Severe Psychiatric Disorders Research Articles

Healthcare Resource Utilization Among Patients With Agitation in Alzheimer Dementia

Background: Agitation in Alzheimer dementia is common, but the associated healthcare burden remains unclear. Objective: This retrospective analysis evaluated baseline characteristics, healthcare resource utilization, and costs among patients with agitation in Alzheimer dementia and those without agitation in Alzheimer dementia. Methods: Medicare beneficiaries from 100% of the Medicare Fee-for-Service claims database (2009-2016) with 2 or more claims 30 or more days apart for both Alzheimer’s disease and dementia and continuous enrollment with medical/pharmacy coverage for 6 months before and 12 months after the index diagnosis were included. Patients with agitation in Alzheimer dementia were identified by 2 or more claims 14 or more days apart using International Classification of Diseases-9-CM/-10-CM codes based on the provisional International Psychogeriatric Association agitation definition. Patients with severe psychiatric disorders were excluded. Two cohorts of patients (with and without agitation) were then defined, and patient characteristics, healthcare resource utilization, and costs were compared in a descriptive exploratory analysis. Results: Of 2 684 704 Fee-for-Service patients with Alzheimer dementia, 769 141 met all inclusion criteria; among these, 281 042 (36.5%) had agitation. The mean age in patients with and without agitation in Alzheimer dementia was 83 years. Most patients in both groups were female, but the proportion of males was slightly higher in the agitation in Alzheimer dementia group (30.3% vs 28.2%, respectively). Patients with agitation in Alzheimer dementia were more likely than those without agitation in Alzheimer dementia to have lower socioeconomic status (dual eligibility for Medicaid, 45.0% vs 41.7%, respectively) or be disabled (10.5% vs 9.4%). Overall, healthcare costs were higher in the agitation in Alzheimer dementia population compared with those without agitation in Alzheimer dementia (mean cost PPPY, $32 322 and $30 121, respectively), with the largest differences observed in inpatient and post-acute care costs. Conclusions: These exploratory findings underscore the substantial economic burden of agitation in Alzheimer dementia and highlight the need for treatment options for the agitation in Alzheimer dementia population to improve associated health outcomes.

Healthcare Resource Utilization Among Patients With Agitation in Alzheimer Dementia

Background: Agitation in Alzheimer dementia is common, but the associated healthcare burden remains unclear. Objective: This retrospective analysis evaluated baseline characteristics, healthcare resource utilization, and costs among patients with agitation in Alzheimer dementia and those without agitation in Alzheimer dementia. Methods: Medicare beneficiaries from 100% of the Medicare Fee-for-Service claims database (2009-2016) with 2 or more claims 30 or more days apart for both Alzheimer’s disease and dementia and continuous enrollment with medical/pharmacy coverage for 6 months before and 12 months after the index diagnosis were included. Patients with agitation in Alzheimer dementia were identified by 2 or more claims 14 or more days apart using International Classification of Diseases-9-CM/-10-CM codes based on the provisional International Psychogeriatric Association agitation definition. Patients with severe psychiatric disorders were excluded. Two cohorts of patients (with and without agitation) were then defined, and patient characteristics, healthcare resource utilization, and costs were compared in a descriptive exploratory analysis. Results: Of 2 684 704 Fee-for-Service patients with Alzheimer dementia, 769 141 met all inclusion criteria; among these, 281 042 (36.5%) had agitation. The mean age in patients with and without agitation in Alzheimer dementia was 83 years. Most patients in both groups were female, but the proportion of males was slightly higher in the agitation in Alzheimer dementia group (30.3% vs 28.2%, respectively). Patients with agitation in Alzheimer dementia were more likely than those without agitation in Alzheimer dementia to have lower socioeconomic status (dual eligibility for Medicaid, 45.0% vs 41.7%, respectively) or be disabled (10.5% vs 9.4%). Overall, healthcare costs were higher in the agitation in Alzheimer dementia population compared with those without agitation in Alzheimer dementia (mean cost PPPY, $32 322 and $30 121, respectively), with the largest differences observed in inpatient and post-acute care costs. Conclusions: These exploratory findings underscore the substantial economic burden of agitation in Alzheimer dementia and highlight the need for treatment options for the agitation in Alzheimer dementia population to improve associated health outcomes.

