Alzheimer's disease: Current therapeutic strategies and emerging perspectives for multifactorial intervention.

ABSTRACT After the sad death of our colleague Ilse Grubrich-Simitis, one aim of this paper is to revisit one of her groundbreaking works, “Drive or Trauma – Drive and Trauma” (1987) after almost 40 years. Grubrich-Simitis integrated drive and object relational aspects on the one hand and trauma-specific perspectives on the other in a creative way, as we discuss regarding some conceptual developments in contemporary psychoanalysis. A short case example illustrates the conceptual richness for treating chronically depressed patients with early trauma available to clinicians today. Considering both drive and trauma belongs to the strengths of modern psychoanalytic treatment techniques, which we would like to discuss alongside recent findings of the LAC1 depression study [Comparative outcome study of psychoanalytic and cognitive behavioral long-term psychotherapy with chronically depressed patients], indicating that these difficult-to-treat patients profit especially well from psychoanalysis.

Mild cognitive impairment (MCI) and dementia represent significant global health challenges requiring innovative intervention approaches. Computerized cognitive training (CCT) offers promising alternatives to traditional face-to-face interventions, providing flexibility and personalized care for individuals with cognitive disorders. This study evaluated the usability of INFORMA, a novel software platform based on Cognitive Activation Therapy (CAT), for delivering telerehabilitation to participants with MCI and mild-to-moderate dementia. A prospective, non-interventional multicenter study enrolled 241 participants (MMSE 20-30, CDR 0.5-1) from 12 Italian Centers for Cognitive Disorders and Dementia. Participants engaged in an 8-week tablet-based telerehabilitation program with weekly supervision. Usability was assessed using the System Usability Scale (SUS), Task Completion Rate (TCR), and Relative Task Completion Time (R-TCT), supplemented by participant and caregiver questionnaires. Of 219 completing participants (mean age 73.5 years), the mean SUS score was 82.0 (95% CI: 80.3-83.8), with 84% exceeding the usability threshold (SUS score > 68). Mean TCR reached 97.8%, while 70.3% demonstrated improved R-TCT. Higher SUS scores correlated with education and MMSE scores but decreased with age. Satisfaction ratings exceeded 87% for participants and 95% for caregivers. INFORMA demonstrated high usability across all educational and cognitive levels, with the hybrid model combining automated exercises and professional supervision being well-received. INFORMA showed significant promise as a user-friendly computerized cognitive stimulation tool, supporting its potential efficacy for MCI and dementia interventions and warranting further therapeutic efficacy studies.

There is growing interest in novel approaches to treating posttraumatic stress disorder (PTSD), including the use of psychedelic substances combined with psychotherapy, often referred to as psychedelic-assisted therapy, to better meet the needs of patients who do not prefer or respond to traditional evidence-based treatments. Among these treatments, 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy (MDMA-AT) has shown promising outcomes in recent randomized controlled trials, with high response and remission rates. However, the U.S. Food and Drug Administration declined to approve MDMA-AT for marketable use in August 2024 due to concerns about insufficient evidence. This paper reviews the current state of the scientific literature on MDMA-AT for PTSD, including putative mechanisms of action; key strengths and limitations of methodologies used to date; gaps in the evidence; and clinical, ethical, and regulatory considerations. Key limitations to be addressed in future studies include challenges with blinding, a lack of active comparator conditions, a lack of head-to-head comparisons of different models, inadequate safety monitoring, and limited sample generalizability. We describe emerging research that integrates MDMA with established trauma-focused therapies, such as prolonged exposure therapy and cognitive processing therapy, to leverage MDMA's effects on known cognitive behavioral mechanisms of action and support future implementation. Future research directions for advancing knowledge and consideration for the dissemination of MDMA-AT are discussed.

