Search Results (840)

Background: Cognitive behavioral therapy (CBT) has shown consistent efficacy in individuals with psychosis, as supported by many trials. One classical distinction is that between affective and non-affective psychosis. Few studies have specifically examined the possible moderating role of substantial affective elements. In this systematic review and meta-regression analysis, we assess how CBT response differs across the affective spectrum in psychosis. Methods: We included studies assessing various CBT modalities, including third-wave therapies, administered in people with psychosis. The study protocol is published in the Open Science Framework. Meta-regression was conducted to assess whether the proportion of participants with affective psychosis (AP), as proxied by a documented diagnosis of schizoaffective (SZA) disorder, moderated CBT efficacy across positive, negative, and depressive symptom domains. Results: The literature search identified 4457 records, of which 39 studies were included. The median proportion of SZA disorder participants was 17%, with a total of 422 AP participants represented. Meta-regression showed a trend toward lower CBT efficacy for positive symptoms with a higher SZA disorder proportion (β = +0.10 SMD per 10% increase in AP; p = 0.12), though it was not statistically significant. No significant associations were found for negative (β = +0.05; p = 0.73) or depressive symptoms (β = −0.02; p = 0.78). Heterogeneity was substantial across all models (I² ranging from 54% to 80%), and funnel plot asymmetry was observed in negative and depressive symptoms, indicating possible publication bias. Risk of bias assessment showed the anticipated inherent difficulty of psychotherapies in blinding and possibly dropout rates affecting some studies. Conclusions: Affective symptoms may reduce the effectiveness of CBT for positive symptoms in psychotic disorders, although the findings did not reach statistical significance. Other patient-level characteristics in psychosis could indicate which patients can benefit most from CBT modalities. Full article

Loneliness is a significant challenge for millions worldwide, with chronic loneliness having harmful effects on physical health, mental well-being, and relationships. Cognitive distortions play an important role in perpetuating loneliness. Psychological interventions targeting such distortions have been effective at alleviating feelings of loneliness. However, less is known about which cognitive distortions are most prevalent among lonely individuals and how these distortions relate to loneliness and mental well-being. This exploratory study prescreened a Census-matched sample of 1000 U.S. adults for loneliness, then asked those in the top quartile (N = 237) to rate multiple patterns of cognitive distortion related to loneliness. Factor analyses identified six common and influential patterns of cognitive distortion (mindreading, future reward, catastrophizing, essentializing, deservedness, and externalizing). Essentializing was the most strongly endorsed factor, followed by mindreading and catastrophizing. Essentializing also evidenced the strongest correlation with loneliness. Additionally, the relationship between loneliness and participants’ stress was completely mediated by mindreading, catastrophizing, and essentializing. These findings highlight the importance of targeting specific cognitive distortions in loneliness interventions to effectively improve the mental well-being of lonely individuals. Full article

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

Background/Objectives: Neuromodulation is under investigation as a possibly effective add-on therapy in Alzheimer’s disease (AD). While transcranial pulse stimulation (TPS) has shown positive short-term effects, long-term effects have not yet been fully explored. This study aims to evaluate the long-term feasibility, safety, and potential cognitive benefits of TPS over one year in patients with Alzheimer’s disease, focusing on domains such as memory, speech, orientation, visuo-construction, and depressive symptoms. Methods: We analyzed preliminary data from the first ten out of thirty-five patients enrolled in a prospective TPS study who completed one year of follow-up and were included in a dedicated long-term database. The protocol consisted of six initial TPS sessions over two weeks, followed by monthly booster sessions delivering 6000 pulses each for twelve months. Patients underwent regular neuropsychological assessments using the Alzheimer Disease Assessment Scale (ADAS), Mini-Mental Status Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Beck Depression Inventory (BDI-II). All adverse events (AEs) were documented and monitored throughout the study. Results: Adverse events occurred in less than 1% of stimulation sessions and mainly included mild focal pain or transient unpleasant sensations, as well as some systemic behavioral or vigilance changes, particularly in patients with underlying medical conditions, with some potentially related to the device’s stimulation as adverse device reactions (ADRs). Cognitive test results showed significant improvement after the initial stimulation cycle (ADAS total improved significantly after the first stimulation cycle (M_pre = 28.44, M_post = 18.56; p = 0.001, d = 0.80, 95% CI (0.36, 1.25)), with stable scores across all domains over one year. Improvements were most notable in memory, speech, and mood. Conclusions: TPS appears to be a generally safe and feasible add-on treatment for AD, although careful patient selection and monitoring are advised. While a considerable number of participants were lost to follow-up for various reasons, adverse events and lack of treatment effect were unlikely primary causes. A multifocal stimulation approach (F-TOP2) is proposed to enhance effects across more cognitive domains. 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

