Treatment Of Depression Research Articles

The cerebral and cognitive changes after intermittent theta burst stimulation (iTBS) treatment for depression: study protocol for a randomized double-blind sham-controlled trial

BackgroundThe therapeutic use of intermittent theta burst stimulation (iTBS) delivered to the left dorsolateral prefrontal cortex (LDLPFC) is a relatively new but promising treatment option for depression. There is a need for more knowledge on the mechanisms involved in its antidepressant effects.MethodsThis is a single-centre, prospective, randomized, double-blind, placebo-controlled trial with two arms, iTBS and sham iTBS. Adult outpatients with unipolar major depressive disorder of at least moderate severity will undergo cognitive assessment with an N-back task (0-back and 2-back), functional and structural magnetic resonance imaging and assessment of depression severity before and after brain stimulation. Neuronavigated iTBS or sham stimulation will be targeted at the LDPFC once a day for 10 consecutive workdays. ITBS will be delivered with the parameters 120% of resting motor threshold, triplet 50 Hz bursts repeated at 5 Hz; 2 s on and 8 s off, 600 pulses per session with a total duration of 3 min 9 s. The severity of depression will be measured with the Montogomery Aasberg Depression Rating Scale and the Beck Depression Inventory – second edition.In the iTBS group relative to sham, we expect significant antidepressant effects and improved N-back performance, associated with increased integrity in white matter tracts functionally connected with the LDLPFC and emotion regulation areas within the rostral anterior cingulate cortices, alongside potential increases in cortical thickness in these regions. On functional imaging, we expect to observe increased brain activity in the LDPFC during the performance of the N-back condition with higher cognitive load (2-back) in the iTBS group relative to sham.DiscussioniTBS is a promising, time-efficient, and considered a safe treatment option for depression according to existing evidence. This trial aims to assess the neurocognitive impact of a 2-week, once-daily iTBS compared to sham iTBS, targeting the LDLPFC in depressed adult outpatients. The study investigates the relationships between changes in cerebral measures and cognitive performance on an N-back task in relation to the antidepressant effect following iTBS. This trial delves into the neurocognitive mechanisms of iTBS in depression, potentially offering novel scientific insights into its treatment effects and mechanisms of action.Trial registrationClinicalTrials.gov NCT06534684. Retrospectively registered on August 1st 2024.

Can an evidence-based mental health intervention be implemented into preexisting home visiting programs using implementation facilitation? Study protocol for a three variable implementation effectiveness context hybrid trial

BackgroundPerinatal mental health conditions are the most common complication of pregnancy and childbirth (1 in 8 women). When left untreated, perinatal depression and anxiety adversely affects the entire family with pregnancy complications and negative outcomes including preterm birth, impaired mother-infant bonding, impaired lactation, substance abuse, divorce, suicide, and infanticide. Significant disparities persist in the diagnosis and treatment of perinatal depression and anxiety and these inequities are often intersectional. Preliminary research with stakeholders including community advisory boards, underrepresented and minority birthing people, and state departments of health, demonstrates the importance of social support as a mechanism for reducing disparities in perinatal depression, particularly in rural geographies. Home visiting programs (HVPs) can provide the social support needed to improve mental health outcomes in pregnant and postpartum women. Our project aims to explore the impact of context on the implementation of a mental health intervention, focusing on the lived experiences of diverse populations served by HVPs to reduce disparities in adverse maternal outcomes.MethodsUsing implementation facilitation, our study will engage multilevel stakeholders (e.g., policymakers, front-line implementers, and intervention recipients) to adapt facilitation to integrate a maternal mental health intervention (i.e., Mothers and Babies) across two midwestern, rural states (Iowa and Indiana) with multiple HVP models. Given the complexity and heterogeneity of the contexts in which Mothers and Babies will be integrated, a three variable hybrid implementation-effectiveness-context trial will test the adapted facilitation strategy compared with implementation as usual (i.e., standard education) and will assess contextual factors related to the outcomes. Using an evidence-based implementation strategy that tailors implementation delivery to the needs of the specific populations and context may improve fidelity and adoption, particularly in rural states where residents have limited access to care.DiscussionThe immediate impact of this research will be to show whether adapted facilitation can improve the uptake and fidelity of Mothers and Babies across multiple HVP models and thus positively affect depressive symptoms and perceived stress of recipients. Our implementation protocol may be used by researchers, practitioners, and policy makers to better integrate evidence-based interventions into diverse contexts, leading to more equitable implementation and improved health outcomes.Trial registrationClinicalTrials.gov Identifier: NCT06575894, registered on August 29, 2024 https://clinicaltrials.gov/study/NCT06575894?id=NCT06575894&rank=1.

