Search Results (63)

22q11.2 deletion syndrome (22q11.2DS) is the most common recurrent microdeletion in humans and a prototypical high-risk neurogenetic copy number variant (CNV) associated with a broad spectrum of neurodevelopmental and psychiatric disorders, including intellectual disability (ID), autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), anxiety, and psychotic symptoms. This hemizygous deletion encompasses multiple genes involved in brain development and neural circuit function, contributing to marked phenotypic variability and multisystem involvement. In pediatric populations, deficits in adaptive functioning are frequently reported and may occur independently of global intellectual impairment, reflecting broader behavioral vulnerabilities within this genetic risk architecture. Background/Objectives: This study aimed to characterize the sociodemographic, clinical, and intellectual profiles of children and adolescents with 22q11.2DS and to examine adaptive functioning and its associations with behavioral difficulties. Methods: Thirty-four patients aged 1–17 years with a confirmed molecular diagnosis of 22q11.2DS were assessed. Standardized instruments were used to evaluate cognitive performance, adaptive functioning, and behavioral outcomes. Results: Intellectual disability was highly prevalent, with most participants showing combined cognitive and adaptive impairments. Adaptive functioning was compromised across domains, with relatively higher socialization scores compared to other areas, such as daily living skills. Multivariate analyses indicated associations between sociodemographic factors and behavioral difficulties, as well as between social problems and lower global adaptive functioning. Conclusions: Together, these findings contribute to the characterization of the adaptive and behavioral phenotype associated with a high-risk neurogenetic CNV and highlight the relevance of adaptive functioning as a key outcome for early evaluation and intervention in pediatric 22q11.2DS. Full article

Background and Objectives: Keratoconus (KC) is a progressive corneal ectasia with multifactorial etiology, increasingly studied for potential associations with psychiatric disorders. This systematic review aimed to evaluate recent evidence linking KC with depression and other psychiatric conditions, including psychotic disorders, personality disorders, attention deficit hyperactivity disorder (ADHD), Tourette syndrome (TS), autism spectrum disorder (ASD), and obsessive–compulsive disorder (OCD). Materials and Methods: Following PRISMA guidelines, PubMed, ScienceDirect and SpringerLink were searched for English-language observational studies published since 2015 that examined psychiatric disorders in adults with keratoconus. We excluded reviews, case reports, pediatric, non-English, and inaccessible articles. Study quality was assessed using the Newcastle–Ottawa Scale and JBI Checklist. Data were narratively summarized and tabulated—without meta-analysis due to heterogeneity. Results: Twelve studies met inclusion criteria, including 41,906 KC patients and 63,267 controls. Eleven studies investigated depression and one ADHD. Findings on depression were mixed: five studies showed higher depressive symptoms among KC patients, while others found no significant association. Most were cross-sectional and of moderate-to-high quality. The single study on ADHD reported a higher prevalence of KC in males, but no evidence of casual association. Evidence on TS, ASD, and OCD was scarce and largely limited to case reports. The review was limited by heterogeneous methodologies, small sample sizes, an absence of longitudinal data, and reliance on self-report or registry data. Conclusions: Current evidence indicates increased psychological burden among some individuals with KC, particularly regarding depressive symptoms, yet casual relationships remain unproven. Male ADHD patients may have an elevated risk of KC, especially in the presence of eye rubbing. Registration: Not registered. Full article

N-Acetylaspartate (NAA) plays a critical role in neuronal function, metabolism, and neurotransmitter release. Evidence from magnetic resonance spectroscopy indicates diminished NAA levels in individuals diagnosed with schizophrenia and bipolar disorder; however, this process is time-consuming, expensive, and not viable in individuals with acute illness exacerbation. In order to address these limitations, we developed a novel method for the quantification of plasma NAA based on tandem mass spectrometry coupled to liquid chromatography (HPLC-MS). Our study aimed to assess whether plasma NAA levels change during hospitalization and whether these changes correlate with symptomatic improvement in patients experiencing acute psychiatric exacerbations. We recruited 31 inpatients with acute symptoms of psychotic (48.39%) and/or mood (51.61%) disorders. Symptom severity was assessed using the brief psychiatric rating scale, Positive and Negative Syndrome Scale, and Clinical Global Impression Scale. Plasma NAA was measured at admission and discharge. We observed a significant decrease in symptom scores and a significant increase in plasma NAA levels between admission and discharge. The initiation of therapy with lithium salts significantly influenced plasma NAA changes. Our study shows that our HPLC-MS method can detect clinically meaningful changes in plasma NAA levels. These results might lay the groundwork for future research exploring the relationship between plasma NAA levels and cerebral NAA levels measured by MRS. Full article

