Search Results (46)

Schizophrenia (SCZ) is a debilitating disorder with substantial societal and economic impacts. The clinical high risk of psychosis (CHR-P) state generally precedes the onset of SCZ, offering a window for early intervention. However, treatment guidelines for CHR-P individuals remain contentious, particularly regarding antipsychotic (AP) medications. Although several studies have examined the effects of APs on reducing the risk of conversion to psychosis, the novelty of this narrative review lies in its focus on differentiating APs’ effects on positive and negative symptoms, as well as cognitive functioning, in CHR-P individuals. Evidence suggests that APs may be cautiously recommended for attenuated positive symptoms to stabilize individuals for psychological interventions, but their use in treating negative symptoms is generally discouraged due to limited efficacy and potential side effects. Similarly, the effects of APs on cognitive abilities remain underexplored, with results indicating a lack of significant neurocognitive outcomes. In conclusion, APs’ use in CHR-P patients requires careful consideration due to limited evidence and potential adverse effects. Future research should focus on individual symptom domains and treatment modalities to optimize outcomes in this critical population. Until then, a cautious approach emphasizing non-pharmacological interventions is advisable. Full article

Background: Anhedonia, defined as the diminished capacity to experience pleasure, represents a core negative symptom in first-episode psychosis (FEP) with profound implications for functional outcomes and long-term prognosis. Despite its clinical significance, comprehensive understanding of anhedonia prevalence, underlying mechanisms, and optimal intervention strategies in early psychosis remains limited. Objectives: To systematically examine the prevalence and characteristics of anhedonia in FEP patients, explore neurobiological mechanisms, identify clinical correlates and predictive factors, and evaluate intervention efficacy. Methods: Following PRISMA 2020 guidelines, we conducted comprehensive searches across PubMed, Embase, PsycINFO, and Web of Science databases from January 1990 to June 2025. Studies examining anhedonia and negative symptoms in FEP patients (≤24 months from onset) using validated assessment instruments were included. Quality assessment was performed using appropriate tools for study design. Results: Twenty-one studies comprising 3847 FEP patients met inclusion criteria. Anhedonia prevalence ranged from 30% at 10-year follow-up to 53% during acute phases, demonstrating persistent motivational deficits across illness trajectory. Factor analytic studies consistently supported five-factor negative symptom models with anhedonia as a discrete dimension. Neuroimaging investigations revealed consistent alterations in reward processing circuits, including ventral striatum hypofunction and altered network connectivity patterns. Social anhedonia demonstrated stronger associations with functional outcomes compared to other domains. Epigenetic mechanisms involving oxytocin receptor methylation showed gender-specific associations with anhedonia severity. Conventional antipsychotic treatments showed limited efficacy for anhedonia improvement, while targeted psychosocial interventions demonstrated preliminary promise. Conclusions: Anhedonia showed high prevalence (30–53%) across FEP populations with substantial clinical burden (13-fold increased odds vs. general population). Meta-analysis revealed large effect sizes for anhedonia severity in FEP vs. controls (d = 0.83) and strong negative correlations with functional outcomes (r =·−0.82). Neuroimaging demonstrated consistent ventral striatum dysfunction and altered network connectivity. Social anhedonia emerged as the strongest predictor of functional outcomes, with independent suicide risk associations. Conventional antipsychotics showed limited efficacy, while behavioral activation approaches demonstrated preliminary promise. These findings support anhedonia as a distinct treatment target requiring specialized assessment and intervention protocols in early psychosis care. Full article

Aberrant salience, defined as the inappropriate attribution of significance to neutral stimuli, is increasingly recognized as a critical mechanism in the onset of psychotic disorders. In young individuals at ultra-high risk (UHR) for psychosis, abnormal salience processing may serve as a precursor to full-blown psychotic symptoms, contributing to distorted perceptions and the onset of psychotic ideation. This review examines current literature on aberrant salience among UHR youth, exploring its neurobiological, psychological, and behavioral dimensions. Through a comprehensive analysis of studies involving neuroimaging, cognitive assessments, and symptomatology, we assess the consistency of findings across diverse methodologies. Additionally, we evaluate factors contributing to aberrant salience, including neurochemical imbalances, dysregulation in dopamine pathways, and environmental stressors, which may jointly increase psychosis vulnerability. Identifying aberrant salience as a measurable trait in UHR populations could facilitate earlier identification and targeted interventions. Implications for clinical practice are discussed, highlighting the need for specialized therapeutic approaches that address cognitive and emotional dysregulation in salience attribution. Recent research underscores the importance of aberrant salience in early psychosis research and advocates for further studies on intervention strategies to mitigate progression to psychosis among UHR individuals. Full article

