RESUMO
OBJECTIVES: There are inconsistencies in the South Africa HIV mortality data reported by Institute of Health Metrics and Evaluation (IHME), Joint United Nations Programme on HIV/AIDS (UNAIDS), and Statistics South Africa (StatsSA) platforms. Between 2006 and 2016, these global data sets (IHME and UNAIDS) show that HIV-related mortalities were improving in South Africa, whereas StatsSA argues the opposite. We explain the causes of this differing stands and highlight areas that may be improved to address such inconsistencies. METHODS: This observational analysis uses data from IHME, UNAIDS, and StatsSA platforms. RESULTS: We demonstrate that IHME and UNAIDS data sets are based on a mathematical compartmental model, which is not dynamic to all HIV epidemiological aspects. Such limitation may cause inflated improvement in HIV mortality outcomes that are not in line with HIV mortality evidence recorded at the household level as demonstrated by StatsSA. CONCLUSION: There is a need to streamline the IHME, UNAIDS, and StatsSA data on HIV to improve the quality of HIV research and programming in South Africa.
Assuntos
Infecções por HIV , Humanos , Infecções por HIV/epidemiologia , África do Sul/epidemiologia , Características da FamíliaRESUMO
The technical advisory group of the World Health Organization (Geneva, Switzerland) has suggested person-centered and community-based mental health services in response to the long-term and far-reaching mental health impacts of the COVID-19 pandemic. Task shifting is a pragmatic approach to tackle the mental health treatment gap in low- and middle-income countries. Pakistan is dismally resourced to address the mental health challenges. Pakistan's government has established a lady health worker's program (LHW-P) which can be effectively utilized to provide some basic mental health services at community doorsteps. However, lady health workers' current curriculum does not include mental health as a subject. WHO's Mental Health Gap Intervention Guide (mhGAP-IG) Version 2.0 for mental, neurological, and substance use disorders in non-specialist health settings can be adapted and utilized to be included as part of the LHW-P curriculum in Pakistan. Thus, the historical lack of access to mental health support workers, counsellors, and specialists can be addressed. Additionally, this will also help to reduce the stigma associated with seeking mental health care outside the boundaries of home, mostly at a huge cost.
Assuntos
COVID-19 , Transtornos Relacionados ao Uso de Substâncias , Humanos , Saúde Mental , Paquistão , PandemiasRESUMO
A novel botanical dietary supplement, formulated as a chewable tablet containing a defined mixture of Souroubea spp. vine and Platanus spp. Bark, was tested as a canine anxiolytic for thunderstorm noise-induced stress (noise aversion). The tablet contained five highly stable triterpenes and delivered 10 mg of the active ingredient betulinic acid (BA) for an intended 1 mg/kg dose in a 10 kg dog. BA in tablets was stable for 30 months in storage at 23 °C. Efficacy of the tablets in reducing anxiety in dogs was assessed in a blinded, placebo-controlled study by recording changes in blood cortisol levels and measures of behavioral activity in response to recorded intermittent thunder. Sixty beagles were assigned into groups receiving: placebo, 0.5×, 1×, 2×, and 4× dose, or the positive control (diazepam), for five days. Reduction in anxiety measures was partially dose-dependent and the 1× dose was effective in reducing inactivity time (p = 0.0111) or increased activity time (p = 0.0299) compared with placebo, indicating a decrease in anxiety response. Cortisol measures also showed a dose-dependent reduction in cortisol in dogs treated with the test tablet.
