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Psychosis

A new horizon for neuroscience: terahertz biotechnology in brain research
Pu Z, Wu Y, Zhu Z, Zhao H and Cui D
Terahertz biotechnology has been increasingly applied in various biomedical fields and has especially shown great potential for application in brain sciences. In this article, we review the development of terahertz biotechnology and its applications in the field of neuropsychiatry. Available evidence indicates promising prospects for the use of terahertz spectroscopy and terahertz imaging techniques in the diagnosis of amyloid disease, cerebrovascular disease, glioma, psychiatric disease, traumatic brain injury, and myelin deficit. In vitro and animal experiments have also demonstrated the potential therapeutic value of terahertz technology in some neuropsychiatric diseases. Although the precise underlying mechanism of the interactions between terahertz electromagnetic waves and the biosystem is not yet fully understood, the research progress in this field shows great potential for biomedical noninvasive diagnostic and therapeutic applications. However, the biosafety of terahertz radiation requires further exploration regarding its two-sided efficacy in practical applications. This review demonstrates that terahertz biotechnology has the potential to be a promising method in the field of neuropsychiatry based on its unique advantages.
Impairment of olfactory identification ability in ultra-high risk for psychosis and drug-naïve first episode psychosis
Ouyang L, Ma X, Yuan L, Fan L, Liao A, Li D, Yang Z, Zhang Z, Liu W, Chen X, Li Z and He Y
Patients with psychotic diseases have been reported to exhibit abnormalities in their olfactory discrimination. These alterations have also been identified in people at high genetic or clinical risk for psychosis, suggesting olfactory discrimination dysfunction may be a potential risk factor for developing psychosis. Thus, the purpose of our study is to explore the difference in olfactory discrimination ability in the prosal stage and early stage of psychosis and to explore the potential risk factor of developed psychosis.
Grief as a Risk Factor for Psychosis: A Systematic Review
Del Pozo-Herce P, Miguel AG, Gonzalez-Rosas L, Alejandro-Rubio O, Pascual-Lapuerta C and Porras-Segovia A
The assessment of the risk of triggering psychosis upon exposure to grief is a challenge in clinical practice. Adequate diagnosis and early prevention are essential and may be helpful in the evolution of normal grief. We aimed to identify studies exploring grief as a risk factor for developing psychosis.
The relationship between schizophrenia or schizoaffective disorder and type 1 diabetes mellitus: a scoping review of observational studies
Liu YC, Liao YT and Lin KH
Both schizophrenia and type 1 diabetes mellitus (T1D) are known as immune-related disorders. We systematically reviewed observational studies to explore the relationship between schizophrenia or schizoaffective disorder and T1D.
Correction to: Service User Representation in Qualitative Research on Cognitive Health and Related Interventions for Psychosis: A Scoping Review
Group arts therapies for patients with schizophrenia: a protocol of systematic review and meta-analysis
Zhang A, Luo X, Lin R, He C, Wang J and Huang G
Schizophrenia, a chronic mental problem, significantly impacts cognition, emotion and social functioning. Conventional pharmacotherapy faces challenges including numerous side effects, low adherence to medication and substantial costs. In this context, group arts therapies (GATs) emerge as a promising complementary approach for symptom alleviation in schizophrenia patients. Nonetheless, the effectiveness and safety of GATs are yet to be firmly established. This study aims to systematically assess the therapeutic impact of all group-based artistic interventions as complementary treatments for schizophrenia, focusing on their potential benefits.
Forensic Assessments of Racial-Ethnic Differences in Genuine and Malingered Psychotic Presentations
Rogers R, Correa AA and Ryan-Jones LD
Competent forensic practice has required continued training and professional practice in differentiating between genuine and malingered presentations, especially within the spectrum of psychotic disorders. Historically, practitioners valued racial, ethnic, and cultural differences but often considered them as peripheral matters. In contemporary forensic practice, however, language and culture play preponderant roles. This commentary is focused on core features of malingering via a cultural lens. Three core, race-informed principles, such as biases against the African American Language, are highlighted and discussed. Related subjects for forensic practice include relevant clinical constructs such as malingering bias and "imposed etics," specifically, the imposition of mainstream values and discounting of cultural differences.
Predictors of Criminal Sentiments Scale-Modified Scores in Outpatients with Legal System Involvement
Pauselli L, Zern A, Fu E, Ashekun O, Ellis S, Jackson E, Pope LG, Watson AC, Wood JD and Compton MT
The Criminal Sentiments Scale-Modified (CSS-M) has been widely used as a measure of criminal attitudes. This analysis examined CSS-M scores in a large sample of outpatients with serious mental illnesses and a criminal legal system history. We compared total and subscale scores in our sample to scores from two other previously published U.S. studies in which the CSS-M was used, and evaluated associations between total CSS-M score and nine variables (age, educational attainment, gender, race, marital status, employment status, diagnostic category, substance use disorder comorbidity, and adverse childhood experiences (ACE) score). Scores were higher than in two prior U.S. studies involving other types of samples. Independently significant predictors of higher CSS-M scores included being younger ( < .001), having a higher ACE score ( < .001), being male ( =03), not identifying as White ( <001), not having a psychotic disorder ( <001), and having a comorbid substance use disorder ( =002). Future research should test the hypothesis that these factors increase risk for arrest and that arrest events, and subsequent criminal legal system involvement, are characterized by negative experiences and perceptions of poor procedural justice, which in turn underpin the negative opinions referred to as "criminal sentiments" or criminal attitudes.
Factor analysis of lifetime psychopathology and its brain morphometric and genetic correlates in a transdiagnostic sample
Krug A, Stein F, David FS, Schmitt S, Brosch K, Pfarr JK, Ringwald KG, Meller T, Thomas-Odenthal F, Meinert S, Thiel K, Winter A, Waltemate L, Lemke H, Grotegerd D, Opel N, Repple J, Hahn T, Streit F, Witt SH, Rietschel M, Andlauer TFM, Nöthen MM, Philipsen A, Nenadić I, Dannlowski U, Kircher T and Forstner AJ
There is a lack of knowledge regarding the relationship between proneness to dimensional psychopathological syndromes and the underlying pathogenesis across major psychiatric disorders, i.e., Major Depressive Disorder (MDD), Bipolar Disorder (BD), Schizoaffective Disorder (SZA), and Schizophrenia (SZ). Lifetime psychopathology was assessed using the OPerational CRITeria (OPCRIT) system in 1,038 patients meeting DSM-IV-TR criteria for MDD, BD, SZ, or SZA. The cohort was split into two samples for exploratory and confirmatory factor analyses. All patients were scanned with 3-T MRI, and data was analyzed with the CAT-12 toolbox in SPM12. Psychopathological factor scores were correlated with gray matter volume (GMV) and cortical thickness (CT). Finally, factor scores were used for exploratory genetic analyses including genome-wide association studies (GWAS) and polygenic risk score (PRS) association analyses. Three factors (paranoid-hallucinatory syndrome, PHS; mania, MA; depression, DEP) were identified and cross-validated. PHS was negatively correlated with four GMV clusters comprising parts of the hippocampus, amygdala, angular, middle occipital, and middle frontal gyri. PHS was also negatively associated with the bilateral superior temporal, left parietal operculum, and right angular gyrus CT. No significant brain correlates were observed for the two other psychopathological factors. We identified genome-wide significant associations for MA and DEP. PRS for MDD and SZ showed a positive effect on PHS, while PRS for BD showed a positive effect on all three factors. This study investigated the relationship of lifetime psychopathological factors and brain morphometric and genetic markers. Results highlight the need for dimensional approaches, overcoming the limitations of the current psychiatric nosology.
Excessive interstitial free-water in cortical gray matter preceding accelerated volume changes in individuals at clinical high risk for psychosis
Cho KIK, Zhang F, Penzel N, Seitz-Holland J, Tang Y, Zhang T, Xu L, Li H, Keshavan M, Whitfield-Gabrieli S, Niznikiewicz M, Stone WS, Wang J, Shenton ME and Pasternak O
Recent studies show that accelerated cortical gray matter (GM) volume reduction seen in anatomical MRI can help distinguish between individuals at clinical high risk (CHR) for psychosis who will develop psychosis and those who will not. This reduction is suggested to represent atypical developmental or degenerative changes accompanying an accumulation of microstructural changes, such as decreased spine density and dendritic arborization. Detecting the microstructural sources of these changes before they accumulate into volume loss is crucial. Our study aimed to detect these microstructural GM alterations using diffusion MRI (dMRI). We tested for baseline and longitudinal group differences in anatomical and dMRI data from 160 individuals at CHR and 96 healthy controls (HC) acquired in a single imaging site. Of the CHR individuals, 33 developed psychosis (CHR-P), while 127 did not (CHR-NP). Among all participants, longitudinal data was available for 45 HCs, 17 CHR-P, and 66 CHR-NP. Eight cortical lobes were examined for GM volume and GM microstructure. A novel dMRI measure, interstitial free water (iFW), was used to quantify GM microstructure by eliminating cerebrospinal fluid contribution. Additionally, we assessed whether these measures differentiated the CHR-P from the CHR-NP. In addition, for completeness, we also investigated changes in cortical thickness and in white matter (WM) microstructure. At baseline the CHR group had significantly higher iFW than HC in the prefrontal, temporal, parietal, and occipital lobes, while volume was reduced only in the temporal lobe. Neither iFW nor volume differentiated between the CHR-P and CHR-NP groups at baseline. However, in many brain areas, the CHR-P group demonstrated significantly accelerated changes (iFW increase and volume reduction) with time than the CHR-NP group. Cortical thickness provided similar results as volume, and there were no significant changes in WM microstructure. Our results demonstrate that microstructural GM changes in individuals at CHR have a wider extent than volumetric changes or microstructural WM changes, and they predate the acceleration of brain changes that occur around psychosis onset. Microstructural GM changes, as reflected by the increased iFW, are thus an early pathology at the prodromal stage of psychosis that may be useful for a better mechanistic understanding of psychosis development.
The Evolving Standard of Care for Autoimmune Neuropsychiatric Illness
He C, Morris N, McNiel D and Binder R
In recent decades, there has been increasing biomedical and public understanding of the role of autoimmunity in neuropsychiatric illness. Popular media have highlighted patients with psychiatric illnesses who were eventually diagnosed with autoimmune neuropsychiatric illnesses such as anti N-methyl-D-aspartate receptor encephalitis. Coverage of these cases has often drawn attention to the effects of misdiagnosis or delayed diagnosis of such diseases in psychiatric patients. Autoimmune encephalitis can have varied presentations and often involves evaluation and management from multiple medical specialties. As a result, there remains considerable uncertainty regarding how courts might gauge the legal standard of care with regard to psychiatric workup of new-onset psychiatric symptoms, and the degree to which autoimmune encephalitis must be considered. In this article we provide a brief overview of autoimmune encephalitis and autoimmune psychosis, including current diagnostic approaches to these conditions. We review case law regarding the standard of care for psychiatric disorders caused by general medical conditions. Finally, we provide a medicolegal perspective on the responsibilities of psychiatrists and other mental health professionals in the evaluation of possible autoimmune encephalitis.
