Improvement In Depressive Symptoms Research Articles

More than a headache—somatic and mental symptom burden in spontaneous intracranial hypotension before and after surgical treatment

IntroductionPatients with spontaneous intracranial hypotension (SIH) frequently present with several symptoms and impaired mental health. This study systematically investigates the somatic and mental symptom burden of SIH and the effect of surgical treatment.MethodsIn this single-center retrospective study, patients with surgical closure of a spinal cerebrospinal fluid leak between September 2022 and July 2023 completed the Somatic Symptom Scale (SSS-8), the Somatic Symptom Disorder – B Criteria Scale (SSD-12), and the Patient Health Questionnaire (PHQ-8) preoperatively and three and 6 months postoperatively.ResultsFifty-seven patients were included. All three scores showed clearly pathological values before surgery (SSS-8: 12 [IQR 6.5–16], SSD-12: 26 [IQR 19.5–33.5], PHQ-8: 11 [IQR 6.5–15]) representing a high somatic symptom burden and relevant current depression. After surgery, there was a significant and sustainable improvement (SSS-8: 8 [IQR 3–11.75], SSD-12: 12.5 [IQR 5–21.75], PHQ-8: 4.5 [IQR 2–9], p < 0.001, respectively) that exceeded the minimal clinically important difference for every score.ConclusionSIH presents with high somatic and mental symptom burden. Surgical treatment leads to a relevant improvement of somatic and depressive symptoms. However, even after surgical success some patients still exhibit elevated depressive scores. Depressive symptoms might be added to the typical symptomatology of SIH.

Efficacy of an online gatekeeper program for relatives of men at risk of suicide – a randomized controlled trial

BackgroundMen at risk for suicide are a challenging population group to reach with suicide prevention strategies. Gatekeepers hold a pivotal role in the prevention of male suicide, yet effective intervention requires them to have a level of knowledge and strategies to provide support.AimThis study aimed to examine the efficacy of an online gatekeeper program for gatekeepers in male suicide prevention, assessing knowledge, perceived preparedness, self-efficacy, and psychopathological symptoms of gatekeepers.MethodsEighty-four participants were randomized to either the intervention (n = 43) or the waitlist control group (n = 41). The intervention comprised four modules providing knowledge and strategies for addressing men in suicidal crises. Outcomes included depression (PHQ-9), distress (PSS-10), burden (BAS), involvement (IEQ), as well as gatekeeper outcomes and knowledge.ResultsCompleter analyses revealed significant improvement of depressive symptoms (d = 0.39) and an increase in gatekeeper outcomes (d = 0.58 to d = 0.84) and knowledge (d = 0.62) from baseline to post-assessment. The effects were maintained for 3 months. No significant effects could be found for burden, distress, and involvement.ConclusionsThe findings indicate that a brief gatekeeper program can serve as a valuable resource. Future research should focus on examining the mental health of gatekeepers themselves and its long-term effects on intervention behavior.Trial registrationGerman Clinical Trials Register, DRKS00030758, registered on 05.12.2022.

Participant Experiences from a Randomized Controlled Trial of Heated Yoga for Depression.

Despite decades of research on yoga and depression, subjective experiences of participants in these studies have rarely been reported, and never in individuals receiving heated yoga for depression. We examined patient-reported qualitative findings from an 8-week randomized controlled trial of heated yoga for depression. Eighty medically healthy participants with moderate-to-severe depression were randomized to 8 weeks of at least twice-weekly heated yoga classes, derived from Bikram yoga, or a waitlist control. Fifty-seven participants received a clinician-administered exit interview at intervention completion/study withdrawal. The exit interview assessed: (1) how participants felt immediately following the heated yoga sessions (acute effects), (2) what they liked or found helpful about heated yoga over the 8-week intervention (positive effects), and (3) what they disliked/did not find helpful over the 8-week intervention (negative effects). Qualitative data were analyzed using thematic analysis. Acute improvements in depressive symptoms (i.e., immediately following yoga) were the most commonly reported (n = 44, 77.2%), followed by overall positive effects on depressive symptoms (i.e., over the course of the 8-week intervention; n = 33, 57.9%), including improvements in sleep (n = 10, 17.5%), energy (n = 13, 22.8%), mood (n = 18, 31.6%), motivation (n = 2, 3.5%), and concentration/decision-making (n = 5, 8.8%). Overall negative effects (i.e., over the course of the 8-week intervention) included dislike of various aspects of the intervention (n = 19, 33.3%), such as instruction (n = 7, 12.3%), difficulty (n = 7, 12.3%), repetitiveness (n = 3, 5.3%), class length (n = 2, 3.5%), and boredom (n = 7, 12.3%). Most participants reported both overall positive and negative effects (n = 37, 64.9%). Of the rest, 19 (33.3%) reported only overall positive effects, and 1 (1.8%) reported only overall negative effects. Most participant experiences were positive. Negative effects were less common and primarily involved dislike of different aspects of the heated yoga. The findings support strong acceptability and subjective improvement in depressive symptoms in depressed individuals.

