Search Results (192)

Background/Objectives: Psychotic relapse affects over 80% of individuals with schizophrenia-spectrum disorders, driving long-term disability and hospitalization. Clinical relapse management relies on symptomatic monitoring without objective neurobiological tools to guide individualized antipsychotic decisions. Methods: This systematic review synthesizes evidence on neurophysiological, blood-based, molecular, neuroimaging, and digital biomarkers for relapse prediction in schizophrenia-spectrum disorders. Results: Following the PRISMA 2020 guidelines, five databases were searched through March 2026 for longitudinal biomarker studies. Quality was assessed using the Newcastle-Ottawa Scale and PROBAST; findings were synthesized narratively due to substantial heterogeneity. From the 6812 citations screened, 21 studies were included across clinical high-risk, first-episode, and established illness populations. Conclusions: Mismatch negativity and P300 event-related potential (P300) showed the most consistent associations with relapse vulnerability, with mismatch negativity demonstrating relative independence from antipsychotic effects. Inflammatory and neuroendocrine markers—interleukin-6, C-reactive protein, and cortisol awakening response—predicted poor treatment response in multiple longitudinal investigations. Peripheral blood gene expression profiling identified TCF4 network dysregulation as a candidate molecular marker of impending relapse. Neuroimaging models did not outperform standard clinical variables. Digital phenotyping showed ecological promise but remains methodologically nascent. No single biomarker achieves sufficient accuracy for clinical implementation. Neurophysiological and inflammatory markers are the most tractable candidates for monitoring protocols. Future research should prioritize multimodal longitudinal designs, external validation, and systematic antipsychotic confounding control. Among the biomarkers reviewed, mismatch negativity and the interleukin-6/cortisol awakening response combination represent the most tractable candidates for pilot clinical implementation, particularly in specialized early psychosis services and antipsychotic dose-reduction research contexts; no biomarker currently achieves sufficient accuracy for routine use in maintenance treatment decisions. Full article

This prospective observational study aimed to estimate the annual service-based incidence of individuals with First Episode Psychosis (FEP) and high-risk states for psychosis presenting to a public Community Mental Health Center within a defined urban catchment area in Northwestern Greece. It offers novel real-world insights into early intervention in psychosis within a resource-constrained, post-crisis health care setting. All individuals aged ≥16 years who presented to the Community Mental Health Center of the University of Ioannina between January 2023 and December 2024 were assessed. Those diagnosed with FEP or identified as being at a high risk for psychosis using the Comprehensive Assessment of At-Risk Mental States were included, while duration of untreated psychosis (DUP) was estimated with the Symptom Onset in Schizophrenia inventory. Among 1115 service users, 51 (4.6%) met criteria for FEP (N = 33) or high-risk states (N = 18), rising to 7.5% among those aged 16–36 years. The annual service-based incidence of FEP was 10.26 per 100,000 in the general population, increasing to 51.62 in individuals aged 16–36 and 63.17 in those aged 16–26. Including high-risk cases, service-based incidence reached 109.71 per 100,000 in the 16–26 age group. Mean DUP was 39.4 weeks but was 7.0 weeks among 80% with DUP < 1 year. Most FEP patients (63.6%) required brief hospitalization, and over half reported family history of mental illness. These findings highlight substantial community caseloads and the need to strengthen early intervention services. Full article

