Search

KCTD10, a member of the potassium channel tetramerization domain (KCTD) family, is implicated in neuropsychiatric disorders and functions as a substrate recognition component within the RING-type ubiquitin ligase complex. A rare de novo variant of KCTD10, p.C124W, was identified in schizophrenia cases, yet its underlying pathogenesis remains unexplored. Here, we demonstrate that heterozygous KCTD10 C124W mice display pronounced synaptic abnormalities and exhibit schizophrenia-like behaviors. Mechanistically, we reveal that KCTD10 undergoes liquid–liquid phase separation (LLPS), a process orchestrated by its intrinsically disordered region (IDR). p.C124W mutation disrupts this LLPS capability, leading to diminished degradation of RHOB and subsequent excessive accumulation in the postsynaptic density fractions. Notably, neither IDR deletion nor p.C124W mutation in KCTD10 mitigates the synaptic abnormalities caused by Kctd10 deficiency. Thus, our findings implicate that LLPS may be associated with the pathogenesis of KCTD10-associated brain disorders and highlight the potential of targeting RHOB as a therapeutic strategy for diseases linked to mutations in KCTD10 or RHOB. [ABSTRACT FROM AUTHOR]

Introduction: Cognitive impairment, marked by a decline in memory and attention, is frequently underdiagnosed, complicating effective management. Cardiovascular risk factors (CVR) and anticholinergic burden (ACB) are significant contributors to dementia risk, with ACB often stemming from medications prescribed for neuropsychiatric disorders. This study evaluates cognitive profiles through three brief cognitive tests, analyzing the impact of CVR and ACB presence. Methods: This cross-sectional study was performed between 2019 and 2023 in community pharmacies and an outpatient clinic in Valencia, Spain. Eligible participants were patients with subjective memory complaints 50 years or older with clinical records of cardiovascular factors. Patients with conflicting information regarding diabetes diagnosis or not taking concomitant medications were excluded. Three brief cognitive tests (Memory Impairment Screening (MIS), Semantic Verbal Fluency Test, and SPMSQ) were assessed. CVR was calculated using the European SCORE2 table, and ACB was assessed using the CALS scale. Results: Among 172 patients with memory complaints and CVR factors, 60% failed at least one cognitive test. These patients were on significantly more medications and had higher blood pressure and HbA1c levels. An increase in CVR and ACB was associated with more failed tests. Additionally, elevated SCORE2 scores were associated with a greater failure rate on the MIS test, while patients with elevated ACB more frequently failed the SPMSQ test. Conclusions: Selecting an adequate brief cognitive test according to patients' characteristics offers an opportunity to screen patients who are probably cognitively impaired. Whereas the MIS test may be helpful for patients with cardiovascular risk, SPMSQ stands out among patients with significant ACB. [ABSTRACT FROM AUTHOR]

Machine learning has been increasingly used to obtain individualized neuroimaging signatures for disease diagnosis, prognosis, and response to treatment in neuropsychiatric and neurodegenerative disorders. Therefore, it has contributed to a better understanding of disease heterogeneity by identifying disease subtypes with different brain phenotypic measures. In this review, we first present a systematic literature overview of studies using machine learning and multimodal magnetic resonance imaging to unravel disease heterogeneity in various neuropsychiatric and neurodegenerative disorders, including Alzheimer's disease, schizophrenia, major depressive disorder, autism spectrum disorder, and multiple sclerosis, as well as their potential in a transdiagnostic framework, where neuroanatomical and neurobiological commonalities were assessed across diagnostic boundaries. Subsequently, we summarize relevant machine learning methodologies and their clinical interpretability. We discuss the potential clinical implications of the current findings and envision future research avenues. Finally, we discuss an emerging paradigm called dimensional neuroimaging endophenotypes. Dimensional neuroimaging endophenotypes dissects the neurobiological heterogeneity of neuropsychiatric and neurodegenerative disorders into low-dimensional yet informative, quantitative brain phenotypic representations, serving as robust intermediate phenotypes (i.e., endophenotypes), presumably reflecting the interplay of underlying genetic, lifestyle, and environmental processes associated with disease etiology. [ABSTRACT FROM AUTHOR]

Slitrk proteins belong the leucine-rich repeat transmembrane family and share structural similarities with the Slits and tropomyosin receptor kinase families, which regulate the development of the nervous system. Slitrks are highly expressed in the developing nervous system of vertebrates, modulating neurite outgrowth and enhancing synaptogenesis; however, the expression and function of Slitrk protein members differ. Slitrk protein variations have been associated with various sensory and neuropsychiatric conditions, including myopia, deafness, obsessive–compulsive disorder, autism spectrum disorders, schizophrenia, attention-deficit/hyperactivity disorder, glioma, and Tourette syndrome; however, the underlying mechanism remains unclear. Therefore, the Slitrk family members' protein expression, roles in the signaling cascade, functions, and gene mutations need to be comprehensively studied to develop therapeutics against neurodegenerative diseases. This study presents complete and pertinent information demonstrating the relationship between Slitrk family proteins and neuropsychiatric illnesses. This review briefly discusses neurodevelopmental disorders, the leucine-rich repeat family, the Slitrk family, and the association of Slitrk with the neuropathology of representative disorders. [ABSTRACT FROM AUTHOR]

KBG syndrome is a rare genetic disorder caused by heterozygous pathogenic variants in ANKRD11. Affected individuals have developmental delay, short stature, characteristic facial features, and other dysmorphic findings. To date, a spectrum of unspecific neuroradiological defects has been reported in KBG patients, such as cortical defects, white matter abnormalities, corpus callosum, and cerebellar vermis hypoplasia. Deep clinical and neuroradiological phenotyping and genotype of a patient presenting with mild cognitive and behavioral problems were obtained after written informed consent. We herein describe the first KBG patient presenting with cerebellar heterotopia, a heterogeneous malformation characterized by the presence of clusters of neurons within the white matter of cerebellar hemispheres. This novel association broadens the neuroradiological spectrum of KBG syndrome, and further prompts to investigate the potential functions of ANKRD11 in cerebellar development. [ABSTRACT FROM AUTHOR]

Abstract Background Attention deficit hyperactivity disorder (ADHD) is one of the more common neuropsychiatric disorders in women of reproductive age. Our objective was to compare perinatal outcomes between women with an ADHD diagnosis and those without. Methods A retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS) United States database. The study included all women who either delivered or experienced maternal death from 2004 to 2014. Perinatal outcomes were compared between women with an ICD-9 diagnosis of ADHD and those without. Results Overall, 9,096,788 women met the inclusion criteria. Amongst them, 10,031 women had a diagnosis of ADHD. Women with ADHD, compared to those without, were more likely to be younger than 25 years of age; white; to smoke tobacco during pregnancy; to use illicit drugs; and to suffer from chronic hypertension, thyroid disorders, and obesity (p