Prevalence of major depression, suicidal ideation, and mental health treatment among cancer survivors.

Cancer diagnosis and treatment can result in a significant psychological burden. This study sought to investigate the prevalence of major depression, associated treatments, and suicidal ideation in cancer survivors compared to a non-cancer cohort. This is a retrospective, population-based study using survey responses from the National Survey on Drug Use and Health collected from January 2015 to December 2019. Survey data sets were queried for all respondents who provided a cancer history. Respondents with a reported history of cancer ("cancer survivors") were further stratified by whether they reported a "recent" cancer diagnosis within the past 12 months. Survey responses were evaluated for recent diagnoses of and treatments for major depressive disorder and suicidal ideation. Among the 212,411 survey respondents identified, 7,635 (3.6%) reported a cancer history, with 1,486 (0.7%) reporting a recent cancer history. There were no differences in prevalence of major depression between cancer survivors and participants without cancer (9.3% vs 9.2%, p = 0.762), though the prevalence was slightly higher among recent cancer survivors (10.0% vs 9.2%, p = 0.259). Among respondents diagnosed with major depression, cancer survivors were significantly more likely to receive treatment for depression (78.6% vs 60.3%, p < 0.001). Suicidal ideation was significantly lower among cancer survivors (5.1% vs 6.2%, p < 0.001) including recent survivors (5.0% vs 6.2%, p < 0.001). There was no overall difference in the prevalence of major depression between cancer survivors and respondents without cancer. Survivors with major depression were more likely to receive treatments. Prevalence of major depression was higher in recent cancer survivors.

Joint anatomical, histological and imaging investigation of the midbrain target region for superolateral medial forebrain bundle (slMFB) DBS.

Deep Brain Stimulation (DBS) of the superolateral branch of the medial forebrain bundle (slMFB) is currently being researched in clinical trials and open case series as a therapeutic option for treatment resistant major depressive disorder (TR-MDD) and treatment resistant obsessive-compulsive disorder (TR-OCD). There are numerous publications describing stimulation in such proximity to the ventral tegmental area (VTA) and open questions remain concerning the stimulation target and its functional environment. As of right now, we are not aware of any publications that compare the typical electrode placements with the histologically supported tractographic depiction of the target structure. We used three cadaver midbrain samples with presumed unaltered anatomy. After fixation, staining and slicing, the histological samples were warped to the MNI (Montreal Neurological Institute) big brain environment. Utilizing a tractographic atlas, a qualitative analysis of the typical slMFB stimulation site in the lateral VTA utilizing a subset of clinically implanted DBS electrodes in n=12 patients, successfully implanted for TR-OCD was performed. A joint qualitative overlay analysis of predominantly tyrosine-hydroxylase stained histology at different resolutions in an anatomical common space was achieved. Localization of the DBS-lead bodies was found in the typical positions in front of the red nuclei in the lateral VTA. DBS lead tip region positions explained the oculomotor side effects of stimulation related to para-nigral or parabrachial pigmented sub-nuclei of the VTA, respectively. The location of active electrode contacts suggest downstream and antidromic effects on the greater VTA related medial forebrain bundle system. This is the first dedicated joint histopathological overlay analysis of DBS electrodes targeting the slMFB and lateral VTA in a common anatomical space. This analysis might serve to better understand the DBS target region for this procedure.