Avoidant Restrictive Food Intake Disorder (ARFID) is a recently recognized feeding and eating disorder characterized by restricted or avoidance of food intake due to the sensory characteristics of the food or fear of the unpleasant consequences of eating without concerns about body image. It commonly presents in childhood and can lead to serious nutritional and developmental outcomes. While reports from high-income countries are increasing, data from low-resource settings remain scarce. In such settings, malnutrition is often attributed to food insecurity or infection, making ARFID an under-recognized cause of severe nutritional deficiency. A seven-year-old male patient presented with generalized edema, night blindness, and growth failure. He had a highly restricted diet, mainly consisting of injera and bread, with complete avoidance of fruits, vegetables, and animal products due to fear. Physical examination and investigations diagnosed both macronutrient (edematous malnutrition) and micronutrient deficiencies (hypoalbuminemia, mixed anemia including iron and megaloblastic anemia, and vitamin A deficiency). Based on the feeding history and clinical features, he was diagnosed with ARFID. Although Hymenolepis nana infection was present and likely contributed to acute clinical deterioration, the child's restrictive eating behavior had been present for several years prior to the infection and represented the primary underlying cause of nutritional deficiency. Nutritional rehabilitation through nasogastric tube feeding and behavioral cognitive therapy led to significant clinical and dietary improvements. Food selectivity may be a common problem in children, especially in pre-school age groups, but it doesn't lead to nutritional deficiency. ARFID is one of the avoidant food disorders commonly found in the childhood age group, which may lead to different nutritional deficiencies in both developed and developing countries. To prevent the acute and long-term complications of ARFID, it's important to have a high index of diagnostic suspicion in varied clinical settings. This case highlights that ARFID can occur even in low-resource settings, where nutritional deficiencies are often presumed to result solely from poverty or infection. Taking a detailed dietary history and exploring reasons for food avoidance are crucial for differentiating ARFID from other causes of malnutrition. Early recognition and multidisciplinary care can prevent severe complications and improve outcomes.

Mindfulness-based interventions (MBIs) have shown promising effects across diverse areas of psychiatry, yet their specific role in bereavement remains insufficiently synthesized. Bereavement is a universal but heterogeneous process, with a minority of individuals at risk of developing prolonged grief disorder (PGD). Understanding the potential benefits of MBIs in this context is crucial for informing clinical practice. Following the methodological framework of systematized narrative reviews, a comprehensive literature search was conducted across major databases. Eligible studies included empirical investigations of MBIs applied to bereavement, without restrictions on type of loss, population, or intervention format. Data were narratively synthesized and summarized in tables; no meta-analysis was performed. Seventeen studies met inclusion criteria. The strongest evidence was found for Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy (MBCT), which demonstrated improvements in grief-related distress, depressive symptoms, and psychological well-being. Across interventions, MBIs were associated with reductions in rumination and experiential avoidance, increased self-compassion, and enhanced emotion regulation. However, most studies were limited by small sample sizes, heterogeneous outcome measures, and a lack of long-term follow-up. MBIs show promise as adjunctive interventions in bereavement care, targeting mechanisms central to grief adaptation, including acceptance, decentering, and self-compassion. Nevertheless, the evidence remains preliminary and methodologically constrained. Future high-quality randomized controlled trials are needed to establish efficacy, clarify mechanisms of action, and define the role of MBIs alongside established grief therapies.

ABSTRACT Background Chronic ischemic stroke survivors experience cognitive, emotional, and participation-related limitations that affect reintegration into the community and life satisfaction. Mindfulness-Based Stress Reduction (MBSR) and Cognitive Rehabilitation Therapy (CRT) may aid in the recovery process of stroke survivors. These rehabilitation programs may act through different mechanisms. However, little is known about the domain-specific responsiveness of stroke survivors to these rehabilitation programs. Objectives The objectives of this study were to investigate the domain-specific functional responsiveness of stroke survivors with chronic ischemic stroke to both mindfulness-based and cognitive rehabilitation programs, especially in terms of participation, communication, and cognitive outcomes. Methods This controlled longitudinal study consisted of 36 stroke survivors with chronic ischemic stroke who were randomly assigned to one of the three groups: MBSR, cognitive rehabilitation based on Powell’s protocol, or a control group. Participants underwent the Stroke Impact Scale (SIS) assessment. Changes in SIS domain scores from baseline to post-intervention and two-month follow-up were evaluated using repeated measures analysis of variance. Results The results revealed that the patterns of domain-specific responsiveness varied between the interventions. It was noted that the mindfulness-based intervention showed better recovery in cognitive-affective domains, especially memory, thinking, and participation/role function. Conversely, cognitive rehabilitation showed better recovery in communication-related outcomes. No significant recovery was noted in the control group for any of the domains. Conclusions The study suggests that both mindfulness-based and cognitive rehabilitation interventions facilitate recovery through unique pathways in chronic ischemic stroke survivors. Domain-specific responsiveness may be a valuable tool for providing clinically relevant information for tailoring rehabilitation approaches according to individual patient characteristics.