Background: Attention deficit hyperactivity disorder (ADHD) is one of the more common neuropsychiatric disorders in women of reproductive age. Our objective was to compare perinatal outcomes between women with an ADHD diagnosis and those without. Methods: A retrospective population-based cohort study utilizing the Healthcare Cost and Utilization Project, Nationwide Inpatient Sample (HCUP-NIS) United States database. The study included all women who either delivered or experienced maternal death from 2004 to 2014. Perinatal outcomes were compared between women with an ICD-9 diagnosis of ADHD and those without. Results: Overall, 9,096,788 women met the inclusion criteria. Amongst them, 10,031 women had a diagnosis of ADHD. Women with ADHD, compared to those without, were more likely to be younger than 25 years of age; white; to smoke tobacco during pregnancy; to use illicit drugs; and to suffer from chronic hypertension, thyroid disorders, and obesity (p < 0.001 for all). Women in the ADHD group, compared to those without, had a higher rate of hypertensive disorders of pregnancy (HDP) (aOR 1.36, 95% CI 1.28–1.45, p < 0.001), cesarean delivery (aOR 1.19, 95% CI 1.13–1.25, p < 0.001), chorioamnionitis (aOR 1.34, 95% CI 1.17–1.52, p < 0.001), and maternal infection (aOR 1.33, 95% CI 1.19–1.5, p < 0.001). Regarding neonatal outcomes, patients with ADHD, compared to those without, had a higher rate of small-for-gestational-age neonate (SGA) (aOR 1.3, 95% CI 1.17–1.43, p < 0.001), and congenital anomalies (aOR 2.77, 95% CI 2.36–3.26, p < 0.001). Conclusion: Women with a diagnosis of ADHD had a higher incidence of a myriad of maternal and neonatal complications, including cesarean delivery, HDP, and SGA neonates. [ABSTRACT FROM AUTHOR]

Neuroimaging and other neurobiological evidences are increasingly introduced in criminal litigation, especially when a neuropsychiatric disorder is suspected. Evaluations of criminal competencies are the most common type of criminal forensic assessment in forensic psychiatry and psychology. Given this, it is critical for forensic evaluators to understand how neuropsychiatric disorders may affect a defendant's criminal competencies and how neurobiological data may be used in competency determinations. This paper reviews the use of neurobiological data, particularly neuroimaging, while considering the limitations and potential misuse of such data in criminal competency evaluations. [ABSTRACT FROM AUTHOR]

Nowadays, high morbidity and mortality of cardiovascular diseases (CVDs) and high comorbidity rate of neuropsychiatric disorders contribute to global burden of health and economics. Consequently, a discipline concerning abnormal connections between the brain and the heart and the resulting disease states, known as psychocardiology, has garnered interest among researchers. However, identifying a common pathway that physicians can modulate remains a challenge. Gut microbiota, a constituent part of the human intestinal ecosystem, is likely involved in mutual mechanism CVDs and neuropsychiatric disorder share, which could be a potential target of interventions in psychocardiology. This review aimed to discuss complex interactions from the perspectives of microbial and intestinal dysfunction, behavioral factors, and pathophysiological changes and to present possible approaches to regulating gut microbiota, both of which are future directions in psychocardiology. [ABSTRACT FROM AUTHOR]

Neuropsychiatric disorders are multifaceted syndromes with confounding neurological explanations. It includes anxiety, depression, autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, Tourette’s syndrome, delirium, dementia, vascular cognitive impairment, and apathy etc. Globally, these disorders occupy 15% of all diseases. As per the WHO, India has one of the largest populations of people with mental illnesses worldwide. The blood-brain barrier (BBB) makes it extremely difficult to distribute medicine to target cells in the brain tissues. However, it is possible through novel advancements in nanotechnology, molecular biology, and neurosciences. One such cutting-edge delivery method, nose-to-brain (N2B) drug delivery using nanoformulation (NF), overcomes traditional drug formulation and delivery limitations. Later offers more controlled drug release, better bioavailability, improved patient acceptance, reduced biological interference, and circumvention of BBB. When medicines are delivered via the intranasal (IN) route, they enter the nasal cavity and go to the brain via connections between the olfactory and trigeminal nerves and the nasal mucosa in N2B. Delivering phytochemical, bioactive and synthetic NF is being investigated with the N2B delivery strategy. The mucociliary clearance, enzyme degradation, and drug translocations by efflux mechanisms are significant issues associated with N2B delivery. This review article discusses the types of neuropsychiatric disorders and their treatment with plant-derived as well as synthetic drug-loaded NFs administered via the IN-delivery system. In conclusion, this review provided a comprehensive and critical overview of the IN applicability of plant-derived NFs for psychiatric disorders.

The immunoglobulin LAMP/OBCAM/NTM (IgLON) family of cell adhesion molecules comprises five members known for their involvement in establishing neural circuit connectivity, fine-tuning, and maintenance. Mutations in IgLON genes result in alterations in these processes and can lead to neuropsychiatric disorders. The two IgLON family members NEGR1 and OPCML share common links with several of them, such as schizophrenia, autism, and major depressive disorder. However, the onset and the underlying molecular mechanisms have remained largely unresolved, hampering progress in developing therapies. NEGR1 and OPCML are evolutionarily conserved in teleosts like the zebrafish (Danio rerio), which is excellently suited for disease modelling and large-scale screening for disease-ameliorating compounds. To explore the potential applicability of zebrafish for extending our knowledge on NEGR1- and OPCML-linked disorders and to develop new therapeutic strategies, we investigated the spatio-temporal expression of the two genes during early stages of development. negr1 and opcml are expressed maternally and subsequently in partially distinct domains of conserved brain regions. Other areas of expression in zebrafish have not been reported in mammals to date. Our results indicate that NEGR1 and OPCML may play roles in neural circuit development and function at stages earlier than previously anticipated. A detailed functional analysis of the two genes based on our findings could contribute to understanding the mechanistic basis of related psychiatric disorders. [ABSTRACT FROM AUTHOR]