Assuntos
Ansiedade/terapia , Suplementos Nutricionais , Ericales/química , Medo/efeitos dos fármacos , Magnoliopsida/química , Triterpenos/farmacologia , Animais , Ansiedade/sangue , Modelos Animais de Doenças , Cães , Relação Dose-Resposta a Droga , Hidrocortisona/sangue , Análise dos Mínimos Quadrados , Comprimidos , Triterpenos/químicaRESUMO
Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are first-line antidepressants but require several weeks to elicit their actions. Chronic SSRI treatment induces desensitization of 5-HT1A autoreceptors to enhance 5-HT neurotransmission. Mice (both sexes) with gene deletion of 5-HT1A autoreceptors in adult 5-HT neurons (1AcKO) were tested for response to SSRIs. Tamoxifen-induced recombination in adult 1AcKO mice specifically reduced 5-HT1A autoreceptor levels. The 1AcKO mice showed a loss of 5-HT1A autoreceptor-mediated hypothermia and electrophysiological responses, but no changes in anxiety- or depression-like behavior. Subchronic fluoxetine (FLX) treatment induced an unexpected anxiogenic effect in 1AcKO mice in the novelty suppressed feeding and elevated plus maze tests, as did escitalopram in the novelty suppressed feeding test. No effect was seen in wild-type (WT) mice. Subchronic FLX increased 5-HT metabolism in prefrontal cortex, hippocampus, and raphe of 1AcKO but not WT mice, suggesting hyperactivation of 5-HT release. To detect chronic cellular activation, FosB+ cells were quantified. FosB+ cells were reduced in entorhinal cortex and hippocampus (CA2/3) and increased in dorsal raphe 5-HT cells of 1AcKO mice, suggesting increased raphe activation. In WT but not 1AcKO mice, FLX reduced FosB+ cells in the median raphe, hippocampus, entorhinal cortex, and median septum, which receive rich 5-HT projections. Thus, in the absence of 5-HT1A autoreceptors, SSRIs induce a paradoxical anxiogenic response. This may involve imbalance in activation of dorsal and median raphe to regulate septohippocampal or fimbria-fornix pathways. These results suggest that markedly reduced 5-HT1A autoreceptors may provide a marker for aberrant response to SSRI treatment.SIGNIFICANCE STATEMENT Serotonin-selective reuptake inhibitors (SSRIs) are effective in treating anxiety and depression in humans and mouse models. However, in some cases, SSRIs can increase anxiety, but the mechanisms involved are unclear. Here we show that, rather than enhancing SSRI benefits, adulthood knockout (KO) of the 5-HT1A autoreceptor, a critical negative regulator of 5-HT activity, results in an SSRI-induced anxiety effect that appears to involve a hyperactivation of the 5-HT system in certain brain areas. Thus, subjects with very low levels of 5-HT1A autoreceptors, such as during childhood or adolescence, may be at risk for an SSRI-induced anxiety response.
Assuntos
Antidepressivos/efeitos adversos , Ansiedade/induzido quimicamente , Autorreceptores/efeitos dos fármacos , Receptor 5-HT1A de Serotonina/deficiência , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Neurônios Serotoninérgicos/efeitos dos fármacos , 8-Hidroxi-2-(di-n-propilamino)tetralina/toxicidade , Animais , Antidepressivos/farmacologia , Química Encefálica/efeitos dos fármacos , Comportamento Exploratório/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Feminino , Fluoxetina/efeitos adversos , Fluoxetina/farmacologia , Hipotermia/induzido quimicamente , Hipotermia/fisiopatologia , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Rede Nervosa/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-fos/análise , Receptor 5-HT1A de Serotonina/efeitos dos fármacos , Receptor 5-HT1A de Serotonina/fisiologia , Neurônios Serotoninérgicos/fisiologia , Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , NataçãoRESUMO
BACKGROUND: Abnormalities in heart rate during sleep linked to impaired neuro-cardiac modulation may provide new information about physiological sleep signatures of depression. This study assessed the validity of an algorithm using patterns of heart rate changes during sleep to discriminate between individuals with depression and healthy controls. METHODS: A heart rate profiling algorithm was modeled using machine-learning based on 1203 polysomnograms from individuals with depression referred to a sleep clinic for the assessment of sleep abnormalities, including insomnia, excessive daytime fatigue, and sleep-related breathing disturbances (n = 664) and mentally healthy controls (n = 529). The final algorithm was tested on a distinct sample (n = 174) to categorize each individual as depressed or not depressed. The resulting categorizations were compared to medical record diagnoses. RESULTS: The algorithm had an overall classification accuracy of 79.9% [sensitivity: 82.8, 95% CI (0.73-0.89), specificity: 77.0, 95% CI (0.67-0.85)]. The algorithm remained highly sensitive across subgroups stratified by age, sex, depression severity, comorbid psychiatric illness, cardiovascular disease, and smoking status. CONCLUSIONS: Sleep-derived heart rate patterns could act as an objective biomarker of depression, at least when it co-occurs with sleep disturbances, and may serve as a complimentary objective diagnostic tool. These findings highlight the extent to which some autonomic functions are impaired in individuals with depression, which warrants further investigation about potential underlying mechanisms.
