Search Results (59)

Substance-induced psychosis is a recognized clinical entity, commonly linked to cannabinoids, stimulants, hallucinogens, alcohol, and polysubstance use. These agents may provoke transient or persistent psychotic symptoms during intoxication or withdrawal. Opioids, however, constitute a noteworthy exception: psychosis is rarely observed during opioid intoxication, and emerging data suggest that opioid agonists might even exert antipsychotic-like effects. This article examines the paradoxical interaction between opioids and psychosis, with attention to clinical reports of psychotic symptoms arising following abrupt discontinuation of methadone or buprenorphine. In numerous cases, symptoms resolved swiftly after reintroduction of the opioid agonist, implying a neuromodulatory role. Opioids, unlike other substances of abuse, seem to lack intrinsic psychotogenic effects and may influence dopaminergic activity via kappa-opioid receptor antagonism and endorphinergic mechanisms. This challenges standard models of substance-induced psychosis and calls for a refined understanding of opioid pharmacodynamics in psychiatric contexts. In psychotic presentations among polysubstance users who also use opioids, restoring opioid agonist therapy should be prioritized, with antipsychotics reserved as second-line options—preferably agents with favorable receptor profiles. Where opioids are not involved, antipsychotics remain first-line, but should be applied judiciously, with efforts to taper when clinically appropriate. Full article

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: 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

Background/Objective: To address the growing demand for mental health services, Nova Scotia Health introduced the Rapid Access Stabilization Program (RASP) through its Mental Health and Addictions Program (MHAP) in April 2023. RASP is designed to help reduce long wait times, frequent emergency department visits, and admissions to provide early intervention for individuals experiencing mental health problems. The RASP focuses on rapid access and early mental health intervention, aiming to prevent the worsening of patients’ symptoms, improve access to psychiatric care, and reduce service pressures on programs like the Community Mental Health Program (CMHP), which provide more extended, ongoing mental health support. This study compared participants’ sociodemographic and clinical profiles in the RASP and the CMHP. Methods: Data were collected from 1392 participants accessing mental health support either through the RASP or CMHP. A comparative analysis of sociodemographic factors (e.g., age, education, and income) and clinical characteristics (e.g., depression, anxiety, resilience, and substance use) was conducted. Chi-square tests and independent sample t-tests were used to evaluate the mean differences between the groups. Results: Significant sociodemographic and clinical differences emerged between the RASP and CMHP participants. The RASP group was older (M = 40.10 vs. 34.52 years) and more socioeconomically stable, with higher rates of employment (55.3% vs. 47.9%) and homeownership (36.5% vs. 17.7%). In contrast, the CMHP group had higher unemployment (25.7% vs. 16.5%) and lower income levels, with 47.5% earning <CAD 29,590 compared to 30.3% in the RASP group. Clinical profiles differed markedly: depression was more prevalent in the RASP (48.2% vs. 19.3%), whereas the CMHP had higher rates of psychosis (10.6% vs. 2.5%) and substance use disorder (7.8% vs. 1.9%). The RASP participants exhibited higher anxiety (GAD-7: M = 14.17 vs. 11.81) and depression symptoms (PHQ-9: M = 16.62 vs. 14.20) but lower resilience (BRS: M = 2.47 vs. 2.77). The CMHP participants had more adverse childhood experiences (ACE: M = 3.92 vs. 3.16) and lower suicidal intent (81.4% vs. 99.4% had no intention to act). Conclusions: The findings highlighted the unique profiles between the RASP and CMHP participants, suggesting the need for program-specific interventions. While the CMHP participants may benefit from integrated social support and trauma-informed care, the RASP participants may require cognitive behavioral therapy and resilience-building interventions. Tailoring mental health services to meet these unique needs could enhance program effectiveness and patient outcomes across both groups. 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

