Neurobiology of COVID‐19‐Associated Psychosis/Schizophrenia: Implication of Epidermal Growth Factor Receptor Signaling

Neuropsychopharmacology Reports, Journal Year: 2025, Volume and Issue: 45(1)

Published: Jan. 4, 2025

ABSTRACT COVID‐19 exhibits not only respiratory symptoms but also neurological/psychiatric rarely including delirium/psychosis. Pathological studies on provide evidence that the cytokine storm, in particular (epidermal growth factor) EGF receptor (EGFR, ErbB1, Her1) activation, plays a central role progression of viral replication and lung fibrosis. Of note, SARS‐CoV‐2 virus (specifically, S1 spike domain) mimics directly transactivates EGFR, preceding inflammatory process. In agreement, anticancer drugs targeting EGFR such as Nimotuzumab tyrosine kinase inhibitors are markedly effective COVID‐19. However, these data might raise provisional caution regarding implication psychiatric disorder schizophrenia. The author's group has been investigating etiologic neuropathologic associations signaling with There significant molecular between schizophrenia ligand levels blood well brain. addition, perinatal challenges ligands intraventricular administration to rodents monkeys both resulted severe behavioral and/or electroencephalographic endophenotypes relevant this disorder. These animal models display postpubertal abnormality soliloquy‐like self‐vocalization intercortical functional connectivity. Here, we discuss neuropsychiatric coronavirus infection its interaction system, by searching related literatures PubMed database end 2023.

Language: Английский

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The role of infections and inflammation in schizophrenia: review of the evidence

Middle East Current Psychiatry, Journal Year: 2024, Volume and Issue: 31(1)

Published: Feb. 2, 2024

Abstract Background Schizophrenia is a severe mental illness affecting approximately 1% of the population worldwide. While its exact causes remain unknown, emerging evidence suggests that infections and inflammation may contribute to disease development in subset individuals. This review comprehensively summarizes linking infections, immune system dysfunction, schizophrenia risk. Main body Several population-based studies have linked serious prenatal or childhood requiring hospitalization increased risk later diagnosis, especially individuals with genetic predisposition. Both central nervous systemic appear confer Specific pathogens including Toxoplasma gondii , herpesviruses Chlamydophila more been implicated. Autoimmune diseases are also associated susceptibility, possibly due blood-brain barrier disruption allowing brain-reactive antibodies access. The recent Coronavirus 2019 (COVID-19) pandemic raises questions about SARS-CoV-2 as factor for new-onset psychosis. mechanisms underlying infection-schizophrenia link likely involve inflammation, cytokines, microglial activation, tryptophan/kynurenine pathway modulation. Treatments targeting showed some efficacy schizophrenia, further supporting an hypothesis. epidemiological mechanistic substantial, research needed conclusively determine dysfunction requires study. Conclusion abnormalities play role, perhaps by interacting environmental factors, instigating pathophysiology patients. More understand these connections clearly which aid future prevention personalized treatment approaches tailored specific subtypes.

Language: Английский

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Sense of agency and its disturbances: A systematic review targeting the intentional binding effect in neuropsychiatric disorders

Psychiatry and Clinical Neurosciences, Journal Year: 2023, Volume and Issue: 78(1), P. 3 - 18

Published: Sept. 26, 2023

Sense of agency (SoA) indicates a person's ability to perceive her/his own motor acts as actually being and, through them, exert control over the course external events. Disruptions in SoA may profoundly affect individual's functioning, observed several neuropsychiatric disorders. This is first article systematically review studies that investigated intentional binding (IB), quantitative proxy for measurement, neurological and psychiatric patients. Eligible were IB involving patients with and/or We included 15 692 individuals. Risk bias was low throughout studies. Abnormally increased action-outcome found schizophrenia Parkinson's disease taking dopaminergic medications or reporting impulsive-compulsive behaviors. A decreased effect Tourette's disorder functional movement disorders, whereas cortico-basal syndrome. The extent deviation from healthy values correlated severity symptoms Inconsistent effects autism spectrum anorexia nervosa, borderline personality disorder. Findings pave way treatments specifically targeting disorders where altered.