Clinical study of different frequency transcranial magnetic stimulation combined with paroxetine in the treatment of poststroke depression with insomnia.

Study the treatment of poststroke depression and insomnia using varied repetitive transcranial magnetic stimulation (rTMS) frequencies alongside paroxetine. Aim to enhance rTMS effectiveness for depression, insomnia, neurological impairment, and daily living skills. Ninety poststroke depression (PSD) patients were randomly divided into a low-frequency group (low-frequency rTMS + enteric-coated paroxetine), a high-frequency group (high-frequency rTMS + enteric-coated paroxetine), and a control group (sham stimulation + enteric-coated paroxetine). The treatment was administered 5 times a week for a total of 2 weeks. Before treatment, at the end of the 2-week treatment, and at the end of the 6-week follow-up, the 3 groups of patients were assessed using the Hamilton Depression Rating Scale (HAMD), Pittsburgh Sleep Quality Index (PSQI), National Institutes of Health Stroke Scale (NIHSS), and Modified Barthel Index (MBI). The mean differences of scores measured at different frequencies and at different times were analyzed by repeated measure one-way analysis of variance. The interaction between different frequency and score before and after treatment was significant. HAMD, PSQI, and NIHSS scores of the 3 groups after 2 weeks of treatment and 6 weeks of follow-up were significantly lower than before treatment, while MBI scores were opposite. The main effect of treatment scores in different frequency groups showed that HAMD, NIHSS, and MBI scores were not significantly different among the 3 groups before treatment. The HAMD, PSQI, and NIHSS scores of the low frequency group and the high frequency group were significantly lower than those of the control group after treatment, and the MBI scores were the opposite, except that there was no significant difference in HAMD-17 scores among the 3 groups at the 6-week follow-up. Among them, HAMD score in high-frequency group was significantly lower than that in low-frequency group, and PSQI score was significantly higher than that in low-frequency group. Low-frequency rTMS combined with medication has a better therapeutic effect on the insomnia symptoms of PSD, while high-frequency rTMS combined with medication has a more pronounced therapeutic effect on the depressive symptoms of PSD. Both high-frequency and low-frequency rTMS have an improving effect on neurofunctional deficits and activities of daily living.

The Mediating Role of Emotion Regulation Difficulties in the Correlation Between Mindfulness and Psychological Resilience in Patients Diagnosed with Depression.

This study aimed to determine the mediating role of emotion regulation difficulties in the correlation between mindfulness and psychological resilience. This study was conducted with a total of 119 patients diagnosed with major depression. Data were collected with Personal Information Form, Mindfulness Scale, Emotion Regulation Difficulties Scale, and Psychological Resilience Scale. The study participants reported moderate levels of mindfulness and emotion regulation difficulties, and above-average levels of psychological resilience. It was found that there was a moderately negative correlation between mindfulness and emotion regulation difficulties (r = -0.553, p < 0.001), as well as between psychological resilience and emotion regulation difficulties (r = -0.429, p < 0.001). A moderately positive correlation was determined between mindfulness and psychological resilience (r = 0.344, p < 0.001). Emotion regulation difficulties fully mediated the correlation between mindfulness and psychological resilience. These findings will guide the development of interventions aimed at enhancing mindfulness, emotion regulation skills, and psychological resilience in depression treatment.

