Search Results (1,016)

This scoping review synthesized evidence on the psychosocial burden of tuberculosis (TB) and on evidence-based psychosocial interventions aimed at improving treatment adherence. Specifically, it examined: (a) the most frequent mental health problems associated with TB; (b) the main barriers to adherence; (c) the components and effects of psychosocial interventions; and (d) gaps in the literature and directions for future research. Bibliographic searches were conducted in PubMed and Scopus, covering articles published between 2005 and 2025. Nineteen studies met the inclusion criteria. Depression and anxiety were the most frequently reported mental health problems, while psychosis appeared mainly in multidrug-resistant TB (MDR-TB) populations. Across studies, stigma, fear of transmission, socioeconomic disadvantage, treatment duration, and medication side effects emerged as major barriers to adherence. Evidence-based interventions—including psychoeducation, motivational enhancement therapy, cognitive behavioral therapy, acceptance and commitment therapy, and multicomponent psychosocial support—were associated with improved psychological outcomes and, in several studies, better adherence-related indicators. Overall, the evidence suggests that psychosocial distress is common among people with TB and may compromise treatment engagement. Integrating psychosocial and mental health support into TB services may therefore strengthen adherence and improve patient-centered outcomes, although more rigorous and context-sensitive research is still needed. Full article

HIV-associated neurocognitive disorders (HAND) arise from HIV infection of the central nervous system, resulting in chronic neuroinflammation and progressive neuronal damage that impair cognitive, motor, and behavioral functions. Clinically, HAND encompasses a spectrum of neurological impairments ranging from asymptomatic neurocognitive impairment to severe HIV-associated dementia. Despite the widespread use of combination antiretroviral therapy (cART) and significant improvements in the life expectancy of people living with HIV, HAND remains prevalent and continues to pose a major clinical challenge. One of the primary limitations of cART is the limited penetration of many antiretroviral drugs across the blood–brain barrier (BBB), thereby allowing the persistence of viral reservoirs within the CNS and contributing to sustained neuroinflammation and neuronal damage. To address these challenges, novel nanotherapeutic strategies have been developed to enhance the delivery of antiretroviral agents to the brain. These approaches include targeted delivery systems and the co-delivery of therapeutics across the BBB through mechanisms such as receptor-mediated transcytosis and other transport pathways. In this review, we discuss the pathophysiological challenges associated with HAND and recent advances in nanotherapeutic approaches designed to improve treatment efficacy. We also discuss the current state of the art in vitro and in vivo models used to test the efficacy of these advanced therapeutics. Finally, we outline the remaining challenges and future prospects for the development of nanotherapeutics to improve the treatment of HAND. Full article

Objective: This study aimed to compare the effectiveness of online cognitive behavioral therapy (CBT) delivered by an AI chatbot versus human peer counselors (participants were told it was AI) in reducing anxiety symptoms in young adults. Methods: Ninety young adults with mild-to-severe anxiety were randomized to a 4-week intervention of AI-CBT (n = 30), peer-counselor-CBT (n = 30), or a no-intervention control (n = 30). The primary outcome, anxiety, was assessed at baseline, mid-point, and post-intervention. Secondary outcomes (the self-efficacy for exercise, sleep quality), psychotherapy benefit, and qualitative user experiences were also evaluated. Results: Both AI and human-delivered interventions led to significant within-group reductions in anxiety (p < 0.05). However, in the primary intention-to-treat analysis, neither intervention demonstrated a statistically significant advantage over the no-intervention control group at post-intervention. A secondary per-protocol analysis suggested a benefit for the human-delivered intervention among study completers. Notably, participants in the AI group reported significantly lower perceived treatment benefit than the human group (p < 0.001). Qualitative analyses indicated that while AI was valued for accessibility and consistency, human intervention was perceived as more flexible in guidance, individualized, emotionally supportive, and conducive to deeper exploration. Conclusions: In this exploratory trial, both AI- and peer-counselor-CBT showed within-group promise, but the evidence does not support their efficacy over a no-intervention control. The AI’s limitations in providing flexible, emotionally supportive, and personalized interaction likely explain the efficacy gap observed between the two interventions. While AI may serve as a scalable support tool, claims of clinical efficacy require significant caution. These preliminary findings warrant replication in a prospectively registered confirmatory trial. Full article