Aberrant dopamine (DA) signalling has been implicated in various neuropsychiatric disorders, including attention‐deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), schizophrenia, bipolar disorder (BPD) and addiction. The availability of extracellular DA is sculpted by the exocytotic release of vesicular DA and subsequent transporter‐mediated clearance, rendering the presynaptic DA transporter (DAT) a crucial regulator of DA neurotransmission. D2‐type DA autoreceptors (D2ARs) regulate multiple aspects of DA homeostasis, including (i) DA synthesis, (ii) vesicular release, (iii) DA neuron firing and (iv) the surface expression of DAT and DAT‐mediated DA clearance. The DAT Val559 variant, identified in boys with ADHD or ASD, as well as in a girl with BPD, supports anomalous DA efflux (ADE), which we have shown drives tonic activation of D2ARs. Through ex vivo and in vivo studies of the DAT Val559 variant using transgenic knock‐in mice, we have uncovered a circuit and sex‐specific capacity of D2ARs to regulate DAT, which consequently disrupts DA signalling and behaviour differently in males and females. Our studies reveal the ability of the construct‐valid DAT Val559 model to elucidate endogenous mechanisms that support DA signalling, findings that may be of translational and/or therapeutic importance. [ABSTRACT FROM AUTHOR]

Vagus nerve stimulation (VNS) has been approved as an adjunctive treatment for epilepsy and depression. As the progress of VNS treatment for these neuropsychiatric disorders continues, its applications have expanded to a wide range of conditions, including inflammatory diseases to cognitive dysfunctions. The branches of the vagal nerves directly or indirectly innervate the anatomical structures implicated in these neuropsychiatric conditions, which has led to promising results regarding the effectiveness of VNS. Previous studies investigating the effectiveness of VNS have mostly utilized invasive forms of stimulation. However, current preclinical and clinical research indicates that non-invasive forms of VNS, such as transcutaneous vagus nerve stimulation, hold the promise for treating various neuropsychiatric conditions. This review aims to delve into relevant clinical studies of VNS in various illness states, different methods of VNS, and the potential mechanisms underlying the therapeutic effects in these neuropsychiatric conditions. [ABSTRACT FROM AUTHOR]

Neuronal synaptic junctions connect neurons to enable neuronal signal transmission in the nervous system. The proper establishment of synaptic connections required many adhesion molecules. Malfunctions of these adhesion molecules can result in neural development disorders and neuropsychiatric disorders. How specific synapses are established by various adhesion molecules for proper neural circuitry is a fundamental question of neuroscience. SynCAMs, also named CADMs, Necl, etc., are among the many adhesion proteins found in synapses. Here, we review the current understanding of the physical properties of SynCAMs and their roles in axon pathfinding, myelination, synaptogenesis, and synaptic plasticity. In addition, we discuss the involvement of SynCAMs in neuropsychiatric disorders. Finally, we propose that SynCAM functions can be better viewed and understood from the perspective of orientational cell adhesions (OCAs). In particular, we discuss the possibilities of how SynCAMs can be regulated at the cell-type specific expression, transcription variants, posttranslational modification, and subcellular localization to modulate the diversity of SynCAMs as OCA molecules. Being major components of the synapses, SynCAMs continue to be an important research topic of neuroscience, and many outstanding questions are waiting to be answered. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children with unknown etiology. Impaired learning ability was commonly reported in ADHD patients and has been associated with dopamine uptake in the striatum of an animal model. Another evidence also indicated that micro-RNA (miR)-200b-3p is associated with learning ability in various animal models. However, the association between miR-200b-3p and ADHD–related symptoms remains unclear. Therefore, the current study investigated the role of miR-200b-3p in ADHD-related symptoms such as inattention and striatal inflammatory cytokines. To verify the influence of miR-200b-3p in ADHD-related symptoms, striatal stereotaxic injection of miR-200b-3p antagomir (AT) was performed on spontaneously hypertensive rats (SHR). The antioxidant activity and expressions of miR-200b-3p, slit guidance ligand 2 (Slit2), and inflammatory cytokines in the striatum of SHR were measured using quantitative real-time polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), immunoblotting, and enzyme-linked immunosorbent assay (ELISA). The spontaneous alternation of SHR was tested using a three-arm Y-shaped maze. The administration of miR-200b-3p AT or taurine significantly decreased striatal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in SHR, along with increased super-oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and significantly higher spontaneous alternation. In this paper, we show that miR-200b-3p AT and taurine alleviates ADHD-related symptoms in SHR. These findings provide insights into ADHD's molecular basis and suggest miR-200b-3p as a potential therapeutic target. Concurrently, this study also suggests broad implications for treating neurodevelopmental disorders affecting learning activity such as ADHD. [ABSTRACT FROM AUTHOR]

Abstract Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood–brain barrier architecture, and intriguingly, the regulation of emotions and behaviors. Microglia have a profound impact on neuronal survival, brain wiring and synaptic plasticity. As professional phagocytic cells in the brain, they remove dead cell debris and neurotoxic agents via an elaborate mechanism. The functional profile of microglia varies considerately depending on age, gender, disease context and other internal or external environmental factors. Numerous studies have demonstrated a pivotal involvement of microglia in neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain and other symptoms associated with major depression disorder, anxiety disorder, autism spectrum disorder and schizophrenia. In this review, we summarized the latest discoveries regarding microglial ontogeny, cell subtypes or state spectrum, biological functions and mechanistic underpinnings of emotional and behavioral disorders. Furthermore, we highlight the potential of microglia-targeted therapies of neuropsychiatric disorders, and propose outstanding questions to be addressed in future research of human microglia.

Slitrk proteins belong the leucine-rich repeat transmembrane family and share structural similarities with the Slits and tropomyosin receptor kinase families, which regulate the development of the nervous system. Slitrks are highly expressed in the developing nervous system of vertebrates, modulating neurite outgrowth and enhancing synaptogenesis; however, the expression and function of Slitrk protein members differ. Slitrk protein variations have been associated with various sensory and neuropsychiatric conditions, including myopia, deafness, obsessive–compulsive disorder, autism spectrum disorders, schizophrenia, attention-deficit/hyperactivity disorder, glioma, and Tourette syndrome; however, the underlying mechanism remains unclear. Therefore, the Slitrk family members’ protein expression, roles in the signaling cascade, functions, and gene mutations need to be comprehensively studied to develop therapeutics against neurodegenerative diseases. This study presents complete and pertinent information demonstrating the relationship between Slitrk family proteins and neuropsychiatric illnesses. This review briefly discusses neurodevelopmental disorders, the leucine-rich repeat family, the Slitrk family, and the association of Slitrk with the neuropathology of representative disorders.