Multivariate brain-behaviour associations in psychiatric disorders
Vieira S, Bolton TAW, Schöttner M, Baecker L, Marquand A, Mechelli A and Hagmann P
Mapping brain-behaviour associations is paramount to understand and treat psychiatric disorders. Standard approaches involve investigating the association between one brain and one behavioural variable (univariate) or multiple variables against one brain/behaviour feature ('single' multivariate). Recently, large multimodal datasets have propelled a new wave of studies that leverage on 'doubly' multivariate approaches capable of parsing the multifaceted nature of both brain and behaviour simultaneously. Within this movement, canonical correlation analysis (CCA) and partial least squares (PLS) emerge as the most popular techniques. Both seek to capture shared information between brain and behaviour in the form of latent variables. We provide an overview of these methods, review the literature in psychiatric disorders, and discuss the main challenges from a predictive modelling perspective. We identified 39 studies across four diagnostic groups: attention deficit and hyperactive disorder (ADHD, k = 4, N = 569), autism spectrum disorders (ASD, k = 6, N = 1731), major depressive disorder (MDD, k = 5, N = 938), psychosis spectrum disorders (PSD, k = 13, N = 1150) and one transdiagnostic group (TD, k = 11, N = 5731). Most studies (67%) used CCA and focused on the association between either brain morphology, resting-state functional connectivity or fractional anisotropy against symptoms and/or cognition. There were three main findings. First, most diagnoses shared a link between clinical/cognitive symptoms and two brain measures, namely frontal morphology/brain activity and white matter association fibres (tracts between cortical areas in the same hemisphere). Second, typically less investigated behavioural variables in multivariate models such as physical health (e.g., BMI, drug use) and clinical history (e.g., childhood trauma) were identified as important features. Finally, most studies were at risk of bias due to low sample size/feature ratio and/or in-sample testing only. We highlight the importance of carefully mitigating these sources of bias with an exemplar application of CCA.
Social influences on the relationship between dissociation and psychotic-like experiences
Heriot-Maitland C, Wykes T and Peters E
Shame is experienced as a threat to social self, and so activates threat-protective responses. There is evidence that shame has trauma-like characteristics, suggesting it can be understood within the same conceptual framework as trauma and dissociation. Evidence for causal links among trauma, dissociation, and psychosis thus warrant the investigation of how shame may influence causal mechanisms for psychosis symptoms.
How far have we advanced in early intervention for bipolar disorder?
Cerqueira R, Surjan J, Lacerda ALT and Noto C
A systematic review of the association between parent-child communication and adolescent mental health
Zapf H, Boettcher J, Haukeland Y, Orm S, Coslar S and Fjermestad K
This systematic review addresses how adolescent-rated parent-child communication (PCC) quality is related to adolescent mental health.
Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context
Taher R, Bhanushali P, Allan S, Alvarez-Jimenez M, Bolton H, Dennison L, Wallace BE, Hadjistavropoulos HD, Hall CL, Hardy A, Henry AL, Lane S, Maguire T, Moreton A, Moukhtarian TR, Vallejos EP, Shergill S, Stahl D, Thew GR, Timulak L, van den Berg D, Viganò N, Stock BW, Young KS and Yiend J
Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence.
Domain-specific associations between psychopathology and neurocognitive functioning
Zoupou E, Moore TM, Calkins ME, Gur RE, Gur RC and Scott JC
Neurocognitive dysfunction is a transdiagnostic finding in psychopathology, but relationships among cognitive domains and general and specific psychopathology dimensions remain unclear. This study aimed to examine associations between cognition and psychopathology dimensions in a large youth cohort.
Association of Problematic Internet Use With Psychotic Experiences and Depression in Adolescents: A Cohort Study
Narita Z, Ando S, Yamasaki S, Miyashita M, DeVylder J, Yamaguchi S, Hosozawa M, Nakanishi M, Hiraiwa-Hasegawa M, Furukawa TA, Kasai K and Nishida A
Problematic internet use (PIU) is prevalent among adolescents. Past research suggested cross-sectional associations between PIU and psychotic experiences, but little information is available on the longitudinal association. We hypothesized that PIU in adolescence may be longitudinally associated with psychotic experiences, adjusting for confounders.
Dim Cap? Or Dull Bulb?
Harris V
Tropicamide-induced psychosis in the context of chemsex practices treated in an emergency department
Sorroche C, Oliveras C and Miquel L
Aligning Stem Cell Models and Postmortem Studies to Query Striatal Neurodevelopment in Schizophrenia
Brennand KJ
The Genesis of Schizophrenia: An Origin Story
Birnbaum R and Weinberger DR
Schizophrenia is routinely referred to as a neurodevelopmental disorder, but the role of brain development in a disorder typically diagnosed during early adult life is enigmatic. The authors revisit the neurodevelopmental model of schizophrenia with genomic insights from the most recent schizophrenia clinical genetic association studies, transcriptomic and epigenomic analyses from human postmortem brain studies, and analyses from cellular models that recapitulate neurodevelopment. Emerging insights into schizophrenia genetic risk continue to converge on brain development, particularly stages of early brain development, that may be perturbed to deviate from a typical, normative course, resulting in schizophrenia clinical symptomatology. As the authors explicate, schizophrenia genetic risk is likely dynamic and context dependent, with effects of genetic risk varying spatiotemporally, across the neurodevelopmental continuum. Optimizing therapeutic strategies for the heterogeneous collective of individuals with schizophrenia may likely be guided by leveraging markers of genetic risk and derivative functional insights, well before the emergence of psychosis. Ultimately, rather than a focus on therapeutic intervention during adolescence or adulthood, principles of prediction and prophylaxis in the pre- and perinatal and neonatal stages may best comport with the biology of schizophrenia to address the early-stage perturbations that alter the normative neurodevelopmental trajectory.
The More Things Change . .
Kahn RS
Neuromelanin-Sensitive MRI: A Biomarker for Treatment-Resistant Schizophrenia?
Vano LJ, Veronese M, McCutcheon RA and Howes OD
Emerging therapies for treatment of agitation, psychosis, or apathy in Alzheimer's disease
Wang HJ, Chinna-Meyyappan A, Feldman OJ and Lanctôt KL
Agitation, psychosis, and apathy are prevalent and highly distressing neuropsychiatric symptoms (NPS) of Alzheimer's disease (AD) that have been linked to numerous negative outcomes, including increased mortality, worsened cognitive decline, and caregiver burden. Current treatments for AD-associated agitation, namely atypical antipsychotics, provide some benefits but may increase the risk of serious adverse events and death. Meanwhile, no pharmacotherapies have been approved by regulatory agencies for the treatment of psychosis or apathy in AD. Over the past decade, many new and repurposed drugs have emerged as potential therapeutic options for managing these challenging NPS.
Cognitive Remediation in Schizophrenia Spectrum Illness: Evidence for Treatment Persistence
Kurtz MM
Adherence, health care utilization, and costs between long-acting injectable and oral antipsychotic medications in South Carolina Medicaid beneficiaries with schizophrenia
Cai C, Kozma C, Patel C, Benson C, Yunusa I, Zhao P, Reeder G, Narasimhan M and Bank RL
Schizophrenia and schizoaffective disorder require long-term antipsychotic treatment with antipsychotic medications, but poor medication adherence can lead to increased health care utilization and costs. Long-acting injectable antipsychotics (LAIs) offer potential therapeutic advantages in that they require less frequent dosing and improved medication adherence. South Carolina has the highest adoption of LAIs among US states, making it an ideal population for comparing the effectiveness of LAIs vs oral antipsychotics (OAPs) in treating schizophrenia or schizoaffective disorder.
Culturally adapted cognitive behavioral therapy for psychosis (CaCBTp): A review of key features of cultural adaptation and considerations for psychologists
Jagtap S, Zahid A, Dere J, Gerritsen C, D'Arcey J, Romanowska S and Best MW
Cognitive behavioral therapy for psychosis is an effective treatment for psychosis. However, psychosis presents differentially according to an individual's cultural context, and it is currently unclear which methods have been used to formulate culturally adapted cognitive behavioral therapy for psychosis (CaCBTp). The current systematic review examines the approaches to CaCBTp that have been evaluated to date and comments on preliminary evidence for the efficacy of CaCBTp. Key features of CaCBTp interventions are discussed in reference to broader cultural adaptations of psychosocial interventions for psychosis and culturally adapted cognitive behavioral therapy for other disorders. Overall, our results identified 12 studies and highlighted five overarching themes of cultural adaptation that clinicians should integrate into the design of future CaCBTp interventions, including family members in treatment, targeting stigma, relying on spiritual leaders, using multifaceted models of mental health, and ensuring adequate language match. The results of this review also highlight the paucity of literature in global CaCBTp interventions, as only 10 studies examining CaCBTp interventions were found. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
A comparison of patient ratings and staff ratings of disability using the World Health Organisation Disability Assessment Schedule in individuals with psychotic spectrum disorders who are forensic psychiatric inpatients
Källman MV, Hedlund-Lindberg M, Kristiansson M and Johansson AGM
Psychosocial rehabilitation in forensic psychiatric services requires sound measurement of patient and staff perceptions of psychosocial function. The recommended World Health Organisation Disability Assessment Schedule 2.0 (WHODAS), designed for this, has not been examined with offender patients.
A multi-country examination of the relationship between perfectionism and disordered eating: the indirect effect of obsessive beliefs and obsessive-compulsive symptoms
Fekih-Romdhane F, Pardini S, Hallit S, Novara C and Brytek-Matera A
Despite the extensive literature on the association between perfectionism and disordered eating (DE), only scant attention has been given to the underlying processes that may mediate this relationship. The present study aimed to contribute to existing literature by investigating the direct and indirect relations between perfectionism and DE through obsessive-compulsive disorder (OCD) symptoms and obsessive beliefs, among community adults from three different countries and cultural backgrounds (i.e. Poland, Italy and Lebanon).
Trajectories of suicidal risk among individuals with first-episode psychosis: Relationship to recovery and symptoms
Wastler HM, Mengda Y, Pan X, Bornheimer LA, Moe AM and Breitborde NJK
This study examined trajectories of suicide-risk and their relationship to symptoms, recovery, and quality of life over time. Data was obtained from the Recovery after an Initial Schizophrenia Episode Early Treatment Program (RAISE-ETP) study. 404 individuals with first-episode psychosis (FEP) completed measures of suicide-risk, depression, positive symptoms, recovery, and quality of life at baseline, 6mo, 12mo, 18mo, and 24mo. Latent class analysis was used to identify temporal trajectories of suicide-risk. General linear mixed models for repeated measures were used to examine the relationship between the latent trajectories of suicide-risk and clinical variables. Results identified three latent trajectories of suicide-risk (low-risk, worsening, and improving). The low-risk and improving classes experienced improvements in depression, positive symptoms, quality of life, and recovery over time. The worsening class experienced improvements in positive symptoms and quality of life, but no change in depression or recovery. These results suggest that some individuals with FEP are at risk for persistent depression and worsening suicide-risk during treatment despite experiencing improvements in positive symptoms and quality of life. These findings have important clinical implications, as persistent depression and worsening suicide-risk might be masked by the primary focus on positive symptoms and quality of life in most FEP clinics.
