Onset Of Disorders Research Articles

Adaptive Hyperactivity and Biomarker Exploration: Insights from Elders in the Blue Zone of Sardinia

Background/Objectives: Adaptive hyperactivity characterized by increased activity levels and novelty-seeking traits without mood disorders is prevalent among older adults in Sardinia’s “blue zone,” an area with high longevity. This study aims to evaluate the adaptive nature of hyperactivity concerning quality of life, social rhythms, and mood symptoms in individuals from this region, particularly among elderly adults over 80. Methods: This observational cross-sectional study included adults and older adults over 80 from Sardinia’s blue zone. This study included a sample of patients followed at the Center for Consultation Psychiatry and Psychosomatics for Bipolar Disorder of the University Hospital of Cagliari and a homogeneous comparison sample of patients without psychiatric pathologies, referred to the Dermatology Clinic of the same hospital, for a period of 6 months, from February to August 2024. The general sample, divided into two parts—cases, represented by patients with psychiatric pathology, and controls, patients without psychiatric pathology—was divided in turn into three sub-groups: “adults” (18–64 years), young elders (65–79), and old elders (over 80 years). The participants underwent psychiatric interviews and completed the Mood Disorder Questionnaire (MDQ), Patient Health Questionnaire (PHQ-9), SF-12, and Brief Social Rhythm Scale (BSRS). Data were compared with national and regional normative data. Results: Older adults in the blue zone demonstrated higher MDQ positivity (22.58%) compared to the national averages (0.87%), without corresponding increases in dysregulated rhythms, depressive symptoms, or reduced quality of life. Younger old persons (65–79 years) showed increased rhythm dysregulation (BSRS score: 20.64 ± 7.02) compared to adults (17.40 ± 6.09, p = 0.040), but this trend was not observed in the oldest group (80+ years). No significant differences were found in the CH3SH and (CH3)2S levels between groups. Conclusions: The hyperactivity observed in older adults from Sardinia’s blue zone appears adaptive and not linked to social rhythm dysregulation, depressive symptoms, or a diminished quality of life, suggesting resilience factors which may contribute to longevity. These findings support the potential classification of such hyperactivity as beneficial rather than pathological, warranting further research into biomarkers and psychoeducational interventions to prevent the onset of bipolar disorders in predisposed individuals.

Adverse Myocardial and vascular side effects of Immune Checkpoint Inhibitors: a prospective multimodal cardiovascular assessment (AMICI study)

Abstract Background Immune checkpoint inhibitors (ICIs) are transformative treatments in oncology, yet they are also associated with a range of cardiovascular (CV) events. Purpose To identify the incidence of CV events (including subclinical) in patients receiving ICIs for solid cancer, either alone or in association with other cancer therapies (e.g., chemotherapies, target therapies). Objectives and methods The Adverse Myocardial and vascular side effects of Immune Checkpoint Inhibitors(AMICI) study prospectively assessed the incidence of CV changes by means of a thorough multimodal assessment. This included repeated CV imaging (transthoracic echocardiograms (TTE), cardiac magnetic resonance imaging (CMR)), serum biomarkers (troponin, brain natriuretic peptides in a single laboratory), and ambulatory ECG monitoring, before and during (at 6 weeks and at 6 months) ICI therapy (Figure). Cardiovascular events included myocarditis, pericarditis, acute coronary syndrome, heart failure (HF), high degree conduction abnormalities (defined as new grade 2 or 3 atrioventricular block) or sustained ventricular arrhythmias (defined as 3 or more ventricular beats at a rate ≥ 120/min), CV death as a composite endpoint, validated by an independent expert panel Results Out of 130 solid cancer patients considered for ICI therapy, 49 patients (38 (77.6%) male; mean age 64.3 (­SD 11.0) years old) were included (June 2020 -December 2021). 22 (55.1%) suffered from kidney or bladder cancer; 7 (14.3%) had CV disease prior to cancer diagnosis; 4 (8.2%) received PD1 and CTLA4 inhibitors. Early CV events were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P=0.035) predicted early CV events at 6 weeks (Table). At 6 months follow-up, 18 CV events were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias or conduction disorders and 4 (8.2%) AF. There was a significant decline in LVEF (P<0.001) in patients even in the absence of CV event (P=0.003) or HF (P=0.003). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P=0.006) predicted HF. Conclusions Cardiovascular complications arising during cancer treatment with ICIs are primarily due to the exacerbation of pre-existing HF or the onset of non-inflammatory heart rhythm disorders. The majority of these CV changes manifest shortly after starting ICIs and do not need hospital admission. Our results suggest that more close follow-up may be needed in patients with underlying CV conditions when starting ICI therapy, by means of CMR and ambulatory ECG holter monitoring.

Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders

Neurovascular unit (NVU) inflammation via activation of glial cells and neuronal damage plays a critical role in neurodegenerative diseases. Though the exact mechanism of disease pathogenesis is not understood, certain biomarkers provide valuable insight into the disease pathogenesis, severity, progression and therapeutic efficacy. These markers can be used to assess pathophysiological status of brain cells including neurons, astrocytes, microglia, oligodendrocytes, specialized microvascular endothelial cells, pericytes, NVU, and blood-brain barrier (BBB) disruption. Damage or derangements in tight junction (TJ), adherens junction (AdJ), and gap junction (GJ) components of the BBB lead to increased permeability and neuroinflammation in various brain disorders including neurodegenerative disorders. Thus, neuroinflammatory markers can be evaluated in blood, cerebrospinal fluid (CSF), or brain tissues to determine neurological disease severity, progression, and therapeutic responsiveness. Chronic inflammation is common in age-related neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia. Neurotrauma/traumatic brain injury (TBI) also leads to acute and chronic neuroinflammatory responses. The expression of some markers may also be altered many years or even decades before the onset of neurodegenerative disorders. In this review, we discuss markers of neuroinflammation, and neurodegeneration associated with acute and chronic brain disorders, especially those associated with neurovascular pathologies. These biomarkers can be evaluated in CSF, or brain tissues. Neurofilament light (NfL), ubiquitin C-terminal hydrolase-L1 (UCHL1), glial fibrillary acidic protein (GFAP), Ionized calcium-binding adaptor molecule 1 (Iba-1), transmembrane protein 119 (TMEM119), aquaporin, endothelin-1, and platelet-derived growth factor receptor beta (PDGFRβ) are some important neuroinflammatory markers. Recent BBB-on-a-chip modeling offers promising potential for providing an in-depth understanding of brain disorders and neurotherapeutics. Integration of these markers in clinical practice could potentially enhance early diagnosis, monitor disease progression, and improve therapeutic outcomes.

LncRNA MSTRG.13,871/miR155-5p/Grip1 network involved in the post-cardiac arrest brain injury

Post-cardiac arrest brain (PCABI) is a severe medical condition characterized by a significant risk of neurological impairment and death. Nevertheless, the specific process and essential molecules responsible for its development are not fully understood. Profiling based on competing endogenous RNAs (ceRNA) has been implicated in the onset and progression of neurological disorders, yet its role in PCABI remains unclear. In this study, we performed RNA transcriptome sequencing analysis to identify differentially expressed genes in the rat model for cardiac arrest and cardiopulmonary resuscitation (CA/CPR). A hub ceRNA regulatory network was constructed using miRWalk 2.0 and Cytohubba plug-in in Cytoscape. Subsequently, real-time quantitative reverse transcription-polymerase chain reaction and dual-luciferase activity assays validated MSTRG.13,871, miR-155-5p, and Grip1 as differentially expressed in CA/CPR group, with MSTRG.13,871 capable of targeting both miR-155-5p and Grip1. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed the ceRNA network enrichment in immunoregulation mechanisms such as mitochondrion, apoptotic process, and negative regulation cell death. Our research highlights the mechanism of PCABI by revealing a critical regulatory axis involving MSTRG.13,871-miR-155-5p-Grip1 in the hippocampus CA1 region after CA/CPR in rats, proposing a feasible controlled mechanism, which may serve as a theoretical basis for designing innovative therapies.

