Search Results (594)

Background/Objectives: Cognitive impairment in older adults has emerged as a growing public health concern, particularly in relation to COVID-19 infection and its associated neuropsychiatric symptoms. The identification of modifiable risk factors may contribute to the development of targeted preventive strategies. This study aimed to assess predictors of cognitive impairment in older adults with and without recent SARS-CoV-2 infection. Methods: A prospective cohort study was conducted from June 2023 to March 2024 at a tertiary hospital in western Mexico. Adults aged 65 years or older with confirmed SARS-CoV-2 infection within the previous six months, along with uninfected controls, were enrolled. Cognitive function (Mini-Mental State Examination), depression (PHQ-9), anxiety (Geriatric Anxiety Inventory), insomnia (Insomnia Severity Index), functional status (Katz Index and Lawton–Brody Scale), and laboratory markers were evaluated at baseline, three months, and six months. The primary outcome was cognitive impairment at six months. Independent predictors were identified using a multivariable generalized linear mixed-effects model. Results: Among the 111 participants, 20 (18.8%) developed cognitive impairment within six months. Low serum magnesium (adjusted risk ratio [aRR] 2.73; 95% CI 1.04–7.17; p = 0.041) and depression (aRR 5.57; 95% CI 1.88–16.48; p = 0.002) were independently associated with a higher risk. A significant synergistic among COVID-19, depression, and hypomagnesemia was observed (RR 44.30; 95% CI 9.52–206.21; p < 0.001), corresponding to the group with simultaneous presence of all three factors compared to the group with none. Conclusions: Depression and hypomagnesemia appear to be independent predictors of cognitive impairment in older adults with recent COVID-19 infection. These findings suggest potential targets for prevention and support the implementation of routine neuropsychiatric and biochemical assessments in this population. Full article

Schizophrenia (SZ) is a complex neuropsychiatric disorder characterized by heterogeneous symptoms, relatively poor clinical outcome, and widespread disruptions in neural connectivity and oscillatory dynamics. This article attempts to review current evidence linking genomic and proteomic alterations with aberrant neural oscillations observed in SZ, including aberrations in all oscillatory frequency bands obtained via human EEG. The numerous genes discussed are mainly involved in modulating synaptic transmission, synaptic function, interneuron excitability, and excitation/inhibition balance, thereby influencing the generation and synchronization of neural oscillations at specific frequency bands (e.g., gamma frequency band) critical for different cognitive, emotional, and perceptual processes in humans. The review highlights how polygenic influences and gene–circuit interactions underlie the neural oscillatory and connectivity abnormalities central to SZ pathophysiology, providing a framework for future research on common genetic-neural function interactions and on potential therapeutic interventions targeting local and global network-level neural dysfunction in SZ patients. As will be discussed, many of these genes affecting neural oscillations in SZ also affect other neurological disorders, ranging from autism to epilepsy. In time, it is hoped that future research will show why the same genetic anomaly leads to one illness in one person and to another illness in a different person. Full article

(1) Insulin-like growth factor-1 (IGF-1) is a neurotrophin with anti-inflammatory properties. Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer’s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with IGF-1 in a rat model of streptozotocin (STZ)-induced neuroinflammation can prevent the emergence of anhedonia and anxiety-like behavior by impacting the peripheral inflammatory responses. (2) Male Wistar rats were subjected to double ICVSTZ (total dose: 3 mg/kg) and ICVIGF-1 injections (total dose: 2 µg). We analyzed the level of anhedonia (sucrose preference), anxiety (elevated plus maze), peripheral inflammation (hematological and cytometric measurement of leukocyte populations, interleukin (IL)-6), and corticosterone concentration at 7 (very early stage, VES), 45 (early stage, ES), and 90 days after STZ injections (late stage, LS). (3) We found that ICVIGF-1 administration reduces behavioral symptoms: anhedonia (ES and LS) and anxiety (VES, ES), and peripheral inflammation: number of leukocytes, lymphocytes, T lymphocytes, monocytes, granulocytes, IL-6, and corticosterone concentration (LS) in the rat model of sAD. (4) The obtained results demonstrate beneficial effects of central IGF-1 administration on neuropsychiatric symptoms and peripheral immune system activation during disease progression in the rat model of sAD. Full article