Mixed results for esmethadone in Phase 3 depression trial

A Phase 3 trial of esmethadone as adjunctive treatment for patients with treatment‐resistant depression did not meet its primary endpoint of significant improvement in depressive symptoms at 28 days compared with placebo. Esmethadone did show significant improvement over placebo in treatment response rate.

Delayed allergic reaction from bupropion in a 27-year-old male with MDD: A case report and literature review

Introduction Bupropion is an antidepressant approved for the treatment of major depressive disorder (MDD), seasonal affective disorder, and smoking cessation. Nausea, headache, tremor, and insomnia are well-known adverse effects of this medication. Less well-recognized adverse effects include delayed allergic reactions, which, in some cases, can appear 2 or more weeks after bupropion initiation. Case Report A 27-year-old male with recurrent MDD was referred for medication treatment at an outpatient mental health clinic and prescribed bupropion XL. On day 28 of treatment, he reported significant improvement in depressive symptoms and the development of itchiness and urticaria on his extremities and back. Bupropion was tapered over the course of 7 days, and he was given cetirizine 10 mg daily. He was transitioned to venlafaxine treatment and experienced complete resolution of hives and pruritus. Discussion Despite published reports on bupropion causing delayed hypersensitivity reactions, there remains limited clinical recognition of this side effect, and the risk of underrecognition may be greater when the onset of the reaction is more than 2 weeks after bupropion initiation. Conclusion Bupropion can cause delayed hypersensitivity reactions, including delayed pruritis and urticaria. The risk may be highest in males aged 17 to 40 years and those with a history of allergic reactions.

The cognitive profile of older adults with treatment-resistant depression: an analysis of the OPTIMUM randomized controlled trial

ObjectiveMajor depressive disorder in older adults (late-life depression; LLD) is frequently associated with cognitive impairment, and some deficits (e.g., executive function) have been associated with a higher level of treatment resistance. However, the cognitive profile of treatment-resistant LLD (TR-LLD) has not been characterized. We hypothesized that patients with TR-LLD would show deficits in cognitive function, especially executive function, and that executive function deficits would predict poorer response to pharmacotherapy. DesignSecondary analysis of baseline cognitive data from OPTIMUM, a multi-center RCT evaluating pharmacotherapy strategies for TR-LLD. SettingFive outpatient academic medical centers (4 US, 1 Canada). Participants369 participants aged 60 and older from the OPTIMUM study. MeasurementsBaseline scores on individual tasks and composite scores from the NIH Toolbox-Cognition Battery were transformed into demographically-adjusted T-scores and compared to published norms. Impairments in the set shifting and inhibitory control tasks were investigated as predictors of depressive symptom change following treatment using ANCOVA models. ResultsParticipants had low performance on tasks evaluating inhibitory control, processing speed, verbal/nonverbal memory, and the fluid composite, but normative performance on working memory and set shifting. Participants had high estimated premorbid IQ (superior Performance on oral reading recognition). Age and physical comorbidity negatively associated with processing speed. Impairments in set shifting predicted less improvement in depressive symptoms; impairments in inhibitory control did not. ConclusionsParticipants with TR-LLD presented with broad cognitive deficits relative to healthy norms. Given poorer outcomes following standard pharmacotherapy associated with impaired set shifting, future research needs to identify alternative treatment strategies.

