RESUMEN
Post-traumatic stress disorder (PTSD) presents distinct sex-specific differences in both symptom expression and treatment outcomes, with the underlying biological mechanisms still remain unclear. Epigenetic modifications, particularly histone acetylation, have been increasingly recognized as critical factors in the pathophysiology of PTSD. Valproic acid (VPA), a potent histone deacetylase (HDAC) inhibitor, has shown promise in modulating epigenetic responses and improving therapeutic outcomes is PTSD, though its effect may differ between sexes. This study aimed to explore the sex-specific epigenetic changes in response to trauma and the impact of VPA treatment in a rat model of PTSD induced by predator scent stress. Sprague-Dawley rats of both sexes were randomly assigned to stressed and non-stressed groups and treated with either VPA (100 mg/kg) or vehicle. Anxiety levels were assessed using the elevated plus maze, followed by analysis of histone H3 and H4 acetylation, HDAC activity, and c-fos expression in the hippocampus. Our findings revealed that traumatic stress led to increased freezing time and anxiety levels, with more pronounced effects observed in females. Additionally, we have identified sex-specific differences in hippocampal epigenetic modifications; stressed females exhibited higher H3 acetylation, and VPA-treated stressed males showed increased H4 acetylation. These results highlight the importance of considering sex differences in the epigenetic mechanism underlying PTSD and suggest that personalized therapeutic approaches may be necessary to address these complexities.
Asunto(s)
Epigénesis Genética , Inhibidores de Histona Desacetilasas , Ratas Sprague-Dawley , Trastornos por Estrés Postraumático , Ácido Valproico , Animales , Ácido Valproico/farmacología , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/genética , Trastornos por Estrés Postraumático/metabolismo , Masculino , Femenino , Epigénesis Genética/efectos de los fármacos , Ratas , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/uso terapéutico , Modelos Animales de Enfermedad , Histonas/metabolismo , Caracteres Sexuales , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Acetilación/efectos de los fármacos , Ansiedad/tratamiento farmacológicoRESUMEN
BACKGROUND: Hemifacial spasm (HFS) is a debilitating disease characterized by involuntary tonic and clonic contractions of muscles innervated by the facial nerve. Botulinum toxin A (BTX-A) is the first-line option and the most effective medical treatment for HFS. The objective of this study was to evaluate the effect of BTX-A therapy on the physical and mental health of HFS patients. METHODS: Participants included 65 HFS patients and 65 matched healthy controls in the study. Cornell Medical Index (CMI) self-assessment questionnaire was used to detect the psychological health of all participants. Local injection of BTX-A was applied, and the Cohen hierarchical criteria were employed to stratify the degree of spasticity, further evaluating the efficacy of BTX-A before and two months after treatment in HFS patients. The HFS patients at two months post-treatment were re-evaluated by CMI self-assessment questionnaire, and the evaluated factors of these patients were compared with those of patients before treatment. RESULTS: The scores of somatization, depression, anxiety, inadaptation, sensitivity, anger, tension, M-R, and total scores in the HFS group were significantly higher than those in the control group (all P<0.05). Two months post-treatment, among 65 HFS patients who received with BTX-A treatment, 42 (64.6%) were completely relieved, 16 (24.6%) were significantly relieved, 7 (10.8%) were partially relieved, and 0 (0%) cases were invalid, and the total effective rate was 89.2%. Two months after BTX-A treatment, the scores of somatization, tension, anxiety, depression, sensitivity, M-R and total scores of patients with HFS were lower than those before treatment (all P<0.05). CONCLUSIONS: Patients with HFS are often accompanied by somatization, anger, inadaptation, sensitivity, anxiety, depression, and tension. BTX-A can not only alleviate the symptoms of HFS, but also improve the somatization, tension, anxiety, depression, and sensitivity.
Asunto(s)
Toxinas Botulínicas Tipo A , Espasmo Hemifacial , Fármacos Neuromusculares , Humanos , Espasmo Hemifacial/tratamiento farmacológico , Toxinas Botulínicas Tipo A/uso terapéutico , Femenino , Masculino , Persona de Mediana Edad , Fármacos Neuromusculares/uso terapéutico , Adulto , Salud Mental , Resultado del Tratamiento , Anciano , Encuestas y Cuestionarios , Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológicoRESUMEN
BACKGROUND: Effective medication adherence is vital for managing acute myocardial infarction (AMI) and enhancing patient well-being. This study aimed to evaluate medication adherence levels and associated factors among AMI patients using standardized assessment tools. METHODS: Employing a cross-sectional descriptive design, the study involved 210 patients diagnosed with acute myocardial infarction. Participants completed the General Medication Adherence Scale (GMAS), Hospital Anxiety and Depression Scale (HADS), and provided socio-demographic details. RESULTS: The study revealed partial adherence to medications among AMI patients, with mean scores of 24.89 (± 3.64) out of 33. Notably, good adherence was observed in non-adherence due to patient behavior (mean ± SD = 11.8 ± 2.3 out of 15) and additional disease burden (mean ± SD = 8.65 ± 2.21 out of 12), while partial adherence was noted in non-adherence due to financial constraints (mean ± SD = 4.44 ± 1.34 out of 6). Patients reported mild anxiety (mean ± SD = 8.38 ± 2.81) and no depressive symptoms (mean ± SD = 7.43 ± 2.42). Multiple linear regression analysis indicated that employed status, younger age, shorter duration of MI, lower anxiety, and depression levels were associated with higher medication adherence. However, factors such as monthly income, gender, educational level, and marital status did not predict medication adherence. CONCLUSION: The study highlights the significance of addressing anxiety and depression levels and considering socio-demographic factors when designing interventions to enhance medication adherence among AMI patients. Further research is needed to explore additional determinants of medication adherence and develop tailored interventions to improve patient outcomes post-AMI.