Mechanisms of glutamate receptors hypofunction dependent synaptic transmission impairment in the hippocampus of schizophrenia susceptibility gene Opcml-deficient mouse model

Schizophrenia is a severe psychiatric disorder with high heritability, characterized by positive and negative symptoms as well as cognitive abnormalities. Dysfunction in glutamate synapse is strongly implicated in the pathophysiology of schizophrenia. However, the precise role of the perturbed glutamatergic system in contributing to the cognitive abnormalities of schizophrenia at the synaptic level remains largely unknown. Although our previous work found that Opcml promotes spine maturation and Opcml-deficient mice exhibit schizophrenia-related cognitive impairments, the synaptic mechanism remains unclear. By using whole-cell patch clamp recording, we found that decreased neuronal excitability and alterations in intrinsic membrane properties of CA1 PNs in Opcml-deficient mice. Furthermore, Opcml deficiency leads to impaired glutamatergic transmission in hippocampus, which is closely related to postsynaptic AMPA/NMDA receptors dysfunction, resulting in the disturbances of E/I balance. Additionally, we found that the aripiprazole which we used to ameliorate abnormal cognitive behaviors also rescued the impaired glutamatergic transmission in Opcml-deficient mice. These findings will help to understand the synaptic mechanism in schizophrenia pathogenesis, providing insights into schizophrenia therapeutics with glutamatergic disruption.

Hospitalization trends among immigrants and natives in an acute psychiatric service: a descriptive study from Italy

Acute psychiatric services are crucial for immigrants who face barriers in accessing outpatient mental healthcare due to socio-economic, cultural, and linguistic challenges. This study compared psychiatric hospitalization characteristics between immigrants and native Italians at the University of Foggia from 2004 to 2019. A total of 536 inpatients, equally divided between immigrants and natives, were analysed for sociodemographic and clinical variables. Findings revealed that immigrants were hospitalized through emergency departments for severe psychiatric disorders such as psychosis, while natives were more often admitted for mood disorders. Immigrants showed a higher incidence of substance abuse and suicidal attempts and a lower number of prior hospitalizations compared to natives, with higher incidence of first episodes of mental illness. Despite presenting with severe psychopathology, natives exhibited better clinical outcomes, longer hospitalizations and higher functioning improvements. We also found that natives received more psychotropic medications but experienced fewer adverse effects compared to immigrants. Differences in pharmacological treatments and hospital outcomes suggested that culturally tailored interventions could improve the effectiveness of psychiatric care for migrants. These findings emphasized the necessity for systemic changes in mental health services to address disparities and improve care for migrant populations.

Developmental Predictors of Suicidality in Schizophrenia: A Systematic Review.

Background/Objectives: Schizophrenia (SZ) is a severe psychiatric disorder characterized by a complex interplay of genetic, developmental, and environmental factors that significantly increase the risk of suicidal ideation (SI) and suicide attempts (SAs). This systematic review synthesizes current research on the developmental predictors of SI in individuals with SZ, aiming to delineate the multifactorial etiology of suicide within this population. Methods: A comprehensive search across Medline, PsycINFO, and EMBASE databases identified 23 eligible studies, emphasizing the varied methodological approaches and the global distribution of research efforts. Results: These studies demonstrate a robust association between early life adversities, particularly childhood trauma such as physical neglect, emotional abuse, and sexual abuse, and the increased prevalence of SI and SAs in SZ. This review also highlights the significant genetic factors associated with the development of suicidality in SZ, raising the possibility that polymorphisms in inflammation-related genes and neurodevelopmental abnormalities may influence susceptibility to SI. Notably, family history of psychiatric conditions may exacerbate the risk of SI through both hereditary and environmental mechanisms. Environmental factors, including socioeconomic status and social support, are also implicated, underscoring the role of broader socio-environmental conditions influencing outcomes. Conclusions: This review supports the integration of biopsychosocial models in understanding SI in SZ, advocating for interventions addressing the complex interplay of risk factors and the need for longitudinal studies to elucidate the dynamic interactions between risk factors over time. This comprehensive understanding is crucial for developing targeted preventive strategies and enhancing the clinical management of SZ, aiming to reduce suicidality in this vulnerable population.