Assuntos
Depressão/fisiopatologia , Eletrocardiografia/métodos , Frequência Cardíaca/fisiologia , Aprendizado de Máquina , Transtornos do Sono-Vigília/fisiopatologia , Sono/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Depressão/diagnóstico , Depressão/psicologia , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia/métodos , Estudos Retrospectivos , Transtornos do Sono-Vigília/diagnóstico , Transtornos do Sono-Vigília/psicologia , Adulto JovemRESUMO
Freud-1/Cc2d1a represses the gene transcription of serotonin-1A (5-HT1A) autoreceptors, which negatively regulate 5-HT tone. To test the role of Freud-1 in vivo, we generated mice with adulthood conditional knock-out of Freud-1 in 5-HT neurons (cF1ko). In cF1ko mice, 5-HT1A autoreceptor protein, binding and hypothermia response were increased, with reduced 5-HT content and neuronal activity in the dorsal raphe. The cF1ko mice displayed increased anxiety- and depression-like behavior that was resistant to chronic antidepressant (fluoxetine) treatment. Using conditional Freud-1/5-HT1A double knock-out (cF1/1A dko) to disrupt both Freud-1 and 5-HT1A genes in 5-HT neurons, no increase in anxiety- or depression-like behavior was seen upon knock-out of Freud-1 on the 5-HT1A autoreceptor-negative background; rather, a reduction in depression-like behavior emerged. These studies implicate transcriptional dysregulation of 5-HT1A autoreceptors by the repressor Freud-1 in anxiety and depression and provide a clinically relevant genetic model of antidepressant resistance. Targeting specific transcription factors, such as Freud-1, to restore transcriptional balance may augment response to antidepressant treatment.SIGNIFICANCE STATEMENT Altered regulation of the 5-HT1A autoreceptor has been implicated in human anxiety, major depression, suicide, and resistance to antidepressants. This study uniquely identifies a single transcription factor, Freud-1, as crucial for 5-HT1A autoreceptor expression in vivo Disruption of Freud-1 in serotonin neurons in mice links upregulation of 5-HT1A autoreceptors to anxiety/depression-like behavior and provides a new model of antidepressant resistance. Treatment strategies to reestablish transcriptional regulation of 5-HT1A autoreceptors could provide a more robust and sustained antidepressant response.
Assuntos
Ansiedade/metabolismo , Autorreceptores/biossíntese , Transtorno Depressivo Resistente a Tratamento/metabolismo , Fluoxetina/uso terapêutico , Receptor 5-HT1A de Serotonina/biossíntese , Proteínas Repressoras/deficiência , Animais , Antidepressivos de Segunda Geração/farmacologia , Antidepressivos de Segunda Geração/uso terapêutico , Ansiedade/tratamento farmacológico , Autorreceptores/antagonistas & inibidores , Autorreceptores/genética , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Transtorno Depressivo Resistente a Tratamento/tratamento farmacológico , Feminino , Fluoxetina/farmacologia , Masculino , Camundongos , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Receptor 5-HT1A de Serotonina/genética , Proteínas Repressoras/genética , Neurônios Serotoninérgicos/efeitos dos fármacos , Neurônios Serotoninérgicos/metabolismoRESUMO
Appreciable evidence suggests that perturbations within the gut microbiome and the immune system may play a key role in the pathogenesis of depression stemming from earlier stressful experiences. In the present investigation we examined whether microbial changes in cecum contents were associated with social avoidance behaviors, a feature of depression, and pro-inflammatory variations among socially stressed mice. Male C57BL/6 mice experienced social defeat or a control condition once a day for 10 consecutive days. Social avoidance behaviors were examined three weeks after the last defeat or control episode and blood, brain, and cecum contents were collected 24h afterward for the determination of corticosterone, pro-inflammatory cytokines, and microbial populations. Mice that were most susceptible to the behavioral effects of chronic social defeat (reflected by severe social avoidance behaviors) displayed the greatest changes within particular sets of bacteria at the phylum and genus taxonomic ranks. Although plasma and brain cytokines were not significantly altered in socially defeated mice, changes in the mRNA expression of interleukin (IL)-1ß and IL-6 within the prefrontal cortex were associated with elevated abundance of Flavobacterium spp. and reduced abundance of Turicibacter spp., which were also strongly correlated to social avoidance severity. Although at this time a causal connection cannot be inferred, these results point to the possibility that specific clusters of bacterial communities in cecum contents may be linked to vulnerability to social deficits stemming from prolonged social stressor experiences.