Neuroinflammation is a key feature of Alzheimer’s disease (AD), and stem cell therapies have emerged as promising candidates due to their immunomodulatory properties. Neuro-Cells (NC), a combination of unmodified mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs), have demonstrated therapeutic potential in models of central nervous system (CNS) injury and neurodegeneration. Here, we studied the effects of NC in APPswe/PS1dE9 mice, an AD mouse model. Twelve-month-old APPswe/PS1dE9 mice or their wild-type littermates were injected with NC or vehicle into the cisterna magna. Five to six weeks post-injection, cognitive, locomotor, and emotional behaviors were assessed. The brain was stained for amyloid plaque density using Congo red, and for astrogliosis using DAPI and GFAP staining. Gene expression of immune activation markers (Il-1β, Il-6, Cd45, Tnf) and plasticity markers (Tubβ3, Bace1, Trem2, Stat3) was examined in the prefrontal cortex. IL-6 secretion was measured in cultured human monocytes following endotoxin challenge and NC treatment. Untreated APPswe/PS1dE9 mice displayed impaired learning in the conditioned taste aversion test, reduced object exploration, and anxiety-like behavior, which were improved in the NC-treated mutants. NC treatment normalized the expression of several immune and plasticity markers and reduced the density of GFAP-positive cells in the hippocampus and thalamus. NC treatment decreased amyloid plaque density in the hippocampus and thalamus, targeting plaques of <100 μm². Additionally, NC treatment suppressed IL-6 secretion by human monocytes. Thus, NC treatment alleviated behavioral deficits and reduced amyloid plaque formation in APPswe/PS1dE9 mice, likely via anti-inflammatory mechanisms. The reduction in IL-6 production in human monocytes further supports the potential of NC therapy for the treatment of AD. Full article

Background: Despite growing interest in the literature on Parkinson’s disease (PD) on cognitive functioning, financial incompetence—a crucial aspect of daily living—and its modulation susceptibility by PD treatment regimens remains relatively understudied. Objective: This systematic review and meta-analysis aimed to synthesize existing evidence on how PD treatments affect financial capacity, assessing both direct financial competence and cognitive or behavioral proxies of financial decision-making. Methods: A comprehensive literature search according to PRISMA protocol was conducted across major biomedical databases, supplemented by gray literature and manual reference list checks. Eligible studies assessed financial capacity directly or indirectly through cognitive proxies (e.g., executive function, decision-making) or financial risk behaviors (e.g., impulse control disorders). Two separate meta-analyses were performed. Heterogeneity (I²), publication bias (Egger’s test), and sensitivity analyses were conducted to assess robustness. Results: Twenty-three studies met inclusion criteria. One study directly measured financial capacity and was analyzed narratively, reporting diminished competence in patients on levodopa therapy. A meta-analysis of cognitive proxies (10 studies) showed a moderate effect size (Hedges’ g = 0.70, 95% CI [0.45, 0.92], p < 0.001), indicating that PD treatments negatively affect executive function and financial decision-making. A second meta-analysis of impulse control and financial risk behaviors (12 studies) revealed a larger effect size (Hedges’ g = 0.98, 95% CI [0.75, 1.22], p < 0.001), strongly linking dopamine agonists to increased financial risk-taking. Moderate heterogeneity (I² = 45.8–60.5%) and potential publication bias (Egger’s test p = 0.027) were noted. Conclusions: These findings suggest that PD treatments negatively impact financial decision-making both directly and indirectly through cognitive and behavioral pathways. Integrating financial decision-making assessments into PD care, particularly for patients on dopamine agonists, is recommended. Future research should prioritize longitudinal studies and standardized neuropsychological measures to guide clinical practice and optimize patient outcomes. Full article

Microglia, as the immune guardians of the central nervous system (CNS), have the ability to maintain neural homeostasis, respond to environmental changes, and remodel the synaptic landscape. However, persistent microglial activation can lead to chronic neuroinflammation, which can alter neuronal signaling pathways, resulting in accelerated cognitive decline. Phosphoinositol 3-kinase (PI3K) has emerged as a critical driver, connecting inflammation to neurodegeneration, serving as the nexus of numerous intracellular processes that govern microglial activation. This review focuses on the relationship between PI3K signaling and microglial activation, which might lead to cognitive impairment, inflammation, or even neurodegeneration. The review delves into the components of the PI3K signaling cascade, isoforms, and receptors of PI3K, as well as the downstream effects of PI3K signaling, including its effectors such as protein kinase B (Akt) and mammalian target of rapamycin (mTOR) and the negative regulator phosphatase and tensin homolog (PTEN). Experiments have shown that the overproduction of certain cytokines, coupled with abnormal oxidative stress, is a consequence of poor PI3K regulation, resulting in excessive synapse pruning and, consequently, impacting learning and memory functions. The review also highlights the implications of autonomously activated microglia exhibiting M1/M2 polarization driven by PI3K on hippocampal, cortical, and subcortical circuits. Conclusions from behavioral studies, electrophysiology, and neuroimaging linking cognitive performance and PI3K activity were evaluated, along with new approaches to therapy using selective inhibitors or gene editing. The review concludes by highlighting important knowledge gaps, including the specific effects of different isoforms, the risks associated with long-term pathway modulation, and the limitations of translational potential, underscoring the crucial role of PI3K in mitigating cognitive impairment driven by neuroinflammation. Full article