Moms &amp; Babies Feeling Better Together: Outcomes of a Technology-Assisted, Entertaining, CBT-Based Depression Treatment for Low-Income Perinatal People Served by a Rural Michigan WIC Clinic

Rural Americans experience higher rates of perinatal depression (PND) than urban peers yet are less likely to receive treatment. The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is a potential setting for offering PND treatment. This pilot study examines the impact of Moms &amp; Babies Feeling Better Together (MBFBT), a technology-assisted depression treatment, on perinatal WIC clients’ depressive symptoms, anxiety, and parenting self-efficacy. A one-group pre-/post-test design assessed changes in outcomes over time. Paired-samples t-test results show statistically significant decreases in depression and anxiety and increases in parenting self-efficacy between baseline and post-treatment. Repeated measures analysis of variance demonstrates significant patterns of difference in expected directions across three timepoints for each outcome. Findings provide preliminary support for MBFBT’s effectiveness and its promise for delivery within rural WIC settings.

Current State of Research on Surf Therapy and its Possible Application as an Intervention for Adolescent Depression

Current State of Research on Surf Therapy and its Possible Application as an Intervention for Adolescent Depression Abstract: Depression is one of the most common mental health disorders experienced in adolescence. Because of its high prevalence rates and significant impact on affected individuals, alternative and complementary interventions are being explored. In recent years, physical activity has received increasing attention as a form of treatment. Current reviews highlight the potential benefits of this therapeutic approach in reducing depressive symptoms. Surf therapy is an innovative approach in the field of physical activity that additionally utilizes the therapeutic effects of the ocean. It combines surfing with structured exercises to promote mental and physical well-being. Internationally, surf therapy is already being applied to children and adolescents dealing with mental health problems as well as to adults diagnosed with conditions such as depression and posttraumatic stress disorder. Initial studies suggest positive effects of surf therapy in terms of symptom reduction, although the research is limited and requires further investigation. We present our pilot study investigating the feasibility and effectiveness of surf therapy for the treatment of adolescent depression in Germany.

Sex versus gender associations with depressive symptom trajectories over 24 months in first-episode schizophrenia spectrum disorders

BackgroundFemales with schizophrenia often experience more severe and persistent depressive symptoms than males, in particular during the acute phase of the illness. In contrast to sex (a biological distinction), little is known about the associations between gender (a societal construct) and depression in schizophrenia. AimWe examined the associations of sex versus gender with visit-wise changes in depressive symptoms over 24 months in patients with first-episode schizophrenia spectrum disorders (FES) (n = 77) compared to matched healthy controls (n = 64). MethodsThe Bem Sex Role Inventory was used to measure feminine gender role endorsement. The Calgary Depression Scale for Schizophrenia was used to measure depressive symptoms at baseline, weeks 2, 4, and 6, and months 3, 6, 9, 12, 15, 18, 21, and 24. We used mixed models for continuous repeated measures to examine the moderating effects of childhood trauma, premorbid adjustment, age of psychosis onset, and cannabis use on the associations of sex and gender with depressive symptoms. ResultsHigher feminine gender role endorsement, independent of biological sex, was associated with more severe baseline depression and worse initial treatment trajectories. Childhood trauma exposure was also associated with worse depression outcomes, and mediated the association between gender and pre-treatment depression severities. ConclusionsGender, but not sex, was associated with depressive symptom trajectories in FES. The consideration of both sex and gender offered a more nuanced insight into depressive symptoms compared to biological sex alone.

Responses to clinical treatment of bipolar versus unipolar depressive episodes in women versus men.