Assuntos
Aprendizagem da Esquiva , Microbioma Gastrointestinal , Comportamento Social , Estresse Psicológico/microbiologia , Animais , Encéfalo/metabolismo , Ceco/microbiologia , Citocinas , Inflamação/complicações , Inflamação/metabolismo , Inflamação/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Estresse Psicológico/complicações , Estresse Psicológico/metabolismoRESUMO
OBJECTIVES: The polyphenol resveratrol has shown regulatory effects on hippocampal neurogenesis, which according to the neurovascular niche hypothesis, is likely to involve stimulation of angiogenesis. In rodents, global cerebral ischemia leads to selective CA1 neuronal damage, spatial memory impairments, lasting changes in corticosterone (CORT) secretion, and increased neurogenesis. This study examined dose-related effects of 21-day RSV treatment on markers associated with neurogenesis (DCX, PSA-NCAM) and angiogenesis (CD31) in the hippocampus at short (7-day) and long-term (85-day) intervals following global ischemia. In parallel, post-ischemic and stress-induced CORT levels and spatial memory in the Morris water maze were determined. METHODS: Five groups of male Wistar rats were included: sham/saline, ischemia/saline, ischemia/1â mg/kg RSV, ischemia/10â mg/kg RSV, and sham/10â mg/kg RSV. Changes in expression of plasticity markers were paralleled by assessment of basal- and stress-induced CORT secretions, and spatial memory performance. RESULTS: Our findings revealed a significant attenuation of ischemia-induced DCX/PSA-NCAM expression in RSV-treated rats, whereas RSV treatment increased angiogenesis in the injured CA1 region. RSV attenuated CORT levels 3â days post-ischemia and a trend toward attenuating CORT secretion in response to 15â minutes restraint stress. Increased swimming latencies in the target quadrant during the MWM probe trial in RSV-treated ischemic rats support beneficial effects of RSV on spatial memory retention. DISCUSSION: Our findings uncover time- and dose-related effects of RSV and global ischemia on the regulation of hippocampal plasticity. Changes in neuro- and angiogenesis are consistent with RSV neuroprotective effects, but appear independent of RSV regulatory effects on corticosterone secretion.
Assuntos
Isquemia Encefálica/fisiopatologia , Neovascularização Fisiológica/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Fármacos Neuroprotetores/administração & dosagem , Traumatismo por Reperfusão/prevenção & controle , Memória Espacial/efeitos dos fármacos , Estilbenos/administração & dosagem , Córtex Suprarrenal/efeitos dos fármacos , Córtex Suprarrenal/metabolismo , Animais , Comportamento Animal/efeitos dos fármacos , Biomarcadores/sangue , Biomarcadores/metabolismo , Isquemia Encefálica/sangue , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Região CA1 Hipocampal/irrigação sanguínea , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Corticosterona/sangue , Corticosterona/metabolismo , Relação Dose-Resposta a Droga , Proteína Duplacortina , Injeções Intraperitoneais , Masculino , Plasticidade Neuronal/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/efeitos adversos , Fármacos Neuroprotetores/uso terapêutico , Distribuição Aleatória , Ratos Wistar , Traumatismo por Reperfusão/etiologia , Resveratrol , Estilbenos/efeitos adversos , Estilbenos/uso terapêuticoRESUMO
BACKGROUND: Major depression is a prevalent mental disorder and imposes considerable burden on health and productivity. Men are not immune to major depression, yet they often delay seeking help because of perceived stigma and gender norms. E-mental health programs hold potential for early prevention of major depression. However, we have little knowledge about men's preferences for design features of e-mental health programs. OBJECTIVES: The objective of this study was to (1) estimate and compare the proportions of Internet use for medical information, preferred design features, and likely use of e-mental health programs; (2) examine factors associated with the likely use of e-mental health programs; and (3) understand potential barriers to the use of e-mental health programs among Canadian working men, who were at high risk of a major depressive episode (MDE). METHODS: A cross-sectional survey in 10 Canadian provinces was conducted between March and December 2015. Random digit dialing method was used through household landlines and cell phones to collect data from 511 working men who were at high risk of having an MDE and 330 working men who were at low risk of having an MDE. RESULTS: High-risk men were more likely to endorse the importance of accessing health resources on the Internet than low-risk men (83.4% vs 75.0%, respectively; P=.01). Of the 17 different features assessed, the top three features most likely to be used by high-risk men were: "information about improving sleep hygiene" (61.3%), "practice and exercise to help reduce symptoms of stress and depression" (59.5%), and "having access to quality information and resources about work stress issues" (57.8%). Compared with men at low risk for MDE, men at high risk for MDE were much more likely to consider using almost every one of the different design features. Differences in preferences for the design features by age among men at high risk of MDE were found only for 3 of 17 features. Differences in preferences for design features between English- and French-speaking participants were found only for 4 out of the 17 features. Analysis of qualitative data revealed that privacy issues, perceived stigma, ease of navigation, personal relevance, and lack of personal interaction, time, and knowledge were identified as barriers to the use of e-mental health programs in working men who were at high risk of MDE. CONCLUSION: E-mental health programs may be a promising strategy for prevention of depression in working men. Development of e-mental health programs should consider men's preferences and perceived barriers to enhance the acceptability of this approach.