Background: Parkinson’s disease (PD) in advanced stages becomes, over time, a significant challenge, as oral medication becomes ineffective, and it may become necessary to switch to device-assisted therapy (DAT). This should be personalized according to the stage of the disease, the cognitive status of the patients, the association of frailty syndrome or other comorbidities, the support in care from the family, etc. Levodopa–carbidopa–entacapone intestinal gel can significantly improve the status of patients, provided that they are correctly selected for this type of treatment. Materials and Methods: We conducted a single-center prospective study including 20 advanced PD patients, who received a levodopa–carbidopa–entacapone gel through an intestinal pump, within the Parkinson’s Disease Multimodal Treatment Center of the Neurology Clinic of the “St. Ap. Andrew” County Emergency Clinical Hospital in Galați, Romania. The evaluations were performed at baseline (T0), after intestinal pump insertion (T1), and 6 months after the procedure (T2). Results: In the study group, the administration of the levodopa–carbidopa–entacapone intestinal gel, using the device for intestinal administration, had significant benefits, especially for motor symptoms. The periods of off, no-on, freezing, sudden-off, as well as dyskinesia and morning akinesia, were significantly reduced. Among the non-motor symptoms, depression and sleep disorders improved, with no changes in cognitive status and psychotic disorders. Conclusions: Adding new data for the use of device-assisted therapy in advanced PD, our study also highlights the need to further research this challenging patient profile. Full article

The life expectancy of patients with psychotic disorders is significantly shorter than that of the general population; antipsychotic-induced metabolic disorders play a significant role in reducing life expectancy. Both metabolic syndrome (MetS) and schizophrenia are multifactorial conditions. One area where the two conditions overlap is oxidative stress, which is present in both diseases. The glutathione-S-transferase (GST) system is a major line of defense against exogenous toxicants and oxidative damage to cells. The aim of our study was to perform an association analysis of gene polymorphisms with metabolic disorders in patients with schizophrenia treated with antipsychotic therapy. Methods: A total of 639 white patients with schizophrenia (ICD-10) from Siberia (Russia) were included in the study. Genotyping was carried out using real-time polymerase chain reaction for two single-nucleotide polymorphisms (SNPs) in the GSTP1 (rs614080 and rs1695) and one SNP in the GSTO1 (rs49252). Results: We found that rs1695*GG genotype of GSTP1 is a risk factor for the development of overweight (OR 2.36; 95% CI: 1.3–4.29; p = 0.0054). In the subgroup of patients receiving first-generation antipsychotics as basic therapy, the risk of overweight was associated with carriage of the rs1695*GG (OR 5.43; 95% CI: 2.24–13.16; p < 0.001) genotype of GSTP1 in a recessive model of inheritance. In contrast, an association of rs1695*G GSTP1 with obesity (OR: 0.42; 95% CI: 0.20–0.87; p = 0.018) was shown in the dominant model of inheritance in patients receiving second-generation antipsychotics. Conclusions: The pilot results obtained confirm the hypothesis of a violation of the antioxidant status, in particular the involvement of GSTP1, in the development of antipsychotic-induced metabolic disorders in schizophrenia. Further studies with larger samples and different ethnic groups are needed to confirm the obtained results. Full article

Aripiprazole (ARZ) is an atypical antipsychotic drug used to treat a variety of mood and psychotic disorders, such as schizophrenia, bipolar disorder, major depressive disorder, autism, and Tourette’s syndrome. Although ARZ offers significant therapeutic benefits, its poor solubility in water requires the development of delivery systems aimed at improving the solubility and bioavailability of the drug. In this work, cryogels based on two natural products—agar and β-cyclodextrin (CD)—were developed and evaluated as a drug delivery system for ARZ. The cryogels were prepared by cryogenic treatment of aqueous solutions of agar and the β-CD/ARZ complex, followed by thawing. The main characteristics of the material, including gel fraction yield, swelling degree, pore volume, elastic properties, and morphology were studied in detail. The release of ARZ from composite cryogels was assessed in two media resembling the pH in stomach and intestine. The system exhibited a pH-dependent release of ARZ, with a slower rate in acidic media (pH 1.2) than in the neutral phosphate buffer (pH 6.8). Under in vitro conditions, the amount of released ARZ over 48 h reached 33%. Full article

