Search Results (338)

Fear is a transdiagnostic construct implicated in multiple psychiatric disorders, reflecting a partial dissociation between clinical phenotypes and underlying neurobiological mechanisms. Converging evidence suggests that aberrant fear processing plays a central role in cognitive and psychopathological models of psychosis. In this narrative review, we synthesize evidence on the neurobiological mechanisms of aberrant fear modulation in schizophrenia from a translational perspective, integrating findings from neuroimaging, preclinical models, pharmacological interventions, and psychotherapy. Schizophrenia is characterized by aberrant emotional processing and inappropriate neural responses to stimuli with reduced or absent objective salience, reflecting impaired discrimination of relevant environmental information. At the system level, evidence implicates dysregulation of cortico-limbic and salience-processing networks in altered fear learning, threat appraisal, and emotional prediction. Neurochemical findings indicate that dopamine–glutamate dysregulation and associated intracellular signaling pathways act as upstream modulatory mechanisms contributing to these network-level abnormalities. Therapeutic interventions, including antipsychotic drugs and psychotherapeutic approaches, partially modulate these systems, although effects remain heterogeneous. Overall, the evidence supports a hierarchical model in which aberrant fear processing in schizophrenia arises from disrupted salience attribution and impaired integration across cognitive, affective, and neurobiological levels. This intermediate dysfunction links molecular alterations to large-scale network disturbances and clinical symptom expression, providing a framework for more mechanism-based therapeutic strategies. Full article

Session dialogue assessment based on machine learning is gradually becoming an effective solution for therapeutic alliance measurement which is an important factor for successful psychotherapy. However, most existing models assume clean and pre-structured dialogue transcripts, whereas real-world counseling documentation often contains heterogeneous case reports. This gap limits the applicability of current automated assessment models in realistic documentation scenarios. In this work, we propose a framework for automated working alliance assessment from complex, multilingual reports. First, language-specific BERT models are fine-tuned to process case reports across different languages, enabling accurate speaker role delineation and dialogue structuring. Second, Gemini-2.5-Flash is leveraged to annotate the dialogues with working alliance ratings. Third, a hybrid feature representation strategy is then developed to jointly capture linguistic style and semantic content from the counseling dialogues. Furthermore, an entropy-based mutual information analysis is conducted to identify the most informative linguistic features. Finally, the extracted hybrid features serve as inputs to XGBoost for alliance assessment. In experiments, the proposed framework shows better performance in the comparison with SOTA methods and generalization ability. Full article

Background: This systematic review and meta-analysis evaluates the efficacy and safety of psilocybin-assisted psychotherapy (PAP) for adults with major depressive disorder (MDD). Methods: A PROSPERO-registered search (CRD42024561979) of CENTRAL, Scopus, PsycINFO, and MEDLINE (2010–2024) identified clinical trials assessing PAP. Risk of bias was assessed using RoB 2 for randomized controlled trials (RCTs), while non-randomized studies were appraised separately. Evidence certainty was evaluated using GRADE. Results: Ten trials were included; eight provided quantitative data. PAP was associated with large short-term reductions in depressive symptom severity. The overall pooled effect was large (d = 1.15, 95% CI 0.83–1.48), though within-subject designs yielded larger estimates (d = 1.63) than between-subject controlled comparisons (d = 0.96). Adverse events were transient and manageable, with no increased risk of serious adverse events on dosing days. Primary risk-of-bias concerns included functional unblinding. Conclusions: PAP may produce clinically meaningful, large short-term reductions in depressive symptoms. However, long-term efficacy remains understudied, and the overall certainty of evidence is low to moderate. Larger, rigorously blinded trials are required. Full article