Language: Английский

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Exploring the relationship between dissociative experiences and recovery in psychosis: cross-sectional study

BJPsych Bulletin, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 10

Published: Jan. 27, 2025

Aims and method This study explored the association among dissociative experiences, recovery from psychosis a range of factors relevant to analysed whether experiences (compartmentalisation, detachment absorption) could be used predict specific stages recovery. A cross-sectional design was used, 75 individuals with were recruited services Gloucestershire Health Care NHS Foundation Trust. Five questionnaires – Dissociative Experiences Scale II (DES), Detachment Compartmentalisation Inventory (DCI), Questionnaire about Process Recovery, Stages Recovery Instrument (STORI), Positive Negative Syndrome proforma collect demographic data. Results Our findings indicated that compartmentalisation, absorption, as measured by DES DCI, do not STORI. Clinical implications The results this suggest there is no simple relationship between psychotic symptoms. They also need assess these symptoms separately in practice indicate special approaches treatment may needed cases where such have significant role.

Language: Английский

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Acute Schizophrenia-like Psychotic Disorder Against the Background of COVID-19

Medicina, Journal Year: 2025, Volume and Issue: 61(2), P. 298 - 298

Published: Feb. 8, 2025

Background and Objectives: Research in this area focuses on acute schizophrenia-like psychotic disorder, as more than half of cases progress to a chronic course, manifesting schizophrenia or schizoaffective disorder. has shown link between viral infection the onset psychosis, influence viruses clinical course disease is also being studied. Consequently, where type psychosis co-occurs with illness, there compelling rationale for identifying commonalities both treatment outcome. The ongoing global pandemic COVID-19 provides unique opportunity assess these changes. aim study twofold: first, examine characteristics disorder context pandemic, second, analyze therapeutic interventions outcomes. Materials Methods: A non-invasive observational was conducted which 310 patients admitted inpatients psychiatric hospital were divided into two groups according presence (group I—F23.2 COVID-19): 222 patients; Group II—F23.2 without COVID-19: 88 patients). After discharge, clinically followed outpatient 36 months. Results: results showed that associated characterized by greater severity productive symptoms inclusion theme symptoms. These given higher doses antipsychotic medication. Conclusions: outcome consistent, irrespective suffered at disease, predominant transition schizophrenic process.

Language: Английский

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Pharmacological Interventions for Negative Symptoms in Schizophrenia: A Systematic Review of Randomised Control Trials

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 540 - 540

Published: Feb. 21, 2025

Background/Objectives: While positive symptoms of schizophrenia are often satisfactorily controlled, negative difficult to treat, persisting despite treatment. Different strategies have been devised deal with this problem. We aimed review drug treatment for in controlled trials marketed drugs. Methods: searched the PubMed database and resulting records’ reference lists identify eligible using schizophrenia[ti] AND “negative symptom*”[ti] as a search strategy. determined eligibility through Delphi rounds among all authors. Results: On 11 February 2025, we identified 1485 records on 3 more from lists. Eligible were 95 records. Most studies double-blind, randomized trials, carried-out add-on patients stabilized antipsychotics. Other antipsychotics most frequent comparators, followed by antidepressants, recently, antioxidants gaining importance trials. Many especially those conducted Western world, found no significant effects compared placebo, while Iranian positive, although not strong effect size. Conclusions: Current research has contributed little progress schizophrenia. The reason might reside absence knowledge mechanisms whereby these generated, which prevents us designing possibly effective strategies, and/or chronicity symptoms, they first be established even when do become fully apparent.

Language: Английский

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Multi‐disciplinary collaborative consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post‐acute sequelae of SARS‐CoV‐2 infection (PASC)