Background/Objectives: Traumatic brain injury is one of the leading causes of death and disability. When traumatic brain injury is repeated over time, it can lead to the development of Chronic Traumatic Encephalopathy, a chronic neurodegenerative disease commonly observed in individuals who engage in contact sports or military personnel involved in activities with a high risk of repeated head trauma. At autopsy, the examination of the brain reveals regional atrophy, corresponding to high concentrations of glutamate receptors. Microscopically, the primary findings are the deposition of neurofibrillary tangles and neuropil threads. The aim of this study is to highlight the clinical and histopathological characteristics of Chronic Traumatic Encephalopathy, providing diagnostic support to forensic pathologists. Additionally, it seeks to aid in the differential diagnosis of similar conditions. Methods: A review of literature was conducted following the PRISMA criteria. Of 274 articles, 7 were selected. Results: According to these papers, most patients were male and exhibited neurological symptoms and neuropsychiatric impairments, and a proportion of them committed suicide or had aggressive behavior. Conclusions: Chronic Traumatic Encephalopathy remains largely underdiagnosed during life. The definitive diagnosis of Chronic Traumatic Encephalopathy is established post-mortem through the identification of pathognomonic tauopathy lesions. Early and accurate antemortem recognition, particularly in at-risk individuals, is highly valuable for its differentiation from other neurodegenerative conditions, thereby enabling appropriate clinical management and potential interventions. Full article

Background/Objectives: The objective of this study was to validate a new parent-reported scale for tracking Pediatric Acute-onset Neuropsychiatric Syndrome (PANS). PANS is a condition characterized by a sudden and severe onset of neuropsychiatric symptoms. To meet diagnostic criteria, an individual must present with either obsessive–compulsive disorder (OCD) or severely restricted food intake, accompanied by at least two additional cognitive, behavioral, or emotional symptoms. These may include anxiety, emotional instability, depression, irritability, aggression, oppositional behaviors, developmental or behavioral regression, a decline in academic skills such as handwriting or math, sensory abnormalities, frequent urination, and enuresis. The onset of symptoms is usually triggered by an infection or an abnormal immune/inflammatory response. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is a subtype of PANS specifically linked to strep infections. Methods: We developed a 101-item PANS/PANDAS and Related Inflammatory Brain Disorders Treatment Evaluation Checklist (PTEC) designed to assess changes to a patient’s symptoms over time along 10 subscales: Behavior/Mood, OCD, Anxiety, Food intake, Tics, Cognitive/Developmental, Sensory, Other, Sleep, and Health. The psychometric quality of PTEC was tested with 225 participants. Results: The internal reliability of the PTEC was excellent (Cronbach’s alpha = 0.96). PTEC exhibited adequate test–retest reliability (r = 0.6) and excellent construct validity, supported by a strong correlation with the Health subscale of the Autism Treatment Evaluation Checklist (r = 0.8). Conclusions: We hope that PTEC will assist parents and clinicians in the monitoring and treatment of PANS. The PTEC questionnaire is freely available at neuroimmune.org/PTEC. Full article

Sleep paralysis (SP), an REM parasomnia, can be characterized as one of the symptoms of narcolepsy. The SP phenomenon involves regaining meta-consciousness by the dreamer during REM, when the physiological atonia of skeletal muscles is accompanied by visual and auditory hallucinations that are perceived as vivid and distressing nightmares. Sensory impressions include personification of an unknown presence, strong chest pressure sensation, and intense fear resulting from subjective interaction with the unfolding nightmare. While the mechanism underlying skeletal muscle atonia is known, the physiology of hallucinations remains unclear. Their complex etiology involves interactions among various membrane receptor systems and neurotransmitters, which leads to altered neuronal functionality and disruptions in sensory perception. According to current knowledge, serotonergic activation of 5-hydroxytryptamine-receptor-2A (5-HT2A)-associated pathways plays a critical role in promoting hallucinogenesis during SP. Furthermore, they share similarities with psychedelic-substance-induced ones (i.e., LSD, psilocybin, and 2,5-dimethoxy-4-iodoamphetamine). These compounds also target the 5-HT2A receptor; however, their molecular mechanism varies from serotonin-induced ones. The current review discusses the intracellular signaling pathways responsible for promoting hallucinations in SP, highlighting the critical role of β-arrestin-2. We propose that the β-arrestin-2 signaling pathway does not directly induce hallucinations but creates a state of network susceptibility that facilitates their abrupt emergence in sensory areas. Understanding the molecular basis of serotonergic hallucinations and gaining better insight into 5-HT2A-receptor-dependent pathways may prove crucial in the treatment of multifactorial neuropsychiatric disorders associated with the dysfunctional activity of serotonin receptors. Full article