Background and clinical significance: Autoimmune encephalitis (AE) is an inflammatory brain disorder that manifests through a diverse, unspecific range of neuropsychiatric symptoms. When AE occurs alongside a primary neurodegenerative disorder, the shared symptoms can create a mixed clinical profile, making diagnosis more difficult and potentially postponing effective management and treatment. Case presentation: We describe the case of a 58-year-old female with a one-year history of progressive behavioral and personality changes who presented a subacute confusional state, psychomotor retardation alternating with psychomotor agitation, apathy, visual hallucinations, and motor symptoms. Examination revealed Parkinsonian symptoms and frontal lobe signs. Neuroimaging showed frontotemporal atrophy, while cerebrospinal fluid analysis excluded infection but demonstrated elevated phosphorylated tau, supporting an underlying neurodegenerative process. An electroencephalogram revealed asymmetric temporal slowing without overt epileptiform activity. An initial diagnosis of behavioral variant frontotemporal dementia (bvFTD) was established. Due to rapid clinical deterioration and fluctuating cognition, autoimmune testing was expanded to a full antibody panel, which identified elevated serum anti-glutamic acid decarboxylase 65 (anti-GAD65) antibodies (60 UI/mL, reference range 0–5 UI/mL), establishing a possible coexisting diagnosis of anti-GAD65 autoimmune encephalitis. Initial treatment with intravenous immunoglobulin produced minimal improvement; however, therapeutic plasma exchange led to the remission of psychosis and significant improvement in rigidity, bradykinesia, and attention, with modest amelioration in global cognition. Conclusions: This case highlights the diagnostic challenges posed by overlapping AE and bvFTD clinical pictures, especially when neurodegenerative features obscure an underlying autoimmune process. Early, panel-based neural antibody testing—and consideration of AE even in patients already diagnosed with a major neurocognitive disorder—is critical for avoiding delays in immunotherapy. Prompt recognition and treatment of AE may substantially improve clinical outcomes, even in complex cases with suspected overlap. Full article

Background: Lay counsellor-delivered psychosocial interventions are increasingly used to address workforce shortages in mental health care. While randomised trials commonly report mean improvements, explicit assessment of clinical deterioration is rare. This secondary analysis evaluated whether a lay counsellor intervention for early psychosis was associated with evidence of deterioration compared with usual care. Methods: Patient-level data from a randomised controlled trial in Thailand (n = 255) were analysed. Deterioration was defined as worsening between baseline and the 6-month follow-up across functional, behavioural, and service utilisation domains. Risk differences were estimated using Newcombe confidence intervals, and risk ratios were calculated using standard methods with the Haldane–Anscombe correction applied, where required. Analyses were conducted for the full sample (UC n = 125; LICM n = 130) and stratified by baseline severity (none/borderline: UC n = 103, LICM n = 103; mild-to-severe: UC n = 22, LICM n = 27). Results: In the full sample, deterioration rates were similar across most domains. A statistically significant reduction in deterioration related to disturbing or aggressive behaviour was observed in the LICM arm (risk difference −14.1%; 95% CI −26.8% to −0.6%; risk ratio 0.45; 95% CI 0.26 to 0.79). No statistically significant excess deterioration was observed in other domains. In severity-stratified analyses, no subgroup showed a statistically significant increase in deterioration attributable to the intervention. However, among participants with mild-to-severe baseline illness, although no statistically significant harm signal was detected, the adverse risk differences and risk ratios observed in socially useful activities, self-care, regular outpatient follow-up visits, and medication adherence among participants with greater baseline severity underscore the importance of careful monitoring in higher-risk subgroups. Conclusions: No statistically significant evidence of excess deterioration was observed in either the full sample or subgroup analyses between the intervention and control arms. However, the adverse absolute difference observed in multiple patient-related domains, among participants with mild-to-severe baseline illness, suggests that lay-counsellor interventions may require a stepped-care approach to safely address the mental health needs of patients with higher levels of severity. Psychosocial trials should routinely report deterioration and subgroup analyses alongside mean improvements. Full article

