Search Results (60)

The serotonergic system, originating in the raphe nuclei, differentially modulates the dorsal and ventral hippocampus, which are implicated in cognition and emotion, respectively. Emerging evidence from rodent models (e.g., neonatal ventral hippocampal lesion, pharmacological NMDA receptor antagonist exposure) and human postmortem studies indicates dorsoventral serotonergic alterations in schizophrenia. These data include elevated 5-HT1A receptor expression in the dorsal hippocampus, linking serotonergic hypofunction to cognitive deficits, and hyperactive 5-HT2A/3 receptor signaling and denser serotonergic innervation in the ventral hippocampus driving local hyperexcitability associated with psychosis and stress responsivity. These dorsoventral serotonergic alterations are shown to disrupt the excitation–inhibition balance, impair synaptic plasticity, and disturb network oscillations, as established by in vivo electrophysiology and functional imaging. Synthesizing these multi-level findings, we propose a novel “dorsoventral serotonin imbalance” model of schizophrenia, in which ventral hyperactivation predominantly contributes to psychotic symptoms and dorsal hypoactivity underlies cognitive deficits. We further highlight promising preclinical evidence that selective targeting of region- and receptor-specific targeting, using both pharmacological agents and emerging delivery technologies, may offer novel therapeutic opportunities enabling symptom-specific strategies in schizophrenia. Full article

Background and Clinical Significance: Herein, we describe the clinical case of a 17-year-old patient with psychotic disorder secondary to cerebral venous thrombosis due to primary thrombophilia, which was related to protein S deficiency and a heterozygous MTHFR gene mutation with the p.Ala222Val variant. Case presentation: A 17-year-old female, with no history of previous illnesses, was admitted to the emergency service department due to a psychotic break. Psychiatric evaluation detected disorganized thought, euphoria, ideas that were fleeting and loosely associated, psychomotor excitement, and deviant judgment. On the fifth day, an inflammatory process in the parotid gland was detected, pointing out a probable viral meningoencephalitis, prompting antiviral and antimicrobial treatment. One week after antiviral and steroidal anti-inflammatory treatments, the symptoms’ improvement was minimal, which led to further neurological workup. MRI venography revealed a filling defect in the transverse sinus, consistent with cerebral venous thrombosis. Consequently, anticoagulation treatment with enoxaparin was initiated. The patient’s behavior improved, revealing that the encephalopathic symptoms were secondary to thrombosis of the venous sinus. Hematological studies indicated the cause of the venous sinus thrombosis was a primary thrombophilia caused by a heterozygous MTHFR mutation variant p.Ala222Val and a 35% decrease in plasmatic protein S. Conclusions: This case highlights the possible relationship between psychiatric and thrombotic disorders, suggesting that both the MTHFR mutation and protein S deficiency could lead to psychotic disorders. Early detection of thrombotic risk factors in early-onset psychiatric disorders is essential for the comprehensive management of patients. Full article

Background/Objective: South Korea continues to have the highest suicide rate among the Organization for Economic Co-operation and Development (OECD) countries, with a growing number of emergency department (ED) admissions related to self-harm and suicide attempts. However, trauma-focused analyses that integrate psychiatric profiles and suicide mechanisms remain limited, hindering effective clinical care and preventive strategies. Methods: This retrospective study analyzed trauma patients who presented to the ED of Wonju Severance Christian Hospital following suicide attempts between October 2015 and December 2023. Of 305 self-harm cases, 208 survivors who underwent psychiatric evaluation were included. The variables analyzed included the mechanism, site, and severity of injury (ISS and AIS); psychiatric diagnosis and prior psychiatric history; repeated suicide attempts; alcohol use; physical pain; interpersonal conflict; and economic vulnerability. Chi-square, Fisher’s exact, and Kruskal–Wallis’ tests were used for statistical comparisons. Results: Stabbing/cutting (56.7%) and falling (35.6%) were the most common attempts. Mood disorders were the predominant psychiatric diagnosis (63.9%), followed by adjustment disorders (26.0%), alcohol use (25.5%), and psychotic disorders (22.1%). Among the fall-related cases, patients were typically younger and predominantly women. The median ISS was highest in fall-related cases (17) compared with stabbing/cutting (4), with 25.96% of patients with an ISS ≥16, indicating severe trauma. A psychiatric history was associated with a higher incidence of falls (44.3%), and previous suicide attempts correlated with the use of high-lethality attempts. Severe physical pain was linked to stabbing/cutting in 10 of 11 cases. Interpersonal conflict was more frequently associated with stabbing/cutting (59.6%) than with falls (31.9%). No significant association was found between alcohol use and the method of suicide attempt. Conclusions: The suicide mechanisms in patients with trauma are closely associated with psychiatric and psychosocial factors. Stabbing/cutting is often impulsive and driven by interpersonal conflict or alcohol use, while falling is more frequent in patients with psychiatric histories of repeated attempts. These findings emphasize the importance of mechanism-informed psychiatric evaluations and trauma protocols. Regionally adapted, interdisciplinary approaches and early psychiatric intervention are crucial for effective post-attempt management and suicide prevention. Full article

