Search Results (615)

Background/Objectives: Adolescent psychiatric inpatient units play a critical role in the management of severe psychiatric disorders and suicide risk. However, limited evidence exists regarding the clinical and familial factors that simultaneously influence suicidal ideation and treatment outcomes in hospitalized adolescents. This study aimed to identify demographic, diagnostic, and clinical predictors of suicidal ideation and clinical improvement among adolescents hospitalized in a tertiary child and adolescent psychiatry inpatient unit. Methods: This retrospective observational study included 75 adolescents aged 12–18 years who were hospitalized in a tertiary child and adolescent psychiatry inpatient unit between November 2023 and June 2025. Sociodemographic and clinical characteristics were obtained from medical records. Clinical improvement was evaluated using the Clinical Global Impression–Improvement (CGI-I) scale. Group comparisons were conducted using chi-square or Fisher’s exact tests for categorical variables and the Mann–Whitney U test for continuous variables. Multivariate logistic regression analyses were performed to determine independent predictors of suicidal ideation and clinical improvement. Results: Clinical improvement was evaluated in the full sample of adolescents (n = 75), and longer length of stay was independently associated with clinical improvement during hospitalization. Among adolescents admitted with suicidal ideation (n = 45), major depressive disorder, previous suicide attempt, irritability at admission, and fewer siblings were identified as independent predictors of suicidal ideation. In addition, female adolescents had higher rates of suicide attempts and non-suicidal self-injury, whereas psychotic disorders were more common among male adolescents. Conclusions: Suicidal ideation in hospitalized adolescents is strongly associated with affective pathology and prior suicidal behavior. Longer inpatient treatment duration appears to facilitate clinical improvement. These findings highlight the importance of early suicide risk stratification and adequate treatment duration in adolescent psychiatric inpatient care. Full article

The endocannabinoid system (ECS) is a fundamental regulator of brain and body homeostasis, integrating neural, immune, and stress-related signaling pathways. Dysregulation of ECS components, including cannabinoid receptors (CB1 and CB2), endocannabinoids such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and their metabolic enzymes (FAAH and MAGL), has been increasingly implicated in the pathophysiology of neuropsychiatric disorders, including mood, anxiety, psychotic, stress-related, and eating disorders. Altered endocannabinoid signaling contributes to maladaptive stress responses, emotional dysregulation, and impaired synaptic plasticity, highlighting the role of the ECS as a core integrative mechanism. Therapeutic strategies targeting ECS, particularly through FAAH inhibition and the use of plant-derived cannabinoids, such as cannabidiol (CBD), show promise in restoring endogenous homeostasis while minimizing the adverse cognitive and affective effects associated with direct CB1 activation. ECS function and treatment response are further influenced by genetic polymorphisms in CNR1, CNR2, FAAH, and MGLL, as well as epigenetic mechanisms, including DNA methylation, histone modifications, and microRNA regulation. Despite these advances, clinical translation remains limited by interindividual variability, the complexity of ECS interactions, and the relatively small size of existing clinical studies. Future research integrating longitudinal clinical trials with multi-omics approaches is essential to support the development of evidence-based, personalized interventions. Overall, understanding ECS mechanisms and dysregulation provides a valuable framework for the development of targeted therapies in neuropsychiatric disorders. 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