Sepsis is a life-threatening syndrome driven by a dysregulated host response to infection and is frequently complicated by sepsis-associated encephalopathy (SAE), which contributes to long-term cognitive and neuropsychiatric sequelae. Despite advances in critical care, effective targeted therapies for SAE remain limited. Aquaporin-4 (AQP4), the predominant astrocytic water channel, plays a central role in cerebral water homeostasis, neuroinflammatory signaling, and blood–brain barrier integrity, suggesting its potential involvement in sepsis-induced cerebral dysfunction and neurorepair processes. Polymicrobial sepsis was induced in C57BL/6J mice using the cecal ligation and puncture (CLP) model. AQP4 activity was pharmacologically modulated through either inhibition or facilitation following sepsis induction. Disease severity was assessed using physiological parameters and a modified murine sepsis score. Neurological outcomes were evaluated through standardized behavioral tests assessing locomotor activity, motor coordination, cognitive performance, and depressive-like behavior. Neuroinflammatory and neuronal changes were examined by immunohistochemical analyses of microglial activation (Iba1), astroglial reactivity (GFAP), neuronal integrity (NeuN), and AQP4 expression. Compared with AQP4 facilitation, pharmacological inhibition of AQP4 was associated with a more favorable clinical recovery profile, reflected by lower sepsis severity scores and a more favorable body weight trajectory during the recovery phase. Behavioral analyses demonstrated preserved cognitive function, enhanced motor coordination, and reduced depressive-like behavior in AQP4 inhibitor-treated mice compared with animals receiving AQP4 facilitation. At the histological level, the inhibitor-treated group showed lower microglial and astroglial activation and better preservation of neuronal markers than the facilitator-treated group, whereas AQP4 facilitation exacerbated neuroinflammatory responses and neuronal alterations. These findings highlight a dual, context-dependent role of AQP4 in sepsis-associated cerebral dysfunction. These findings suggest that AQP4 modulation influences sepsis-associated cerebral dysfunction in a context-dependent manner. Within our experimental design, AQP4 facilitation was associated with worse outcomes, whereas AQP4 inhibition was associated with a comparatively more favorable neurobehavioral and histological profile. Full article

Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition that impairs psychological functioning and increases susceptibility to various chronic illnesses, including inflammatory, metabolic, and cognitive disorders. Recent advances in neuroscience and microbiology have identified the brain–gut–microbiota axis as a key mediator of neuroimmune and neuroendocrine regulations, providing new insight into the pathophysiology of PTSD. This review synthesizes current findings from preclinical and clinical studies on gut microbiome alterations in PTSD, highlighting the underlying mechanistic pathways. Dysbiosis in PTSD is associated with immune dysregulation, altered neuroendocrine signaling, and neurotransmitter imbalances. Animal models, particularly those using the single prolonged stress paradigm, have demonstrated behavioral and microbial changes that mirror the characteristics of human PTSD. Human studies have revealed reduced abundance of beneficial bacterial taxa and increased inflammation-associated genera in patients with PTSD. Although emerging evidence supports the role of gut microbiota in PTSD, further research is needed to establish causal relationships and optimize microbiome-targeted therapies. Overall, the gut microbiome offers a novel and potentially modifiable target for the prevention and treatment of PTSD. Full article

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory loss and cognitive decline. Its main pathological features are extracellular plaques composed of aggregated amyloid-β (Aβ) peptides and intracellular neurofibrillary tangles formed by hyperphosphorylated tau. The Aβ hypothesis proposes that Aβ accumulation is a key driver of AD, influencing tau pathology, neuroinflammation, and neurodegeneration. However, therapies that reduce Aβ have shown limited clinical benefits. This suggests that the mechanisms underlying peptide-mediated modulation of AD pathology are much more complex. Both Aβ and tau undergo various post-translational modifications (PTMs) that affect their structure, aggregation, and toxicity. In addition, these abnormal proteins are not efficiently cleared in AD, indicating dysfunction of the protein quality control (PQC) system that maintains proteostasis. Such abnormal PTMs and impaired PQC likely work together to drive disease progression, which may explain the limited success of Aβ-reduction therapies. In this review, we describe how major PTMs, including phosphorylation, ubiquitination, acetylation, glycosylation, and oxidation, regulate the pathological behavior of Aβ and tau. We also discuss the role of the PQC systems in the pathology of AD. We propose that dysregulation of PTMs and PQC constitutes a convergent mechanism underlying AD pathogenesis. Therapeutic strategies targeting these processes may provide more effective and sustained disease modification than approaches focused solely on Aβ reduction. Full article