Stigma and discrimination remain significant challenges to the quality of life and social integration of individuals with chronic mental disorders, particularly schizophrenia, one of the most stigmatized conditions. The paradox of insight, in which greater awareness of illness correlates with poorer psychosocial outcomes in the presence of high internalized stigma, provides a critical framework for understanding these challenges. This study examined the moderation between insight and internalized stigma and its influence on psychosocial outcomes in 83 male participants diagnosed with psychotic spectrum disorders. Using K-means clustering, three distinct profiles emerged: (1) good insight and minimal stigma, (2) poor insight and mild stigma, and (3) good insight and severe stigma. These profiles showed significant differences in depression, quality of life, and global functioning. Findings confirmed that internalized stigma moderates the relationship between insight and psychosocial well-being, exacerbating the negative influence of insight on quality of life and psychological health when stigma levels are high. The results emphasize the need for psychoeducational interventions to normalize experiences of psychosis, family and community engagement to reduce stigma, and cognitive-behavioral therapies to address stigma-related beliefs. These strategies are essential for improving psychosocial well-being and supporting recovery in this population. Full article

Background: Clinical High Risk for Psychosis (CHR-P) is a psychopathological condition requiring early prevention, particularly in adolescence. Methods: We enrolled 151 patients to assess the potential of the Rorschach Performance Assessment System (R-PAS) in predicting the course of CHR-P and transitions to psychosis. Adolescents with DSM-5 Attenuated Psychotic Symptoms (APS) at baseline were compared with those diagnosed with Early-Onset Psychosis (EOP) and those with other conditions (non-APS). We also examined whether antipsychotics influenced patients’ performance in the R-PAS. Finally, we analyzed correlations between DSM-5 diagnoses at one-year follow-up and baseline R-PAS indexes. Results: APS and EOP patients exhibited similar R-PAS profiles, with APS showing greater impairments in specific Perception and Thinking Problem indexes. Antipsychotic use did not confound results. A distinct R-PAS profile emerged for individuals at risk of psychosis after one year, with the most significant alterations in the Self and Other Representation and the Stress and Distress domains. Conclusions: This study highlights the R-PAS as a valuable tool for early psychosis risk detection and prevention strategies. Targeted, person-centered interventions (i.e., psychotherapy, mindfulness, and relaxation techniques) are recommended to address vulnerabilities. Integrating psychological assessment into early intervention frameworks may enhance outcomes and improve patients and families’ quality of life. Full article

Patients intoxicated with alcohol or other substances are often assessed and assisted in the context of the Emergency Department (ED) by emergency physicians, who usually require a psychiatric assessment. This study aims to analyse the characteristics of a sample of patients receiving a psychiatric consultation in the ED setting of the Maggiore della Carità University Hospital in Novara, Italy, in the period from 1 January 2021 to 31 December 2023, to find out whether and how patients screening positive for alcohol/drugs differ from those screening negative. Socio-demographic and clinical history information and clinical data related to the ED psychiatric consultations were extracted from the PsNet database, a collection of data extracted from the application that serves as the electronic medical record for patients accessing the ED. Statistical analyses were performed using SAS 9.4 and STATA version 17 software. Chi-square/Fisher tests, t-tests, and both univariate and multivariate logistic models were employed. Most of the findings regarding socio-demographic characteristics, symptoms observed during the 1362 psychiatric consultations, and treatments received by a total of 922 patients in the ED were consistent with the literature on this topic. However, some results only partially aligned with previous studies, particularly concerning the higher frequency of anxiety and psychotic symptoms, as well as cognitive impairments, observed in consultations for patients who tested negative for alcohol or substances. Interpreting these findings is complex and raises important questions, which may be addressed more effectively by expanding the sample size (extending the research to other EDs) and analysing its characteristics in greater detail. In this regard, improving diagnostic methods for detecting substance use through laboratory tests would also be beneficial. Full article