Challenges and Prospects in Epilepsy Monitoring Units: A Comprehensive Review of Logistic Barriers
Albarrak A
Epilepsy is one of the most common neurological diseases with a prevalence ranging from 0.5% to 2% in different sittings. The World Health Organization (WHO) estimated that nearly 80% of this burden is borne by resource-poor countries where even conventional electroencephalogram (EEG) coverage is dramatically short.  Video EEG monitoring applied for days as conducted in epilepsy monitoring units (EMUs) is aimed at seizure localization, anti-seizure medication (ASM) adjustment, or epilepsy surgery evaluation and planning. However, the EEG approach in EMUs has its obstacles. The present article is aimed to concentrate on the logistic challenges of EMUs, discussing existing data and limitations and offering suggestions for future planning to enhance the utilization of existing technology. Shortages of adult and pediatric epileptologists, qualified nurses, as well as EEG technologists have been reported in different countries. Moreover, injuries and falls, psychosis, status epilepticus, and unexpected death have been stated to be the most frequent safety issues in EMUs. Enhancements to mitigate logistical and healthcare system-related barriers in EMUs include the implementation of large cohort studies and the utilization of artificial intelligence (AI) for the identification and categorization of specific risks among EMU admissions. The establishment of EMUs and their associated challenges and barriers are best acknowledged through discussions and dialogue with various stakeholders.
Post-Traumatic Stress-Disorder in Epilepsy: Meta-analysis of current evidence
Pepi C, Mercier M, Salimbene L, Galati C, Specchio N and de Palma L
Epilepsy, a chronic neurological condition characterized by unpredictable seizures, poses considerable challenges, including disability, stigma, and increased mortality. Psychiatric comorbidities are prevalent in 20-30% of epilepsy patients, notably mood or anxiety disorders, psychotic symptoms, and personality disorders. Trauma and childhood adversities are pivotal risk factors for psychopathology, yet the link between Post-Traumatic Stress Disorder (PTSD) and epilepsy remains underexplored. This meta-analysis is aimed to establish updated estimates of PTSD prevalence among individuals with epilepsy. Fifteen studies, comprising 996 epilepsy patients, were included. The overall pooled prevalence of PTSD in epilepsy patients was 18%. Notably, patients with epilepsy exhibited a three-fold increased risk of developing PTSD compared to the general population. Subgroup analysis revealed a higher PTSD prevalence in uncontrolled studies (25%) compared to controlled studies (14%). Additionally, patients with Psychogenic Non-Epileptic Seizures (PNES) demonstrated higher PTSD prevalence than epilepsy patients, with a threefold higher risk in healthy controls compared to PNES controls. While gender prevalence did not significantly affect PTSD occurrence, drug resistant epilepsy did not correlate with PTSD prevalence. Moreover, age of epilepsy onset showed no significant correlation with PTSD prevalence. This meta-analysis underscores the substantial burden of PTSD among epilepsy patients, potentially attributable to the traumatic nature of seizures and the chronic stigma associated with epilepsy. Improved recognition and management of psychiatric conditions, particularly PTSD, are crucial in epilepsy care pathways to enhance patients' quality of life. Further research and comprehensive diagnostic tools are imperative to better understand and address the prevalence of PTSD in epilepsy patients.
Understanding ageism towards older nursing staff and service users: A systematic mapping review from the perspective of clinical leaders and healthcare managers
Schüttengruber G, Olsson MM, Holmberg C, Großschädl F, Hessman E, Sjöblom H and Heckemann B
Ageist attitudes negatively affect the quality of care for service users and the working conditions of older nursing staff. Clinical leaders' perceptions of older service users and nursing staff are unknown.
Depressed mood as a transdiagnostic target relevant to anxiety and/or psychosis: a scoping review protocol
Dambi J, Mavindidze E, Nyamayaro P, Beji-Chauke R, Tunduwani TD, Shava BK, Mavhu W, Abas M, Chibanda D and Nhunzvi C
Depressed mood is a psychological state characterised by sadness or loss of interest in activities. Depressed mood is a highly prevalent symptom across major mental disorders. However, there is limited understanding of the burden and management of comorbid depressed mood across major mental disorders. Therefore, this scoping review aims to summarise knowledge on depressed mood among persons with anxiety and/or psychosis. The specific aims are to describe the epidemiology and risk factors of depressed mood as a transdiagnostic target among persons with anxiety and/or psychosis, to identify commonly used outcome measures for depressed mood and to outline initial evidence of psychometric robustness and to identify and summarise the effectiveness of commonly applied depressed mood modification interventions. Our hope is that the proposed review will provide insights into the burden of depressed mood in persons with anxiety and psychosis and help to identify evidence gaps and recommendations for future research.
Statins as an adjuvant therapy for patients with schizophrenia: An up-to-date systematic review and meta-analysis
Peng TR, Lin HH, Lee MC and Chen SM
Evidence suggests that inflammatory processes play a role in the pathophysiology of schizophrenia. Statins exert anti-inflammatory and antioxidant effects and may be effective in improving the symptoms of schizophrenia. This study explored whether statins, as an adjunctive therapy, can alleviate the symptoms of schizophrenia.
The contribution of alexithymia, childhood maltreatment, impulsivity, C-reactive protein, lipid profile, and thyroid hormones to aggression and psychological distress (depression and anxiety) in schizophrenia
Khosravani V, Sharifibastan F, Aghaeimazraji M, Berk M and Samimi Ardestani SM
There are individual effects of alexithymia, childhood maltreatment, impulsivity, and some biological markers on aggression and psychological distress in schizophrenia. However, the combined effects of these psychological and biological markers have not yet been fully studied. This study therefore aimed to investigate the influence of these psychological and biological markers on aggression and psychological distress (e.g., depression and anxiety) in inpatients with schizophrenia (n = 355). Participants completed self-report and clinician-rated scales, and blood samples were collected. There were no significant differences between patients with and without alexithymia regarding biological markers. Patients with childhood maltreatment exhibited higher levels of free triiodothyronine (FT3) and C-reactive protein (CRP), as well as lower total cholesterol (TC) levels, compared to non-traumatized individuals. Aggression was positively predicted by psychological distress, alexithymia, childhood maltreatment, impulsivity, CRP, and FT3, and negatively by TC and low-density lipoprotein cholesterol. Negative symptoms, childhood maltreatment, alexithymia, aggression, and CRP positively, and high-density lipoprotein cholesterol negatively emerged as predictors of psychological distress. The study highlights the connections between childhood maltreatment, alexithymia, impulsivity, and potentially related biological dysregulation in explaining aggression and negative mood states as a bio-psychological model of aggression and mood in schizophrenia.
Treating depression in patients with borderline personality disorder: clinical clues on the use of antidepressants
Tomasetti C, Autullo G, Ballerini A, de Bartolomeis A, Dell'Osso B, Fiorentini A, Tonioni F, Villari V and De Berardis D
Personality disorders (PD) are described as enduring patterns of markedly deviant and pervasive inner experiences and behaviors, with onset in adolescence, which lead to severe distress or impairment. Patients suffering from major depressive disorder (MDD) display higher rates of comorbidity with personality disorders, often complicating the treatment, and worsening the outcomes. Borderline personality disorder (BPD) is the most common of PD and is frequently associated with MDD, with which shares several features. The most part of research agrees on the fact that comorbid BPD in MDD patients quite doubles the poor response to treatments. Moreover, no treatment strategy stands out currently to emerge as more effective in these cases, thus urging the call for the need of new approaches. Herein, we revise the current literature on BPD, its neurobiology and comorbidity with MDD, as well as the more recent treatment strategies used. Then, based on its pharmacology, we propose a possible role of trazodone as a valuable tool to approach comorbid BPD-MDD.
NOVEL THERAPEUTIC APPROACHES IN THALASSEMIAS, SICKLE CELL DISEASE AND OTHER RED CELL DISORDERS
Pinto VM, Mazzi F and De Franceschi L
In this last decade, a deeper understanding of the pathophysiology of hereditary red cell disorders and the development of novel classes of pharmacologic agents have provided novel therapeutic approaches to thalassemias, sickle cell disease (SCD) and other red cell disorders. Here, we analyze and discuss the novel therapeutic options according to their targets and taking into consideration the complex process of erythroid differentiation, maturation, and survival of erythrocytes in the peripheral circulation. We focus on active clinical exploratory and confirmatory trials on thalassemias, SCD and other red cell disorders. Beside -thalassemia and SCD, we found that the development of new therapeutic strategies has allowed the design of clinic studies also for hereditary red cell disorders still lacking valuable therapeutic alternative such as -thalassemias, congenital dyserythropoietic anemia or Blackfan Diamond anemia. In addition, reduction of heme synthesis, which can be achieved by the repurposed anti-psychotic drug Bitopertin, might affect not only hematological disorders but multiorgan diseases such as erythropoietic protoporphyria. Finally, our review highlights the current state of therapeutic scenarios, in which multiple indications targeting different red cell disorders are being considered for a single agent. This is welcome change which will hopefully expand therapeutic option for patients affected by thalassemias, SCD and other red cell disorders.
Behavioral meaures of psychotic disorders: Using automatic facial coding to detect nonverbal expressions in video
Martin EA, Lian W, Oltmanns JR, Jonas KG, Samaras D, Hallquist MN, Ruggero CJ, Clouston SAP and Kotov R
Emotional deficits in psychosis are prevalent and difficult to treat. In particular, much remains unknown about facial expression abnormalities, and a key reason is that expressions are very labor-intensive to code. Automatic facial coding (AFC) can remove this barrier. The current study sought to both provide evidence for the utility of AFC in psychosis for research purposes and to provide evidence that AFC are valid measures of clinical constructs. Changes of facial expressions and head position of participants-39 with schizophrenia/schizoaffective disorder (SZ), 46 with other psychotic disorders (OP), and 108 never psychotic individuals (NP)-were assessed via FaceReader, a commercially available automated facial expression analysis software, using video recorded during a clinical interview. We first examined the behavioral measures of the psychotic disorder groups and tested if they can discriminate between the groups. Next, we evaluated links of behavioral measures with clinical symptoms, controlling for group membership. We found the SZ group was characterized by significantly less variation in neutral expressions, happy expressions, arousal, and head movements compared to NP. These measures discriminated SZ from NP well (AUC = 0.79, sensitivity = 0.79, specificity = 0.67) but discriminated SZ from OP less well (AUC = 0.66, sensitivity = 0.77, specificity = 0.46). We also found significant correlations between clinician-rated symptoms and most behavioral measures (particularly happy expressions, arousal, and head movements). Taken together, these results suggest that AFC can provide useful behavioral measures of psychosis, which could improve research on non-verbal expressions in psychosis and, ultimately, enhance treatment.