Proactive control for conflict resolution is intact in subclinical obsessive-compulsive individuals

BackgroundObsessive-compulsive (OC) traits (i.e., tendency to implement stereotyped behaviors to avoid negative consequences) are transversally observed in psychiatric disorders largely differing in terms of clinical manifestations and etiopathogenesis. Interestingly, OC traits were also extensively found in the prodromal phases of the full-blown psychopathology and in healthy relatives of affected individuals. Moreover, OC traits were found to be associated—and possibly underlain by—cognitive control impairments. Nonetheless, the role of such interplay in the onset of OC disorders is yet to be understood. We hypothesized that OC traits are associated with abnormalities in proactively implement cognitive control for solving conflict.MethodsWe administered healthy individuals (n = 104) with the perifoveal spatial Stroop task to measure their ability of solving conflict in a proactive fashion, and with Obsessive-Compulsive Inventory (OCI) to stratify population according to the severity of OC traits.ResultsAnalysis of response times by means of Linear Mixed-effect models revealed that proactive control performance was not associated with and the severity of OC traits. Furthermore, an equivalence test (Two One-Sided Test) revealed that the association between OCI scores and task performance was equivalent to zero.ConclusionThese results suggest that the interplay between OC traits and proactive control abnormalities might not contribute to the development of OC-related disorders. Therefore, the role of other cognitive endophenotypes should be scrutinized for exploiting alternative prevention and intervention strategies.

Multi-modal EEG NEO-FFI with Trained Attention Layer (MENTAL) for mental disorder prediction.

Early detection and accurate diagnosis of mental disorders is difficult due to the complexity of the diagnostic process, resulting in conditions being left undiagnosed or misdiagnosed. Previous studies have demonstrated that features of Electroencephalogram (EEG) data, such as Power Spectral Density (PSD), are useful biomarkers for indicating the onset of various mental disorders. Existing models using EEG data are typically trained to distinguish between healthy and afflicted individuals, and they are unable to distinguish between individuals with different disorders. We propose MENTAL (Multi-modal EEG NEO-FFI with Trained Attention Layer) to predict an individual's mental state using both EEG and Neo-Five Factor Inventory (NEO-FFI) personality data. We include an attention layer that captures the interactions between personality traits and PSD features, and emphasizes the important PSD features. MENTAL features a Recurrent Neural Network (RNN) to model the temporal nature of EEG data. We train our model with the Two Decades Brainclinics Research Archive for Insights in Neuroscience (TDBRAIN) dataset, which consists of 1274 healthy and psychiatric individuals including over 30 different diagnoses. MENTAL is able to achieve 93.3% accuracy when trained to classify between healthy individuals and those with ADHD. When trained to identify individuals with ADHD from among 33 disorder classes, MENTAL improves accuracy from 70.5 to 81.7%. MENTAL also demonstrates over 20% improvement in predictive accuracy when trained for MDD prediction. For the multi-class classification task of three classes, MENTAL improves accuracy by 4%, and for five classes, by nearly 8%. MENTAL is the first multi-modal model that utilizes both EEG and NEO-FFI data for the task of mental disorder prediction. We are one of the first groups to utilize TDBRAIN for automated disorder classification. MENTAL is accessible and cost-effective, as EEG is more affordable than other neuroimaging methods such as MRI, and the NEO-FFI is a self- reported survey. Our model can lead to acceptance and support for individuals living with mental health challenges and improve quality of life in our society.

Enhancing Athletic Recovery: Scar Treatment Using Microneedling, Dermal Fillers, and Lasers

Introduction and purpose: Scars represent a prevalent skin irregularity encountered by a significant portion of the population. Beyond merely impacting physical appearance, they can also contribute to the onset of depression and anxiety disorders, which may hinder athletic recovery. The treatment landscape for scars is diverse, spanning non-invasive to invasive procedures. This literature review endeavors to explore scar management, particularly focusing on methodologies involving microneedling, dermal fillers, and laser interventions. By examining these innovative approaches, we aim to provide insights into their efficacy and implications for clinical practice, with a particular emphasis on facilitating a faster return to sport and optimal athletic performance. Material and methods: The literature was conducted using "Pub Med" and "Google Scholar" databases with the keywords „scars”, „microneedling”, „dermal fillers”, „lasers” Brief description of the state of knowledge: Scar therapy using microneedling, dermal fillers, and lasers has shown high effectiveness and significantly improves the lives of patients undergoing treatment. Results and conclusions: Treating scars using microneedling, dermal fillers, and laser therapy has led to significant enhancements in both physical functioning and psychological well-being among patients with visible scars. These procedures exert their efficacy by promoting collagen synthesis and facilitating skin regeneration, thereby ameliorating skin redness, erythema, and scar tissue formation. However, it's important to note that the effectiveness of these interventions varies depending on factors such as the type and depth of the scar, as well as the age of the patient.

The development of the Negative Mental Imagery Questionnaire (MIQ-N).

