Background: In utero cannabis exposure is associated with deleterious offspring neural development and behaviors that emerge across the lifespan. We explored if brain morphology differed in neonates exposed and unexposed to cannabis in utero in the first month of life.Objective: To evaluate differences in global and subcortical regional brain volume (in the amygdala and hippocampus) in neonates in the first month of life according to in utero cannabis exposure.Methods: Prospective pre-birth prospective cohort study of mother-infant pairs selected on the basis of prenatal cannabis use in the absence of alcohol, tobacco, or illegal drug use. The presence of cannabinoids using ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) was quantified in maternal and neonatal biological samples. Neonatal MRI was conducted to evaluate differences in global and subcortical brain morphology between the exposed and unexposed infants (18 exposed, 21 unexposed). Inverse probability of treatment weighting was utilized in a generalized linear model framework to remove structural confounding bias between exposure groups. Clinical Trial Registration: NCT03718520.Results: The sex distribution of neonates was 43% female. Neonates exposed to cannabis in utero had significantly lower total brain volume (estimated effect size = 26,496.90 mm³, p = .02), independent of confounders including maternal stress, compared to unexposed infants. The unadjusted difference in brain volume was 29,159.82 mm³, p = .05). Regional volumetric differences were not detected in the amygdala or hippocampus.Conclusion: Given the evidence of the adverse effects of exogenous cannabinoids on fetal brain development, it is vital to prioritize prevention and cessation efforts targeting pregnant women.

Tuberculosis (TB) remains a major public health issue across the world and national TB guidelines are an important resource for diagnosis and treatment. This scoping review aimed to analyze how countries with the highest TB burdens approach the integration of comorbidity and risk factor screening, diagnosis and treatment, TB recurrence, and post-TB lung disease (PTLD) diagnosis and management, within their TB guidelines. We used the Arksey and O'Malley methodological framework to conduct a scoping review of TB guidelines among the WHO list of highest-TB burden countries. We identified drug-susceptible, drug-resistant, and consolidated guidelines through web searches and personal contacts within TB programs. We translated guidelines into English as needed and systematically extracted, recorded, and reviewed the guidelines to aggregate and describe our findings. Among the 49 countries with the highest TB burden, we successfully identified, translated, and analyzed 43 guidelines (24 drug-sensitive, 9 drug-resistance, and 10 consolidated) from 34 countries. Recommendations for screening varied by comorbidity or risk factor with the four most recommended being HIV/AIDS (100%), pregnancy (73%) and liver disease (59%) and mental health (59%). Recommendations for linkage to care were more infrequent and also varied with the top four being HIV (88%), liver disease (47%), diabetes (44%), and mental health (44%). Only 27 (79%) countries specified diagnostic tests to assess for TB recurrence among individuals presenting with symptoms post-TB treatment, with 25 recommending GeneXpert MTB/RIF. Notably, only 7 (21%) countries mentioned PTLD in their guidelines, with wide variations in their specific recommendations regarding screening, diagnosis, and management. Our findings highlight the lack of detailed guidance on how to properly diagnose and refer patients to appropriate care for various comorbidities or risk factors which may significantly impact microbiological and clinical TB treatment outcomes, including PTLD and ultimately point to an important opportunity for improvement in future guidelines.

Background and Clinical Significance: Avatar Therapy (AT) for individuals with treatment-resistant auditory verbal hallucinations (AVHs) in schizophrenia aims to address emotional responses, beliefs about voices, self-perception, and coping strategies. This study focuses on three participants who, during AT, shifted their belief about the origin of their most distressing voice from an external source to a self-generated one. Case Presentation: The objective of this study was to explore the evolution of the reattribution of the participants' most distressing voice to oneself during AT and the patients' perception of this reattribution. Immersive sessions and semi-structured interviews were transcribed and qualitatively described to provide a session-by-session account of the evolution of each participant's AVH reattribution to themselves during the course of AT, along with their perceptions of this reattribution. This process led to the recognition that initially perceived as external voices were internally generated thoughts, reflecting how participants viewed themselves. Two participants reported a reduction in AVH severity. All three described positive changes in how they related to their voices and self-perception. Additional improvements were observed in emotional regulation, social functioning, and engagement in personal projects. Conclusions: This reassignment of the voice from an external source to an internal one suggests that AT can modify how individuals relate to their voices and may empower them to regain control over their hallucinations. However, given the exploratory nature of this study, the results should be interpreted as examples.