Neuropsychiatric disorders (NPD) are prevalent and devastating, posing an enormous socioeconomic burden to modern society. Recent genetic studies of NPD have identified a plethora of common genetic risk variants with small effect sizes and rare risk variants of high penetrance. While exciting, there is a pressing need to translate these genetic discoveries into better understanding of disease biology and more tailored clinical interventions. Human induced pluripotent stem cell (hiPSC)-derived 2D and 3D neural cultures are becoming a promising cellular model for bridging the gap between genetic findings and disease biology for NPD. Leveraging the accessibility of patient biospecimen to convert into stem cells and the power of genome editing technology to engineer disease risk variants, hiPSC model holds the promise to disentangle the disease polygenicity, model genetic interaction with environmental factors, and uncover convergent gene pathways that may be targeted for more tailored clinical intervention.

Microglia are so versatile that they not only provide immune surveillance for central nervous system, but participate in neural circuitry development, brain blood vessels formation, blood–brain barrier architecture, and intriguingly, the regulation of emotions and behaviors. Microglia have a profound impact on neuronal survival, brain wiring and synaptic plasticity. As professional phagocytic cells in the brain, they remove dead cell debris and neurotoxic agents via an elaborate mechanism. The functional profile of microglia varies considerately depending on age, gender, disease context and other internal or external environmental factors. Numerous studies have demonstrated a pivotal involvement of microglia in neuropsychiatric disorders, including negative affection, social deficit, compulsive behavior, fear memory, pain and other symptoms associated with major depression disorder, anxiety disorder, autism spectrum disorder and schizophrenia. In this review, we summarized the latest discoveries regarding microglial ontogeny, cell subtypes or state spectrum, biological functions and mechanistic underpinnings of emotional and behavioral disorders. Furthermore, we highlight the potential of microglia-targeted therapies of neuropsychiatric disorders, and propose outstanding questions to be addressed in future research of human microglia. [ABSTRACT FROM AUTHOR]

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) syndrome is one of the most controversial diseases in pediatric rheumatology. Despite first being described more than 25 years ago as the sudden and rapid onset of obsessive–compulsive disorder (OCD) and/or tic disorder symptoms as complications of a Group A beta-hemolytic Streptococcus (GAS) infection, precise epidemiological data are still lacking, and there are no strong recommendations for its treatment. Recent advances in the comprehension of PANDAS pathophysiology are largely attributable to animal model studies and the understanding of the roles of Ca++/calmodulin-dependent protein kinase (CaM kinase) II, disrupted dopamine release in the basal ganglia, and striatal cholinergic interneurons. The diagnosis of PANDAS should be made after an exclusion process and should include prepubescent children with a sudden onset of OCD and/or a tic disorder, with a relapsing/remitting disease course, a clear temporal association between GAS infection and onset or exacerbation of symptoms, and the association with other neurological abnormalities such as motoric hyperactivity and choreiform movements. Antibiotic medications are the primary therapeutic modality. Nonetheless, there is a paucity of randomized studies and validated data, resulting in a scarcity of solid recommendations. [ABSTRACT FROM AUTHOR]

Psychedelics represent one of the most promising classes of experimental medicines for the treatment of neuropsychiatric disorders due to their ability to promote neural plasticity and produce both rapid and sustained therapeutic effects following a single administration. Conventional wisdom holds that peak mystical experiences induced by psychedelics are a critical component of their therapeutic mechanisms of action, though evidence supporting that claim is largely correlational. Here, I present data suggesting that the subjective effects induced by psychedelics may not be necessary to produce long-lasting changes in mood and behavior. Understanding the role of subjective effects in the therapeutic mechanisms of psychedelics will have important implications for both basic neuroscience and for increasing patient access to the next generation of medicines developed as a result of psychedelic research.

Addiction is best described as a disorder of maladaptive neuroplasticity involving the simultaneous strengthening of reward circuitry that drives compulsive drug seeking and weakening of circuits involved in executive control over harmful behaviors. Psychedelics have shown great promise for treating addiction, with many people attributing their therapeutic effects to insights gained while under the influence of the drug. However, psychedelics are also potent psychoplastogens-molecules capable of rapidly re-wiring the adult brain. The advent of non-hallucinogenic psychoplastogens with anti-addictive properties raises the intriguing possibility that hallucinations might not be necessary for all therapeutic effects of psychedelic-based medicines, so long as the underlying pathological neural circuitry can be remedied. One of these non-hallucinogenic psychoplastogens, tabernanthalog (TBG), appears to have long-lasting therapeutic effects in preclinical models relevant to alcohol and opioid addiction. Here, we discuss the implications of these results for the development of addiction treatments, as well as the next steps for advancing TBG and related non-hallucinogenic psychoplastogens as addiction therapeutics.

Anti-melanoma differentiation-associated gene 5 (MDA5) dermatomyositis (DM) is a rare disease that can be easily misdiagnosed. Anti-MDA5 dermatomyositis is a subtype of DM. It is distinguished by the presence of significant mucocutaneous characteristics, palmar papules, panniculitis, interstitial lung disease (ILD), and clinically amyopathic dermatomyositis (CADM). When combined with rapidly progressing ILD (RP-ILD), anti-MDA5 DM can be fatal. The literature indicates that nervous system involvement is uncommon in patients with anti-MDA5 DM. We report a case of anti-MDA5 DM with neuropsychiatric abnormalities and ILD. The patient suffered from persistent worsening mental disorders, while his ILD was relatively stable. The patient's neuropsychiatric abnormalities gradually subsided after receiving treatment with glucocorticoids, immunoglobulins, and immunosuppressants, leaving only a slow response and memory loss.

The aim of the study was to examine the possible relation between adolescent ADHD and high BMI, studying also eating behavior and physical activity. The data were collected from the Northern Finland Birth Cohort 1986. The follow-up at the age of 16 consisted of a self-assessment form and clinical examination where height and weight were measured and questionnaires on physical activity and eating habits was completed. ADHD diagnosis was based on a diagnostic interview with adolescents and parents according to DSM-IV-TR criteria. The participants were divided into the following study groups: individuals with adolescent ADHD (n = 90), those with only childhood ADHD (n = 40), and community controls (n = 269). Results showed no significant differences in BMI, but adolescents with ADHD seemed to have unhealthier eating habits than controls; they ate less often vegetables and breakfast, devoured more often, and consumed more fast food, soft drinks, sweets, and potato crisps daily. Individuals with adolescent ADHD reported light exercise more often but strenuous exercise more seldom than controls. Those with only childhood ADHD did not significantly differ from community controls regarding health behaviors. There was no relation between ADHD and high BMI but adolescents with ADHD had unhealthier eating habits than those without ADHD. It is conceivable that unhealthy eating behaviors in adolescence might be a risk factor for the development of later overweight; however, the longitudinal associations between ADHD, unhealthy eating behaviors and overweight have not been considered in the present study and remain to be examined further. [ABSTRACT FROM AUTHOR]