Post-traumatic stress disorder (PTSD) remains inadequately treated by existing pharmacological and psychological interventions, prompting growing interest in psychedelic-assisted psychotherapy. Although randomised controlled trials have evaluated several psychedelic agents for PTSD, to our knowledge, no prior PTSD-specific synthesis has quantitatively examined multiple agent classes within a single review framework. This systematic review and meta-analysis searched PsycINFO, CINAHL, Embase, MEDLINE, and clinical trial registries to identify RCTs of psychedelic-assisted psychotherapy for PTSD. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool, and random-effects meta-analyses were conducted for efficacy outcomes; safety and therapeutic protocols were synthesised narratively. Eleven RCTs involving 358 participants met inclusion criteria, evaluating MDMA, ketamine, and cannabidiol, of which eight contributed to meta-analyses. MDMA-assisted psychotherapy demonstrated a significant moderate-to-large reduction in PTSD symptom severity with negligible heterogeneity, and participants were significantly more likely to achieve clinical response and loss of PTSD diagnosis. The pooled effect for ketamine was small and non-significant, and a single cannabidiol trial showed no clear benefit. All agents were generally well tolerated. MDMA-assisted psychotherapy showed a promising efficacy signal for PTSD symptom reduction, although safety data were heterogenous and remain insufficient for strong comparative conclusions. Evidence for ketamine and cannabidiol remains too limited to support clinical implementation and it is noted that the current evidence base is dominated by MDMA trials. Further adequately powered trials with standardised outcomes and direct comparative studies across agents are needed. Full article

Psychotherapy is an effective treatment for a wide range of mental disorders, yet treatment outcomes remain highly variable across patients. The emerging field of precision psychotherapy seeks to address this variability by tailoring interventions to the characteristics and needs of individual patients. Recent advances in artificial intelligence (AI) have accelerated this effort by enabling predictive models that identify patients at risk for treatment non-response and support personalized treatment selection. However, most current approaches to precision psychotherapy focus primarily on predicting outcomes or stratifying patients into subgroups, while offering limited tools for supporting clinical decision-making within the therapeutic process itself. This paper proposes that advancing precision psychotherapy may benefit from conceptual frameworks capable of representing therapeutic interactions as they unfold within clinical sessions. Psychotherapy is fundamentally a communicative process in which psychological change is understood to emerge through the evolving dialogue between therapist and patient. To help structure this process, we introduce a dimensional framework that conceptualizes mental activity as organized across five hierarchical dimensions: action, thought, emotion, experience, and being. These dimensions provide a structured representation of the forms in which psychological activity appears in therapeutic dialogue and may allow therapeutic interaction to be described as a sequence of dimensional transitions between therapist and patient. Such a representation could serve as a conceptual basis for the future development of computational tools aimed at analyzing therapeutic dialogue and identifying patterns that may be associated with therapeutic processes such as change, rupture, or shifts in interaction. Integrated with AI-based analysis of psychotherapy sessions, this framework may inform the design of systems intended to support the analysis of therapeutic processes, such as monitoring patterns of interaction or identifying potential shifts in patient experience, while preserving the central role of clinical judgment. By providing a formalized representation of therapeutic dialogue, this approach is intended as a conceptual and methodological step toward the development of more precise, process-informed approaches to psychotherapy. Full article

Background/Objectives: Limited data exist on care delivery, engagement, and clinical outcomes among rural populations accessing telehealth mental health services, particularly within integrated psychotherapy-and-psychiatry models. This retrospective observational 12-week cohort study aimed to examine access, engagement, and preliminary clinical outcomes for rural and non-rural patients receiving services through a national outpatient telehealth mental health program. Engagement and clinical outcomes were expected to be comparable among rural and non-rural patients. Methods: Descriptive and inferential analyses were conducted to examine access to care, engagement, and changes in depressive symptoms, anxiety symptoms, and suicidal ideation among rural and non-rural patients receiving telehealth mental health services over a 12-week treatment period. Clinical outcomes were evaluated using the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7). The full sample included 8354 rural and 177,864 non-rural patients and was used to assess access and engagement in treatment. A clinical sample (rural n = 2096; non-rural n = 43,067) that included patients who completed 12 weeks of care was further examined to assess symptom improvement outcomes. Results: Rural patients demonstrated greater baseline symptom severity and medical complexity relative to non-rural patients. Mean time to first appointment was 5.2 days among rural patients and 5.5 days among non-rural patients, with comparable engagement across groups and rural patients averaging approximately 1–2 touch points per week in care. Patient satisfaction ratings averaged 4.9 out of 5. Within the clinical sample, rural patients demonstrated clinically meaningful symptom improvement across depression and anxiety outcomes. Mean PHQ-9 scores improved by 7.0 points (95% CI: 6.72–7.28), and mean GAD-7 scores improved by 6.1 points (95% CI: 5.83–6.37). Additionally, 70.5% of rural patients achieved a minimal clinically important difference in PHQ-9 or GAD-7 scores, and 66.7% of patients reporting suicidal ideation at baseline no longer endorsed suicidal ideation at endline. Conclusions: These findings support the feasibility and preliminary effectiveness of large-scale virtual mental health care models for rural populations. Rural patients demonstrated engagement and clinical outcomes comparable to non-rural patients despite greater baseline severity and medical complexity. Full article