Background: Psychosis is one of the leading causes of disability worldwide. Individuals with early-onset psychosis (EOP) tend to experience a worse prognosis and shorter life expectancy. The etiology of EOP remains unclear, but epigenetic mechanisms are known to serve as the interface between environmental exposures and biological processes to better understand its etiology. Objectives: We characterized the sociodemographic and clinical characteristics, as well as genome-wide epigenetic markers, in Mexican patients with EOP. Methods: We estimated epigenetic age, performed an epigenome-wide association study, and finally developed an epigenetic risk score (MRS) to predict manifestations of psychosis. Results: We found that patients with EOP have a higher epigenetic age using Wu’s clock (p = 0.015). Moreover, accelerated epigenetic age was correlated with chronological age (PedBE clock, p = 0.046), global functioning (Wu’s clock, p = 0.027), and psychiatric admissions (DNAmTL, p = 0.038). In addition, we observed that a reduction in years of schooling is associated with an increase on epigenetic age (Levine’s clock, β = 5.07, p = 0.001). In our epigenome-wide association study, we identified eight CpGs associated with EOP. Noteworthy, a psychosis-methylation risk score (EOP-MRS) was associated with panic disorder (β = 1.36, p = 0.03), as well as auditory (β = 1.28, p = 0.04) and visual (β = 1.22, p = 0.04) hallucinations. Conclusions: Years of education have an impact on epigenetic age. Additionally, our study suggests associations of DNA methylation with EOP. Finally, we developed an MRS that associates clinical manifestations of psychosis. Full article

Background: Cognitive impairment is a common feature of schizophrenia spectrum disorders and has been associated with functional disruption preceding the onset of psychosis. Understanding how cognitive deficits interact with clinical symptoms and functioning in early psychosis remains challenging. In this study, we aim to investigate whether a distinct “cognitive signature” characterizes functional disruption at the onset of psychosis. Material and Methods: Clinical, cognitive, and functional data were collected from 101 first episode psychosis patients at their first hospitalization. Stepwise regression models were used to identify predictors of global functioning and symptom severity at the time of onset, as well as diagnostic outcomes at discharge. Path analysis was used to explore the relationship among symptom severity, cognition, and functional outcomes. Results: Deficits in visual memory were selectively predictive of lower functioning and higher global symptom severity at the time of psychosis onset. Reduced visual-spatial abilities were also associated with unemployment at the time preceding hospitalization and predicted a non-affective schizophrenia spectrum diagnosis at discharge. Path analysis found that visual memory fully mediated the relationship between negative symptoms and level of functioning. Conclusions: Impairment in visual cognition seems to be uniquely associated with functional impairment and global symptom severity at the onset of psychosis and to mediate the relationship between negative symptoms and functioning. The results might indicate a primary relevance of visual cognitive aspects in marking functional disruption and symptom exacerbation at psychosis onset. This might have implications for early detection and inform treatment plans. Full article

Background: Psychosis, particularly schizophrenia (SZ), is influenced by genetic and environmental factors. The neurodevelopmental hypothesis suggests that genetic factors affect neuronal circuit connectivity during perinatal periods, hence causing the onset of the diseases. In this study, we performed a genome-wide association study (GWAS) in a sample of the first episode of psychosis (FEP). Methods: A sample of 147 individuals diagnosed with non-affective psychosis and 102 controls were recruited and assessed. After venous blood and DNA extraction, the samples were genotyped. Genetic data underwent quality controls, genotype imputation, and a case-control genome-wide association study (GWAS). After the GWAS, results were investigated using an in silico functional mapping and annotation approach. Results: Our GWAS showed the association of 27 variants across 13 chromosomes at genome-wide significance (p < 1 × 10⁻⁷) and a total of 1976 candidate variants across 188 genes at suggestive significance (p < 1 × 10⁻⁵), mostly mapping in non-coding or intergenic regions. Gene-based tests reported the association of the SUFU (p = 4.8 × 10⁻⁷) and NCAN (p = 1.6 × 10⁻⁵) genes. Gene-sets enrichment analyses showed associations in the early stages of life, spanning from 12 to 24 post-conception weeks (p < 1.4 × 10⁻³) and in the late prenatal period (p = 1.4 × 10⁻³), in favor of the neurodevelopmental hypothesis. Moreover, several matches with the GWAS Catalog reported associations with strictly related traits, such as SZ, as well as with autism spectrum disorder, which shares some genetic overlap, and risk factors, such as neuroticism and alcohol dependence. Conclusions: The resulting genetic associations and the consequent functional analysis displayed common genetic liability between the non-affective psychosis, related traits, and risk factors. In sum, our investigation provided novel hints supporting the neurodevelopmental hypothesis in SZ and—in general—in non-affective psychoses. Full article