Omega-3 polyunsaturated fatty acids in depression: insights from recent clinical trials

Purpose of review This review examines evidence from recent clinical trials on the therapeutic potential of omega-3 polyunsaturated fatty acids (PUFAs) in major depressive disorder (MDD). We focus on the effects in MDD with comorbidities, younger populations, and high-inflammation presentations. Recent findings PubMed, Cochrane, and Embase databases were systematically searched for studies published between May 2022 and May 2024. The search was conducted on randomized controlled trials using omega-3 PUFAs with participants with a clinical diagnosis of depression. Higher doses of eicosapentaenoic acid (EPA) (>1 g/day) improved measures of depression, particularly in MDD with elevated inflammation markers, comorbid cardiovascular diseases, late-life onset, and children and adolescent populations. Improvements in depressive symptoms were associated with increases in omega-3 PUFA-derived anti-inflammatory and proresolving lipid mediators. As adjuvant treatments, omega-3 PUFAs have potential benefits in mood, cognitive and metabolic functions, kynurenine and serotonin pathways, and alterations in corticolimbic functional connectivity. Summary While evidence suggests promise, particularly for high-dose EPA and in inflammatory MDD subtypes, more research is needed to establish optimal dosing regimens, treatment duration, and patient subgroups most likely to benefit. Future studies should focus on sex differences, long-term effects, and potential synergies with other treatments.

The effects of exercise on antenatal depression: a systematic review and meta-analysis.

The aim of this study was to conduct a systematic evaluation of exercise interventions' effectiveness on antenatal depressive symptoms in pregnant women and to investigate the impact of different intervention factors on the relationship between exercise and antenatal depressive symptoms. We conducted comprehensive searches in several databases, including PubMed, Embase, Web of Science, Cochrane Library, and others. The search period covered from database inception to May 2023. After thorough screening, a total of 7 papers with 524 subjects were included in the analysis. The meta-analysis revealed that the overall effect size of exercise intervention on antenatal depressive symptoms in pregnant women was SMD = -0.41, with a 95% confidence interval of [-0.78, -0.05], and P = 0.03, indicating a significant improvement in depressive symptoms due to exercise intervention during the antenatal period. However, some degree of heterogeneity was observed among the studies, with I² = 74%, P = 0.0007. The results indicate that exercise interventions significantly contribute to the improvement of antenatal depressive symptoms in pregnant women, as inferred from the combined findings of the studies. Notably, static exercise intervention showed better results than dynamic exercise intervention. Moreover, interventions conducted before 20 weeks' gestation had superior outcomes compared to those conducted after 20 weeks' gestation, and interventions lasting longer than the trimester duration exhibited more favorable effects than shorter interventions. However, to validate these findings and optimise exercise intervention protocols for better antenatal maternal depressive symptom management, larger sample sizes and more comprehensive studies are required, given the observed heterogeneity and potential limitations in the present study. https://www.crd.york.ac.uk/prospero/ PROSPERO, identifier (CRD42023422315).

Effect of sleep quality on repetitive transcranial magnetic stimulation outcomes in depression.

While repetitive transcranial magnetic stimulation (rTMS) is effective for 50-60% of those treatment-resistant depression, it is critical to identify predictors of response for optimal patient selection to improve therapy. Insomnia is a known symptom of depression that is both correlated with depression severity and associated with poor antidepressant response. Therefore, understanding this relationship may open new opportunities for the optimization of rTMS treatment. We aimed to explore whether baseline sleep quality, specifically insomnia, is associated with rTMS outcomes in a naturalistic sample of 975 patients (age 18-90; 63.9% F) receiving a standard course of rTMS treatment from two outpatient TMS clinics located within psychiatric hospitals in the United States. One site additionally collected information on concurrent medication use on 350 patients; among these, we examined whether pharmacological treatment of insomnia affected TMS treatment response. Depression was measured using the 30-item Inventory of Depressive Symptomology Self Report (IDS-SR) in site one and an abbreviated 16-item Quick Inventory of Depressive Symptomology (QIDS) derived from the IDS-SR in site two. Sleep disturbances were measured using three insomnia-related questions. Multilevel logistic regression was used to determine whether baseline insomnia scores were associated with TMS treatment outcome. Upon dichotomous categorization of the sample by insomnia and sleep-medication use, depression and sleep scores were analyzed across time using mixed repeated measures ANOVA. We found that sleep quality improves after TMS (p<.001) and correlates with improvement in non-insomnia related depression symptoms (r= .318, p<.001). We found that among those who had significant insomnia at baseline, those not using sleep medications had significantly worse post-treatment IDS-SR scores compared to those using sleep medications (p=. 021) despite no difference in final insomnia score. Together, our results suggest that while baseline insomnia is not associated with TMS effectiveness, treating insomnia may affect the trajectory of TMS therapy. Future prospective studies are needed to examine the effect of insomnia treatment alongside TMS for depression.