Mental health issues, such as depression and anxiety, are rising globally, and while conventional therapies like medications and psychotherapy remain common, they face limitations, including side effects and accessibility. This highlights the need for effective non-pharmacological interventions. Painting-based art interventions are a promising non-pharmacological approach for improving scale-assessed mental health outcomes, but quantitative evidence across age groups and outcome types remains limited. This meta-analysis synthesizes data from 45 randomized controlled trials to assess the impact of painting-based art interventions on mental health. The study explores potential moderating factors such as intervention duration, type of art, gender, and age group. A rigorous quality assessment of included studies was performed using Cochrane’s risk of bias tool. The pooled effect size for painting-based interventions on mental health was significant, indicating a large positive impact. Subgroup analyses revealed that interventions of various durations, art forms, and gender compositions produced similar effects. Notably, older adults benefited the most from these interventions. Painting-based art interventions were associated with improved scale-assessed mental health outcomes. These findings should be interpreted as evidence for one visual art-making approach within broader art therapy practice, rather than as defining art therapy solely by painting-based methods. Full article

Benzodiazepines (BZDs) are among the most widely prescribed psychotropic drugs in modern healthcare, primarily used as anxiolytics, hypnotics, anticonvulsants, and muscle relaxants. However, rising global consumption and prolonged use raise significant concerns about safety and dependence. Recent studies report that up to 35.8% of patients continue BZD therapy beyond three months, with long-term use observed in over 5% of the general population. These patterns highlight the need for evidence-based strategies to improve prescribing practices. BZDs are recommended primarily for short-term management of severe anxiety or transient insomnia, typically limited to 2–4 weeks. In anxiety disorders, SSRIs and SNRIs are first-line treatments. BZD use is particularly discouraged in older adults due to increased risks of cognitive impairment, falls, and dependence. Rational prescribing requires individualized assessment, minimal effective dosing, gradual withdrawal protocols, and patient education. Enhanced regulatory oversight and improved access to psychotherapy are essential for safer benzodiazepine use. Full article

Trauma-related autobiographical memories can manifest as involuntary, vivid, emotionally charged intrusions that perpetuate avoidance, negative emotions, and functional impairment. While these memories are central to post-traumatic stress disorder (PTSD), they also occur across diagnoses and are often reported in depressive disorders, including treatment-resistant depression (TRD). Although trauma-focused psychotherapies are effective, their routine implementation can be limited by dropout, residual symptoms, and difficulty engaging patients with severe depression, dissociation, or complex comorbidities. Intranasal esketamine is an approved rapid-acting treatment for TRD and has been hypothesized to create transient conditions that may facilitate psychotherapeutic work on traumatic memories. This narrative review synthesizes clinical and translational evidence on ketamine and esketamine for PTSD and trauma-related symptoms, with particular attention to the distinction between intravenous ketamine studies, intranasal esketamine data, and studies combining these compounds with psychotherapy. Currently, the most robust evidence in this area comes from three randomised trials of intravenous ketamine for PTSD. In contrast, data on intranasal esketamine and psychotherapy-combination approaches are mainly from pilot studies, retrospective analyses, or case reports. We additionally propose a pragmatic, feasibility-oriented protocol integrating intranasal esketamine with a structured traumatic-memory intervention for TRD patients with clinically relevant trauma-memory symptoms. The novelty of the proposal does not lie in claiming efficacy, but in specifying a standardised imagery rescripting module and predefining two timing hypotheses. The proposal targets patients with TRD with relevant trauma-memory symptoms, and it embeds the intervention within existing esketamine-care infrastructure. Overall, the available literature supports mechanistic plausibility and preliminary feasibility more than clinical efficacy. The evidence base remains small, heterogeneous, and largely uncontrolled, and controlled studies are needed before efficacy claims can be made. 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

