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Pediatric acute-onset neuropsychiatric syndrome (PANS) is a condition characterized by the abrupt, dramatic onset of obsessive&ndash, compulsive disorder (OCD) or eating restriction accompanied by equally abrupt and severe comorbid neuropsychiatric symptoms. PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection) is a heterogeneous syndrome identified as post-Streptococcus pyogenes infection (&beta, hemolytic Streptococcus group A) complications regarding the central nervous system with specific involvement of neuropsychiatric and behavioral skills. In the first part of our study, we share our experience in the treatment of a group of extreme-grade (according to CY-BOCS severity scale) symptomatic patients with intravenous immunoglobulin (IVIG), following the most recent studies regarding the dosage of the drug. Our contribution is to share our experience made on a sample of 55 patients all in the highest level of a severity grade. In the second part of our study, we also analyze the literature on PANS/PANDAS rehabilitation therapy, since in the literature there is no discussion of union and comparison on this method. Objective: This study aims to evaluate the clinical features of the patients observed from different Italian cohorts, with the attempt at evaluating clinical response to IVIG treatment in children with an extreme severity grade of PANS/PANDAS disease. Furthermore, after having analyzed the literature, we propose rehabilitation therapy as an added value to the pharmacological treatment. Materials and Methods: A total of 55 patients with a diagnosis of PANS/PANDAS, who belonged to an extreme grade of disease, were enrolled. All patients were administered with IVIG treatment at 2 g/kg per day for two consecutive days. Results: From our study, a noticeable improvement (until complete remission) of symptoms was evident for at least one year in 47 out of 55 (85%) observed children, while 11 out of these 43 (25%) showed an evident symptoms remission in a single attempt and the remaining 32 (75%) required a second administration to notice a lasting symptomatic improvement.

Introduction Tourette syndrome (TS) is a complex neuropsychiatric disorder. A small percentage of individuals with TS will persist to experience severe, refractory, and impairing tics. Deep brain stimulation (DBS) has been increasingly used for symptom management especially in these settings. In this article, we aim to evaluate the rate and reasons for removal or explantation of DBS hardware in TS patients. Methods Data was analyzed from patients enrolled in the Tourette Association of America's International Tourette Syndrome Registry and Database. Results Fifteen of 269 (5.6%) patients required removal of their DBS systems. The mean age at explantation was 33.8 years. In these cases we observed a rate of 1.9 explantations per year of follow up from implantation. None of the removals took place in the immediate post-operative period. Infection was the most common cause (46.7%). Only one patient received explantation for tic resolution. There were no significant associations between explantation and the presence of specific psychiatric comorbidities, including OCD, depression, anxiety, or ADHD. Discussion The rate of removal of 5.6% was lower than the previously reported rate in the TS DBS literature. Infections account for nearly half of the TS DBS explantations. No relationship to psychiatric comorbidities has been established.

Introduction. It has been hypothesized that pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS) etiology results from an abnormal immune response to streptococcal infection. There is evidence that the serotonergic system is involved in both obsessive-compulsive disorder (OCD) physiopathology and immunological processes. In the 5’ promoter region of 5-HTT, gene encoding for the serotonin transporter we can find the 5-HTTLPR polymorphism that has been associated with OCD. Being PANDAS a disorder with OCD symptoms and likely immune abnormalities, 5-HTT polymorphisms may be particularly relevant for this disorder. Objective. This study aimed to test the association between the 5-HT genotypes and the presence of serum antibodies in patients with PANDAS. Method. We compared the genotype frequencies and serum anti-streptococcal, anti-neural, and anti-enolase antibodies titers between 56 patients with PANDAS and 20 healthy controls from Mexico and Cuba. Results. Antibody titers were higher (anti-enolase, anti-streptococcal) in PANDAS patients compared to healthy controls. No differences in anti-neural antibody levels between both groups were detected. The anti-enolase and anti-neural antibody titer increased according to the polymorphism of the PANDAS patients as follows: LL >SL >SS. Discussion and conclusion. This is the first study evaluating the association between the 5-HTTLPR genotypes and antibody titers in PANDAS patients. Associations between polymorphisms in serotonergic genes and immune response could provide valuable information about the interaction between both systems. Our results suggest an association between the S allele and elevated antibody levels in PANDAS patients.

