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The re-ignition of memory reconsolidation research sparked by Karim Nader in the early 2000s led to great excitement that 'reconsolidation-based' interventions might be developed for mental health disorders such as post-traumatic stress disorder and substance use disorder. Two decades on, it is clear that reconsolidation-based interventions have been more challenging to translate to the clinic than initially thought. We argue that this challenge could be addressed with a better understanding of how prior expectations interact with information presented in a putative memory reactivation / cue reminder session, and through the identification of non-invasive biomarkers for memory destabilisation that would allow reminder sessions to be 'tuned' to enhance memory lability in an ad hoc manner.

Psychobiotics, a novel group of probiotics and prebiotics, are a relatively recent discovery, found to modulate central nervous system (CNS)-related functions and behaviors via neuronal, immunological, and metabolic pathways, thus improving not only gastrointestinal (GI) functions, but also suggesting strong antidepressant and anxiolytic potential. Scientists are moving closer to the possibility of treating mental and behavioral illnesses with advanced and cost-effective approaches, targeting dietary modifications in the form of “psychobiotic" supplements consisting of brain-benefiting bacteria, as they uncover more and more about the gut-brain axis. This review examines the relevant scientific work that has been generated so far, analyzing the efficacy of psychobiotic treatment in improving mental health and neuropsychiatric disorders, providing a complete assessment of its potential as an alternative therapy for psychiatric disorders and its future prospects in this domain.

IntroductionPrevious studies have indicated that patients with celiac disease (CD) may have an increased risk of developing neuropsychiatric disorders. However, large-scale epidemiologic studies on the topic are still scarce. We aimed to examine the association between CD and development of neuropsychiatric disorders during an 18-year follow-up period.MethodsWe conducted a prospective cohort study. All Danish patients with an incident diagnosis of CD (ICD-10 K90.0) from 2000 to 2018 were identified in nationwide registries and compared with birthdate- and sex-matched controls (variable 1:10 ratio) for the development of a neuropsychiatric disease. Individual neuropsychiatric diseases were also examined. The absolute risk was calculated by the cumulative incidence, and the relative risk was estimated in Cox regression models.ResultsWe identified a cohort of 6329 patients with CD diagnosed from 2000 to 2018 and 63,287 matches at risk for developing incident neuropsychiatric disorders. The cumulative incidence of development of any neuropsychiatric disorder was 3.9%, 14.9%, 24.8%, 35.9% after 1, 5, 10, and 15 years of follow-up, respectively, in patients with CD compared with 1.8%, 9.3%, 18.3%, and 27.0% in controls. Gray's test for equality p ConclusionsIn this nationwide study including more than 6000 patients with CD, we found an increased risk of development of a neuropsychiatric disorder compared with age- and sex-matched controls. The causes and the clinical relevance of these associations remain to be elucidated. Introduction: Previous studies have indicated that patients with celiac disease (CD) may have an increased risk of developing neuropsychiatric disorders. However, large-scale epidemiologic studies on the topic are still scarce. We aimed to examine the association between CD and development of neuropsychiatric disorders during an 18-year follow-up period. Methods: We conducted a prospective cohort study. All Danish patients with an incident diagnosis of CD (ICD-10 K90.0) from 2000 to 2018 were identified in nationwide registries and compared with birthdate- and sex-matched controls (variable 1:10 ratio) for the development of a neuropsychiatric disease. Individual neuropsychiatric diseases were also examined. The absolute risk was calculated by the cumulative incidence, and the relative risk was estimated in Cox regression models. Results: We identified a cohort of 6329 patients with CD diagnosed from 2000 to 2018 and 63,287 matches at risk for developing incident neuropsychiatric disorders. The cumulative incidence of development of any neuropsychiatric disorder was 3.9%, 14.9%, 24.8%, 35.9% after 1, 5, 10, and 15 years of follow-up, respectively, in patients with CD compared with 1.8%, 9.3%, 18.3%, and 27.0% in controls. Gray's test for equality p < 0.001. The relative risk was HR = 1.58 (95% confidence interval: 1.49–1.68) in CD patients compared with matches. For the individual outcomes, CD was associated with an increased relative risk of developing anxiety, depression, eating disorders, epilepsy, migraine, and stress. We also found indications of an increased relative risk of ADHD, alcoholism, bipolar disorders, and drug abuse, although the associations were less clear. No associations were found between CD and dementia, Parkinson's disease, and schizophrenia. Conclusions: In this nationwide study including more than 6000 patients with CD, we found an increased risk of development of a neuropsychiatric disorder compared with age- and sex-matched controls. The causes and the clinical relevance of these associations remain to be elucidated.

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a rare autoimmune entity in psychiatry literature that occurs when antibodies attack NMDA-type glutamate receptors in the brain. Principle clinical features include a neurological domain such as seizure, orofacial dyskinesia, dystonia, and choreic-like movements of extremities. Also the psychiatric manifestations of this form of encephalitis may vary from psychotic-like symptoms to mood symptoms like depression or mania. Herein we report on five female child cases diagnosed with anti-NMDAR encephalitis, presented with both neurological and psychiatric clinical picture, and highlight the trajectory of disorder from a psychiatric perspective.

Stress represents a main risk factor for psychiatric disorders. Whereas it is known that even a single trauma may induce psychiatric disorders in humans, the mechanisms of vulnerability to acute stressors have been little investigated. In this study, we generated a new animal model of resilience/vulnerability to acute footshock (FS) stress in rats and analyzed early functional, molecular, and morphological determinants of stress vulnerability at tripartite glutamate synapses in the prefrontal cortex (PFC). We found that adult male rats subjected to FS can be deemed resilient (FS-R) or vulnerable (FS-V), based on their anhedonic phenotype 24 h after stress exposure, and that these two populations are phenotypically distinguishable up to two weeks afterwards. Basal presynaptic glutamate release was increased in the PFC of FS-V rats, while depolarization-evoked glutamate release and synapsin I phosphorylation at Ser9 were increased in both FS-R and FS-V. In FS-R and FS-V rats the synaptic expression of GluN2A and apical dendritic length of prelimbic PFC layers II–III pyramidal neurons were decreased, while BDNF expression was selectively reduced in FS-V. Depolarization-evoked (carrier-mediated) glutamate release from astroglia perisynaptic processes (gliosomes) was selectively increased in the PFC of FS-V rats, while GLT1 and xCt levels were higher and GS expression reduced in purified PFC gliosomes from FS-R. Overall, we show for the first time that the application of the sucrose intake test to rats exposed to acute FS led to the generation of a novel animal model of resilience/vulnerability to acute stress, which we used to identify early determinants of maladaptive response related to behavioral vulnerability to stress.

A critical aspect of drug development in the therapy of neuropsychiatric diseases is the “Target Problem”, that is, the selection of a proper target after not simply the etiopathological classification but rather the detection of the supposed structural and/or functional alterations in the brain networks. There are novel ways of approaching the development of drugs capable of overcoming or at least reducing the deficits without triggering deleterious side effects. For this purpose, a model of brain network organization is needed, and the main aspects of its integrative actions must also be established. Thus, to this aim we here propose an updated model of the brain as a hyper-network in which i) the penta-partite synapses are suggested as key nodes of the brain hyper-network and ii) interacting cell surface receptors appear as both decoders of signals arriving to the network and targets of central nervous system diseases. The integrative actions of the brain networks follow the “Russian Doll organization” including the micro (i.e., synaptic) and nano (i.e., molecular) levels. In this scenario, integrative actions result primarily from protein-protein interactions. Importantly, the macromolecular complexes arising from these interactions often have novel structural binding sites of allosteric nature. Taking G protein-coupled receptors (GPCRs) as potential targets, GPCRs heteromers offer a way to increase the selectivity of pharmacological treatments if proper allosteric drugs are designed. This assumption is founded on the possible selectivity of allosteric interventions on G protein-coupled receptors especially when organized as “Receptor Mosaics” at penta-partite synapse level.