Background: Post-psychotic depression (PPD) is an underestimated but clinically significant affective syndrome that occurs during remission from psychosis, particularly in schizophrenia. Material and Methods: This comprehensive review traces the evolution of this concept over five decades of research, starting from its initial differentiation from primary depression and schizoaffective disorders in the 1970s. Relying on more than thirty studies, we analyze historical definitions, biological and psychosocial mechanisms, diagnostic controversies, and therapeutic implications. Results: Research indicates that PPD develops from multiple contributing factors, including psychological insight, autobiographical disturbances, pharmacological influences, and social losses, rather than simply as a byproduct of psychosis or pharmacological treatment. We discuss the persistence of depressive symptoms after acute remission, their role in suicidal tendencies, and the diagnostic challenges arising from the overlap of negative symptoms and demoralization. Despite its exclusion from current diagnostic standards, PPD continues to affect a significant fraction of patients, particularly those with high insight and early onset. Conclusions: Effective treatment requires a multidimensional, phase-specific approach combining antidepressants, atypical antipsychotics such as lurasidone, and psychological interventions targeting identity, self-esteem, and narrative processing. We argue that PPD should be reintroduced as a distinct clinical unit and incorporated into psychiatric guidelines to reduce diagnostic oversights and improve patient outcomes. Full article

Background/Objectives: In recent years, research on psychosis has increasingly focused on prevention, aiming to implement early interventions that mitigate or reduce its impact. Within this framework, the analysis of linguistic markers in individuals with at-risk mental states (ARMS) has proven valuable for identifying those at risk and predicting psychosis onset. Artificial intelligence tools, particularly natural language processing (NLP), have emerged as effective resources for detecting these language-based indicators. This study aims to synthesize the existing scientific evidence on linguistic markers analyzed through NLP techniques in individuals with ARMS. Methods: A systematic review following the PRISMA 2020 protocol was conducted. Three databases (PubMed, PsycInfo, and Scopus) were searched for published articles from their inception to October 2025. Rayyan software was used to manage references and article downloads. Out of ninety initial search results, fifteen studies involving 1313 participants from diverse groups were included in the review. Results: The findings indicated that alterations in semantic coherence, syntactic complexity, referential cohesion, and speech/content poverty differentiated ARMS individuals from healthy controls. Several of these markers, analyzed with NLP methods, predicted the onset of psychosis with accuracy levels ranging from 79% to 100%, although these findings should be interpreted with caution due to the significant methodological heterogeneity and variability in sample sizes across the included studies. Conclusions: NLP techniques offer a powerful approach for detecting language alterations that distinguish ARMS individuals and provide meaningful predictions of psychosis onset, highlighting their potential as a complement to traditional clinical assessments for early identification and prevention. Full article

Recent revisions of personality disorder (PD) classifications have moved from categorical diagnoses toward dimensional models, raising renewed questions about the nosological status and clinical utility of borderline personality disorder (BPD). This narrative review traces the development of the borderline construct from early descriptions of patients positioned between neurosis and psychosis, through its theoretical consolidation within the concept of borderline personality organization, to the operationalization of BPD in DSM-III and subsequent diagnostic revisions. A central section summarizes contemporary controversies regarding the validity and utility of BPD features. Arguments for abandoning the diagnosis emphasize the absence of a distinct borderline factor in factor analytic studies, the tendency of the construct to capture fluctuating symptoms and patterns of behaviour rather than stable maladaptive personality traits, the stigmatizing and non-selective use of the label, and the lack of disorder-specific treatment approaches. In contrast, converging evidence supports the view that core borderline symptoms frequently function as markers of general PD pathology and of the severity of impairments in self and interpersonal functioning. The paper integrates the concept of the borderline level of personality functioning, conceptualizing borderline pathology as a dynamic dimension of dysfunction with potential transient regressions, and links this concept to the Level of Personality Functioning (LPF, Criterion A) within the DSM 5 Alternative Model for Personality Disorders (AMPD). Retaining borderline pathology as a dimension may support contemporary PD assessment by offering a clinically recognizable marker of overall dysfunction, a guide for rating severity, an indicator of personality structure and need for psychotherapy, without disrupting continuity with an extensive clinical and research tradition. Full article