This study on juvenile SLE patients aimed to evaluate retrospectively the impact of a tertiary center's management policy of the disease severity on its long-term progression and cumulative damage development as well as provision of quality-driven medical care (QmC).Disease activity was assessed by the Physician Global Assessment and SLEDAI-2K, flares by SELENA/SLEDAI, and damage by the pediatric SLICC/DI at diagnosis, 6 months post-diagnosis, and annually thereafter. At the same time, QmC was evaluated by relevant indices and quality of life was captured by the Greek version of the General Health Questionnaire only at the last visit.A total of 35 patients (25/35 females) aged at diagnosis 5.5-15.16 years (median 11.83) with a median lag time to diagnosis 1.8 months had a follow-up of 5 (35/35) and 10 years (13/35), respectively. The predominant baseline manifestations were consistent with those previously reported. Out of 35 patients, 24 (68.5%) were clinically inactive at year 5, and 5/13 (38%) at year 10. All patients received immunosuppressives and 7/35 biologics in addition. At the end of their follow-up, damage was found in 9/35 patients, but none of them had a neuropsychiatric disorder. Over the study, 28/35 patients were compliant with the QmC recommendations.An early diagnosis combined with a longitudinal quantitative assessment of the disease activity and severity contributes to the continuous evaluation of the disease state. They are the key determinants for the selection of an early, targeted, and personalized management; they restrict the cumulative damage development and contribute to an optimal outcome. Key Points • Juvenile SLE has a heavier introductory profile than in adults and an unpredictable trajectory. • The application of contemporary metric tools for assessing the disease state leads to an objective assessment and regimen selection. • An early diagnosis combined with longitudinal quantitative assessment is a key determinant for an optimal management and a minimal damage development.

OBJECTIVE: Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable neuropsychiatric disorder. ADHD often co-occurs with intellectual disability, and shared overlapping genetics have been suggested. The aim of this study was to identify novel ADHD genes by investigating whether genes carrying rare mutations linked to intellectual disability contribute to ADHD risk through common genetic variants. Validation and characterization of candidates were performed using Drosophila melanogaster. METHODS: Common genetic variants in a diagnostic gene panel of 396 autosomal intellectual disability genes were tested for association with ADHD risk through gene set and gene-wide analyses, using ADHD meta-analytic data from the Psychiatric Genomics Consortium for discovery (N=19,210) and ADHD data from the Lundbeck Foundation Initiative for Integrative Psychiatric Research for replication (N=37,076). The significant genes were functionally validated and characterized in Drosophila by assessing locomotor activity and sleep upon knockdown of those genes in brain circuits. RESULTS: The intellectual disability gene set was significantly associated with ADHD risk in the discovery and replication data sets. The three genes most consistently associated were MEF2C, ST3GAL3, and TRAPPC9. Performing functional characterization of the two evolutionarily conserved genes in Drosophila melanogaster, the authors found that their knockdown in dopaminergic (dMEF2) and circadian neurons (dTRAPPC9) resulted in increased locomotor activity and reduced sleep, concordant with the human phenotype. CONCLUSIONS: This study reveals that a large set of intellectual disability-related genes contribute to ADHD risk through effects of common alleles. Utilizing this continuity, the authors identified TRAPPC9, MEF2C, and ST3GAL3 as novel ADHD candidate genes. Characterization in Drosophila suggests that TRAPPC9 and MEF2C contribute to ADHD-related behavior through distinct neural substrates.