Purpose: The current study set out to identify therapeutic plants with psychoactive qualities that were being utilized to treat neuropsychiatric disorders in patients with nervous system diseases as well as general and complex neuropsychiatric disorders. Objective: The core or base objective of this study is to identify plant originated psychoactive molecules or psychotropic actives and its relation in the area of neuropsychiatric or neurologic treatment. Design/Methodology/Approach: The majority of the material utilized to construct the study is secondary and comes from a variety of sources, including clinical literature, journals, websites, etc. Additionally, primary data has been employed to boost the paper's correctness and dependability. Clinical psychopathologists, cardiologists, neuropsychologists, and behavioral medicine experts provided the primary data. To prevent any mistakes and inaccuracies, a comprehensive, rigorous clinical examination of the data has been performed using all of these databases Findings/ Results: The findings list 66 plant species that are utilized to treat neuropsychiatric disorders. The primary plant components utilized were roots (36.2%) and leaves (29%) These components, either alone or in combination, were utilized to make medications primarily through the decoction and trituration processes. Drinks, external treatments, and fumigation were all used to provide remedies. This research suggests that local conventional medicine in many regions of the world has a thorough understanding of neuropsychiatric diseases. The therapeutic treatments recommended in this article are a genuine effort to combat neurological and mental illnesses. Future research on antipsychotic or neuroprotective chemicals may utilize identified plants. Originality and value: To cover the relevant study issue and increase the validity and reliability of the material, a thorough analysis and interpretation have been done. A fresh approach is used to spread knowledge regarding the relationship between medicinal plants and the human mind. Paper type: Secondary Clinical Report Analysis/ Interpretive.&nbsp

Cognitive Symptom Management and Rehabilitation Training (CogSMART) and Compensatory Cognitive Training (CCT) are evidence-based compensatory cognitive training interventions that improve cognition in persons with a history of traumatic brain injury or other neuropsychiatric disorders. Despite demonstrated efficacy, use and effectiveness of CogSMART/CCT in real-world settings is not known.We used a multi-method design to collect and analyze quantitative and qualitative survey data from several domains of the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework to gather information about use of CogSMART/CCT in real-world settings from provider and patient perspectives. Surveys were sent to email addresses from persons who registered on the CogSMART website seeking access to training manuals and other resources. Descriptive statistics were generated, and we used Natural Language Processing methods to study the self-report free responses. Using n-gram analysis, we identified the most frequently reported responses.We found CogSMART/CCT was broadly used in real-world settings and delivered by a variety of providers for several patient groups with high attendance and overall high satisfaction. CogSMART/CCT seemed to be offered in VA- or university-related clinics more than in private practice or rehabilitation centers. The diversity of providers and variety of formats by which to deliver CogSMART/CCT (i.e., individual, group, telehealth) seemed to play a role in its widespread implementation, as did its adaptability. Most providers made adaptations to the intervention that reduced the length or number of sessions. These changes were most likely to be based on client characteristics. The low rates of formal training, however, may have contributed to lower levels of perceived helpfulness among patients.Reach and Adoption of a cognitive rehabilitation intervention improved by increasing access to the manuals. Attention to characteristics of dissemination and implementation in the design of an intervention may enhance its use in real-world settings. The relevant outcomes, easy access to training manuals, and adaptability of CogSMART/CCT seem to have been important factors in its use in a variety of settings and for several disorders with cognitive impairment. The adoption of CogSMART/CCT by a variety of providers other than neuropsychologists suggests its use may be broadened to other healthcare providers, if adequately trained, to increase access to an intervention with demonstrated efficacy for cognitive rehabilitation for several neuropsychiatric disorders.

Objective We sought to identify and correlate the severity of traumatic brain injuries (TBIs) associated with olfactory dysfunction with cognitive and behavioral profiles. Participants and setting Patients with TBI undergoing treatment in a specialized neuro-rehabilitation hospital. Design Prospective study. Main measures Glasgow Coma Scale (GCS) at the time of injury and during posttraumatic amnesia. Motor functions were assessed with the Functional Instrument Measure and Disability Rating Scales. The Wechsler Adult Intelligence test was used for neuropsychologic assessment and the Neuropsychiatric Inventory was used to assess behavioral changes. The Barcelona Smell Test-24 was used to study subjective smell loss. Results A total of 111 patients with TBI were enrolled (33 females; mean age 32.86 years); 38.73% exhibited smell loss. Patients with no olfactory impairment (OI) had worse TBIs than those with OI (GCS scores 5.65 and 7.74, respectively); no significant differences in cognitive behaviors, such as attention memory, visuoperception, and visuoconstruction, were observed. However, patients with TBI and olfactory dysfunction showed statistically significant alterations in neuropsychiatric behavioral performances such as feeding when compared with patients with TBI without smell loss. Conclusion Olfactory dysfunction in patients with a TBI correlates with altered neuropsychiatric behavioral performances such as feeding, sleeping, and motor behavior.

The microbiota-gut-brain axis is a bidirectional signaling mechanism between the gastrointestinal tract and the central nervous system. The complexity of the intestinal ecosystem is extraordinary; it comprises more than 100 trillion microbial cells that inhabit the small and large intestine, and this interaction between microbiota and intestinal epithelium can cause physiological changes in the brain and influence mood and behavior. Currently, there has been an emphasis on how such interactions affect mental health. Evidence indicates that intestinal microbiota are involved in neurological and psychiatric disorders. This review covers evidence for the influence of gut microbiota on the brain and behavior in Alzheimer disease, dementia, anxiety, autism spectrum disorder, bipolar disorder, major depressive disorder, Parkinson’s disease, and schizophrenia. The primary focus is on the pathways involved in intestinal metabolites of microbial origin, including short-chain fatty acids, tryptophan metabolites, and bacterial components that can activate the host’s immune system. We also list clinical evidence regarding prebiotics, probiotics, and fecal microbiota transplantation as adjuvant therapies for neuropsychiatric disorders.

Background The NMDA receptor (NMDAR) plays a key role in the central nervous system, e.g., for synaptic transmission. While synaptic NMDARs are thought to have protective characteristics, activation of extrasynaptic NMDARs might trigger excitotoxic processes linked to neuropsychiatric disorders. Since extrasynaptic NMDARs are typically GluN2B-enriched, the subunit is an interesting target for drug development and treatment monitoring. Recently, the novel GluN2B-specific PET radioligand (R)-[11C]Me-NB1 was investigated in rodents and for the first time successfully translated to humans. To assess whether (R)-[11C]Me-NB1 is a valuable radioligand for (repeated) clinical applications, we evaluated its safety, biodistribution and dosimetry. Methods Four healthy subjects (two females, two males) underwent one whole-body PET/MR measurement lasting for more than 120 min. The GluN2B-specific radioligand (R)-[11C]Me-NB1 was administered simultaneously with the PET start. Subjects were measured in nine passes and six bed positions from head to mid-thigh. Regions of interest was anatomically defined for the brain, thyroid, lungs, heart wall, spleen, stomach contents, pancreas, liver, kidneys, bone marrow and urinary bladder contents, using both PET and MR images. Time-integrated activity coefficients were estimated to calculate organ equivalent dose coefficients and the effective dose coefficient. Additionally, standardized uptake values (SUV) were computed to visualize the biodistribution. Results Administration of the radioligand was safe without adverse events. The organs with the highest uptake were the urinary bladder, spleen and pancreas. Organ equivalent dose coefficients were higher in female in almost all organs, except for the urinary bladder of male. The effective dose coefficient was 6.0 µSv/MBq. Conclusion The GluN2B-specific radioligand (R)-[11C]Me-NB1 was well-tolerated without reported side effects. Effective dose was estimated to 1.8 mSv when using 300 MBq of presented radioligand. The critical organ was the urinary bladder. Due to the low effective dose coefficient of this radioligand, longitudinal studies for drug development and treatment monitoring of neuropsychiatric disorders including neurodegenerative diseases are possible., EJNMMI Research, 12 (1), ISSN:2191-219X

The relaxins (RLNs) are a group of peptide hormone/neuromodulators that can regulate a wide range of physiological processes ranging from reproduction to brain function. All the family members have originated from a RLN3-like ancestor via different rounds of whole genome and gene specific duplications during vertebrate evolution. In mammals, including human, the divergence of the different family members and the emergence of new members led to the acquisition of specific functions for the various relaxin family peptide and associated receptor genes. In particular, in mammals, it was shown, that the role of RLN3 is correlated to the modulation of arousal, stress responses, emotion, social recognition, and other brain functions, positioning this gene/peptide as a potential therapeutic target for neuropsychiatric disorders. This review highlights the evolutionary conservation of relaxin family peptide and receptor gene expression and their associated brain neural circuits. In the zebrafish, the expression pattern of the different relaxin family members has specific features that are conserved in higher species, including a likely similar functional role for the ancestral RLN3-like gene. The use of different model organisms, particularly the zebrafish, to explore the diversification and conservation of relaxin family ligands and receptor systems, provides a relatively high-throughput platform to identify their specific conserved or differential neuromodulatory roles in higher species including human.

