From Signals to Solutions: Exploring Early Detection of Neuropsychiatric and Neurodevelopment Disorders through Biomarkers

In 2013, the percentage of children ranging from 5 to 17 years who reported being diagnosed with autism surged to 1.2% from 0.1% in 1997 [1]. Alongside this increase in the incidence of autism in children, there were findings of a 21% increase in children who displayed behavioral and conduct problems from 2019 to 2020 [2]. Early detection of neuropsychiatric and neurodevelopmental disorders in children is critical for timely intervention and improved long-term outcomes. With early intervention, there is better aptitude to support healthy development and give proper treatment to attain a better quality of life. This paper explores studies aimed at enhancing the early detection of these disorders through the use of biomarkers with the aim of creating a bridge between the worlds of research and clinical practice. The disorders in this paper specifically discussed are Major Depressive Disorder, Bipolar Disorder, and Autism Spectrum Disorder. With this bridge, we can foster collaborations and encourage further advancement in the field of early detection and intervention.

Advancing Neuropsychiatric Care through Genetic and Molecular Insights

Neuropsychiatric diseases, including ADHD, schizophrenia, and bipolar disorder, are increasingly prevalent but poorly understood at the molecular level. The complexities of diagnosing and treating these disorders emphasize the need for objective, quantitative data to improve diagnostic accuracy and treatment efficacy. This study aims to explore the genetic underpinnings of neuropsychiatric diseases, contrasting them with well-characterized diseases like breast cancer, and discuss the role of specific genetic mutations and their implications for personalized treatment. The paper delves into the genetic and molecular insights of neuropsychiatric diseases, examining the role of specific genetic mutations and the potential for gene editing technologies like CRISPR. It contrasts the genetic underpinnings of neuropsychiatric diseases with well-characterized diseases like breast cancer, highlighting the potential for a shift towards molecular and genetic-based diagnostics and treatments. The study argues that a shift towards molecular and genetic-based diagnostics and treatments could revolutionize our approach to neuropsychiatric diseases, much like how biomarker tests have transformed breast cancer treatment. It concludes by advocating for a more personalized approach to healthcare, tailored to an individual’s unique genetic makeup, as the future of neuropsychiatric disease diagnosis and treatment.

Legacy of neuropsychiatric symptoms associated with past COVID-19 infection:A cause of concern

Although primarily affecting the respiratory system,growing attention is being paid to the neuropsychiatric consequences of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infections.Acute and sub-acute neuropsychiatric manifestations of coronavirus disease 2019(COVID-19)disease and their mechanisms are better studied and understood currently than they had been when the pandemic began;however,many months or years will be necessary to fully comprehend how significant the consequences of such complications will be.In this editorial,we discuss the possible long-term sequelae of the COVID-19 pandemic,deriving our considerations on experiences drawn from past coronaviruses’outbreaks,such as the SARS and the middle east respiratory syndrome,and from the knowledge of the mechanisms of neurotropism and invasiveness of SARS-CoV-2.Acknowledging the global spread of COVID-19 and the vast number of people affected,to date amounting to many millions,the matter of this pandemic’s neuropsychiatric legacy appears concerning.Public health monitoring strategies and early interventions seem to be necessary to manage the possible emergence of a severe wave of neuropsychiatric distress among the survivors.

Neuropsychiatric Symptoms,Parenting Stress and Social Support in Chinese Mothers of Children with Autism Spectrum Disorder