Gilles de la Tourette syndrome (TS) is a childhood neuropsychiatric disorder characterised by the presence of motor and vocal tics. Patients with malignant TS experience severe disease sequelae; risking morbidity and mortality due to tics, self-harm, psychiatric comorbidities and suicide. By definition, those cases termed ‘malignant’ are refractory to all conventional psychiatric and pharmacological regimens. In these instances, deep brain stimulation (DBS) may be efficacious. Current 2015 guidelines recommend a 6-month period absent of suicidal ideation before DBS is offered to patients with TS. We therefore wondered whether it may be ethically justifiable to offer DBS to a minor with malignant TS. We begin with a discussion of non-maleficence and beneficence. New evidence suggests that suicide risk in young patients with TS has been underestimated. In turn, DBS may represent an invaluable opportunity for children with malignant TS to secure future safety, independence and fulfilment. Postponing treatment is associated with additional risks. Ultimately, we assert this unique risk-benefit calculus justifies offering DBS to paediatric patients with malignant TS. A multidisciplinary team of clinicians must determine whether DBS is in the best interest of their individual patients. We conclude with a suggestion for future TS-DBS guidelines regarding suicidal ideation. The importance of informed consent and assent is underscored.

Tourette syndrome is a complex neuropsychiatric disorder with a wide phenotypic spectrum, including tics and psychiatric comorbidities, such as obsessive-compulsive disorder and attention-deficit disorder. Often considered a neurodevelopmental disorder, it is most prevalent during childhood and treatment strategies can vary according to degree of severity and patient-specific symptom manifestations. This review focuses on established and emerging management options for tics, including behavioral interventions and nonpharmacologic therapies, medication management, and promising surgical approaches.

Objective Autism spectrum disorder (ASD) is regarded a severe neuropsychiatric disorder. The objective of this study was to compare the status of the oral health between children with and without ASDs. Methods A total of 95 children (44 with ASD and 51 without ASD) were included. dmft/DMFT (d/D: decay; m/M: missing; f/F: filling; t/T: teeth) scores and plaque data of all participants were recorded. Saliva Streptococcus mutans and lactobacilli load were determined using CRT bacteria. Results Streptococcus mutans load was >105 CFU in 54.5% of the ASD group and 43.1% in the non-ASD group. Lactobacilli load was >105 CFU in 47.70% of the ASD group and 49.0% in the non-ASD group. There was no statistically significant difference in the S. mutans or lactobacilli loads between the ASD and non-ASD groups. A total of 83.1% of the ASD group had caries, with dmft = 3.25 and DMFT = 5.10. In the non-ASD group, 81.10% of patients had caries, with dmft = 3.10 and DMFT = 4.90; 38.6% of the ASD group and 29.4% of the non-ASD group had no clinical signs of periodontal disease. Conclusion The examination of the amount of saliva S. mutans and lactobacilli at intervals with these patients will provide quantitative data to evaluate the effectiveness of oral health care.

AMAÇ: Obsesif-kompulsif bozukluk (OKB), tekrarlayan girici düşünceler ve dürtüler ile bunlara bağlı sıkıntıyı azaltmaya yönelik açık veya gizli davranışlarla karakterize nöropsikiyatrik bir bozukluktur. Çalışmalar, OKB belirtilerini spesifik bilişlerle ilişkilendirmiştir, ancak kişilerarası ilişkiler ve kişisel başarılarla ilişkili bilişsel hatalar ile OKB belirtileri arasındaki ilişki yeteri kadar araştırılmamıştır. GEREÇ VE YÖNTEM: OKB ve kontrol grubunun sosyodemografik özellikleri bir psikiyatrist tarafından belirlendi. Bu çalışmada bozukluk belirtileri Maudsley Obsesif Kompulsif Soru Listesi (MOKSL), Belirti Tarama Testi-90-Revize Edilmiş Hali (SCL-90-R) ile değerlendirildi. İşlevsellik, global değerlendirme ölçeği (GAS) ve klinik global izlenim ölçeği (KGİÖ) ile değerlendirildi. Düşünce Özellikleri Ölçeği (DÖÖ) bilişsel hataları değerlendirmek için kullanıldı. BULGULAR: Hem hasta hem kontrol grubu 41 olgudan oluşuyordu. Yaş ve eğitim süreleri her iki grupta benzerdi (p>0.05). Hastalık başlangıç yaşı ortalama 23.12±4.62 yıldı. MOKSL, SCL-90-R, DÖÖ, KGİÖ ve GAS puanları hasta grubunda kontrol grubuna göre belirgin olarak yüksekti. MOKSL ile SCL-90-R alt ölçekleri arasında anlamlı pozitif korelasyonlar bulunurken, MOKSL ile CDS alt ölçekleri arasında korelasyon tespit edilmedi. SONUÇ: Bu çalışma OKB’ye ek psikiyatrik belirtilerin eşlik ettiğini, bu belirtilerin OKB belirtileri ile ilişkili olduğunu, OKB’de bilişsel hata düzeyinin yüksek olduğunu göstermesi bakımından önemlidir. OKB belirti türlerinin bilişsel hata türleri ile ilişkisinin ortaya konulması için ilerleyen çalışmalara ihtiyaç duyulmaktadır.