Tyrosine kinase inhibitors (TKIs) are widely used in gastrointestinal stromal tumors (GISTs). The aim of this study is to evaluate the reporting frequency of neuropsychiatric adverse drug reactions (ADRs) for TKIs through the analysis of European individual case safety reports (ICSRs). All ICSRs collected in EudraVigilance up to 31 December 2021 with one TKI having GISTs as an indication (imatinib (IM), sunitinib (SU), avapritinib (AVA), regorafenib (REG), and ripretinib (RIP)) were included. A disproportionality analysis was performed to assess the frequency of reporting for each TKI compared to all other TKIs. The number of analyzed ICSRs was 8512, of which 57.9% were related to IM. Neuropsychiatric ADRs were reported at least once in 1511 ICSRs (17.8%). A higher reporting probability of neuropsychiatric ADRs was shown for AVA. Most neuropsychiatric ADRs were known, except for a higher frequency of lumbar spinal cord and nerve root disorders (reporting odds ratio, ROR 4.46; confidence interval, CI 95% 1.58–12.54), olfactory nerve disorders (8.02; 2.44–26.33), and hallucinations (22.96; 8.45–62.36) for AVA. The analyses of European ICSRs largely confirmed the safety profiles of TKIs in GISTs, but some ADRs are worthy of discussion. Further studies are needed to increase the knowledge of the neuropsychiatric disorders of newly approved TKIs.

BET proteins function as histone code readers of acetylated lysins that determine the positive regulation in transcription of genes involved in cell cycle progression, differentiation, inflammation, and many other pathways. In recent years, thanks to the development of BET inhibitors, interest in this protein family has risen for its relevance in brain development and function. For example, experimental evidence has shown that BET modulation affects neuronal activity and the expression of genes involved in learning and memory. In addition, BET inhibition strongly suppresses molecular pathways related to neuroinflammation. These observations suggest that BET modulation may play a critical role in the onset and during the development of diverse neurodegenerative and neuropsychiatric disorders, such as Alzheimer’s disease, fragile X syndrome, and Rett syndrome. In this review article, we summarize the most recent evidence regarding the involvement of BET proteins in brain physiology and pathology, as well as their pharmacological potential as targets for therapeutic purposes.

A spectrum of neuropsychiatric disorders is a common complication from stroke. Neuropsychiatric disorders after stroke have negative effects on functional recovery, increasing the rate of mortality and disability of stroke survivors. Given the vital significance of maintaining physical and mental health in stroke patients, neuropsychiatric issues after stroke have raised concerns by clinicians and researchers. This mini-review focuses on the most common non-cognitive functional neuropsychiatric disorders seen after stroke, including depressive disorders, anxiety disorders, post-traumatic stress disorder, psychosis, and psychotic disorders. For each condition, the clinical performance, epidemiology, identification of the therapeutic implication, and strategies are reviewed and discussed; the main opinions and perspectives presented here are based on the latest controlled studies, meta-analysis, or updated systematic reviews. In the absence of data from controlled studies, consensus recommendations were provided accordingly.

Significance Variation is rampant throughout human genomes: some of it affects disease risk, and most does not; to separate the two requires a plethora of hypothesis tests. This challenge of multiple testing—limiting false positives while maximizing power—arises in many “omics” studies and sciences. One approach is to control the false discovery rate (FDR), and a recent selective inference method for controlling FDR, adaptive P-value thresholding (AdaPT), facilitates incorporation of auxiliary information (covariates) related to each hypothesis test. How AdaPT performs on data is an open question. We apply AdaPT to results from genomic association studies and include many covariates. This adaptive search discovers a more complex and interpretable model with far greater power than classic multiple testing procedures., To correct for a large number of hypothesis tests, most researchers rely on simple multiple testing corrections. Yet, new methodologies of selective inference could potentially improve power while retaining statistical guarantees, especially those that enable exploration of test statistics using auxiliary information (covariates) to weight hypothesis tests for association. We explore one such method, adaptive P-value thresholding (AdaPT), in the framework of genome-wide association studies (GWAS) and gene expression/coexpression studies, with particular emphasis on schizophrenia (SCZ). Selected SCZ GWAS association P values play the role of the primary data for AdaPT; single-nucleotide polymorphisms (SNPs) are selected because they are gene expression quantitative trait loci (eQTLs). This natural pairing of SNPs and genes allow us to map the following covariate values to these pairs: GWAS statistics from genetically correlated bipolar disorder, the effect size of SNP genotypes on gene expression, and gene–gene coexpression, captured by subnetwork (module) membership. In all, 24 covariates per SNP/gene pair were included in the AdaPT analysis using flexible gradient boosted trees. We demonstrate a substantial increase in power to detect SCZ associations using gene expression information from the developing human prefrontal cortex. We interpret these results in light of recent theories about the polygenic nature of SCZ. Importantly, our entire process for identifying enrichment and creating features with independent complementary data sources can be implemented in many different high-throughput settings to ultimately improve power.

Aim. To study the dental status of patients with neuropsychiatric disorders in dental debridement under general anaesthesia. Methods. A comparison of the prevalence of oral pathology among patients depending on gender, age, and nosological group was performed. It was studied the dependence of the prevalence of both acute and chronic forms of dental pathology on the type of background disease and compared the frequency of dental pathology depending on the background disease. Results. 50.8% of patients were male and 63.82% were female. All patients had poor oral hygiene and lack of knowledge about personal hygiene practices. Dentin caries (K01.2) was in 39 (30.5%) patients, irreversible pulpitis (K04.0) in 31 (24.2%) patients, and chronic forms of periodontitis and their exacerbation (K04.5) in 99 (77.3%) patients. In our study, most patients with neuropsychiatric disorders (35.9%) had Cerebral palsy (G80), 28.1% had mental retardation (F70F73), and 10.2% had schizophrenia (F20). Irreversible pulpitis (K04.0) was statistically significantly more common in patients diagnosed with cerebral palsy (G80) 21.7%, while in patients with mental retardation (F70F73) only in 5.6% (p=0.007). The prevalence of periodontitis was highest in patients with mental retardation (F70F73) 86.1%, medium in patients with schizophrenia (F20) 46.2% and lowest in other diseases (39.4%); the differences were statistically significant (p=0.001). Conclusion. We identified characteristics of the dental status, intensity and prevalence of dental diseases in patients with neuropsychiatric disorders in dental debridement under general anaesthesia.

Glycogen synthase kinase 3β (GSK3) is a multifaceted serine/threonine (S/T) kinase expressed in all eukaryotic cells. GSK3β is highly enriched in neurons in the central nervous system where it acts as a central hub for intracellular signaling downstream of receptors critical for neuronal function. Unlike other kinases, GSK3β is constitutively active, and its modulation mainly involves inhibition via upstream regulatory pathways rather than increased activation. Through an intricate converging signaling system, a fine-tuned balance of active and inactive GSK3β acts as a central point for the phosphorylation of numerous primed and unprimed substrates. Although the full range of molecular targets is still unknown, recent results show that voltage-gated ion channels are among the downstream targets of GSK3β. Here, we discuss the direct and indirect mechanisms by which GSK3β phosphorylates voltage-gated Na+ channels (Nav1.2 and Nav1.6) and voltage-gated K+ channels (Kv4 and Kv7) and their physiological effects on intrinsic excitability, neuronal plasticity, and behavior. We also present evidence for how unbalanced GSK3β activity can lead to maladaptive plasticity that ultimately renders neuronal circuitry more vulnerable, increasing the risk for developing neuropsychiatric disorders. In conclusion, GSK3β-dependent modulation of voltage-gated ion channels may serve as an important pharmacological target for neurotherapeutic development.