Whether responses to treatment of major depressive episodes differ between women and men or with bipolar (BD) and major depressive disorders (MDD) remains unresolved. To test for diagnostic and sex differences in responses to treatment of depression. We compared changes in the 21-item Hamilton Depression Rating Scale (HDRS21) ratings of depression (n = 3243) between women (64.7%) and men, and between DSM-5-TR BD ([n = 253] and subtypes I [BD1] vs II [BD2]) and MDD (n = 2990), using bivariate comparisons and multivariate modeling. Treatments included clinically individualized use of antidepressants (by 92.4%, in doses averaging 90.0 mg/day imipramine-equivalent), sometimes with mood-stabilizing agents (32.1%), second-generation antipsychotics (18.8%), or psychotherapy (38.6%). Depression ratings decreased by 60.6% to a final mean HDRS score of 7.44; response rate (⩾50% reduction in HDRS) averaged 63.7%. Outcomes were very similar in women and men as well as with BD versus MDD, and between BD subtypes. Moreover, age, duration of illness, initial HDRS score, dose of antidepressant, and weeks of treatment, as well as sex and diagnosis were not associated with improvement of HDRS with treatment. Only 6/42 comparisons involving 21 individual HDRS items differed significantly in improvement between sexes or diagnoses. Results were very similar to the Montgomery-Åsberg Depression Rating Scale depression ratings. Only 2.0% of the subjects experienced mood-switching into clinical (hypo)mania and the final Young Mania Rating Scale ratings averaged 0.63. Responses to clinical treatment (as % reduction of HDRS score, response rate, or final HDRS score) of depressed women versus men, and BD (including BD1 vs BD2) versus MDD were substantial and very similar.

Facilitating Thought Progression to Reduce Depressive Symptoms: Randomized Controlled Trial.

The constant rise in the prevalence of major depressive disorder calls for new, effective, and accessible interventions that can rapidly and effectively reach a wide range of audiences. Recent developments in the digital health domain suggest that dedicated online platforms may potentially address this gap. Focusing on targeting ruminative thought, a major symptomatic hallmark of depression, in this study we hypothesized that delivering a digital health-based intervention designed to systematically facilitate thought progression would substantially alleviate depression. The study aims to investigate the efficacy of a novel digital intervention on the reduction of depressive symptoms. This intervention was designed as an easy-to-use gamified app specifically aimed to facilitate thought progression through intense practicing of associative, semantically broad, fast, and creative thought patterns. A randomized clinical trial was conducted, comparing changes in depression symptoms between participants who used the app in the intervention group (n=74) and waitlist control group (n=27) over the course of 8 weeks. All participants filled out a battery of clinical questionnaires to assess the severity of depression at baseline and 4 and 8 weeks after starting the study. These primarily included the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Patient Health Questionnaire-9 as well as the Positive Affect Negative Affect Scale-Negative Affect Score, Ruminative Response Scale, and Symptoms of Depression Questionnaire. Additional questionnaires were implemented to assess anxiety, positive affect, anhedonia, and quality of life. The results indicate that across multiple clinical measurements, participants in the intervention group who played the gamified app showed greater and faster improvement in depressive symptoms compared with their waitlist control counterparts. The difference between the groups in MADRS improvement was -7.01 points (95% CI -10.72 to -3.29; P<.001; Cohen d=0.67). Furthermore, the difference in improvement between groups persisted up to 4 weeks posttrial (MADRS differences at week 12: F49,2=6.62; P=.003; ηp2=0.21). At the end of the trial, participants who played the app showed high interest in continuing using the app. The results demonstrate that a gamified app designed to facilitate thought progression is associated with improvement in depressive symptoms. Given its innovative and accessibility features, this gamified method aiming to facilitate thought progression may successfully complement traditional treatments for depression in the future, providing a safe and impactful way to enhance the lives of individuals experiencing depression and anxiety. ClinicalTrials.gov NCT05685758; https://clinicaltrials.gov/study/NCT05685758.

Psychiatric considerations of multiple sclerosis

Multiple sclerosis is a degenerative neuroinflammatory disease that affects the central nervous system with a wide range of neurological and psychiatric symptoms. A correct differential diagnosis is crucial for the management of pathology and there are specific diagnostic methods. This study presents the case of a 53-year-old patient diagnosed with Strumpell-Lorrain disease resistant to psychopharmacological treatment for depression and anxiety who, after the change of diagnosis and therapy to multiple sclerosis, showed clinical improvement in psychiatric symptoms.

