Search Results (225)

Background: Depression that is resistant to two or more adequate treatment trials—treatment-resistant depression (TRD)—is a prevalent clinical challenge. Although psychotherapies have been recommended by clinical guidelines as an alternative or adjunctive treatment strategy, the effectiveness of psychotherapy in individuals with TRD has not yet been evaluated through meta-analytic methods, primarily due to a limited number of trials. This highlights the necessity of personalized research targeting this specific population. This systematic review and meta-analysis aimed to summarize the evidence on psychotherapy in treating TRD. Methods: A systematic search was conducted following the Guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles were included if they quantitatively examined the efficacy of psychotherapy on depression symptoms in individuals diagnosed with depression who had not responded to at least two prior treatments (i.e., pharmacotherapy and/or psychotherapy). Results: A total of 12 studies were included. The quality of evidence was evaluated as being globally moderate. When pooling all psychotherapies, a small-to-moderate, but significant, effect on depressive symptoms was observed compared to the control group (SMD = −0.49, CI = −0.63; −0.34). The observed effect remained unchanged after removing the outlier (SMD = −0.47, CI = −0.62; −0.32). When examining depressive symptoms by type of psychotherapy, Mindfulness-Based Cognitive Therapy (SMD = −0.51, CI = −0.76; −0.25), Cognitive Behavioral Therapy (SMD = −0.53, CI = −0.92; −0.14), and Cognitive Therapy (SMD = −0.51, CI = −1.01; −0.01) showed a moderately significant effect on depressive symptoms compared to the control group. Conclusions: Although this potentially represents the first meta-analysis in this area, the number of studies specifically addressing this complex population remains limited, and the existing literature is still in its early stages. Research focusing on TRD is notably sparse compared to the broader body of work on depression without treatment resistance. Consequently, it was not possible to conduct meta-analyses by type of psychotherapy across all treatment modalities and by type of control group. Due to several study limitations, there is currently limited evidence available about the effectiveness of psychotherapy for TRD, and further trials are needed. Beyond the treatments usually offered for depression, it is possible that TRD requires a personalized medicine approach. Full article

Objectives: This study assessed the effectiveness of a cognitive behavioral therapy (CBT)-based fine dust education program, grounded in the Health Belief Model (HBM), on elementary students’ fine dust knowledge, related behaviors, and mental health (depression, anxiety, stress, sleep quality). Methods: From September to November 2024, 95 students (grades 4–6) living near a coal-fired power plant in midwestern South Korea were assigned to either an intervention group (n = 44) or a control group (n = 51). The intervention group completed a three-session CBT-based education program; the control group received stress management education. Assessments were conducted at weeks 1, 2, 4, and 8 using standardized mental health and behavior scales (PHQ: Patient Health Questionnaire, GAD: Generalized Anxiety Disorder Assessment, PSS: Perceived Stress Scale, ISI: Insomnia Severity Index). Results: A chi-square test was conducted to compare pre- and post-test changes in knowledge and behavior related to PM2.5. The intervention group showed significant improvements in seven fine dust-related knowledge and behavior items (e.g., PM2.5 awareness rose from 33.3% to 75.0%; p < 0.05). The control group showed limited gains. Regarding mental health, based on a mixed-design ANCOVA, anxiety scores significantly declined over time in the intervention group, with group and interaction effects also significant (p < 0.05). Depression scores showed time effects, but group and interaction effects were not significant. No significant changes were observed for stress, sleep, or group × PM2.5 interactions. Conclusions: The CBT-based education program effectively enhanced fine dust knowledge, health behaviors, and reduced anxiety among students. It presents a promising, evidence-based strategy to promote environmental and mental health in school-aged children. Full article