Recent advances in genetics, molecular biology, and stem cell biology have accelerated our understanding of neuropsychiatric disorders, like autism spectrum disorder (ASD), major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SZ). This progress highlights the incredible complexity of both the human brain and mental illnesses from the biochemical to the cellular level. Contributing to the complexity of neuropsychiatric disorders are their polygenic nature, cellular and brain region interconnectivity, and dysregulation of human-specific neurodevelopmental processes. Here, we discuss available tools, including CRISPR-Cas9, and the applications of these tools to develop cell-based two-dimensional (2D) models and 3D brain organoid models that better represent and unravel the intricacies of neuropsychiatric disorder pathophysiology.

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.

Epileptic seizure prediction is one of the most used therapeutic adjuvant strategies for drug-resistant epilepsy. Conventional approaches commonly collect training and testing samples from the same patient due to inter-individual variability. However, the challenging problem of domain shift between various subjects remains unsolved, resulting in a low conversion rate to the clinic. In this work, a domain adaptation (DA)-based model is proposed to circumvent this issue. The short-time Fourier transform (STFT) is employed to extract the time-frequency features from raw EEG data, and an autoencoder is developed to map these features into high-dimensional space. By minimizing the inter-domain distance in the embedding space, this model learns the domain-invariant information, such that the generalization ability is improved by distribution alignment. Besides, to increase the feasibility of its application, this work mimics the data distribution under the clinical sampling situation and tests the model under this condition, which is the first study that adopts the assessment strategy. Experimental results on both intracranial and scalp EEG databases demonstrate that this method can minimize the domain gap effectively compared with previous approaches.

Despite the availability of over 30 antiseizure medications (ASMs), there is no "one size fits it all," so there is a continuing search for novel ASMs. There are divergent data demonstrating that modulation of distinct serotonin (5-hydroxytryptamine, 5-HT) receptors subtypes could be beneficial in the treatment of epilepsy and its comorbidities, whereas only a few ASM, such as fenfluramine (FA), act via 5-HT. There are 14 different 5-HT receptor subtypes, and most epilepsy studies focus on one or a few of these subtypes, using different animal models and different ligands. We reviewed the available evidence of each 5-HT receptor subtype using MEDLINE up to July 2021. Our search included medical subject heading (MeSH) and free terms of each "5-HT subtype" separately and its relation to "epilepsy or seizures." Most research underlines the antiseizure activity of 5-HT1A,1D,2A,2C,3 agonism and 5-HT6 antagonism. Consistently, FA, which has recently been approved for the treatment of seizures in Dravet syndrome, is an agonist of 5-HT1D,2A,2C receptors. Even though each study focused on a distinct seizure/epilepsy type and generalization of different findings could lead to false interpretations, we believe that the available preclinical and clinical studies emphasize the role of serotonergic modulation, especially stimulation, as a promising avenue in epilepsy treatment. ispartof: EPILEPSIA OPEN vol:7 issue:2 pages:231-246 ispartof: location:United States status: published

Introduction: Few studies have focused on the long-term effects of the COVID-19 pandemic on mental health. The objective of our work was to evaluate the changes in emotional and behavioral symptoms in patients with neuropsychiatric disorders and the impact on parenting stress 1 year after the first national lockdown. Methods: We enrolled 369 patients aged 1.5–18 years of age referred to the Child and Adolescent Neuropsychiatry Unit of the University Hospital of Salerno (Italy) by their parents. We asked their parents to complete two standardized questionnaires for the assessment of emotional/behavioral symptoms (Child Behavior CheckList, CBCL) and parental stress (Parenting Stress Index, PSI) prior to the pandemic (Time 0), during the first national lockdown (Time 1) and after 1 year (Time 2), and we monitored the changes in symptoms over time. Results: After 1 year from the start of the first national lockdown, we found a significant increase of internalizing problems, anxiety, depression, somatization, and social and oppositional-defiant problems in older children (6–18 years), and a significant increase of somatization, anxiety problems, and sleep problems in younger children (1.5–5 years). We also observed a significant relationship between emotional/behavioral symptoms and parental stress. Conclusion: Our study showed that parental stress levels increased compared to the pre-pandemic months and continues to persist over time, while internalizing symptoms of children and adolescents showed a significant worsening during 1 year follow-up from the first COVID-19 lockdown.

Despite some innate limitations, animal models are a potent investigative tool when used to model specific symptoms of a disorder. For example, MK-801, an N-methyl-D-aspartate receptor antagonist, is used as a pharmacological tool to induce symptoms found in some neuropsychiatric disorders. However, a close examination of literature suggests that the application window of MK-801 doses is relatively narrow between individual behavioral paradigms, necessitating careful characterization of the evoked behavioral aberrations and the doses used to induce them. Moreover, variation in behaviors depending on the animal strain, gender of the subject, and the timing of administration is observed, making it difficult to compare the behavioral characteristics reported in different studies. We aim to characterize the behavioral aberrations induced by different doses of MK-801 in CD-1 mice and create a ready reference for future studies. We used CD-1 mice to recapitulate behavioral impairments resulting from acute administration of MK-801. In 0.1 mg kg−1, we observed diminished spontaneous alteration during the Y-maze test, while 0.12 mg kg−1 resulted in hyperlocomotion and social deficit. Mice treated with 0.2 and 0.3 mg kg−1 of MK-801 demonstrated a decreased self-grooming. Finally, all doses significantly impaired cliff avoidance behaviors suggesting increased impulsivity. These results affirm that MK-801 can effectively model various symptoms of different neuropsychiatric disorders in a dose-dependent manner. The observed sensitivity against spatial-memory impairment and impulsive behaviors at low concentration of MK-801 suggest that MK801 may modulate cognitive function and impulsivity in even lower concentration before it can modulate other behavioral domains.

A bidirectional relationship exists between hypertension and psychiatric disorders, including unipolar and bipolar depression, anxiety, post-traumatic stress disorder (PTSD), psychosis, schizophrenia, mania, and dementia/cognitive decline. Repurposing of antihypertensive drugs to treat mental disorders is thus being explored. A systematic knowledge of the mechanisms of action and clinical consequences of the use of antihypertensive agents on neuropsychiatric functions has not been achieved yet. In this article, we review the putative role of antihypertensive agents in psychiatric disorders, discuss the targets and mechanisms of action, and examine how and to what extent specific drug classes/molecules may trigger, worsen, or mitigate psychiatric symptoms. In addition, we review pharmacokinetics (brain penetration of drugs) and pharmacogenetics data that add important information to assess risks and benefits of antihypertensive drugs in neuropsychiatric settings. The scientific literature shows robust evidence of a positive effect of α1 blockers on PTSD symptoms, nightmares and sleep quality, α2 agonists on core symptoms, executive function, and quality of life in Attention-Deficit/Hyperactivity Disorder, PTSD, Tourette’s syndrome, and β blockers on anxiety, aggression, working memory, and social communication. Renin-angiotensin system modulators exert protective effects on cognition, depression, and anxiety, and the loop diuretic bumetanide reduced the core symptoms of autism in a subset of patients. There is no evidence of clear benefits of calcium channel blockers in mood disorders in the scientific literature. These findings are mainly from preclinical studies; clinical data are still insufficient or of anecdotal nature and seldom systematic. The information herewith provided can support a better therapeutic approach to hypertension, tailored to patients with, or with high susceptibility to, psychiatric illness. It may prompt clinical studies exploring the potential benefit of antihypertensive drugs in selected patients with neuropsychiatric comorbidities that include outcomes of neuropsychiatric interest and specifically assess undesirable effects or interactions.