The brain constantly adapts to changes in the environment, a capability that underlies memory and behavior. Long-term adaptations require the remodeling of neural circuits that are mediated by activity-dependent alterations in gene expression. Over the last two decades, it has been shown that the expression of protein-coding genes is significantly regulated by a complex layer of non-coding RNA (ncRNA) interactions. The aim of this review is to summarize recent discoveries regarding the functional involvement of ncRNAs during different stages of neural circuit development, activity-dependent circuit remodeling, and circuit maladapations underlying neurological and neuropsychiatric disorders. In addition to the intensively studied microRNA (miRNA) family, we focus on more recently added ncRNA classes, such as long ncRNAs (lncRNAs) and circular RNAs (circRNAs), and discuss the complex regulatory interactions between these different RNAs. We conclude by discussing the potential relevance of ncRNAs for cell-type and -state-specific regulation in the context of memory formation, the evolution of human cognitive abilities, and the development of new diagnostic and therapeutic tools in brain disorders. In this review, Soutschek and Schratt summarize recent progress related to the function of different non-coding RNA families in the development and plasticity of neural circuits in vertebrates. They further highlight implications for human brain evolution and neuropsychiatric disorders. [ABSTRACT FROM AUTHOR]

The intake of psychobiotic bacteria appears to be a promising adjunct to neuropsychiatric treatment, and their consumption may even be beneficial for healthy people in terms of mental functioning. The psychobiotics' mechanism of action is largely outlined by the gut-brain axis; however, it is not fully understood. Based on very recent studies, we provide compelling evidence to suggest a novel understanding of this mechanism: bacterial extracellular vesicles appear to mediate many known effects that psychobiotic bacteria exert on the brain. In this mini-review paper, we characterize the extracellular vesicles derived from psychobiotic bacteria to demonstrate that they can be absorbed from the gastrointestinal tract, penetrate to the brain, and carry the intracellular content to exert beneficial multidirectional action. Specifically, by regulating epigenetic factors, extracellular vesicles from psychobiotics appear to enhance expression of neurotrophic molecules, improve serotonergic neurotransmission, and likely supply astrocytes with glycolytic enzymes to favor neuroprotective mechanisms. As a result, some data suggest an antidepressant action of extracellular vesicles that originate even from taxonomically remote psychobiotic bacteria. As such, these extracellular vesicles may be regarded as postbiotics of potentially therapeutic application. The mini-review is enriched with illustrations to better introduce the complex nature of brain signaling mediated by bacterial extracellular vesicles and indicates knowledge gaps that require scientific exploration before further progress is made. In conclusion, bacterial extracellular vesicles appear to represent the missing piece of the puzzle in the mechanism of action of psychobiotics. [ABSTRACT FROM AUTHOR]

The NMDA subtype of glutamate receptor serves as an attractive drug target for the treatment of disorders evolving from hyper‐ or hypoglutamatergic conditions. Compounds that optimize the function of NMDA receptors are of great clinical significance. Here, we present the pharmacological characterization of a biased allosteric modulator, CNS4. Results indicate that CNS4 sensitizes ambient levels of agonists and reduces higher‐concentration glycine & glutamate efficacy in 1/2AB receptors, but minimally alters these parameters in diheteromeric 1/2A or 1/2B receptors. Glycine efficacy is increased in both 1/2C and 1/2D, while glutamate efficacy is decreased in 1/2C and unaltered in 1/2D. CNS4 does not affect the activity of competitive antagonist binding at glycine (DCKA) and glutamate (DL‐AP5) sites; however, it decreases memantine potency in 1/2A receptors but not in 1/2D receptors. Current–voltage (I‐V) relationship studies indicate that CNS4 potentiates 1/2A inward currents, a phenomenon that was reversed in the absence of permeable Na+ ions. In 1/2D receptors, CNS4 blocks inward currents based on extracellular Ca2+ concentration. Further, CNS4 positively modulates glutamate potency on E781A_1/2A mutant receptors, indicating its role at the distal end of the 1/2A agonist binding domain interface. Together, these findings reveal that CNS4 sensitizes ambient agonists and allosterically modulates agonist efficacy by altering Na+ permeability based on the GluN2 subunit composition. Overall, the pharmacology of CNS4 aligns with the need for drug candidates to treat hypoglutamatergic neuropsychiatric conditions such as loss function GRIN disorders and anti‐NMDA receptor encephalitis. [ABSTRACT FROM AUTHOR]

Background and Aim: Toxoplasmosis is the most widespread zoonotic disease that affects one‐third of the world's population, and imposes a major public health problem worldwide. This study aimed to assess the prevalence of toxoplasmosis among patients with neuropsychiatric patients. Methods: Electronic databases PubMed, Google Scholar, Web of Science, Research Gate, and Scopus were thoroughly searched from February to March 2022 to identify all relevant studies. The quality of studies was evaluated using the Newcastle−Ottawa quality scale for case‐control and cross‐sectional studies. Statistical analysis was done using STATA version 12 software. A random effect model was used to compute the global pooled seroprevalence of Toxoplasma gondii infection. Heterogeneity was quantified by using I2 value. Subgroup analysis was done, and publication bias was assessed using a funnel plot and Egger's test. Result: Of 1250 studies, 49 containing 21,093 participants and conducted in 18 countries were included. The global pooled seroprevalence of T. gondii IgG antibody was 38.27% (95% CI: 32.04−44.9) among neuropsychiatric patients and 25.31% (95% CI: 21.53−29.08) in healthy controls with substantial heterogeneity of 98.3%. The prevalence of T. gondii IgG antibody was higher in males (17.52%) than in females (12.35%) neuropsychiatric patients. The highest pooled prevalence of T. gondii IgG antibody was in Europe (57%) followed by Africa (45.25%) and Asia (43%). Time based analysis showed the highest pooled prevalence of T. gondii IgG antibody in 2012−2016 (41.16%). The global pooled seroprevalence T. gondii IgM antibody among neuropsychiatric patients and healthy controls was 6.78% (95% CI: 4.87−8.69) and 3.13% (95% CI: 2.02−4.24), respectively. Conclusion: The pooled prevalence of chronic and acute T. gondii infection among neuropsychiatric patients was 38.27% and 6.78%, respectively. This showed a high burden of toxoplasmosis among neurological and psychiatric patients and urges routine screening of those patients and providing appropriate treatment. It also indicates the need for different stakeholders to develop targeted prevention and control strategies for T. gondii infection. [ABSTRACT FROM AUTHOR]

