To achieve its precise neural connectivity, the developing mammalian nervous system undergoes extensive activity-dependent synapse remodelling. Recently, microglial cells have been shown to be responsible for a portion of synaptic pruning, but the remaining mechanisms remain unknown. Here we report a new role for astrocytes in actively engulfing central nervous system synapses. This process helps to mediate synapse elimination, requires the MEGF10 and MERTK phagocytic pathways, and is strongly dependent on neuronal activity. Developing mice deficient in both astrocyte pathways fail to refine their retinogeniculate connections normally and retain excess functional synapses. Finally, we show that in the adult mouse brain, astrocytes continuously engulf both excitatory and inhibitory synapses. These studies reveal a novel role for astrocytes in mediating synapse elimination in the developing and adult brain, identify MEGF10 and MERTK as critical proteins in the synapse remodelling underlying neural circuit refinement, and have important implications for understanding learning and memory as well as neurological disease processes.
C. Long-Smith, Kenneth J. O'Riordan, G. Clarke
et al.
The traditional fields of pharmacology and toxicology are beginning to consider the substantial impact our gut microbiota has on host physiology. The microbiota-gut-brain axis is emerging as a particular area of interest and a potential new therapeutic target for effective treatment of central nervous system disorders, in addition to being a potential cause of drug side effects. Microbiota-gut-brain axis signaling can occur via several pathways, including via the immune system, recruitment of host neurochemical signaling, direct enteric nervous system routes and the vagus nerve, and the production of bacterial metabolites. Altered gut microbial profiles have been described in several psychiatric and neurological disorders. Psychobiotics, live biotherapeutics or substances whose beneficial effects on the brain are bacterially mediated, are currently being investigated as direct and/or adjunctive therapies for psychiatric and neurodevelopmental disorders and possibly for neurodegenerative disease, and they may emerge as new therapeutic options in the clinical management of brain disorders. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 60 is January 6, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
Summary Background Comparable data on the global and country-specific burden of neurological disorders and their trends are crucial for health-care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study provides such information but does not routinely aggregate results that are of interest to clinicians specialising in neurological conditions. In this systematic analysis, we quantified the global disease burden due to neurological disorders in 2015 and its relationship with country development level. Methods We estimated global and country-specific prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs), and years lived with disability (YLDs) for various neurological disorders that in the GBD classification have been previously spread across multiple disease groupings. The more inclusive grouping of neurological disorders included stroke, meningitis, encephalitis, tetanus, Alzheimer's disease and other dementias, Parkinson's disease, epilepsy, multiple sclerosis, motor neuron disease, migraine, tension-type headache, medication overuse headache, brain and nervous system cancers, and a residual category of other neurological disorders. We also analysed results based on the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility, to identify patterns associated with development and how countries fare against expected outcomes relative to their level of development. Findings Neurological disorders ranked as the leading cause group of DALYs in 2015 (250·7 [95% uncertainty interval (UI) 229·1 to 274·7] million, comprising 10·2% of global DALYs) and the second-leading cause group of deaths (9·4 [9·1 to 9·7] million], comprising 16·8% of global deaths). The most prevalent neurological disorders were tension-type headache (1505·9 [UI 1337·3 to 1681·6 million cases]), migraine (958·8 [872·1 to 1055·6] million), medication overuse headache (58·5 [50·8 to 67·4 million]), and Alzheimer's disease and other dementias (46·0 [40·2 to 52·7 million]). Between 1990 and 2015, the number of deaths from neurological disorders increased by 36·7%, and the number of DALYs by 7·4%. These increases occurred despite decreases in age-standardised rates of death and DALYs of 26·1% and 29·7%, respectively; stroke and communicable neurological disorders were responsible for most of these decreases. Communicable neurological disorders were the largest cause of DALYs in countries with low SDI. Stroke rates were highest at middle levels of SDI and lowest at the highest SDI. Most of the changes in DALY rates of neurological disorders with development were driven by changes in YLLs. Interpretation Neurological disorders are an important cause of disability and death worldwide. Globally, the burden of neurological disorders has increased substantially over the past 25 years because of expanding population numbers and ageing, despite substantial decreases in mortality rates from stroke and communicable neurological disorders. The number of patients who will need care by clinicians with expertise in neurological conditions will continue to grow in coming decades. Policy makers and health-care providers should be aware of these trends to provide adequate services. Funding Bill & Melinda Gates Foundation.