Although little is known about the current situation regarding autism spectrum disorder(ASD)in main land China,psychiatric disorders are common among Chinese mothers of preschool children with ASD.Previous studies showed ASD child's behavioral symptoms,maternal anxiety,and maternal depressive symptoms were associated with overall parenting stress in northern China.In the present study,we retrospectively analyzed medical records at the hospital related to neuropsychiatric symptoms,parenting stress and social support in mothers of children with ASD from southern China.A total of 80 mothers of children with ASD were screened.Among them,34 mothers were in low-functioning ASD group(L-ASD group)and 46 mothers were in highfunctioning ASD group(H-ASD group).Identification of the ASD cases was confirmed with a Revised Autism Diagnostic Inventory.Neuropsychiatric symptoms,parenting stress and social support were measured by neuropsychiatric inventory(NPI),parenting stress index short form(PSISF),and multi-dimensional scale of perceived social support(MSPSS).Total mean score of the NPI in the L-ASD group was significantly higher than that in the H-ASD group(P<0.01).The subscale scores of NPI,including depression,anxiety,apathy,irritability,agitation,night time behavior disturbances and change in appetite were significantly higher in the L-ASD group than those in the H-ASD group(P<0.01 or P<0.05).Meanwhile,the total PSI-SF scores and the scores of parental distress(PD),parental-child dysfunctional interaction(PCDI)and difficult child(DC)in the L-ASD group were significantly higher than those in the H-ASD group(P<0.01 or P<0.05).The total score of MSPSS was also higher in the L-ASD group than in the H-ASD group(P<0.01).This study goes further to show the neuropsychiatric symptoms and parenting stress are significantly higher in mothers of children with ASD,and more social supports are needed for mothers of children with ASD from southern China,especially for mothers of children with low-functioning ASD.

Neuropsychiatric Symptoms and Cognitive Impairment in Chinese Patients with Parkinson's Disease in Han and Hui Ethnicity

Nenropsychiatric symptoms are common in patients with Parkinson's disease(PD)and they are likely to outweigh the motor symptoms and become a major factor affecting the quality of life of PD patients.However,the studies focusing on the non-motor symptoms in Chinese PD patients from different ethnicity are scarce.The aim of this retrospective study was to investigate neuropsychiatric symptoms and cognitive impairment in Chinese PD patients from Han and Hui populations from central China.Seventy-two Han Chinese PD patients(Han PD group)and 71 age-and sex-matched Hui Chinese PD patients(Hui PD group)were enrolled from Zhongnan Hospital of Wuhan University between Sept.2011 and Aug.2014 in the study.The neuropsychiatric symptoms and cognitive impairment were assessed using Neuropsychiatric Inventory(NPI)and Mini Mental State Examination(MMSE).We found that the proportion of depression,anxiety,apathy,irritability,euphoria and night time behavior disturbances were higher in the Han PD group than in the Hui PD group(P<0.05 or P<0.01).But the proportion of delusion,hallucination,agitation,disinhibition,aberrant motor behavior and change in appetite were not significantly different between the Han PD group and the Hui PD group(P>0.05).The total mean scores of the MMSE from patients in the Han PD group were similar to those in the Hui PD group(P>0.05).However,the subscale scores of recall domain and language domain in the Han PD group were significantly different from those in the Hui PD group(P<0.05).No significant difference was noted in the orientation,memory and calculation domains between the two PD groups(P>0.05).This study first showed the recall domain and language domain were different between the Han PD patients and the Hui PD patients.Depression,anxiety,apathy,irritability,euphoria and night time behavior disturbances were less presented in the Hui PD patients.All these differences may be related to the different ethnicity,which would be helpful for clinical physicians to recognize the different non-motor symptoms in Chinese PD patients with different ethnicity.

nNOS-mediated protein-protein interactions:promising targets for treating neurological and neuropsychiatric disorders

Neurological and neuropsychiatric disorders are one of the leading causes of disability worldwide and affect the health of billions of people.Nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS)in the brain.Inhibiting nNOS benefits a variety of neurological and neuropsychiatric disorders,including stroke,depression and anxiety disorders,posttraumatic stress disorder,Parkinson’s disease,Alzheimer’s disease,chronic pain,and drug addiction.Due to critical roles of nNOS in learning and memory and synaptic plasticity,direct inhibition of nNOS may cause severe side effects.Importantly,interactions of several proteins,including post-synaptic density 95(PSD-95),carboxyterminal PDZ ligand of nNOS(CAPON)and serotonin transporter(SERT),with the PSD/Disc-large/ZO-1 homologous(PDZ)domain of nNOS have been demonstrated to influence the subcellular distribution and activity of the enzyme in the brain.Therefore,it will be a preferable means to interfere with nNOS-mediated proteinprotein interactions(PPIs),which do not lead to undesirable effects.Herein,we summarize the current literatures on nNOS-mediated PPIs involved in neurological and neuropsychiatric disorders,and the discovery of drugs targeting the PPIs,which is expected to provide potential targets for developing novel drugs and new strategy for the treatment of neurological and neuropsychiatric disorders.