Background Delirium is a prevalent neuropsychiatric disorder associated with increased morbidity and mortality. Half the cases remain misdiagnosed. Objective Assess the effectiveness of the Stanford Proxy Test for Delirium (S-PTD) in detecting delirium in an inpatient setting. Methods This is a comparison study. Daily assessment with S-PTD, by the patient's nurse, and a neuropsychiatric assessment by a psychiatrist. Assessments were blinded. Inclusion criteria included 18 years or older. Exclusion criteria included patient's or surrogate's unwillingness to participate, inability to consent if a surrogate was not available, and inability to communicate in English or Spanish. A total of 309 patients were approached: 27 declined participation, 4 were excluded, and 278 subjects were followed up throughout their hospital stay. In the end, 78 were excluded for lack of neuropsychiatric assessment, S-PTD, or both. One was excluded for lack of demographic data. The sensitivity and specificity of the S-PTD in detecting delirium when compared with a neuropsychiatric assessment. Results Participants were on average 60.8 years old and 54.3% were male. Patients who developed delirium were, on average, older (15.12 y, confidence interval: 8.94–21.32). A total of 199 patients were analyzed; 43 patients (21.6%) met criteria for delirium. S-PTD detected 67 days with delirium (16.5%) of 405 hospital days, while neuropsychiatric evaluation identified 83 (20.5%). S-PTD had a sensitivity of 80.72% and a specificity of 90.37%. Conclusion S-PTD is an effective, comprehensive, and simple screening tool for delirium, which is robust despite fluctuating symptoms and lack of cooperation. The use of S-PTD may enhance early diagnosis of delirium.

Asymptomatic female carriers of the FMR1 premutation at childbearing age have been mostly identified through prenatal genetic testing, which is routinely proposed in Israel. During the last few years, a premutation phenotype in males and females has been defined-FXAND, including neuropsychiatric disorder, learning difficulties, endocrine dysfunction, and premature ovarian failure. So when a family at risk is identified, should individuals be tested for premutation even if minors? In order to understand what professionals' views are with regard to testing FMR1 premutation in minors, we performed a questionnaire testing both ethical attitudes and knowledge. Eighty-two percent of professionals would positively consider fragile X testing in minors, and an additional 15.4% would consider it in boys only. The specific phenotype of full mutation is recognized well by health professionals, while the premutation phenotype is not well known. There is a need to expand awareness on the fragile X premutation phenotype through better information. Testing of fragile X premutation status in minors should be considered, when at risk due to family history.

Objective As a newly established tuberous sclerosis clinic (TSC) clinic at The Hospital for Sick Children, we reviewed our referrals to determine if children with TSC received appropriate surveillance as advised by the 2012 International Tuberous Sclerosis Complex Consensus Recommendations. Methods We completed a retrospective review of all patients seen in the TSC clinic from January 2016 to December 2017 to determine if children referred to the clinic had appropriate surveillance as suggested by the Tuberous Sclerosis Complex Consensus Recommendations. Results Ninety patients were seen in the TSC clinic. The median age at first visit was 9.9 years, and 47 were males. Seventy-six percent had undergone genetic testing before the initial clinic visit; however, genetic counseling was completed in only 66%. Brain magnetic resonance imaging was completed in 94%, abdominal imaging was completed in 91%, and an echocardiography and electrocardiography in 88% and 83%, respectively. In addition, dermatology and ophthalmology evaluations were completed in 78% and 91%, respectively. Assessment of TSC-associated neuropsychiatric disorders (TAND) was only completed in 4% of the patients. Conclusions Systems surveillance was completed in the majority before the first TSC clinic visit. However, TSC-associated neuropsychiatric disorder screening was completed in few cases. This suggests that referring physicians may not be familiar with the neuropsychiatric manifestations of TSC and that there may be underdiagnosed or undertreated illness. Future emphasis should be placed on educating all practitioners to assess and treat tuberous sclerosis complex-associated neuropsychiatric disorder in tuberous sclerosis complex.