Background: Posttraumatic stress disorder (PTSD) in ages 3–18 is associated with disturbances in attention, working memory, processing speed, and executive control, as well as persistent difficulties in affect regulation. These neuropsychological vulnerabilities might interfere with learning, peer relationships, and the consolidation of age-appropriate developmental skills. Methods: We conducted a narrative review informed by a structured literature search in PubMed, Scopus, PsycINFO, Embase, EBSCOhost, Web of Science, and Google Scholar. English-language publications from 1990 to 2025 were considered if they examined (1) neuropsychological outcomes of trauma exposure or PTSD in youth and/or (2) interventions with potential to modify neurocognitive or affective functioning, including trauma-focused cognitive behavioral therapy (TF-CBT), mindfulness-based interventions, cognitive rehabilitation strategies, and biofeedback/neurofeedback. Results: Across study designs, trauma exposure and PTSD in youth are consistently linked to impairments in attentional control and executive functioning, with downstream effects on everyday memory and academic performance. Neurobiological studies commonly implicate altered reactivity within amygdala-centered threat circuits and reduced top-down modulation by prefrontal networks, although findings vary with trauma type, developmental stage, and comorbidity. TF-CBT remains the best-supported intervention for pediatric PTSD symptoms; however, neurocognitive outcomes are measured less frequently. Mindfulness-based programs show promise for strengthening attention and emotion regulation when carefully adapted for trauma-exposed youth. Neurofeedback and targeted cognitive rehabilitation represent emerging approaches with preliminary evidence, but the literature remains heterogeneous. Conclusions: An intervention strategy that combines symptom-focused trauma therapy with explicit targeting of executive control, memory processes, and affect regulation may represent a developmentally informed clinical framework for trauma-exposed youth. Future trials need to incorporate standardized neuropsychological endpoints and examine moderators that inform treatment matching. Full article

Digital mental health interventions (DMHIs) can help bridge treatment gaps experienced by young adults with co-occurring substance misuse and depression. However, it remains unclear whether engagement with these interventions differs for young adults with co-occurring conditions compared to those experiencing substance misuse or depression alone. To investigate this issue, we assessed working alliance and subjective engagement with a digital avatar-assisted cognitive-behavioral therapy (CBT) treatment platform (RITch^®CBT), comparing young adults with substance use, depression, and the co-occurrence of the two. A secondary data analysis was conducted on a sample of 99 young adults aged 18–28 years who presented at an urban university clinic. Participants rated their alliance and engagement following two brief sessions of the RITch^®CBT platform. Participants were then categorized into behavioral health groups. Repeated exposure to the program had a greater impact on subjective engagement and usability across diagnostic conditions, but there was no difference in working alliance reported across sessions or behavioral health groups. Further, participants’ depressive symptoms were significantly correlated with the number of sessions they expressed they were willing to engage in and attend. Our findings suggest that digital tools may support early engagement in treatment for young adults, regardless of presenting problem. Full article

Background: Autism Spectrum Disorder (ASD) is characterized by social communication deficits, restricted/repetitive behaviors, sensory processing atypicalities, and impaired adaptive functioning. Neuropsychomotor Therapy of Early Development (TNPEE) integrates motor, cognitive, and socio-emotional domains, promoting functional skills, while Therapy in Aquatic Motor Activities (TAMA) targets motor and sensory engagement. This multicenter, 18-month study compared TNPEE, TAMA, and their combination, hypothesizing that TNPEE would drive core symptom and adaptive improvements, with TAMA providing complementary benefits. Methods: Seventy-seven children with Autism Spectrum Disorder (31.6% females) were recruited from four Italian centers (Palermo, Perugia, Sarno, Messina) and allocated to three groups: TAMA only, TNPEE combined with TAMA, and TNPEE only. Assessments included the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2), the Childhood Autism Rating Scale, Second Edition (CARS-2), Vineland Adaptive Behavior Scales, Sensory Processing Measure and HAARS at baseline, 6, 12, and 18 months. Results: By 18 months, children receiving TNPEE, alone or combined with TAMA, exhibited significant reductions in autism severity, significant improvements in adaptive functioning, and enhanced sensory processing. In contrast, the TAMA-only group demonstrated improvements in aquatic competence (HAARS) but no statistically significant changes in ASD severity or adaptive functioning. Conclusions: TNPEE was the intervention most consistently associated with improvements in ASD severity, adaptive functioning, and sensory processing, whereas TAMA alone showed a more limited impact on broader developmental outcomes. Full article