Background: Synthetic cathinones and cannabinoids have emerged as significant public health concerns, particularly in pediatric populations. Marketed under deceptive names such as “bath salts” and “K2/Spice”, these substances pose unique challenges due to their accessibility, potency, and unpredictable effects. This narrative review synthesizes evidence on the toxicological effects of synthetic cathinones and cannabinoids in pediatric patients, emphasizing clinical presentations, management challenges, and public health implications. Methods: A structured narrative review was conducted using PubMed and Scopus databases to identify peer-reviewed studies published between January 2010 and September 2024. The selected articles focus on neuropsychiatric, systemic, and management outcomes associated with these substances in individuals aged 0–18 years. Results: Five studies demonstrate that synthetic cathinones frequently cause seizures, sympathomimetic toxidrome (tachycardia, hypertension), and neuropsychiatric effects like paranoia and catatonia. Seven studies show synthetic cannabinoids induce psychosis, respiratory depression requiring ventilation in 12% of cases, and cardiovascular complications like myocardial ischemia. One study highlighted severe outcomes in pediatric accidental exposures, emphasizing the unpredictable and life-threatening effects of these substances, often exacerbated by co-ingestion with alcohol or THC. Conclusions: Pediatric exposure to synthetic cathinones and cannabinoids results in severe and unpredictable toxicological effects, necessitating tailored clinical management strategies and enhanced diagnostic capabilities. Public health measures, including stringent regulatory controls, targeted education initiatives, and robust surveillance systems, are critical to mitigating these risks. A multidisciplinary approach is essential to safeguard vulnerable pediatric populations from the escalating dangers posed by synthetic drugs, and future research must address the long-term impacts and mechanisms of toxicity. Full article

The perinatal period, due to the many physical, psychological, and social changes in future mothers, may represent a critical phase with an increased risk for mental health. Postpartum depression (PPD) is one of the main syndromes that affect around 17 percent of women after pregnancy and in the first months of motherhood. This systematic review, following PRISMA guidelines, aimed to identify the main pre-partum psychiatric risk factors that may influence the occurrence and diagnosis of PPD with a focus on the antenatal and clinical history of depression, bipolar disorders, obsessive–compulsive disorder, and psychosis. From the search in main scientific databases (Web of Science, Pubmed, Psychinfo, and Scopus), 37 articles were included for the critical evaluation. The studies showed that antenatal depression and depressive episodes during pregnancy represent higher risk factors for PPD. Also, a clinical history of major depression, especially if associated with other risk factors (such as poor demographic or social conditions) increases the risk for PPD. From the systematic analysis emerged a paucity of studies considering the other psychiatric syndromes that should be overcome. PPD represents a multisystemic syndrome involving all the aspects of a mother’s life as well as affecting children’s development; for this reason, exploring the role of mental health risk factors for PPD onset, progression, and prognosis is relevant, from a clinical point of view, to find the best way to promote the mother’s psychological well-being from the antenatal period. 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

Biased agonists of G-protein-coupled receptors (GPCRs) have emerged as promising selective modulators of signaling pathways by offering therapeutic advantages over unbiased agonists to minimize side effects. The dopamine D3 receptor (D3R), a pivotal GPCR in the central nervous system, has gained significant attention as a therapeutic target for neurological diseases, including Parkinson’s disease (PD), addiction, psychosis, depression, and anxiety. We have recently designed and tested SK609, a G-protein biased D3R selective agonist, and demonstrated its efficacy in reducing motor impairment and improving cognitive effects in a rodent model of PD. The molecular mechanism by which SK609 recruits G-protein but not β-arrestin pathways is poorly understood. Utilizing all-atom molecular dynamics simulations, we investigated the distinct conformational dynamics imparted by SK609 and the reference unbiased agonist Pramipexole (PRX). Results from these studies show that the flexibility of transmembrane 3 is key to unbiased signaling, with a ~30° and ~17° shift in tilt angle in the D3R-Gi and D3R-βarrestin2 complexes, respectively. Additionally, untargeted phosphoproteomics analysis reveals unique phosphorylation sites by SK609 and PRX in D3R. These results suggest that SK609 induces conformational changes and unique phosphorylation patterns that promote interactions with G-proteins and are not conducive for β-arrestin2 recruitment and signaling. 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