Background: Schizophrenia is a complex disorder characterized by positive symptoms (e.g., hallucinations), negative symptoms (e.g., social withdrawal), and disorganized symptoms (e.g., thought disorder). Alongside these, cognitive and depressive symptoms often emerge, with depressive symptoms sometimes dominating the clinical picture. Understanding the factors that influence the development of depressive symptoms in schizophrenia could clarify the dynamics between depressive and psychotic symptoms and guide clinical interventions. Methods: A total of 105 patients with schizophrenia (66 women, 39 men) were assessed using several clinical scales: PANSS, BPRS, DOCS, DES, HAM-D, and the Luria-Nebraska Neuropsychological Battery for cognitive evaluation. Statistical analyses, including correlation and regression, were conducted using SPSS to determine the significance of associations. Results: Disorganized and obsessive-compulsive symptoms were identified as primary factors associated with depressive symptoms in patients with schizophrenia. Conversely, a longer duration of untreated psychosis was linked to a lower severity of depressive symptoms, suggesting that early intervention may alter the depressive symptom trajectory. Conclusions: Here, we suggest a complex interaction between psychotic and depressive symptoms, possibly indicating a biological antagonism. The association of depressive symptoms with disorganized and obsessive-compulsive features may reflect an adaptive psychological response, attempting to stabilize amidst the disintegration of schizophrenia. These insights support a more integrated approach to treatment, addressing both psychotic and depressive symptoms to improve patient outcomes. Full article

Psychotic disorders in youth pose significant challenges for mental health services, necessitating a detailed understanding of the interplay between risk factors and resilience. This systematic review aimed to assess how resilience factors might buffer the adverse effects of risk factors on the development of psychosis among youth, thereby informing targeted interventions. Studies were selected based on criteria including a focus on individuals aged up to 25 years old at risk for psychosis, the examination of both risk factors and resilience, and the use of validated instruments for measuring outcomes. Literature searches were conducted across several databases, such as PubMed, Scopus, and Web of Science. Data extraction emphasized odds ratios (ORs) and hazard ratios (HRs) for risk factors, including familial, developmental, and socio-environmental influences. The review included and analyzed nine studies, encompassing a diverse sample of 140,972 participants. Significant findings indicate that highly supportive familial and community environments significantly reduce the risk of psychosis onset. For instance, children with strong family support and engagement in structured activities demonstrated a 40% lower incidence of developing psychotic symptoms [p < 0.05]. Furthermore, the presence of neurobehavioral deficits, such as impaired verbal memory and attention, emerged as significant predictors of psychosis, with these children exhibiting a threefold increase in risk compared to their peers [OR = 3.2, 95% CI: 2.1–4.8, p < 0.01]. Resilience factors play a critical role in mitigating the impact of psychosocial and neurobiological risks in the development of psychosis among youths. Interventions enhancing resilience could potentially alter the trajectory of psychosis development, emphasizing the need for early and targeted psychosocial interventions to support at-risk populations. This study underscores the importance of fostering resilience through both individual-focused and community-based strategies to prevent the onset of psychotic disorders in vulnerable young populations. Full article

Background: Increasing research data suggest that the dysfunction of emotional brain systems may be an important contributor to the pathophysiology of schizophrenia. However, contemporary psychopathology consistently underestimates the role of emotions in the phenomenology of the disease. Psychotic arousal (PA) is a conceptually defined psychopathological construct aiming to portray the experiential emotional state of acute psychosis. The concept provides an explanatory model for the emergence of psychosis, and the formation and maintenance of delusions based on neurobiological models on the formation of core consciousness and subjectivity. This is the first exploratory study of the major assumptions, endorsed in the project summarized as follows: (1) psychotic arousal is a discrete state, eligible for investigation; (2) abnormal experiential feelings are an integral part of this state; and (3) the state is responsive to antipsychotic intervention during the first weeks of treatment. Methods: We developed the Psychotic Arousal Scale (PAS) accordingly, explored its first psychometric properties and tested its relation to other psychopathological measures. Fifty-five acute schizophrenia patients were evaluated with the PAS, the Positive and Negative Syndrome Scale, the Brown Assessment of Beliefs Scale, the Hamilton Anxiety Scale, and the Calgary Depression Scale. Cronbach α coefficients, t-test analysis, correlations and mixed linear regression models were applied for testing the internal reliability of the scale, associations between parameters and sensitivity to change in three time periods during therapeutic intervention. Results: The results of the study support that (PA) is eligible for investigation as a discrete psychopathological state. Abnormal experiential feelings are an integral part of this state, presenting high affinity with other affective measures; their degree of severity relates to the delusions’ conviction and are amenable to antipsychotics early in treatment during the acute psychotic episode. Conclusions: The findings of this exploratory study are connotative of the presence of an emotional arousal permeated by abnormal experiential feelings during acute psychosis, largely overlooked by contemporary psychopathology. Full article