Connecting the dots: sex, depression, and musculoskeletal health.

Depression and multiple musculoskeletal disorders are overrepresented in women compared with men. Given that depression is a modifiable risk factor and improvement of depressive symptoms increases positive outcomes following orthopedic intervention, efforts to improve clinical recognition of depressive symptoms and increased action toward ameliorating depressive symptoms among orthopedic patients are positioned to reduce complications and positively affect patient-reported outcomes. Although psychosocial factors play a role in the manifestation and remittance of depression, it is also well appreciated that primary biochemical changes are capable of causing and perpetuating depression. Unique insight for novel treatments of depression may be facilitated by query of the bidirectional relationship between musculoskeletal health and depression. This Review aims to synthesize the diverse literature on sex, depression, and orthopedics and emphasize the potential for common underlying biological substrates. Given the overrepresentation of depression and musculoskeletal disorders among women, increased emphasis on the biological drivers of the co-occurrence of these disorders is positioned to improve women's health.

A hospital and community-based violence intervention program for Black & Latino youth and their caregivers.

Black and Latino youth are disproportionately affected by trauma from community violence, but to date, few data support the benefit of evidence-based treatments for these youth or of including peer support to engage these youth in mental health services. From 2018 until 2020, a hospital and community-based violence intervention program in Philadelphia pilot tested the integration of home and community-based Trauma-Focused Cognitive Behavioral Therapy (TF-CBT) with peer services and case management for youth impacted by community violence. This study describes the implementation of this intervention. Data was gathered by querying the program's database. The Child Post Traumatic Stress Symptom Severity Scale (CPSS-SR-5) and the Short Mood and Feelings Questionnaire (SMFQ) were utilized to evaluate the participants' pre- and post-intervention assessment of PTSD and depression. The sample (N = 50) consisted of Black and Latino youth, mean age 14. Twenty-nine (58%) completed TF-CBT, and 82% met peer and case management goals. Youth who completed therapy showed significant improvement in both PTSD and depression symptoms at post-test. To our knowledge, this is the first study describing the implementation of home and community-based TF-CBT with peer support and case management. The study's limitations and need for further research are discussed.

Implementation of collaborative care for depression in VA HIV clinics: Translating Initiatives for Depression into Effective Solutions (HITIDES): protocol for a cluster-randomized type 3 hybrid effectiveness-implementation trial