Copy number variants (CNVs), involving duplication or deletion of susceptible intervals of the human genome, underlie a range of neurodevelopmental and neuropsychiatric disorders. As accessible in vivo animal models of these disorders often cannot be generated, induced pluripotent stem cell (iPSC) models derived from patients carrying these CNVs can reveal alterations of brain development and neuronal function that contribute to these disorders. CNVs involving deletion versus duplication of a particular genomic interval often result both in distinct clinical phenotypes and in differential phenotypic penetrance. This review initially focuses on CNVs at 15q13.3, which contribute to autism spectrum disorder, attention deficit/hyperactivity disorder, and schizophrenia. Like most CNVs, deletions at 15q13.3 usually cause severe clinical phenotypes, while duplications instead result in highly variable penetrance, with some carriers exhibiting no clinical phenotype. Here, we describe cellular and molecular phenotypes seen in iPSC-derived neuronal models of 15q13.3 duplication and deletion, which may contribute both to the differential clinical consequences and phenotypic penetrance. We then relate this work to many other CNVs involving both duplication and deletion, summarizing findings from iPSC studies and their relationship to clinical phenotype. Together, this work highlights how CNVs involving duplication versus deletion can differentially alter neural development and function to contribute to neuropsychiatric disorders. iPSC-derived neuronal models of these disorders can be used both to understand the underlying neurodevelopmental alterations and to develop pharmacological or molecular approaches for phenotypic rescue that may suggest leads for patient intervention. Top: Deletion versus duplication of the same genomic interval results in different clinical phenotypes and degrees of phenotypic penetrance. Example findings schematized. Bottom: iPSC-derived neurons from individuals with these CNVs involving deletion versus duplication likewise often differential phenotypes (increases or decreases) in the categories shown. Figure created with BioRender.com. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Shanghai Physical Education Institute / Shanghai Tiyu Xueyuan Xuebao is the property of Shanghai Physical Education Institute and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children with unknown etiology. Impaired learning ability was commonly reported in ADHD patients and has been associated with dopamine uptake in the striatum of an animal model. Another evidence also indicated that micro-RNA (miR)-200b-3p is associated with learning ability in various animal models. However, the association between miR-200b-3p and ADHD–related symptoms remains unclear. Therefore, the current study investigated the role of miR-200b-3p in ADHD-related symptoms such as inattention and striatal inflammatory cytokines. To verify the influence of miR-200b-3p in ADHD-related symptoms, striatal stereotaxic injection of miR-200b-3p antagomir (AT) was performed on spontaneously hypertensive rats (SHR). The antioxidant activity and expressions of miR-200b-3p, slit guidance ligand 2 (Slit2), and inflammatory cytokines in the striatum of SHR were measured using quantitative real-time polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), immunoblotting, and enzyme-linked immunosorbent assay (ELISA). The spontaneous alternation of SHR was tested using a three-arm Y-shaped maze. The administration of miR-200b-3p AT or taurine significantly decreased striatal tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 in SHR, along with increased super-oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and significantly higher spontaneous alternation. In this paper, we show that miR-200b-3p AT and taurine alleviates ADHD-related symptoms in SHR. These findings provide insights into ADHD’s molecular basis and suggest miR-200b-3p as a potential therapeutic target. Concurrently, this study also suggests broad implications for treating neurodevelopmental disorders affecting learning activity such as ADHD.

The gastrointestinal tract harbors a densely populated community of microbes that exhibits sexual dimorphism. Dysbiosis of this community has been associated with chronic human disease states ranging from metabolic diseases to neuropsychiatric disorders (NPDs). The gut microbiota–gut–brain axis (GMGBA) is a bi-directional pathway that facilitates the interaction of the gut microflora with host physiological functions. Recently, research surrounding the potential roles of the GMGBA in the development of NPDs (e.g., depression, anxiety, and autism spectrum disorders (ASDs)) has increased. However, the role of the GMGBA in attention-deficit/hyperactivity disorder (ADHD), an NPD that affects an estimated 8.4% of children (5.1% of female and 11.5% of male children) and 4% of adults (with a male–female odds ratio of 1.6) in the United States, remains understudied. Herein, we synthesize the current literature regarding the GMGBA, ADHD, and the potentially relevant intersections between the GMGBA and ADHD. Recommendations are presented for pathways of future research into the role(s) of the GMGBA in ADHD etiology and symptomatology. Particular focus is given to the potential for the variable of host sex to act as an outcome modifier of the relationship between the GMGBA and ADHD.

Abstract Background and Aim Toxoplasmosis is the most widespread zoonotic disease that affects one‐third of the world's population, and imposes a major public health problem worldwide. This study aimed to assess the prevalence of toxoplasmosis among patients with neuropsychiatric patients. Methods Electronic databases PubMed, Google Scholar, Web of Science, Research Gate, and Scopus were thoroughly searched from February to March 2022 to identify all relevant studies. The quality of studies was evaluated using the Newcastle−Ottawa quality scale for case‐control and cross‐sectional studies. Statistical analysis was done using STATA version 12 software. A random effect model was used to compute the global pooled seroprevalence of Toxoplasma gondii infection. Heterogeneity was quantified by using I2 value. Subgroup analysis was done, and publication bias was assessed using a funnel plot and Egger's test. Result Of 1250 studies, 49 containing 21,093 participants and conducted in 18 countries were included. The global pooled seroprevalence of T. gondii IgG antibody was 38.27% (95% CI: 32.04−44.9) among neuropsychiatric patients and 25.31% (95% CI: 21.53−29.08) in healthy controls with substantial heterogeneity of 98.3%. The prevalence of T. gondii IgG antibody was higher in males (17.52%) than in females (12.35%) neuropsychiatric patients. The highest pooled prevalence of T. gondii IgG antibody was in Europe (57%) followed by Africa (45.25%) and Asia (43%). Time based analysis showed the highest pooled prevalence of T. gondii IgG antibody in 2012−2016 (41.16%). The global pooled seroprevalence T. gondii IgM antibody among neuropsychiatric patients and healthy controls was 6.78% (95% CI: 4.87−8.69) and 3.13% (95% CI: 2.02−4.24), respectively. Conclusion The pooled prevalence of chronic and acute T. gondii infection among neuropsychiatric patients was 38.27% and 6.78%, respectively. This showed a high burden of toxoplasmosis among neurological and psychiatric patients and urges routine screening of those patients and providing appropriate treatment. It also indicates the need for different stakeholders to develop targeted prevention and control strategies for T. gondii infection.