TRATAMENTO FARMACOLÓGICO DA ESQUIZOFRENIA: PASSADO, PRESENTE E FUTURO

Schizophrenia is a chronic and severe psychiatric disorder characterised by the manifestation of positive and negative symptoms and/or cognitive dysfunction. Treatment typically includes psychotherapy, sociotherapy and pharmacological therapy, which consists of the use of typical and atypical antipsychotic drugs, as well as dopaminergic system stabilisers. Although they do not provide a cure, these treatments can reduce the intensity and frequency of symptoms, resulting in improved quality of life and a quicker reintegration into social life. Thus, the aim of the present study was to conduct a narrative literature review on the clinical evolution of antipsychotic use throughout history, as well as to discuss potential new drugs that are still in clinical research. Studies have shown that typical antipsychotics are effective in treating positive symptoms but have no impact on negative symptoms and can even exacerbate or provoke them. Additionally, they produce highly limiting side effects, such as movement disorders. Atypical antipsychotics, on the other hand, are capable of reducing both positive and negative symptoms, and they also present fewer side effects related to the extrapyramidal motor system. However, they tend to cause metabolic disturbances. Conversely, dopaminergic system stabilisers also treat both positive and negative symptoms, with side effects that are generally better tolerated, along with a lower propensity to cause weight gain and motor disturbances. It is worth noting that many patients are unable to tolerate the various adverse reactions of the available antipsychotics. Moreover, some patients are or become refractory to their therapeutic effects. Consequently, there is currently a focus on developing new agents that have different pharmacological targets. Some of these potential new drugs have shown efficacy in refractory patients, representing a potential paradigm shift in the treatment of the disorder.

Irregularity of visual motion perception and negative symptoms in schizophrenia.

Schizophrenia (SZ) is a severe psychiatric disorder characterized by perceptual, emotional, and behavioral abnormalities, with cognitive impairment being a prominent feature of the disorder. Recent studies demonstrate irregularity in SZ with increased variability on the neural level. Is there also irregularity on the psychophysics level like in visual perception? Here, we introduce a methodology to analyze the irregularity in a trial-by-trial way to compare the SZ and healthy control (HC) subjects. In addition, we use an unsupervised clustering algorithm K-means + + to identify SZ subgroups in the sample, followed by validation of the subgroups based on intraindividual visual perception variability and clinical symptomatology. The K-means + + method divided SZ patients into two subgroups by measuring durations across trials in the motion discrimination task, i.e., high, and low irregularity of SZ patients (HSZ, LSZ). We found that HSZ and LSZ subgroups are associated with more negative and positive symptoms respectively. Applying a mediation model in the HSZ subgroup, the enhanced irregularity mediates the relationship between visual perception and negative symptoms. Together, we demonstrate increased irregularity in visual perception of a HSZ subgroup, including its association with negative symptoms. This may serve as a promising marker for identifying and distinguishing SZ subgroups.

Therapeutic ketogenic diet as treatment for anorexia nervosa.

Anorexia nervosa (AN) is a severe psychiatric disorder. However, we lack neurobiological models and interventions to explain and treat the core characteristics of food restriction, feeling fat, and body size overestimation. Research has made progress in understanding brain function involved in the pathophysiology of AN, but translating those results into biological therapies has been challenging. Studies have suggested that metabolic factors could contribute to developing and maintaining AN pathophysiology. Here, we describe a neurobiological model for why using a therapeutic ketogenic diet could address key alterations in brain function in AN and prevent the desire for weight loss and associated eating disorder-specific symptoms. This translational model is based on animal studies and human data and integrates behavioral traits, brain neural energy metabolism, and neurotransmitter function. Pilot data indicate that the intervention can dramatically reduce eating and body-related fears, although larger studies across illness stages still need to be conducted.