Background/Objectives: This study aimed to (i) cross-culturally adapt the Inventory of Hyperacusis (IHS) into Danish and (ii) assess its usability, validity, and reliability in Danish adults with hyperacusis. Methods: The translation followed established guidelines for adapting hearing-related questionnaires. A two-phase design ensured linguistic and cultural adaptation and evaluated test-retest reliability and construct validity. The IHS, consisting of 25 items, was translated and tested in seven participants through cognitive debriefing. In phase two, temporal consistency was assessed in 32 patients. Results: Thirty-two participants (twenty-eight female; mean age 49.8 years) completed the study over 2-4 weeks (mean 22 days). Eight used hearing aids, and twenty-four reported tinnitus. The Danish IHS showed good reliability (Cronbach's alpha = 0.95) and acceptable test-retest reliability, except for the General Loudness factor. While no systematic score changes occurred, significant variability in score changes were noted. Conclusions: The Danish IHS appears to be a reliable and valid tool for assessing hyperacusis. Further research is needed, but the IHS-DK shows potential as an effective clinical and research tool for evaluating hyperacusis impact and treatment outcomes.

Background/Objectives: Oppositional defiant disorder (ODD) and conduct disorder (CD) are important behavior disorders in children and adolescents, often linked with long-term psychosocial problems. Antipsychotics are frequently prescribed to manage severe symptoms and improve behavior, but their efficacy in this population is still unclear and a lot of physicians are remittent in prescribing them. This systematic review aims to assess the effectiveness of antipsychotic treatment in reducing symptoms associated with ODD and CD in children and adolescents. Methods: Studies that investigated how effective antipsychotic treatments are for children and teens diagnosed with oppositional defiant disorder (ODD) and conduct disorder (CD) were reviewed. Only studies that met a few main criteria were included: participants were between 5 and 18 years old with an ODD or CD diagnosis; the treatment could be any type of antipsychotic, whether typical or atypical; the accepted study designs were randomized controlled trials (RCTs), cohort studies, systematic reviews with meta-analysis, or observational studies. The outcomes of interest were reductions in aggressive or defiant behaviors, improvements in social functioning, and the occurrence of any adverse effects from the medications. There was no restriction on the language of publication, and studies published from 2000 to 2024 were considered. Studies that focused only on non-antipsychotic drugs or behavioral therapies, as well as case reports, expert opinions, and non-peer-reviewed articles did not meet the inclusion criteria. Results: The review consisted of 13 studies. The results suggest that some antipsychotic drugs-especially atypical antipsychotics-can substantially reduce aggressive and defiant behavior in children and adolescents who have oppositional defiant disorder (ODD) or conduct disorder (CD). Common side effects of these medications include weight gain, sedation, and metabolic problems. Conclusions: Although adverse effects are a concern, the potential of these medications to manage disruptive behaviors should not be overlooked. When used in combination with behavioral therapy and other forms of treatment, antipsychotics can markedly improve the outcomes of these very difficult-to-treat patients. Clinicians who treat these patients need to consider antipsychotics as a serious option. If they do not, they are denying their patients medication that could greatly benefit them.