New psychoactive substances (NPSs) are a heterogenous group of psychotropic molecules and diverted pharmaceutical drugs sold worldwide as legal substitutes for controlled drugs. The psychiatric consequences of NPS use are relatively unknown, although evidence of related psychotic symptoms has been described in the literature. We sought to summarize the available evidence on NPS-related psychiatric disorders, to facilitate the interpretation of the molecular mechanism underlying their specific pathologies. A literature search of Scopus, PubMed and Google Scholar was conducted including studies published between 2013 and 2024, in which a correlation between NPS consumption and psychiatric symptoms was reported. Furthermore, the short- and long-term psychopathological effects were included. The literature search resulted in 109 NPS-related intoxication cases in which acute or chronic psychiatric symptoms were reported, mostly related to synthetic cannabinoids, followed by synthetic cathinones, hallucinogens, natural NPSs and stimulants. The most common acute symptoms were hallucinations, aggressiveness, and psychotic and bizarre behavior, related to the molecular disbalance of neurotransmitters in the central nervous systems, with different mechanisms. The lack of clear diagnostic criteria and toxicological analyses has resulted in crucial complications in psychiatric diagnoses related to NPS intoxication. Hence, the implementation of toxicological screening procedures in emergency rooms, including the main NPS classes, should support the diagnosis of acute intoxication and its proper therapeutic treatment. Finally, proper follow-up should be implemented to assess the chronic sequelae. Full article

Background: Autism spectrum disorder (ASD) is a persistent neurodevelopmental disorder frequently co-occurring with attention-deficit/hyperactivity disorder (ADHD) and behavior-related disorders. While behavioral therapy is the first-line option to manage the core symptoms of ASD, pharmacological therapy is sometimes needed to treat acute problems, such as agitation and aggressive behaviors. Recent guidelines recommend the use of neuroleptics to reduce psychomotor agitation in patients with ASD. However, as children with ASD are often drug-resistant, alternative treatments are often justified. Reports from the literature have indicated that intravenous valproate (IV-VPA) can be effective in reducing agitation in psychiatric patients, with a lower frequency of adverse events compared to conventional treatments. However, as the related findings are occasionally inconsistent, IV-VPA is not yet an approved option in the context of clinical psychiatry. We aim to improve knowledge of the IV-VPA treatment option for emergency psychiatric treatment in pediatric patients. Methods: We report the case of an 11-year-old boy suffering from a complex neurodevelopmental condition who experienced a psychotic episode with severe aggressive and disruptive behaviors and was successfully treated with IV-VPA. Furthermore, we provide an updated literature review on this topic. Conclusion: In our case, first-line therapies proved to be ineffective. To the contrary, IV-VPA led to safe and prompt clinical success, which is in line with other reports. Based on our literature review, IV-VPA can be highly effective and reduces the risk of adverse events that frequently occur with the use of high-dose standard medications in emergency psychiatry. Full article

It is crucial to regulate N-methyl-D-aspartate (NMDA) function bivalently depending on the central nervous system (CNS) conditions. CNS disorders with NMDA hyperfunction are involved in the pathogenesis of neurotoxic and/or neurodegenerative disorders with elevated D-serine, one of the NMDA receptor co-agonists. On the contrary, NMDA-enhancing agents have been demonstrated to improve psychotic symptoms and cognition in CNS disorders with NMDA hypofunction. Serine racemase (SR), the enzyme regulating both D- and L-serine levels through both racemization (catalysis from L-serine to D-serine) and β-elimination (degradation of both D- and L-serine), emerges as a promising target for bidirectional regulation of NMDA function. In this study, we explored using dimethyl malonate (DMM), a pro-drug of the SR inhibitor malonate, to modulate NMDA activity in C57BL/6J male mice via intravenous administration. Unexpectedly, 400 mg/kg DMM significantly elevated, rather than decreased (as a racemization inhibitor), D-serine levels in the cerebral cortex and plasma. This outcome prompted us to investigate the regulatory effects of dodecagalloyl-α-D-xylose (α12G), a synthesized tannic acid analog, on SR activity. Our findings showed that α12G enhanced the racemization activity of human SR by about 8-fold. The simulated and fluorescent assay of binding affinity suggested a noncooperative binding close to the catalytic residues, Lys56 and Ser84. Moreover, α12G treatment can improve behaviors associated with major CNS disorders with NMDA hypofunction including hyperactivity, prepulse inhibition deficit, and memory impairment in animal models of positive symptoms and cognitive impairment of psychosis. In sum, our findings suggested α12G is a potential therapeutic for treating CNS disorders with NMDA hypofunction. Full article