Asunto(s)
Ansiedad , Depresión , Cumplimiento de la Medicación , Infarto del Miocardio , Humanos , Masculino , Infarto del Miocardio/psicología , Infarto del Miocardio/tratamiento farmacológico , Cumplimiento de la Medicación/estadística & datos numéricos , Cumplimiento de la Medicación/psicología , Femenino , Persona de Mediana Edad , Estudios Transversales , Ansiedad/psicología , Ansiedad/tratamiento farmacológico , Depresión/psicología , Depresión/tratamiento farmacológico , Anciano , AdultoRESUMEN
BACKGROUND: Psychedelic-assisted therapy refers to a group of therapeutic practices involving psychedelics taken under therapeutic supervision from physicians, psychologists, and others. It has been hypothesised that psychedelic-assisted therapy may reduce symptoms of anxiety, depression, and existential distress in patients facing life-threatening diseases (e.g. cancer). However, these substances are illegal in most countries and have been associated with potential risks. OBJECTIVES: To assess the benefits and harms of psychedelic-assisted therapy compared to placebo or active comparators (e.g. antidepressants) for treatment of anxiety, depression, and existential distress in people with life-threatening diseases. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, and two trial registers on 30 March 2024. In addition, we undertook reference checking, citation searching, and contact with study authors to identify additional studies. We used no language or date restrictions. SELECTION CRITERIA: We included randomised controlled trials (RCTs), with no restrictions regarding comorbidity, sex, or ethnicity. Interventions comprised a substance-induced psychedelic experience preceded by preparatory therapeutic sessions and followed by integrative therapeutic sessions. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. MAIN RESULTS: We included six studies in the review, which evaluated two different interventions: psychedelic-assisted therapy with classical psychedelics (psilocybin ('magic mushrooms') and lysergic acid diethylamide (LSD)), and psychedelic-assisted therapy with 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy'). The studies randomised 149 participants with life-threatening diseases and analysed data for 140 of them. The age range of participants was 36 to 64 years. The studies lasted between 6 and 12 months, and were conducted in outpatient settings in the USA and in Switzerland. Drug companies were not involved in study funding, but funding was provided by organisations that promote psychedelic-assisted therapy. Primary outcomes (at 1 to 12 weeks) Anxiety Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in anxiety when compared to active placebo (or low-dose psychedelic): State Trait Anxiety Inventory (STAI-Trait, scale 20 to 80) mean difference (MD) -8.41, 95% CI -12.92 to -3.89; STAI-State (scale 20 to 80) MD -9.04, 95% CI -13.87 to -4.21; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on anxiety, compared to placebo, is very uncertain: STAI-T MD -14.70, 95% CI -29.45 to 0.05; STAI-S MD -16.10, 95% CI -33.03 to 0.83; 1 study, 18 participants; very low certainty evidence. Depression Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) may result in a reduction in depression when compared to active placebo (or low-dose psychedelic): Beck Depression Inventory (BDI, scale 0 to 63) MD -4.92, 95% CI -8.97 to -0.87; 4 studies, 112 participants; standardised mean difference (SMD) -0.43, 95% CI -0.79 to -0.06; 5 studies, 122 participants; low-certainty evidence. The effect of psychedelic-assisted therapy using MDMA on depression, compared to placebo, is very uncertain: BDI-II (scale: 0 to 63) MD -6.30, 95% CI -16.93 to 4.33; 1 study, 18 participants; very low certainty evidence. Existential distress Psychedelic-assisted therapy using classical psychedelics (psilocybin, LSD) compared to active placebo (or low-dose psychedelic) may result in a reduction in demoralisation, one of the most common measures of existential distress, but the evidence is very uncertain (Demoralisation Scale, 1 study, 28 participants): post treatment scores, placebo group 39.6 (SEM 3.4), psilocybin group 18.8 (3.6), P ≤ 0.01). Evidence from other measures of existential distress was mixed. Existential distress was not measured in people receiving psychedelic-assisted therapy with MDMA. Secondary outcomes (at 1 to 12 weeks) Quality of life When classical psychedelics were used, one study had inconclusive results and two reported improved quality of life, but the evidence is very uncertain. MDMA did not improve quality of life measures, but the evidence is also very uncertain. Spirituality Participants receiving psychedelic-assisted therapy with classical psychedelics rated their experience as being spiritually significant (2 studies), but the evidence is very uncertain. Spirituality was not assessed in participants receiving MDMA. Adverse events No treatment-related serious adverse events or adverse events grade 3/4 were reported. Common minor to moderate adverse events for classical psychedelics were elevated blood pressure, nausea, anxiety, emotional distress, and psychotic-like symptoms (e.g. pseudo-hallucination where the participant is aware they are hallucinating); for MDMA, common minor to moderate adverse events were anxiety, dry mouth, jaw clenching, and headaches. Symptoms subsided when drug effects wore off or up to one week later. Certainty of the evidence Although all six studies had intended to blind participants, personnel, and assessors, blinding could not be achieved as this is very difficult in studies investigating psychedelics. Using GRADE criteria, we judged the certainty of evidence to be low to very low, mainly due to high risk of bias and imprecision (small sample size). AUTHORS' CONCLUSIONS: Implications for practice Psychedelic-assisted therapy with classical psychedelics (psilocybin, LSD) may be effective for treating anxiety, depression, and possibly existential distress, in people facing a life-threatening disease. Psychedelic-assisted therapy seemed to be well tolerated, with no treatment-emergent serious adverse events reported in the studies included in this review. However, the certainty of evidence is low to very low, which means that we cannot be sure about these results, and they might be changed by future research. At the time of this review (2024), psychedelic drugs are illegal in many countries. Implications for research The risk of bias due to 'unblinding' (participants being aware of which intervention they are receiving) could be reduced by measuring expectation bias, checking blinding has been maintained before cross-over, and using active placebos. More studies with larger sample sizes are needed to reduce imprecision. As the US Drug Enforcement Administration (DEA) currently classifies psychedelics as Schedule I substances (i.e. having no accepted medical use and a high potential for abuse), research involving these drugs is restricted, but is steadily increasing.