Comparing hospitalized adult patients with chronic anorexia nervosa with versus without prior hospitalizations

BackgroundAnorexia nervosa (AN) is a severe psychiatric disorder, from which recovery is often protracted. The role of prior specialized inpatient treatment on subsequent treatment attempts for adults with chronic AN and predictors of treatment response for severe and enduring AN (SE-AN) are needed to improve outcomes.MethodParticipants (N = 135) with chronic AN (ill ≥7 years) admitted to an integrated inpatient-partial hospitalization eating disorders (ED) unit with prior ED hospitalization(s) (+ PH; n = 100) were compared to those without prior ED hospitalizations (-PH; n = 35) on admission characteristics (BMI, length of illness, outpatient ED treatment history, symptomatology (ED, anxiety, and depressive), history of suicide attempts or non-suicidal self-injury (NSSI)), treatment motivation and recovery self-efficacy, and discharge outcomes (discharge BMI, rate of weight gain, length of stay, clinical improvement).ResultsGroups were similar with regard to age, years ill, and admission BMI. The + PH group had lower desired weight, lifetime nadir BMI and self-efficacy for normative eating, and higher state and trait anxiety than the -PH group. +PH were also more likely to endorse history of NSSI and suicide attempt. Regarding discharge outcomes, most patients achieved weight restoration at program discharge (mean discharge BMI = 19.8 kg/m2). Groups did not differ on rate of weight gain, likelihood of attending partial hospital, partial hospital length of stay, program discharge BMI, or likelihood of clinical improvement (p’s > 0.05) although inpatient length of stay was longer for the + PH group.ConclusionsParticipants with chronic AN + PH exhibited more severe psychiatric comorbidity and lower self-efficacy for normative eating than AN -PH, however short-term discharge outcomes were similar. Future research should determine whether weight restoration and targeting comorbidities impacts relapse risk or need for rehospitalization among chronic and severe + PH. Despite similar illness durations, those with chronic AN -PH may be able to transition to partial hospital earlier. Conversely there is risk of undertreatment of chronic AN + PH given the recent shift promoting briefer self-directed admissions for adults with SE-AN. Research comparing + PH and -PH adults with chronic AN may facilitate efforts to individualize care and characterize relapse risk following intensive treatment.

Central innate immunization induces tolerance against post-traumatic stress disorder-like behavior and neuroinflammatory responses in male mice

Post-traumatic stress disorder (PTSD) is a severe psychiatric disorder associated with abnormally elevated neuroinflammatory responses. Suppression of neuroinflammation is considered to be effective in ameliorating PTSD-like behaviors in rodents. Since pre-stimulation of microglia prior to stress exposure can prevent neuroinflammation, we hypothesized that pre-stimulation of microglia may prevent PTSD in animals. The results show that a single injection of a classical immune stimulant, lipopolysaccharide (LPS), at 50, 100 or 500, but not 10 μg/kg, one day before stress exposure, prevented the anxiety- and fear-like behaviors induced by modified single prolonged stress (mSPS). The time-dependent analysis shows that a single injection of LPS (100 μg/kg) either one or five, but not ten, days before stress prevented mSPS-induced anxiety- and fear-like behaviors. A second low-dose LPS injection 10 days after the first injection or a repeated LPS injection (4 × ) 10 days before stress induced tolerance to mSPS. Mechanistic studies show that a single injection of LPS one day before stress stimulation prevented mSPS-induced increases in levels of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6 mRNA in the hippocampus and medial prefrontal cortex. Inhibition of microglia by pretreatment with minocycline or depletion of microglia by PLX3397 abolished the preventive effect of low-dose LPS pre-injection on mSPS-induced anxiety- and fear-like behavior and neuroinflammatory responses. These results suggest that pre-stimulation of microglia may prevent the development of PTSD-like behaviors by attenuating the development of neuroinflammatory responses. This could help to develop new strategies to prevent the damaging effects of harmful stress on the brain.