Background/Objectives: Muscle dysmorphia (MD), a subtype of body dysmorphic disorder, is prevalent among males who engage in the non-medical use of anabolic–androgenic steroids (AASs) and performance-enhancing drugs (PEDs). These individuals often experience severe psychopathology, including mood instability, compulsivity, and a distorted body image. Despite its clinical severity, no randomized controlled trials (RCTs) have evaluated structured psychological treatments in this subgroup. This study aimed to assess the efficacy of a manualized cognitive behavioral therapy (CBT) protocol in reducing MD symptoms and associated psychological distress among male steroid users. Results: Participants in the CBT group showed significant reductions in MD symptoms from the baseline to post-treatment (MDDI: p < 0.001, d = 1.12), with gains sustained at follow-up. Large effect sizes were also observed in secondary outcomes including depressive symptoms (PHQ-9: d = 0.98), psychological distress (K10: d = 0.93), disordered eating (EDE-Q: d = 0.74), and exercise addiction (EAI: d = 1.07). No significant changes were observed in the control group. Significant group × time interactions were found for all outcomes (all p < 0.01), indicating CBT’s specific efficacy. Discussion: This study provides the first RCT evidence that CBT significantly reduces both core MD symptoms and steroid-related psychopathology in men engaged in AAS/PED misuse. Improvements extended to mood, body image perception, and compulsive exercise behaviors. These findings support CBT’s transdiagnostic applicability in addressing both the cognitive–behavioral and affective dimensions of MD. Materials and Methods: In this parallel-group, open-label RCT, 59 male gym-goers with DSM-5-TR diagnoses of MD and a history of AAS/PED use were randomized to either a 12-week CBT intervention (n = 30) or a waitlist control group (n = 29). CBT sessions were delivered weekly online and targeted distorted muscularity beliefs, compulsive behaviors, and emotional dysregulation. Primary and secondary outcomes—Muscle Dysmorphic Disorder Inventory (MDDI), PHQ-9, K10, EDE-Q, EAI, and BIG—were assessed at the baseline, post-treatment, and 3-month follow-up. A repeated-measures ANOVA and paired t-tests were used to analyze time × group interactions. Conclusions: CBT offers an effective, scalable intervention for individuals with muscle dysmorphia complicated by anabolic steroid use. It promotes broad psychological improvement and may serve as a first-line treatment option in high-risk male fitness populations. Future studies should examine long-term outcomes and investigate implementation in diverse clinical and cultural contexts. Full article

Background/Objectives: With the rapid progression of technology, applications have been proposed as a promising alternative to conventional psychotherapeutic treatment. Nonetheless, research on unguided self-help applications for binge eating remains scarce, with most existing studies utilizing cognitive behavioral therapy (CBT) principles. Therefore, this paper presents the protocol for a randomized controlled trial designed to evaluate the efficacy and acceptability of eMOTE, a standalone application designed specifically for women in Portugal who binge eat. eMOTE, adapted from dialectical behavior therapy (DBT), is unique in that it focuses on teaching emotion regulation skills while also integrating core CBT strategies. Methods: At least 68 females who self-report binge eating episodes will be randomized into an intervention group with access to eMOTE for eight weeks or a delayed waitlist, which will have access to eMOTE after the T1 assessment. Assessments will be conducted at baseline (T0), post-intervention (T1), and at 2-month follow-up (T2). The primary outcomes will include objective and subjective binge eating frequency and binge eating symptomatology, while secondary outcomes will assess global levels of ED psychopathology, shape concern, weight concern, eating concern, dietary restraint, compensatory behaviors, mindfulness, emotion regulation difficulties, intuitive eating, psychological distress, and body mass index. Conclusions: This study will contribute to the limited literature on the use of smartphone technology as an alternative to traditional psychotherapy. Furthermore, this standalone application will offer insights into the use of emotion regulation and food monitoring components designed for adult females experiencing binge eating episodes. Full article