Objectives: Autism Spectrum Disorder (ASD) and psychotic disorders have long been considered separate diagnostic entities, yet increasing evidence highlights shared neurodevelopmental mechanisms and symptom overlap. Psychotic-like experiences have been frequently reported in individuals with ASD, while subthreshold autistic traits (ATs) in first-degree relatives may also confer vulnerability to psychotic symptoms. This cross-sectional study aimed to compare psychotic spectrum manifestations among adults with ASD, their first-degree relatives (BAP), and controls (HCs), to explore associations between psychotic and ATs, and to evaluate whether psychotic symptoms predict diagnostic group membership. Methods: 22 adults with ASD, 22 BAP, and 24 HCs were evaluated with the Psychotic Spectrum–Self Report (PSY-SR) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). Results: ASD participants scored significantly higher on the PSY-SR. BAP individuals showed higher PSY-SR total scores compared to HCs, though less severe than in ASD. All PSY-SR domains positively correlated with all AdAS Spectrum domains, with few exceptions. Multinomial regressions showed that higher PSY-SR total scores significantly predicted ASD and BAP membership, and that the PSY-SR Paranoid domain score specifically predicted inclusion in both groups in relation to HCs. Conclusions: Psychotic spectrum symptoms are elevated not only in individuals with ASD but also among first-degree relatives, supporting a continuum linking autistic and psychotic vulnerabilities. The strong association between paranoid symptoms and ATs highlights a dimension of potential clinical relevance for early identification and assessment. These findings reinforce shared neurodevelopmental pathways between the autism and psychosis spectra and underscore the importance of dimensional approaches across diagnostic categories. Full article

Studies conducted in first-episode psychosis (FEP) patients have shown alterations in inflammation and metabolism. Our objective was to investigate potential treatment-related effects on these systems in Italian FEP patients undergoing either an experimental treatment consisting of a multi-element psychosocial intervention (EXP), including cognitive–behavioural therapy, or treatment as usual (TAU). A total of 191 FEP patients with first contact between April 2010 and March 2011 were clinically assessed at baseline and after 9 months of treatment, and the serum levels of 19 analytes were determined through single or multiplex enzyme-linked immunosorbent assays (ELISAs). A significant increase was observed in leptin levels and a significant decrease in Glucagon-Like Peptide-1 (GLP-1) levels during the treatment (time effect, p < 0.001 for both), with no significant interaction between time and treatment type. Although ghrelin levels changed significantly over time in the whole cohort (p = 0.008), a significant decrease was observed only in the EXP group (post hoc test: p = 0.001). None of the biomarkers measured at baseline showed a predictive effect on treatment efficacy, and no significant associations were identified between changes in clinical scores and changes in biomarker levels. These results suggest that early-phase psychosis treatments are associated with possible effects on metabolic regulation. Full article

Parkinson disease (PD) and mood disorders represent two substantial global health burdens that increasingly co-occur as both conditions rise in prevalence worldwide. Diagnosing Parkinson disease in patients with pre-existing mood disorders is clinically challenging due to overlapping symptoms, medication effects, and shared neurobiological mechanisms. Apathy, psychomotor slowing, and fatigue may mimic depressive symptoms, leading to delayed recognition of early parkinsonism. Development of an underlying neurodegenerative disorder could account for some treatment-resistant symptoms or treatment failures if not recognized. Therefore, the identification of PD will change the treatment and management plan significantly. Accurate diagnosis of PD requires a detailed neurologic examination focusing on bradykinesia, rigidity, and resting tremor, supported when appropriate by dopamine transporter imaging (DaT scan) or other emerging biomarkers. Understanding the temporal relationship between psychiatric and motor features helps differentiate prodromal PD from primary mood disorders. Management of patients with both mood disorders and PD integrates dopaminergic replacement therapy for motor symptoms with individualized treatment of psychiatric comorbidities. Levodopa remains the cornerstone for motor control, while dopamine agonists, MAO-B inhibitors, and COMT inhibitors can be added as needed. For depression and anxiety, SSRIs and SNRIs are first-line choices; quetiapine or clozapine are preferred when treatment for psychosis is necessary. Intentional, thoughtful polypharmacy is frequently required. Non-pharmacologic interventions—including cognitive behavioral therapy, structured exercise, and patient–caregiver education—enhance mood, function, and quality of life. Multidisciplinary collaboration between neurology, psychiatry, and allied health professionals is essential for optimal outcomes. This review offers guidance to healthcare providers as well as other interested parties involved in patients with mood disorders who may also be developing or have PD, especially to those who may have limited access to neurologic resources. Full article