AGOMELATINE ETHOSOMES FOR ENHANCED TRANSDERMAL DRUG DELIVERY

Objective: The current study aimed to prepare and optimize Agomelatine (AMN) ethosomes for enhanced transdermal drug delivery. Methods: In this study cold method was employed to manufacture the AMN-loaded ethosomes with dissimilar quantities of Phosphatidyl Choline (PC): Cholesterol: Ethanol. Transmission Electron Microscopy (TEM) was employed to evaluate the appearance of the formed ethosomes. Other formulation parameters like vesicle size and zeta potential, polydispersity index, transition temperature, and entrapment efficiency were also investigated. Results: The microscopy results showed that AMN ethosomes have a smooth surface. It was discovered that the AMN-3 formulation of transdermal ethosomes had 92.15±1.3 entrapment efficiency with good vesicle diameter. The release of agomelatine adhered to the zero-order release model. The polydispersity Index (PI) and zeta potential of the optimized formulation were found to be 0.209 and-14.09±1.95 mV, respectively. The maximum flux for the ethosome formulation (AMN-3) was 34.29 µg. h/cm2. A 10.71 fold increment was observed in the bioavailability of optimized formulation than control (oral suspension). A higher drug concentration in the blood suggested better systemic absorption of ethosomes. The optimized formula has a Tmax of 4.0±0.08h and 73.38±1.37 of Cmax. The AMN ethosomes were found to be more stable when stored at 4 °C. Conclusion: The current study suggests that ethosomal vesicles may improve transdermal dispersion without causing skin irritation. Agomelatine-loaded ethosome has the potential to be one of the most important transdermal application techniques for the treatment of depression.

Plants with Potential Importance in Supporting the Treatment of Depression: Current Trends, and Research.

Depression is one of the most common diseases in the world, and it is also the most common mental disorder. Depressive disorders are a real threat not only to individuals, but also to the general population. This disease is a leading cause of disability and inability to work. Due to the numerous side effects of conventional drugs, attention is increasingly being paid to other solutions, including herbal medicines. Many plant species are known for their traditional uses in the treatment of anxiety, insomnia, and depression. The clinically proven effects of adaptogenic raw materials on depression symptoms are probably related to the positive impact of some secondary metabolites (terpenoids, alkaloids, glucosinolates, phenols). Currently, it is emphasized that in many cases the antioxidant and anti-inflammatory properties of plant substances play a protective role at the neurocellular level. Among the medicinal plants analyzed in clinical trials for the treatment of depression, the following seem to be particularly interesting: saffron (Crocus L.), turmeric (Curcuma L.), ginkgo (Ginkgo L.), St. John's wort (Hypericum L.), and passionflower (Passiflora L.), which have broad and strong biological activity, well-documented history of action and use, and effectiveness in preventing and/or treating anxiety and depression. These plants are still in the sphere of biochemical and phytopharmaceutical research, the results of which are very promising.

Self-Rated ECT Outcomes in Patients With Depression: A Naturalistic Single-Site Study.

Electroconvulsive therapy (ECT) is considered to be the most effective treatment for severe depression. This study investigated recent ECT outcomes for depression at a large tertiary center, which also provides community care. Data were obtained from Mayo Clinic Rochester patients ages 18 and older who received an acute course of ECT between August 1, 2017 and April 30, 2024. Patients were included if there was a depressive disorder diagnosis (unipolar or bipolar) and a self-rated Patient Health Questionnaire-9 (PHQ-9) within 10 days of the start and end of the acute course. Patients were excluded if the starting PHQ-9 score was less than 10. The age, sex, number of acute course treatments, stimulus electrode lead placement, and PHQ-9 scores were collected. Response (PHQ-9 improvement ≥50%) and remission (PHQ-9 < 5) rates were calculated. Linear and logistic regressions were performed to investigate predictors of response and remission. Of 1206 patients identified, 408 met final inclusion and exclusion criteria. The response rate was 80.4%, and remission rate was 52.7%. Logistic regression for response showed no significant predictors; the P value for age just missed statistical significance (odds ratio, 1.0152; 95% confidence interval, 0.9991-1.0316; P = 0.0641). Logistic regression for remission showed only a lower baseline PHQ-9 score (odds ratio, 0.9465; 95% confidence interval, 0.9049-0.9891; P = 0.0152) as a significant predictor. Our results affirmed the high efficacy of ECT in severe depression. No other established treatment for depression can report a response rate as high as 80% in a naturalistic study. This study supports the continued relevance and place of ECT for severe depression.