Assuntos
Transtorno Depressivo Maior/prevenção & controle , Internet , Telemedicina/métodos , Adolescente , Adulto , Idoso , Canadá , Estudos Transversais , Transtorno Depressivo Maior/psicologia , Emprego/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Adulto JovemRESUMO
Neuropeptides act as signaling molecules that regulate a range of aspects of brain function. Gastrin-releasing peptide (GRP) is a 27-amino acid mammalian neuropeptide, homolog of the amphibian peptide bombesin. GRP acts by binding to the GRP receptor (GRPR, also called BB2), a member of the G-protein coupled receptor (GPCR) superfamily. GRP produced by neurons in the central nervous system (CNS) plays a role in synaptic transmission by activating GRPRs located on postsynaptic membranes, influencing several aspects of brain function. Here we review the role of GRP/GRPR as a system mediating both stress responses and the formation and expression of memories for fearful events. GRPR signaling might integrate the processing of stress and fear with synaptic plasticity and memory, serving as an important component of the set of neurobiological systems underlying the enhancement of memory storage by aversive information.
Assuntos
Medo/fisiologia , Peptídeo Liberador de Gastrina/fisiologia , Memória/fisiologia , Receptores da Bombesina/fisiologia , Transdução de Sinais/fisiologia , Estresse Psicológico/metabolismo , Animais , HumanosRESUMO
Abnormal function of the neuroendocrine stress system has been implicated in the behavioral impairments observed following brain ischemia. The current study examined long-term changes in stress signal regulation 30days following global cerebral ischemia. Experiment 1 investigated changes in the expression of corticotropin releasing hormone (CRH) and its subtype 1 receptor (CRHR1), glucocorticoid receptors (GR) in the paraventricular nucleus of the hypothalamus (PVN), the central nucleus of the amygdala (CeA), and the CA1 subfield of the hippocampus. Tyrosine hydroxylase (TH) was determined at the locus coeruleus (LC). Experiment 2 investigated the role of central CRHR1 activation on corticosterone (CORT) secretion at multiple time intervals following global ischemia after exposure to an acute stressor. Findings from Experiment 1 demonstrated a persistent increase in GR, CRH and CRHR1 immunoreactivity (ir) at the PVN, reduced GR and CRHR1 expression in pyramidal CA1 neurons, and increased LC TH expression in ischemic rats displaying working memory errors in the radial arm Maze. Findings from Experiment 2 revealed increased CORT secretion up to 7 days, but no longer present 14 and 21 days post ischemia. However upon an acute restraint stress induced 27 days following reperfusion, ischemic rats had increased plasma CORT secretions compared to sham-operated animals, suggesting HPA axis hypersensitivity. Antalarmin (2 µg/2 µl) pretreatment significantly attenuated post ischemic elevation of basal and stress-induced CORT secretion. These findings support persistent neuroendocrine dysfunctions following brain ischemia likely to contribute to emotional and cognitive impairments observed in survivors of cardiac arrest and stroke.