Asunto(s)
Ansiedad , Depresión , Alucinógenos , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Alucinógenos/uso terapéutico , Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológico , Depresión/terapia , Psilocibina/uso terapéutico , Dietilamida del Ácido Lisérgico/uso terapéutico , Antidepresivos/uso terapéutico , Sesgo , Existencialismo , Placebos/uso terapéutico , Adulto , Distrés Psicológico , Neoplasias/psicologíaRESUMEN
Omeprazole, a drug of choice for the management of gastric hyperacidity, influences serotonergic neurotransmission in brain regions and its long-term use is known to cause stress-related behavioral deficits including anxiety. Aim of the current study was to explore the effects of omeprazole treatment on immobilization-induced anxiety in rats, specifically on the role of serotonin (5-HT). In view of the role of serotonin-1A (5-HT1A) autoreceptor in the availability of 5-HT in brain regions, mRNA expression of this autoreceptor was performed in raphe nuclei. Similarly, because of the role of hippocampal 5-HT neurotransmission in anxiety-like disorders, expression of the 5-HT1A heteroreceptors was determined in this region. We found that the treatment with omeprazole reduces anxiety-like behavior in rats, increases the expression of 5-HT1A autoreceptor in the raphe and decreases the hippocampal expression of 5-HT1A heteroreceptor. This suggests a role of 5-HT1A receptor types in omeprazole-induced behavioral changes. It also indicates a potential role of omeprazole in the management of serotonergic disorders.
Asunto(s)
Ansiedad , Modelos Animales de Enfermedad , Hipocampo , Omeprazol , Receptor de Serotonina 5-HT1A , Estrés Psicológico , Animales , Receptor de Serotonina 5-HT1A/metabolismo , Receptor de Serotonina 5-HT1A/efectos de los fármacos , Omeprazol/farmacología , Masculino , Ratas , Ansiedad/tratamiento farmacológico , Ansiedad/metabolismo , Estrés Psicológico/metabolismo , Estrés Psicológico/tratamiento farmacológico , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Ratas Wistar , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Serotonina/metabolismo , Núcleos del Rafe/metabolismo , Núcleos del Rafe/efectos de los fármacos , ARN Mensajero/metabolismo , Restricción Física , InmovilizaciónRESUMEN
The medicinal properties of resveratrol have garnered increasing attention from researchers. Extensive data have been accumulated on its use in treating cardiovascular diseases, immune system disorders, cancer, neurological diseases, and behavioral disorders. The protective mechanisms of resveratrol, particularly in anxiety-related stress disorders, have been well documented. However, less attention has been given to the side effects of resveratrol. This review explores not only the mechanisms underlying the anxiolytic effects of resveratrol but also the mechanisms that may lead to increased anxiety following resveratrol treatment. Understanding these mechanisms is crucial for enhancing the efficacy of resveratrol in managing anxiety disorders associated with stress and PTSD.
Asunto(s)
Ansiolíticos , Trastornos de Ansiedad , Ansiedad , Resveratrol , Resveratrol/farmacología , Humanos , Ansiolíticos/farmacología , Ansiolíticos/uso terapéutico , Animales , Ansiedad/tratamiento farmacológico , Trastornos de Ansiedad/tratamiento farmacológico , Estrés Psicológico/tratamiento farmacológico , Trastornos por Estrés Postraumático/tratamiento farmacológicoRESUMEN
BACKGROUND: Patients with psoriatic arthritis (PsA) often suffer from anxiety disorders. While upadacitinib has shown effectiveness in reducing various disease activity indicators in active PsA, its impact on anxiety disorders in PsA patients needs further investigation. METHODS: In this 12-week randomized, open-label, controlled trial, PsA patients with coexisting anxiety were randomly assigned to either the upadacitinib group or the adalimumab group in a 1:1 ratio. The upadacitinib group received a daily dose of 15 mg, while the adalimumab group received 40 mg every 2 weeks. The primary outcome measured the change in Hospital Anxiety Self-Assessment Scale (HADS-A) total scores after the 12-week intervention. Secondary outcomes included changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI), the percentage of participants meeting the ACR20 criteria compared to baseline after 12 weeks, and the percentage of participants achieving a grade 0 or 1 in the psoriasis static Investigator's overall assessment (sPGA) at week 12 with an improvement of at least 2 points from baseline (sPGA 0/1). One-way analysis of variance (ANOVA) was used to compare the means of normally distributed variables between the upadacitinib and adalimumab groups. DISCUSSION: The impact of upadacitinib on anxiety in PsA patients remains uncertain. This 12-week open randomized controlled trial aims to provide insights into disease progression and underscore the importance of addressing PsA-related anxiety during treatment. TRIAL REGISTRATION: ChiCTR2400079755. Registered on January 11, 2024, with ChiCTR. https://www.chictr.org.cn/showproj.html?proj=216538.