Amphetamine Derivatives as Potent Central Nervous System Multitarget SERT/NET/H3 Agents: Synthesis and Biological Evaluation.

In this research, a variety of novel amphetamine derivatives were synthesized and assessed for their potential as multifaceted antidepressant agents. Among these compounds, compound 11b demonstrated potent inhibitory effects on both serotonin and noradrenaline transporters (SERT/NET) and high affinity for histamine H3 receptor (H3R), and displayed low affinity for off-target receptors (H1, α1) and hERG channels, which can reduce the prolongation of the QT interval. Molecular docking studies offered a rational binding model of compound 11b when it forms a complex with SERT, NET, and the histamine H3 receptor. In vivo behavioral studies, compound 11b dose-dependently reduced the immobility duration in the mouse FST and TST assays without a stimulatory effect on the locomotor activity. Furthermore, compound 11b had a favorable pharmacokinetic profile in rats. Thus, compound 11b has the potential to develop a novel class of drugs for the treatment of depression.

Fabrication and application of a dual drug-loaded nanoniosomes encapsulating rutin and berberine: optimization, in vitro and ex vivo evaluation

Rutin and berberine are naturally occurring polyphenols but their usefulness is restricted by their low bioavailability and poor solubility. Thus, by delivering rutin–berberine in the form of niosomes simultaneously and hoped to enhance the permeability through nasal route for the treatment of depression. Thin-film hydration approach was used to generate dual drug-loaded niosomes (rutin–berberine) encapsulating rutin and berberine. Various analytical techniques were used to characterize the morphology, size, compatibility, and leakage of the particles. These techniques included transmission electron microscopy, dynamic light scattering, UV spectrophotometry, and differential scanning calorimetry. The optimized formulation (rutin–berberine optimized niosomal formulation) was subjected to additional characterization for drug release, ex-vivo penetration investigation, confocal laser scanning microscopy, and 2,2-diphenyl-1-picrylhydrazyl assay. The rutin–berberine optimized niosomal formulation analysis showed that the drug release was 76.66 ± 1.24% at 24 hours, the entrapment efficiency was 74.8 ± 2.13% (rutin), and 79.0 ± 3.47% (berberine) and the vesicle size was 72.6 nm with a polydispersion index of 0.208. The antioxidant activity showed 73.67 ± 2.5% which is close to regular ascorbic acid. Studies on permeation ex-vivo revealed that rutin–berberine optimized niosomal formulation had considerably higher permeation (84.89 ± 3.15%) compared to rutin–berberine suspension (37.28 ± 2.33%). Furthermore, rhodamine B-loaded rutin–berberine optimized niosomal formulation appeared to have higher penetration than the control (rhodamine B-solution) according to the confocal laser scanning microscope results of the nasal mucosa. Based on all the experimental data, rutin–berberine optimized niosomal formulations were determined to be a viable and successful intranasal delivery formulation.

Magnesium depletion score and depression: a positive correlation among US adults.