Reelin is an extracellular matrix protein that is mainly produced in Cajal-Retzius cells and controls neuronal migration, which is important for the proper formation of cortical layers in the developmental stage of the brain. In the adult brain, Reelin plays a crucial role in the regulation of N-methyl-D-aspartate receptor-dependent synaptic function, and its expression decreases postnatally. Clinical studies showed reductions in Reelin protein and mRNA expression levels in patients with psychiatric disorders; however, the causal relationship remains unclear. Reelin-deficient mice exhibit an abnormal neuronal morphology and behavior, while Reelin supplementation ameliorates learning deficits, synaptic dysfunctions, and spine loss in animal models with Reelin deficiency. These findings suggest that the neuronal deficits and brain dysfunctions associated with the down-regulated expression of Reelin are attenuated by enhancements in its expression and functions in the brain. In this review, we summarize findings on the role of Reelin in neuropsychiatric disorders and discuss potential therapeutic approaches for neuropsychiatric disorders associated with Reelin dysfunctions.

Neurodevelopmental and neuropsychiatric disorders, such as autism spectrum disorder and schizophrenia, have strong genetic risk components, but the underlying mechanisms have proven difficult to decipher. Rare, high-risk variants may offer an opportunity to delineate the biological mechanisms responsible more clearly for more common idiopathic diseases. Indeed, different rare variants can cause the same behavioral phenotype, demonstrating genetic heterogeneity, while the same rare variant can cause different behavioral phenotypes, demonstrating variable expressivity. These observations suggest convergent underlying biological and neurological mechanisms; identification of these mechanisms may ultimately reveal new therapeutic targets. At the 2021 Keystone Symposium “Neuropsychiatric and Neurodevelopmental Disorders: Harnessing Rare Variants”, a panel of experts in this field of research described significant progress in genomic discovery and human phenotyping and raised several consistent issues, including the need for detailed natural history studies of rare disorders, the challenges in cohort recruitment, and the importance of viewing phenotypes as quantitative traits that are impacted by rare variants.

The mechanisms associated with neophobia and anhedonia remain largely unknown. Neuropsychological disorders such as depression and schizophrenia are associated with excessive fear and anhedonia, and have been linked to microRNA 137. We hypothesized that microRNAs (miRNAs) in the snail Lymnaea stagnalis are important for regulating feeding behaviour through either preventing neophobia or establishing hedonic value. To test these hypotheses, we used an injection of poly-l-lysine (PLL) to inhibit miRNA biogenesis and observed its effects on feeding behaviour. We repeated these experiments with pre-exposure to novel stimuli capable of eliciting neophobia to disentangle the processes predicted to regulate feeding behaviour. Next, we exposed snails to food stimuli of high hedonic value after PLL injection to reset their hedonic value for that food. Finally, we consolidated our results with previous research by examining the effect of PLL injection on a one-trial appetitive classical conditioning procedure (1TT) to induce long-term memory (LTM). We found that miRNAs are likely not required for preventing neophobia. Moreover, we discovered that snails experienced anhedonia in response to inhibition of miRNA biogenesis, resulting in diminished feeding behaviour for food stimuli with a previously high hedonic value. Snails showed diminished feeding behaviour for multiple food stimuli of high hedonic value post-1TT with PLL injection. This finding suggests that PLL causes anhedonia rather than an impairment of LTM formation following the 1TT procedure. This is the first evidence suggesting that inhibiting the biogenesis of miRNAs contributes to anhedonia in L. stagnalis.

The coronavirus disease 2019 (COVID-19) pandemic has generated a lot of stress and anxiety among not only infected patients but also the general population across the globe, which disturbs cerebral immune homeostasis and potentially exacerbates the SARS-CoV-2 virus-induced neuroinflammation, especially among people susceptible to neuropsychiatric disorders. Here, we used a chronic unpredictable mild stress (CUMS) mouse model to study its effects on glia-mediated neuroinflammation and expression of SARS-CoV2 viral receptors. We observed that female mice showed depressive-like behavior after CUMS, whereas male mice showed enhanced anxiety and social withdrawal. Interestingly, CUMS led to increased amounts of total and MHCII+ microglia in the hippocampi of female mice but not male mice. mRNA levels of SARS-CoV-2 viral receptors angiotensin-converting enzyme 2 (Ace2) and basigin (Bsg) were also upregulated in the prefrontal cortices of stressed female mice but not male mice. Similarly, sex-specific changes in SARS-CoV-2 viral receptors FURIN and neuropilin-1 (NRP1) were also observed in monocytes of human caregivers enduring chronic stress. Our findings provided evidence on detrimental effects of chronic stress on the brain and behavior and implied potential sex-dependent susceptibility to SARS-CoV-2 infection after chronic stress.

Objectives: The key characteristics of this study are to highlight the research trend pertaining to the use of machine learning in the diagnosis and management of neuropsychiatric conditions. Methods: The last ten years (2011-2020) Scopus data related to the use of machine learning techniques in the diagnosis and management of neuropsychiatric disorders in human beings have been collected and examined using VOSviewer. The global internet trend for neuropsychiatric disorders and machine learning techniques during the observation period (1-Jan-2010 to 30-Nov-2020) has been also explored using Google Trend. Results: The mean values of the Google trend for neuropsychiatric disorders and machine learning are 52.09 and 40.00 respectively. Moreover, the correlation coefficient for the Google trend of USA, UK and the world found to be significantly (0.98) higher. Likewise, the mean values of web trend for USA, UK, and China are 42.17, 38.55, and 30.90. Additionally, the Google trend for the term ‘machine learning’ in the observation period (1-Jan-2010 to 30-Nov-2020) has been also explored. Conclusion: It is observed that the researchers from the US (32.4%), UK (9.2%) and China (7.4%) are the prime contributors as far as mining and management of the neuropsychiatric disorders using machine learning is concerned. Moreover, the study revealed that neuropsychiatric disorders (seizure, eating, mood, sleep, conduct, and intellectual) need more attention as far as machine learning is concerned.

Most mental disorders, such as addictive diseases or schizophrenia, are characterized by impaired cognitive function and behavior control originating from disturbances within prefrontal neural networks. Their often chronic reoccurring nature and the lack of efficient therapies necessitate the development of new treatment strategies. Brain-computer interfaces, equipped with multiple sensing and stimulation abilities, offer a new toolbox whose suitability for diagnosis and therapy of mental disorders has not yet been explored. This study, therefore, aimed to develop a biocompatible and multimodal neuroprosthesis to measure and modulate prefrontal neurophysiological features of neuropsychiatric symptoms. We used a 3D-printing technology to rapidly prototype customized bioelectronic implants through robot-controlled deposition of soft silicones and a conductive platinum ink. We implanted the device epidurally above the medial prefrontal cortex of rats and obtained auditory event-related brain potentials in treatment-naïve animals, after alcohol administration and following neuromodulation through implant-driven electrical brain stimulation and cortical delivery of the anti-relapse medication naltrexone. Towards smart neuroprosthetic interfaces, we furthermore developed machine learning algorithms to autonomously classify treatment effects within the neural recordings. The neuroprosthesis successfully captured neural activity patterns reflecting intact stimulus processing and alcohol-induced neural depression. Moreover, implant-driven electrical and pharmacological stimulation enabled successful enhancement of neural activity. A machine learning approach based on stepwise linear discriminant analysis was able to deal with sparsity in the data and distinguished treatments with high accuracy. Our work demonstrates the feasibility of multimodal bioelectronic systems to monitor, modulate and identify healthy and affected brain states with potential use in a personalized and optimized therapy of neuropsychiatric disorders.

The gut microbiome has attracted increasing attention from researchers in recent years. The microbiota can have a specific and complex cross-talk with the host, particularly with the central nervous system (CNS), creating the so-called “gut–brain axis”. Communication between the gut, intestinal microbiota, and the brain involves the secretion of various metabolites such as short-chain fatty acids (SCFAs), structural components of bacteria, and signaling molecules. Moreover, an imbalance in the gut microbiota composition modulates the immune system and function of tissue barriers such as the blood–brain barrier (BBB). Therefore, the aim of this literature review is to describe how the gut–brain interplay may contribute to the development of various neurological disorders, combining the fields of gastroenterology and neuroscience. We present recent findings concerning the effect of the altered microbiota on neurodegeneration and neuroinflammation, including Alzheimer’s and Parkinson’s diseases, as well as multiple sclerosis. Moreover, the impact of the pathological shift in the microbiome on selected neuropsychological disorders, i.e., major depressive disorders (MDD) and autism spectrum disorder (ASD), is also discussed. Future research on the effect of balanced gut microbiota composition on the gut–brain axis would help to identify new potential opportunities for therapeutic interventions in the presented diseases.