Effectiveness of a mental health literacy module on stigma related mental health knowledge and behaviour among youth in two educational settings in Chennai, South India: A quasi-experimental study
Raghavan V, Chandrasekaran S, Paul V, Pattabiraman R, Mohan G, Durairaj J, Currie G, Lilford R, Furtado V, Madan J, Birchwood M, Meyer C, Sood M, Chadda R, Mohan M, Shah J, John S, Padmavati R, Iyer S, Thara R, Singh S and
Improving mental health literacy (MHL) can reduce stigma towards mental illness, decreasing delays in help-seeking for mental disorders such as psychosis. We aimed to develop and assess the impact of an interactive MHL intervention on stigma related mental health knowledge and behaviour (SRMHKB) among youth in two urban colleges in South India.
Delineating the Molecular Mechanisms of Hippocampal Neurotoxicity Induced by Chronic Administration of Synthetic Cannabinoid AB-FUBINACA in Mice
Alzu'bi A, Abu-El-Rub E, Almahasneh F, Tahat L, Athamneh RY, Khasawneh R, Alzoubi H, Ghorab DS, Almazari R, Zoubi MSA and Al-Zoubi RM
Chronic use of synthetic cannabinoids (SCs) has been associated with cognitive and behavioural deficits and an increased risk of neuropsychiatric disorders. The underlying molecular and cellular mechanisms of the neurotoxic effects of long-term use of SCs have not been well investigated in the literature. Herein, we evaluated the in vivo effects of chronic administration of AB-FUBINACA on the hippocampus in mice. Our results revealed that the administration of AB-FUBINACA induced a significant impairment in recognition memory associated with histopathological changes in the hippocampus. These findings were found to be correlated with increased level of oxidative stress, neuroinflammation, and apoptosis markers, and reduced expression of brain-derived neurotrophic factor (BDNF), which plays an essential role in modulating synaptic plasticity integral for promoting learning and memory in the hippocampus. Additionally, we showed that AB-FUBINACA significantly decreased the expression of NR1, an important functional subunit of glutamate/NMDA receptors and closely implicated in the development of toxic psychosis. These findings shed light on the long-term neurotoxic effects of SCs on hippocampus and the underlying mechanisms of these effects. This study provided new targets for possible medical interventions to improve the treatment guidelines for SCs addiction.
Peri-ictal psychiatric manifestations in people with epilepsy: An umbrella review
Alva-Diaz C, Cabanillas-Lazo M, Navarro-Flores A, Martinez-Rivera RN, Valdeiglesias-Abarca M, Acevedo-Marino K, Pacheco-Barrios K, Ruiz-Garcia R and Burneo J
We aimed to conduct an umbrella review to summarize the existing evidence regarding the prevalence of peri-ictal psychiatric manifestations (PM) in people with epilepsy (PWE) including pre-ictal, ictal, and postictal stages.
Anhedonia as a potential transdiagnostic phenotype with immune-related changes in recent onset mental health disorders
Lalousis PA, Malaviya A, Khatibi A, Saberi M, Kambeitz-Ilankovic L, Haas SS, Wood SJ, Barnes NM, Rogers J, Chisholm K, Bertolino A, Borgwardt S, Brambilla P, Kambeitz J, Lencer R, Pantelis C, Ruhrmann S, Salokangas RKR, Schultze-Lutter F, Schmidt A, Meisenzahl E, Dwyer D, Koutsouleris N, Upthegrove R, Griffiths SL and
Chronic low-grade inflammation is observed across mental disorders and is associated with difficult-to-treat-symptoms of anhedonia and functional brain changes - reflecting a potential transdiagnostic dimension. Previous investigations have focused on distinct illness categories in those with enduring illness, with few exploring inflammatory changes. We sought to identify an inflammatory signal and associated brain function underlying anhedonia among young people with recent onset psychosis (ROP) and recent onset depression (ROD).
Barriers and facilitators to mental health treatment access and engagement for LGBTQA+ people with psychosis: a scoping review protocol
Gonçalves CC, Waters Z, Quirk SE, Haddad PM, Lin A, Williams LJ and Yung AR
The prevalence of psychosis has been shown to be disproportionately high amongst sexual and gender minority individuals. However, there is currently little consideration of the unique needs of this population in mental health treatment, with LGBTQA+ individuals facing barriers in accessing timely and non-stigmatising support for psychotic experiences. This issue deserves attention as delays to help-seeking and poor engagement with treatment predict worsened clinical and functional outcomes for people with psychosis. The present protocol describes the methodology for a scoping review which will aim to identify barriers and facilitators faced by LGBTQA+ individuals across the psychosis spectrum in help-seeking and accessing mental health support.
Navigating Treatment Challenges: A Case Study on Refractory Psychosis in a Chronic MDMA (3,4-Methylenedioxymethamphetamine) User
Litenski MN, O'Reardon AB, Pabon N, Hernandez M, Niyazov Y and Cruz J
MDMA (3,4-methylenedioxy​methamphetamine), also known as Ecstasy, is a synthetic amphetamine with hallucinogenic and stimulant properties, which has become increasingly favored as a substance for recreational use. Despite its deceptive reputation as "safe," chronic MDMA use is associated with neuropsychiatric complications, including psychosis. We describe a case of a 23-year-old woman with chronic MDMA use disorder and childhood trauma, who presented with severe psychosis and catatonic features. While initial diagnostic possibilities included drug-induced psychosis and mood disorders, the patient's history and presentation supported a diagnosis of bipolar I disorder with psychotic features, which was exacerbated by MDMA use. Conventional antipsychotics failed to improve psychotic symptoms and led to worsening of catatonia, requiring electroconvulsive therapy (ECT) for improvement. Socioeconomic barriers hindered follow-up care, leading to an Emergency Department (ED) admission shortly after discharge. This case highlights the intricate interplay between substance use, psychiatric illness, and trauma, and showcases ECT's efficacy in severe psychosis. It emphasizes the necessity for comprehensive mental health services, especially for vulnerable populations, and calls for further research into MDMA's psychiatric effects and optimal treatment approaches for individuals with co-occurring substance use and psychiatric disorders.
Psychosis as a disorder of muscarinic signalling: psychopathology and pharmacology
McCutcheon RA, Weber LAE, Nour MM, Cragg SJ and McGuire PM
Dopaminergic receptor antagonism is a crucial component of all licensed treatments for psychosis, and dopamine dysfunction has been central to pathophysiological models of psychotic symptoms. Some clinical trials, however, indicate that drugs that act through muscarinic receptor agonism can also be effective in treating psychosis, potentially implicating muscarinic abnormalities in the pathophysiology of psychosis. Here, we discuss understanding of the central muscarinic system, and we examine preclinical, behavioural, post-mortem, and neuroimaging evidence for its involvement in psychosis. We then consider how altered muscarinic signalling could contribute to the genesis and maintenance of psychotic symptoms, and we review the clinical evidence for muscarinic agents as treatments. Finally, we discuss future research that could clarify the relationship between the muscarinic system and psychotic symptoms.
A service evaluation study of the impact of ageless policy in a London inner-city early intervention in psychosis service
Johnston-Webber C, Gyawali S, Akyuz EU, Zlate M, Nerantzis G, Beauvillain N, Andlauer O and Gupta S
Schizophreniform disorders tend to have an early onset. Early intervention in psychosis (EIP) services aim to provide early treatment, reduce long-term morbidity and improve social functioning. In 2016, changes to mental health policy in England mandated that the primarily youth-focused model should be extended to an ageless one, to prevent ageism; however, this was without strong research evidence.
New drug treatments for schizophrenia: a review of approaches to target circuit dysfunction
Howes OD, Dawkins E, Lobo MC, Kaar SJ and Beck K
Schizophrenia is a leading cause of global disease burden. Current drug treatments are associated with significant side-effects and have limited efficacy for many patients; highlighting the need to develop new approaches that target other aspects of the neurobiology of schizophrenia. Preclinical, in vivo imaging, post-mortem, genetic and pharmacological studies have highlighted the key role of cortical GABA-glutamatergic microcircuits and their projections to subcortical dopaminergic circuits in the pathoetiology of negative, cognitive and psychotic symptoms. Antipsychotics primarily act downstream of the dopaminergic component of this circuit. However, multiple drugs are currently in development that could target other elements of this circuit to treat schizophrenia. These include drugs for GABA or glutamatergic targets, including glycine transporters, d-amino acid oxidase, sodium channels or potassium channels. Other drugs in development are likely to primarily act on pathways that regulate the dopaminergic system such as muscarinic or trace amine receptors or serotonin 2A receptors, whilst phosphodiesterase 10 A inhibitors are being developed to modulate the downstream consequences of dopaminergic dysfunction. Our review considers where new drugs may act on this circuit and their latest clinical trial evidence in terms of indication, efficacy and side-effects. Limitations of the circuit model, including whether there are neurobiologically distinct subgroups of patients, and future directions are also considered. Several drugs based on the mechanisms reviewed have promising clinical data, with the muscarinic agonist KarXT most advanced. If they are approved for clinical use, they have the potential to revolutionise understanding of the pathophysiology and treatment of schizophrenia.
Designing and implementing a physical exercise intervention for people with first episode psychosis using experience-based co-design: A pilot study from Chennai, India
Vijayalakshmi U, Padmavati R, Raghavan V, Chandrasekaran S, Mohan G, Durairaj J, Currie G, Lilford R, Furtado V, Madan J, Birchwood M, Meyer C, Sood M, Chadda R, Mohan M, Shah J, John S, Iyer SN, Thara R and Singh S
Physical exercise can improve outcomes for people with first-episode psychosis (FEP). Co-designing physical exercise interventions with end users has the potential to enhance their acceptability, feasibility, and long-term viability. This study's objective was to use experience-based co-design (EBCD) methodology to develop a physical exercise intervention for FEP, and pilot test it.
Two Cases of Montelukast-Associated Psychosis in Children
Jumaili WA, Gburi NA, Chaudhary N, Brown K and Jain S
An analysis of financial hardship faced by patients with First Episode Psychosis, and their families, in an Indian setting
Bhogal J, Singh SP, Chadda R, Sood M, Shah JL, Iyer SN, Madan J and
The economic burden of psychotic disorders is not well documented in LMICs like India, due to several bottlenecks present in Indian healthcare system like lack of adequate resources, low budget for mental health services and inequity in accessibility of treatment. Hence, a large proportion of health expenditure is paid out of pocket by the households.
Brain Age Gap in Early Illness Schizophrenia and the Clinical High-Risk Syndrome: Associations With Experiential Negative Symptoms and Conversion to Psychosis
Hua JPY, Abram SV, Loewy RL, Stuart B, Fryer SL, Vinogradov S and Mathalon DH
Brain development/aging is not uniform across individuals,spawning efforts to characterize brain age from a biological perspective to model the effects of disease and maladaptive life processes on the brain. The brain age gap represents the discrepancy between estimated brain biological age and chronological age (in this case, based on structural magnetic resonance imaging, MRI). Structural MRI studies report an increased brain age gap (biological age > chronological age) in schizophrenia, with a greater brain age gap related to greater negative symptom severity. Less is known regarding the nature of this gap early in schizophrenia (ESZ), if this gap represents a psychosis conversion biomarker in clinical high-risk (CHR-P) individuals, and how altered brain development and/or agingmap onto specific symptom facets.