Introduction: Antipsychotic (AP) medications are widely prescribed beyond psychotic disorders, yet their long-term safety profile regarding breast cancer (BC) risk remains uncertain. Methods: We conducted a systematic review and meta-analysis of observational studies evaluating the association between AP exposure and incident BC. Eligible studies reported adjusted odds ratios (ORs) with 95% confidence intervals for any AP, prolactin-increasing antipsychotics (PIAPs), or prolactin-sparing antipsychotics (PSAPs). Study quality was assessed using the modified Newcastle-Ottawa Scale (mNOS), and certainty of evidence was graded with the GRADE framework. Random-effect models were used to pool effect estimates by exposure category, duration, and cumulative Defined Daily Dose (DDD). Results: Nine high-quality observational studies encompassing 108 effect estimates were included. Most studies achieved mNOS scores of 9, yet GRADE certainty ranged from very low to moderate, with the overall body of evidence graded as low certainty due primarily to residual confounding. Any AP exposure was associated with a modestly increased BC risk, particularly with long-term use: use for >5 years yielded pooled ORs around 1.5–1.6, while short-to-medium duration (1–5 years) showed smaller increases (pooled ORs in the range 1.2–1.3). For PIAPs, both longer duration (>5 years) and higher cumulative exposure (>1000–2000 DDDs) were consistently associated with ORs/HRs in the 1.3–1.6 range, suggesting a possible dose–response pattern. Histological analyses indicated stronger associations for ductal than lobular BC, and elevated risks were observed across age strata, including women aged <55 and ≥70 years. Discussion: This meta-analysis suggests that chronic exposure to prolactin-increasing antipsychotics is associated with a potentially clinically relevant increase in BC risk, whereas prolactin-sparing agents do not show a clear signal of harm. However, the certainty of this association is limited by inconsistently measured confounders and by the observational nature of the data. These findings support a cautious, individualized approach in which clinicians preferentially consider PSAPs when appropriate, discuss BC risk as part of shared decision-making, and integrate tailored screening strategies for women requiring long-term PIAP therapy. Further high-quality pharmacoepidemiologic studies with better confounder control and mechanistic integration are needed to refine risk estimates and inform preventive neuropsychopharmacology. Full article

Depression is one of the most prevalent psychiatric disorders worldwide, with a steadily increasing incidence and complex, multifactorial pathophysiology. Beyond classical neurochemical mechanisms, growing evidence points to the role of systemic low-grade inflammation and immuno-metabolic disturbances in its development. Gut microbiota dysbiosis has emerged as a key factor linking metabolic, immune, and neuroendocrine pathways, potentially exacerbating neuroinflammation and contributing to the onset and progression of depressive symptoms. Immune activation, which is a result of gut dysbiosis, may play a crucial role in the pathogenesis of immuno-metabolic depression. Thyroid dysfunction appears to be an important, yet insufficiently understood component of this network. Thyroid hormones play a crucial role in regulating metabolism, immune responses, and central nervous system function. Alterations in thyroid function, even within subclinical ranges, have been associated with mood disturbances and may share common inflammatory and metabolic pathways with depression. Furthermore, emerging data suggest that gut microbiota may influence thyroid hormone metabolism, including deiodinase activity, linking dysbiosis with thyroid axis dysregulation. Despite these insights, the integrated interactions between thyroid function, gut microbiota, metabolic syndrome, and inflammation in depression remain largely unexplored. This review explores current evidence to highlight gaps in existing research and synthesizes current knowledge, aiming to clarify mechanisms underlying immuno-metabolic depression. Understanding these relationships may provide a rationale for redefining depression as an immuno-metabolic disorder and support the development of more integrative therapeutic strategies targeting not only the brain, but also the gut-thyroid axis. Full article

Mild behavioral impairment (MBI) is a clinical syndrome characterized by the late-life onset and persistence of neuropsychiatric symptoms (NPSs), representing a change from longstanding behavior or personality and considered a potential prodrome of neurodegenerative disease. MBI is classified into five domains: decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and psychotic symptoms. In this narrative review, we synthesize clinical, neuroanatomical, and molecular evidence linking MBI to the spectrum of tauopathies, including Alzheimer’s disease (AD), frontotemporal spectrum disorders (FTSDs), and primary four-repeat tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Emerging evidence suggests that early behavioral symptoms associated with MBI may reflect the selective vulnerability of frontolimbic, salience, default mode, and frontostriatal networks to tau-mediated neurodegeneration. Mechanistically, converging findings support roles for tau-related synaptic dysfunction, including synaptotoxic soluble tau species, cytoskeletal and axonal transport disruption, monoaminergic neurotransmitter imbalance in brainstem systems, and neuroinflammatory and glial pathways. We also highlight genotype-related behavioral profiles in genetic frontotemporal lobar degeneration and discuss how scalable blood-based biomarkers, including neurofilament light chain, glial fibrillary acidic protein, and plasma phospho-tau species, may complement MBI-based phenotyping for differential diagnosis and prognostic stratification in clinical research. Full article