Background: Studies assessing the psychological impact of the COVID-19 pandemic on populations highlight the emergence of mental health difficulties, especially if a mental health disorder is already present. Patients with severe mental illnesses (SMIs) may be even more vulnerable to the psychosocial effects of the pandemic. However, little is known regarding the possible impact of the pandemic on SMI patients supported by community-based mental health day centers. Methods: A two-year prospective study comprising 29 individuals with SMI was conducted by the Skitali Mental Health Day Center in Ioannina, Northwest Greece. The described group of examined patients consisted mainly of psychotic patients (65.5%). Patients were assessed using the Health of Nations Outcome Scale and the Global Assessment of Functioning scale, and scores prior to and after the onset of the pandemic were compared. Results: The results indicated that participants did not present any significant decline in their overall clinical status during the COVID-19 pandemic and the national lockdown measures. Conclusions: This finding is relevant because previous research has shown that the pandemic may negatively impact adherence to treatment and service attendance and that the symptomatology of patients with SMIs may further deteriorate. It is suggested that the operation of mental health day centers during collective stressful events should be preserved, but further research is needed to evaluate their role in maintaining continuity of care during such events. Full article

Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDARE) is a complex neuropsychiatric syndrome known for its diverse neurological manifestations, often involving psychiatric symptoms and seizures that elevate the risk of suicidal ideation and behavior. We present a case illustrating the potentially lethal nature of anti-NMDARE, wherein an unexpected suicide attempt occurred 10 days after the onset of seizures in a 21-year-old man. Upon arrival at the emergency room, immediate interventions addressed hypovolemic shock, followed by subsequent neurosurgical and orthopedic procedures. Six days after cessation of sedation, the patient exhibited atypical focal seizures, behavioral arrest, psychotic responses, and delusions. Despite normal brain magnetic resonance imaging and cerebrospinal fluid (CSF) analysis results, a high CSF immunoglobulin G index and posterior hypometabolism on brain F-fluorodeoxyglucose positron emission tomography raised suspicion of autoimmune encephalitis. Steroids and intravenous immunoglobulins were administered. A comprehensive evaluation ruled out other conditions. Serum and CSF tests confirmed the presence of anti-NMDAR antibodies. This case highlights the potential lethality of the acute stage of anti-NMDARE, emphasizing the absence of apparent psychiatric symptoms before a suicide attempt. Further studies on suicidality associated with anti-NMDARE are crucial, underscoring the importance of vigilance in cases involving newly diagnosed seizures or psychoses. Full article

The administration of intravenous lipid emulsion (ILE) is a proven antidote used to reverse local anesthetic-related systemic toxicity. Although the capacity of ILE to generate blood tissue partitioning of lipophilic drugs has been previously demonstrated, a clear recommendation for its use as an antidote for other lipophilic drugs is still under debate. Venlafaxine (an antidepressant acting as a serotonin–norepinephrine reuptake inhibitor (SNRI)) and quetiapine (a second-generation atypical antipsychotic) are widely used in the treatment of psychotic disorders. Both are lipophilic drugs known to induce cardiotoxicity and central nervous depression. We report the case of a 33-year-old man with a medical history of schizoaffective disorder who was admitted to the emergency department (ED) after having been found unconscious due to a voluntary ingestion of 12 g of quetiapine and 4.5 g of venlafaxine. Initial assessment revealed a cardiorespiratory stable patient but unresponsive with a GCS of 4 (M2 E1 V1). In the ED, he was intubated, and gastric lavage was performed. Immediately after the admission to the intensive care unit (ICU), his condition quickly deteriorated, developing cardiovascular collapse refractory to crystalloids and vasopressor infusion. Junctional bradycardia occurred, followed by spontaneous conversion to sinus rhythm. Subsequently, frequent ventricular extrasystoles, as well as patterns of bigeminy, trigeminy, and even episodes of non-sustained ventricular tachycardia, occurred. Additionally, generalized tonic–clonic seizures were observed. Alongside supportive therapy, antiarrhythmic and anticonvulsant therapy, intravenous lipid emulsion bolus, and continuous infusion were administered. His condition progressively improved over the following hours, and 24 h later, he was tapered off the vasopressor. On day 2, the patient repeated the cardiovascular collapse and a second dose of ILE was administered. Over the next few days, the patient’s clinical condition improved, and he was successfully weaned off ventilator and vasopressor support. ILE has the potential to become a form of rescue therapy in cases of severe lipophilic drug poisoning and should be considered a viable treatment for severe cardiovascular instability that is refractory to supportive therapy. Full article