Assuntos
Isquemia Encefálica/fisiopatologia , Corticosterona/sangue , Sistema Límbico/metabolismo , Sistemas Neurossecretores/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Pirimidinas/farmacologia , Pirróis/farmacologia , Receptores de Hormônio Liberador da Corticotropina/metabolismo , Estresse Psicológico/fisiopatologia , Animais , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Isquemia Encefálica/metabolismo , Região CA1 Hipocampal/metabolismo , Núcleo Central da Amígdala/metabolismo , Hormônio Liberador da Corticotropina/metabolismo , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Límbico/efeitos dos fármacos , Locus Cerúleo/metabolismo , Masculino , Memória de Curto Prazo/fisiologia , Sistemas Neurossecretores/efeitos dos fármacos , Sistemas Neurossecretores/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Sistema Hipófise-Suprarrenal/efeitos dos fármacos , Sistema Hipófise-Suprarrenal/metabolismo , Pirimidinas/administração & dosagem , Pirróis/administração & dosagem , Ratos , Ratos Wistar , Receptores de Hormônio Liberador da Corticotropina/antagonistas & inibidores , Receptores de Glucocorticoides/metabolismo , Estresse Psicológico/metabolismo , Fatores de Tempo , Tirosina 3-Mono-Oxigenase/metabolismoAssuntos
Moduladores de Receptores de Canabinoides/farmacologia , Endocanabinoides/metabolismo , Maconha Medicinal/farmacologia , Receptor CB1 de Canabinoide/metabolismo , Transtornos de Estresse Pós-Traumáticos/tratamento farmacológico , Animais , Humanos , Transtornos de Estresse Pós-Traumáticos/metabolismo , Transtornos de Estresse Pós-Traumáticos/fisiopatologiaRESUMO
The mode of action of the anxiolytic medicinal plant Souroubea sympetala was investigated to test the hypothesis that extracts and the active principle act at the pharmacologically important GABAA-benzodiazepine (GABAA-BZD) receptor. Leaf extracts prepared by ethyl acetate extraction or supercritical extraction, previously determined to have 5.54 mg/g and 6.78 mg/g of the active principle, betulinic acid, respectively, reduced behavioural parameters associated with anxiety in a rat model. When animals were pretreated with the GABAA-BZD receptor antagonist flumazenil, followed by the plant extracts, or a more soluble derivative of the active principle, the methyl ester of betulinic acid (MeBA), flumazenil eliminated the anxiety-reducing effect of plant extracts and MeBA, demonstrating that S. sympetala acts via an agonist action on the GABAA-BZD receptor. An in vitro GABAA-BZD competitive receptor binding assay also demonstrated that S. sympetala extracts have an affinity for the GABAA-BZD receptor, with an EC50 value of 123 µg/mL (EtOAc leaf extract) and 154 µg/mL (supercritical CO2 extract). These experiments indicate that S. sympetala acts at the GABAA-BZD receptor to elicit anxiolysis.
Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Agonistas GABAérgicos/uso terapêutico , Extratos Vegetais/uso terapêutico , Receptores de GABA-A/metabolismo , Triterpenos/uso terapêutico , Animais , Ansiolíticos/farmacologia , Ansiedade/psicologia , Flumazenil/farmacologia , Agonistas GABAérgicos/farmacologia , Antagonistas GABAérgicos/farmacologia , Masculino , Fitoterapia , Casca de Planta/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Plantas Medicinais , Ratos Sprague-Dawley , Triterpenos/farmacologiaRESUMO
Background: The increasing emergencies and humanitarian challenges have worsened the mental health condition of women in the Eastern Mediterranean Region. Aim: To assess the prevalence, determinants and interventions to address mental health among women in fragile and humanitarian settings in the Eastern Mediterranean Region. Methods: Using the Preferred Reporting Items for Systematic Review and Meta-analysis guidelines, we reviewed 59 peer-reviewed published studies (PubMed, IMEMR) and grey literature (WHO/IRIS) from January 2001 to February 2023, focusing on women's mental health in the Eastern Mediterranean Region. We then conducted a descriptive analysis of the sociodemographic characteristics. Results: Among the 59 studies reviewed, only 13 of the 48 peer-reviewed studies focused primarily on women's mental health, 11 grey literature records mostly presented grouped regional data, 11 of the 25 studies on mental health among migrants were about those taking refuge in high-income countries. The average prevalence of mental disorders from 32 cross-sectional studies on women aged 12-75 years was 49%, average prevalence of anxiety was 68%, post-traumatic stress disorder was 52%, and depression was 43%. Women exhibited higher level depression than men. Age, educational disparities, and limited access to services were important risk factors for mental health disorder. Several promising interventions emerged. Conclusion: More efforts should be made to provide customized, context-specific solutions to the mental health challenges of women in humanitarian and fragile settings in the Eastern Mediterranean Region, including allocation of more resources to mental health programmes, addressing barriers, enhancing mental health surveillance, and reduction of stigma.