Diabetic encephalopathy affects over 40% of diabetic patients globally, yet effective treatments remain critically limited. This study investigated the synergistic neuroprotective potential of alpha-lipoic acid (ALA) and metformin through the coordinated activation of Nrf2 and AMPK signaling pathways in type 2 diabetes mellitus (T2DM)-induced encephalopathy. Using a clinically relevant streptozotocin-nicotinamide-induced T2DM rat model, sixty male Sprague–Dawley rats were randomly assigned to five groups: control, diabetic, ALA-treated (300 mg/kg), metformin-treated (50 mg/kg), and combination-treated groups over eight weeks. Combination therapy produced statistically validated synergistic effects with significant interaction terms (p < 0.01) across all evaluated parameters. Nuclear Nrf2 translocation increased 3.9-fold and AMPK phosphorylation rose 3.2-fold compared to monotherapies, surpassing mathematical additivity. Mitochondrial function was remarkably restored, with ATP production increasing to 92% of control levels. Cognitive performance was normalized, with spatial memory approaching control values. Combination index analysis (CI < 1.0) confirmed true synergistic interactions across molecular, cellular, and behavioral endpoints. These findings establish a novel convergent mechanism providing compelling evidence for combination ALA–metformin therapy as an innovative treatment strategy for diabetes-associated neurodegeneration. Full article

Alzheimer’s disease (AD) is a neurodegenerative condition in which amyloid-beta (Aβ) plaques trigger oxidative stress (OS) and neuroinflammation, causing memory loss. OS and neurodegeneration can also be caused by reactive astrocytes, thereby promoting AD via toxic metabolite accumulation in the astrocytic urea cycle. However, the effect of molecular hydrogen (H₂) on this cycle remains unknown. Therefore, we investigated whether H₂ treatment could reduce OS-induced neurodegeneration and memory loss. 5xFAD (n = 14) and wild-type (n = 15) mice were randomized into four groups and treated with either 3% hydrogen gas (H₂) or vehicle for 60 days. Cognitive behaviors were evaluated using the Morris water maze and Y-maze tests. In addition, we used biochemical assays to measure ammonia and hydrogen peroxide (H₂O₂) levels in the hippocampi of the mice and AβO-treated primary mouse astrocytes. Aβ, γ-aminobutyric acid (GABA), and the expression of inflammatory markers were evaluated using immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). We observed that H₂ treatment significantly prevented cognitive deficits, oxidative stress, the accumulation of toxic metabolites, and the increase in inflammatory markers in 5xFAD mice. These results suggest that H₂ therapy can mitigate toxic metabolites in the astrocytic urea cycle, thereby reducing neurodegeneration and memory loss in AD. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily characterized by motor impairments resulting from dopaminergic neuron degeneration in the substantia nigra. However, PD is increasingly recognized as a multisystem disorder, where non-motor symptoms such as cognitive impairment, mood disturbances, sleep disorders, and autonomic dysfunction significantly impact patients’ quality of life. These non-motor symptoms often exhibit poor responsiveness to traditional dopaminergic therapies, underscoring a critical gap in current treatment strategies. Our systematic review investigates established methods of PD induction in rodent models and evaluates the methodologies used to assess non-motor symptoms. The review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Cochrane handbook. Thirty-two studies from 832 articles were included. The studies were characterized by MPTP, 6-OHDA, and rotenone. Our results indicate that there was considerable heterogeneity in behavioral and motor tests, which poses challenges for data comparability and highlights the lack of consensus regarding the most appropriate modeling strategies for specific PD-related behavioral outcomes. All three models demonstrated behavioral changes consistent with dopaminergic impairment when compared to control groups. MPTP-induced models showed significant non-motor deficits across various tests, except in social recognition and novelty-suppressed feeding. The 6-OHDA model consistently produced non-motor impairments, supporting its utility in replicating PD-like neurotoxicity. Rotenone-treated animals exhibited reduced social interaction, decreased sucrose preference, and increased immobility in behavioral assays, further supporting its validity. Overall, our findings indicate that these neurotoxin-based models are effective in reproducing non-motor symptoms of PD, though methodological heterogeneity highlights the need for greater standardization in future preclinical research. Full article