Preliminary evidence has indicated that attachment style may be an important variable that can influence emotion regulation among individuals with experiences of psychosis. Yet there is a dearth of therapeutic approaches examined that address both constructs. More integrative approaches, such as Metacognitive Reflection and Insight Therapy (MERIT), may be well suited to address these concerns given its integrative approach to increasing insight. To explore this, this article presents a case report of an individual diagnosed with schizoaffective disorder who completed 24 sessions of MERIT. This individual presented with constricted affect and limited ability to access emotional content. Emotion regulation was measured before, during, and after treatment, while attachment security to the therapist was measured during and after treatment. Reliable change index (RCI) analyses of the individual’s scores revealed significant changes in domains of subjective emotion regulation abilities and attachment security to the therapist. A qualitative analysis of session transcripts is presented as well. Treatment was found to be feasible and acceptable to the client, and improvements were noted in the areas of emotion regulation and attachment security to the therapist. Clinical implications and limitations are also discussed. Full article

Eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED), are complex psychiatric conditions characterized by high morbidity and mortality. Increasing evidence suggests that beyond disorder-specific symptomatology, shared transdiagnostic mechanisms contribute to their onset and persistence. This narrative review synthesizes current data on neurobiological and nutritional factors implicated in EDs, with particular emphasis on trait–state interactions and starvation-induced neuroadaptations. Predisposing vulnerabilities such as heightened anxiety, cognitive rigidity, and perfectionism appear to interact with state-dependent biological alterations induced by malnutrition. Chronic dietary restriction is associated with measurable alterations in serotonergic and dopaminergic systems, altered reward processing, and persistent activation of the hypothalamic–pituitary–adrenal (HPA) axis. Experimental studies suggest that acute tryptophan depletion may transiently reduce anxiety in individuals with anorexia nervosa, suggesting that, in some individuals, food restriction may function as a biologically reinforced strategy of affect regulation. Furthermore, disturbances in leptin and ghrelin signaling, along with widespread micronutrient deficiencies—including zinc, iron, selenium, and B vitamins—may exacerbate cognitive inflexibility, mood instability, and impaired decision-making. These metabolic and endocrine adaptations may contribute to a self-perpetuating cycle in which starvation-induced neurochemical changes reinforce restrictive or dysregulated eating behaviors. Importantly, several of these mechanisms extend beyond anorexia nervosa and may represent common transdiagnostic processes across eating disorders and related mental health conditions, including anxiety, depression, and addictive behaviors. Recognition of these biological and nutritional factors has significant implications for treatment. Nutritional rehabilitation should be conceptualized not solely as weight restoration, but as a neurobiological recalibration of stress regulation, reward sensitivity, and affective processing systems. An integrative treatment approach that combines behavioral stabilization with attention to underlying neurobiological and relational mechanisms may offer a more comprehensive framework for long-term recovery. Full article

Background/Objectives: Schizophrenia is a severe psychiatric disorder frequently characterised by sleep and circadian disturbances, which are closely linked to cognitive dysfunction, symptom exacerbation, and poor functional outcomes. A growing body of evidence implicates the orexin (hypocretin) system—an essential regulator of arousal, sleep–wake stability, metabolic processes, and motivated behaviour—in the pathophysiology and treatment response of psychotic disorders. We aimed to investigate the relationships between the orexinergic system and psychoses. Methods: On 3 March 2026, we searched the PubMed, Scopus, PsycInfo/Articles and Cinahl databases for studies dealing with the orexin system and psychotic disorders and treatment response. Results: We found 20 eligible studies reporting variable and inconsistent alterations in orexin signalling in patients with schizophrenia. Studies were mostly cross-sectional and heterogeneous in design. Antipsychotic medications interfere with orexin-dependent pathways, potentially contributing to both therapeutic effects and adverse outcomes such as sleep disruption and metabolic dysregulation. Conclusions: While evidence from preclinical studies could point to an influence of dopaminergic activity through orexinergic mechanisms, with possible attenuation of antipsychotic-induced motor side effects and improvement of attentional deficits associated with NMDA receptor hypofunction, the utility of dual orexin receptor antagonists (DORAs) in psychoses is unclear. Despite the high prevalence of insomnia in schizophrenia, its pharmacological management remains suboptimal, with current treatments often limited by reduced efficacy or tolerability concerns. DORAs, which are currently approved medications for the treatment of insomnia, represent a novel and mechanistically distinct therapeutic option that may improve sleep while modulating arousal- and cognition-related circuits relevant to psychosis. Full article