Cognitive impairment is a prevalent and disabling feature of multiple sclerosis (MS), significantly impacting patients' quality of life (QoL) and psychological well-being. Despite its clinical relevance, there are currently no approved pharmacological treatments for cognitive deficits in MS, highlighting the need for effective non-pharmacological interventions. This narrative review explores evidence from studies evaluating the efficacy of cognitive re-education (CR) approaches (including traditional, group-based, computer-assisted, virtual reality, and innovative methods such as music therapy) on cognitive and QoL outcomes in people with MS. The findings demonstrate that while CR consistently influences cognitive domains such as memory, attention, and executive function, its effects on QoL are more variable and often depend on intervention type, duration, and individual patient characteristics. Notably, integrative approaches like virtual reality and music therapy show promising results in enhancing both cognitive performance and psychosocial well-being. Several studies report that cognitive gains are accompanied by improvements in mental health and functional QoL, particularly when interventions are tailored to individual needs and delivered within multidisciplinary frameworks. However, some interventions yield only limited or transient QoL benefits, underlining the importance of personalized, goal-oriented strategies that address both cognitive and psychosocial dimensions. Further research is needed to optimize intervention strategies and clarify the mechanisms linking cognitive and QoL outcomes.

Throughout years of research, the well-known behavioral parent training program, Parent-Child Interaction Therapy (PCIT), has been adapted and enhanced to tailor the treatment to the needs of families in community-based clinical care. This study wished to evaluate an add-on to PCIT that could be engaging for parents. As a way to enlarge practice opportunity and potentially allow parents to achieve positive treatment effects sooner, this study added virtual reality (VR) to PCIT.

This study aimed to increase positive parenting skills at a faster pace with the use of PCIT-VR, on the basis that practicing positive parenting skills in the VR tool would increase parents' overall practice time, thus leading to more confidence in their skills, which could consequently increase the pace of skill acquisition. Furthermore, we hypothesized that due to the overall increase in positive parenting skills, PCIT treatment effects such as diminishment of child disruptive behavior and parenting stress would decrease at a faster pace when VR was introduced.

Families were recruited from a specialized child and adolescent psychiatry clinical practice in the Netherlands. Using a single-case experimental design, 11 families, equating to 18 participants, signed informed consent forms and received the staggered introduction of VR to treatment. As is common with a single-case experimental design, visual inspection analyses and randomization tests were conducted. Group differences were evaluated with nonparametric tests and reliable change indices.

Overall, our study reaffirmed that PCIT is an effective intervention for this population as there were positive treatment effects found in almost all cases. Nevertheless, there did not seem to be a clear relationship between the use of the VR tool and PCIT treatment effects, although positive parenting skills seemed to increase when VR was introduced to treatment for some parents. For all parents, questions and comments decreased with the introduction of VR. These findings tentatively suggest that practicing with VR could potentially increase positive parenting skills and also have an impact on other treatment-related outcomes, such as child disruptive behavior and parenting stress.

This was the first time that PCIT has been supplemented with VR. We provide preliminary evidence of its added value. We cautiously suggest that VR could provide added value to PCIT and increase confidence in parenting skills for certain parents, although there are complex factors that play into treatment success that must simultaneously be considered. These factors include parents having the motivation and mental capacity to change and the complex psychological problems some families face. Although promising, we believe that due to the novelty of our VR practice tool and the variety of results from our study, more research is necessary into PCIT-VR to draw further conclusions on its effects.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a liver condition linked to cardiometabolic diseases and mental health issues, with studies highlighting disruptions in gut microbiota activity, including bile acid (BA) metabolism. Therefore, the main aim of this exploratory analysis was to assess microbiota-derived metabolites, specifically BAs and short-chain fatty acids (SCFAs), as potential biomarkers of depressive disorder (DD) in women with morbid obesity at MASLD risk. In this pilot study, 33 females with morbid obesity who were scheduled for bariatric surgery were evaluated. Medical and clinical data were collected, and microbial metabolites from pre-surgery blood samples were analyzed. Patients were stratified according to the presence of DD. Analysis with Spearman's rank test was used to assess correlations and logistic regression models were built to evaluate biomarkers as predictors of DD risk using both receiver operating characteristic (ROC) and precision-recall curves. In this cohort, 30.3% of females were reported to have DD, in addition to significantly elevated levels of certain BAs and SCFAs, including glycodeoxycholic acid (GDCA) and propionate, which were also correlated with some metabolic biomarkers. However, there were no differences in the incidence of MASLD or metabolic syndrome between patients with DD or without. In conclusion, microbiota-derived metabolites such as GDCA and propionate may influence DD risk in females with morbid obesity; however, their potential use as predictive biomarkers should be further investigated to confirm their role in psycho-metabolic conditions.