Mental imagery plays a key role in the onset and maintenance of psychological disorders, and has become the target of psychological interventions for the treatment of several anxiety-related conditions. However, there are currently no transdiagnostic measures designed to assess the varied dimensions of mental imagery relevant to psychopathology. To develop and validate a new measure assessing the experiences and appraisals of negative mental imagery. The initial item pool was generated through a comprehensive literature review and interviews with subject-matter experts. An online community sample provided data for the exploratory (n=345) and confirmatory (n=325) factor analyses. The new 16-item Negative Mental Imagery Questionnaire demonstrated four subscales (Intrusiveness, Controllability, Beliefs about Mental Imagery, and Realness). Reliability and validity were good to excellent for both the full- and sub-scales. Appraisals of mental imagery captured by the new measure are consistent with previous research on mental imagery and psychopathology.

Uric Acid: A Biomarker and Pathogenic Factor of Affective Disorders and Neurodegenerative Diseases.

Uric acid (UA), the end-product of purine metabolism, has a complicated physiological role in the body, showing the combination of regulating inflammatory response, promoting oxidation/anti-oxidation, and modifying autophagy activity in vivo. Meanwhile, various research and theories support that inflammation, oxidative stress, and other risk factors promote the onset and progression of affective disorders and neurodegenerative diseases. Existing studies suggest that UA may be involved in the pathophysiological processes of affective disorders in various ways, and there has been a gradual advance in the understanding of the interplay between UA levels and affective disorders and neurodegenerative diseases. This review summarized the role of UA in the process of inflammation, oxidative stress, and autophagy. On this basis, we discussed the correlation between UA and affective disorders and several neurodegenerative diseases, and simultaneously analyzed the possible mechanism of its influence on affective disorders and neurodegenerative diseases, to provide a theoretical basis for UA as a biomarker or therapeutic target for the diagnosis of these diseases.

Impacts of Maternal Preeclampsia Exposure on Offspring Neuronal Development: Recent Insights and Interventional Approaches.

Preeclampsia, a hypertensive disorder during pregnancy, frequently correlates with adverse neurological outcomes in offspring, including cognitive impairments, autism spectrum disorder, depressive disorder, attention deficit hyperactivity disorder, and cerebral palsy. Despite these known consequences, the understanding of neuronal damage in the offspring of preeclamptic mothers remains insufficient. Here, we review the neuronal abnormalities resulting from maternal preeclampsia exposure, which include disrupted neurogenesis, loss of neuronal cell integrity, accumulation of cellular debris, decreased synaptogenesis and myelination, and increased neurite growth stimulated by maternal preeclampsia serum. The underlying mechanisms potentially driving these effects involve microglial activation, inflammatory responses, and reduced angiogenesis. Intervention strategies aimed at improving fetal neuronal outcomes are also discussed, encompassing pharmacological treatments such as pravastatin, tadalafil, and melatonin, as well as non-pharmacological approaches like dietary modifications, maternal exercise, and standard care for children. These interventions hold promise for clinical application, offering avenues to address early neuronal abnormalities and prevent the onset of long-term neurological disorders.

The impact of climate change-related disasters on mental health and epigenetics: a narrative review

Climate change has contributed to an increase in the frequency and intensity of natural disasters such as droughts, wildfires, hurricanes, and floods, leading to both immediate physical harm and long-term mental health consequences. Survivors often experience psychological distress, including anxiety, depression, and post-traumatic stress disorder (PTSD), as a result of these traumatic events. This narrative review explores the intersection of climate change-related disasters, mental health outcomes, and epigenetic modifications. Specifically, we summarize recent findings on how environmental stressors influence both mental health and epigenetic changes, such as DNA methylation. Emerging evidence suggests that epigenetic mechanisms, particularly DNA methylation, could mediate the effects of climate change-related stress on mental health, potentially contributing to the onset of mental disorders like depression, panic disorder, autism spectrum disorder, and attention deficit hyperactivity disorder. We also discuss other epigenetic mechanisms, such as histone modifications and non-coding RNAs, and emphasize the importance of longitudinal studies to capture the dynamic nature of epigenetic changes over time. Finally, we propose future research directions to deepen our understanding of the complex relationships between climate change-related disasters, mental health outcomes, and epigenetic mechanisms, which will pave the way for more effective mental health interventions and policy integration.

Serum Otoconin-90 and Otolin-1 Concentrations in Benign Paroxysmal Positional Vertigo.