PM&R, Journal Year: 2023, Volume and Issue: 15(12), P. 1588 - 1604

Published: Nov. 8, 2023

Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC), also called Long COVID (coronavirus disease), is the experience new or worsened signs, symptoms, conditions that develop after resolution phase a COVID-19 infection. Although some people with recover well, others have persisting symptoms.1 PASC can manifest as wide-ranging constellation disabling sequelae, including mental health conditions.2 Anxiety and depression been reported second third most common symptoms PASC, respectively.3 Furthermore, in narrative review summarizing neuropsychiatric dimensions anxiety, post-traumatic stress disorder (PTSD), were among both ongoing symptomatic PASC. Pooled prevalence each was: anxiety 19.1% (95% confidence interval [CI], 13.3%–26.8%), PTSD 15.7% CI, 9.9%–24.1%), 12.9% 7.5%–21.5%).4 Despite high often impact PASC-related emerging data persist for months years,5 limited guidance currently exists regarding assessment treatment patients Addressing setting involves several unique complexities, addressing stigma may interfere appropriate diagnosis(es) treatment, insufficient availability professionals, differentiating physical diagnoses. Many described being questioned about their way feels dismissive and/or mistakenly attributed to an underlying condition.6 effects pandemic on individuals society exacerbate direct from SARS-CoV-2 infection, increasingly evidence supports be component caused by SARS- CoV-2 pre-existing exacerbated yet are not, themselves, overall cause PASC.7-9 Another challenge disorders national global shortage professionals.10 This further intensified because clinicians who not specialists express discomfort perception training discuss patients. Nevertheless, report they want broach topic acknowledge interplay between health.11-13 Finally, studies found due condition, but mimic disorder. These include fatigue, dysautonomia, disordered sleep, cognitive dysfunction,14, 15 which patient's ability fully participate first-line recommendations. The goal this consensus statement present practical treat Specifically, addresses initial depression, (including panic), PTSD. People worsening suicidal ideation, psychosis, obsessive compulsive (OCD), pandemic-related grief survivor's remorse8, 16-18; however, specific focus these outside scope statement. recommendations applicable all experiencing regardless time course. Of note, reflects current base related expert panel care professionals regularly should preclude clinical judgment must applied context patient, adjustments patient preferences, comorbidities, other factors. American Academy Physical Medicine Rehabilitation (AAPM&R) Multi-Disciplinary Collaborative (PASC Collaborative) was convened address pressing need members experts across variety disciplines specialties PM&R, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, primary care. following iterative, modified Delphi process achieve presented series statements symptoms. A full description methodology has published previously.19 informed established centers managing range symptoms.20-26 Whenever possible, existing specifically incorporated into statement, body somewhat evolving. As needed, guided applying general, well-established, approaches considerations intentional equity disparities critical factor contributing widespread outcomes, considered addressed. Collaborative's broaden understanding practices, only guide management, identify gaps opportunities future research. According original definition U.S. Centers Disease Control Prevention (CDC), "Long (PASC) broadly defined continue 4 weeks more infection; multisystemic; relapsing–remitting pattern progression over time, possibility life-threatening events even years CDC uses 4-week timeframe describing post-COVID emphasize importance evaluation supportive during 12 COVID-19.27 Based feedback our process, we advocate improving access beneficial interventions facilitating early evaluation, diagnosis, management experienced For purposes recommend if within 1 month symptom onset. Emotional mood fluctuations part normal everyday life, persistent, distressing disturbances emotional regulation, behavior, cognition indicative Diagnostic Statistical Manual Mental Disorders, Fifth Edition (DSM-5) depressive characterized primarily persistent sadness, emptiness, irritability, loss pleasure interest activities (anhedonia). They associated secondary poor concentration, psychomotor agitation retardation, fatigue energy, sleep difficulty (insomnia hypersomnia), feelings low self-worth excessive guilt, hopelessness future, changes appetite weight, thoughts dying suicide. fear, worry, apprehension, dread out proportion perceived threat. intrusive memories, dreams, dissociative reactions (flashbacks), prolonged psychological distress, physiological occur exposure actual threatened traumatic event.28 resulted 28% increase cases major (MDD) 26% worldwide 2020.29, 30 It estimated 137 additional disability-adjusted life (DALYs) per 100,000 MDD 116 DALYs disorders, incidence higher than influenza infections.15, 31, 32 Both women underrepresented race ethnic minority groups type(s) sequelae.33, 34 Women autoimmune diseases men, risk factors developing PASC35 conditions. at increased women, older adults, potentially Black/African socioeconomic strata.36, 37 In addition effect health, cumulative burden chronic (allostatic load) grown stressors concerns such fear death, short- long-term financial uncertainty, quarantine-associated social isolation, familial stress, guilt.38 surrounding disruptions system diminished services, frequent dismissal patients' community, particularly those without formal laboratory infection.39 Moreover, worse outcomes illness, hospitalization, PASC.39-44 pathophysiology still under investigation, it surmised cytokine storm created virus affect initiating central inflammatory response, reducing serotonin production attenuates downstream monoamine neurotransmission, increasing brain glutamate upregulation N-methyl-d-aspartate (NMDA) receptors.7, 8 aggregate, produce damaging neuronal excitotoxicity subsequent synaptic pruning loss. compounded cytokine-mediated reduction trophic induction new-onset re-exacerbation conditions.8, 9 role cytokines similar pro-inflammatory That is, appropriately generated response peripheral when cross brain, normal, evolutionarily conserved, protective illness allowing cope fever, lethargy, malaise.45 However, activation immune sustained beyond duration (e.g., disease, systemic cancer, PASC), resulting signaling lead exacerbation development vulnerable individuals.46 addition, biologic directly viral reservoirs, microvascular blood clots endothelial dysfunction, altered gut microbiome, autoimmunity.47-50 encountering stigmatization, disbelief, assumptions whole state,51 despite contrary.50 led fractured