Neuropsychiatric issues after stroke: Clinical significance and therapeutic implications

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.

Impact of SARS-CoV-2 on neuropsychiatric disorders

Evolving data show a variable expression of clinical neurological manifestations in patients suffering with coronavirus disease 2019(COVID-19)from early disease onset.The most frequent symptoms and signs are fatigue,dizziness,impaired consciousness,ageusia,anosmia,radicular pain,and headache,as well as others.Based on the high number of series of cases reported,there is evidence for the implication of the immune system in the pathological mechanism of COVID-19.Although the exact role of the immunological mechanism is not elucidated,two main mechanisms are suggested which implicate the direct effect of severe acute respiratory syndrome coronavirus 2 infection in the central nervous system and neuroinflammation.In the context of neurological manifestations associated with COVID-19,neuropsychiatric disorders show an exacerbation and are described by symptoms and signs such as depression,anxiety,mood alterations,psychosis,post-traumatic stress disorder,delirium,and cognitive impairment,which appear to be common in COVID-19 survivors.A worsened score on psychopathological measures is seen in those with a history of psychiatric comorbidities.We review the neuropsychiatric manifestations associated with COVID-19 and some critical aspects of the innate and adaptive immune system involved in mental health disorders occurring in COVID-19.

Evidence for accuracy of pain assessment and painkillers utilization in neuropsychiatric symptoms of dementia in Calabria region,Italy

During the clinical course of dementia,beside cognitive impairment and memory loss,a very complex challenge is posed by the neuropsychiatric symptoms（NPSs）.Accurate evaluation and treatment of pain impacts positively the agitation of demented patients aged ≥ 65 years.To gather information on the utilization of pain killers in demented patients a preliminary survey has been conducted in collaboration with the Calabrian Pharmacovigilance Territorial Service of the health district of Catanzaro（Italy）.The study has taken into consideration the prescriptions of acetylcholinesterase inhibitors and memantine during the period ranging from July 2015 to June 2016 and the percentage of patients treated against pain with non steroidal antinflammatory drugs,opioids,and anticonvulsants have been monitored.The latter have been evaluated statistically for difference between the treatment before（pre） and after（post） the settlement of acetylcholinesterase inhibitors（ACh EI） or memantine therapy.The results do support accuracy in painkillers utilization in the course of dementia in the regional population of Calabria（Italy）.

Impact of COVID-19 pandemic on the neuropsychiatric status of Wilson’s disease

We have read with interest the Letter to the Editor by Drs.Zhuang and Zhong,who presented the clinical data of 68 patients with Wilson’s disease(WD)who were admitted to the hospital before and during the coronavirus disease 2019(COVID-19)pandemic,and appreciated their findings on hepatic and some extrahepatic manifestations.Nevertheless,given the strong impact of the pandemic on patients with neurological and psychiatric disorders,we would have expected a worsening of the psychiatric and/or neurological impairments in these patients.In contrast,according to the authors,these manifestations remained,somewhat unexpectedly,unchanged.This finding is in contrast with most of the current literature that highlights not only an increased incidence of mental health disorders in the general population but also an exacerbation of neurological and psychiatric symptoms in patients with chronic diseases,especially in those with pre-existing neuropsychiatric disorders,such as WD.Although the study was mainly focused on the hepatic features of WD patients taking anti-copper treatment,a generic and cumulative definition of neurological and psychiatric manifestations,as in this study,does not allow for further considerations.Future studies during and after the pandemic are necessary to clarify the real impact,either direct or indirect,of the COVID-19 pandemic on the neurological and psychiatric symptoms of WD patients.