Biomarkers of neurodegeneration in schizophrenia: systematic review and meta-analysis
Wilson JC, Liu KY, Jones K, Mahmood J, Arya U and Howard R
Does neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of dementia in people with schizophrenia compared with the general population. This may reflect a higher risk of developing neurodegenerative diseases such as vascular dementia or Alzheimer's disease (AD). Alternatively, this may reflect non-pathological, age-related cognitive decline in a population with low cognitive reserve.
Exploring intra-diagnosis heterogeneity and inter-diagnosis commonality in genetic architectures of bipolar disorders: association of polygenic risks of major psychiatric illnesses and lifetime phenotype dimensions
Baek JH, Lee D, Lee D, Jeong H, Cho EY, Ha TH, Ha K and Hong KS
Bipolar disorder (BD) shows heterogeneous illness presentation both cross-sectionally and longitudinally. This phenotypic heterogeneity might reflect underlying genetic heterogeneity. At the same time, overlapping characteristics between BD and other psychiatric illnesses are observed at clinical and biomarker levels, which implies a shared biological mechanism between them. Incorporating these two issues in a single study design, this study investigated whether phenotypically heterogeneous subtypes of BD have a distinct polygenic basis shared with other psychiatric illnesses.
The association of adverse childhood experiences with long-term outcomes of psychosis: a 21-year prospective cohort study after a first episode of psychosis
Peralta V, García de Jalón E, Moreno-Izco L, Peralta D, Janda L, Sánchez-Torres AM, Cuesta MJ and
Evidence suggests a possible relationship between exposure to childhood adversity (CA) and functional impairment in psychosis. However, the impact of CA on long-term outcomes of psychotic disorders remains poorly understood.
Enhancing Postpartum Psychosis Care With Qualitative Research: Current Findings and Future Directions
Kobylski LA, Le HN, Freeman MP, Cohen LS and Vanderkruik R
[Ethical Considerations of Including Minors in Clinical Trials Using the Example of the Indicated Prevention of Psychotic Disorders]
Schultze-Lutter F, Banaschewski T, Barth GM, Bechdolf A, Bender S, Flechtner HH, Hackler S, Heuer F, Hohmann S, Holzner L, Huss M, Koutsouleris N, Lipp M, Mandl S, Meisenzahl E, Munz M, Osman N, Peschl J, Reissner V, Renner T, Riedel A, Romanos M, Romer G, Schomerus G, Thiemann U, Uhlhaas PJ, Woopen C, Correll CU and Care-Konsortium D
As a vulnerable group, minors require special protection in studies. For this reason, researchers are often reluctant to initiate studies, and ethics committees are reluctant to authorize such studies. This often excludes minors from participating in clinical studies. This exclusion can lead to researchers and clinicians receiving only incomplete data or having to rely on adult-based findings in the treatment of minors. Using the example of the study "Computer-Assisted Risk Evaluation in the Early Detection of Psychotic Disorders" (CARE), which was conducted as an 'other clinical investigation' according to the Medical Device Regulation, we present a line of argumentation for the inclusion of minors which weighs the ethical principles of nonmaleficence (especially regarding possible stigmatization), beneficence, autonomy, and fairness. We show the necessity of including minors based on the development-specific differences in diagnostics and early intervention. Further, we present specific protective measures. This argumentation can also be transferred to other disorders with the onset in childhood and adolescence and thus help to avoid excluding minors from appropriate evidence-based care because of insufficient studies.
Unveiling the patterns: exploring social and clinical characteristics of frequent mental health visits to the emergency department-a comprehensive systematic review
Zhang Z and Das S
Frequent presenters (FPs) are a group of individuals who visit the hospital emergency department (ED) frequently for urgent care. Many among the group present with the main diagnosis of mental health conditions. This group of individual tend to use ED resources disproportionally and significantly affects overall healthcare outcomes. No previous reviews have examined the profiles of FPs with mental health conditions.
Volumetric mesoscopic electrophysiology: a new imaging modality for the non-human primate
Teichert T, Papp L, Vincze F, Burns N, Goodell B, Ahmed Z, Holmes A, Gray CM, Chamanzar M and Gurnsey K
The primate brain is a densely interconnected organ whose function is best understood by recording from the entire structure in parallel, rather than parts of it in sequence. However, available methods either have limited temporal resolution (functional magnetic resonance imaging), limited spatial resolution (macroscopic electroencephalography), or a limited field of view (microscopic electrophysiology). To address this need, we developed a volumetric, mesoscopic recording approach ( ) by tessellating the volume of a monkey hemisphere with 992 electrode contacts that were distributed across 62 chronically implanted multi-electrode shafts. We showcase the scientific promise of MePhys by describing the functional interactions of local field potentials between the more than 300,000 simultaneously recorded pairs of electrodes. We find that a subanesthetic dose of ketamine -believed to mimic certain aspects of psychosis- can create a pronounced state of functional disconnection and prevent the formation of stable large-scale intrinsic states. We conclude that MePhys provides a new and fundamentally distinct window into brain function whose unique profile of strengths and weaknesses complements existing approaches in synergistic ways.
Consanguineous marriage and associated diseases among their children and grandchildren in India: evidence from large-scale data
Kundu S and Jana A
Worldwide, more than 130 million infants are born each year and a considerable number of 13.5 million of these children have inbred parents. The present study aimed to investigate the association between parents' consanguinity and chronic illness among their children and grandchildren in India. The nationally representative data, Longitudinal Aging Study in India, 2017-2018, Wave 1 was used for the present study. Bivariate analysis, a probit model, and propensity score estimation were employed to conduct the study. The study observed the highest prevalence of consanguinity marriage in the state of Andhra Pradesh (28%) and the lowest in Kerala (5%) among the south Indian States. People who lived in rural areas, belonged to the richer wealth quintile and Hindu religion were the significant predictors of consanguinity marriage in India. For individuals who were in consanguineous marriages, there was 0.85%, 0.84%, 1.57% 0.43%, 0.34%, and 0.14% chances of their children and grandchildren developing psychotic disorders, heart disease, hypertension stroke, cancer, and diabetes, respectively. Moreover, around 4.55% of the individuals have a history of birth defects or congenital disorders. To address the risk of complicated illnesses due to the consanguinity of marriage, medical, genetic, and social counselling services are required.
Clinical presentation of first episode psychosis in people with and without HIV in KwaZulu-Natal, South Africa
Chhagan U, Ntlantsana V, Karim E, Thela L, Tomita A, Chiliza B and Paruk S
Mental disorders and HIV are the main contributors to the increase in years lived with disability rates per person in sub-Saharan Africa. A complex inter-relationship exists between HIV and mental illness, especially in a region with a high HIV prevalence. We examined the duration of untreated psychosis (DUP), and the nature of psychotic and cognitive symptoms in people with first episode psychosis (FEP) living with and without HIV.
Handling conflict situations in psychosis inpatient care: Nursing staff experiences of the Interactive Approach model
Arturén H, Zetherström J, Sjöström N, Abrams D and Johansson L
WHAT IS KNOWN ON THE SUBJECT?: In inpatient wards, there is a risk that conflicts occur when nursing staff interact with psychotic patients. The Interactive Approach (IA) model is an action-based model, used in psychiatric settings, to manage conflict situations. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: The IA model can be used to improve communication between nursing staff and patients in numerous critical situations. Using a structured risk scale to evaluate a conflict can be an effective way to guide action and sort out the different aspects of communication between nursing staff and psychotic patients. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: The clarity of an action-based model will help sort out which interventions are most likely to succeed in each conflict situation. The IA model highlights the importance of understanding and strengthening the patient's perspective, being flexible for each individual patient, and providing the patient with clear information about the situation. ABSTRACT: Introduction The Interactive Approach (IA) model is a structured management tool used to improve communication between caregivers and patients in psychiatric care settings. Aim/Question To examine the nursing staff's experiences of the IA model. How do they use the interventions in conflict situations with psychotic patients? Method A sample of nursing staff (n = 11) was recruited from three psychosis inpatient care units. Semi-structured questions covered staff experiences of working with the problem-solving interventions in the IA model. Transcribed data were analysed by qualitative content analysis. Results Three categories were defined: (1) 'To apply a flexible approach' describes how staff tried to adapt to each patient and situation; (2) 'Try to understand the person's inner world' describes the importance of active listening and exploring the patient's concerns; and (3) 'To communicate clearly' relates to experiences of clear communication and the setting up of boundaries. Discussion The risk scale and training in communication skills helped the interaction between staff and patients in conflict situations. Different interventions were used with a focus on maintaining patient alliance. Implications for Practice The findings highlight the importance of educational efforts and practical training, to prevent violence and the use of coercive measures.
Management of First-Episode Psychosis and Schizophrenia: Guidelines From the VA/DoD
Arnold MJ
Altered N-linked glycosylation in depression: A pre-clinical study
Yang Y, Li Y, Wang WD, He S, Yuan TF, Hu J and Peng DH
Neuroimmune plays an important role in major depressive disorders (MDD). N-linked protein glycosylation (NLG) might contribute to depression by regulating the neuroinflammatory response. As microglia is the main executor of neuroimmune function in the central neural system (CNS), targeting the process of N-linked protein glycosylation of microglia in the mice used for studying depression might potentially offer new avenues for the strategy for MDD.
G protein-specific mechanisms in the serotonin 5-HT receptor regulate psychosis-related effects and memory deficits
Kossatz E, Diez-Alarcia R, Gaitonde SA, Ramon-Duaso C, Stepniewski TM, Aranda-Garcia D, Muneta-Arrate I, Tepaz E, Saen-Oon S, Soliva R, Shahraki A, Moreira D, Brea J, Loza MI, de la Torre R, Kolb P, Bouvier M, Meana JJ, Robledo P and Selent J
G protein-coupled receptors (GPCRs) are sophisticated signaling machines able to simultaneously elicit multiple intracellular signaling pathways upon activation. Complete (in)activation of all pathways can be counterproductive for specific therapeutic applications. This is the case for the serotonin 2 A receptor (5-HTR), a prominent target for the treatment of schizophrenia. In this study, we elucidate the complex 5-HTR coupling signature in response to different signaling probes, and its physiological consequences by combining computational modeling, in vitro and in vivo experiments with human postmortem brain studies. We show how chemical modification of the endogenous agonist serotonin dramatically impacts the G protein coupling profile of the 5-HTR and the associated behavioral responses. Importantly, among these responses, we demonstrate that memory deficits are regulated by G protein activation, whereas psychosis-related behavior is modulated through G stimulation. These findings emphasize the complexity of GPCR pharmacology and physiology and open the path to designing improved therapeutics for the treatment of stchizophrenia.