Asunto(s)
Adalimumab , Ansiedad , Artritis Psoriásica , Compuestos Heterocíclicos con 3 Anillos , Humanos , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/psicología , Adalimumab/uso terapéutico , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Ansiedad/diagnóstico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Femenino , Persona de Mediana Edad , Adulto , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Factores de TiempoRESUMEN
BACKGROUND: People living in care homes often have problems with pain, anxiety and depression. Whether being on analgesia, anxiolytics or antidepressants has any bearing on pain severity and quality of life (QoL) in this population, requires further investigation. OBJECTIVES: (i) to examine the relationship between pain, anxiety and depression and medication use in care home residents and (ii) to compare those on medications to treat pain, anxiety and depression, and those who were not, and associations with pain severity and overall QoL. METHODS: This was a secondary analysis of a randomised controlled trial testing a falls prevention intervention in care homes. We recorded pain, anxiety and depression, QoL measurements and prescribed medication use. RESULTS: In 1589 participants, the mean age was 84.7 years (±9.3 SD), 32.2% were male and 67.3% had a diagnosis of dementia. 54.3% and 53.2% of participants had some level of pain and anxiety or depression respectively, regardless of prescribed medication use. There was a direct association between pain severity and being on any analgesia, opioid analgesia, and antidepressants, but no associations between pain severity and use of paracetamol and anxiolytics. QoL was best for residents with no pain and not on any analgesia, anxiolytics or antidepressants and worst for those with moderate-extreme pain and taking at least two of these classes of medications. CONCLUSION: Many care home residents live with pain, anxiety and depression. Addressing residents' pain may also increase their quality of life, but using medication alone to reach this goal may be inadequate.
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Analgésicos , Ansiolíticos , Antidepresivos , Ansiedad , Depresión , Hogares para Ancianos , Casas de Salud , Dimensión del Dolor , Dolor , Calidad de Vida , Humanos , Masculino , Femenino , Ansiolíticos/uso terapéutico , Anciano , Anciano de 80 o más Años , Antidepresivos/uso terapéutico , Dolor/tratamiento farmacológico , Dolor/psicología , Dolor/diagnóstico , Depresión/tratamiento farmacológico , Depresión/psicología , Depresión/diagnóstico , Ansiedad/psicología , Ansiedad/tratamiento farmacológico , Ansiedad/diagnóstico , Analgésicos/uso terapéutico , Accidentes por Caídas/prevención & control , Accidentes por Caídas/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
OBJECTIVE: To investigate the efficacy and safety of Aviandr in the treatment of anxiety in patients with adjustment disorders after COVID-19. MATERIAL AND METHODS: A multicenter prospective open-label study included 109 patients of both sexes aged 18 to 65 years (70 women, 39 men, average age - 41.4±13.18 years) with a leading complaint of anxiety (Hamilton scale score, HAM-A ≥18 - ≤24), which arose after acute coronavirus infections. Clinical manifestations had to meet the diagnostic criteria F43.2 ICD-10. The drug Aviander was prescribed 20 mg 2 times a day for 4 weeks. At the end of taking the drug, patients were monitored for another 1 week (a delayed follow-up visit). Psychopathological, statistical and parametric research methods were used using standardized HAM-A, Montgomery-Asberg scales (MADRS), visual analog asthenia scale (VASH-A), Sheehan Disability Scale (SDS), digital character substitution test (DSST), general clinical impression scale (CGI). RESULTS: Data from 109\110 patients were analyzed to evaluate efficacy\safety. Aviandr was administered 20 mg 2 times daily for 4 weeks. Patients were followed for 1 week (delayed follow-up visit) at the end of treatment. Reducing the intensity of anxiety on the HAM-A scale was - 14.2±4.92 or 69.4±22.66% by the end of treatment. The response rate to therapy (responders are patients with a decrease in the total score on the HAM-A ≥50%) was 83.49%. Remission was achieved (sum of HAM-A scores ≤7) by the end of treatment 68.81% of patients, and 79.8% of patients at the follow-up visit. Significant changes were obtained on the MADRS, VAS-A, SDS and DSST scales. According CGI 45.9% of patients had «much improved¼ and 43.1% of patients had «very much improved¼ by the end of treatment; 58.7% of patients had «much improved¼ and of 33.9% patients had «very much improved¼ at the follow-up visit. 38 adverse events were reported in 27 (24.55%) patients during the study. A definite association with study drug was reported between 5 mild adverse events in 4 (3.64%) patients. No subjects withdrew from the study due to an adverse event. Positive dynamics (reduction of anxiety symptoms, decrease in asthenia) persisted after discontinuation of the study drug. No cases of withdrawal syndrome were observed. CONCLUSION: According to the results of the study, the anxiolytic, antidepressant, antiasthenic and pro-cognitive effects of Aviandr were observed. An increase in the social activity of patients was observed.