Spectrum of neuropsychiatric symptoms in chronic post-stroke aphasia

BACKGROUND Neuropsychiatric symptoms(NPS)have been insufficiently examined in persons with aphasia(PWA)because most previous studies exclude participants with language and communication disorders.AIM To report a two-part study consisting of a literature review and an observational study on NPS in post-stroke aphasia.METHODS Study 1 reviewed articles obtained from PubMed,PsycINFO,Google Scholar and Cochrane databases after cross-referencing key words of post-stroke aphasia to NPS and disorders.Study 2 examined language deficits and activities of daily living in 20 PWA(median age:58,range:28-65 years;13 men)with the Western Aphasia Battery-Revised and the Barthel Index,respectively.Informants of these 20 PWA were proxy-evaluated with the Neuropsychiatric Inventory and domain-specific scales,including the Stroke Aphasia Depression Questionnaire-10 item version and the Starkstein Apathy Scale.In addition,an adapted version of the Hospital Anxiety and Depression Scale was directly administered to the PWA themselves.This observational study is based on the baseline assessment of an intervention clinical trial(EudraCT:2017-002858-36;ClinicalTrials.gov identifier:NCT04134416).RESULTS The literature review revealed a broad spectrum of NPS in PWA,including depression,anxiety,apathy,agitation/aggression,eating and sleep disorders,psychosis,and hypomania/mania.These findings alert to the need for improving assessment and treatment approaches of NPS taking into consideration their frequent occurrence in PWA.Study 2 showed that the 20 participants had mild-to-moderate aphasia severity and were functionally independent.A wide range of comorbid NPS was found in the post-stroke aphasic population(median number of NPS:5,range:1-8).The majority of PWA(75%)had depressive symptoms,followed by agitation/aggression(70%),irritability(70%),anxiety(65%)and appetite/eating symptoms(65%).Half of them also presented symptoms of apathy,whereas euphoria and psychotic symptoms were rare(5%).Domain-specific scales revealed that 45%of participants had apathy and 30%were diagnosed with depression and anxiety.CONCLUSION Concurrent NPS are frequent in the chronic period of post-stroke aphasia.Therefore,further research on reliable and valid assessment tools and treatment for this aphasic population is strongly warranted.

Does COVID-19 increase the risk of neuropsychiatric sequelae? Evidence from a mendelian randomization approach

Observational studies based on electronic health records (EHR) report anincreased risk of neurological/neuropsychiatric sequelae for patients who havehad coronavirus disease 2019 (COVID-19). However, these studies may sufferfrom biases such as unmeasured confounding, residual reverse causality, or lackof precision in EHR-based diagnoses. To rule out these biases, we tested causallinks between COVID-19 and different potential neurological/neuropsychiatricsequelae through a two-sample Mendelian randomization analysis of summarystatistics from large Genome-Wide Association Scans of susceptibility to COVID-19 and different neurological and neuropsychiatric disorders, including majordepression, anxiety, schizophrenia, stroke, Parkinson’s and Alzheimer’s diseases.We found robust evidence suggesting that COVID-19 – notably the hospitalizedand most severe forms – carries an increased risk of neuropsychiatric sequelae,particularly Alzheimer’s disease, and to a lesser extent anxiety disorder. In linewith a large longitudinal EHR-based study, this evidence was stronger for moresevere COVID-19 forms. These results call for a targeted screening strategy totackle the post-COVID neuropsychiatric pandemic.

Pathogenesis of Neuropsychiatric Syndromes of Systemic Lupus Erythematosus

The pathogenesis of neuropsychiatric syndromes of systemic lupus erythematosus (NPSLE) is multifactorial and can involve various inflammatory cytokines, autoantibodies such as anti-neuronal antibodies, anti-ribosomal P antibodies, anti-NR2 glutamate receptor binding antibodies, anti-Sm antibodies, anti-U1-RNP antibodies and anti-phospholipid antibodies, and immune complexes (IC). Disruption of the blood-brain barrier (BBB) is integral to the neuropathology of SLE. Recently the possibility has been reported that aforementioned autoantibodies in the circulation may be strongly associated with disruption of the BBB. Each of these mechanisms might contribute to the pathogenesis of focal NPSLE (for example, cerebrovascular disease, movement disorders, myelopathy, seizures and cranial neuropathy) or diffuse NPSLE (for example, acute confusional state, psychosis and cognitive dysfunction) to varying degrees. In this review we focus on how the aforementioned autoantibodies, the BBB, IC and cytokines as well as chemokines are associated with the appearance of NPSLE.