Neuropsychological profiles in first-episodes psychosis and their relationship with clinical, metacognition and social cognition variables
Espinosa V, Bagaeva A, López-Carrilero R, Barajas A, Barrigón ML, Birulés I, Frígola-Capell E, Díaz-Cutraro L, González-Higueras F, Grasa E, Gutiérrez-Zotes A, Lorente-Rovira E, Pélaez T, Pousa E, Ruiz-Delgado I, Verdaguer-Rodríguez M, and Ochoa S
An increasing interest in the assessment of neuropsychological performance variability in people with first-episode psychosis (FEP) has emerged. However, its association with clinical and functional outcomes requires further study. Furthermore, FEP neuropsychological subgroups have not been characterized by clinical insight or metacognition and social cognition domains. The aim of this exploratory study was to identify specific groups of patients with FEP based on neuropsychological variables and to compare their sociodemographic, clinical, metacognition and social cognition profiles. A sample of 149 FEP was recruited from adult mental health services. Neuropsychological performance was assessed by a neuropsychological battery (WAIS-III; TMT; WSCT; Stroop Test; TAVEC). The assessment also included sociodemographic characteristics, clinical, functional, metacognition and social cognition variables. Two distinct neuropsychological profiles emerged: one neuropsychological impaired cluster (N = 56) and one relatively intact cluster (N = 93). Significant differences were found between both profiles in terms of sociodemographic characteristics (age and level of education) (p = 0.001), clinical symptoms (negative, positive, disorganized, excitement and anxiety) (p = 0.041-0.001), clinical insight (p = 0.038-0.017), global functioning (p = 0.014), as well as in social cognition domains (emotional processing and theory of mind) (p = 0.001; p = 0.002). No significant differences were found in metacognitive variables (cognitive insight and 'jumping to conclusions' bias). Relationship between neurocognitive impairment, social cognition and metacognition deficits are discussed. Early identifying of neuropsychological profiles in FEP, characterized by significant differences in clinical and social cognition variables, could provide insight into the prognosis and guide the implementation of tailored early-intervention.
The association between maximal muscle strength, disease severity and psychopharmacotherapy among young to middle-aged inpatients with affective disorders - a prospective pilot study
Ramming H, Theuerkauf L, Hoos O, Lichter K and Kittel-Schneider S
Motor alterations and lowered physical activity are common in affective disorders. Previous research has indicated a link between depressive symptoms and declining muscle strength primarily focusing on the elderly but not younger individuals. Thus, we aimed to evaluate the relationship between mood and muscle strength in a sample of N = 73 young to middle-aged hospitalized patients (18-49 years, mean age 30.7 years) diagnosed with major depressive, bipolar and schizoaffective disorder, with a focus on moderating effects of psychopharmacotherapy. The study was carried out as a prospective observational study at a German psychiatric university hospital between September 2021 and March 2022.
Polygenic risk of social isolation behavior and its influence on psychopathology and personality
Socrates AJ, Mullins N, Gur RC, Gur RE, Stahl E, O'Reilly PF, Reichenberg A, Jones H, Zammit S and Velthorst E
Social isolation has been linked to a range of psychiatric issues, but the behavioral component that drives it is not well understood. Here, a genome-wide associations study (GWAS) was carried out to identify genetic variants that contribute specifically to social isolation behavior (SIB) in up to 449,609 participants from the UK Biobank. 17 loci were identified at genome-wide significance, contributing to a 4% SNP-based heritability estimate. Using the SIB GWAS, polygenic risk scores (PRS) were derived in ALSPAC, an independent, developmental cohort, and used to test for association with self-reported friendship scores, comprising items related to friendship quality and quantity, at age 12 and 18 to determine whether genetic predisposition manifests during childhood development. At age 18, friendship scores were associated with the SIB PRS, demonstrating that the genetic factors can predict related social traits in late adolescence. Linkage disequilibrium (LD) score correlation using the SIB GWAS demonstrated genetic correlations with autism spectrum disorder (ASD), schizophrenia, major depressive disorder (MDD), educational attainment, extraversion, and loneliness. However, no evidence of causality was found using a conservative Mendelian randomization approach between SIB and any of the traits in either direction. Genomic Structural Equation Modeling (SEM) revealed a common factor contributing to SIB, neuroticism, loneliness, MDD, and ASD, weakly correlated with a second common factor that contributes to psychiatric and psychotic traits. Our results show that SIB contributes a small heritable component, which is associated genetically with other social traits such as friendship as well as psychiatric disorders.
Glutamatergic neurotransmission in schizophrenia: A systematic review and quantitative synthesis of proton magnetic resonance spectroscopy studies across schizophrenia spectrum disorders
Lopes JJ, Carruthers SP, Meyer D, Dean B and Rossell SL
Studies using proton magnetic resonance spectroscopy reveal substantial inconsistencies in the levels of brain glutamate, glutamine and glutamate + glutamine across schizophrenia spectrum disorders. This systematic review employs qualitative and quantitative methods to analyse the patterns and relationships between glutamatergic metabolites, schizophrenia spectrum disorders and brain regions.
An Dissection, and Analysis of Socio-Affective Symptoms related to Cerebellum-Midbrain Reward Circuitry in Humans
Hoffman LJ, Foley JM, Leong JK, Sullivan-Toole H, Elliott BL and Olson IR
Emerging research in non-human animals implicates cerebellar projections to the ventral tegmental area (VTA) in appetitive behaviors, but these circuits have not been characterized in humans. Here, we mapped cerebello-VTA white-matter connectivity in humans using probabilistic tractography on diffusion imaging data from the Human Connectome Project. We uncovered the topographical organization of these connections by separately tracking from parcels of cerebellar lobule VI, crus I/II, vermis, paravermis, and cerebrocerebellum. Results revealed that connections from the cerebellum to the VTA predominantly originate in the right hemisphere, interposed nucleus, and paravermal cortex, and terminate mostly ipsilaterally. Paravermal crus I sends the most connections to the VTA compared to other lobules. We discovered a medial-to-lateral gradient of connectivity, such that the medial cerebellum has the highest connectivity with the VTA. Individual differences in microstructure were associated with measures of negative affect and social functioning. By splitting the tracts into quarters, we found that the socio-affective effects were driven by the third quarter of the tract, corresponding to the point at which the fibers leave the deep nuclei. Taken together, we produced detailed maps of cerebello-VTA structural connectivity for the first time in humans and established their relevance for trait differences in socio-affective regulation.
Referral pathways to early intervention services for psychosis and their influence on perceptions of care: An interpretive phenomenological analysis
Senger B, MacDonald Q, Pencer A, Crocker CE, Hughes J and Tibbo PG
Most young adults experiencing psychosis enter early intervention services (EIS) via inpatient and emergency departments. These experiences are suggested to negatively impact their views of treatment and engagement in EIS. However, limited research has examined the impact of young adults' prior help-seeking experiences on these outcomes. The present study aimed to explore how young adults engaged in EIS have experienced initial help-seeking and make sense of these experiences in the context of their current treatment.
Schizophrenia and the bodily self
Gallese V, Ardizzi M and Ferroni F
Despite the historically consolidated psychopathological perspective, on the one hand, contemporary organicistic psychiatry often highlights abnormalities in neurotransmitter systems like dysregulation of dopamine transmission, neural circuitry, and genetic factors as key contributors to schizophrenia. Neuroscience, on the other, has so far almost entirely neglected the first-person experiential dimension of this syndrome, mainly focusing on high-order cognitive functions, such as executive function, working memory, theory of mind, and the like. An alternative view posits that schizophrenia is a self-disorder characterized by anomalous self-experience and awareness. This view may not only shed new light on the psychopathological features of psychosis but also inspire empirical research targeting the bodily and neurobiological changes underpinning this disorder. Cognitive neuroscience can today address classic topics of phenomenological psychopathology by adding a new level of description, finally enabling the correlation between the first-person experiential aspects of psychiatric diseases and their neurobiological roots. Recent empirical evidence on the neurobiological basis of a minimal notion of the self, the bodily self, is presented. The relationship between the body, its motor potentialities and the notion of minimal self is illustrated. Evidence on the neural mechanisms underpinning the bodily self, its plasticity, and the blurring of self-other distinction in schizophrenic patients is introduced and discussed. It is concluded that brain-body function anomalies of multisensory integration, differential processing of self- and other-related bodily information mediating self-experience, might be at the basis of the disruption of the self disorders characterizing schizophrenia.
Unraveling the Concept of Childhood Adversity in Psychosis Research: A Systematic Review
Sætren SS, Bjørnestad JR, Ottesen AA, Fisher HL, Olsen DAS, Hølland K and Hegelstad WTV
During the last decades, an abundance of studies has investigated childhood adversity in relation to psychosis. This systematic review critically examines the methodologies employed to investigate childhood adversity in psychosis over the past decade, including operational definitions, measurement tools and characteristics, and psychometric properties of instruments used in these studies.
Effects of antipsychotic medications in glucose and lipid metabolism at the fasted state in drug-naïve first episode patients with psychosis after six months and three years of treatment
Petrikis P, Tigas S, Tzallas AT, Ntritsos G, Sioka C, Georgiou G, Karampas A, Skapinakis P, Mantas C and Hyphantis T
Diabetes and dyslipidemia are common in patients with psychosis and may be related to adverse effects of antipsychotic medications. Metabolic disturbances in first-episode patients with psychosis are common, even prior to any antipsychotic treatment, and antipsychotic medications are implicated in the development of metabolic syndrome, at least in the long run. We therefore aimed to follow a group of drug-naïve, first-episode patients with psychosis at different time points (baseline, six months, and 36 months after the initiation of antipsychotic treatment) in order to evaluate the progression of metabolic abnormalities after antipsychotic therapy and the time-course of their onset. We assessed glucose and lipid metabolism during the fasted state in 54 drug-naïve patients with first-episode psychosis (FEP) before the initiation of any antipsychotic treatment and compared them with matched controls. The same parameters were assessed in the patient group (n=54) after six months of antipsychotic treatment and in a subgroup of patients (n=39) after three years of continuous and stable treatment in comparison to baseline. Measurements were obtained for fasting serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL), glucose, insulin, connecting peptide (C-peptide), homeostatic model assessment index (HOMA-IR), glycated hemoglobin (HbA1c) and body mass index (BMI). Insulin, C-peptide, triglyceride levels, and HOMA-IR index were significantly higher compared to controls. Total cholesterol, triglyceride levels and BMI, increased significantly in the patient group after six months of antipsychotic treatment. After three years of continuous antipsychotic treatment, we found statistically significant increases in fasting glucose, insulin, total cholesterol, triglyceride levels, HbA1c, HOMA-IR index, and BMI compared to baseline. In conclusion, FEP patients developed significant increases in BMI and serum lipid levels as soon as six months after antipsychotic treatment. These metabolic abnormalities persisted following 36 months of treatment and in addition, increases in fasting glucose, insulin, HbA1c and HOMA-IR were observed compared to baseline.