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COVID-19 , Humanos , Femenino , Masculino , Adulto , Persona de Mediana Edad , COVID-19/complicaciones , COVID-19/psicología , Estudios Prospectivos , Anciano , Adulto Joven , Resultado del Tratamiento , Trastornos de Adaptación/tratamiento farmacológico , Adolescente , Ansiedad/tratamiento farmacológico , Ansiedad/etiología , SARS-CoV-2 , Trastornos de Ansiedad/tratamiento farmacológico , Ansiolíticos/uso terapéutico , Ansiolíticos/efectos adversosRESUMEN
Background: The management of preoperative anxiety in pediatric patients, as well as its implications, has remained challenging for anesthesiologists. In this study, we compared the safety and efficacy of intranasal dexmedetomidine, midazolam, and ketamine as surgical premedication in children. Methods: This double-blinded randomized clinical trial was conducted at two tertiary hospitals in January 2014, on 90 children aged between 2-7 years old. The participants' American Society of Anesthesiologists (ASA) physical status was I or II, and they were scheduled for elective unilateral inguinal herniorrhaphy. Using the block randomization method, the patients were randomly assigned to three groups, each receiving intranasal dexmedetomidine (2 µg/Kg), midazolam (0.2 mg/Kg), and ketamine (8 mg/Kg) 60 min before induction of anesthesia. Anxiety and sedation state were evaluated before drug administration, and then every 10 min for the next 50 min. Parental separation anxiety, mask acceptance, postoperative agitation, pain, nausea, and vomiting were also recorded and compared between these groups. All the statistical analyses were performed using SPSS software (version 21.0). P<0.05 was considered statistically significant. Results: Ketamine indicated the strongest sedative effect 10, 20, and 30 min after administration of premedication (P<0.001, P=0.03, P=0.01, respectively). However, dexmedetomidine was more effective than other drugs after 40 and 50 min (P<0.001). Other variables indicated no statistically significant difference. Conclusion: In case of emergencies, intranasal ketamine, with the shortest time of action, could be administered. Intranasal dexmedetomidine, which was revealed to be the most potent drug in this study, could be administrated 40-50 min before elective pediatric surgeries.Trial registration number: IRCT2013081614372N1.
Asunto(s)
Administración Intranasal , Dexmedetomidina , Hipnóticos y Sedantes , Ketamina , Midazolam , Humanos , Ketamina/uso terapéutico , Ketamina/farmacología , Ketamina/administración & dosificación , Dexmedetomidina/farmacología , Dexmedetomidina/uso terapéutico , Dexmedetomidina/administración & dosificación , Midazolam/uso terapéutico , Midazolam/farmacología , Midazolam/administración & dosificación , Preescolar , Masculino , Femenino , Niño , Administración Intranasal/métodos , Hipnóticos y Sedantes/farmacología , Hipnóticos y Sedantes/uso terapéutico , Hipnóticos y Sedantes/administración & dosificación , Método Doble Ciego , Procedimientos Quirúrgicos Ambulatorios/métodos , Ansiedad/tratamiento farmacológicoRESUMEN
Neoponcirin causes anxiolytic-like effects in mice when administered intraperitoneally but not orally. Neoponcirin is non-water-soluble and insoluble in solvents, and in medium acid, it isomerizes, reducing its bioavailability. To improve the pharmacological properties of neoponcirin, we formed a neoponcirin complex with beta-cyclodextrin (NEO/ßCD), which was characterized by FT-IR, UV-Vis, and NMR, and their solubility profile. We evaluated the antidepressant-like effects of NEO/ßCD acutely administered to mice orally in the behavioral paradigms, the tail suspension (TST) and the forced swimming (FST) tests. We also analyzed the benefits of repeated oral doses of NEO/ßCD on depression- and anxiety-like behaviors induced in mice by chronic unpredictable mild stress (CUMS), using the FST, hole board, and open field tests. We determined the stressed mice's expression of stress-related inflammatory cytokines (IL-1ß, IL-6, and TNFα) and corticosterone. Results showed that a single or chronic oral administration of NEO/ßCD caused a robust antidepressant-like effect without affecting the ambulatory activity. In mice under CUMS, NEO/ßCD also produced anxiolytic-like effects and avoided increased corticosterone and IL-1ß levels. The effects of the NEO/ßCD complex were robust in both the acute and the stress chronic models, improving brain neurochemistry and recovering immune responses previously affected by prolonged stress.
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Antidepresivos , Depresión , Estrés Psicológico , beta-Ciclodextrinas , Animales , beta-Ciclodextrinas/farmacología , beta-Ciclodextrinas/química , Ratones , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Masculino , Estrés Psicológico/tratamiento farmacológico , Depresión/tratamiento farmacológico , Conducta Animal/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Ansiedad/tratamiento farmacológico , Ansiolíticos/farmacología , Natación , Administración OralRESUMEN
The phytoestrogens daidzein and genistein are ubiquitous in human food. This study aimed to elucidate their anxiety-liked effects, their effects on the reproductive organs, and the molecular mechanism behind any anxiety-liked effects in intact adult male Wistar rats. These phytoestrogens are of interest due to their posited health benefits, particularly for female, but with some effect on males as well. This study comprised two experiments: (1) Male Wistar rats received either a vehicle, daidzein, or genistein (0.25, 0.50, or 1.00â¯mg/kg) by subcutaneously injection for four weeks. They were then tested for anxiety-liked behaviors. Then, the brain monoamines in anxiolytic rats were determined; (2) The modulation of gamma aminobutyric acid receptors by phytoestrogens was further analyzed by administration of diazepam to phytoestrogen-treated rats before behavioral tests. In the first experiment, the biological parameters measured, including body weight, daily food intake and reproductive organ weights were unaffected by either genistein or daidzein. However, anxiolytic-like effect was observed in the low-dose daidzein (0.25â¯mg/kg) group. Higher doses of daidzein or genistein of all doses had no effect. Further, the low-dose daidzein did not alter brain monoamine levels. In the second experiment, the anxiolytic-like behavior of daidzein-treated rats receiving diazepam did not differ from that of the rats treated with just diazepam or just daidzein. In conclusion, 4-week exposure to daidzein or genistein had no negative effects on the reproductive organs, body weight, food intake, anxiogenic-like behavior, or monoaminergic and diazepam-modulated GABAergic neurotransmissions of intact male rats. However, beneficial anxiolytic-like effects were apparent after low-dose treatment with daidzein.