Background: Head and neck cancer (HNC) presents unique challenges due to impairments in vital functions and appearance. This narrative synthesis of systematic review synthesizes evidence on the prevalence and predictors of distress in HNC and proposes a Multifactorial Cycle of Distress to explain how psychological burdens compromise clinical outcomes. Methods: A systematic search of PubMed and Scopus was conducted (up to June 2025). From 342 articles, 32 were included, covering HNC patients with quantitative or qualitative distress assessments related to quality of life (QoL) and survival. Results: Distress prevalence ranged from 23–47%, with 30% of survivors experiencing persistent symptoms long-term. Key predictors included advanced tumor stage, radiotherapy-induced side effects, and pre-treatment depression, which increased distress risk 2- to 3-fold. Notably, distress was associated with a 25% reduction in radiotherapy completion and a 55% increased risk of mortality. Additionally, 71% of patients experienced decision regret, further impacting outcomes. Psychosocial interventions, including cognitive-behavioral therapy and mindfulness, showed potential in reducing anxiety by 15–20%. Conclusions: Distress in HNC functions as a self-perpetuating cycle where physical morbidity triggers psychological barriers that directly impair treatment adherence and survival. Routine screening using tools like the Distress Thermometer or DIC-2 and integrated multidisciplinary care are essential to break this cycle and improve patient and caregiver well-being. Full article

Frontotemporal dementia (FTD) is a heterogeneous disorder for which disease-modifying treatments are lacking. Non-invasive brain stimulation (NIBS) has emerged as a potential therapeutic approach to modulate dysfunctional neural networks and support residual plasticity. This systematic review aims to provide an updated overview of current NIBS applications across the main clinical syndromes associated with FTD, namely behavioral variant FTD (bvFTD), semantic variant of primary progressive aphasia (svPPA), and nonfluent variant of PPA (nfvPPA). According to PRISMA guidelines, twenty-seven studies investigating NIBS interventions in major FTD phenotypes met the inclusion criteria, predominantly employing transcranial direct current stimulation (tDCS) or repetitive transcranial magnetic stimulation (rTMS). tDCS, particularly when combined with language therapy, consistently improved several language abilities in PPA, with some evidence of maintenance over time. Benefits were most consistently reported in nfvPPA, whereas effects in svPPA were more limited and domain-specific. rTMS studies showed short-term improvements in language and executive functions, especially following stimulation of left frontal regions. In bvFTD, findings were heterogeneous, with social–cognitive outcomes appearing more sensitive to stimulation, whereas global cognitive measures showed more variable effects. NIBS, particularly tDCS combined with behavioral interventions, shows symptomatic potential in selected FTD phenotypes, but methodological heterogeneity and small samples warrant larger, well-controlled trials. Full article

Psychosis presents significant treatment challenges, and standard Cognitive Behavioral Therapy for psychosis often faces limitations due to patient engagement issues and reliance on subjective self-reporting. The integration of Virtual Reality (VR), physiological biosensors, and artificial intelligence offers a transformative opportunity to address these challenges. A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines. A thorough literature search was performed across seven databases. Twelve randomized controlled trials involving 1504 participants were included to assess VR-assisted CBT, VR treatment, and AVATAR therapy. Meta-analyses showed that VR interventions significantly decreased auditory verbal hallucinations (pooled SMD = −0.24, p = 0.0011) and paranoid thoughts (SMD = −0.26, p < 0.0001) compared to control conditions. This review supports integrating multi-modal biosensors to collect real-time, objective physiological data. Such integration enables the development of AI-driven, closed-loop systems that dynamically adjust the virtual environment based on the patient’s physiological state. VR-assisted therapies effectively reduce positive symptoms of psychosis. Incorporating biosensors is a crucial step toward a data-driven approach for personalized, closed-loop psychiatric care. Future efforts should focus on large-scale clinical trials, biomarker validation, and robust ethical frameworks to ensure safe and effective implementation. Full article