Franz Felix Konen, Steffen Pfeuffer, Konstantin Fritz Jendretzky
et al.
Anti-CD20 antibodies and cladribine are established therapies for active relapsing multiple sclerosis (RMS). Increasing evidence suggests that switching between these therapies may be beneficial in patients with ongoing disease activity under current treatment. In this multicenter retrospective study across six German MS centres, a total of 90 patients with active RMS were considered for inclusion, of whom 71 patients were switched either from anti-CD20 antibodies to cladribine (n = 31) or from cladribine to anti-CD20 antibodies (n = 40), with a minimum follow-up of 12 months. At treatment initiation, patients switching from anti-CD20 antibodies were older, had a longer disease duration, and a higher disability score compared to those switching from cladribine (p = 0.0040, p = 0.0447, p = 0.0028, respectively). The primary reason for switching was disease activity. Following the switch, the proportion of patients with relapsing disease activity was markedly reduced (from 55 % to 16 % for anti-CD20 to cladribine, and from 83 % to 25 % for cladribine to anti-CD20). Clinical outcomes improved, while serum biomarkers such as neurofilament light chain and glial fibrillary acidic protein remained stable over six months. Notably, the prevalence of hypogammaglobulinemia decreased after switching from anti-CD20 therapies to cladribine. These results indicate that patients with active RMS can achieve clinical stabilization after switching therapies in either direction, underscoring the complementary mechanisms of action and the safety of such an approach in real-world practice.
IntroductionDigital therapeutics (DTx) require structured methodologies to translate evidence-based psychotherapy into immersive digital formats. In response to this need, this study proposes a practical framework for the digital transformation of Acceptance and Commitment Therapy (ACT) into an interactive virtual reality (VR) system.MethodsDTx-ACT, designed as a therapeutic intervention for depression, is a VR-based system that delivers ACT through an immersive virtual experience. Its development followed five structured phases: preliminary research, design, development, advancement, and commercialization. The original ACT protocol was modularized into VR environments using the Session Structuring System (SSS) model. To enhance user engagement, gamification and multimodal arts strategies were incorporated. As part of the development process, evaluation metrics were defined to assess both clinical effectiveness and user interaction.ResultsThe final system comprises five immersive VR sessions, each lasting 6 to 12 minutes. These modules incorporate ACT metaphors, interactive tasks, and multisensory feedback to enhance therapeutic engagement. To support the digital transformation of ACT, three core components were established: (1) an evidence-based therapeutic protocol, (2) interactive VR elements—including gamification and multimodal arts-based guidance, and (3) a data-driven evaluation framework. Evaluation metrics, derived from a pilot study, were integrated into the system, which collects clinical and interaction data—such as real-time behavioral patterns and sensor-based information—to enable comprehensive evaluation.DiscussionBased on this development process, we propose a practical framework for designing interactive VR-based DTx. This framework bridges clinical structure, creative engagement, and real-time evaluation to support personalized and scalable applications in digital mental healthcare. It contributes to the standardization of digital transformation in evidence-based therapy and offers a transferable model for future therapeutic content development.
Anne Stekkinger-de Vries, Elisa van Ee, Rianne Verschuur
et al.