BackgroundDepression is the most diagnosed mental health condition among people living with HIV. Collaborative care is an effective intervention for depression, typically delivered in primary care settings. The HIV Translating Initiatives for Depression into Effective Solutions (HITIDES) clinical intervention involves a depression care team housed off-site that supports depression care delivery by HIV care providers. In a randomized controlled trial, HITIDES significantly improved depression symptoms for veterans living with HIV and delivered cost savings. However, no HIV clinics in the Veterans Health Administration (VHA) have implemented HITIDES; as such, it is unclear what implementation strategies are necessary to launch and sustain this intervention.MethodsThis hybrid type-3 effectiveness-implementation trial examines the implementation and effectiveness of HITIDES in 8 VHA HIV clinics randomly assigned to one of two implementation arms. Each arm uses a different implementation strategy package. Arm 1 includes an intervention operations guide; an on-site clinical champion who, with the help of a peer community of practice, will work with local clinicians and leadership to implement HITIDES at their site; and patient engagement in implementation tools. Arm 2 includes all strategies from Arm 1 with assistance from an external facilitator. The primary implementation outcomes is reach; secondary outcomes include adoption, implementation dose, depressive symptoms, and suicidal ideation. We will conduct a budget impact analysis of the implementation strategy packages. We hypothesize that Arm 2 will be associated with greater reach and adoption and that Arm 1 will be less costly.DiscussionPreliminary work identified implementation strategies acceptable to veterans living with HIV and HIV care providers; however, the effectiveness and cost of these strategies are unknown. While the depression care team can deliver services consistently with high quality, the ability of the depression care team to engage with HIV care providers at sites is unknown. Findings from this study will be used to inform selection of implementation strategies for a broad rollout to enhance depression and suicide care for people living with HIV.Trial registrationClinicalTrials.gov ID: NCT05901272, Registered 10 May 2023, https://clinicaltrials.gov/study/NCT05901272

Digital cognitive behavioural therapy for insomnia versus digital sleep education control in an Australian community-based sample: a randomised controlled trial.

Insomnia is a prevalent condition in Australia that increases the risk of depression and anxiety symptoms. Cognitive behaviour therapy for insomnia (CBT-i) is the recommended 'first line' treatment but is accessed by a minority of people with insomnia. To improve CBT-i access in Australia, we aimed to develop and test a self-guided interactive digital CBT-i program. An online randomised controlled trial was conducted from August 2022 to August 2023 to investigate the effect of digital CBT-i, versus digital sleep education control, on symptoms of insomnia (ISI), depression (PHQ-9), anxiety (GAD-7), fatigue, sleepiness and maladaptive beliefs about sleep at 8-week follow-up. The control group accessed the intervention after the 8-week follow-up. Questionnaires were additionally administered at 16 and 24 weeks. Intent-to-treat mixed models and complete-case chi-squared analyses were used. Participants included 62 adults with insomnia symptoms (age M (SD) = 52.5 (16.3), 82% female, ISI = 18.6 (2.9)). There were no between-group differences in baseline characteristics or missing 8-week data (14.5%). After adjusting for baseline scores, CBT-i was associated with lower insomnia (Diffadj (95% CI) = 7.32 (5.0-9.6), P < 0.001, d = 1.64), depression (3.36 (1.3-5.4), p = 0.002, d = 0.84), fatigue (5.2 (2.5-7.9), P < 0.001, d = 1.00) and maladaptive beliefs about sleep (11.0 (4.1-18.0), P = 0.002, d = 0.82), but not anxiety symptoms at 8 weeks (1.84 (-0.1 to 3.8), p = 0.060, d = 0.50). Compared to control, CBT-i was associated with greater rates of insomnia remission (ISI <8; 0.0%, vs 40.0%, P < 0.001) and response at 8 weeks (ISI reduction ≥6; 7.1% vs 72.0%, P < 0.001). Improvements in insomnia and depression were maintained at 24 weeks in the CBT-i group. This interactive digital CBT-i program resulted in large and sustained improvements in symptoms of insomnia, depression, fatigue and maladaptive beliefs about sleep in Australian adults with insomnia symptoms. Implementation programs are required to increase digital CBT-i access and uptake.

Effect of depression treatment on health behaviors and cardiovascular risk factors in primary care patients with depression and elevated cardiovascular risk: data from the eIMPACT trial.

Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk. Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care. CVD-relevant health behaviors (self-reported CVD prevention medication adherence, sedentary behavior, and sleep quality) and traditional CVD risk factors (blood pressure and lipid fractions) were assessed over 12 months. Incident CVD events were tracked over four years using a statewide health information exchange. The intervention group exhibited greater improvement in depressive symptoms (p < 0.01) and sleep quality (p < 0.01) than the usual care group, but there was no intervention effect on systolic blood pressure (p = 0.36), low-density lipoprotein cholesterol (p = 0.38), high-density lipoprotein cholesterol (p = 0.79), triglycerides (p = 0.76), CVD prevention medication adherence (p = 0.64), or sedentary behavior (p = 0.57). There was an intervention effect on diastolic blood pressure that favored the usual care group (p = 0.02). The likelihood of an incident CVD event did not differ between the intervention (13/107, 12.1%) and usual care (9/109, 8.3%) groups (p = 0.39). Successful depression treatment alone is not sufficient to lower the heightened CVD risk of people with depression. Alternative approaches are needed. ClinicalTrials.gov Identifier: NCT02458690.