Background and Objectives: Growing evidence suggested that abnormal lipid metabolism (ALM) was associated with an increased severity of depressive symptoms, but no previous studies have examined the differences in comorbid ALM in major depressive disorder (MDD) patients of different ages of onset. We aim to compare the differences in the prevalence and clinical correlates of ALM between early-onset and late-onset patients with first-episode and drug-naive (FEDN) MDD patients. Methods: Using a cross-sectional design, we recruited a total of 1718 FEDN MDD outpatients in this study. We used the 17-item Hamilton Rating Scale for Depression (HAMD-17), The Hamilton Anxiety Rating Scale (HAMA), the Positive and Negative Syndrome Scale (PANSS) positive subscale, and Clinical Global Impression-Severity Scale (CGI-S) to assess their depression, anxiety, and psychotic symptoms and clinical severity, respectively. Results: There were 349 patients (20.3%) in the early-onset subgroup and 1369 (79.7%) in the late-onset subgroup. In this study, 65.1% (1188/1718) of patients were diagnosed with ALM. The prevalence of ALM in the late-onset group (81.5%, 1116/1369) was significantly higher than that in the early-onset group (20.6%, 72/349) (p = 0.36, OR = 1.147, 95%CI = 0.855–1.537). The HAMD total score (OR = 1.34, 95% CI = 1.18–1.53, p < 0.001) was the only risk factor for ALM in early-onset MDD patients. In late-onset MDD patients, the HAMD total score (OR = 1.19, 95% CI = 1.11–1.28, p < 0.001), TSH (OR = 1.25, 95% CI = 1.16–1.36, p < 0.001), CGI (OR = 1.7, 95% CI = 1.31–2.19, p < 0.001), and anxiety (OR = 2.22, 95% CI = 1.23–4.02, p = 0.008) were risk factors for ALM. Conclusion and Scientific Significance: Our results suggest that there are significant differences in the prevalence and clinical factors of comorbid ALM between early-onset and late-onset FEND MDD patients. Full article

Metabolic syndrome (MetS) is the most common adverse drug reaction from psychiatric pharmacotherapy. Neuroreceptor blockade by the antipsychotic drug clozapine induces MetS in about 30% of patients. Similar to insulin resistance, clozapine impedes Akt kinase activation, leading to intracellular glucose and glutathione depletion. Additional cystine shortage triggers tryptophan degradation to kynurenine, which is a well-known AhR ligand. Ligand-bound AhR downregulates the intracellular iron pool, thereby increasing the risk of mitochondrial dysfunction. Scavenging iron stabilizes the transcription factor HIF-1, which shifts the metabolism toward transient glycolysis. Furthermore, the AhR inhibits AMPK activation, leading to obesity and liver steatosis. Increasing glucose uptake by AMPK activation prevents dyslipidemia and liver damage and, therefore, reduces the risk of MetS. In line with the in vitro results, feeding experiments with rats revealed a disturbed glucose-/lipid-/iron-metabolism from clozapine treatment with hyperglycemia and hepatic iron deposits in female rats and steatosis and anemia in male animals. Decreased energy expenditure from clozapine treatment seems to be the cause of the fast weight gain in the first weeks of treatment. In patients, this weight gain due to neuroleptic treatment correlates with an improvement in psychotic syndromes and can even be used to anticipate the therapeutic effect of the treatment. Full article

A wide array of biological abnormalities in psychotic illness appear to reflect non-cerebral involvement. This review first outlines the evidence for such a whole-body concept of schizophrenia pathobiology, focusing particularly on cardiovascular disease, metabolic syndrome and diabetes, immunity and inflammation, cancer, and the gut–brain axis. It then considers the roles of miRNAs in general and of miRNA-143 in particular as they relate to the epidemiology, pathobiology, and treatment of schizophrenia. This is followed by notable evidence that miRNA-143 is also implicated in each of these domains of cardiovascular disease, metabolic syndrome and diabetes, immunity and inflammation, cancer, and the gut–brain axis. Thus, miRNA-143 is an exemplar of what may be a class of molecules that play a role across the multiple domains of bodily dysfunction that appear to characterize a whole-body perspective of illness in schizophrenia. Importantly, the existence of such an exemplary molecule across these multiple domains implies a coordinated rather than stochastic basis. One candidate process would be a pleiotropic effect of genetic risk for schizophrenia across the whole body. 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