Association between the copy number variations of Methyl-CpG binding domain family and schizophrenia

Schizophrenia is recognized as one of the most severe psychiatric disorders, with its pathogenesis likely involving genetic, epigenetic, developmental, and environmental factors. Members of the Methyl-CpG Binding Domain (MBD) Family play a crucial role in the regulation of genomic DNA methylation, and studies have implicated the association between MBD family and neurodevelopmental disorders. Copy number variations (CNVs) are a significant genetic basis for human genomic variation, also playing a critical role in the genetic processes of schizophrenia. Therefore, we aimed to evaluate the susceptibility of MBD family CNVs to schizophrenia by exploring and validating them in two separate populations using CNVplex™ and qPCR methods, and to explore the relationship between MBD family CNVs and clinical phenotypes in the overall population using chi-square tests and Fisher’s exact tests. Results suggest that an increase in MBD1 gene copy number and a deficiency in MBD2 gene copy number may be associated with the risk of schizophrenia. The deficiency in MBD2 gene copy number may increase the risk of delusion of reference and delusion of persecutory in the overall sample, as well as in males. This research provides preliminary evidence supporting the association between MBD family CNVs and schizophrenia, highlighting the potential role of the MBD family in the pathogenesis of schizophrenia.

DCC, a potential target for controlling fear memory extinction and hippocampal LTP in male mice receiving single prolonged stress

Post-traumatic stress disorder (PTSD) is a severe stress-dependent psychiatric disorder characterized by impairment of fear memory extinction; however, biological markers to determine impaired fear memory extinction in PTSD remain unclear. In male mice with PTSD-like behaviors elicited by single prolonged stress (SPS), 19 differentially expressed proteins in the hippocampus were identified compared with controls. Among them, a biological macromolecular protein named deleted in colorectal cancer (DCC) was highly upregulated. Specific overexpression of DCC in the hippocampus induced similar impairment of long-term potentiation (LTP) and fear memory extinction as observed in SPS mice. The impairment of fear memory extinction in SPS mice was improved by inhibiting the function of hippocampal DCC using a neutralizing antibody. Mechanistic studies have shown that knocking down or inhibiting μ-calpain in hippocampal neurons increased DCC expression and induced impairment of fear memory extinction. Additionally, SPS-triggered impairment of hippocampal LTP and fear memory extinction could be rescued through activation of the Rac1–Pak1 signaling pathway. Our study provides evidence that calpain-mediated regulation of DCC controls hippocampal LTP and fear memory extinction in SPS mice, which likely through activation of the Rac1–Pak1 signaling pathway.

Vitamin D Status and Behavioral Impulsivity in Anorexia Nervosa: Insights from a Longitudinal Study.

Anorexia nervosa (AN) is a severe psychiatric disorder marked by extreme weight control behaviors and significant impacts on physical and psychosocial health. This study explores the relationship between vitamin D (Vit-D) levels and impulsivity in women with AN. Forty-six cisgender White women participants were assessed upon admission and before discharge from a specialized eating disorder treatment center, with an average duration of 2.5 ± 0.10 months. Methods included self-reported questionnaires and behavioral tasks to measure impulsivity, alongside serum Vit-D levels. Our results showed significant improvements in Vit-D levels and certain impulsivity measures, such as faster reaction times and fewer errors on the go/no-go task, correlating with higher Vit-D levels. However, no significant correlations were found between Vit-D levels and self-reported impulsivity. These findings suggest that adequate Vit-D levels may enhance cognitive functions related to impulse control in AN. Given this study's limitations, including its exclusive focus on women and small sample size, future research should involve larger, more diverse populations and randomized clinical trials to better understand the causal relationships and therapeutic potential of Vit-D in managing AN-related impulsivity.

The Impact of Yoga on Athletes' Mental Well-Being: An Experimental Study.