Background/Objectives: Schizophrenia Spectrum Disorders (SSDs) carry a debilitating burden of disease which, even after pharmacological and psychological treatment are optimized, remains difficult to fully target. New online-delivered and user-led interventions may provide an appropriate, cost-effective answer to this problem. This study aims to retrieve the currently gathered findings on the efficacy of these interventions across several outcomes, such as symptom severity, social cognition, functioning and others. Methods: A systematic review of the current available literature was conducted. Of 29 potentially relevant articles, 26 were included and assigned at least one of four intervention types: Web-Based Therapy (WBT), Web-Based Psycho-Education (WBP), Online Peer Support (OPS) and Prompt-Based Intervention (PBI). Results: The findings were grouped based on outcome. Of 24 studies evaluating the effects of symptom severity, 14 have achieved statistically significant results, and 10 have not. WBT (such as online-delivered Cognitive Behavioral Therapy, Acceptance and Commitment Therapy, social cognition training and Mindfulness Training) seemed to be the most effective at targeting symptoms. Of 14 studies evaluating functioning, seven achieved significant results, four involving a form of social or neurocognitive training, suggesting a potential pathway towards functional improvements through interventions targeting cognition and motivation. Regarding social cognition, all seven studies measuring the effects of an intervention on this outcome produced significant results, indicating that this outcome lends itself well to remote, online administration. This may be linked with the nature of social cognition exercises, as they are commonly administered through a digital medium (such as pictures, videos and auditory exercises), a delivery method that suits the online-user led model very well. Conclusions: Online user-led interventions show promise as a new way to tackle functional deficits in SSD patients and achieve these improvements through targeting social cognition, a hard-to-reach component of the burden of SSDs which seems to be successfully targetable in a remote, user-led fashion. Symptomatic improvements can also be achievable, through the combination of these interventions with treatment as usual. Full article

The limited efficacy of antipsychotics in treating the negative and cognitive symptoms of schizophrenia has prompted the exploration of adjuvant therapies. Several drugs developed for other indications—including caffeine, metformin, and furosemide—have shown procognitive potential. This study evaluated the effects of these agents on behavioral parameters using the reward-based Ambitus test, and on the cerebral D2 dopamine receptor (D2R) expression and binding. The drugs were administered individually and in combination in a schizophrenia-like triple-hit animal model (Lisket rats), derived from the Long Evans (LE) strain. Lisket rats received 14 days of drug treatment via drinking water; water-drinking LE rats served as the controls. The Ambitus test was conducted before treatment and on days 11–14. Caffeine enhanced activity without affecting learning or memory. Metformin and furosemide reduced exploratory behavior but improved reference memory; these effects were inhibited by caffeine co-administration. Although no statistically significant behavioral differences were found compared to water-treated Lisket rats, a trend toward reduced exploratory visits was observed in the triple-combination group. Lisket rats exhibited moderately reduced D2R binding in the cortex and increased binding in the hippocampus. Caffeine alone and in combination enhanced hippocampal D2R binding, while furosemide increased cortical D2R expression. This study is the first to highlight the behavioral and molecular effects of these non-antipsychotic agents in a schizophrenia model, supporting their potential for adjunctive use. Full article

Background and Objectives: Psychological distress is a pervasive yet often undertreated aspect of the cancer experience, contributing to reduced quality of life, poorer treatment adherence, and worse health outcomes. This systematic review and meta-analysis evaluated the efficacy of non-pharmacological, evidence-based psychological interventions on distress, depression, anxiety, coping capacity, and quality of life in adult cancer patients. Interventions were grouped into three domains: structured psychotherapeutic therapies (e.g., Cognitive Behavioral Therapy [CBT], Acceptance and Commitment Therapy [ACT], Meaning-Centered Psychotherapy [MCP]); mindfulness and stress reduction programs (e.g., Mindfulness-Based Stress Reduction [MBSR], Mindfulness-Based Cognitive Therapy [MBCT]); and coping and resilience-enhancing modalities (e.g., Promoting Resilience in Stress Management [PRISM], expressive writing). Materials and Methods: Following PRISMA guidelines, 42 randomized controlled trials published between 2015 and 2025 were included. A stratified meta-analytic approach calculated pooled standardized mean differences for each intervention class and outcome. Heterogeneity, subgroup, and moderator analyses explored drivers of effect variability. Results: Structured psychotherapeutic interventions yielded the largest effects, especially for depression. Mindfulness-based interventions produced moderate but significant improvements in distress and emotional regulation. Coping and resilience programs provided smaller yet statistically significant gains in adaptive coping. Between-study heterogeneity was moderate, partly explained by intervention type, delivery modality, and cancer subtype. Conclusions: These findings support integrating psychosocial care into standard oncology protocols and endorse its routine implementation as a core component of comprehensive cancer treatment. Full article