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Ansiolíticos , Ansiedad , Genisteína , Isoflavonas , Ratas Wistar , Animales , Masculino , Genisteína/farmacología , Genisteína/administración & dosificación , Ansiolíticos/farmacología , Ansiolíticos/administración & dosificación , Isoflavonas/farmacología , Isoflavonas/administración & dosificación , Ansiedad/tratamiento farmacológico , Ratas , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Relación Dosis-Respuesta a Droga , Fitoestrógenos/farmacología , Fitoestrógenos/administración & dosificación , Diazepam/farmacología , Ingestión de Alimentos/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Tamaño de los Órganos/efectos de los fármacosRESUMEN
The symptoms of post-traumatic stress disorder (PTSD) include re-experiencing trauma, avoidance behaviors, negative alterations in cognition and mood. However, the underlying molecular mechanisms are unclear. Dysfunction of hypothalamic-pituitary-adrenal axis (HPA-axis) and dysregulation of glutamatergic and GABAergic systems were shown during PTSD. Therefore, regulating hormonal change or glutamate energy metabolism are considered as a therapeutic approach to alleviate this condition. Herbal medicine may be effective in treating PTSD due to its ability to target multiple underlying mechanisms with various compounds. Hominis placenta (HP) is a traditional medicine widely used in East Asia for various conditions. However, the effect on PTSD has not been clarified. We aimed to investigate the effects of HP treatment in single-prolonged stress with shock (SPSS)-induced PTSD mice and explore its possible mechanisms. HP treatment at ST36 acupoints, combined with herbal medicine and acupuncture point stimulation, was applied three times/week for 2 weeks. HP treatment effectively alleviated anxiety and cognitive decline in SPSS-induced PTSD mice, as detected by Open field and the Y-maze test. Additionally, HP decreased the corticosterone levels and proinflammatory cytokines in the serum, modulated brain energy metabolism, and inhibited glutamate excitotoxicity, while regulating neuronal activity through modulating brain-derived neurotrophic factor (BDNF) levels, as demonstrated by western blot and immunohistochemistry, and flow cytometry analyses. These findings reveal that HP treatment effectively alleviates PTSD-like behaviors by regulating energy metabolism and neuronal activity though modulation of the HPA-axis and BDNF levels in PTSD mice, indicating that HP treatment is a promising therapeutic approach for PTSD.
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Conducta Animal , Metabolismo Energético , Neuronas , Trastornos por Estrés Postraumático , Animales , Trastornos por Estrés Postraumático/metabolismo , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/psicología , Metabolismo Energético/efectos de los fármacos , Femenino , Ratones , Embarazo , Masculino , Conducta Animal/efectos de los fármacos , Neuronas/metabolismo , Neuronas/efectos de los fármacos , Placenta/metabolismo , Modelos Animales de Enfermedad , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ansiedad/metabolismo , Ansiedad/tratamiento farmacológico , Corticosterona/sangre , Sistema Hipotálamo-Hipofisario/metabolismo , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Citocinas/metabolismoRESUMEN
Alzheimer's disease (AD), the most common cause of dementia, leads to neurodegeneration and cognitive decline. We investigated the therapeutic effects of L-carnitine on cognitive performance and anxiety-like behavior in a rat model of AD induced by unilateral intracerebroventricular injection of ß-amyloid1-42 (Aß1-42). L-carnitine (100 mg/kg/day) was administered intraperitoneally for 28 consecutive days. Following this, the open-field test, novel object recognition test, elevated plus-maze test, Barnes maze test, and passive avoidance learning test were used to assess locomotor activity, recognition memory, anxiety-like behavior, spatial memory, and passive avoidance memory, respectively. Plasma and hippocampal oxidative stress markers, including total oxidant status (TOS) and total antioxidant capacity (TAC), were examined. In addition, histological investigations were performed in the dentate gyrus of the hippocampus using Congo red staining and hematoxylin and eosin staining. The injection of Aß1-42 resulted in cognitive deficits and increased anxiety-like behavior. These changes were associated with an imbalance of oxidants and antioxidants in plasma and the hippocampus. Also, neuronal death and Aß plaque accumulation were increased in the hippocampal dentate gyrus region. However, injection of L-carnitine improved recognition memory, spatial memory, and passive avoidance memory in AD rats. These findings provide evidence that L-carnitine may alleviate anxiety-like behavior and cognitive deficits induced by Aß1-42 through modulating oxidative-antioxidant status and preventing Aß plaque accumulation and neuronal death.
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Enfermedad de Alzheimer , Péptidos beta-Amiloides , Ansiedad , Carnitina , Modelos Animales de Enfermedad , Trastornos de la Memoria , Estrés Oxidativo , Ratas Wistar , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/psicología , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Ansiedad/tratamiento farmacológico , Masculino , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/prevención & control , Ratas , Carnitina/farmacología , Carnitina/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Fragmentos de Péptidos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Reacción de Prevención/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Memoria Espacial/efectos de los fármacosRESUMEN
5-Hydroxytryptamine (5-HT) plays a substantial role in mitigating depression and anxiety. However, the potential effects of 5-HT against posttraumatic stress disorder (PTSD) and its underlying mechanisms remain unclear. Elevated plus maze test evaluates anxiety-related behaviors, and the open field test is used to assess overall activity levels and anxiety. Inflammatory cytokine levels were determined using ELISA. The levels of 5-HT and dopamine were measured using HPLC. mRNA and protein levels were examined by PCR and Western blot, respectively. Rats exposed to single prolonged stress (SPS) exhibited typical PTSD-like phenotypes, with decreased levels of 5-HT in the hippocampus and significant reductions in its downstream targets, brain-derived neurotrophic factor (BDNF) and TrkB. In addition, it was discovered that the autophagy signaling pathway might be involved in regulating hippocampal BDNF in rats exposed to SPS. Subsequent treatment with an intracerebral injection of sh-SERT significantly inhibited anxiety and cognitive dysfunction in rats. Moreover, sh-SERT treatment was observed to substantially reverse the increase in autophagy signaling protein expression and consequently improve the expression of BDNF and TrkB proteins, which had been reduced. The current study demonstrates that sh-SERT exhibits significant anti-PTSD effects, potentially mediated in part through the reduction of cellular autophagy to enhance hippocampal synaptic plasticity.NEW & NOTEWORTHY The study demonstrated that sh-SERT exhibits significant anti-posttraumatic stress disorder (PTSD) effects, potentially mediated in part through the reduction of cellular autophagy to enhance hippocampal synaptic plasticity.