Interdisciplinary CBT treatment for patients with odontophobia and dental anxiety related to psychological trauma experiences: a case series

BackgroundWhile cognitive-behavioural therapy (CBT) is a well-established treatment for odontophobia, research is sparse regarding its effect on patients with dental anxiety related to psychological trauma experiences. This study aimed to evaluate changes in symptoms and acceptability of interdisciplinary Torture, Abuse, and Dental Anxiety (TADA) team treatment for patients with odontophobia or dental anxiety. We also wanted to describe the sample’s oral health status. The TADA teams offer targeted anxiety treatment and adapted dental treatment using a CBT approach.MethodsThe study used a naturalistic, case series design and included 20 consecutively referred outpatients at a public TADA dental clinic. Pre- and post-treatment assessments included questionnaires related to the degree of dental anxiety, post-traumatic stress, generalized anxiety, and depression. Patients underwent a panoramic X-ray before treatment. Before dental restoration, patients underwent an oral health examination to determine the mucosal and plaque score (MPS) and the total number of decayed, missing, and filled teeth (DMFT). Patients were referred to dentist teams for further dental treatment and rehabilitation (phase 2) after completing CBT in the TADA team (Phase 1). Results from the dental treatment in phase 2 is not included in this study.ResultsAll patients completed the CBT treatment. There were significant improvements in symptoms of dental anxiety, post-traumatic stress, and depression and moderate changes in symptoms of generalized anxiety. Dental statuses were heterogeneous in terms of the severity and accumulated dental treatment needs. The TADA population represented the lower socioeconomic range; 15% of patients had higher education levels, and half received social security benefits. All patients were referred to and started adapted dental treatment (phase 2).ConclusionsTADA treatment approach appears acceptable and potentially beneficial for patients with odontophobia and dental anxiety related to psychological trauma experiences. The findings suggest that further research, including larger controlled studies, is warranted to validate these preliminary outcomes.Trial registrationThe study was approved by the regional ethical committee in Norway (REK-Midt: 488462) and by the Data Protection Board at Møre and Romsdal County Authority.

A mixed-method randomised controlled feasibility trial of digital CBT and emotion regulation skills training for employees in the workplace (REST)

Background and aimDigital interventions for depression and anxiety can be as effective as face-to-face therapy. One in six workers experience some form of mental health problems, making the workplace a potential avenue to deliver mental health interventions as part of a stepped care model. This study aimed to assess the acceptability, feasibility, and preliminary efficacy of a digital cognitive behavioural therapy (dCBT) on depression and anxiety for employees in the workplace.MethodsA mixed-methods evaluation of employees allocated to dCBT (n=25), or a waitlist control group (n=27) was used to assess five feasibility objectives related to recruitment of employers and employees, engagement, study procedure and preliminary efficacy of the intervention. Quantitative outcome measures and qualitative interviews at 8 weeks post-randomisation were used. Quantitative outcomes were also assessed within subject at 3-, 6-, and 12-month follow-up. Qualitative data was analysed using thematic and framework analysis in Nvivo, whilst quantitative outcomes were analysed using mixed effect linear models between and within subject in R and SPSS.ResultsThirty-Three businesses agreed to facilitate the delivery of three trials run by the University of Warwick in their workplaces. 52 participants consented into the REST trial. Adherence/usage of participants of the treatment platform was just over 50% across the whole sample. There was a reduction in depression and anxiety symptoms post-intervention and at follow-up timepoints across all participants and over time although there were no statistically significant between group differences. High acceptability and satisfaction of the intervention were reported by participants based on qualitative interview data at post-intervention.ConclusionsResults from this feasibility study suggests that the dCBT programme (REST) was acceptable and shows improvement in depression and anxiety symptoms, albeit not over and above the treatment effects in the control group. Recruitment of participants and engagement with the intervention made the feasibility of the delivery somewhat challenging. With better recruitment promotion and engagement strategies, as well as implementing the learnings from the feasibility trial, a fully powered study can inform the efficacy of the REST intervention.Trial registrationThe study is registered in the BMC Springer Nature ISRCTN registry ISRCTN31161020 (registered on 08/06/2021).