The aim was to evaluate the value of otolith-associated protein otoconin-90 (OC90) and otolin-1 in the pathogenesis research and clinical treatment of benign paroxysmal positional vertigo (BPPV). The study included 50 patients with BPPV admitted to neurology and otorhinolaryngology departments and 30 healthy subjects with no history of dizziness as a control group. BPPV and controls were similar in terms of gender and age. Otolin-1 concentration was significantly greater in the BPPV group than in the controls (710.44 [584.35-837.39] vs 280.45 [212.7-419.61]; p < 0.001). No statistical significance was found, although OC90 was higher in the BPPV group than in the controls. There was a strong positive correlation between otolin-1 and OC90, a moderate negative correlation between otolin-1 and vitamin D, and a strong negative correlation between OC90 and vitamin D in the BPPV patient group. Otolin-1 had high specificity and AUC values for BPPV (AUC: 0.933; 95% CI: 0.881-0.986, 79.2% sensitivity, 100% specificity with a cutoff greater than 525). High serum concentrations of otolin-1 were associated with an increased risk of BPPV, but high concentrations of OC90 were not. Serum concentrations of otolin-1 can potentially be used as a biomarker for the acute onset of inner ear disorders due to the significant increase in patients with BPPV. Vitamin D has high specificity and sensitivity in patients with BPPV. It also provides evidence that BPPV patients with vitamin D deficiency may improve their symptoms with replacement therapy. More large-scale prospective studies are required to confirm these associations and clarify the exact mechanisms.

Longitudinal associations between early post-injury serum BDNF levels and the development of post-traumatic stress disorder over two years

BackgroundThis study investigated the longitudinal associations between serum BDNF (sBDNF) levels measured early after injury and the onset of post-traumatic stress disorder (PTSD) across two years. MethodsPatients with moderate to severe physical injuries were enrolled from a trauma center. At baseline, sBDNF levels were measured and a comprehensive socio-demographic and clinical data were collected. The range of time from physical injuries to blood collection was 1–28 days, with a median (IQR) of 8.0 (6.0) days. PTSD diagnoses were determined at 3, 6, 12, and 24 months post-injury using the CAPS-5. Linear regression analyses assessed the relationship between sBDNF levels and PTSD diagnoses. ResultsOut of 923 patients, 112 (12.1 %) developed PTSD during the study. Prevalence rates were 8.8 % at 3 months, 7.6 % at 6 months, 4.8 % at 12 months, and 3.7 % at 24 months. Significantly, lower sBDNF levels were associated with PTSD at 12 and 24 months, after adjusting for covariates and applying Bonferroni corrections, but not at earlier assessments. LimitationsFocusing on patients with moderate to severe injuries from a single center may limit the findings' generalizability. ConclusionEarly post-injury sBDNF levels are predictive biomarkers for PTSD, especially significant at 12 and 24 months post-injury.

Research Progress on NMDA Receptor Enhancement Drugs for the Treatment of Depressive Disorder.

Major depressive disorder (MDD) is a severe mental illness with a complex etiology. Currently, many medications employed in clinical treatment exhibit limitations such as delayed onset of action and a high incidence of adverse reactions. Therefore, there is a pressing need to develop antidepressants that exhibit enhanced efficacy and safety. The N-methyl-D-aspartate receptor (NMDAR), a distinctive glutamate-gated ion channel receptor, has been implicated in the onset and progression of depressive disorder, as evidenced by both preclinical and clinical research. The NMDAR antagonist, ketamine, exhibits rapid and sustained antidepressant effects, holding promise as a novel therapeutic approach for depressive disorder. However, its psychotomimetic impact and potential for addiction have restricted its widespread clinical application. Notably, over the past decade, studies have suggested that enhancing NMDAR functionality can produce antidepressant effects with improved safety, especially with the emergence of NMDAR-positive allosteric modulators (PAMs). We view this as a potential novel strategy for treating depression, forming the basis for the narrative review that follows.