The intake of psychobiotic bacteria appears to be a promising adjunct to neuropsychiatric treatment, and their consumption may even be beneficial for healthy people in terms of mental functioning. The psychobiotics’ mechanism of action is largely outlined by the gut-brain axis; however, it is not fully understood. Based on very recent studies, we provide compelling evidence to suggest a novel understanding of this mechanism: bacterial extracellular vesicles appear to mediate many known effects that psychobiotic bacteria exert on the brain. In this mini-review paper, we characterize the extracellular vesicles derived from psychobiotic bacteria to demonstrate that they can be absorbed from the gastrointestinal tract, penetrate to the brain, and carry the intracellular content to exert beneficial multidirectional action. Specifically, by regulating epigenetic factors, extracellular vesicles from psychobiotics appear to enhance expression of neurotrophic molecules, improve serotonergic neurotransmission, and likely supply astrocytes with glycolytic enzymes to favor neuroprotective mechanisms. As a result, some data suggest an antidepressant action of extracellular vesicles that originate even from taxonomically remote psychobiotic bacteria. As such, these extracellular vesicles may be regarded as postbiotics of potentially therapeutic application. The mini-review is enriched with illustrations to better introduce the complex nature of brain signaling mediated by bacterial extracellular vesicles and indicates knowledge gaps that require scientific exploration before further progress is made. In conclusion, bacterial extracellular vesicles appear to represent the missing piece of the puzzle in the mechanism of action of psychobiotics.

Abstract The NMDA subtype of glutamate receptor serves as an attractive drug target for the treatment of disorders evolving from hyper‐ or hypoglutamatergic conditions. Compounds that optimize the function of NMDA receptors are of great clinical significance. Here, we present the pharmacological characterization of a biased allosteric modulator, CNS4. Results indicate that CNS4 sensitizes ambient levels of agonists and reduces higher‐concentration glycine & glutamate efficacy in 1/2AB receptors, but minimally alters these parameters in diheteromeric 1/2A or 1/2B receptors. Glycine efficacy is increased in both 1/2C and 1/2D, while glutamate efficacy is decreased in 1/2C and unaltered in 1/2D. CNS4 does not affect the activity of competitive antagonist binding at glycine (DCKA) and glutamate (DL‐AP5) sites; however, it decreases memantine potency in 1/2A receptors but not in 1/2D receptors. Current–voltage (I‐V) relationship studies indicate that CNS4 potentiates 1/2A inward currents, a phenomenon that was reversed in the absence of permeable Na+ ions. In 1/2D receptors, CNS4 blocks inward currents based on extracellular Ca2+ concentration. Further, CNS4 positively modulates glutamate potency on E781A_1/2A mutant receptors, indicating its role at the distal end of the 1/2A agonist binding domain interface. Together, these findings reveal that CNS4 sensitizes ambient agonists and allosterically modulates agonist efficacy by altering Na+ permeability based on the GluN2 subunit composition. Overall, the pharmacology of CNS4 aligns with the need for drug candidates to treat hypoglutamatergic neuropsychiatric conditions such as loss function GRIN disorders and anti‐NMDA receptor encephalitis.

Background: Pediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by a wide spectrum of symptoms, including the onset of obsessive-compulsive disorder and/or severely restricted food intake, associated with emotional symptoms, behavioral symptoms, developmental regression, and somatic symptoms. Among the possible triggering agents, infectious agents have been extensively explored. More recently, sporadic case reports describe a possible association between PANS and SARS-CoV-2 infection but data on clinical presentation and treatment are still scarce. Methods: We describe a case series (10 children) with acute onset or relapse of PANS symptoms after SARS-CoV-2 infection. Standardized measures (CBCL, CPRS, C-GAS, CGI-S, Y-BOCS, PANSS, and YGTSS) were used to describe the clinical picture. The efficacy of a pulse treatment with steroids for three consecutive months was assessed. Results: Our data suggest that the clinical presentation of the COVID-19-triggered PANS is largely similar to that reported in typical PANS, including acute onset, with OCD and/or eating disorders, and associated symptoms. Our data suggest that treatment with corticosteroids may be beneficial for both global clinical severity and global functioning. No serious adverse effects were observed. Both OCD symptoms and tics consistently improved. Among psychiatric symptoms, affective and oppositional symptoms appeared more sensitive to the steroid treatment than the other symptoms. Conclusion: Our study confirms that COVID-19 infection in children and adolescents could trigger acute-onset neuropsychiatric symptoms. Thus, in children and adolescents with COVID-19, a specific neuropsychiatric follow-up should be routinely included. Even if a small sample size and a follow-up with only two points (baseline and endpoint, after 8 weeks) limit the conclusions, it seems that steroid treatment in the acute phase may be beneficial and well tolerated. [ABSTRACT FROM AUTHOR]

Convolutional neural networks (CNNs) provide high-precision automatic classification of neuropsychiatric disorders based on images. However, the "black box" nature leads to poor interpretability of CNN. This study constructs an integrated model for neuropsychiatric disorders classification from multi-modal data. The proposed model consists of a novel multi-scale image features extraction neural network (MSFM) and a XGBoost. The proposed MSFM extracts the pixel context semantic information from fMRI images with different scales, which employs token and channel-mixing strategy to enhance the information communication between context semantic information. XGBoost is used to extract phenotypic feature from phenotypic records. Based on the integration of phenotypic and image features, a comparative interpretable classification of mental disorders can be achieved. The overall accuracy, sensitivity, and recall of the binary classification (healthy controls & neuropsychiatric disorders) of the integrated model are 90.23%, 91.08%, and 89.33%, respectively. The visualization of image features and the phenotypic features present consistency in the brain regions, increasing the interpretability of the MSFM. Especially, through visual statistical analysis of the test set, it was found that there are differences in the distribution of ADHD, BD, and SD in the brain regions. Our solution may provide psychiatrists with ideas for comparative examinations and diagnosis. • A multi-modal extraction integrated model is proposed for neuropsychiatric disorders classification, the integrated model consists of MSFM network and XGBoost. • The proposed MSFM extracts multi-scale pixel context semantic information from fMRI images. XGBoost is used to extract phenotypic features from phenotypic records. • The visualization of image features and phenotypic features presents consistency in the brain regions, increasing the interpretability of the MSFM. • Deep visualization analysis reveals differences between subtypes of NDs. [ABSTRACT FROM AUTHOR]