Background: Cough reflex sensitivity during cough challenge testing has been found to be modifiable with distraction in groups of healthy individuals. The purpose of this study was to examine this phenomenon in healthy controls and patients with refractory chronic cough (RCC) to advance our understanding of the role attention plays in cough modulation and shed light on avenues for therapeutic advances for RCC. Methods: Thirteen adults with RCC (mean age = 60, 12 women) and twelve healthy controls (mean age = 60, 11 women) participated in this study. The participants completed cough challenge testing with nebulized capsaicin doses tailored to their individual cough reflex sensitivity under distraction and no-distraction conditions. The distraction condition consisted of cough challenge testing while completing a cognitive (visual memory) task on a tablet. Capsaicin doses included the dose that elicited two coughs (C2), and up to three doubling doses above C2. Capsaicin doses were administered in serial order with a placebo dose randomized into the order to control for an anticipation effect during each condition. For each dose administered, the participants were instructed to cough if they needed to. Cough frequency within 15 s and maximal urge-to-cough with each dose were recorded. The order of conditions (distraction or no distraction) was alternated, and all testing was completed within one session. Results: There were no meaningful differences in the dose–response rate parameters for cough frequency or urge-to-cough, respectively, when comparing the results from the RCC group in the condition without distraction to the condition with distraction (p = 0.647, 95% CI = −2.25, 1.15; p = 0.783, 95% CI = −1.94, 0.84), and to the healthy control group without distraction (p = 0.921, 95% CI = −2.11, 2.73, p = 0.887, 95% CI = −1.40, 0.80), and with distraction (p = 0.970, 95% CI = −2.16, 3.36), p = 0.808, 95% CI = −1.49, 0.89). Conclusions: Distraction with the cognitive task chosen in this study did not influence cough reflex sensitivity in either group, which is contrary to studies on healthy volunteers and anecdotal evidence reported by RCC patients. Attentional resources may not have been sufficiently taxed, or too few capsaicin doses were administered to capture an effect as there was high individual variability in cough frequency and urge-to-cough. Additional research is needed to tailor the difficulty of the cognitive task to each participant and incorporate a real-world distraction scenario that may better reveal how attentional manipulation could be harnessed to optimize the effectiveness of behavioral cough suppression therapy for patients with refractory chronic cough. Full article

This study aimed to compare 4 weeks of cranial electrotherapy stimulation (CES) versus cognitive behavioral therapy for insomnia (CBT-I) in athletes with poor sleep quality pre-competition as measured by changes in daily mood state and physiologic parameters of sleep. Athletes with poor sleep quality in their pre-competition phase were recruited. Four weeks of CES and CBT-I were used to compare the effects on daily mood state and physiologic parameters of sleep. The participants were divided into a CES and a CBT-I group. The Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), Profile of Mood States (POMS), nighttime heart rate variability (HRV), and sleep architecture of cardiopulmonary coupling (CPC) analyses were assessed before and after the interventions. Twenty-four participants (time to competition = 46.71 ± 11.21 days) completed the study. Decreases in PSQI and ESS scores were observed in both groups. A decrease in confusion and tension scores and improvement of sleep efficiency were noted after CBT-I (p < 0.05). Changes in light sleep (stages S1 and S2) and deep sleep (stages S3 and S4) were observed (p < 0.05), accompanied by alterations in HRV (p < 0.05). Both interventions for athletes experiencing poor sleep quality before competition had efficacy in improving sleep quality and reducing daytime sleepiness. CES could cause alterations in sleep architecture and autonomic nervous regulation, and CBT-I contributed to a reduction in negative mood states. This study is tiny and limited by the absence of a control group, which may introduce psychological bias, and future research should include control conditions and extended follow-up assessments to validate these findings. Full article