Background Social Anxiety Disorder (SAD) is maintained by maladaptive cognitive patterns, yet most virtual reality (VR) interventions focus on exposure-based strategies, neglecting cognitive restructuring. To address this gap, we developed VR CHANGE, a mobile-based virtual reality cognitive therapy (VRCT) program targeting cognitive distortions in SAD. The program guides users through structured training tasks, including identifying automatic thoughts, recognizing cognitive distortions, and modifying maladaptive thinking. This study examined the program’s feasibility and validity. Methods Twenty-four individuals with SAD completed the VRCT program, consisting of Theoretical Learning, Basic Training (beginner, intermediate, and advanced), and Applied Training, in two sessions spaced 1 week apart. Data collected for analysis included automatically recorded performance on behavioral tasks within the program, measures of social anxiety symptoms and cognitive distortions before and after the program, and a post-program user experience evaluation. Results Participants showed significant reductions in social anxiety and cognitive distortion scores post-intervention. Treatment satisfaction and content comprehension were high, and user experience ratings fell within an acceptable range. Behavioral data supported the program’s construct, content, and convergent validity. In detail, error rates in cognitive distortion identification decreased with progression through training levels, and thought modification ability was associated with baseline cognitive distortion levels. Social anxiety-related scenario-induced distress increased appropriately across stages and correlated with social anxiety scales. Content validity was supported by differentiated task difficulty across cognitive distortion types. Conclusion VR CHANGE demonstrated strong feasibility and validity as a cognitive therapy intervention for SAD, suggesting that its structured, multimedia-supported format reduced cognitive load and facilitated therapeutic learning. The findings support its value as a subject for a large-scale randomized controlled trial to determine whether VRCT can be effectively used to treat SAD.

This paper examined the psychological, social and nutritional health-related aspects that relate to drug use among higher education students. The study was a descriptive cross-sectional study on 1,055 students in various colleges. The data was obtained by using self-administered questionnaire, which measured demographic, psychological, and social variables and nutritional health indicators in terms of drug use. The study identified living alone as a significant demographic predictor in the multivariate logistic regression analysis. Positive and neutral attitudes towards drug use (OR = 0.044 and OR = 0.324, respectively), as well as protective or irregular behavioral practices (OR = 0.002) were significantly protective, psychologically. There were no significant differences in nutritional health indicators between users and non-users, but 98 % of the entire population sample had indications of mild malnutrition risk. To conclude, the issue of drug use among university students was more of a psychological and social process rather than a physical and nutritional health issue. Prevention plans are supposed to focus on cognitive and behavioral therapies. Even though drug use has not reached the stage of demonstrating any quantifiable physical health impact, the fact that malnutrition risk is high demonstrates that parallel nutrition-based health promotion interventions are necessary. KEYWORDS Cognitive–behavioral interventions, community influences, malnutrition risk, preventive strategies, psycho-emotional determinants, substance consumption.

Moral injury (MI) is a proposed syndrome that develops when someone is exposed to, participates in, or fails to prevent an action that fundamentally violates their moral code and results in maladaptive cognitions about oneself and humanity. Post-traumatic stress disorder (PTSD) is a disorder based on maladaptive cognitions that develops following a traumatic event. Decades of PTSD research underscore that the experience of mental defeat, or the perception that one was completely defeated during the traumatic event, plays a significant role in the development and maintenance of PTSD. Less work, however, has been done to develop a cognitive model of MI and to understand how mental defeat plays a role in the underlying maladaptive cognitions. Understanding the cognitive model of MI is key to developing effective cognitive therapy. In this paper, we first examine the role of mental defeat in PTSD cognitive models and then compare the PTSD cognitive model to proposed cognitive models for MI. Based on these comparisons and overlapping symptomology, we suggest that mental defeat plays an important role in MI cognitive models.