BACKGROUND: Emotion recognition constitutes a pivotal process of social cognition. It involves decoding social cues (e.g., facial expressions) to maximise social adjustment. Current theoretical models posit the relationship between social withdrawal factors (social disengagement, lack of social interactions and loneliness) and emotion decoding.OBJECTIVE: To investigate the role of social withdrawal in patients with schizophrenia (SZ) or probable Alzheimer's disease (AD), neuropsychiatric conditions associated with social dysfunction.METHODS: A sample of 156 participants was recruited: schizophrenia patients (SZ; n = 53), Alzheimer's disease patients (AD; n = 46), and two age-matched control groups (SZc, n = 29; ADc, n = 28). All participants provided self-report measures of loneliness and social functioning, and completed a facial emotion detection task.RESULTS: Neuropsychiatric patients (both groups) showed poorer performance in detecting both positive and negative emotions compared with their healthy counterparts (p CONCLUSIONS: Our findings help to detail the similarities and differences in social function and facial emotion recognition in two disorders rarely studied in parallel, AD and SZ. Transdiagnostic patterns in these results suggest that social withdrawal is associated with heightened sensitivity to negative emotion expressions, potentially reflecting hypervigilance to social threat. Across the neuropsychiatric groups specifically, this hypervigilance associated with social withdrawal extended to positive emotion expressions, an emotional-cognitive bias that may impact social functioning in people with severe mental illness.

Neurological and psychiatric disorders during developmental ages affect an increasing share of the pediatric population, both due to the increased understanding and attention paid to these issues and due to increased risk factors [...]

The objective of our study was to evaluate the impact of the COVID-19 pandemic on the emotional and behavioral symptoms in minors with neuropsychiatric disorders and on parental stress through a standardized neuropsychological assessment, comparing the data collected before the pandemic with those collected during the lock-down. Another goal of our study was to analyze the relationship between parental stress and behavioral/emotional symptoms in children. Our study was conducted on 383 families of patients who had already been referred at the Child Neuropsychiatry Unit of the University Hospital of Salerno for different neuropsychiatric conditions. All the parents completed two neuropsychological standardized questionnaires for the assessment of parental stress (PSI—Parenting Stress Index-Short Form) and the emotional/behavioral problems of their children (Child Behaviour CheckList). The data collected during the pandemic were compared with those collected from questionnaires administered during the six months preceding the pandemic, as is our usual clinical practice. The comparison between the mean scores of PSI and CBCL before and after the pandemic showed a statistically significant increase in all subscales analyzed in the total sample. The correlation analysis showed significant positive relationship between the subscale Total Stress of PSI and the subscales Total Problems and Internalizing Problems of CBCL. Our study suggested that the COVID-19 pandemic and the corresponding measures adopted led to an increase in internalizing and externalizing symptoms in children and adolescents with neuropsychiatric disorder. Similarly, parental stress increased during COVID-19 and ahigher level of stress in parents can be related to the internalizing symptoms of their children.

International journal of molecular sciences 23(12), 6596 (2022). doi:10.3390/ijms23126596, The human genetic variant BDNF (V66M) represents the first example of neurotrophin family member that has been linked to psychiatric disorders. In order to elucidate structural differences that account for the effects in cognitive function, this hproBDNF polymorph was expressed, refolded, purified, and compared directly to the WT variant for the first time for differences in their 3D structures by DSF, limited proteolysis, FT-IR, and SAXS measurements in solution. Our complementary studies revealed a deep impact of V66M polymorphism on hproBDNF conformations in solution. Although the mean conformation in solution appears to be more compact in the V66M variant, overall, we demonstrated a large increase in flexibility in solution upon V66M mutation. Thus, considering that plasticity in IDR is crucial for protein function, the observed alterations may be related to the functional alterations in hproBDNF binding to its receptors p75NTR, sortilin, HAP1, and SorCS2. These effects can provoke altered intracellular neuronal trafficking and/or affect proBDNF physiological functions, leading to many brain-associated diseases and conditions such as cognitive impairment and anxiety. The structural alterations highlighted in the present study may pave the way to the development of drug discovery strategies to provide greater therapeutic responses and of novel pharmacologic strategy in human populations with this common polymorphism, ultimately guiding personalized medicine for neuropsychiatric disorders., Published by Molecular Diversity Preservation International, Basel