IntroductionPregnant and postpartum women face major psychological stressors that put them at higher risk of developing common mental disorders, such as depression and anxiety. Yet, their limited access to and uptake of traditional mental health care is inequitable, especially during the COVID-19 pandemic. Mobile interventions emerged as a potential solution to this discontinued healthcare access, but more knowledge is needed about their effectiveness and impact on health equity. This equity-focused systematic review examined the effectiveness and equity impact of mobile interventions targeting common mental disorders among pregnant and postpartum women.Methods and resultsWe systematically searched MEDLINE, EMBASE, PsychINFO and 3 other databases, from date of database inception and until January 2021, for experimental studies on mobile interventions targeting pregnant and postpartum women. We used pooled and narrative synthesis methods to analyze effectiveness and equity data, critically appraised the methodological rigour of included studies using Cochrane tools, and assessed the certainty of evidence using the GRADE approach. Our search identified 6148 records, of which 18 randomized and non-randomized controlled trials were included. Mobile interventions had a clinically important impact on reducing the occurrence of depression (OR = 0.51 [95% CI 0.41 to 0.64]; absolute risk reduction RD: 7.14% [95% CI 4.92 to 9.36]; pConclusionAs the COVID-19 pandemic has increased the need for virtual mental health care, mobile interventions show promise in preventing and managing common mental disorders among pregnant and postpartum women. Such interventions carry the potential to address health inequity but more rigorous research that examines patients’ intersecting social identities is needed.

In the last decade, Autism has broadened and often shifted its diagnostics criter a, allowing several neuropsychiatric and neurological disorders of known etiology. This has resulted in a highly heterogeneous spectrum with apparent exponential rates in prevalence. I ask if it is possible to leverage existing genetic information about those disorders making up Autism today and use it to stratify this spectrum. To that end, I combine genes linked to Autism in the SFARI database and genomic information from the DisGeNet portal on 25 diseases, inclusive of non-neurological ones. I use the GTEx data on genes’ expression on 54 human tissues and ask if there are overlapping genes across those associated to these diseases and those from SFARI-Autism. I find a compact set of genes across all brain-disorders which express highly in tissues fundamental for somatic-sensory-motor function, self-regulation, memory, and cognition. Then, I offer a new stratification that provides a distance-based orderly clustering into possible Autism subtypes, amenable to design personalized targeted therapies within the framework of Precision Medicine. I conclude that viewing Autism through this physiological (Precision) lens, rather than viewing it exclusively from a psychological behavioral construct, may make it a more manageable condition and dispel the Autism epidemic myth.

The role of lateral mobility and nanodomain organization of G protein-coupled receptors in modulating subcellular signaling has been under increasing scrutiny. Investigation of D2 dopamine receptor diffusion dynamics is of particular interest, as these receptors have been linked to altered neurotransmission in affective disorders and represent the primary target for commonly prescribed antipsychotics. Here, we applied our single quantum dot tracking approach to decipher intrinsic diffusion patterns of the wild-type long isoform of D2 dopamine receptor and its genetic variants previously identified in several cohorts of schizophrenia patients. We identified a subtle decrease in the diffusion rate of the Val96Ala mutant that parallels its previously reported reduced affinity for potent neuroleptics clozapine and chlorpromazine. Slower Val96Ala variant diffusion was not accompanied by a change in receptor-receptor transient interactions as defined by the diffraction-limited quantum dot colocalization events. In addition, we implemented a Voronoї tessellation-based algorithm to compare nanoclustering of D2 dopamine receptor to the dominant anionic phospholipid phosphatidylinositol 4,5-bisphosphate in the plasma membrane of live cells.

Electroconvulsive therapy (ECT) was applied for the first time in humans in 1938: after 80 years, it remains conceptually similar today except for modifications of the original protocol aimed to reduce adverse effects (as persistent memory deficits) without losing clinical efficacy. We illustrate the stages of development as well as ups and downs of ECT use in the last eighty years, and the impact that it still maintains for treatment of certain psychiatric conditions. Targeted, individualized and safe noninvasive neuromodulatory interventions are now possible for many neuropsychiatric disorders thanks to repetitive transcranial magnetic stimulation (rTMS) that injects currents in the brain through electromagnetic induction, powerful enough to depolarize cortical neurons and related networks. Although ECT and rTMS differ in basic concepts, mechanisms, tolerability, side effects and acceptability, and beyond their conceptual remoteness (ECT) or proximity (rTMS) to “precision medicine” approaches, the two brain stimulation techniques may be considered as complementary rather than competing in the current treatment of certain neuropsychiatric disorders.

BackgroundGamma-hydroxybutyrate (GHB; or sodium oxybate) is an endogenous GHB-/gamma-aminobutyric acid B receptor agonist. It is approved for application in narcolepsy and has been proposed for the potential treatment of Alzheimer’s disease, Parkinson’s disease, fibromyalgia, and depression, all of which involve neuro-immunological processes. Tryptophan catabolites (TRYCATs), the cortisol-awakening response (CAR), and brain-derived neurotrophic factor (BDNF) have been suggested as peripheral biomarkers of neuropsychiatric disorders. GHB has been shown to induce a delayed reduction of T helper and natural killer cell counts and alter basal cortisol levels, but GHB’s effects on TRYCATs, CAR, and BDNF are unknown.MethodsTherefore, TRYCAT and BDNF serum levels, as well as CAR and the affective state (Positive and Negative Affect Schedule [PANAS]) were measured in the morning after a single nocturnal dose of GHB (50 mg/kg body weight) in 20 healthy male volunteers in a placebo-controlled, balanced, randomized, double-blind, cross-over design.ResultsIn the morning after nocturnal GHB administration, the TRYCATs indolelactic acid, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid; the 3-hydroxykynurenine to kynurenic acid ratio; and the CAR were significantly reduced (P < 0.05–0.001, Benjamini-Hochberg corrected). The quinolinic acid to kynurenic acid ratio was reduced by trend. Serotonin, tryptophan, and BDNF levels, as well as PANAS scores in the morning, remained unchanged after a nocturnal GHB challenge.ConclusionsGHB has post-acute effects on peripheral biomarkers of neuropsychiatric disorders, which might be a model to explain some of its therapeutic effects in disorders involving neuro-immunological pathologies. This study was registered at ClinicalTrials.gov as NCT02342366.

Serotonin (5-hydroxytriptamine; 5-HT) is a fascinating neurotransmitter that thanks to an extensive axonal network is released throughout the entire central nervous system (CNS) and exerts its action on the modulation of a countless number of physiological, behavioral and cognitive processes. In addition, cumulating evidences have linked alteration in 5-HT neurotransmission with the onset of psychiatric and neurodevelopmental disorders, such as depression, autisms and schizophrenia. Nevertheless only 5% of the total body content of serotonin exerts its action in the CNS, while the rest is synthetized and stored in peripheral tissues where it acts as an autacoid. In 2003 it became evident that two distinct isoforms of tryptophan hydroxylase (Tph), the rate-limiting enzyme for the synthesis of serotonin, are selectively expressed in peripheral tissues and in the CNS, with Tph2 as the brain specific isoform. In the present review we describe how the discovery of Tph2 has improved our understanding on the role of serotonergic neurotransmission. We mainly focus on the analysis of animal models generated by genetic manipulation of Tph2, in which the synthesis of brain serotonin was either reduced or disrupted. The consequences of an altered serotonergic neurotransmission on brain development, as well as on physiological and behavioral processes will be assessed. Finally, we report on several association studies that have linked single nucleotide polymorphisms (SNPs) in the human TPH2 gene with behavioral disturbances and neuropsychiatric disorders.