Therapeutic termination of pregnancy (TToP) represents an intervention that is performed for medical reasons, such as risks to maternal health or severe fetal anomalies. Advances in prenatal screening and diagnostic tools—including serum markers, ultrasound, cell-free fetal DNA, chorionic villus sampling and amniocentesis—have significantly improved early detection and clinical decision-making. This narrative review synthesizes current knowledge on the genetic, environmental and psychosocial determinants that influence the decision of the patients to pursue TToP. The literature search was performed primarily using PubMed database, while Scopus and Google Scholar were used to identify additional relevant studies. Some of the selected studies, as well as certain sections of this review, address both therapeutic and voluntary termination of pregnancy, whereas others focus exclusively on TToP. Moreover, this review describes the types of abortion (medical or surgical/aspiration) along with their management strategies to prevent or address potential complications. It is well known that demographic, cultural and socio-economic factors continue to influence the access to TToP, as well as the perceptions of it. Psychiatric comorbidities (such as anxiety, affective and psychotic disorders) are observed with a higher prevalence among women undergoing TToP and may influence both the decision and psychological outcomes post-procedure. While most women report emotional relief after TToP, some of them experience depression, post-traumatic stress disorder or substance misuse. Legal and ethical considerations further complicate access to safe abortion, leading to situations where patients may resort to unsafe procedures, which result in higher rates of morbidity and mortality. Data from the EUROCAT network show rising trends in congenital anomalies like trisomy 13, trisomy 18 and caudal regression syndrome (conditions commonly associated with TToP). Therefore, it is mandatory to form a multidisciplinary team in these cases, integrating medical, psychological and ethical dimensions. Ensuring safe, evidence-based and compassionate access to TToP remains a critical component of reproductive healthcare. Full article

Cognitive impairments are a core feature of psychotic disorders and are strongly associated with long-term functional disability. Although Cognitive Remediation Therapy (CRT) is an evidence-based intervention for improving cognition in psychosis, its feasibility and preliminary effects in acute inpatient settings—particularly using web-based platforms—remain underexplored. This single-arm, pre–post pilot study evaluated the feasibility of delivering a web-based CRT program and examined preliminary cognitive outcomes in a secure psychiatric inpatient facility. Thirteen inpatients with psychotic and non-psychotic diagnoses completed a 15-week intervention comprising twice-weekly sessions that included adaptive computerized CRT exercises (Happy Neuron Pro) and therapist-led bridging discussions focused on metacognitive reflection and functional application. Cognitive performance was assessed pre- and post-intervention using the MATRICS Consensus Cognitive Battery. All participants completed the study with no withdrawals or adverse events, attending a mean of 27.77 of 30 sessions (93.0%). Pre–post improvements were observed in processing speed, verbal learning, and overall composite cognition, with large within-sample effect sizes that remained robust in sensitivity analyses. Exploratory analyses suggested potential associations between sex, history of self-harm, and cognitive change, though these findings require cautious interpretation. Findings support the feasibility of inpatient web-based CRT and provide preliminary cognitive effect-size estimates. Given the single-arm design and absence of systematic medication monitoring, results should be interpreted as exploratory signals warranting controlled validation. Overall, findings support the feasibility of inpatient web-based CRT and provide preliminary signals of cognitive benefit, warranting evaluation in larger controlled studies. 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