For several decades, the dopamine hypothesis contributed to the discovery of numerous typical and atypical antipsychotics and was the sole hypothesis for the pathophysiology of schizophrenia. However, neither typical nor atypical antipsychotics, other than clozapine, have been effective in addressing negative symptoms and cognitive impairments, which are indices for the prognostic and disability outcomes of schizophrenia. Following the development of atypical antipsychotics, the therapeutic targets for antipsychotics expanded beyond the blockade of dopamine D2 and serotonin 5-HT2A receptors to explore the partial agonism of the D2 receptor and the modulation of new targets, such as D3, 5-HT1A, 5-HT7, and metabotropic glutamate receptors. Despite these efforts, to date, psychiatry has not successfully developed antipsychotics with antipsychotic properties proven to be superior to those of clozapine. The glutamate hypothesis, another hypothesis regarding the pathophysiology/pathomechanism of schizophrenia, was proposed based on clinical findings that N-methyl-D-aspartate glutamate receptor (NMDAR) antagonists, such as phencyclidine and ketamine, induce schizophrenia-like psychotic episodes. Large-scale genome-wide association studies (GWASs) revealed that approximately 30% of the risk genes for schizophrenia (the total number was over one hundred) encode proteins associated with glutamatergic transmission. These findings supported the validation of the glutamate hypothesis, which was inspired by the clinical findings regarding NMDAR antagonists. Additionally, these clinical and genetic findings suggest that schizophrenia is possibly a syndrome with complicated pathomechanisms that are affected by multiple biological and genetic vulnerabilities. The glutamate hypothesis has been the most extensively investigated pathophysiology/pathomechanism hypothesis, other than the dopamine hypothesis. Studies have revealed the possibility that functional abnormalities of the NMDAR play important roles in the pathophysiology/pathomechanism of schizophrenia. However, no antipsychotics derived from the glutamatergic hypothesis have yet been approved for the treatment of schizophrenia or treatment-resistant schizophrenia. Considering the increasing evidence supporting the potential pro-cognitive effects of glutamatergic agents and the lack of sufficient medications to treat the cognitive impairments associated with schizophrenia, these previous setbacks cannot preclude research into potential novel glutamate modulators. Given this background, to emphasize the importance of the dysfunction of the NMDAR in the pathomechanism and/or pathophysiology of schizophrenia, this review introduces the increasing findings on the functional abnormalities in glutamatergic transmission associated with the NMDAR. Full article

Background: Psychotic disorders are major psychiatric disorders that can impact multiple domains including physical, social, and psychological functioning within individuals with these conditions. Being able to better predict the outcomes of psychotic disorders will allow clinicians to identify illness subgroups and optimize treatment strategies in a timely manner. Objective: In this scoping review, we aimed to examine the accuracy of the use of artificial intelligence (AI) methods in predicting the clinical outcomes of patients with psychotic disorders as well as determine the relevant predictors of these outcomes. Methods: This review was guided by the PRISMA Guidelines for Scoping Reviews. Seven electronic databases were searched for relevant published articles in English until 1 February 2024. Results: Thirty articles were included in this review. These studies were mainly conducted in the West (63%) and Asia (37%) and published within the last 5 years (83.3%). The clinical outcomes included symptomatic improvements, illness course, and social functioning. The machine learning models utilized data from various sources including clinical, cognitive, and biological variables such as genetic, neuroimaging measures. In terms of main machine learning models used, the most common approaches were support vector machine, random forest, logistic regression, and linear regression models. No specific machine learning approach outperformed the other approaches consistently across the studies, and an overall range of predictive accuracy was observed with an AUC from 0.58 to 0.95. Specific predictors of clinical outcomes included demographic characteristics (gender, socioeconomic status, accommodation, education, and employment); social factors (activity level and interpersonal relationships); illness features (number of relapses, duration of relapses, hospitalization rates, cognitive impairments, and negative and disorganization symptoms); treatment (prescription of first-generation antipsychotics, high antipsychotic doses, clozapine, use of electroconvulsive therapy, and presence of metabolic syndrome); and structural and functional neuroimaging abnormalities, especially involving the temporal and frontal brain regions. Conclusions: The current review highlights the potential and need to further refine AI and machine learning models in parsing out the complex interplay of specific variables that contribute to the clinical outcome prediction of psychotic disorders. Full article