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Autofagia , Factor Neurotrófico Derivado del Encéfalo , Hipocampo , Plasticidad Neuronal , Ratas Sprague-Dawley , Serotonina , Trastornos por Estrés Postraumático , Animales , Trastornos por Estrés Postraumático/tratamiento farmacológico , Trastornos por Estrés Postraumático/metabolismo , Trastornos por Estrés Postraumático/fisiopatología , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Autofagia/efectos de los fármacos , Autofagia/fisiología , Plasticidad Neuronal/efectos de los fármacos , Plasticidad Neuronal/fisiología , Masculino , Serotonina/metabolismo , Ratas , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ansiedad/tratamiento farmacológico , Receptor trkB/metabolismo , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Modelos Animales de EnfermedadRESUMEN
Monoamine neurotransmitter system dysfunctions lead to behavioral disorders, cognitive metabolic, and other pathological conditions. In this case, different amino acids are precursors of monoamines, while the parenteral path of monoamine administration has pharmacological restrictions. Therefore, intranasal administration one of the most promising methods of delivering an active substance is. The purpose of the work is to study the effect of intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide on behavioral and neurochemical changes in acute and chronic experiments. MATERIAL AND METHODS: The studies used outbred Wistar and DAT-KO rats, and inbred C57Bl6 and TAAR1-KO mice. Using intranasal administration of a chelate complex of zinc arginyl-glycinate and alpha-glutamyl-tryptophan dipeptide we tested methods for evaluating different behavioral indicators and the level of cerebral monoamines and their metabolites. RESULTS: An anxiolytic effect of zinc arginyl-glycinate and its combination with alpha-glutamyl-tryptophan was revealed. Both drugs have a physiological effect on the autonomic nervous system, but the determination of their operating mechanisms requires further research. CONCLUSION: Thus, these data indicate that intranasal delivery of the dipeptides is effective during acute and chronic intranasal administration in rodents, the latter showed a change in the anxiety indicator. Acute AG intranasal administration demonstrated signs of lower anxiety and depressive-like behavior in C57Bl6 mice. The acute intranasal administration of a chelate complex zinc arginyl-glycinate and combination with alpha-glutamyl-tryptophan in doses of 50-100 mg/kg of body weight may be used for pre-clinical studies as a new anxiolytic/antidepressant.
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Administración Intranasal , Dipéptidos , Ratones Noqueados , Ratas Wistar , Animales , Dipéptidos/administración & dosificación , Dipéptidos/farmacología , Ratones , Conducta Animal/efectos de los fármacos , Ratones Endogámicos C57BL , Masculino , Ratas , Quelantes/administración & dosificación , Quelantes/farmacología , Zinc/administración & dosificación , Zinc/farmacología , Ansiedad/tratamiento farmacológico , Ansiolíticos/administración & dosificación , Ansiolíticos/farmacología , Monoaminas Biogénicas/metabolismoRESUMEN
Depression and anxiety are prominent symptoms of withdrawal syndrome, often caused by the abuse of addictive drugs like morphine. N-palmitoylethanolamide (PEA), a biologically active lipid, is utilized as an anti-inflammatory and analgesic medication. Recent studies have highlighted PEA's role in mitigating cognitive decline and easing depression resulting from chronic pain. However, it remains unknown whether PEA can influence negative emotions triggered by morphine withdrawal. This study seeks to explore the impact of PEA on such emotions and investigate the underlying mechanisms. Mice subjected to morphine treatment underwent a 10-day withdrawal period, followed by assessments of the effect of PEA on anxiety- and depression-like behaviors using various tests. Enzyme-linked immunosorbent assay was conducted to measure levels of monoamine neurotransmitters in specific brain regions. The findings indicate that PEA mitigated anxiety and depression symptoms and reduced 5-hydroxytryptamine, noradrenaline, and dopamine levels in the hippocampus and prefrontal cortex. In summary, PEA demonstrates a significant positive effect on negative emotions associated with morphine withdrawal, accompanied with the reduction in levels of monoamine neurotransmitters in key brain regions. These insights could be valuable for managing negative emotions arising from morphine withdrawal.