Background: Parents of adolescents with autism spectrum disorder (ASD) and severe emotional dysregulation (ED) often experience trauma symptoms related to their child's behaviour, including aggression, self-injury and suicide attempts. These traumatic experiences can lead to parental posttraumatic stress symptoms, which are linked to heightened parental stress, reduced capacity for mentalisation, and difficulties co-regulating their child. These challenges have the potential to intensify pre-existing emotional dysregulation, thereby undermining the effectiveness of treatment for the adolescent. Nevertheless, child-related PTSD is rarely addressed in mental health services. This study aims to address this gap in mental health by examining the effects of trauma-focused treatment for these parents.Method: This single-case design study involved seven parents (five mothers and two fathers) of six adolescents (aged 16–21) diagnosed with ASD and emotional dysregulation (ED). Parents received EMDR-therapy and were assessed weekly during a randomised baseline (3–5 weeks), treatment phase (4–6 weeks), post-intervention (3 weeks), and follow-ups at 6 weeks and 3 months.Results: All parents showed a reduction of PTSD-symptoms after EMDR-therapy, with none of the parents meeting PTSD criteria after treatment and follow-up. A significant reduction in parental stress was reported by all parents at post-treatment and follow-up. Furthermore, five out of seven parents reported reduced ED in their adolescents after treatment, an effect maintained in three cases at follow-up.Conclusions: This study demonstrates the value of trauma-focused treatment for parents coping with PTSD as a result of exposure to child-related traumatic events. The findings of this study provide valuable insights into the possible nature of parental stress in parents of adolescents with severe ED, as well as how this can be effectively addressed. The results support the hypothesis that when parents feel emotionally regulated, they may exhibit increased engagement and support for their adolescents’ treatment, potentially leading to improved treatment outcomes.
Mansoor Ahmad Dar, Rehana Amin, Rasikha Rasool Khan
et al.
Abstract Background Mental disorders, particularly anxiety and depression, affect a significant portion of the global population, with 1 in 8 people, or approximately 970 million individuals, experiencing such conditions. Despite this burden, mental health service gaps are huge, especially in low-resource settings like India. Objective To explore the first help-seeking behaviour and referral patterns for individuals experiencing psychiatric morbidity in South Kashmir, Jammu and Kashmir. Methods A semi-structured questionnaire was used to assess sociodemographic characteristics, clinical features, and the help-seeking behaviour of 903 individuals with lifetime psychiatric morbidity. The psychiatric diagnosis was made by using structured interview scale (MINI — Mini-International Neuropsychiatric Interview). Results The findings revealed that a significant portion of individuals (29.79%) never sought professional help, with faith healers (33%) and general physicians (27.35%) being the most common sources of initial support. Only a small percentage visited psychiatrists, either in hospitals (3.54%) or private clinics (6.32%). Among mental health services, patients preferred to see psychiatrists in private clinic, with males having more such preference. Furthermore, only 11.97% of individuals were referred for further psychiatric care, with faith healers being more likely to make referrals than physicians. The highest number of referrals from general physicians was for psychotic disorders, suicide, and substance use disorders. Conclusion This study highlights significant gaps in the identification and treatment-seeking behaviour for mental health issues in the population of South Kashmir. The importance of addressing barriers to mental health care access, including sociocultural beliefs and a lack of awareness, is highlighted. Healthcare planners should emphasize the need for improved mental health infrastructure and referral systems in underserved regions like ours.
Enhanced recovery after surgery (ERAS) is a multidisciplinary collaborative diagnosis and treatment model based on evidence-based medicine. By optimizing the perioperative management strategy, we can reduce the incidence of postoperative complications, minimize the physiological and psychological trauma stress reaction of patients, shorten the hospitalization period, and promote the functional recovery of patients. The diagnosis and treatment system integrates the advantages of surgery, anesthesiology, nursing, clinical nutrition and other disciplines, and constructs a whole process optimization path through preoperative evaluation, intraoperative management and postoperative rehabilitation, which fully embodies the patient-centered medical service concept. Postoperative pain, as a key factor affecting the rehabilitation process of patients, is closely related to the long-term quality of life of patients. Therefore, the optimization of pain management has become an indispensable and important part of eras. At present, multimodal analgesia (MMA) strategy has been widely recommended as the gold standard for postoperative pain management. This paper aims to review the latest research progress, clinical application strategies and future development direction of MMA in eras. It includes the theoretical basis, core drugs and technologies, application in different surgical fields, impact on patient prognosis, current challenges and future trends of MMA, and provides evidence-based basis for optimizing perioperative pain management.