Serotoninomics is an expanding field that focuses on the comprehensive study of the serotoninergic system, including serotonin’s biosynthesis, metabolism, and regulation, as well as related scientific methodologies 5-hydroxytryptamine (5-HT). This field explores serotonin’s complex roles in various physiological and pathological contexts. The essential amino acid tryptophan (Trp) is a precursor for several metabolic and catabolic pathways, with the kynurenine (KYN) pathway being particularly significant, representing about 95% of Trp metabolism. In contrast, only a small portion (1–2%) of dietary Trp enters the serotonin pathway. Anthranilic acid (AA), a metabolite in the KYN pathway, has emerged as a potential biomarker and therapeutic target for schizophrenia. Elevated serum AA levels in patients with schizophrenia have been associated with neurotoxic effects and disruptions in neurotransmission, suggesting AA’s critical role in the disorder’s pathophysiology. Furthermore, the 5-HT_2A receptor’s involvement is particularly noteworthy, especially in relation to schizophrenia’s positive symptoms. Recent findings indicate that 5-HT_2A receptor hyperactivity is linked to positive symptoms of schizophrenia, such as hallucinations and delusions. This study investigates serotoninomics’ implications for neuropsychiatric disorders, focusing on AA in schizophrenia and analysing recent research on serotonin signalling pathways and AA’s neurochemical effects. Understanding the roles of the 5-HT_2A receptor and AA in neuropsychiatric disorders could lead to the development of more precise and less invasive diagnostic tools, specific therapeutic strategies, and improved clinical outcomes. Ongoing research is essential to uncover these pathways’ exact mechanisms and therapeutic potential, thereby advancing personalised medicine and innovative treatments in neuropsychiatry. Full article

Tobacco use disorder remains a leading cause of preventable mortality, with nicotine playing a central role in the development and maintenance of dependence, mainly through its action on α4β2 nicotinic acetylcholine receptors (nAChRs). Smoking cessation treatments must address both physiological withdrawal and the affective disturbances (such as anxiety, irritability, and mood lability) which often facilitate relapses. This review compares two pharmacotherapies used in smoking cessation, varenicline and cytisinicline (cytisine), with particular focus on their impact on emotional regulation, psychological symptoms, and neuropsychiatric safety. Varenicline, a high-affinity partial agonist at α4β2 nAChRs, has demonstrated superior efficacy in maintaining abstinence and is well-supported by robust clinical data, including in psychiatric populations. However, its use may be limited by adverse effects such as nausea and sleep disorders. Cytisinicline, a structurally similar but less potent partial agonist, has recently gained renewed interest due to its lower cost, favorable tolerability profile, and comparable effectiveness in the general population. Although less extensively studied in patients with serious mental illness, preliminary data suggest cytisinicline may offer a better side effect profile, particularly regarding sleep disturbances and emotional reactivity. Both agents appear to ameliorate withdrawal-related affective symptoms without significantly increasing psychiatric risk. Ultimately, pharmacotherapy choice should be guided by individual clinical features, mental health status, treatment tolerability, and resource availability. Further research is needed to establish cytisinicline’s efficacy and safety across diverse clinical contexts, particularly among individuals with severe psychiatric comorbidities. Full article