Estrogen plays a crucial role in regulating reproductive and neuroendocrine functions, yet the molecular mechanisms underlying its effects on the hypothalamus remain incompletely understood. This study investigates the transcriptional and behavioral changes induced by ovariectomy (OVX) and estradiol (E2) supplementation in female C57BL/6J mice. RNA sequencing was performed to identify differentially expressed genes (DEGs) across control (CK), E2, OVX, and OVX+E2 groups, followed by functional enrichment and pathway analyses. Behavioral assessments, including open field, Y-maze, and elevated plus maze tests, were conducted to evaluate anxiety-like and cognitive behaviors. Results revealed significant alterations in GnRH signaling, neurotransmission, and inflammatory pathways, with key genes such as Elk1, Prkcb, and Camk2a differentially expressed in response to estrogen modulation. OVX-induced neuroendocrine disruptions were partially reversed by E2 treatment, as evidenced by transcriptomic and behavioral outcomes. Pearson correlation analysis further linked gene expression patterns with phenotypic traits, providing insights into estrogen’s regulatory mechanisms in the hypothalamus. These findings enhance our understanding of estrogen-mediated neuroendocrine regulation and may have implications for hormone replacement therapies in postmenopausal disorders. Full article

Shift workers are at increased risk of insomnia. The standard treatment (cognitive behavioral therapy for insomnia) poses significant challenges for this demographic due to irregular work and sleep schedules. New approaches are still considered insufficient due to high attrition or insufficient effectiveness. Our preliminary study identified sleep-relevant state and trait factors (see secondary outcomes) for incorporation into an innovative manual that addresses sleep in an implicit manner. The objective was to reduce the focus on insomnia and to replace regularity-based interventions. With a sample of 55 insomniacs (67.74% male, mean age 41.62 years), standard and customized treatments were compared using pre-treatment, post-treatment, and three-month follow-up measurements (RCT, self-assessment data). Our linear mixed models revealed the main significant effects of the measurement point for the primary (insomnia severity, sleep quality, sleep onset latency, total sleep time, daytime sleepiness) and the secondary outcomes (selection: anxiety/depression, dysfunctional beliefs, arousal, emotional stability, concern). No main effects of the condition or interaction effects were identified. Non-inferiority and equivalence tests demonstrated that the customized treatment is equivalent to standard therapy, which is a favorable outcome in light of the implicit approach. Consequently, this innovative approach warrants further exploration, incorporating the present results. Full article

Background: Sleep and physical activity (PA) are bidirectionally related, with PA having a positive effect on sleep, and sleep quality influencing PA the following day. However, little is known about the effects of clinical interventions for sleep disorders on PA. Therefore, the aim of this secondary analysis is to evaluate the impact of cognitive behavioral therapy for insomnia (CBT-I), the first-line treatment for insomnia, on PA. Methods: Thirty-eight nurses with shift work disorder and insomnia were randomly assigned to either CBT-I or a waitlist control group. PA was measured for one week before (T0) and after the intervention/waiting period (T1) using actigraphy and sleep diary items. The impact of CBT-I on the PA parameters was analyzed using linear mixed models. In addition, correlations of pre-to-post-treatment changes in PA and pre-to-post-treatment changes in the clinical outcomes (insomnia severity, sleep efficiency, depression) were explored in the CBT-I group. Results: CBT-I increased actigraphy-derived PA during the two hours (β = 26.17, SE = 9.41, p = 0.009) and one hour (β = 13.24, SE = 4.57, p = 0.006) after time in bed, and resulted in a higher percentage of self-reported days with PA (β = 19.11, SE = 9.36, p = 0.049) compared to the waitlist control group. No significant correlations were found between the changes in PA and clinical outcomes, except for a moderate positive correlation between changes in self-reported sleep efficiency and changes in PA one hour before time in bed (r = 0.56, p = 0.013). Conclusions: This is the first study to investigate the impact of CBT-I on PA, providing preliminary evidence of the potential positive effects. Further studies with larger sample sizes and randomized controlled designs with continuous PA monitoring are needed to confirm these preliminary results. Full article