Schizophrenia is a complex, chronic psychiatric disorder with significant global impact, characterized by persistent positive, negative, and cognitive symptoms that are not fully addressed by current treatments. This review aims to synthesize established theories and advancing mechanistic concepts and also critically compare the latest international treatment guidelines. Recent evidence expands beyond the traditional dopamine hypothesis to include glutamatergic, serotonergic, and cholinergic dysfunctions, as well as emerging mechanisms such as neuroinflammation, oxidative stress, iron dysregulation, and gut–brain interactions. A review of major international guidelines (APA, NICE, CINP, WFSBP, and others) confirms consensus on the use of second-generation antipsychotics as first-line therapy and the early introduction of clozapine for treatment-resistant cases. All guidelines emphasize the essential role of integrated psychosocial interventions, including cognitive behavioral therapy for psychosis, family psychoeducation, and supported employment. Differences remain regarding the prioritization of precision medicine, pharmacogenomics, and digital health innovations. Prognosis varies widely but improves with early intervention, sustained treatment adherence, and comprehensive physical health monitoring. Overall, schizophrenia care is evolving toward a precision-based, recovery-oriented model that integrates biological, psychological, and social strategies to improve long-term outcomes and quality of life. Full article

Background: Creative Expressive Therapies, including Art Therapy and Dance/Movement Therapy (DMT), are increasingly integrated as adjunctive interventions in the treatment of complex psychiatric conditions. However, comparative evidence regarding their differential effects across diagnostic groups remains limited. Methods: This exploratory quasi-experimental 2 × 2 factorial study compared Art Therapy and DMT, delivered as adjuncts to treatment as usual, in patients with first-episode psychosis (FEP) and eating disorders (EDs) (N = 36). Participants received ten weekly group sessions. Changes in perceived well-being, emotional tension regulation, and physical tension regulation were assessed at baseline and post-intervention using self-report measures. Data were analyzed using repeated-measures ANOVA and linear mixed-effects models. Results: Significant pre–post improvements were observed across all outcome domains, indicating a transdiagnostic effect of Creative Expressive Therapies. Differential response patterns emerged according to clinical profile and therapeutic modality. DMT was associated with relatively greater improvements in physical tension regulation in patients with EDs, whereas Art Therapy showed relatively greater effects on emotional tension regulation in patients with FEP. Conclusions: Within the limitations of an exploratory, non-randomized design and the use of non-validated outcome measures, the findings suggest modality-specific patterns of response to Creative Expressive Therapies. These results should be considered hypothesis-generating and support further investigation through adequately powered randomized controlled trials employing validated clinical and neurobiological outcomes. Full article

Background/Objectives: This study aimed to investigate whether therapy with perampanel is associated with the development of psychosis or psychosis-like symptoms in patients with epilepsy. Methods: We conducted systematic electronic searches in PubMed, Google Scholar, ScienceDirect, and Scindex databases. We included articles published as case reports/case series, as well as conference abstracts and letters from the editor, if they contained enough data for analysis and quality assessment. The main inclusion criteria relate to patients who experienced psychosis or psychosis-like symptoms described by the authors during perampanel therapy or during its recent use. Results: Publications (n = 17) describing a total of 33 patients who met the inclusion criteria were included. Patient ages ranged from 11 to 70 years, and the majority of them were female (66.67%). A confirmed personal psychiatric history was identified in 60.61% of patients. The time interval between the initiation of perampanel and the onset of adverse events varied significantly across cases. The most frequently reported symptom was aggression (75.75%), followed by irritability (30.30%), while delusions or hallucinations were observed in 8 patients (24.24%). Conclusions: Clinicians should be aware that psychosis or psychosis-like symptoms may represent dose-dependent adverse effects of perampanel with a satisfactory prognosis. Identified risk factors for these developments were positive personal psychiatric history, antiseizure polytherapy at high doses, women’s gender, and focal epilepsies with secondary generalization, mainly manifested as tonic–clonic seizures. Early recognition of symptoms, followed by drug discontinuation, dose reduction, symptomatic treatment, or a combination of the mentioned strategies, is crucial for achieving better outcomes. Full article