BackgroundMaternal polycystic ovary syndrome (PCOS) has been proposed as a model for investigating the role of prenatal androgen exposure in the development of neuropsychiatric disorders. However, women with PCOS are at higher risk of developing psychiatric conditions and previous studies are likely confounded by genetic influences.MethodsA Swedish nationwide register-based cohort study was conducted to disentangle the influence of prenatal androgen exposure from familial confounding in the association between maternal PCOS and offspring attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and Tourette's disorder and chronic tic disorders (TD/CTD). PCOS-exposed offspring (n = 21 280) were compared with unrelated PCOS-unexposed offspring (n = 200 816) and PCOS-unexposed cousins (n = 17 295). Associations were estimated with stratified Cox regression models.ResultsPCOS-exposed offspring had increased risk of being diagnosed with ADHD, ASD, and TD/CTD compared with unrelated PCOS-unexposed offspring. Associations were stronger in girls for ADHD and ASD but not TD/CTD [ADHD: adjusted hazard ratio (aHR) = 1.61 (95% confidence interval (CI) 1.31–1.99), ASD: aHR = 2.02 (95% CI 1.45–2.82)] than boys [ADHD: aHR = 1.37 (95% CI 1.19–1.57), ASD: aHR = 1.46 (95% CI 1.21–1.76)]. For ADHD and ASD, aHRs for girls were stronger when compared with PCOS-unexposed cousins, but slightly attenuated for boys.ConclusionsEstimates were similar when accounting for familial confounding (i.e. genetics and environmental factors shared by cousins) and stronger in girls for ADHD and ASD, potentially indicating a differential influence of prenatal androgen exposure v. genetic factors. These results strengthen evidence for a potential causal influence of prenatal androgen exposure on the development of male-predominant neuropsychiatric disorders in female offspring of women with PCOS.

Psychological theory and interpretation of research are key elements influencing clinical treatment development and design in Attention Deficit Hyperactivity Disorder (ADHD). Research-based treatment recommendations primarily support Cognitive Behavioural Therapy (CBT), an extension of the cognitive behavioural theory, which promotes a deficit-focused characterisation of ADHD and prioritises symptom reduction and cognitive control of self-regulation as treatment outcomes. A wide variety of approaches have developed to improve ADHD outcomes in adults, and this review aimed to map the theoretical foundations of treatment design to understand their impact. A scoping review and analysis were performed on 221 documents to compare the theoretical influences in research, treatment approach, and theoretical citations. Results showed that despite variation in the application, current treatments characterise ADHD from a single paradigm of cognitive behavioural theory. A single theoretical perspective is limiting research for effective treatments for ADHD to address ongoing issues such as accommodating context variability and heterogeneity. Research into alternative theoretical characterisations of ADHD is recommended to provide treatment design opportunities to better understand and address symptoms.

Background Looked after children are defined as children who are in the care of their local authority. Previous studies have reported that looked after children have poorer mental and physical health, increased behavioural problems, and increased self-harm and mortality compared to peers. They also experience poorer educational outcomes, yet population-wide research into the latter is lacking, particularly in the United Kingdom. Education and health share a bidirectional relationship; therefore, it is important to dually investigate both outcomes. Our study aimed to compare educational and health outcomes for looked after children with peers, adjusting for sociodemographic, maternity, and comorbidity confounders. Methods and findings Linkage of 9 Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions, unemployment, and looked after children provided retrospective data on 715,111 children attending Scottish schools between 2009 and 2012 (13,898 [1.9%] looked after). Compared to peers, 13,898 (1.9%) looked after children were more likely to be absent (adjusted incidence rate ratio [AIRR] 1.27, 95% confidence interval [CI] 1.24 to 1.30) and excluded (AIRR 4.09, 95% CI 3.86 to 4.33) from school, have special educational need (SEN; adjusted odds ratio [AOR] 3.48, 95% CI 3.35 to 3.62) and neurodevelopmental multimorbidity (AOR 2.45, 95% CI 2.34 to 2.57), achieve the lowest level of academic attainment (AOR 5.92, 95% CI 5.17 to 6.78), and be unemployed after leaving school (AOR 2.12, 95% CI 1.96 to 2.29). They were more likely to require treatment for epilepsy (AOR 1.50, 95% CI 1.27 to 1.78), attention deficit hyperactivity disorder (ADHD; AOR 3.01, 95% CI 2.76 to 3.27), and depression (AOR 1.90, 95% CI 1.62 to 2.22), be hospitalised overall (adjusted hazard ratio [AHR] 1.23, 95% CI 1.19 to 1.28) for injury (AHR 1.80, 95% CI 1.69 to 1.91) and self-harm (AHR 5.19, 95% CI 4.66 to 5.78), and die prematurely (AHR 3.21, 95% CI 2.16 to 4.77). Compared to children looked after at home, children looked after away from home had less absenteeism (AIRR 0.35, 95% CI 0.33 to 0.36), less exclusion (AIRR 0.63, 95% CI 0.56 to 0.71), less unemployment (AOR 0.53, 95% CI 0.46 to 0.62), and better attainment (AIRR 0.31, 95% CI 0.23 to 0.40). Therefore, among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. The main limitations of this study were lack of data on local authority care preschool or before 2009, total time spent in care, and age of first contact with social care. Conclusions Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system., In this record-linkage study in Scotland, Michael Fleming and colleagues compare educational and health outcomes for children who are in the care of their local authority with the outcomes of their peers., Author summary Why was this study done? Looked after children, defined as children placed in the care of their local authority, comprise a vulnerable cohort exhibiting poorer educational and health outcomes compared to peers. Only a few small sample studies have been conducted in the UK, and a recent systematic review reported an urgent need for more population-wide research into the educational outcomes of children placed in social care services. To our knowledge, no previous UK studies have dually investigated educational and health outcomes of looked after children compared to peers using an unselected, nationwide cohort. What did the researchers do and find? We linked together 9 Scotland-wide databases to compare educational and health outcomes of looked after children against peers, adjusting for sociodemographic, maternity, and comorbidity confounders. Looked after children had increased risk of school absenteeism and exclusion; special educational need (SEN); poor academic attainment; unemployment; hospitalisation and mortality; and treatment for epilepsy, attention deficit hyperactivity disorder (ADHD), depression, and neurodevelopmental multimorbidity. Among children in care, those looked after away from home had less absenteeism, less exclusion, less unemployment, and better attainment. What do these findings mean? Looked after children had poorer health and educational outcomes than peers independent of increased neurodevelopmental conditions and SEN. Among those in care, being cared for away from home appeared to be a protective factor resulting in better educational outcomes. Further work is required to understand whether poorer outcomes relate to reasons for entering care, including maltreatment and adverse childhood events, neurodevelopmental vulnerabilities, or characteristics of the care system.

Purpose Mental health is a significant problem following exposure to a traumatic event. This study aimed to examine quarantine-related experiences, traumatic stress, and coping strategies among adults quarantined in Saudi Arabia due to coronavirus disease 2019 (COVID-19) exposure or travel history. Methods Individuals aged ≥ 18 years who were quarantined in Saudi Arabia due to COVID-19 exposure or travel history were included. We used a sequential mixed methods design, using an online survey followed by in-depth individual telephonic interviews. The Impact of Event Scale-Revised (IES–R) was used to measure post-traumatic stress disorder (PTSD) symptoms after the quarantine. To identify factors associated with significant symptoms (IES–R score ≥ 33), prevalence ratios (PR) with 95% confidence intervals were computed using Poisson regression with robust error variance. In the next phase, a subset of the participants (n = 26) were interviewed to elicit their quarantine-related experiences and coping responses. Major themes and subthemes were identified. Results Of the 111 adults who completed the survey, 32 (28.8% [95% CI, 21.1–38.0%]) had significant PTSD symptoms (IES–R score ≥ 33) and 27 (24.3% [95% CI, 17.2–33.3%]) had severe symptoms (IES–R score > 37). Marital status was the only variable that was significantly associated with significant PTSD symptoms (P = 0.028). Significant symptoms were twice as prevalent in married adults than among other marital groups (PR 2.00, 95% CI, 1.08–3.72). Participants reported negative emotions such as overwhelming fear, helplessness, anxiety, and disgust. Participants utilized both problem-centered coping (e.g., use of social support) and emotion-centered coping (e.g., use of positive diversionary activities) during the quarantine period. Conclusion PTSD symptoms were present in one out of every four quarantined persons. The quarantine experience is viewed negatively. These findings highlight the need for increased awareness about stress-related disorders among quarantined individuals. Efforts are needed to detect and manage these symptoms early while making the quarantine experience more satisfying for the involved individuals and groups.