Internet-based cognitive behavioral therapy has demonstrated encouraging outcomes for patients diagnosed with social anxiety disorder (SAD). However, the impact of additional therapist-guidance remains debatable. The present study evaluates the effectiveness of the cognitive therapy app "Mindable: Social Phobia" comparing a therapist-guided (vCT) and unguided self-help app (iCT) against a waitlist control group (WLC). We assigned 164 patients diagnosed with SAD randomly to one of the three groups, treatment lasting 12 weeks with 8 manualized video-conference delivered sessions in vCT. Assessments took place pre-treatment, midtreatment, posttreatment and follow-up 6 months after treatment (follow-up). The primary outcome was clinician-rated symptom severity (Liebowitz Social Anxiety Scale; LSAS), secondary outcomes included symptoms of depression and interpersonal pleasure. Drop-out rates were 9.3% in WLC, 42.6% in iCT and 15% in vCT (χ2=19.5, p<.01). Both treatments reached significant stronger reduction of LSAS scores compared to WLC in all analyses (d [iCT vs. WLC]=-1.01, d [vCT vs. WLC]=-1.1). Using multiple imputation analyses, no significant difference was found in the LSAS between the two treatment groups (t=-0.22, p=.830, d=0.04). Patterns of results were similar for secondary outcomes. At follow-up, both treatment groups maintained treatment gains. Overall, the app demonstrates promising results, with patients clearly benefiting from the intervention. The add-on effects of the therapist-guidance favor provision of blended care as it prevents drop-out.

Psychosocial interventions targeting cognition improve objective cognitive test performance, strategy use, emotional well-being, and quality of life in individuals with mild cognitive impairment and early dementia. These interventions have been labeled as cognitive training, cognitive remediation, cognitive rehabilitation, cognitive stimulation, and overlap with cognitive (psycho)therapy. The inconsistent labeling of the interventions has resulted in ambiguity of what a cognitive intervention entails and limits the translation of interventions into clinical practice. To address this, we propose a new framework, "PICC-M", that classifies cognitive interventions based on five active ingredients or the mechanisms resulting in clinically significant change. These ingredients are psychotherapeutic support (P), individualized patient goals (I), cognitive exercises (C), compensatory strategies (C), and metacognitive strategies (M). We examine three intervention programs to illustrate how this framework clarifies each intervention's active ingredients and their relation to cognitive, psychological, and functional outcomes. The PICC-M framework lays the foundation for dismantling studies to isolate and test the effectiveness of specific active ingredients and ultimately support clinical delivery of evidence-based interventions for older individuals with neurocognitive deficits.

Background Post-traumatic headache (PTH) is typically described as migraine- or tension-type-like and treated based on presentation. However, the actual presentations of PTH are not well characterized. The aim of this study is to provide a phenotypic characterization of persistent PTH and co-occurring neurological symptoms from a previously completed clinical trial and characterize PTH treatment utilization. Methods This study is a secondary analysis of veterans ( N = 193) recruited to participate in a randomized clinical trial of cognitive-behavioral therapy, cognitive processing therapy, or treatment as usual for PTH. Descriptive statistics were examined across characteristics of PTH, including age, gender, neurobehavioral symptoms, headache-related disability, pain characteristics, pain locations, accompanying symptoms, and aura symptoms and treatment utilization. Results The median presentation of PTH in this study was a headache with severe pain, lasting about 4 h, and with about 13 headache episodes per month. About half the participants reported a pulsating quality and/or nausea that accompanied head pain. Most characteristics were uncorrelated to each other. The majority of participants used medication to treat persistent PTH. Neurostimulation was the most common non-pharmacological treatment. Conclusions The results of this study show that characteristics associated with migraine are more frequently reported with PTH. Correlations among the migraine characteristics were moderate overall, and there was notable variability among reported characteristics of PTH. Treatment utilization for PTH was not associated with current neurobehavioral symptoms and included both pharmacological and non-pharmacological options. Trial Registration ClinicalTrials.gov Identifier: NCT02419131.

