Psychiatry and Clinical Neurosciences最新文献

Aim: Social anxiety disorder (SAD) is a mental disorder that requires early detection and treatment. However, some individuals with SAD avoid face-to-face evaluations, which leads to delayed detection. We aim to predict individuals with SAD based on their communication logs and social network data from a massively multiplayer online game (MMOG).

Method: The study included 819 users of Pigg Party, a popular MMOG in Japan. Participants completed the Japanese version of the Liebowitz Social Anxiety Scale (LSAS-J) and a social withdrawal scale (hikikomori) questionnaire. Participants scoring ≥60 on the LSAS-J were classified as having SAD, while those scoring <60 were classified as not having SAD (non-SAD). A total of 142,147 users' communication logs and 613,618 social edges from Pigg Party were used as input to predict whether participants had SAD or non-SAD. Graph sample and aggregated embeddings (Graph SAGE) was utilized as a graph neural network model.

Results: Individuals with SAD were more likely to be socially withdrawn in the physical community (hikikomori), had fewer friends, spent less time in other users' virtual houses, and showed lower entropy in their visitation times in MMOG. Based on their social network data, the Graph SAGE model predicted SAD, with an F1 score of 0.717.

Conclusion: The communication logs and social network data in an MMOG include indicators of interpersonal avoidance behaviors, which is typical of individuals with SAD; this suggests their potential use as digital biomarkers for the early detection of SAD.

Aim: Vafidemstat is a brain-penetrant, orally bioavailable, small molecule irreversible inhibitor of the histone lysine-specific demethylase KDM1A (also known as LSD1), which corrects memory deficits and behavior alterations including aggression and social interaction deficits in preclinical models.

Methods: Here, we report the results of REIMAGINE, a phase IIa, single-center, open-label, one-arm basket trial that evaluated the safety and efficacy of vafidemstat on aggression in adult patients with borderline personality disorder (BPD), attention-deficit/hyperactivity disorder (ADHD), and autistic spectrum disorder (ASD). Participants received 1.2 mg/day of vafidemstat for 8 weeks.

Results: Vafidemstat was shown to be safe and well tolerated, and no drug-related clinically significant adverse events were observed. Furthermore, all neuropsychiatric scales assessed showed notable efficacy signals, whether assessing agitation/aggression (Clinical Global Impression for Severity [CGI-S] and Clinical Global Impression for Improvement [CGI-I] and Neuropsychiatric Inventory [NPI] questionnaire for Agitation-Aggression [NPI-AA]), overall patient functioning (total NPI), or disease-specific features (Attention-Deficit/Hyperactivity Disorder Rating Scale [ADHD-RS] and Borderline Personality Disorder Checklist [BPDCL]). Statistically significant improvements were observed in the aggregated data (all participants) and for each of the three disease groups independently. Changes were evident within the first 2 weeks of treatment.

Conclusion: In summary, the REIMAGINE study supports that vafidemstat is safe, well tolerated, and causes a significant and consistent reduction in agitation/aggression and nonaggression features in BPD, ADHD, and ASD. These data support continuing the development of vafidemstat as a new treatment option for these psychiatric disorders.

Psychiatric disorders are a common source of disease morbidity with high rates of refractoriness to first-line treatments. As such, many have investigated the utility of neurosurgical interventions for treatment-resistant forms of these conditions. More recently among these, functional neurosurgical techniques using high- and low-intensity focused ultrasound (FUS) have emerged as promising options in this arena, largely due to their minimally-invasive nature and encouraging early safety and efficacy data. Existing clinical data have thus far demonstrated FUS to be a potentially useful intervention for treatment-refractory forms of obsessive-compulsive disorder, major depressive disorder, various anxiety disorders, substance-use disorder, and schizophrenia. This report presents a comprehensive review of existing clinical trial data, summarizing key findings, study specifications, and providing critical analysis. In addition to giving the most complete summary of modern clinical research on this topic to date, this report characterizes the current state of this body of literature using bibliometric analysis, succinctly highlighting the most investigated topics and the most promising areas of modern investigation. Based on our review of the literature, current work on this topic is highly heterogeneous with regard to specific treatment protocols and anatomic targets for FUS - targeting multiple nuclei at a wide variety of intensities. We recommend that future studies aim to clarify more precise therapeutic targets and specific treatment protocols which optimize the efficacy of these techniques.

Aims: People with anorexia nervosa (AN) often engage in compulsive exercise to control weight and manage emotions, altering the reward associated with physical activity. Delay-discounting evaluates preference for immediate over delayed rewards, potentially indicating struggles with prioritizing long-term gains. However, the impact of AN on these factors remains unexplored. This study aims to assess the attitudes of individuals with AN using a modified exercise delay discount task, comparing them with the general population.

Methods: A sample of 76 individuals (70 women, 92.1%) with a diagnosis of AN was compared with a sample of 124 people (115 women, 92.7%) without a lifetime diagnosis of any eating disorder. Two different delay discount tasks were used to evaluate different constructs: a standardized monetary delay discount task and a modified version focused on physical activity.