relationships patients, inherently degree able offer We encourage model approach based best practices myalgic encephalomyelitis/chronic (ME/CFS). take supportive, open, nonjudgmental stance; consider multifaceted biological aspects complex medical health–related treatments truly requires types interventions.52 especially challenging underreport clinician will attribute health. phenomenon contribute trend likely receiving significantly below-optimal level care.53 Therefore, helpful reassure let them know although one well-documented manifestations potential severe.53 Intentional effective challenging. Some delay accurate diagnosis dismissed purely psychosomatic manifestations.6 light context, suggest introduce validating PASC.50 by, mimic, worsen, coexisting why essential.2, 54 example, generalized post-exertional malaise another, result impairments function.55 developed fatigue.20, 22 Clinicians great driver(s) functional impairment treatment. When thorough facilitated collateral information close friends family members. Collateral history impaired memory, awareness how functioning long function impaired, otherwise would independently reporting sleep-related snoring, dozing off daytime, nighttime awakenings, etc.).22, 26 Loved ones important course severity observed mood, coping abilities, energy level, appetite, daily function, participation usual (Table 1). Patients screened signs using validated tools instruments, appropriate. Note: suicide screening screen positive plan place prior screening. questionnaires efficient implements questionnaires, understand whether questionnaire assesses somatic instance, Patient Health Questionnaire (PHQ-9) concentrating, disorders.56 autonomic dysfunction,20-26 so PHQ-9 overpredict presence multiple PASC.57 contrast, Patient-Reported Outcomes Measurement Information System (PROMIS) Depression scale does inquire reduce confounding comorbidities (such PASC) health.58 Other measures used PHQ-2 (for screening), Generalized Disorder 7 (GAD-7) Hospital Scale (HADS) screening). Regardless tool(s) used, follow-up interview clarify settings versus select school/work, home, contexts), plans. Common PCL-5 (PTSD Checklist DSM-5) IES (Impact Events Scale). confirmation require referral specialist extensive testing. Suspicion raised survivors intensive unit (ICU),59 had confirmed frontline workers, quarantined. flashback-like reactions; efforts avoid trauma-related thoughts, feelings, places, people; negative mood; hyperarousal, difficulties, irritability.60-63 delivering tool responses. given encounter before any provided, answering questions thoughtfully honestly when: (1) team member describes relevance purpose introduced them, (2) acknowledges responses explains results recommendations.11 assessing ideation depressed lack familiarity immediate next steps expresses active ideation. Psychological Association provides continuing education intervening (https://www.apa.org/monitor/2022/06/continuing-education-intervene-suicide), Columbia University, through Lighthouse Project, disseminates Protocol—also known Columbia-Suicide Severity Rating (C-SSRS) https://cssrs.columbia.edu/. establish what endorse consultation in-clinic worker psychologist interdisciplinary setting, contacting crisis worker, hotline (988 National Alliance Illness [NAMI] hotline), center detailed inquiry necessary intervention maintain safety patient. If left unsupervised. assure acknowledging distress providing care, transfer hospital emergency department psychiatric hospital. Urgent equally situations managed equal immediacy. selecting tools, administration approaches, informants, essential chronological/mental age, educational history, environments. reading (in language administered), read aloud rather self-administered. cases, sensitive acceptability bias tool. manage neurodevelopmental judicious measurements informants. Assessment sensorimotor proxy inventories focused largely behaviors subjective experiences, informants characterize onset, changes). extent possible comprehension self caregiver, teacher, etc.) assessments diagnostic evaluation. Literature intellectual disabilities suggested mixed agreement self- caregiver-report health-related factors, better correlation activity engagement, support.64 identity race, ethnicity sexual orientation gender identity, make conscious effort own implicit (unconscious) biases. aware cultural differences exist expressed certain cultures hesitant concern acceptability.65 appropriate, tests reviewed obtained evaluate masquerade tachycardia palpitations cardiovascular dysfunction.23, 24 having condition presents as, contributes to, conditions, lower strata.66 There considerable overlap neurologic commonly Commonly overlapping pain, apathy, changes, changes. Major categories disease neurodegenerative Parkinson Huntington's Alzheimer's vascular inflammatory/infectious/autoimmune trauma, metabolic/endocrine disturbances, nutritional deficiencies, structural disorders. Post-intensive (PICS) coexist movement PICS PASC.67 Factors (or coexisting) opposed isolated include: features atypical disorder, unusual age paroxysmal recent substance abuse/intoxication leading encephalopathy, prescription medicine overuse, resistant respond unusually conventional treatment.66 DSM-5 considers careful assess Because wellness bidirectionally person's engage tasks, vice versa. explore baseline self-care instrumental living bathing, dressing, grooming, ambulating use adaptive equipment, cooking, cleaning, shopping, attending household chores, paying needs/bills). limit attend work, school, social, activities, limitations can, turn, coping, satisfaction life.68 Decreased engagement added strain, feeling feel pressured worsens malaise. Understanding patient-specific prerequisite patient-centered interrelated impairments, skills, premorbid triggers Reported include, foods, menstrual cycles,69 conditions,70 prescribed over-the-counter medications, alcohol drug misuse,71 psychosocial uninsured underinsured, unemployed underemployed, socially isolated, support assist transportation, translation, needs), personal safety, food insecurity, stable housing.72-74 prevalent PASC.72,73 itself, as: distancing, childcare, media coverage infection.75 varies widely Symptoms COVID-19.76, 77 Available suggests general principles treating generally mirror do (see Table 2).78, 79 Patients' constellations, impairment, quality impacted approach. impacting life/function practice clinician, (examples therapist, counselor, neuropsychologist, psychologist, psychiatrist) expertise psychological/psychiatric (and worsen) note provided recognizes typically cluster systems, might co-existing always suggesting test rehabilitation. plan, encouraged unknowns prognosis, well benefits risks screens aforementioned interview, adequate comfort psychopharmacologic provide in-office means offering intervention. referrals psychiatrist,