Existential, spiritual, and religious themes often evoke strong emotions in therapy, yet little is known about how clients’ emotion regulation relates to these aspects. Spiritual psychotherapy for inpatient residential and intensive treatment (SPIRIT) integrates meaning in life within a cognitive-behavioral treatment (CBT) framework in acute and intensive mental health care and provides an appropriate context for examining this. This qualitative study explores: (1) clients’ beliefs about expressing, managing, or suppressing emotions related to meaning in life, spirituality, or religion (MSR); (2) how emotion regulation strategies (e.g., reappraisal, acceptance, and distress tolerance) are influenced by addressing MSR in therapy; and (3) whether engaging with MSR activates emotion regulation mechanisms for clients’ experienced distress. We analyzed 118 client evaluation forms and 19 semi-structured client interviews using a thematic approach informed by emotion regulation theory. SPIRIT-CBT made implicit beliefs about (MSR-related) emotion regulation explicit, and group interactions sometimes led to changes. Clients showed various regulation strategies, for example: MSR-based reappraisal, connectedness, reflection, and positive refocusing. However, emotional tension and suppression were also reported. Particularly from the interviews, it emerged that the therapy facilitated regulation mechanisms, including narrative processing, perspective shifting, sense-making, and social belonging. Focusing on MSR and existential themes addresses an important gap in mental health care and may contribute to supporting clients’ emotional recovery and overall well-being. Full article

Cyclin-Dependent Kinase-Like 5 (CDKL5) Deficient Disorder (CDD) is a rare X-linked developmental and epileptic encephalopathy characterized by early-onset refractory epilepsy, severe neurodevelopmental impairment, and lifelong disability. Although more than thirty anti-seizure medications are available, most CDD patients remain pharmaco-resistant. Gene-based therapies are emerging, but therapeutic development is hindered by marked clinical heterogeneity, small patient populations, and the lack of robust, translatable brain-based biomarkers for clinical trials. Genetically engineered Cdkl5 mouse models recapitulate many cognitive, behavioral, and molecular features of CDD, yet their utility is limited by the absence of overt seizures, precluding seizure-based outcome measures. Here, we establish high-definition brain network (HDBN) biomarkers using advanced diffusion MRI tractography combined with graph-theoretical analysis to quantify whole-brain network organization in Cdkl5 knockout mice. Diffusion MRI enables non-invasive mapping of axonal connectivity by leveraging anisotropic water diffusion, while high-angular-resolution acquisition overcomes key limitations of conventional diffusion tensor imaging in regions with complex fiber architecture. We demonstrate that Cdkl5 knockout mice exhibit reproducible and region-specific disruptions in brain network organization, prominently affecting the somatosensory and somatomotor cortex, hippocampus, hypothalamus, amygdala, and superior colliculus—regions implicated in cognition, learning and memory, homeostasis, anxiety, and visual–motor function. In contrast, networks within the entorhinal cortex remain largely preserved. These findings identify HDBN metrics as sensitive, non-invasive biomarkers that capture clinically relevant circuit-level abnormalities in CDD. Because diffusion MRI–based network analyses are directly translatable across species, HDBN biomarkers provide a unified framework for therapeutic evaluation in mouse models, large animals, and human clinical trials, enabling longitudinal monitoring of disease progression and treatment response. Full article

Home has been recognized as a health infrastructure through hospital-at-home, home care, and direct-to-consumer wellness and fitness products. However, the patient home environment has been largely overlooked by healthcare as a means to improve therapy outcomes for difficult-to-treat chronic conditions, such as migraine; high-impact pain; and treatment-resistant depression, anxiety, or insomnia. Growing research evidence enables the formulation of a therapeutic home environment standard consisting of three pillars: biophilic design, indoor environmental quality, and intentional self-care spaces that serve as habit cues and foster sleep hygiene, stress management, relaxation, physical activity, and social interactions. Together, these environmental and behavioral interventions can transform real-world inputs into clinical benefits through autonomic, circadian, and emotional regulation. We also highlight the converging roles of self-management, self-efficacy, self-regulation, and self-compassion in sustaining patient engagement and healing at home. The applicability of the therapeutic home environment as an adjunct is illustrated in the case of chronic migraine, a debilitating neurological condition commonly associated with comorbidities. Current challenges in achieving migraine freedom with FDA-approved pharmacotherapies, neuromodulation devices, and digital health technologies are underscored by the high prevalence of refractory, chronic, episodic, and pediatric migraine. Perspectives on developing a personalized, multimodal cure for migraine are illustrated through a hypothetical drug + digital combination therapy comprising anti-CGRP drugs and an AI-powered digital health platform that promotes daily self-care practices within the therapeutic home environments. In conclusion, achieving sustained freedom from high-morbidity conditions requires end-to-end care ecosystems that integrate pharmacological, cognitive, behavioral, and environmental interventions into real-world settings. Full article