In recent years, imaginative techniques have effectively addressed the growing demand for brief, evidence-based treatments applicable in various contexts. Among these, Imagery with Rescripting (ImRs) was developed within the Schema Therapy model. ImRs can be applied individually or in combination with other protocols, demonstrating significant outcomes even after just one session. This narrative review aims to provide an overview of the applications of ImRs, with a specific focus on its effectiveness in trauma-related disorders. The search string used was “(‘imagery with Rescripting’) AND ((‘Trauma’ OR ‘PTSD’ OR ‘dissociation’))”. The following databases were utilized: PubMed, Scopus, Web of Science, Medline, Embase, and PsychInfo. The research included English-language and Italian-language studies, encompassing experimental and observational designs, case reports, and case series. Samples consisted of healthy participants or clinical populations aged 18 years and older, with no temporal limitations. A total of 56 articles were selected. The results highlight the efficacy of this intervention, whether administered individually or as part of combined protocols, across a wide range of diagnostic categories, including healthy samples, post-traumatic stress disorder (PTSD), borderline personality disorder (BDP), sleep disorders, psychotic spectrum disorders, chronic pain, anxiety disorders, depression, and eating disorders. The studies also support hypotheses about the mechanisms underlying the technique: ImRs facilitates the reprocessing of the meaning associated with mental representations and reduces the occurrence of negative intrusive images related to past events. This process alters and rewrites the individual’s negative memories and images. The narrative review supports the effectiveness of ImRs in treating various psychopathological disorders, both trauma-related and non-trauma-related. In addition to highlighting the effectiveness of ImRs when appropriately integrated with other techniques, the review emphasizes the importance of conducting efficacy studies on larger samples to evaluate ImRs as a standalone intervention model. Full article

Background/Objectives: An extensive body of data suggests that inflammation may contribute to the pathophysiological mechanisms of psychiatric illness. Circumstantial evidence implied that low-dose aspirin (LDA) may enhance the therapeutic efficacy of psychotropic drugs. We examined whether LDA administration with psychotropic medications is associated with medication regimen stability and other therapeutic effects in patients with bipolar disorder (BD), schizophrenia, and schizoaffective disorder (SAD). Methods: This retrospective study analyzed data from Clalit Health Services’ Southern District database in Israel, including 1924 patients treated between 2017 and 2019. The Study Group consisted of patients treated with LDA plus psychotropic medications, whereas the Control Group included patients treated only with psychotropic medications. Study outcomes included suicide attempts and pharmacotherapy-related negative events, defined as psychotropic dose escalation, augmentation, or switching. Results: The study group included 137 patients (55% males, age 63.3 ± 12.3 years), and the control group included 1787 patients (60% males, age 47 ± 16.9 years). Significant differences were observed across nearly all outcomes, favoring the LDA co-treatment group. Patients in the study group exhibited lower rates of medication dosage increase (40 [29%] vs. 726 [40.5%], p = 0.01); fewer changes and/or additions of psychotropic medications (37 [26.9%] vs. 778 [43.5%], p < 0.001); and a non-significantly lower rate of suicide attempts (0 [0%] vs. 16 [0.9%], p = 0.53). Conclusions: Overall, LDA co-treatment was associated with better clinical outcomes among patients with BD, schizophrenia, and SAD. Follow-up large-scale epidemiological studies and prospective randomized clinical trials are needed to examine the therapeutic potential of add-on LDA to psychotropic medications. Full article

Background: Dual disorders (DDs) describe the coexistence of substance use disorder (SUD) and another mental health condition, commonly within psychotic and affective categories. These conditions represent a significant challenge in clinical management due to their bidirectional interactions and complexity. This study aims to evaluate the efficacy and safety of quetiapine, a second-generation antipsychotic, in patients with schizophrenia spectrum disorders and comorbid substance use disorders. Methods: A total of 28 participants with schizophrenia spectrum disorder and comorbid SUD underwent psychometric evaluations at baseline (T0), one month (T1) and three months post-initiation of quetiapine treatment (T2), administered at a mean dosage of 165 mg/day. Key outcome measures included psychopathological burden (PANSS), aggressivity (MOAS), substance craving (VAS Craving), and quality of life (Q-LES-Q-SF scales). Results: Quetiapine demonstrated significant reductions in psychopathological symptoms, with decreased PANSS total scores (p < 0.001). Positive symptoms (p < 0.001), negative symptoms (p = 0.002), substance craving (p = 0.001), and aggressivity (p = 0.006) also showed notable reductions. Quality of life significantly improved across Q-LES-Q-SF scores (p < 0.001). Quetiapine was well-tolerated, with no dropouts related to drug-induced side effects. Conclusions: This study provides preliminary evidence supporting the efficacy and safety of quetiapine in individuals with dual disorders. Improvements in psychopathology, substance craving, and quality of life underscore the importance of integrating tailored and comprehensive treatment strategies to address the multifaceted challenges of this challenging population. Full article