Background Athletes have a variety of obstacles that might shrink their chances of getting adequate rest, including competing and training times, travel, stress, academic responsibilities, and overtraining. Furthermore, athletes have been reported to have poor self-reports of their sleep length and quality. The study aims to assess the impact of yoga practice on sleep quality, stress, anxiety, psychological rigidity, and experience avoidance. Methods A pre- and post-testrandomized design was applied for the research. Forty-four recreational athletes (age 18-45 years)were selected per the inclusion criteria from the athletes studying at Banaras Hindu University. Exclusion criteria are a likely severe psychiatric disorder, chronic illness, substance abuse, disability, endocrine or metabolic disorders, and history of using psychotropic drugsand smoking. The Yogic intervention contains the Pranayama and meditation, which was practiced for six weeks in the intervention group. Outcome variables were stress, sleep, anxiety, mindfulness, psychological rigidity, and experience avoidance. The Perceived Stress Scale (PSS), Pittsburgh Sleep Quality Index (PSQI),Sport Competition Anxiety Test, Mindful Attention AwarenessScale (MAAS), and Acceptance and Action Questionnaire-II (AAQ-II) were applied to measure the outcomes. Results The majority of the participants(30 (68%)) were male, and 44 (100%) had more than two years of sports experience. Of the participants, 18 (40.90%) had a habit of 3-5 hours of internet surfing. We noticed that there was a significant mean difference from pre- to post-intervention in terms of stress, sleep, anxiety, mindfulness, psychological rigidity, and experience avoidance (p < 0.0001). Conclusion The results concluded positive effects of yoga on athletes' stress, sleep, anxiety, mindfulness, psychological rigidity, and experience avoidance in athletes.Stress alleviationand reduced anxiety are the strongest predictors of improving psychological flexibility skills in athletes' daily lives. Improving mindfulness and supporting good sleep patternscould be good indicators of improving psychological rigidity and experience avoidance.

Genetic determinants of coping, resilience and self-esteem in schizophrenia suggest a primary role for social factors and hippocampal neurogenesis

Schizophrenia is a severe psychiatric disorder, associated with a reduction in life expectancy of 15–20 years. Available treatments are at least partially effective in most affected individuals, and personal resources such as resilience (successful adaptation despite adversity) and coping abilities (strategies used to deal with stressful or threatening situations), are important determinants of disease outcomes and long-term sustained recovery. Published findings support the existence of a genetic background underlying resilience and coping, with variable heritability estimates. However, genome-wide analyses concerning the genetic determinants of these personal resources, especially in the context of schizophrenia, are lacking. Here, we performed a genome-wide association study coupled with accessory analyses to investigate potential genetic determinants of resilience, coping and self-esteem in 490 schizophrenia patients. Results revealed a complex genetic background partly overlapping with that of neuroticism, worry and schizophrenia itself and support the importance of social aspects in shapingthese psychological constructs. Hippocampal neurogenesis and lipid metabolism appear to be potentially relevant biological underpinnings, and specific miRNAs such as miR-124 and miR-137 may warrant further studies as potential biomarkers. In conclusion, this study represents an important first step in the identification of genetic and biological correlates shaping resilience, coping resources and self-esteem in schizophrenia.

The Efficacy of the Herbal Formula of Bunium persicum and Coriandrum sativum on Clinical Symptoms of Patients with Functional Dyspepsia: A Double-Blind Randomized Controlled Trial

Introduction: Functional dyspepsia (FD) is one of the most prevalent chronic disorders affecting up to 30% of the world population with considerable impairment of quality of life. This study evaluated the efficacy of the herbal preparation of Bunium persicum (Boiss.) B.Fedtsch. and Coriandrum sativum L. on symptom severity, symptom frequency, and quality of life of patients with FD. Methods: This double-blind randomized controlled clinical trial, with parallel groups allocation ratio of 1:1, was conducted in a referral clinic of Afzalipour Hospital affiliated with Kerman University of Medical Sciences in Kerman, southeastern Iran. A total of 90 patients with FD (diagnosed based on the Rome IV criteria) were included in this study. The patients with complications during the intervention, pregnancy or lactation, a history of allergy to herbal drugs, use of other medication that affect the symptoms of FD during the study, and severe organic or psychiatric disorders were excluded. The participants received one capsule containing 500 mg of herbal preparation or placebo twice a day for 4 weeks and were subsequently followed up for 4 more weeks. Clinical outcomes were assessed via the Dyspepsia Severity Questionnaire, the Rome IV Diagnostic Questionnaire, and Nepean Dyspepsia Index Questionnaire. Results: A total 40 participants in each group completed the follow-up period, and their data were analyzed statistically. All clinical outcomes showed significant improvements by herbal preparation compared to the placebo without serious side effects (p < 0.05). Conclusions: This herbal preparation can significantly improve the quality of life, and symptoms of FD compared to placebo.