Assuntos
Transtornos Mentais , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Região do Mediterrâneo/epidemiologia , Transtornos Mentais/epidemiologia , Saúde Mental/estatística & dados numéricos , Oriente Médio/epidemiologia , Prevalência , Saúde da MulherRESUMO
OBJECTIVES: There are irregularities in investment cases generated by the Mental Health Compartment Model. We discuss these irregularities and highlight the costing techniques that may be introduced to improve mental health investment cases. METHODS: This analysis uses data from the World Bank, the World Health Organization Mental Health Compartment Model, the United Nations Development Program, the Kenya Ministry of Health, and Statistics from the Kenyan National Commission of Human Rights. RESULTS: We demonstrate that the Mental Health Compartment Model produces irrelevant outcomes that are not helpful for clinical settings. The model inflated the productivity gains generated from mental health investment. In some cases, the model underestimated the economic costs of mental health. Such limitation renders the investment cases poor in providing valuable intervention points from the perspectives of both the users and the providers. CONCLUSIONS: There is a need for further calibration and validation of the investment case outcomes. The current estimated results cannot be used to guide service provision, research, and mental health programming comprehensively.
Assuntos
Países em Desenvolvimento , Serviços de Saúde Mental , Humanos , Serviços de Saúde Mental/economia , Quênia , Saúde Mental/estatística & dados numéricos , Investimentos em Saúde/estatística & dados numéricos , Investimentos em Saúde/tendênciasRESUMO
BACKGROUND: There is a dearth of specialized mental health workforce in low- and middle-income countries. Use of mobile technology by frontline community health workers (CHWs) is gaining momentum in Pakistan and needs to be explored as an alternate strategy to improve mental well-being. OBJECTIVE: The aim of this study is to assess the feasibility, acceptability, and usefulness of an app-based counseling intervention delivered by government lady health workers (LHWs) to reduce anxiety and depression in rural Pakistan. METHODS: Project mPareshan is a single-arm, pre- and posttest implementation research trial in Badin District, Sindh, using mixed methods of data collection executed in 3 phases (preintervention, intervention, and postintervention). In the preintervention phase, formative qualitative assessments through focus group discussions and in-depth interviews assess the acceptability and appropriateness of intervention through perceptions of all concerned stakeholders using a specific interview guide. A REDCap (Research Electronic Data Capture)-based baseline survey using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 Scale (GAD-7) determines the point prevalence of depression and anxiety among consenting men and women older than 18 years. Individuals with mild and moderate anxiety and depression are identified as screen positives (SPs) and are eligible for mPareshan app-based intervention. Mental health literacy of health workers is improved through customized training adapting the World Health Organization's Mental Health Gap Action Programme guide 2.0. The intervention (mPareshan app) consists of tracking, counseling, and referral segments. The tracking segment facilitates participant consent and enrollment while the referral segment is used by LHWs to transfer severe cases to the next level of specialist care. Through the counseling segment, identified SPs are engaged during LHWs' routine home visits in 6 face-to-face 20-minute counseling sessions over 6 months. Each session imparts psychoeducation through audiovisual aids, breathing exercises, and coping skills to reduce stress. Clinical and implementation outcomes include change in mean anxiety and depression scores and identification of facilitators and barriers in intervention uptake and rollout. RESULTS: At the time of this submission (April 2024), we are analyzing the results of 366 individuals who participated in the baseline prevalence survey, the change in knowledge and skills of 72 health workers who took the mPareshan training, change in anxiety and depression scores of 98 SPs recruited for app-based counseling intervention, and perceptions of stakeholders pre- and postintervention gathered through 8 focus group discussions and 18 in-depth interviews. CONCLUSIONS: This trial will assess the feasibility of early home-based mental health screening, counseling, and prompt referrals by frontline health workers to reduce anxiety and depression in the community. The study findings will set the stage for integrating mental health into primary health care. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry ACTRN12622000989741; https://tinyurl.com/5n844c8z. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54272.
Assuntos
Ansiedade , Agentes Comunitários de Saúde , Depressão , População Rural , Humanos , Paquistão/epidemiologia , Agentes Comunitários de Saúde/educação , Ansiedade/epidemiologia , Ansiedade/prevenção & controle , Ansiedade/terapia , Depressão/prevenção & controle , Depressão/epidemiologia , Feminino , Masculino , Adulto , Aconselhamento/métodos , Telemedicina , Aplicativos MóveisRESUMO
Rhodiola rosea is a medicinal plant used by the indigenous Inuit people of Nunavik and Nunatsiavut, Eastern Canada, as a mental and physical rejuvenating agent. This traditional use led to the present investigation of R. rosea in the context of anxiety disorders. An alcohol extract of R. rosea roots was characterized phytochemically and orally administered for three consecutive days to Sprague-Dawley rats at 8 mg/kg, 25 mg/kg, and 75 mg/kg body weight. The rats were subjected to three behavioral paradigms of anxiety, including the elevated plus maze, social interaction, and contextual conditioned emotional response tests. Rhodiola rosea showed dose-dependent anxiolytic activity in the elevated plus maze and conditioned emotional response tests, with moderate effects in the higher-anxiety SI test. The active dose varied according to the anxiety test. In order to elucidate a mechanism, the extract was further tested in an in vitro GABAA-benzodiazepine receptor-binding assay, where it demonstrated low activity. This study provides the first comparative assessment of the anxiolytic activity of Nunavik R. rosea in several behaviour models and suggests that anxiolytic effects may be primarily mediated via pathways other than the GABAA-benzodiazepine site of the GABAA receptor.
Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Fitoterapia , Extratos Vegetais/uso terapêutico , Rhodiola , Administração Oral , Animais , Ansiolíticos/farmacologia , Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Canadá , Proteínas de Transporte/metabolismo , Relação Dose-Resposta a Droga , Humanos , Indígenas Norte-Americanos , Masculino , Aprendizagem em Labirinto , Medicina Tradicional , Extratos Vegetais/farmacologia , Raízes de Plantas , Plantas Medicinais , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/metabolismoRESUMO
Objective: This study proposes to identify and validate weighted sensor stream signatures that predict near-term risk of a major depressive episode and future mood among healthcare workers in Kenya. Approach: The study will deploy a mobile app platform and use novel data science analytic approaches (Artificial Intelligence and Machine Learning) to identifying predictors of mental health disorders among 500 randomly sampled healthcare workers from five healthcare facilities in Nairobi, Kenya. Expectation: This study will lay the basis for creating agile and scalable systems for rapid diagnostics that could inform precise interventions for mitigating depression and ensure a healthy, resilient healthcare workforce to develop sustainable economic growth in Kenya, East Africa, and ultimately neighboring countries in sub-Saharan Africa. This protocol paper provides an opportunity to share the planned study implementation methods and approaches. Conclusion : A mobile technology platform that is scalable and can be used to understand and improve mental health outcomes is of critical importance.
RESUMO
Background: Interventions targeting combined sexual and reproductive health, Human Immunodeficiency Virus (HIV) management and mental health care in sub-Saharan Africa (SSA) are few. There is a need to address common determinants of poor mental, psychosocial and sexual and reproductive health and rights (SRHR) through multimodal and multipronged interventions for adolescents. The main objective of this study was to identify whether and how interventions targeting adolescent SRHR and HIV with a focus on pregnant and parenting adolescents in SSA include mental health components and how these components and their outcomes have been reported in the literature. Methods: We carried out a two process scoping review approach between 01.04.2021 and 23.08.2022. In the first stage, we searched the PubMed database to identify studies focusing on adolescents and young people aged 10 to 24 from 2001 to 2021. We identified studies focusing on HIV and SRHR that had mental health and psychosocial aspects to the interventions. Our search yielded 7025 studies. Of these 38 were eligible based on our screening criteria that covered interventions, and on further scrutiny, using PracticeWise, an established coding system, we identified select problems and practices to provide a more granular assessment of how interventions developed for this context mapped on to specific problems. At this second stage process, we selected 27 studies for inclusion as actual interventional designs for further systematic scoping of their findings and we used the Joanna Briggs Quality Appraisal checklist to rate these studies. This review was registered within the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42021234627. Findings: Our first set of findings is that when coding problems and solutions, mental health concerns were the least common category of problems targeted in these SRHR/HIV interventions; nevertheless, psychoeducation and cognitive behavioral strategies such as improved communication, assertiveness training, and informational support were offered widely. Of the 27 interventional studies included in the final review, 17 RCTs, 7 open trials, and 3 mixed designs, represented nine countries of the 46 countries in SSA. Intervention types included peer, community, family, digital, and mixed modality interventions. Eight interventions focused on caregivers and youth. Social or community ecology associated problems (being an orphan, sexual abuse, homelessness, negative cultural norms) were the most common risk factors and were more frequent than medical issues associated with HIV exposure. Our findings highlight the relevance and centrality of social issues related to adolescent mental and physical health along with the need to strengthen multimodal interventions along the lines of problems we have identified in our review. Interpretation: Combined interventions jointly addressing adolescent SRHR, HIV, and mental health have been relatively understudied, despite evidence that adverse social and community factors are rampant in this population. Funding: MK was funded by Fogarty International CenterK43 TW010716-05 and lead the initiative.