H. Juárez Olguín, D. Calderón Guzmán, E. Hernández García
et al.
Dopamine is a neurotransmitter that is produced in the substantia nigra, ventral tegmental area, and hypothalamus of the brain. Dysfunction of the dopamine system has been implicated in different nervous system diseases. The level of dopamine transmission increases in response to any type of reward and by a large number of strongly additive drugs. The role of dopamine dysfunction as a consequence of oxidative stress is involved in health and disease. Introduce new potential targets for the development of therapeutic interventions based on antioxidant compounds. The present review focuses on the therapeutic potential of antioxidant compounds as a coadjuvant treatment to conventional neurological disorders is discussed.
Background: Studies using tasks that measure suicide-specific attentional biases have not specified which attentional processes are related to risk for suicidal thoughts and behaviors. This study distinguished suicide-specific engagement and disengagement biases from other forms of cognitive processing and investigated under which affective conditions suicide-specific biases emerged. Method: An ethnoracially and socioeconomically diverse sample of 153 young adults (87 % female; 52 % Non-Hispanic White), ages 18–34, with moderate-to-high symptoms of anxiety, depression, or recent suicide ideation were randomly assigned to experience positive, negative, or neutral affect, completed cognitive tasks of attention, construct accessibility, and threat bias, and self-report measures. Results: Individuals with recent ideation displayed facilitated disengagement from suicide-specific stimuli irrespective of affective state. Those with distal ideation showed slower disengagement from suicide-specific stimuli in the sad condition only. Conclusions: Individuals with recent suicide ideation display automatic processing of suicide-related information, perhaps due to recent rehearsal of suicide-related content. In contrast, individuals with distal ideation experiencing negative affect appear to have difficulty disengaging attention from suicide-related content. Limits to generalizability of the findings include a predominantly female sample, although the sample’s racial, ethnic, and socioeconomic diversity increase generality of the research.
BackgroundThe relationship between depressive symptoms and chronic liver disease (CLD) is still unclear. We aimed to determine whether depressive symptoms are associated with CLD in a large population sample.MethodsThe data was from the China Health and Retirement Longitudinal Study (CHARLS), an ongoing nationally representative prospective cohort study. Depressive symptoms were assessed with the catchment-area epidemiology survey-depression (CES-D). CLD was identified by the patient’s self-report about a physician’s diagnosis at each visit. Multi-adjusted logistic regression and Cox regression models were used.ResultsA total of 14,995 participants (53.1% female; mean age: 58.85 ± 9.87 years) and 13,405 participants (53.64% female; mean age: 58.58 ± 9.69 years) were included in the cross-sectional and longitudinal analyses, respectively. In the cross-sectional analysis, the odds ratio of CLD in patients with moderate and severe depressive symptoms were 1.46 [95% confidence interval (CI), 1.16–1.83] and 1.78 (95% CI, 1.23–2.56) than those with none/mild depressive symptoms, respectively. In the longitudinal analysis, compared to participants with none/mild depressive symptoms, the hazard rates of CLD in those with moderate and severe depressive symptoms were 1.65 (95%CI, 1.33–2.03) and 1.80 (95%CI, 1.24–2.60). And the 50th percentile difference of time (years) at the incidence of CLD in participants with moderate and severe depressive symptoms were − 0.83 (95%CI, −1.18, −0.49) and − 0.96 (95%CI, −1.56, −0.35), respectively.ConclusionElevated depressive symptoms were associated with an increased risk of CLD among middle-aged and older adults in China.
Michel Hofmann, Françoise Jermann, Stéphanie Baggio
et al.