Erythrocyte membrane fatty acid concentrations and myelin integrity in young people at ultra-high risk of psychosis
Collins M, Bartholomeusz C, Mei C, Kerr M, Spark J, Wallis N, Polari A, Baird S, Buccilli K, Dempsey SA, Ferguson N, Formica M, Krcmar M, Quinn AL, Wannan C, Oldham S, Fornito A, Mebrahtu Y, Ruslins A, Street R, Loschiavo K, McGorry PD, Nelson B and Amminger GP
Decreased white matter (WM) integrity and disturbance in fatty acid composition have been reported in individuals at ultra-high risk of psychosis (UHR). The current study is the first to investigate both WM integrity and erythrocyte membrane polyunsaturated fatty acid (PUFA) levels as potential risk biomarkers for persistent UHR status, and global functioning in UHR individuals. Forty UHR individuals were analysed at baseline for erythrocyte membrane PUFA concentrates. Tract-based spatial statistics (TBSS) was used to analyse fractional anisotropy (FA) and diffusivity measures. Measures of global functioning and psychiatric symptoms were evaluated at baseline and at 12-months. Fatty acids and WM indices did not predict functional outcomes at baseline or 12-months. Significant differences were found in FA between UHR remitters and non-remitters (individuals who no longer met UHR criteria versus those who continued to meet criteria at 12-months). Docosahexaenoic acid (DHA) was found to be a significant predictor of UHR status at 12-months, as was the interaction between the sum of ώ-3 and whole brain FA, and the interaction between the right anterior limb of the internal capsule and the sum of ώ-3. The results confirm that certain fatty acids have a unique relationship with WM integrity in UHR individuals.
Air and Noise Pollution Exposure in Early Life and Mental Health From Adolescence to Young Adulthood
Newbury JB, Heron J, Kirkbride JB, Fisher HL, Bakolis I, Boyd A, Thomas R and Zammit S
Growing evidence associates air pollution exposure with various psychiatric disorders. However, the importance of early-life (eg, prenatal) air pollution exposure to mental health during youth is poorly understood, and few longitudinal studies have investigated the association of noise pollution with youth mental health.
A systematic review of users experiences of using digital interventions within psychosis: a thematic synthesis of qualitative research
Dennard S, Patel R, Garety P, Edwards C and Gumley A
Although the development of digital mental health support for people with psychosis has been increasing, the development and opportunities to access this have been more limited compared to other mental health conditions. Qualitative research exploring the experiences of using digital interventions amongst people with psychosis is even less well developed; however, such research is crucial in capturing the experiences of using digital interventions to ensure they are meeting the needs of people with psychosis. This paper aimed to synthesise qualitative data related to the experiences of people with psychosis who have used digital interventions.
Identification of youth at clinical high-risk for psychosis: A community-based study from India
Tikka SK, Malathesh BC, Spoorthy MS, Kusneniwar GN, Agarwal N, d'Avossa G and Katshu MZUH
A two-stage process, wherein self-report screening precedes the structured interview, is suggested for identifying individuals at clinical high-risk for psychosis (CHR-P) in community samples. Aim of this study was to screen a community youth sample from India for CHR-P using the two-stage method. Specific objectives were to assess concordant validity of the self-report measure and predictive validity of the two-stage method.
Neurobiology-based Cognitive Biotypes Using Multi-scale Intrinsic Connectivity Networks in Psychotic Disorders
Andrés-Camazón P, Diaz-Caneja CM, Ballem R, Chen J, Calhoun VD and Iraji A
Understanding the neurobiology of cognitive dysfunction in psychotic disorders remains elusive, as does developing effective interventions. Limited knowledge about the biological heterogeneity of cognitive dysfunction hinders progress. This study aimed to identify subgroups of patients with psychosis with distinct patterns of functional brain alterations related to cognition (cognitive biotypes).
High circulating MIF levels indicate the association with atypical antipsychotic-induced adverse metabolic effects
Chen X, Gao P, Qi Y, Li Z, Huang H, Shi Y, Wang L, Cui D and Qi D
Atypical antipsychotics (AAPs) are primary medications for schizophrenia (SZ). However, their use is frequently associated with the development of adverse metabolic effects, and the mechanisms behind these negative effects remain inadequately elucidated. To investigate the role of macrophage migration inhibitory factor (MIF) in regulating antipsychotic-induced metabolic abnormalities, between 2017 and 2020, a cross-sectional study was conducted, involving 142 healthy individuals and 388 SZ patients undergoing treatment with either typical antipsychotic (TAP) or AAP medications. Symptoms of SZ patients were evaluated using the Positive and Negative Syndrome Scale (PANSS), and measurements of metabolic indices and plasma MIF levels were performed on all individuals. A significant increase in plasma MIF levels was observed in groups receiving five major AAP monotherapies in comparison to healthy controls (all p < 0.0001). There was no such increase shown in the group receiving TAP treatment (p > 0.05). Elevated plasma MIF levels displayed a notable correlation with insulin resistance (β = 0.024, p = 0.020), as well as with the levels of triglycerides (β = 0.019, p = 0.001) and total cholesterol (β = 0.012, p = 0.038) in the groups receiving AAPs. However, while the TAP group also displayed certain metabolic dysfunction compared to healthy controls, no significant association was evident with plasma MIF levels (all p > 0.05). In conclusion, plasma MIF levels exhibit a distinctive correlation with metabolic abnormalities triggered by AAPs. Hence, there is potential for further development of MIF as a distinctive marker for monitoring adverse metabolic effects induced by AAPs in clinical settings.
First 150 years of catatonia: Looking back at its complicated history and forward to the road ahead
Csihi L, Ungvari GS, Caroff SN and Gazdag G
Karl Ludwig Kahlbaum (1828-1899) was the first to conceptualize and describe the main clinical features of a novel psychiatric illness, which he termed catatonia in his groundbreaking monograph published 150 years ago. Although Kahlbaum postulated catatonia as a separate disease entity characterized by psychomotor symptoms and a cyclical course, a close examination of his 26 cases reveals that most of them presented with motor symptom complexes or syndromes associated with various psychiatric and medical conditions. In his classification system, Kraepelin categorized catatonic motor symptoms that occur in combination with psychotic symptoms and typically have a poor prognosis within his dementia praecox (schizophrenia) disease entity. Because of the substantial influence of Kraepelin's classification, catatonia was predominantly perceived as a component of schizophrenia for most of the 20 century. However, with the advent of the psychopharmacotherapy era starting from the early 1950s, interest in catatonia in both clinical practice and research subsided until the early 2000s. The past two decades have witnessed a resurgence of interest in catatonia. The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition, marked a paradigmatic shift by acknowledging that catatonia can occur secondary to various psychiatric and medical conditions. The introduction of an independent diagnostic category termed "Catatonia Not Otherwise Specified" significantly stimulated research in this field. The authors briefly review the history and findings of recent catatonia research and highlight promising directions for future exploration.
Reduction of DUP in early intervention programmes: No pain… almost no gain
Frischherz M, Conus P and Golay P
Considering the negative impact of long duration of untreated psychosis (DUP) on outcome, its reduction has become one of the aims of early intervention programmes. The TIPP programme (Treatment and early Intervention in Psychosis Program) was implemented in 2004 in Lausanne and hoped to reduce DUP, without any specific campaign in this regard, through the provision of accessible and specialized treatment. The aim of this study was to evaluate the evolution of patients' DUP over time and the characteristics of patients with extreme DUP.
Bipolar Disorder Predisposition in a Greek Male With β-Thalassemia Trait: External Factors, Including COVID-19, and Other Clinical Implications
Tedesco S, Reyes K, Meiselman AI, Secondino JA and Tarnoverskyy N
The present case study examines an adult male of Greek descent diagnosed with the β-thalassemia trait during adulthood. The individual had psychiatric symptoms after the sudden cessation of anabolic steroid injections, which had been utilized improperly for nearly a decade. Furthermore, the administration of an increased dosage of bupropion in conjunction with the absence of treatment for manic symptoms may have contributed to worsening his illness. The individual's contraction of COVID-19 and the subsequent discontinuation of steroid medication resulted in a notable psychosis despite the absence of any prior psychiatric conditions. Following initial therapy and hospitalization, which resulted in a stable discharge, the patient experienced a relapse due to later alterations in his medication. Consequently, this relapse necessitated a second admission to the hospital. The patient's therapeutic regimen consisted of a concurrent administration of lithium, antipsychotics, and an intense program of psychiatric counseling. This particular example highlights the distinctive connection between β-thalassemia and bipolar disorder, focusing on a Greek patient with the β-thalassemia trait and a genetic predisposition to mood disorders. The present study provides a comprehensive narrative of the patient's clinical progression, with particular emphasis on the impact of the β-thalassemia trait on his mental health trajectory. This observation highlights the limited availability of data about the interplay between hemoglobinopathies and mood disorders, hence emphasizing the need for further research in this niche intersection of genetics and psychiatry.
First-episode psychiatric disorder risk from SARS-CoV-2 infection, a clinical analysis with Chinese psychiatric inpatients
Xie Y, Xu Z, Zhang Y, Li Y, Du P and Wang C
The extensive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout China in late 2022 has underscored the correlation between this virus and severe psychiatric disorders. Nevertheless, there remains a dearth of reported corresponding clinical and pathological features. Accordingly, we retrospectively reviewed the electronic medical records of psychiatric inpatients for seven days from early January 2023. Twenty-one inpatients who developed first-episode psychiatric disorders within two weeks after SARS-CoV-2 infection were recruited, while 24 uninfected the first-episode psychiatric inpatients were selected as controls. Comparative analyses of clinical manifestations, routine laboratory, and imaging examinations were performed. Our investigation revealed a 330% increase in first-episode psychiatric inpatients incidence after SARS-CoV-2 infection in 2023 compared to the preceding year without infections. Most cases exhibited psychiatric symptoms within a week of infection, resolving about two weeks with no residual symptoms after a three month. One-way ANOVA analysis between inpatients characterized by psychotic symptoms and hyperthermia was significant. Infected inpatients displayed elevated cytokine levels of interleukin-4, interleukin-8, and interferon-α, and decreased levels of eosinophils and basophils. These finding suggested that SARS-CoV-2 may contribute to the development of psychiatric disorders, likely mediated by the virus-induced inflammatory response and neuronal dysfunction in the context of psychological distress.
Rapidly Progressive Dementia Presenting as Schizophrenia Spectrum Disorder: A Diagnostic Dilemma
Gautam I and Aloney S
Rapidly progressive dementia (RPD) presenting initially as schizophrenia spectrum disorder poses significant diagnostic challenges. We present the case of a 55-year-old woman initially diagnosed with schizophrenia spectrum disorder due to symptoms including social withdrawal, disorganized behavior, and psychosis. However, the rapid progression of cognitive decline and motor dysfunction prompted further investigation, leading to the diagnosis of anti-N-methyl-d-aspartate (NMDA) receptor antibody-mediated encephalitis. Cerebrospinal fluid analysis revealed the presence of anti-NMDA receptor antibodies, guiding targeted immunomodulatory therapy with intravenous immunoglobulin and corticosteroids. This resulted in significant clinical improvement, highlighting the importance of comprehensive diagnostic evaluation and timely initiation of immunomodulatory therapy in autoimmune-mediated RPD. This case underscores the complexities of overlapping psychiatric and neurological conditions and emphasizes the need for a multidisciplinary approach to diagnosis and management.