Psychiatric disorder before and after exposure to violent injury: A nationwide Norwegian register-based cohort study

Interpersonal violent injury is associated with increased risk of subsequent psychological problems, but pre-existing psychopathology may complicate this association in ways that are poorly understood. Using nationwide longitudinal registry data from Norway, we tested how psychiatric history modified the association between violent injury exposure and subsequent psychiatric disorder, and examined disorder continuity before vs. after violent injury. We identified all individuals presenting to emergency services in 2010–2018 with a violent injury, along with sex- and age-matched comparison individuals from the general population. The primary outcome was subsequent psychiatric disorder, observed through December 31, 2018, with secondary analyses examining psychiatric diagnoses pre- vs. post-injury. Of the 28,276 violence-injured patients, 20% had a history of psychiatric disorder, vs. 6% of the 282,760 comparison individuals. In Cox regression models, violence-injured patients had substantially higher rates of any subsequent psychiatric disorder when compared to matched peers (HRadj: 2.36; 95% CI: 2.29, 2.42), but this association was confounded and modified by psychiatric history. Continuity of psychiatric diagnosis before and after injury was high among violence-injured patients, but they were also more likely than the comparison group to receive a new diagnosis, potentially indicating incident onset of new psychiatric disorder associated with violence exposure. Violence-injured patients face substantial burden of psychiatric disorder, especially for substance use and mood/anxiety disorders; clinical and public health strategies are needed to address this burden, which precedes violent injury in some cases but is likely provoked by it in others.

Differential effects of lifetime stressors on major depressive disorder severity: a longitudinal community-based cohort study.

Stressors across the lifespan are associated with the onset of major depressive disorder (MDD) and increased severity of depressive symptoms. However, it is unclear how lifetime stressors are related to specific MDD subtypes. The present study aims to examine the relationships between MDD subtypes and stressors experienced across the lifespan while considering potential confounders. Data analyzed were from the Zone d'Épidémiologie Psychiatrique du Sud-Ouest de Montréal (N = 1351). Lifetime stressors included childhood maltreatment, child-parent bonding, and stressful life events. Person-centered analyses were used to identify the clusters/profiles of the studied variables and multinomial logistic regression analyses were performed to examine the relationships between stressors and identified MDD subtypes. Intersectional analysis was applied to further examine how distal stressors interact with proximal stressors to impact the development of MDD subtypes. There was a significant association between proximal stressors and melancholic depression, whereas severe atypical depression and moderate depression were only associated with some domains of stressful life events. Additionally, those with severe atypical depression and melancholic depression were more likely to be exposed to distal stressors such as childhood maltreatment. The combinations of distal and proximal stressors predicted a greater risk of all MDD subtypes except for moderate atypical depression. MDD was characterized into four subtypes based on depressive symptoms and severity. Different stressor profiles were linked with various MDD subtypes. More specific interventions and clinical management are called to provide precision treatment for MDD patients with unique stressor profiles and MDD subtypes.

IVIG response in pediatric acute-onset neuropsychiatric syndrome correlates with reduction in pro-inflammatory monocytes and neuropsychiatric measures.

Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is characterized by abrupt onset of obsessive-compulsive disorder or eating restriction along with the abrupt onset of other co-occurring symptoms (tics, behavioral and cognitive regression, etc.). PANS is thought to be a post-infectious immunopsychiatric disorder, although as with most post-infectious disorders, it is challenging to establish a causal relationship with proposed infectious triggers. Intravenous immunoglobulin (IVIG) can modulate inflammation and support the elimination of infection and has been used for treatment of many post-infectious inflammatory disorders and autoimmune conditions. The aim of the study is to explore the pro-inflammatory state in PANS before and after administration of IVIG. Children with moderate-to-severe PANS received six infusions of IVIG (Octagam 5%, Octapharma) every 3 weeks with post treatment follow-up. Blood samples and psychiatric measures were obtained at Visits 1 (pre-treatment), 7 and 8 (4 and 11 weeks after last infusion, respectively). Myeloid cell activation was assessed via flow cytometry. All ten patients included in the study were male, White, with mean age 12.4 years (range 6-16). Statistically significant improvements following IVIG treatment were demonstrated in all psychometric assessments and parent questionnaires including CY-BOCS (obsessive compulsive scale), YGTSS (tic scale) and a parent PANS rating scale (for all scales p<0.001). The fraction of pro-inflammatory monocytes and dendritic cells decreased from pre-IVIG treatment levels. The proportional reductions were not compensated by increases in total white blood cells; pro-inflammatory monocytes post-IVIG were decreased as a proportion of CD14+ myeloid cells and in absolute number. The results of this study suggest that active PANS is associated with a pro-inflammatory state. This pro-inflammatory profile and psychometric scores improved following IVIG treatment. Future work will aim to further elucidate the roles of innate and adaptive immune responses in PANS and the regulatory mechanism(s) of IVIG in PANS treatment.