Assessing the efficacy and safety of combined buspirone and venlafaxine treatment in late-life depression accompanied by cognitive impairment: A randomized controlled trial

BackgroundLate-life depression, often accompanied by cognitive impairment, poses significant clinical challenges owing to its complex etiology and diverse manifestations. While antidepressants like venlafaxine and anxiolytics such as buspirone are effective for treating depression, their effects on cognitive function remain less well-understood. With the aging population increasingly experiencing geriatric depression, there is an urgent need for innovative treatment approaches that address both depressive symptoms and cognitive impairments. ObjectiveThis study aimed to evaluate the clinical efficacy and safety of combined buspirone and venlafaxine therapy in elderly patients diagnosed with geriatric depression accompanied by cognitive impairment. MethodsA 12-week, randomized controlled trial was conducted involving 170 elderly patients. Participants were randomized into two groups: one receiving venlafaxine alone (control group) and the other receiving a combination of venlafaxine and buspirone (experimental group). The primary analysis was performed using an Intent-to-Treat (ITT) approach with mixed-effects linear models to assess changes in depressive symptoms, cognitive function, and anxiety levels. A supplementary Per-Protocol (PP) analysis, utilizing repeated measures ANOVA, was also conducted. ResultsThe ITT analysis showed that the combination therapy significantly reduced depressive symptoms, as indicated by the HAMD-17 scores (p = 0.033 at week 12). Cognitive function, as measured by MoCA scores, also improved significantly in the experimental group by week 12 (p = 0.025). However, no statistically significant differences were observed in anxiety reduction between the groups (p = 0.127). The PP analysis confirmed these findings, demonstrating consistent improvements in depressive symptoms and cognitive function, particularly in those who completed the full course of treatment. The incidence of adverse events was comparable between groups, primarily mild and manageable symptoms like dry mouth, dizziness, and fatigue. ConclusionThe combination of buspirone and venlafaxine was found to be effective in reducing depressive symptoms and enhancing cognitive function in elderly patients with geriatric depression. However, the long-term benefits, especially regarding anxiety reduction, require further investigation. Future studies should consider larger sample sizes, longer follow-up periods, and the inclusion of placebo controls to fully assess the efficacy and safety of this treatment approach.

RIPK1 inhibition mitigates neuroinflammation and rescues depressive-like behaviors in a mouse model of LPS-induced depression

BackgroundDepression is often linked to inflammation in the brain. Researchers have been exploring ways to reduce this inflammation to improve depression symptoms. One potential target is a protein called RIPK1, which is known to contribute to brain inflammation. However, it’s unclear how RIPK1 influences depression. Our study aims to determine whether RIPK1 inhibition could alleviate neuroinflammation-associated depression and elucidate its underlying mechanisms.MethodsTo investigate our research objectives, we established a neuroinflammation mouse model by administering LPS. Behavioral and biochemical assessments were conducted on these mice. The findings were subsequently validated through in vitro experiments.ResultsUsing LPS-induced depression models, we investigated RIPK1’s role, observing depressive-like behaviors accompanied by elevated cytokines, IBA-1, GFAP levels, and increased inflammatory signaling molecules and NO/H2O2. Remarkably, Necrostatin (Nec-1 S), a RIPK1 inhibitor, mitigated these changes. We further found altered expression and phosphorylation of eIF4E, PI3K/AKT/mTOR, and synaptic proteins in hippocampal tissues, BV2, and N2a cells post-LPS treatment, which Nec-1 S also ameliorated. Importantly, eIF4E inhibition reversed some of the beneficial effects of Nec-1 S, suggesting a complex interaction between RIPK1 and eIF4E in LPS-induced neuroinflammation. Moreover, citronellol, a RIPK1 agonist, significantly altered eIF4E phosphorylation, indicating RIPK1’s potential upstream regulatory role in eIF4E and its contribution to neuroinflammation-associated depression.ConclusionThese findings propose RIPK1 as a pivotal mediator in regulating neuroinflammation and neural plasticity, highlighting its significance as a potential therapeutic target for depression.