Understanding the Impact of Adverse Childhood Experiences on Non-suicidal Self-Injury in Youth: A Systematic Review
Suhail Usmani S, Mehendale M, Yousif Shaikh M, Sudan S, Guntipalli P, Ouellette L, Sajid Malik A, Siddiqi N, Walia N, Shah K, Saeed F, De Berardis D and Shoib S
Non-suicidal self-injury (NSSI), defined as a deliberate destruction of one's own body without a suicidal intent, is a global public health issue. Adverse childhood events (ACEs) have been shown to be associated with various mental illnesses; however, to date the impact of such events on NSSI in youth has not been reviewed.
Validity and Reliability of the Premorbid Adjustment Scale in a Sample of Turkish Schizophrenic Patients
Altunsoy N, Kocabaş T, Bayad S, Elbir M and Aydemir Ö
The Premorbid Adjustment Scale (PAS) has gained a reputation as the foremost retrospective assessment tool, although little is known about its reliability and validity. The aim of the study is to examine the psychometric properties of the PAS in a sample of Turkish schizophrenic patients.
Auditory Cortex Thickness Is Associated With N100 Amplitude in Schizophrenia Spectrum Disorders
Slapø NB, Nerland S, Nordbø Jørgensen K, Mørch-Johnsen L, Pettersen JH, Roelfs D, Parker N, Valstad M, Pentz A, Timpe CMF, Richard G, Beck D, Werner MCF, Lagerberg TV, Melle I, Agartz I, Westlye LT, Steen NE, Andreassen OA, Moberget T, Elvsåshagen T and Jönsson EG
The auditory cortex (AC) may play a central role in the pathophysiology of schizophrenia and auditory hallucinations (AH). Previous schizophrenia studies report thinner AC and impaired AC function, as indicated by decreased N100 amplitude of the auditory evoked potential. However, whether these structural and functional alterations link to AH in schizophrenia remain poorly understood.
SARS-CoV-2 infection is associated with an increase in new diagnoses of schizophrenia spectrum and psychotic disorder: A study using the US national COVID cohort collaborative (N3C)
Rahman A, Russell M, Zheng W, Eckrich D, Ahmed I and
Amid the ongoing global repercussions of SARS-CoV-2, it is crucial to comprehend its potential long-term psychiatric effects. Several recent studies have suggested a link between COVID-19 and subsequent mental health disorders. Our investigation joins this exploration, concentrating on Schizophrenia Spectrum and Psychotic Disorders (SSPD). Different from other studies, we took acute respiratory distress syndrome (ARDS) and COVID-19 lab-negative cohorts as control groups to accurately gauge the impact of COVID-19 on SSPD. Data from 19,344,698 patients, sourced from the N3C Data Enclave platform, were methodically filtered to create propensity matched cohorts: ARDS (n = 222,337), COVID-19 positive (n = 219,264), and COVID-19 negative (n = 213,183). We systematically analyzed the hazard rate of new-onset SSPD across three distinct time intervals: 0-21 days, 22-90 days, and beyond 90 days post-infection. COVID-19 positive patients consistently exhibited a heightened hazard ratio (HR) across all intervals [0-21 days (HR: 4.6; CI: 3.7-5.7), 22-90 days (HR: 2.9; CI: 2.3 -3.8), beyond 90 days (HR: 1.7; CI: 1.5-1.)]. These are notably higher than both ARDS and COVID-19 lab-negative patients. Validations using various tests, including the Cochran Mantel Haenszel Test, Wald Test, and Log-rank Test confirmed these associations. Intriguingly, our data indicated that younger individuals face a heightened risk of SSPD after contracting COVID-19, a trend not observed in the ARDS and COVID-19 negative groups. These results, aligned with the known neurotropism of SARS-CoV-2 and earlier studies, accentuate the need for vigilant psychiatric assessment and support in the era of Long-COVID, especially among younger populations.
On the Road to Individualizing Pharmacotherapy for Adolescents and Adults with Schizophrenia - Results from an Expert Consensus Following the Delphi Method
Guinart D, Fagiolini A, Fusar-Poli P, Giordano GM, Leucht S, Moreno C and Correll CU
Schizophrenia is a severe mental illness that usually begins in late adolescence or early adulthood. Current pharmacological treatments, while acceptably effective for many patients, are rarely clinically tailored or individualized. The lack of sufficient etiopathological knowledge of the disease, together with overall comparable effect sizes for efficacy between available antipsychotics and the absence of clinically actionable biomarkers, has hindered the advance of individualized medicine in the treatment of schizophrenia. Nevertheless, some degree of stratification based on clinical markers could guide treatment choices and help clinicians move toward individualized psychiatry. To this end, a panel of experts met to formally discuss the current approach to individualized treatment in schizophrenia and to define how treatment individualization could help improve clinical outcomes.
Challenges and proposed solutions to conducting Alzheimer's disease psychosis trials
Ballard C, Tariot P, Soto-Martin M, Pathak S and Liu IY
Alzheimer's disease psychosis (ADP) produces a significant burden for patients and their care partners, but at present there are no approved treatments for ADP. The lack of approved treatments may be due to the challenges of conducting clinical trials for this disease. This perspective article discusses distinct challenges and proposed solutions of conducting ADP trials involving seven key areas: (1) methods to reduce the variable and sometimes high rates of placebo response that occur for treatments of neuropsychiatric symptoms; (2) the use of combined or updated criteria that provide a precise, consensus definition of ADP; (3) the use of eligibility criteria to help recruit individuals representative of the larger ADP population and overcome the difficulty of recruiting patients with moderate-to-severe ADP; (4) consideration of multiple perspectives and implementation of technology to reduce the variability in the administration and scoring of neuropsychiatric symptom assessments; (5) the use of clinically appropriate, defined severity thresholds and responder cutoffs; (6) the use of statistical approaches that address absolute effect sizes and a three-tier approach to address the fluctuation of neuropsychiatric symptoms; and (7) the implementation of feasible diagnostic and target-engagement biomarkers as they become available. The goal of these proposed solutions is to improve the evaluation of potential ADP therapies, within the context of randomized, placebo-controlled trials with clinically meaningful endpoints and sustained treatment responses.
Association between the frontoparietal network, clinical symptoms and treatment response in individuals with untreated anorexia nervosa
He Q, Zheng H, Zhang J, Yue L, Kang Q, Lian C, Guo L, Chen Y, Hu Y, Wang Y, Peng S, Wang Z, Liu Q and Chen J
Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN.
Efficacy of clozapine versus standard treatment in adult individuals with intellectual disability and treatment-resistant psychosis (CLOZAID): study protocol of a multicenter randomized clinical trial
Alemany-Navarro M, Sánchez-Barbero B, Reguera-Pozuelo P, Altea-Manzano L, Gómez-Garrido A, Rocha-González I, Garrido-Torres N, Ruiz-Veguilla M, García-Cerro S, Rosso-Fernández CM, Villagrán-Moreno JM, Sarramea F, Cervilla-Ballesteros J, Martínez-Leal R, Mayoral-Cleries F, and Crespo-Facorro B
Intellectual disability (ID) affects approximately 1% of the worldwide population and individuals with ID have a higher comorbidity with mental illness, and specifically psychotic disorders. Unfortunately, among individuals with ID, limited research has been conducted since ID individuals are usually excluded from mental illness epidemiological studies and clinical trials. Here we perform a clinical trial to investigate the effectiveness of clozapine in the treatment of resistant psychosis in individuals with ID. The article highlights the complexity of diagnosing and treating psychopathological alterations associated with ID and advocates for more rigorous research in this field.
Efficacy and safety of long-acting injectable oral antipsychotics in the treatment of patients with early-phase schizophrenia-spectrum disorders: a systematic review and meta-analysis
Vita G, Tavella A, Ostuzzi G, Tedeschi F, De Prisco M, Segarra R, Solmi M, Barbui C and Correll CU
Long-acting injectable antipsychotics (LAIs) have advantages over oral antipsychotics (OAPs) in preventing relapse and hospitalization in chronically ill patients with schizophrenia-spectrum disorders (SSDs), but evidence in patients with first-episode/recent-onset, that is, early-phase-SSDs is less clear.
Emotional tone in clinical high risk for psychosis: novel insights from a natural language analysis approach
Olson GM, Damme KSF, Cowan HR, Alliende LM and Mittal VA
Individuals at clinical high risk (CHR) for psychosis experience subtle emotional disturbances that are traditionally difficult to assess, but natural language processing (NLP) methods may provide novel insight into these symptoms. We predicted that CHR individuals would express more negative emotionality and less emotional language when compared to controls. We also examined associations with symptomatology.
Brief psychotic disorder related to areca nut use: a case report
Li S, Li Z, Chen J, Wang F, Ou Y, Huang Y and Li Z
Areca Nut (AN) is the fourth most commonly abused drug after nicotine, ethanol, and caffeine, due to its psychoactive properties provided by bioactive substances. Although previous studies have demonstrated AN's anxiolytic-like activity and potential benefits in ameliorating symptoms of depression and schizophrenia, there remains limited awareness regarding its association with brief psychotic disorder.
Widespread reductions in cortical thickness following ketamine abuse
Tang J, Wu Q, Qi C, Xie A, Liu J, Sun Y, Yuan T, Chen W, Liu T, Hao W, Shao X and Liao Y
Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine.
Prediction of aneurysmal subarachnoid hemorrhage in comparison with other stroke types using routine care data
Kanning JP, van Os HJA, Rakers M, Wermer MJH, Geerlings MI and Ruigrok YM
Aneurysmal subarachnoid hemorrhage (aSAH) can be prevented by early detection and treatment of intracranial aneurysms in high-risk individuals. We investigated whether individuals at high risk of aSAH in the general population can be identified by developing an aSAH prediction model with electronic health records (EHR) data. To assess the aSAH model's relative performance, we additionally developed prediction models for acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) and compared the discriminative performance of the models. We included individuals aged ≥35 years without history of stroke from a Dutch routine care database (years 2007-2020) and defined outcomes aSAH, AIS and ICH using International Classification of Diseases (ICD) codes. Potential predictors included sociodemographic data, diagnoses, medications, and blood measurements. We cross-validated a Cox proportional hazards model with an elastic net penalty on derivation cohorts and reported the c-statistic and 10-year calibration on validation cohorts. We examined 1,040,855 individuals (mean age 54.6 years, 50.9% women) for a total of 10,173,170 person-years (median 11 years). 17,465 stroke events occurred during follow-up: 723 aSAH, 14,659 AIS, and 2,083 ICH. The aSAH model's c-statistic was 0.61 (95%CI 0.57-0.65), which was lower than the c-statistic of the AIS (0.77, 95%CI 0.77-0.78) and ICH models (0.77, 95%CI 0.75-0.78). All models were well-calibrated. The aSAH model identified 19 predictors, of which the 10 strongest included age, female sex, population density, socioeconomic status, oral contraceptive use, gastroenterological complaints, obstructive airway medication, epilepsy, childbirth complications, and smoking. Discriminative performance of the aSAH prediction model was moderate, while it was good for the AIS and ICH models. We conclude that it is currently not feasible to accurately identify individuals at increased risk for aSAH using EHR data.
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Psychiatry AI RAISR 4D System Psychiatry + Mental Health