Genomic variants that cause neurodevelopmental/psychiatric disorders (NPD) are relatively prevalent and highly penetrant. This study aimed to understand adults’ immediate responses to receiving NPD-related results to inform inclusion in population-based genomic screening programs. Nine recurrent, pathogenic copy number variants (CNVs) were identified from research exome data, clinically confirmed, and disclosed to adult participants of the Geisinger MyCode Community Health Initiative DiscovEHR cohort by experienced genetic counselors. A subset of in-person genetic counseling sessions (n = 27) were audio-recorded, transcribed, and coded using a grounded theory approach. Participant reactions were overwhelmingly positive and indicated that an NPD genetic etiology was highly valuable and personally useful. Participants frequently reported learning disabilities or other NPD that were not documented in their electronic health records and noted difficulties obtaining support for NPD needs. Most intended to share their genetic result with family members and health care providers and were interested in how their result could improve their healthcare. This study indicates that results from population-based NPD genomic screening can provide personal value for adults with NPD, were viewed positively by participants, and could improve clinical outcomes by informing symptom monitoring for NPD and co-morbidities, promoting improved health behaviors, and enhancing psychotherapeutic approaches.

Despite the severe psychological impact of the COVID-19 pandemic, some individuals do not develop high levels of psychological distress and can be termed resilient. Using the ecological resilience model, we examined factors promoting or hindering resilience in the COVID-19 pandemic. Of the 1034 participants (49.9±16.2 years; females 51.2%) from Italian general population, 70% displayed resilient outcomes and 30% reported moderate-severe anxiety and/or depression. A binary regression model revealed that factors promoting resilience were mostly psychological (e.g., trait resilience, conscientiousness) together with social distancing. Conversely, factors hindering resilience included COVID-19-anxiety, COVID-19-related PTSD symptoms, intolerance of uncertainty, loneliness, living with children, higher education, and living in regions where the virus was starting to spread. In conclusion, the ecological resilience model in the COVID-19 pandemic explained 64% of the variance and identified factors promoting or hindering resilient outcomes. Critically, these findings can inform psychological interventions supporting individuals by strengthening factors associated with resilience.

Aim Toxoplasma gondii (Tg) is an intracellular parasite infecting more than a third of the human population. Yet, the impact of Tg infection on sleep, a highly sensitive index of brain functions, remains unknown. We designed an experimental mouse model of chronic Tg infection to assess the effects on sleep‐wake states. Methods Mice were infected using cysts of the type II Prugniaud strain. We performed chronic sleep‐wake recordings and monitoring as well as EEG power spectral density analysis in order to assess the quantitative and qualitative changes of sleep‐wake states. Pharmacological approach was combined to evaluate the direct impact of the infection and inflammation caused by Tg. Results Infected mouse exhibited chronic sleep‐wake alterations over months, characterized by a marked increase (>20%) in time spent awake and in cortical EEG θ power density of all sleep‐wake states. Meanwhile, slow‐wave sleep decreased significantly. These effects were alleviated by an anti‐inflammatory treatment using corticosteroid dexamethasone. Conclusion We demonstrated for the first time the direct consequences of Tg infection on sleep‐wake states. The persistently increased wakefulness and reduced sleep fit with the parasite's strategy to enhance dissemination through host predation and are of significance in understanding the neurodegenerative and neuropsychiatric disorders reported in infected patients., When mice are infected chronically by Toxoplasma gondii, an intracellular parasite, they exhibit a marked increase in wakefulness and activities, thus promoting encounters with cats, its natural predators. It is likely that by this strategy to modify its hosts’ sleep‐wake and behavioral states, Toxoplasma gondii would enhance its own dissemination, thus explaining why it infects a wide range of animals and about one third of the world population.

The Rey–Osterrieth Complex Figure (ROCF) test is a commonly used neuropsychological assessment tool. It is widely used to assess the visuo-constructional ability and visual memory of neuropsychiatric disorders, including copying and recall tests. By drawing the complex figure, the functional decline of a patient in multiple cognitive dimensions can be assessed, including attention and concentration, fine-motor coordination, visuospatial perception, non-verbal memory, planning and organization, and spatial orientation. This review first describes the different versions and scoring methods of ROCF. It then reviews the application of ROCF in the assessment of visuo-constructional ability in patients with dementia, other brain diseases, and psychiatric disorders. Finally, based on the scoring method of the digital system, future research hopes to develop a new digital ROCF scoring method combined with machine learning algorithms to standardize clinical practice and explore the characteristic neuropsychological structure information of different disorders.

Introduction Over the past two decades, there have been several global interventions including the Sustainable Development Goals (SDGs), aimed at improving health outcomes. Despite efforts by countries to achieve the SDG targets, mental health challenges remain major public health concerns globally. We examined the prevalence and predictors of depression, anxiety, and stress as well as the comorbidities of these mental health issues among adults. Materials and methods This was a community-based cross-sectional study conducted among 2456 adults in four districts of the Volta Region of Ghana using data from the UHAS-Yonsei University Partnership Project. We analysed the data using frequency, percentage, mean, standard deviation, correlation, and binary logistic regression. Results Overall, 51.8% of the participants had at least one of the mental health issues examined. The prevalence of a mental health issue was 25.2%, 53.3%, and 9.7% for depression, anxiety, and stress respectively. Participants constituting 8.3% experienced all three mental health issues as comorbidities. Participants’ level of formal education and income significantly predicted depression, anxiety, and stress respectively at the multivariable level. Adults with a tertiary level of education were, for instance, 68% (AOR = 0.32, 95%CI = 0.15–0.66), 65% (AOR = 0.35, 95%CI = 0.17–0.73), and 50% (AOR = 0.50, 95%CI = 0.33–0.76) less likely to experience depression, anxiety, and stress, respectively compared with those who had no formal education. Conclusion The majority of our study participants either experienced depression, anxiety, or stress. There were quite high comorbidities of the mental health issues among the adult population. To accelerate progress towards the achievement of SDG 3.4 target of promoting mental health and wellbeing for all by the year 2030, there is a need for effective implementation of the country’s 2012 Mental Health Act which makes provisions for the establishment of a Mental Health Fund. This could improve the financial circumstances of indigenes as income has been realised in the present study as an important factor influencing depression, anxiety, and stress among the adult population.

Although numerous studies have examined the relationship between adverse childhood experiences (ACEs) and suicide, research is needed that studies the effects of specific ACEs, including subclasses of ACEs, independent of the effect of other ACEs. We explored the relationship between ACEs and suicidal ideation (SI) with special attention to patterns according to generation cohort (millennials: 22–37 years old, generation X: 38–53 years old, and baby boomers: 54–72 years old), and assessed the extent to which mood and anxiety disorders account for the relationship between ACEs and suicidal ideation. Patients in behavioral healthcare services of a large federally qualified health center (n = 4,392) were assessed at baseline on ACEs, SI, and mood and anxiety disorders. Logistic regression modeling was used to examine the data. Emotional neglect was the strongest predictor of SI among Millennials (OR = 1.59), Generation X (OR = 1.81), and Baby Boomers (OR = 1.88) after controlling for mood and anxiety disorders, race/ethnicity, and gender. Findings suggest ACEs predict an increased likelihood of having SI over and above the influence of mood and anxiety disorders, in models adjusted for gender and race/ethnicity. Across generations, the association with suicidal ideation was strongest for any child abuse and neglect, but not for household dysfunction. The observed association of ACEs with suicidal ideation suggests that ACEs should be considered as a risk factor and incorporated into screening assessments for suicidal ideation. Lastly, additional research on the association of ACEs and suicidality in individuals not actively being managed in behavioral healthcare settings is also warranted.