Background/Objectives: Schizophrenia is a severe psychiatric disorder, with onset typically occurring in late adolescence or early adulthood. Early identification of psychotic symptoms, especially those occurring before age 12, has been linked to better long-term outcomes. This study aims to assess the presence of psychotic spectrum symptoms before the age of 12 in adult schizophrenia patients and explore their clinical implications for early detection and intervention. Methods: This retrospective, observational study included 170 adult patients diagnosed with schizophrenia, confirmed by the SCID-5. Patients were recruited from the University of Siena Medical Center and completed the modified lifetime version of the Psychotic Spectrum Self-Report (PSY-SR) questionnaire, which assessed the onset of specific psychotic symptoms before and after age 12. Symptom severity was evaluated using the Brief Psychiatric Rating Scale (BPRS) and the Clinical Global Impression Scale (CGI). This study also examined the impact of the duration of untreated psychosis (DUP) on symptom severity. Results: In our cohort, 21% of patients exhibited prodromal symptoms before age 12 (95% CI: 15–27%). Prodromal symptoms were linked to a 9.53-point increase in the BPRS scores (p = 0.0478) and a 0.50-point increase in the CGI scores (p = 0.0347). The age of symptom onset negatively correlated with the BPRS scores (p < 0.0001), with each year of delay resulting in a 1.33-point decrease. The DUP correlated significantly with both the BPRS (ρ = 0.97) and CGI scores (ρ = 0.94). The multivariate analysis revealed that a longer DUP was associated with significant increases in both scores: a 27.16-point increase in the BPRS (p < 0.0001) for a moderate DUP and a 67.51-point increase (p < 0.0001) for a severe DUP. The CGI scores increased by 1.11 points with a moderate DUP and 3.17 points with a severe DUP (p < 0.0001). However, the interaction between the DUP and prodromal symptoms at age 12 was not significant, indicating similar impacts of the DUP regardless of early symptom onset. Conclusions: The results support the critical importance of early detection and intervention in schizophrenia. Early psychotic spectrum symptoms, particularly those occurring before age 12, are significant predictors of later severity and functional impairment. This study underscores the value of screening tools like the PSY-SR for identifying prodromal symptoms and facilitating timely intervention. Our findings highlight the need for the early identification of psychotic symptoms, particularly in at-risk populations, to improve long-term outcomes. Intervening before the onset of full-blown psychosis may reduce the severity of schizophrenia and promote better clinical outcomes. 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

Background: Individuals with severe mental illness live, on average, up to 30 years less than the general population, with cardiovascular disease being the leading cause of death. Metabolic syndrome (MetS) plays a significant role in this, making it crucial to manage this issue in individuals with psychosis at the onset of the illness. The approach to managing this issue has evolved from a focus on calorie counting to a deeper understanding of hormone function, particularly the role of insulin resistance in MetS. Therefore, incorporating this perspective into mental health nursing consultations with individuals experiencing psychosis is of great interest. Methods: In accordance with the SPIRIT guidelines, an open randomized clinical trial is proposed, involving patients from a first-episode psychosis program. Results: The primary outcome will be significant weight loss (≥5%). Secondary outcomes will include changes in metabolic parameters, psychopathological status, quality of life, and physical activity. Participants will be assigned to two groups: one group will attend a series of six previously manualized nursing consultations, while the other will continue with their usual treatment. Results will be evaluated at six months and one year. Conclusions: This study will determine whether a mental health nursing consultation based on the carbohydrate–insulin model of obesity is effective in reducing weight and the risk of MetS in individuals with early-onset psychosis. This study was retrospectively registered on Clinical Trials—NCT06650943. Full article

Studies of the composition of the gut microbiome have consistently shown that psychiatric disorders such as schizophrenia are associated with gut dysbiosis. However, research focusing on adolescents with early-onset psychosis remains limited. This study aimed to characterize the microbial communities and their potential metabolic functions in these populations. We identified that genera Desulfovibrionaceae_Incertae_Sedis, Paraprevotella, and several genera from the Oscillospiraceae family were significantly more abundant in patients with schizophrenia compared to non-psychotic individuals, while Dorea showed decreased levels in schizophrenia patients. Furthermore, patients with early-onset psychosis demonstrated a significant reduction in Staphylococcus abundance. Additionally, we observed an increase in Prevotellaceae Leyella and Prevotellaceae Incertae Sedis in patients receiving atypical antipsychotic treatment, along with a rise in the genus Weissella among those treated with sertraline. Conversely, patients on valproate treatment exhibited decreased levels of Desulfovibrionaceae Incertae Sedis, while showing increased levels of Kandleria and Howardella. Functional prediction analysis using PICRUSt2 revealed significant differences in the expression of key enzymes associated with fatty acid metabolism. Gene orthology analysis identified 10 differentially expressed genes in the early-onset psychosis and schizophrenia groups. Our findings underscore the importance of considering dietary factors, pharmacological treatments, and microbial composition in understanding the gut–brain axis in psychiatric disorders. 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