Glia as a New Target for Therapeutic Actions of Electroconvulsive Therapy.

Although electroconvulsive therapy (ECT) has immediate and profound effects on severe psychiatric disorders compared to pharmacotherapy, the mechanisms underlying its therapeutic effects remain elusive. Increasing evidence indicates that glial activation is a common pathogenetic factor in both major depression and schizophrenia, raising the question of whether ECT can inhibit glial activation. This article summarizes the findings from both clinical and experimental studies addressing this key question. Based on the findings, it is proposed that the suppression of glial activation associated with neuroinflammation is the mechanism by which ECT restores brain homeostasis and exerts its therapeutic effects.

Neurobiology of Obsessive-Compulsive Disorder from Genes to Circuits: Insights from Animal Models.

Obsessive-compulsive disorder (OCD) is a chronic, severe psychiatric disorder that has been ranked by the World Health Organization as one of the leading causes of illness-related disability, and first-line interventions are limited in efficacy and have side-effect issues. However, the exact pathophysiology underlying this complex, heterogeneous disorder remains unknown. This scenario is now rapidly changing due to the advancement of powerful technologies that can be used to verify the function of the specific gene and dissect the neural circuits underlying the neurobiology of OCD in rodents. Genetic and circuit-specific manipulation in rodents has provided important insights into the neurobiology of OCD by identifying the molecular, cellular, and circuit events that induce OCD-like behaviors. This review will highlight recent progress specifically toward classic genetic animal models and advanced neural circuit findings, which provide theoretical evidence for targeted intervention on specific molecular, cellular, and neural circuit events.

Aberrant brain functional connectivity mediates the effects of negative symptoms on cognitive function in schizophrenia: A structural equation model

BackgroundSchizophrenia is a severe psychiatric disorder, characterized by positive symptoms, negative symptoms, and cognitive deficits. Elucidating the mechanism of negative symptom and cognitive deficits could contribute to the treatment and prognosis of schizophrenia. We hypothesized that abnormal functional connectivity would be involved in the indirect effects of negative symptoms on cognitive function. MethodsA total of 150 schizophrenia male patients and 108 healthy controls matched for age, education and gender were enrolled in the study. The scores of Brief Negative Symptom Scale were divided into two factors: motivation and pleasure deficits (MAP) and diminished expression (EXP). Subsequently, a series of classic neurocognitive tests were used to evaluate cognitive functions. Resting-state fMRI data was collected from all participants. The Anatomical Automatic Labeling template was employed to establish regions of interest, thereby constructing the functional connectivity network across the entire brain. Eventually, scores of patients' negative symptoms scale, cognitive function, and strengths of abnormal functional connectivity were incorporated into a structural equation model to explore the interactions among variables. ResultsMAP exhibited a distinctly and significantly negative impact on cognitive function. The functional connectivity between the left insula and left precuneus, along with that between the left precuneus and right angular gyrus, collectively served as intermediaries, contributing to the indirect effects of MAP and EXP on cognitive function. ConclusionsOur findings demonstrated the moderating role of aberrant brain functional connectivity between negative symptoms and cognitive function, providing clues about the neural correlates of negative symptoms and cognitive deficits in schizophrenia.

Perturbations in gut microbiota composition in schizophrenia.

Schizophrenia is a severe, complex and long-term psychiatric disorder with unclear etiology. Gut microbes influence the central nervous system via the gut-brain axis. Consequently, investigations of the relationship between gut microbes and schizophrenia are warranted. This study involved 29 patients with schizophrenia and 30 age-matched normal controls. After 16S rRNA gene sequencing and whole-genome shotgun metagenomic sequencing, we analyzed microbial diversity, composition, and function. According to 16S rRNA and metagenomic gene sequencing results, patients with schizophrenia had higher abundances of Clostridium and Megasphaera. Functional analysis showed that sphingolipid, phosphonates and phosphinates, as well as glutamine metabolism were associated with the occurrence and development of schizophrenia. Our data suggest that the gut microbiota exerts an effect on patients with schizophrenia, providing valuable insights into the potential regulation of in the context of this disorder.