Background/Objective: To examine whether patients with late-onset schizophrenia (LOS) and very-late-onset schizophrenia-like psychosis (VLOS) are at a higher risk of developing dementia than patients with early-onset schizophrenia (EOS). Methods: A random sample of incident cases of patients with schizophrenia with an age of onset after age 40 (LOS) and age 60 (VLOS) was selected from a psychiatric case register covering all psychiatric services within the city of The Hague, The Netherlands, between 1997 and 2012. Schizophrenia diagnosis and age of onset were audited by systematic review of all case notes up to 2019. Patients who were initially misclassified as LOS/VLOS in the registry but, after this audit, had an age of onset before age 40, were classified as EOS. The risk of developing dementia was compared between the groups using a logistic regression model with correction for age, gender, and stroke as possible confounders. Results: Our study groups consisted of 74 patients with EOS, 81 with LOS, and 25 with VLOS. Dementia was present in 10 patients at follow-up, 7 out of 106 (6.6%) patients in the combined LOS and VLOS groups, and 3 out of 74 (4.1%) patients in the EOS group. However, after correction for confounders, logistic regression showed no statistically significant higher change in the development of dementia in LOS nor VLOS patients compared to EOS patients, nor with age of onset as a continuous variable. Conclusions: Patients with LOS and VLOS are not at a higher risk of developing dementia compared to patients with EOS. These results do not support the hypothesis that LOS and especially VLOS, are precursors of dementia. Full article

Background: Approximately 20–30% of ultra-high risk (UHR) individuals transition to psychosis within 2–3 years. Neurobiological markers predicting conversion remain critical for precision prevention strategies. Objective: To systematically identify and evaluate structural and functional neuroimaging biomarkers at UHR baseline that predict subsequent conversion to psychosis. Methods: Following PRISMA 2020 guidelines, we searched five databases from January 2000 to February 2025. Two independent reviewers screened studies and assessed quality using the Newcastle–Ottawa Scale. Eligible studies examined baseline neuroimaging measures (structural MRI, functional MRI, diffusion tensor imaging, magnetic resonance spectroscopy) as predictors of psychosis conversion in UHR cohorts. Results: Twenty-five studies comprising 2436 UHR individuals (627 converters, 25.7%) were included (80.0% high quality). Reduced baseline gray matter volume in medial temporal structures (hippocampus: Cohen’s d = −0.45 to −0.68; parahippocampal gyrus: d = −0.52 to −0.71) and prefrontal cortex (d = −0.41 to −0.68) consistently predicted conversion. Progressive gray matter loss in superior temporal gyrus distinguished converters (d = −0.72). Reduced prefrontal–temporal functional connectivity predicted conversion (AUC = 0.73–0.82). Compromised white matter integrity in uncinate fasciculus (fractional anisotropy: d = −0.47 to −0.71) and superior longitudinal fasciculus predicted transition. Elevated striatal glutamate predicted conversion (d = 0.52–0.76). Thalamocortical dysconnectivity showed large effects (Hedges’ g = 0.66–0.88). Multimodal imaging models achieved 78–85% classification accuracy. Conclusions: Neuroimaging biomarkers, particularly medial temporal and prefrontal structural alterations, functional dysconnectivity, and white matter abnormalities, demonstrate moderate-to-large effect sizes in predicting UHR conversion. Multimodal approaches combining structural, functional, and neurochemical measures show promise for individualized risk prediction and early intervention targeting in precision prevention strategies. Full article