 首次发作精神病的青少年可能与奥氮平相关的特发性颅内高压。
Pub Date : 2023-08-11
Ahmed Naguy, Camellia Naguy, Sanaa Sabir

Pseudotumor cerebri or idiopathic intracranial hypertension (IIH) secondary to psychotropic drugs is a very rare occurrence. Lithium is typically the culprit agent. Here, authors report on an interesting case of an adolescent with early-onset schizophrenia that develops a reversible IIH putatively related to olanzapine-induced weight gain. This is followed by discussion of purported pharmacodynamic mechanisms and brief review of literature. Clinicians should be cognizant to this serious complication given the propensity of the majority of atypical antipsychotics to induce significant weight gain especially in younger population.

继发于精神药物的脑假瘤或特发性颅内高压是一种非常罕见的情况。锂通常是罪魁祸首。在这里,作者报告了一个有趣的案例,一名患有早发性精神分裂症的青少年发展出一种可逆的IIH,被认为与奥氮平诱导的体重增加有关。随后对所谓的药效机制进行了讨论,并对文献进行了简要回顾。临床医生应该认识到这种严重的并发症,因为大多数非典型抗精神病药物都有导致体重显著增加的倾向,尤其是在年轻人群中。
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引用次数: 0
Association Between Symptom Severity and Medication Adherence in Adolescents with Bipolar Disorder Demonstrating Suboptimal Adherence. 表现出次优依从性的双相情感障碍青少年症状严重程度与药物依从性的关系。
Pub Date : 2023-08-11
Martha Sajatovic, Jennifer B Levin, Avani Modi, Molly McVoy, Larry F Forthun, Raechel Cooley, Jessica Black, Carla Conroy, Kaylee Sarna, Farren B Briggs, Melissa DelBello

Objective: While medication non-adherence is common in bipolar disorder (BD), few studies have specifically assessed non-adherent BD adolescents and young adults (AYAs). This analysis, using screening and baseline data from an ongoing randomized controlled trial, examined the relationship between BD symptoms and adherence in poorly adherent AYAs.

Methods: AYAs ages 13-21 had sub-optimal adherence defined as missing ⩾ 20% of prescribed BD medication. Mean sample (N = 36) age was 19.1 years (SD = 2.0), 66.7 % (N = 24) female, 25.0 % (n = 9) non-white. Adherence was measured via: 1) self-reported Tablets Routine Questionnaire (TRQ) and 2) electronic monitoring (SimpleMed pillbox). Symptoms were measured with the Hamilton Depression Rating Scale (HAM-D), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression Scale (CGI).

Results: Mean percentage of missed BD medications using TRQ was 34.9 (SD = 28.9) at screening and 30.6 (SD = 33.0) at baseline. Mean percentage of missed medication using SimpleMed at baseline was 42.1 (SD = 37.0). The correlation between TRQ and SimpleMed was r = 0.36 (p = 0. 13). Neither CGI nor age were correlated with adherence. Neither TRQ nor SimpleMed were significantly related to HAM-D. YMRS was positively associated with worse adherence for TRQ (r = 0.36, p = 0.03), but not significantly associated with SimpleMed. Adherence did not differ by other demographic attributes.

Conclusion: Adherence levels varied widely in AYA with BD. Adherence monitoring increased adherence by approximately 4.5%, and use of electronic pill monitoring identified a greater proportion of missed medication vs. self-report. BD symptoms may not consistently identify AYA with adherence challenges.

目的:虽然药物不依从性在双相情感障碍(BD)中很常见,但很少有研究专门评估不依从性BD青少年和年轻人(AYAs)。这项分析使用了一项正在进行的随机对照试验的筛查和基线数据,检查了粘附性差的AYA的BD症状与依从性之间的关系。方法:13-21岁的AYA有次优依从性,定义为缺少20%的处方BD药物。平均样本(N=36)年龄为19.1岁(SD=2.0),66.7%(N=24)为女性,25.0%(N=9)为非白人。通过以下方式测量依从性:1)自我报告的片剂常规问卷(TRQ)和2)电子监测(SimpleMed碉堡)。症状采用汉密尔顿抑郁量表(HAM-D)、青年躁狂量表(YMRS)和临床整体印象量表(CGI)进行测量。结果:使用TRQ的BD药物错过率在筛查时为34.9(SD=28.9),在基线时为30.6(SD=33.0)。基线时使用SimpleMed的平均漏药百分比为42.1(SD=37.0)。TRQ与SimpleMed之间的相关性为r=0.36(p=0。13) 。CGI和年龄均与依从性无关。TRQ和SimpleMed均与HAM-D无显著相关性。YMRS与TRQ依从性较差呈正相关(r=0.36,p=0.03),但与SimpleMed无显著相关性。依从性在其他人口特征方面没有差异。结论:患有BD的AYA患者的依从性水平差异很大。依从性监测使依从性增加了约4.5%,使用电子药丸监测发现与自我报告相比,漏药的比例更大。BD症状可能无法一致地识别AYA与依从性挑战。
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引用次数: 0
Transcranial Magnetic Stimulation (TMS) for Major Depressive Disorder-Modus Operandi! 经颅磁刺激治疗重度抑郁症Modus Operandi!
Pub Date : 2023-08-11
Saxby Pridmore, Yvonne Turnier-Shea, Marzena Rybak, Ahmed Naguy

Background: Transcranial magnetic stimulation (TMS) is effective in the management of treatment resistant major depressive disorder (MDD) and has recently become widely available. Our aim was to explore the literature for evidence of the mechanism of action.

Method: We examined our own accumulating TMS library, the reference lists of all available papers and used a search engine to collect information. We collated and examined this information under relevant heading.

Results: TMS produces a large number of physiological changes including site of stimulation neurochemical, brain wave and blood flow effects, and distant structure effects including neurotransmitter effects and volume increase. TMS also corrects generalized and local functional connectivity (FC) abnormalities which are a feature of MDD.

Conclusion: TMS produces a range of physiological changes. It is unclear which of these underpin its antidepressant. It is likely more than one work synergistically to this end-almost certainly the capacity to correct MDD induced FC abnormalities makes a strong antidepressant contribution.

背景:经颅磁刺激(TMS)在治疗难治性重度抑郁障碍(MDD)方面是有效的,并且最近已经广泛可用。我们的目的是探索文献,寻找作用机制的证据。方法:我们检查了我们自己积累的TMS库,所有可用论文的参考文献列表,并使用搜索引擎收集信息。我们在相关标题下整理和审查了这些信息。结果:TMS产生大量的生理变化,包括刺激部位神经化学、脑电波和血流效应,以及神经递质效应和体积增加等远处结构效应。TMS还可以纠正MDD的一个特征——全身和局部功能连接(FC)异常。结论:TMS会产生一系列生理变化。目前尚不清楚其中哪一种是其抗抑郁药的基础。这可能是不止一项协同工作,几乎可以肯定的是,纠正MDD诱导的FC异常的能力对抗抑郁药有很大的贡献。
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引用次数: 0
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Psychopharmacology bulletin
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