Anemia in the Elderly: Neuropsychiatric Repercussions

The purpose of this review is to evaluate the role of chronic anemia on neuropsychiatric symptoms and conditions among the elderly. Anemia is defined as hemoglobin levels below 120 and 130 g/L for women and men, respectively. Anemia is not a consequence of the aging process. It is common in the elderly and easily overlooked. Nevertheless, chronic anemia is a risk factor associated with increased mortality, several geriatric syndromes including functional and cognitive impairments. Investigations have shown that anemic elderly and those with hemoglobin borderline levels may present higher proportion of neuropsychiatric impairment, such as Executive Function Disorder and Alzheimer disease. The association between anemia and depression is well established, but its causal pathway is not known: anemia can be regarded as cause or consequence of depression. There is evidence that dementia due to anemia can be prevented;renal chronic anemic patients who received erythropoietin (EPO) replacement therapy showed a lower risk for dementia, compared to those who did not receive it. Anemia may be associated with chronic psychiatric diseases such as bipolar disorders and cause their symptoms to become more severe.

Neuropsychiatric Systemic Lupus Erythematosus Complicated with Acute Pericarditis in Patient with Hyperprolactinaemia: A Case Report

Neuropsychiatric systemic lupus erythematosus (NP-SLE) is one of the major cause of morbidity in systemic lupus erythematosus patients and its treatment depends on identification of pathogenic mechanisms. We describe the rare case of neuropsychiatric systemic lupus erythematosus (NP-SLE) complicated by pericardial effusion combined to low C4 level persisting and hyperprolactinaemia. A cyclophosphamide therapy showed a good response in a 21-year old woman with disturbances in thought processes and an acute confusional state with sierositis. This paper confirms that a cyclophosphamide therapy contributes to control a disease activity by a mechanism of prolactin level reduction. Other studies occur to evaluate this hypothesis.

Effectiveness of music intervention on cognitive function and neuropsychiatric symptoms in the elderly with dementia:a meta-analysis

Dementia is increasing dramatically with an increasing elderly population.Pharmacological interventions are proven to have limited efficacy to treat many of the features of dementia.In such a situation,non-pharmacological means become important to help people with dementia,especially music therapy.The efficacy of music intervention on cognition has been barely explored in the literature,and the few studies that are available present inconsistent results.The aim of this systematic review is to have a meta-analysis on the effect of music therapy for improvements in cognitive functions as well as neuropsychiatric symptoms in the elderly with dementia.

Advances in Diagnosis and Treatment of Neuropsychiatric Systemic Lupus Erythematosus

1 Introduction Neuropsychiatric systemic lupus erythematosus(NPSLE)is a serious complication of systemic lupus erythematosus(SLE),with an incidence of about 30%to 40%[1].No matter early or late SLE patients are prone to concurrent,so early diagnosis and treatment of NPSLE is extremely important.

nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story

In the central nervous system,nitric oxide(NO),a free gas with multitudinous bioactivities,is mainly produced from the oxidation of L-arginine by neuronal nitric oxide synthase(nNOS).In the past 20 years,the studies in our group and other laboratories have suggested a significant involvement of nNOS in a variety of neurological and neuropsychiatric disorders.In particular,the interactions between the PDZ domain of nNOS and its adaptor proteins,including post-synaptic density 95,the carboxy-terminal PDZ ligand of nNOS,and the serotonin transporter,significantly influence the subcellular localization and functions of nNOS in the brain.The nNOS-mediated protein-protein interactions provide new attractive targets and guide the discovery of therapeutic drugs for neurological and neuropsychiatric disorders.Here,we summarize the work on the roles of nNOS and its association with multiple adaptor proteins on neurological and neuropsychiatric disorders.

Belimumab shows promise in neuropsychiatric lupus:Another challenge to find the offender

Introduction:Agents that can be used for the treatment of neuropsychiatric lupus(NPSLE)are lacking in the therapeutic armamentarium.Belimumab is a monoclonal antibody targeting the B-cell activating factor(BAFF)and is approved by the US Food and Drug Administration as an additional treatment for systemic lupus erythematosus patients with persistent disease activity and lupus nephritis(LN);however,severe active central nervous system manifestations were excluded.Case Report:We report on a treatment-naïve LN patient with refractory NPSLE complicated with progressive posterior reversible encephalopathy syndrome(PRES)who was successfully treated via the combination of mycophenolate and belimumab,resulting in reversal of persistent headache and neuroradiologic manifestations.Conclusion:Research on this topic could be relevant for identifying a possible correlation between BAFF and psychiatric NPSLE manifestations.

Human stem cell modeling of neuropsychiatric disorders:from polygenicity to convergence

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.