Maternal mental illness significantly impacts caregiving, influencing both mothers and their children. This narrative review examines the challenges faced by mothers with conditions such as depression, anxiety, bipolar disorder, and schizophrenia, which often disrupt caregiving routines, emotional stability, and social integration. These difficulties can hinder secure attachments and contribute to adverse developmental outcomes in children, including heightened risks of anxiety, depression, behavioral issues, and cognitive impairments. Children of mothers with mental illnesses are 1.8 times more likely to develop emotional or behavioral problems and face a 2.7 times higher risk of suicidal ideation during adolescence. Intergenerational transmission of mental illness is also prevalent, with affected children showing a 2.5 times greater likelihood of developing mental illnesses in adulthood. Effective interventions include cognitive behavioral therapy (CBT), family-based approaches, and community programs integrating parenting education and mental health resources. These strategies have demonstrated improvements in maternal well-being and child resilience. The review highlights the need for comprehensive policies addressing maternal mental health, early intervention for children, and culturally sensitive support systems to break cycles of intergenerational mental illness. Future research should prioritize evaluating long-term intervention effectiveness and exploring innovative tools like digital mental illnesses solutions to support affected families. Full article

Background: Multiple Chemical Sensitivity (MCS) is a complex, disabling condition marked by non-specific symptoms in response to low-level chemical exposures. It often leads to substantial impairments in quality of life, psychological health, and daily functioning. Although non-pharmacological approaches—such as lifestyle and psychological interventions—are widely used, their clinical effectiveness remains unclear. Objective: We aim to evaluate the effectiveness of lifestyle-based approaches in improving clinical and psychosocial outcomes in adults with Multiple Chemical Sensitivity. Methods: A systematic review was conducted in accordance with PRISMA guidelines (PROSPERO: CRD420251013537). Literature searches were carried out in MEDLINE (PubMed), CINAHL, Google Scholar, and ResearchGate between March and April 2025. Eligible studies included adults (≥18 years) with a confirmed diagnosis of MCS and reported outcomes such as perceived stress, anxiety, depressive symptoms, or quality of life. Methodological quality and risk of bias were independently assessed using the PEDro scale, NIH Quality Assessment Tool, CEBMa checklist, and Cochrane RoB 2.0. Results: Twelve studies (N = 378) met the inclusion criteria. Cognitive and behavioral therapies demonstrated the most consistent evidence of efficacy, with reductions in symptom severity, maladaptive cognitive patterns, and functional limitations. Mindfulness-based stress reduction showed favorable outcomes, while other mindfulness-based interventions yielded mixed results. Exposure-based therapies contributed to increased chemical tolerance and reduced avoidance behavior. Electromagnetic and biomedical approaches demonstrated preliminary but limited effectiveness. Aromatherapy was well tolerated and perceived as relaxing, though its clinical impact was modest. Conclusions: Cognitive and behavioral therapies appear to be most effective among lifestyle-based interventions for MCS/IEI. However, study heterogeneity limits the generalizability of findings, underscoring the need for more rigorous research. 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

Temporal lobe epilepsy (TLE) is a common drug-resistant form of epilepsy, often accompanied by cognitive and emotional disturbances, highlighting the urgent need for novel therapies. Scorpion Venom Heat-Resistant Synthetic Peptide (SVHRSP), isolated and synthetically derived from scorpion venom, has shown anti-epileptic and neuroprotective potential. This study evaluated the anti-epileptic effects of SVHRSP in a kainic acid (KA)-induced TLE rat model. Our results demonstrated that SVHRSP (0.81 mg/kg/day) reduced the frequency and severity of spontaneous seizures. Behavioral tests showed improved cognitive performance in the novel object recognition, object location, and T-maze tasks, as well as reduced anxiety-like behavior in the open-field test. Moreover, SVHRSP mitigated hippocampal neuronal loss and glial activation. Transcriptomic analysis indicated that SVHRSP upregulates genes involved in adhesion molecule-triggered and axon guidance pathways. Western blotting and immunofluorescence further confirmed that SVHRSP restored dendritic (MAP2), axonal (NFL), and synaptic (PSD95) marker expression, elevated the functionally important L1CAM fragment (L1-70), and increased myelin basic protein-induced serine protease activity responsible for L1-70 generation. Blockade of L1CAM expression diminished the neuroprotective effects of SVHRSP, suggesting a critical role for L1CAM-mediated synapse functions. This study is the first to reveal the therapeutic potential of SVHRSP in TLE via L1CAM-associated mechanisms. Full article