The Magnesium depletion score (MDS) serves as a novel metric for quantifying magnesium deficiency in the human body, comprehensively assessing four indicators: diuretic use, proton pump inhibitor use, estimated glomerular filtration rate, and alcohol abuse. However, there have been no studies examining the potential association between MDS and depression. The study population for this cross-sectional study comprised adults from the National Health and Nutrition Examination Survey database from 2009 to 2018. Participants with a score of 10 or above on the Patient Health Questionnaire-9 were defined as having depression. We employed multivariable logistic regression models to investigate the association between MDS and depression. Furthermore, subgroup analyses were conducted to assess potential differences in this association among populations with diverse characteristics. A total of 13,197 participants were included in this study. After adjusting for all covariates, a significant positive correlation was observed between MDS and depression. Specifically, for every unit increase in MDS, the likelihood of developing depression increased by 13% (OR = 1.13, 95% CI: 1.04-1.22, p = 0.0025). This positive correlation was consistent across MDS groups, with a 19% increase in depression likelihood in the medium group (OR = 1.19, 95% CI: 1.01-1.41, p = 0.0404) and a 58% increase in the high group (OR = 1.58, 95% CI: 1.21-2.07, p = 0.0007), using the low subgroup as a reference. Subgroup analyses revealed significant differences in the relationship between MDS and depression across races, marital statuses, and hypertension status. Our study has uncovered a significant positive association between MDS and depression. Reducing MDS in individuals may play a positive role in both the prevention and treatment of depression.

Top-funded companies offering digital health interventions for the prevention and treatment of depression: a systematic market analysis

BackgroundDigital innovations can reduce the global burden of depression by facilitating timely and scalable interventions. In recent years, the number of commercial Digital Health Interventions for Depression (DHIDs) has been on the rise. However, there is limited knowledge on their content and underpinning scientific evidence. This study aimed to: (i) identify the top-funded companies offering DHIDs and (ii) provide an overview of their interventions, including scientific evidence, psychotherapeutic approaches and use of novel technologies.MethodsA systematic search was conducted using two venture capital databases to identify the top-30 funded companies offering DHIDs. In addition, studies related to the DHIDs’ were identified via academic databases and hand-searching. The methodological quality of the publications was evaluated using the Mixed Methods Appraisal Tool.ResultsThe top-30 funded companies offering DHIDs received a total funding of 2,592 million USD. Less than half of the companies produced any scientific research associated with their DHIDs, with a total of 83 publications identified. Twenty-five publications were randomised control trials, of which 15 reported moderate-to-large effects in reducing depression symptoms. Regarding novel technologies, few DHIDs incorporated the use of conversational agents or low-burden sensing technologies.ConclusionsFunding received by top-funded companies was not related to the amount of scientific evidence provided on their DHIDs. There was a strong variation in the quantity of evidence produced and an overall need for more rigorous effectiveness trials. Few DHIDs used automated approaches such as conversational agents, limiting their scalability.

The role of astrocytes in depression, its prevention, and treatment by targeting astroglial gliotransmitter release

The role of ventral hippocampus (vHipp) astroglial gliotransmission in depression was studied using chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) rodent models. CRS increased Cx43 hemichannel activity and extracellular glutamate levels in the vHipp and blocking astroglial Cx43 hemichannel-dependent gliotransmission during CRS prevented the development of depression and glutamate buildup. Moreover, the acute blockade of Cx43 hemichannels induced antidepressant effects in rats previously subjected to CRS or CUMS. This antidepressant effect was prevented by coinjection of glutamate and D-serine. Furthermore, Cx43 hemichannel blockade decreased postsynaptic NMDAR currents in vHipp slices in a glutamate and D-serine-dependent manner. Notably, chronic microinfusion of glutamate and D-serine, L-serine, or the NMDAR agonist NMDA, into the vHipp induced depressive-like symptoms in nonstressed rats. We also identified a small molecule, cacotheline, which blocks Cx43 hemichannels and its systemic administration induced rapid antidepressant effects, preventing stress-induced increases in astroglial Cx43 hemichannel activity and extracellular glutamate in the vHipp, without sedative or locomotor side effects. In conclusion, chronic stress increases Cx43 hemichannel-dependent release of glutamate and D-/L-serine from astrocytes in the vHipp, overactivating postsynaptic NMDARs and triggering depressive-like symptoms. This study highlights the critical role of astroglial gliotransmitter release in chronic stress-induced depression and suggests it can be used as a target for the prevention and treatment of depression.