A two-factor account has been proposed as an explanatory model for the formation and maintenance of delusions. The first factor refers to a neurocognitive process leading to a significant change in subjective experience; the second factor has been regarded as a failure in hypothesis evaluation characterized by an impairment in metacognitive ability. This study was focused on the assessment of metacognition in patients with schizophrenia. The aims of the study were to measure the overconfidence in metacognitive judgments through the prediction of word list recall and to analyze the correlation between basic neurocognition (memory and executive function) and metacognition through a metamemory test and the severity of psychotic symptoms. Method: Fifty-one participants with a diagnosis of schizophrenia were evaluated. The Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of psychiatric symptoms, and the subtest of metamemory included in the Executive Functions and Frontal Lobe-2 battery (BANFE-2) was used to evaluate overconfidence and underestimation errors, intrusion and perseverative response, total volume of recall, and Brief Functioning Assessment Scale (FAST) for social functioning. Results: The strongest correlation is observed between overconfidence errors and the positive factor of the PANSS (r = 0.774, p < 0.001). For the enter model in the multiple linear regression (r = 0.78, r² = 0.61; F = 24.57, p < 0.001), the only significant predictor was overconfidence errors. Conclusion: Our results highlight the relevance of a metacognitive bias of overconfidence, strongly correlated with psychotic symptoms, and support the hypothesis that metacognitive defects contribute to the failure to reject contradictory evidence. From our perspective, these findings align with current mechanistic models of schizophrenia that focus on the role of the prefrontal cortex. Full article

Rehabilitation involves all types of patients, including people with schizophrenia. Schizophrenia is considered a complex syndrome characterized in general by fundamental and characteristic distortions of thinking and perception. The quality of life of a person with schizophrenia can be compromised by difficulty in carrying out their daily tasks and by the social stigma of their condition. The importance of training and sensitizing students in rehabilitation areas to this type of problem to improve the rehabilitation processes in which they will participate as future professionals involves empathy and the ability to communicate with these populations. It is possible through virtual reality to create immersive environments to simulate some psychotic symptoms characteristic of people with schizophrenia, such as visual hallucinations and hearing voices. The aim of this study was to test the effect of exposure to experiences characteristic of schizophrenia through two different types of immersive environments, graphical computational virtual reality and 360° video, on students from areas of social rehabilitation regarding empathy, social distance, and attitudes towards people with schizophrenia. Although the results were positive for the three parameters under study, no significant differences were found for each of them between the environments to which the participants were exposed. This study concluded that the choice between the two types of immersive environments should be based on the project’s objectives, the target audience’s needs, and available resources, rather than the type of environment itself, as their impact was similar. Full article

Background: Dual disorders (DDs) involve the coexistence of a substance use disorder (SUD) with another mental illness, often from the psychotic and affective categories. They are quite common in clinical practice and present significant challenges for both diagnosis and treatment. This study explores the effectiveness of brexpiprazole, a third-generation antipsychotic, in an Italian sample of individuals diagnosed with schizophrenia spectrum disorder and a comorbid SUD. Methods: Twenty-four patients, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and enrolled in several Italian hospitals, underwent a psychometric assessment at baseline (T0) and one month (T1) after starting brexpiprazole treatment administered at a mean dosage of 2 mg/day. Results: Brexpiprazole demonstrated significant reductions in psychopathological burden (Positive and Negative Syndrome Scale/PANSS total score: p < 0.001). Positive (p = 0.003) and negative (p = 0.028) symptoms, substance cravings (VAS craving: p = 0.039), and aggression (MOAS scale: p = 0.003) were notably reduced. Quality of life improved according to the 36-item Short Form Health Survey (SF-36) subscales (p < 0.005). Conclusions: This study provides initial evidence supporting brexpiprazole’s efficacy and safety in this complex patient population, with positive effects not only on psychopathology and quality of life, but also on cravings. Further studies involving larger cohorts of subjects and extended follow-up periods are needed. Full article