Background: Chemsex has been defined as the deliberate use of drugs for prolonged sexual intercourse between gay and bisexual men and other men who have sex with men (MSM). Drugs associated with chemsex can trigger mental health problems such as anxiety, depression, risk of psychosis and suicidal ideation, social isolation, stigmatization, and even loss of impulse control and lack of coping strategies. Currently, the increase in illicit drugs in a sexual context is considered an outbreak of a public health emergency. Objective: The aim of this study is the construction and validation of the Chem-Sex Inventory (CSI), a new scale to assess the mental health risk of chemsex behaviors. Methods: A cross-sectional design was conducted to study 563 participants. Data were collected through an online questionnaire between January and April 2023, and the construct validity of the CSI was assessed through exploratory and confirmatory factor analysis. Results: The sample was, on average, 36 years old (SD: ±9.2). The majority of gender identity was cisgender (97.7%). A factor structure was found that can be summarized in four dimensions: emotional instability, risk of psychosis, altered body perception, and risk of suicide. The confirmatory factor analysis (CFA) presents adequate reliability values, with a Cronbach’s alpha above 0.87 for all dimensions and a McDonald’s omega above 0.88 with a good fit of the 42 items. Conclusions: Our study has shown that the Chem-Sex Inventory (CSI) scale has factorial validity and could be used in clinical practice and research to measure the behavioral contribution of the chemsex phenomenon in MSM. Full article

Neurodegenerative disease is a major global health problem with 150 million people predicted to have dementia by 2050. Genetic factors, environmental factors, demographics, and some diseases have been associated with dementia. In addition to associations between diseases such as hypertension and cerebrovascular disease and dementia, emerging findings associate some psychiatric disorders with incident dementia. Because of the high and increasing global prevalence of dementia and the high worldwide prevalence of psychiatric disorders, the primary objective of this narrative review was to evaluate published findings that evaluate the association between bipolar disorder, depression, anxiety, post-traumatic stress disorder, obsessive–compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorder, schizophrenia and other psychosis syndromes, and personality disorders and personality traits and incident dementia. Here, we highlight findings indicating possible associations between these psychiatric disorders and subsequent dementia and suggest that some psychiatric disorders may be risk factors for incident dementia. Further research, including more large longitudinal studies and additional meta-analyses, however, is needed to better characterize the associations between psychiatric disorders and incident dementia, to identify possible mechanisms for these putative associations, and to identify risk factors within psychiatric disorders that predispose some people with a psychiatric disorder but not others to subsequent dementia. Additional important questions concern how the treatment of psychiatric disorders might affect the risk of incident dementia. Full article

Clinical High Risk for psychosis (CHR) refers to a phase of heightened risk for developing overt psychosis. CHR often emerges during adolescence or early adulthood. CHR has been identified as a group to target for intervention, with the hope that early intervention can both stave off prolonged suffering and intervene before mental health challenges become part of an individual’s identity. However, there are few treatment modalities that can address some of the specific needs of CHR. Metacognitive Reflection and Insight Therapy (MERIT) is an integrative psychotherapy that can be applied to the CHR population. MERIT offers unique advantages to working with the CHR population as it aims to improve self-direction and recovery through stimulation of metacognitive capacity, a phenomenon that has been associated with recovery. This paper explores unique aspects of the CHR population and how MERIT can address barriers to recovery for individuals experiencing psychosis-like symptoms. Several case examples and a clinical vignette using MERIT to support patients with CHR are offered to exemplify this approach. MERIT offers a way to assist persons with CHR to address barriers to their personal recovery and to develop nuanced understandings of ways to master challenges. Full article