Accelerated brain aging is a possible mechanism of pathology in schizophrenia. Advances in MRI-based brain development algorithms allow for the calculation of predicted brain age (PBA) for individuals. Here, we assessed PBA in 70 first-episode schizophrenia-spectrum individuals (FESz) and 76 matched healthy neurotypical comparison individuals (HC) to determine if FESz showed advanced aging proximal to psychosis onset and whether PBA was associated with neurocognitive, social functioning, or symptom severity measures. PBA was calculated with BrainAgeR (v2.1) from T1-weighted MR scans. There were no differences in the PBAs between groups. After controlling for actual age, a “younger” PBA was associated with higher vocabulary scores among all individuals, while an “older” PBA was associated with more severe negative symptom “Inexpressivity” component scores among FESz. Female participants in both groups had an elevated PBA relative to male participants. These results suggest that a relatively younger brain age is associated with a better semantic memory performance. There is no evidence for accelerated aging in FESz with a late adolescent/early adult onset. Despite a normative PBA, FESz with a greater residual PBA showed impairments in a cluster of negative symptoms, which may indicate some underlying age-related pathology proximal to psychosis onset. Although a period of accelerated aging cannot be ruled out with disease course, it does not occur at the time of the first episode. Full article

While both Attention deficit hyperactivity disorder (ADHD) and schizophrenia are considered to have neurodevelopmental origins with associated impairments in executive functioning, there is a paucity of clinical guidelines pertaining specifically to this comorbidity. We sought to summarize the existing literature on ADHD in early psychosis patients, focusing on issues that would be most relevant to clinical practice. For this narrative review, we completed a search on PubMed and PsycINFO with 22 papers meeting criteria for review. Overall, it appears that a diagnosis of ADHD in childhood increases the risk of the subsequent development of a primary psychotic disorder. This risk may be modified by higher rates of substance use and could be related to shared premorbid risk factors for both conditions, such as obstetrical complications. Stimulant use has been associated with the onset of psychotic symptoms in some individuals, but it is unclear whether certain subgroups are more susceptible. Despite the fact that these two conditions co-occur relatively frequently, there is currently a lack of objective diagnostic tests for ADHD specific to populations with primary psychotic disorders, and a paucity of evidence on whether stimulants are effective for ADHD symptoms in this sub-group. Future research is warranted to investigate whether stimulant treatment confers any additional risks for symptom exacerbation in individuals with primary psychotic disorders taking antipsychotic maintenance treatment. Full article

Background: Psychosis is defined as a series of symptoms that impair the mind and lead to a kind of loss of reference to reality. Development of psychosis is usually preceded by the appearance of prodromal symptoms. Numerous attempts have been made to find out how psychoactive substances can influence the onset and development of psychotic disorders, but to date there are no studies that show a link between the onset of prodromal symptoms and the use of psychoactive substances. Methods: A survey consisting of epidemiological and demographic questions, the Drug Use Disorders Identification Test (DUDIT), and the Prodromal Questionnaire Brief Version (PQ-B) was conducted on social media among users of illegal psychoactive substances, covering 703 study participants. Results: A total of 39.8% of the respondents had been treated by a psychiatrist, and the most popular drugs used by respondents in their lifetime were tetrahydrocannabinol-containing products, MDMA, amphetamines, and LSD. A significant correlation was found between the DUDIT and the PQ-B values. Conclusions: Intensity of psychoactive substance use correlated positively with the risk of appearance and intensity of prodromal symptoms of psychosis. Early exposure to psychoactive substances increased the risk of heavy substance use in adulthood and led to more frequent prodromal states. Full article

First-episode psychosis (FEP) typically marks the onset of severe psychiatric disorders and represents a critical period in the field of mental health. The early diagnosis of this condition is essential for timely intervention and improved clinical outcomes. In this study, the classification of FEP was investigated using the analysis of electroencephalography (EEG) signals and circulant spectrum analysis (ciSSA) sub-band signals. FEP poses a significant diagnostic challenge in the realm of mental health, and it is aimed at introducing a novel and effective approach for early diagnosis. To achieve this, the LASSO method was utilized to select the most significant features derived from entropy, frequency, and statistical-based characteristics obtained from ciSSA sub-band signals, as well as their hybrid combinations. Subsequently, a high-performance classification model has been developed using machine learning techniques, including ensemble, support vector machine (SVM), and artificial neural network (ANN) methods. The results of this study demonstrated that the hybrid features extracted from EEG signals’ ciSSA sub-bands, in combination with the SVM method, achieved a high level of performance, with an area under curve (AUC) of 0.9893, an accuracy of 96.23%, a sensitivity of 0.966, a specificity of 0.956, a precision of 0.9667, and an F1 score of 0.9666. This has revealed the effectiveness of the ciSSA-based method for classifying FEP from EEG signals. Full article