Currently, electroencephalogram (EEG) is mostly analyzed in a supervised way, which requires EEG labels (e.g., EEG classification). With the ever-increasing amount of unlabeled/mislabeled EEG in neuropsychiatric disorder diagnosis, BCI, and rehabilitation, manually labeling of EEG data is a labor intensive and time-consuming process, and few labs have developed algorithms to analyze EEG in an unsupervised manner (i.e., EEG clustering). In this paper, we propose a cooperative game inspired approach to cluster multi-trial EEG data. The idea is to map multi-trial EEG clustering to the coalition formation in a cooperative game, and then identify cluster center (the EEG trial with highest Shapley value) and assign EEG trials into proper clusters based on their cross correlation-transformed Shapley values. We demonstrate the mapped EEG cooperative game is convex, and it leads to an algorithm for multi-trial EEG clustering named CoGEEGc. The CoGEEGc yields high-quality multi-trial EEG clustering with respect to intra-cluster compactness and inter-cluster scatter. We show that CoGEEGc outperforms 15 state-of-the-art EEG or time series clustering approaches through detailed experimentation on real-world multi-trial EEG datasets. Comparison against 15 methods with four theoretical properties of clustering further illustrates the superiority of CoGEEGc, as it satisfies two properties while other approaches only satisfy one.

Alpha oscillations (7–13 Hz) are the dominant rhythm in both the resting and active brain. Accordingly, translational research has provided evidence for the involvement of aberrant alpha activity in the onset of symptomatological features underlying syndromes such as autism, schizophrenia, major depression, and Attention Deficit and Hyperactivity Disorder (ADHD). However, findings on the matter are difficult to reconcile due to the variety of paradigms, analyses, and clinical phenotypes at play, not to mention recent technical and methodological advances in this domain. Herein, we seek to address this issue by reviewing the literature gathered on this topic over the last ten years. For each neuropsychiatric disorder, a dedicated section will be provided, containing a concise account of the current models proposing characteristic alterations of alpha rhythms as a core mechanism to trigger the associated symptomatology, as well as a summary of the most relevant studies and scientific contributions issued throughout the last decade. We conclude with some advice and recommendations that might improve future inquiries within this field.

Dissertation, RWTH Aachen University, 2022; Aachen : RWTH Aachen University 1 Online-Ressource : Illustrationen, Diagramme (2022). = Dissertation, RWTH Aachen University, 2022, The sense of smell guides our basic human functions - beyond that, it strongly shapes emotion and memory functions and is essential for complex behaviors. The computations mastering brain functions underlying the sense of smell are not yet understood – neither in the healthy brain state, nor when interrupted in neurological conditions. 1) In this doctoral work, we combined two-photon calcium imaging with an AAV-mediated retrograde tracing approach to record from target-defined output streams in the olfactory bulb. We give the first evidence for parallel processing mechanisms in the olfactory system and add new insights into the complexity and multifaceted strategy of neuronal coding efficiency. 2) Using the genetic SHANK3 mouse model for autism, we first of all developed olfactory assays to decipher autism-associated changes in olfactory behavior. Secondly, we established chronic two-photon calcium imaging of GABAergic interneurons in SHANK3 mice during an olfactory discrimination learning task. Our preliminary data could point to a potential contribution of GABAergic interneurons to altered olfactory bulb circuit function, related to the autism risk gene SHANK3 and open up an interesting avenue to decipher the neural cause of Autism Spectrum Disorder., Published by RWTH Aachen University, Aachen