Enhanced network synchronization connectivity following transcranial direct current stimulation (tDCS) in bipolar depression: Effects on EEG oscillations and deep learning-based predictors of clinical remission

AimTo investigate oscillatory networks in bipolar depression, effects of a home-based tDCS treatment protocol, and potential predictors of clinical response. Methods20 participants (14 women) with bipolar disorder, mean age 50.75 ± 10.46 years, in a depressive episode of severe severity (mean Montgomery-Åsberg Rating Scale (MADRS) score 24.60 ± 2.87) received home-based transcranial direct current stimulation (tDCS) treatment for 6 weeks. Clinical remission defined as MADRS score < 10. Resting-state EEG data were acquired at baseline, prior to the start of treatment, and at the end of treatment, using a portable 4-channel EEG device (electrode positions: AF7, AF8, TP9, TP10). EEG band power was extracted for each electrode and phase locking value (PLV) was computed as a functional connectivity measure of phase synchronization. Deep learning was applied to pre-treatment PLV features to examine potential predictors of clinical remission. ResultsFollowing treatment, 11 participants (9 women) attained clinical remission. A significant positive correlation was observed with improvements in depressive symptoms and delta band PLV in frontal and temporoparietal regional channel pairs. An interaction effect in network synchronization was observed in beta band PLV in temporoparietal regions, in which participants who attained clinical remission showed increased synchronization following tDCS treatment, which was decreased in participants who did not achieve clinical remission. Main effects of clinical remission status were observed in several PLV bands: clinical remission following tDCS treatment was associated with increased PLV in frontal and temporal regions and in several frequency bands, including delta, theta, alpha and beta, as compared to participants who did not achieve clinical remission. The highest deep learning prediction accuracy 69.45 % (sensitivity 71.68 %, specificity 66.72 %) was obtained from PLV features combined from theta, beta, and gamma bands. ConclusionstDCS treatment enhances network synchronization, potentially increasing inhibitory control, which underscores improvement in depressive symptoms. Baseline EEG-based measures might aid predicting clinical response.

Impairments of neurovascular coupling after stroke lower glymphatic system function and lead to depressive symptom: A longitudinal cohort study

BackgroundRespective changes in neurovascular coupling (NVC) and glymphatic function have been reported in post-stroke depression (PSD). Recent studies have found a link between NVC and waste clearance by the glymphatic system, which has not been illustrated in PSD. MethodWe prospectively recruited ninety-six stroke patients and forty-four healthy controls (HC), with fifty-nine patients undergoing a second MRI scan. NVC metrics were investigated by exploring Pearson correlation coefficients and ratios between cerebral blood flow (CBF) and BOLD-derived quantitative maps (ALFF, fALFF, REHO maps). Diffusion tensor imaging along the perivascular (DTI-ALPS) index was used to reflect glymphatic function. We first analyzed the altered NVC metrics in stroke patients relative to the HC group. Then, we explored the relationship between NVC metrics, ALPS index and depressive symptoms at baseline and during the follow-up period through correlation and mediation analyses. ResultsStroke patients exhibited significantly lower global CBF-fALFF coupling and ALPS index. At the regional level, abnormal NVC alterations in brain regions involved in cognition, emotion, and sensorimotor function in PSD. Baseline analyses showed that ALPS index exhibited positive associations with both global and local NVC and abnormal regional NVC may contribute to generation of PSD by reducing glymphatic function (β = −0.075, p < 0.05, CI = [−0.169 to −0.012]). Longitudinal analyses similarly showed that ALPS index changes were positively associated with changes in NVC and mediated improvements in depressive symptoms. ConclusionOur findings suggest that NVC abnormalities leading to impaired glymphatic system function may be a potential neurobiological mechanism of PSD.