The protozoan parasite Toxoplasma gondii (T. gondii) has been implicated in various neuropsychiatric disorders, including depression. Our aim in this study was to assess the seroprevalence of T. gondii IgG antibodies as well as potential risk factors associated with seropositivity in patients with depression compared to healthy blood donors. This seroepidemiological study included 230 participants from Western Romania, divided equally into two groups: 115 patients diagnosed with depressive disorders which represented the study group and 115 age and gender-matched healthy blood donors, representing the control group. A structured questionnaire was used to assess risk factors potentially linked to T. gondii infection. The T. gondii IgG antibodies overall seroprevalence was significantly higher in the depression group (70.43%) compared to the control group (45.22%) (OR = 2.89; 95% CI: 1.68–4.97; p < 0.001). Higher seropositivity was noted in patients aged 50–59, 60+ years and in females. Patients with lower educational attainment showed significantly increased odds of T. gondii seropositivity (72.29% vs. 44.3%, OR = 3.28; 95% CI: 1.71–6.31; p < 0.001) compared with the control group. Stratification by ICD-10 diagnostic subtypes revealed significantly higher seropositivity in all categories, with the strongest association in patients with recurrent severe depressive episodes without psychotic symptoms (F33.2) (81.25%, OR = 3.5; 95% CI: 1.51–8.13; p = 0.004). These findings suggest a possible link between T. gondii infection and depression, particularly in relation to disease severity and sociodemographic factors. To our knowledge, this is the first study to investigate T. gondii seroprevalence and associated risk factors in Romanian patients with depression, providing a foundation for future longitudinal and preventive research. Full article

Pediatric delirium (PD) is an acute neuropsychiatric syndrome marked by fluctuating disturbances in attention and cognition, frequently observed in pediatric intensive care units (PICUs) and associated with increased morbidity, mortality, and long-term cognitive impairment. Despite its clinical significance, PD remains underdiagnosed due to challenges inherent in assessing consciousness and cognition in children at varying developmental stages. Several bedside tools have been developed and validated in recent years, including the Cornell Assessment of Pediatric Delirium (CAPD), PreSchool Confusion Assessment Method for the Intensive Care Unit (psCAM-ICU); Pediatric Confusion Assessment Method for the Intensive Care Unit (pCAM-ICU), and Sophia Observation Withdrawal Symptoms—Pediatric Delirium Scale (SOS-PD), enhancing early recognition and management of PD in critically ill children. This narrative review explores the historical background, epidemiology, risk factors, pathophysiology, clinical subtypes, diagnostic tools, and current prevention and treatment strategies for PD from newborns to 21 years old. The screening tools available and the integration of non-pharmacological interventions, such as environmental modifications and family-centered care, as well as cautious and selective pharmacological management, are emphasized in this review. Early identification and targeted interventions are essential to mitigate the adverse outcomes associated with PD. Full article

Background: Attention-Deficit/Hyperactivity Disorder (ADHD) is a complex neurodevelopmental condition typically requiring information from multiple informants for accurate diagnosis. However, the consistency and diagnostic value of reports from teachers, parents, primary care providers (PCPs), and other professionals remain debated. This study aimed to examine the role and diagnostic accuracy of different informants in the referral and diagnostic process for ADHD in children aged 3–11. Methods: This retrospective study analyzed data from 120 children referred for suspected ADHD. Initial reports were obtained from teachers, parents, PCPs, and other professionals, and final diagnoses were determined through comprehensive neuropsychiatric evaluations. Diagnostic concordance and informant-specific contributions were assessed. Results: Of the 120 children, 64 (53.3%) received an ADHD diagnosis. Teachers were the most frequent informants, followed by parents, with fewer referrals from PCPs and other professionals. No significant differences in diagnostic accuracy were found among informants, aligning with previous studies suggesting that no single informant is superior in identifying ADHD. Notably, over 93% of referred children were diagnosed with a neuropsychiatric disorder, though not necessarily ADHD. Conclusions: The findings underscore the importance of combining reports from parents and teachers to capture symptom expression across different environments, which is essential for accurate ADHD diagnosis. Enhanced training for informants and a multidisciplinary approach is recommended to improve diagnostic accuracy and support early identification and intervention efforts. These results support nuanced evaluation strategies that account for informant variability and help mitigate potential misinterpretations of ADHD symptoms. Full article

Background: Persisting symptoms after concussion is a complex syndrome warranting exploration into further treatment options. Emerging research highlights the potential of classic psychedelics, such as psilocybin, in managing neuropsychiatric conditions and promoting neuroprotection. Case Report: A case is presented of a 22-year-old male intercollegiate athlete who sustained a concussion and developed persisting symptoms despite multidisciplinary standard care. The symptom burden remained relatively stable for the first month post-concussion. He independently administered three 250 milligram (mg) doses of the dried fruiting body of Psilocybe cubensis (2.5 mg of psilocybin) on days 42, 45, and 46 post-injury. He reported immediate symptom relief, including improvements in headache, noise sensitivity, and cognitive function. His symptom severity score decreased from 25 to 11 and his affective symptom burden resolved completely. Functional improvements allowed him to return to full activity. No adverse effects were reported. Conclusions: This case highlights the potential role of classic psychedelics as adjuvant agents in treating persisting symptoms after concussion. Clinicians should be aware that athletes may explore psychedelics as alternative treatments. Further research is needed to evaluate the efficacy and safety of psilocybin in concussion recovery. Full article