Cerebral small vessel disease (cSVD) is a common cause of stroke and dementia. Ageing, hypertension, hyperglycaemia, and smoking make up the biggest risk factors for cSVD. They individually or collectively increase the levels of reactive oxygen species, pro-inflammatory cytokines and matrix metalloproteinases, decrease the bioavailability of nitric oxide, and, in the process, compromise the structural integrity and function of the vascular endothelium, blood-brain barrier, and brain parenchyma. These then appear as white matter hyperintensities, enlarged perivascular spaces, cerebral microbleeds, and atrophy in cerebral imaging. As there is currently no curative therapy for cSVD, prevention or delay of cSVD remains of particular importance to preserve quality of life for as long as possible. Bearing that in mind, this review explores whether drugs used for other neurovascular conditions may prevent neuroinflammation and oxidative damage and effectively maintain endothelial function and blood-brain barrier integrity. It also examines whether potential benefits may be extended to cSVD. The list of drugs includes anti-anginal drugs, acetylcholine esterase inhibitors, β-hydroxy β-methylglutaryl-CoA reductase inhibitors, lithium drugs, phosphodiesterase inhibitors, oral antihyperglycaemic drugs, and tetracycline antibiotics. This review discusses the mechanisms of action of these agents and critically evaluates preclinical, translational, and clinical research pertaining to cSVD.

Frmpd3 (FERM and PDZ Domain Containing 3), a scaffold protein potentially involved in excitatory synaptic function, has not been thoroughly characterized in terms of its expression and functional role in vivo. Here, we investigated the distribution of Frmpd3 in the central nervous system and its potential regulatory role in epilepsy, a neurological disorder characterized by disrupted excitatory-inhibitory balance. The distribution of Frmpd3 throughout the mouse brain was investigated by immunofluorescence. Western blotting was conducted to examine potential alterations in Frmpd3 protein expression in the hippocampus of a pentylenetetrazol (PTZ)-induced chronic epilepsy model. Using stereotaxic techniques, we delivered Frmpd3 siRNA-AAV9 into the hippocampal CA1 region to achieve targeted protein knockdown. Then, the functional consequences of Frmpd3 depletion were assessed through behavioral observations and electrophysiological recordings in PTZ-treated mice. Finally, protein-protein interactions were investigated using immunoprecipitation and Western blot analysis. Immunofluorescence analysis revealed Frmpd3 expression in cortical, hypothalamic, cerebellar, and hippocampal neurons of adult mice. Subcellular localization studies demonstrated predominant distribution of Frmpd3 in the excitatory postsynaptic density (PSD) of hippocampal CA1 neurons, with additional expression in inhibitory neurons. Quantitative analysis showed significantly elevated Frmpd3 protein levels in the hippocampus of PTZ-induced epileptic mice compared to controls. Frmpd3 knockdown in the CA1 region resulted in the following: (1) reduced seizure frequency, (2) prolonged seizure latency, and (3) decreased incidence of PTZ-induced generalized seizures. Local field potential (LFP) recordings demonstrated that seizure amplitude tended to be reduced, and epileptic discharge durations tended to be shorter in Frmpd3-depleted mice compared to controls. Furthermore, we observed decreased membrane expression of the AMPA receptor GluA2 subunit in the hippocampus of Frmpd3 knockdown mice. Molecular interaction studies revealed that Frmpd3 forms complexes with glutamate receptor-interacting protein (GRIP) and GluA2. Our findings identify Frmpd3 as a novel regulatory scaffold protein that modulates epileptic susceptibility through molecular interactions with GRIP and GluA2. The underlying mechanism appears to involve Frmpd3-mediated regulation of GluA2 trafficking from the cytoplasm to the membrane, ultimately enhancing neuronal excitability through increased membrane expression of GluA2-containing AMPA receptors.