A Systematic Review of Resilience in At-Risk Youth for Psychotic Disorders: An Analysis of Protective and Risk Factors from Recent Literature.

Psychotic disorders in youth pose significant challenges for mental health services, necessitating a detailed understanding of the interplay between risk factors and resilience. This systematic review aimed to assess how resilience factors might buffer the adverse effects of risk factors on the development of psychosis among youth, thereby informing targeted interventions. Studies were selected based on criteria including a focus on individuals aged up to 25 years old at risk for psychosis, the examination of both risk factors and resilience, and the use of validated instruments for measuring outcomes. Literature searches were conducted across several databases, such as PubMed, Scopus, and Web of Science. Data extraction emphasized odds ratios (ORs) and hazard ratios (HRs) for risk factors, including familial, developmental, and socio-environmental influences. The review included and analyzed nine studies, encompassing a diverse sample of 140,972 participants. Significant findings indicate that highly supportive familial and community environments significantly reduce the risk of psychosis onset. For instance, children with strong family support and engagement in structured activities demonstrated a 40% lower incidence of developing psychotic symptoms [p < 0.05]. Furthermore, the presence of neurobehavioral deficits, such as impaired verbal memory and attention, emerged as significant predictors of psychosis, with these children exhibiting a threefold increase in risk compared to their peers [OR = 3.2, 95% CI: 2.1-4.8, p < 0.01]. Resilience factors play a critical role in mitigating the impact of psychosocial and neurobiological risks in the development of psychosis among youths. Interventions enhancing resilience could potentially alter the trajectory of psychosis development, emphasizing the need for early and targeted psychosocial interventions to support at-risk populations. This study underscores the importance of fostering resilience through both individual-focused and community-based strategies to prevent the onset of psychotic disorders in vulnerable young populations.

Early wave reflection of carotid artery is associated with 18F-FDG PET hypometabolism in Alzheimer's brain areas of cognitively normal adults.

Arterial stiffening likely plays a role in Alzheimer disease (AD) pathogenesis. The current study investigated whether inter-individual variations in arterial stiffness and pressure wave parameters were associated with 18F-FDG positron emission tomography (PET) metabolism in AD-associated brain areas throughout adulthood, independently of age and before the onset of any neuropsychological disorders. A prospective, large age-range population of 67 patients (17 young, 16 middle-aged, and 34 older adults; 37 women) underwent a: brain 18F-FDG PET, blood pressure recording, and carotid/femoral pulse wave-based measurements, including the time-to-peak of the reflected backward carotid pulse wave (bT), on the same day. Multivariable and quantitative voxel-to-voxel analyses (P-voxel < 0.005, corrected for cluster volumes) were conducted to assess associations between vascular parameters and 18F-FDG PET metabolism in AD-associated brain areas. In the multivariable analysis, only increased age and decreased bT were independently associated with the decline of metabolic activity in AD-associated brain areas (P < 0.001). In the voxel-to-voxel analysis with age as a covariate, bT was strongly associated with the metabolic activity of 40 clusters in AD-associated brain areas (clusters cumulative volume: 63 cm3; T score max: 5.7). In a large age-range population of adult patients, who are still unaffected by neuropsychological disorders, an early reflected arterial pressure wave, as evidenced by a decreased bT value, is strongly associated with hypometabolic activity of AD-associated brain areas, independently of age.

Refining criteria for a neurodevelopmental sub-phenotype of bipolar disorders: a FondaMental Advanced Centers of Expertise for Bipolar Disorders study

Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. Neurodevelopmental factors were suggested to contribute to the etiology of BD, yet a specific neurodevelopmental phenotype of the disorder remains unidentified. Our objective was to define and characterize a neurodevelopmental phenotype (NDP) in BD and validate its associations with clinical outcomes, polygenic risk scores (PGS), and treatment responses. We analyzed the FACE-BD cohort of 4,468 BD patients, a validation cohort of 101 BD patients, and two independent replication datasets of 274 and 89 BD patients. Using factor analyses, we identified a set of criteria for defining NDP. We next developed a scoring system for NDP-load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and sex with bootstrap replications. Our study established a NDP in BD consisting of nine clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention deficit hyperactivity disorder (ADHD), early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, specific learning disorders. Patients with higher NDP-load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between the NDP-load and PGS for ADHD suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and ADHD. The proposed NDP constitutes a promising clinical tool for patient stratification in BD.