Background: Caregiving can be a challenging experience, particularly for caregivers of people with Parkinson’s disease, given the array of motor and neuropsychiatric symptoms. Elevated care tasks and demands related to these symptoms may result in greater care burden, heightened caregiving-related strain, and, in turn, poorer health for Parkinson’s disease (PD) caregivers compared to non-PD caregivers. Guided by the Stress Process Model, the purpose of this study was to explore the pathways connecting PD caregiving and caregiver health, with attention to the role of care burden and caregiving-related strain. Methods: We applied path analysis in a structural equation modeling framework to data from 3116 PD and non-PD caregivers participating in the National Alliance for Caregiving and AARP’s Caregiving in the U.S. 2015 and 2020 surveys. We estimated pathways between PD caregiving, care burden, caregiving-related strain (i.e., emotional, physical, and financial), and caregiver self-reported health simultaneously, then decomposed these pathways into total, indirect, and direct effects. Results: Findings show PD caregiving is indirectly linked to poorer health among caregivers through increased care burden and heightened caregiving-related strain, with additional path analysis models pointing to physical strain as an important component of caregiving-related strain in mediating the associations between PD caregiving and overall health. Conclusions: Our findings suggest a need to be especially attentive to the accumulation of care burden and caregiving-related strain—particularly physical strain—among PD caregivers, given the potential consequences for caregiver health. Solutions are needed, such as caregiver screening and caregiver-specific care plans, to better support reductions in burden and strain among PD caregivers, thereby promoting their overall health. Full article

The neurobiological mechanisms underlying methamphetamine use disorder (MUD) remain elusive, and specific treatment modalities as well as diagnostic markers are scarce. The emergence of exosomes has opened up possibilities for developing diagnostic and assessment biomarkers for neuropsychiatric disorders. Hence, the present study aimed to preliminarily explore the alterations in exosomal miRNA expression in MUD patients and the potential mechanisms involved in MUD. First, miRNA sequencing and RT-qPCR were used to verify the differential expression of peripheral blood exosomal miR-184-3p and miR-4433a-5p in MUD patients. Subsequently, the diagnostic ability of these two miRNAs for MUD was evaluated using ROC analysis. Finally, the regulatory relationship between miRNA-184-3p and its downstream target gene CRTC1 was verified by dual luciferase reporter assay. The results demonstrated that exosomal miR-184-3p and miR-4433a-5p were markedly decreased in MUD patients. However, the expression level of miR-4433a-5p was influenced by anxiety-depressive symptoms. The ROC analysis revealed that the AUCs of exosomal miRNA-184-3p in the training and validation sets of MUD patients were 0.902 and 0.823, respectively. In conclusion, exosomal miR-184-3p levels in peripheral blood may be a potential biomarker for the diagnosis and assessment of MUD, and it may be involved in the pathophysiological process of MUD through the targeted regulation of the CRTC1/CREB pathway. Full article

Small cell lung cancer (SCLC) is an aggressive form of lung cancer characterized by rapid growth and early metastases. As a neuroendocrine tumour, SCLC is especially notorious for various paraneoplastic syndromes, one of which is a rare neurological syndrome called paraneoplastic limbic encephalitis (PLE) that manifests with amnestic cognitive impairment and seizures. Here, we describe a case of a 53-year-old female who presented with neuropsychiatric symptoms of delusions, hallucinations, and cognitive impairment that started months prior to being diagnosed with extensive-stage SCLC. With no previous neuropsychiatric history, this raised the question of whether her presentation was related to PLE rather than a primary psychiatric condition, as initially diagnosed. Her symptoms improved with chemotherapy and radiation treatment of the underlying cancer, favouring a paraneoplastic etiology. Overall, this case underscores the importance of considering paraneoplastic syndromes in patients presenting with new neuropsychiatric symptoms, as early recognition and treatment can improve prognosis. Full article