Language: Английский

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COVID-19-Associated Acute Psychotic Disorder—Longitudinal Case Report and Brief Review of Literature

Medicina, Journal Year: 2023, Volume and Issue: 59(2), P. 408 - 408

Published: Feb. 19, 2023

Even though since the beginning of COVID-19 pandemic, literature became more and abundant on data hypotheses about various consequences people’s lives, clarity needs to be added existing information. Besides stressful experiences related SARS-CoV-2 infection has been proven impact brain functioning through direct indirect pathogenic mechanisms. In this context, we report a case patient presenting with first episode psychosis following COVID-19. our case, 28-year-old male no personal or family psychiatric history developed psychotic symptoms (delusions, hallucinations, disorganized behaviour) that required antipsychotic treatment inpatient hospitalization one week after he was discharged from hospital At six-month one-year follow-up, in remission without any signs symptoms. A brief review is also provided. The presented article outlines possibility post-COVD-19 recovery period might crucial time for onset acute disorder, therefore, routine assessments should carried out during all phases disease. clearer picture pandemic mental health will most likely revealed future as many need long-term evaluation.

Language: Английский

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Increase in presentations with new-onset psychiatric disorders in a psychiatric emergency department in Berlin, Germany during the second wave of the COVID-19 pandemic – a retrospective cross-sectional study

Frontiers in Psychiatry, Journal Year: 2023, Volume and Issue: 14

Published: Oct. 12, 2023

While numerous studies have identified an increase in symptoms of depression as well anxiety and distress due to the COVID-19 pandemic, relatively few investigated new-onset psychiatric diseases during pandemic.

Language: Английский

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The effect of SARS-CoV-2 virus on resting-state functional connectivity during adolescence: Investigating brain correlates of psychotic-like experiences and SARS-CoV-2 related inflammation response

Psychiatry Research Neuroimaging, Journal Year: 2023, Volume and Issue: 336, P. 111746 - 111746

Published: Nov. 5, 2023

Language: Английский

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