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Amidas , Ansiedad , Depresión , Etanolaminas , Morfina , Ácidos Palmíticos , Síndrome de Abstinencia a Sustancias , Animales , Síndrome de Abstinencia a Sustancias/psicología , Síndrome de Abstinencia a Sustancias/metabolismo , Síndrome de Abstinencia a Sustancias/tratamiento farmacológico , Etanolaminas/farmacología , Ácidos Palmíticos/farmacología , Ratones , Masculino , Morfina/farmacología , Depresión/metabolismo , Depresión/tratamiento farmacológico , Depresión/psicología , Depresión/etiología , Amidas/farmacología , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Ansiedad/metabolismo , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Emociones/efectos de los fármacos , Serotonina/metabolismo , Dependencia de Morfina/metabolismo , Dependencia de Morfina/psicología , Corteza Prefrontal/metabolismo , Corteza Prefrontal/efectos de los fármacos , Norepinefrina/metabolismo , Encéfalo/metabolismo , Encéfalo/efectos de los fármacosRESUMEN
Obesity impacts mental health greatly. Psychological factors may influence the effectiveness of its treatment. This study aimed to compare symptoms of generalised anxiety disorder and depression among adult women across different weight categories. The study sample comprised 1105 adult women. The computer-assisted web interview (CAWI) utilising the seven-item Generalised Anxiety Disorders Scale (GAD-7) and the nine-item Patient Health Questionnaire (PHQ-9) was used. Both GAD-7 and PHQ-9 scores correlated positively with BMI (r = 0.121, p < 0.001 and r = 0.173, p < 0.001, respectively) and negatively with age (r = -0.106, p < 0.001 and r = -0.103, p < 0.001, respectively). Patients undergoing treatment with semaglutide scored lower for both anxiety symptoms (8.71 ± 6.16, p = 0.013) and depression symptoms (9.76 ± 6.37, p = 0.013). Women who underwent bariatric surgery screened less frequently for anxiety (8.03 ± 6.27, p = 0.002) but not for depression. An interdisciplinary approach involving mental health professionals within the therapeutic team can comprehensively address factors contributing to obesity development and treatment outcomes. Further investigation of semaglutide's use is needed due to the promising evidence suggesting a positive effect on decreasing the severity of depression and anxiety symptoms to assess the direct or indirect character of this influence.
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Trastornos de Ansiedad , Depresión , Obesidad , Humanos , Femenino , Adulto , Obesidad/psicología , Obesidad/tratamiento farmacológico , Persona de Mediana Edad , Trastornos de Ansiedad/tratamiento farmacológico , Depresión/tratamiento farmacológico , Polonia , Fármacos Antiobesidad/uso terapéutico , Péptidos Similares al Glucagón/uso terapéutico , Ansiedad/tratamiento farmacológico , Cuestionario de Salud del Paciente , Adulto Joven , Cirugía Bariátrica , Índice de Masa Corporal , Encuestas y CuestionariosRESUMEN
This work was done to investigate the ameliorating impact of 4-methylumbilliferon (4-MU) on spatial learning and memory dysfunction and restraint stress (STR)-induced anxiety-like behaviors in male Wistar rats and the underlying mechanisms. Thirty-two animals were assigned into 4 cohorts: control, 4-MU, STR, and STR+4-MU. Animals were exposed to STR for 4 h per day for 14 consecutive days or kept in normal conditions (healthy animals without exposure to stress). 4-MU (25 mg/kg) was intraperitoneally administered once daily to STR rats before restraint stress for 14 consecutive days. The behavioral tests were performed through Morris water maze tests and elevated-plus maze to examine learning/memory function, and anxiety levels, respectively. The levels of the antioxidant defense biomarkers (GPX, SOD) and MDA as an oxidant molecule in the brain tissues were measured using commercial ELISA kits. Neuronal loss or density of neurons was evaluated using Nissl staining. STR exposure could cause significant alterations in the levels of the antioxidant defense biomarkers (MDA, GPX, and SOD) in the prefrontal cortex and hippocampus, induce anxiety, and impair spatial learning and memory function. Treatment with 4-MU markedly reduced anxiety levels and improved spatial learning and memory dysfunction via restoring the antioxidant defense biomarkers to normal values and reducing MDA levels. Moreover, more intact cells with normal morphologies were detected in STR-induced animals treated with 4-MU. 4-MU could attenuate the STR-induced anxiety-like behaviors and spatial learning and memory dysfunction by reducing oxidative damage and neuronal loss in the prefrontal cortex and hippocampus region. Taken together, our findings provide new insights regarding the potential therapeutic effects of 4-MU against neurobehavioral disorders induced by STR.
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Ansiedad , Muerte Celular , Trastornos de la Memoria , Neuronas , Estrés Oxidativo , Ratas Wistar , Animales , Estrés Oxidativo/efectos de los fármacos , Masculino , Ansiedad/tratamiento farmacológico , Ansiedad/metabolismo , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Ratas , Muerte Celular/efectos de los fármacos , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Estrés Psicológico/complicaciones , Aprendizaje por Laberinto/efectos de los fármacos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Antioxidantes/farmacología , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismoRESUMEN
Depression and anxiety disorders are prevalent stress-related neuropsychiatric disorders and involve multiple molecular changes and dysfunctions across various brain regions. However, the specific and shared pathophysiological mechanisms occurring in these regions remain unclear. Previous research used a rat model of chronic mild stress (CMS) to segregate and identify depression-susceptible, anxiety-susceptible, and insusceptible groups; then the proteomes of six distinct brain regions (the hippocampus, prefrontal cortex, hypothalamus, pituitary, olfactory bulb, and striatum) were separately and quantitatively analyzed. To gain a comprehensive and systematic understanding of the molecular abnormalities, this study aimed to investigate and compare differential proteomics data from the six regions. Differentially expressed proteins (DEPs) were identified in between specific regions and across all regions and subjected to a series of bioinformatics analyses. Regional comparisons showed that stress-induced proteomic changes and corresponding gene ontology and pathway enrichments were largely distinct, attributable to differences in cell populations, protein compositions, and brain functions of these areas. Additionally, a notable degree of overlap in the significantly enriched terms was identified, potentially suggesting strong connections in the enrichment across different regions. Furthermore, intra-regional and inter-regional protein-protein interaction networks and drug-target-DEP networks were constructed. Integrated analysis of the three association networks in the six regions, along with the DisGeNET database, identified ten DEPs as potential targets for anti-depression/anxiety drugs. Collectively, these findings revealed commonalities and differences across different brain regions at the protein level induced by CMS, and identified several novel protein targets for the development of new therapeutics for depression and anxiety.