Results: The standardized monetary delay discount task confirmed the existence of varied monetary rewards in different subtypes of AN. The exercise-related task demonstrated a specific emphasis on exercise within AN, showing a tendency to delay physical activity by looking for a greater amount of exercise. On the contrary, the general population opted for immediate exercise proposals.

Conclusions: Our findings suggest that the tendency to delay physical activity could be related to the compulsive nature of exercise in patients with AN, with a possible change in cognitive evaluation based on the magnitude of exercise. Finally, in addition to psychological problems related to eating disorders, additional cognitive factors likely contribute to exercise compulsiveness, necessitating further research exploration.

Aims: Borderline personality disorder (BPD) patients show negative emotional reactions to both excluding and including social scenarios, with levels normalizing only during extreme inclusion. Prior research among healthy individuals highlights the right ventrolateral prefrontal cortex (rVLPFC) role in regulating emotional responses to social exclusion, since transcranial direct current stimulation (tDCS) of rVLPFC decreases rejection-related emotions following social exclusion. This pilot study investigated whether, in BPD patients, tDCS over the rVLPFC reduces rejection-related emotions not only after social exclusion but also after fair social inclusion.

Methods: Forty BPD patients randomly received either real or sham tDCS on rVLPFC before participating in the Cyberball paradigm, which involved phases of inclusion, exclusion, and over-inclusion. Participants self-reported their level of rejection-related emotions following each phase.

Results: Transcranial direct current stimulation reduced rejection-related emotions during both social exclusion and fair inclusion, but not during over-inclusion. Specifically, those in the Real tDCS group exhibited comparable emotional responses to fair and over-including scenarios, unlike those in the Sham group who experienced heightened rejection-related emotions during fair inclusion compared to over-inclusion.

Conclusions: Transcranial direct current stimulation over the rVLPFC reduces BPD patients' tendency to feel rejected both in fairly including and excluding scenarios. These findings confirm the rVLPFC involvement in emotional regulation and highlight a therapeutic potential for tDCS in moderating BPD's typical heightened rejection-related emotional responses to fairly including scenarios. This study supports the application of tDCS in BPD treatment, providing new insights into neuromodulatory interventions that can aid BPD patients to better regulate their emotions during varying social scenarios.

Aims: The way that individuals subjectively experience the world greatly influences their own mental well-being. However, it remains a considerable challenge to precisely characterize the breadth and depth of such experiences. One persistent problem is the lack of objective tools for directly quantifying and comparing narrative reports of subjective experiences. Here, we develop a new approach to map and compare reports of experience using the latent space of artificial neural networks.

Methods: Using a series of 31 prompts, including 30 images and one open-ended question, we quantified how the verbal reports provided by participants (n = 210, 50% female) deviate from one another and how these variations are linked to subjective experience and mental health.

Results: We found that latent space embeddings of experience can accurately predict subjective judgments of valence and arousal in a series of emotional pictures. Furthermore, we show that narrative reports to ambiguous images can accurately predict transdiagnostic factors of mental health. While distortions in the latent space of artificial neural networks are notoriously difficult to interpret, we propose a new approach to synthesize visual stimuli with generative artificial intelligence that can be used to explore semantic distortions in reported experiences.

Conclusions: In sum, latent space cartography could offer a promising avenue for objectively quantifying distortions of subjective experience in mental health and could ultimately help identify new therapeutic targets for clinical interventions.

Aim: Epigenetic clocks, quantifying biological age through DNA methylation (DNAmAge), have emerged as potential indicators of brain aging. As the variety of DNAmAge algorithms grows, consensus on their efficacy in predicting age-related changes is lacking. This study aimed to explore the intricate relationship between diverse DNAmAge algorithms and structural and cognitive markers of brain aging.

Methods: Within a cohort of 796 elderly patients (mean age, 65.8 ± 7.9 years), we scrutinized 11 DNAmAge algorithms, including Horvath, Hannum, Zhang's clocks, PhenoAge, GrimAge, DunedinPACE, and principal component (PC)-based PCHorvath, PCHannum, PCPhenoAge, and PCGrimAge. We evaluated their association with baseline cognition and cognitive decline, assessed through follow-up evaluations at three (T1) and six (T2) years postbaseline. Additionally, we examined their relationship with structural magnetic resonance imaging markers of brain aging, including white matter.

Results: Zhang's clock was the best predictor of decline in memory (β = -0.04) and global cognition (β = -0.03), whereas PCGrimAge was the best predictor of speed decline (β = -0.17). The DNAmAge algorithms were the second-best predictors in explaining cognitive variability after education in memory and global cognition (R² _partial = 1.66% to 2.82%) and the best predictors for speed decline (R² _partial = 2.13%). PC-trained DNAmAge algorithms outperformed their respective original version.

Conclusion: DNAmAge algorithms are strong and independent predictors of cognitive decline in the normal elderly population and explain additional variability in cognitive decline beyond that accounted for by conventional risk factors.