Childhood maltreatment and mood disorders are associated and linked to self-stigma. In this study, we assessed the relationship between childhood trauma and self-stigma in patients with mood disorders. Patients with bipolar disorder (n = 69) and unipolar disorder (n = 111) were recruited from the Mood Disorders Unit of the Geneva University Hospitals in Switzerland. All participants underwent a semi-structured interview to assess mood disorder and fulfilled the Internalized Stigma of Mental Illness (ISMI) scale and the Childhood Trauma Questionnaire (CTQ). The results showed that overall self-stigma was not significantly different between the groups. Linear regression modeling revealed that the ISMI total score was significantly associated with the CTQ total score (estimate = 0.01, p = 0.045). Our findings support the assumption that childhood trauma promotes the development of self-stigma in patients with mood disorders. Therefore, this study underscores the importance of assessing childhood trauma in the management of self-stigma in patients with unipolar and bipolar disorder.
Courtney J. Wright, Snezana Milosavljevic, Ana Pocivavsek
Sleep is a vital and evolutionarily conserved process, critical to daily functioning and homeostatic balance. Losing sleep is inherently stressful and leads to numerous detrimental physiological outcomes. Despite sleep disturbances affecting everyone, women and female rodents are often excluded or underrepresented in clinical and pre-clinical studies. Advancing our understanding of the role of biological sex in the responses to sleep loss stands to greatly improve our ability to understand and treat health consequences of insufficient sleep. As such, this review discusses sex differences in response to sleep deprivation, with a focus on the sympathetic nervous system stress response and activation of the hypothalamic-pituitary-adrenal (HPA) axis. We review sex differences in several stress-related consequences of sleep loss, including inflammation, learning and memory deficits, and mood related changes. Focusing on women's health, we discuss the effects of sleep deprivation during the peripartum period. In closing, we present neurobiological mechanisms, including the contribution of sex hormones, orexins, circadian timing systems, and astrocytic neuromodulation, that may underlie potential sex differences in sleep deprivation responses.
Neurosciences. Biological psychiatry. Neuropsychiatry, Neurology. Diseases of the nervous system
S. Castelao-Almodovar, R. Ojea Quintana, A. Arrieta Artigas
et al.
Introduction
Since the start of the COVID19 pandemic, numerous patients have exhibited symptoms related to the viral infection once the acute phase has resolved. The most frequent are fatigue or weakness, cognitive difficulties, insomnia, and anxiety or depression. It has been observed that the persistence of these symptoms is more common in cases of severe infections.
Objectives
We expose a case that exemplifies it; A 60-year-old man suffering from severe COVID19 infection during 2021, with bilateral pneumonia and secondary pneumothorax. Three months after the acute episode, he continues to present related symptoms, such as dyspnea, asthenia, arthromyalgia, nausea, hyporexia, memory lapses, anxiety and depressive mood with apathy, anhedonia and suicidal ideas.
Methods
The patient starts follow-up in Mental Health and antidepressant treatment with Vortioxetine 10mg. In the following months he presented significant improvement consisting in decrease of the asthenia, dyspnea, arthromyalgia and especially in anxious symptoms and depressive mood, disappearing the apathy, anhedonia and suicidal ideation. However, the persistence of memory failures draws attention, which remain in a similar degree or with slight subjective improvement.
The exploration and complementary test were the following:
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Chest CT: Hydropneumothorax, parenchymal infiltrates, alveolar consolidations, left lamellar pneumothorax.
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Head CT, complete analysis, microbiological and cytological studies without relevant resolution.
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Assessment by the Rehabilitation and Neurology service.
Results
This case exposes the existence of a post-COVID syndrome, where the symptoms related to the infection persist, including anxious-depressive symptoms of moderate-severe intensity. The different diagnoses that were considered were the following: Post-COVID syndrome, Adjustment disorder with mixed anxious-depressive symptomatology, Depressive episode.
Conclusions
We consider that in this case and in others that are similar, which are increasingly common in routine clinical practice, the etiopathogenesis of the syndrome is of interest. We found that it is difficult to discern the origin of the symptoms, not being able to differentiate an adaptive difficulty to the infection situation (added to the COVID pandemic context), versus a more organic affectation that improves when receiving pharmacological treatment, as in this case with antidepressants.
Disclosure of Interest
None Declared