• The use of antibiotics in prenatal and postnatal period had 7 % and 5 % increased risks of overall neuropsychiatric disorder, respectively. • A synergistic effect of prenatal and postnatal exposure was also observed with 12 % increased risks. • The association became more pronounced as the number and duration of antibiotic prescriptions increased. • The risk of severe neuropsychiatric disorder was higher than that of common. • This study suggests antibiotic use during early life should be undergone with benefit-risk assessment, considering the potential of adverse outcomes in childhood. We aimed to assess the association between antibiotic exposure in fetal and postnatal life (within six months after birth) and the risk of neuropsychiatric disorders in childhood. A nationwide, population-based birth cohort study(infants, n = 3,163,206; paired mothers, n = 2,322,735) was conducted in South Korea, with a mean follow-up duration of 6.8 years, using estimates of hazard ratio [HR] and 95 % confidence intervals (CIs). Following propensity score matching including the baseline variables, antibiotic exposure in both fetal (HR,1.07 [95 % CI, 1.05–1.08]) and postnatal life (1.05 [1.03–1.07]) was associated with an increased risk of overall childhood neuropsychiatric disorders. A synergistic effect was observed with prenatal and postnatal exposures (1.12 [1.09–1.15]). The risk increases with the increasing number and duration of prescriptions. Significant associations were found for both common (1.06 [1.05–1.08]) and severe outcomes (1.17 [1.09–1.26]), especially for intellectual disability (1.12 [1.07–1.17]), ADHD (1.10 [1.07–1.13]), anxiety (1.06 [1.02–1.11]), mood (1.06 [1.00–1.12]), and autism (1.03 [1.01–1.07]). When comparing siblings with different exposure statuses to consider familial factors, prenatal and postnatal exposure risk increased to 10 % (95 % CI, 6–12) and 12 % (7–17), respectively. Similar results were observed in the unmatched and health screening cohort, which considers maternal obesity, smoking, and breastfeeding. Based on these findings, clinicians may consider potential long-term risks when assessing the risk-benefit of early-life antibiotic prescription. [ABSTRACT FROM AUTHOR]

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) syndrome is one of the most controversial diseases in pediatric rheumatology. Despite first being described more than 25 years ago as the sudden and rapid onset of obsessive–compulsive disorder (OCD) and/or tic disorder symptoms as complications of a Group A beta-hemolytic Streptococcus (GAS) infection, precise epidemiological data are still lacking, and there are no strong recommendations for its treatment. Recent advances in the comprehension of PANDAS pathophysiology are largely attributable to animal model studies and the understanding of the roles of Ca++/calmodulin-dependent protein kinase (CaM kinase) II, disrupted dopamine release in the basal ganglia, and striatal cholinergic interneurons. The diagnosis of PANDAS should be made after an exclusion process and should include prepubescent children with a sudden onset of OCD and/or a tic disorder, with a relapsing/remitting disease course, a clear temporal association between GAS infection and onset or exacerbation of symptoms, and the association with other neurological abnormalities such as motoric hyperactivity and choreiform movements. Antibiotic medications are the primary therapeutic modality. Nonetheless, there is a paucity of randomized studies and validated data, resulting in a scarcity of solid recommendations.

Huntington’s Disease is a progressive neurodegenerative disorder inherited in an autosomal dominant fashion with distinct phenotypesas chorea and dystonia, incoordination, cognitive disorders, and behavioural problems. In addition to cognitive and motor symptoms,neuropsychiatric symptoms are among the core symptoms of the disease. Neuropsychiatric symptoms are quite common in Huntington’sDisease and the prevalence of neuropsychiatric disorders in different stages of the disease is estimated to be 33-76%. Although the prevelanceof neuropsychiatric symptoms varies among the stages of the disease, it is also known that the onset of these symptoms may be years beforethe onset of motor symptoms. Common neuropsychiatric symptoms and disorders in Huntington’s Disease include depression, anxiety, suicide,irritability, apathy, obsessive-compulsive symptoms, perseverations, psychosis, sleep disorders, and sexual dysfunctions. Neuropsychiatricsymptoms constitute one of the most important factors for the burden on families, and are considered to be the most important predictors ofdecrease in daily functionality and institutionalizations in care centers and hospitalizations. Considering both its frequency and outcomes, it isvery important for patients, their relatives and caregivers to recognize and intervene in neuropsychiatric symptoms of Huntington’s Disease.Although there are no studies with a high level of evidence on the treatment of neuropsychiatric symptoms of the disease, studies with lowerlevels of evidence, case reports and treatment guidelines based on expert opinions are found in the literature in recent years. Another issue tobe considered in this area is the evaluation of individuals at genetic risk, genetic counseling and setting a safe protocol during these evaluations.In this article, neuropsychiatric disorders common in Huntington’s Disease, the management of these disorders and the conditions to beconsidered in the evaluation of individuals at genetic risk are reviewed in the light of current literature.

BackgroundPediatric acute-onset neuropsychiatric syndrome (PANS) is characterized by a wide spectrum of symptoms, including the onset of obsessive-compulsive disorder and/or severely restricted food intake, associated with emotional symptoms, behavioral symptoms, developmental regression, and somatic symptoms. Among the possible triggering agents, infectious agents have been extensively explored. More recently, sporadic case reports describe a possible association between PANS and SARS-CoV-2 infection but data on clinical presentation and treatment are still scarce.MethodsWe describe a case series (10 children) with acute onset or relapse of PANS symptoms after SARS-CoV-2 infection. Standardized measures (CBCL, CPRS, C-GAS, CGI-S, Y-BOCS, PANSS, and YGTSS) were used to describe the clinical picture. The efficacy of a pulse treatment with steroids for three consecutive months was assessed.ResultsOur data suggest that the clinical presentation of the COVID-19-triggered PANS is largely similar to that reported in typical PANS, including acute onset, with OCD and/or eating disorders, and associated symptoms. Our data suggest that treatment with corticosteroids may be beneficial for both global clinical severity and global functioning. No serious adverse effects were observed. Both OCD symptoms and tics consistently improved. Among psychiatric symptoms, affective and oppositional symptoms appeared more sensitive to the steroid treatment than the other symptoms.ConclusionOur study confirms that COVID-19 infection in children and adolescents could trigger acute-onset neuropsychiatric symptoms. Thus, in children and adolescents with COVID-19, a specific neuropsychiatric follow-up should be routinely included. Even if a small sample size and a follow-up with only two points (baseline and endpoint, after 8 weeks) limit the conclusions, it seems that steroid treatment in the acute phase may be beneficial and well tolerated.

It is now possible to estimate an individual's brain age via brain scans and machine-learning models. This validated technique has opened up new avenues for addressing clinical questions in neurology, and, in this review, we summarize the many clinical applications of brain-age estimation in neuropsychiatry and general populations. We first provide an introduction to typical neuroimaging modalities, feature extraction methods, and machine-learning models that have been used to develop a brain-age estimation framework. We then focus on the significant findings of the brain-age estimation technique in the field of neuropsychiatry as well as the usefulness of the technique for addressing clinical questions in neuropsychiatry. These applications may contribute to more timely and targeted neuropsychiatric therapies. Last, we discuss the practical problems and challenges described in the literature and suggest some future research directions. [ABSTRACT FROM AUTHOR]