The therapeutic alliance is widely recognized as a central mechanism of change in psychotherapy; however, much existing research risks reifying it as a measurable and static construct, obscuring its fluid, co-constructed nature and the ways it is shaped by power, identity, and social context. This study aimed to explore how psychotherapists understand, construct, and enact the therapeutic alliance in their everyday practice, with particular attention to diversity, anxiety, rupture, and the reciprocal impact of the therapeutic relationship on the therapist. Using a qualitative design, semi-structured interviews were conducted with 14 psychotherapists primarily working in private practice, and the data were analyzed using reflexive thematic analysis. Six interrelated themes were identified: moving from technique to relational presence; diversity as relational negotiation; anxiety as a co-created relational process; rupture as inevitable and generative; therapist transformation through the therapeutic relationship; and navigating professional role and human authenticity. The findings suggest that effective therapeutic work relies less on rigid adherence to technique and more on reflexivity, emotional attunement, and a willingness to engage with discomfort, difference, and relational rupture. The study highlights the need for psychotherapy training to prioritize relational, ethical, and reflexive capacities alongside technical skills, and contributes a more process-oriented understanding of the therapeutic alliance from therapists’ lived perspectives. Full article

Peripheral nerves provide a direct connection between the brain and the tumor microenvironment. This connection allows the nervous system to influence processes associated with the development, progression, and metastasis of different tumor types. Therefore, tumor innervation by peripheral nerve fibers is currently emerging as a characteristic that contributes to multiple hallmarks of cancer. Several experimental studies have shown that cancer progression involves actively inducing the ingrowth of autonomic and sensory nerve fibers into tumor tissue. In this process, known as neoaxonogenesis, cancer and other cells in the tumor microenvironment play an important role by synthesizing and releasing neurotrophic factors (e.g., nerve growth factor, brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor), axonal guidance molecules (netrins, semaphorins, ephrins, slits), exosomes (containing microRNA and axonal guidance molecules), and other molecules present in the tumor microenvironment (e.g., granulocyte colony-stimulating factor, leukemia inhibitory factor), which modulate the ingrowth of nerve fibers into the tumor. This results in an increased nerve supply to tumor tissue, which is primarily linked to its growth. However, there are also studies demonstrating the protective effects of increased nerve fiber density against processes associated with cancer progression in certain types of cancer. The findings from these studies contribute to the complexity of neuro-cancer interactions, which is probably based on the type of cancer and the physiological specializations of the nerve fibers in a given organ. Despite contrasting findings, the stimulatory effects of nerve fibers on cancer growth are supported by several studies that described reducing the negative impact of nerve fibers on tumors and thus inhibiting cancer progression. The most significant approaches to reducing neural effects appear to be denervation, the administration of neurotransmitter receptor antagonists, the administration of local anesthetics, and the administration of antibodies against neurotrophic factors. Other significant approaches include methods that improve quality of life, such as psychotherapy and heart rate variability biofeedback. Despite their therapeutic potential, there are several limitations to using approaches that manipulate cancer innervation in clinical practice. These limitations include impaired normal tissue function and nervous system function, as well as the problematic direct application of the therapeutic agent to the tumor site, dosage-dependent, cancer type-dependent, cancer stage-dependent, duration-dependent, and timing-dependent effects. Procedures that modify neoaxonogenesis and nerve fiber signaling appear to be a promising new therapeutic approach in oncology. However, more research is needed to better understand their effects on cancer progression. In the future, the assessment of the presence and density of nerve fibers in tumors, as well as the evaluation of approaches aimed at reducing their negative impact, could be part of personalized anticancer therapy. As part of this therapy, a fresh tumor sample would be collected from the patient to generate patient-derived organoid models to test and consider the possibility of using supportive therapy and to predict its efficacy. Based on these results, it would be possible to evaluate the applicability of nerve-fiber-targeted therapy for a given patient. This review article summarizes and describes the current knowledge concerning the significance of nerve fibers in cancer progression, with a particular emphasis on neoaxonogenesis in tumors and the various factors that influence this process. Full article