Objectives Cognitive Stimulation Therapy (CST) is widely used in UK dementia care to support cognitive and social functioning. Music therapy (MT) also shows cognitive benefits for people living with dementia (PLwD) but is not routinely available through the NHS due to limited cost-effectiveness evidence. This study evaluated the combined use of CST and MT compared to CST alone, providing a realistic assessment of the added value of MT within standard care. Method A decision analytic model was constructed using a cost utility framework with a healthcare perspective, over a three-month time horizon. It compared CST+MT with CST alone for community-dwelling people with moderate dementia. The clinical effectiveness outcome was cognitive improvement measured by MMSE score. Model parameters were informed by existing literature and clinical trial data where available. Results Over a three-month period, MT+CST was more effective than CST alone in improving cognitive function but was not cost-effective due to higher initial costs, including setup and equipment. However, when cognitive benefits were assumed to persist over six months, CST+MT became cost-effective. Conclusion MT combined with CST may offer cost-effective cognitive benefits for PLwD over a six-month period. The model provides valuable evidence for decision-makers considering the broader adoption of MT.

The Role of the Therapeutic Alliance in Dropout in Cognitive Processing Therapy for Posttraumatic Stress Disorder.

Preliminary treatment outcomes of transition-aged youth receiving cognitive processing therapy for PTSD: A brief report

A protocol for a randomized comparative effectiveness trial for treating PTSD symptoms for LGBTQIA+ people.

Psychological distress, including depression, anxiety, and stress, is highly prevalent among adults with cancer. Mindfulness-based interventions (MBIs), such as Mindfulness-Based Stress Reduction (MBSR) and Mindfulness-Based Cognitive Therapy (MBCT), are increasingly used to address these symptoms. However, no prior review has comprehensively stratified MBI effects across intervention types, symptom domains, cancer populations, and geographic regions. To evaluate the effectiveness of MBIs, including standard and adapted formats, on depression, anxiety, and stress in adults with cancer. A systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted in accordance with PRISMA guidelines. Six databases were searched from January 2010 to July 2025. Eligible studies included RCTs comparing MBIs to control conditions in adults with cancer, reporting validated outcomes for depression, anxiety, or stress. Random-effects meta-analyses were performed using Hedges' g, with subgroup analyses by intervention type, duration, geographic region, and cancer type. Across 84 effect sizes from 45 RCTs (N=7395), mindfulness-based interventions were evaluated. MBIs significantly reduced depression (g=-0.92), anxiety (g=-1.06), and stress (g=-1.50). Modified MBIs MBIs demonstrated the largest effects (g=-1.57), followed by MBSR (g=-0.72) and MBCT (g=-0.68). The strongest effects were observed in breast cancer populations (g=-1.48) and in studies conducted in North America (g=-1.21) and Asia (g=-1.07). Mindfulness-based interventions (MBIs) were associated with reduced depression, anxiety, and stress in adults with cancer, though heterogeneity was high and evidence was largely from breast cancer trials. MBIs appear scalable, particularly for women with breast cancer, but broader conclusions remain limited. Findings support their inclusion in tailored psychosocial care, with a need for more diverse and rigorously controlled research.

Care coordinator delivered method of levels therapy to improve engagement and other outcomes in early psychosis (CAMEO): A feasibility cluster-randomised controlled trial.

Background/Objectives: Mindfulness-Based Cognitive Therapy (MBCT) is a well-documented treatment option for chronic pain. However, few studies have examined the emotional state experienced by participants with chronic pain during the sessions. This study aimed to assess the trajectory of mood experiences in an MBCT program and evaluate the effect on temporal mood state. Methods: The Temporary Mood Scale (TMS) was used to assess vigor, fatigue, anger-hostility, depression-dejection, tension-anxiety, and confusion before and after each MBCT session from July 2018 to May 2019. A total of 33 patients with chronic pain who attended the MBCT program were included in the study. A mixed-effect model was used to identify single-session and overall effects on each mood state. Pearson's correlation analysis was used to examine the associations between changes in the six mood states and baseline conditions, including pain-related factors. Results: The mixed-effect model identified significant improvements in single-session effects on all mood states (p < 0.001). Significant overall effects were identified on vigor (p < 0.01), depression-dejection (p < 0.01), tension-anxiety (p < 0.001), and confusion (p < 0.05) states throughout the sessions. Moreover, participants with higher tension-anxiety at baseline showed significantly greater improvements in anger-hostility (p < 0.05), depression-dejection (p < 0.01), tension-anxiety (p < 0.05), and confusion (p < 0.01). Conclusions: Individual sessions and the overall MBCT program significantly improved the mood states of patients with chronic pain. Patients with higher tension-anxiety are likely to be effective treatment targets for MBCT programs.