Background: Intimate partner violence (IPV) is a pervasive medical concern affecting millions of people worldwide, with the majority being women. IPV is linked to a number of long-term physical and mental health consequences, including brain injuries and associated persistent post-concussion symptoms (PPCS) and post-traumatic stress disorder (PTSD). Despite the high prevalence of these conditions, there is sparse literature assessing accessible and effective therapeutic avenues specific to IPV victim-survivors. Methods: This narrative review had two aims: to identify therapeutic studies addressing PTSD and PPCS in women IPV survivors, and to provide a narrative overview of potential therapeutic categories, including psychotherapy, mindfulness and meditation, exercise, and pharmacotherapy. A comprehensive literature search was conducted using PubMed and Google Scholar. Inclusion criteria required full-text, peer-reviewed articles published in English, conducted in women with a history of IPV, reporting treatment outcomes related to PTSD or PPCS. Where no IPV-specific evidence was identified, findings from closely related populations including military veterans, athletes, and general TBI samples were narratively reviewed to inform potential therapeutic implications. Results: Nineteen studies addressing PTSD in women IPV survivors were identified, predominantly utilizing psychotherapeutic or mindfulness and meditation-based interventions. No intervention studies targeting PPCS specifically in IPV survivors were identified. Consequently, results for PPCS are largely extrapolated from adjacent populations. Although potential therapeutic avenues were narratively identified across psychotherapy, mindfulness and meditation, exercise, and pharmacotherapy, IPV-specific evidence remains limited, and validation for PTSD and PPCS in this population is needed before clinical recommendations can be made. Conclusions: While 19 studies identified promising therapeutic options for IPV-related PTSD, no IPV-specific PPCS interventions were identified, and implications for PPCS management remain largely inferential. Validation and integrated trauma-informed approaches addressing the intersection of PTSD and PPCS are needed for this understudied population. Full article

This review examines what constitutes heart rate variability (HRV), the relationship between HRV and the autonomic nervous system, and the physiology driving HRV. HRV is correlated with vagal nerve activity and parasympathetic nervous activation. Higher HRV is correlated with youth, active lifestyle, adaptive capacity, and good health. Next, the review examines the medical significance of HRV, especially the correlation between lower HRV and the presence of medical and psychological disorders. In general, HRV serves as a biomarker for health and disease, an index of autonomic nervous system dysregulation, an index of prefrontal cortical functionality, and a marker for psychopathology across diagnoses. Higher HRV is associated with several characteristics associated with successful psychotherapy and hypnotherapy: social engagement, compassion, emotional regulation, and cognitive flexibility. Given this association, somatic regulation should be regarded as integral to treatment alongside psychotherapy and hypnosis. Understanding HRV can enable the psychotherapist and hypnotherapist to optimize treatment. In effect, the therapist can harness the power of the brain and nervous system to better prepare the patient for therapy and to enhance the process of therapy. This review encourages therapists to utilize several strategies and interventions to increase patients’ HRV levels prior to and during therapy. The review will be most applicable for those hypnotherapists who integrate hypnosis into counseling and psychotherapy. The review describes the process by which HRV biofeedback training guides the individual to voluntarily increase HRV. It also identifies a number of lifestyle parameters and self-care practices (including self-hypnosis) that increase HRV. Encouraging lifestyle and self-care practices to increase HRV can support a greater response to hypnotherapy and psychotherapy. With additional training, hypnotherapists can integrate HRV biofeedback into a hypnosis practice. Further, several simple interventions already within the scope of most hypnosis practitioners can be utilized to enhance HRV at the beginning of a hypnotherapy process, and again during the process of therapy. Full article