NPJ Schizophrenia最新文献

The molecular events underlying the development, manifestation, and course of schizophrenia, bipolar disorder, and major depressive disorder span from embryonic life to advanced age. However, little is known about the early dynamics of gene expression in these disorders due to their relatively late manifestation. To address this, we conducted a secondary analysis of post-mortem prefrontal cortex datasets using bioinformatics and machine learning techniques to identify differentially expressed gene modules associated with aging and the diseases, determine their time-perturbation points, and assess enrichment with expression quantitative trait loci (eQTL) genes. Our findings revealed early, mid, and late deregulation of expression of functional gene modules involved in neurodevelopment, plasticity, homeostasis, and immune response. This supports the hypothesis that multiple hits throughout life contribute to disease manifestation rather than a single early-life event. Moreover, the time-perturbed functional gene modules were associated with genetic loci affecting gene expression, highlighting the role of genetic factors in gene expression dynamics and the development of disease phenotypes. Our findings emphasize the importance of investigating time-dependent perturbations in gene expression before the age of onset in elucidating the molecular mechanisms of psychiatric disorders.

Innate immunity has been shown to be associated with schizophrenia (Sch). This study explored the relationship between symptoms and neutrophil-to-lymphocyte ratio (NLR) (a marker of innate immunity) in patients with Sch. Ninety-seven first-episode medication-naïve (FEMN) patients with Sch and 65 healthy controls were recruited in this study. We measured the complete blood count and assessed the clinical symptoms using the PANSS scales. We found higher NEU counts and NLR in patients with Sch compared with control subjects. Male patients showed a higher NEU count than female patients. In addition, FEMN patients with higher NLR and NEU values showed higher PANSS-p, PANSS-g, and PANSS-total scores (all p < 0.05). Regression analysis revealed that NLR was a predictor for PANSS total scores in patients with Sch. Higher NLR value was observed in patients with Sch and the significant associations between NLR and psychotic symptoms indicate that an imbalance in inflammation and innate immune system may be involved in the pathophysiology of Sch.

Previous studies on putative neural mechanisms of negative symptoms in schizophrenia mainly used single modal imaging data, and seldom utilized schizophrenia patients with prominent negative symptoms (PNS).This study adopted the multimodal fusion method and recruited a homogeneous sample with PNS. We aimed to identify negative symptoms-related structural and functional neural correlates of schizophrenia. Structural magnetic resonance imaging (sMRI) and resting-state functional MRI (rs-fMRI) were performed in 31 schizophrenia patients with PNS and 33 demographically matched healthy controls.Compared to healthy controls, schizophrenia patients with PNS exhibited significantly altered functional activations in the default mode network (DMN) and had structural gray matter volume (GMV) alterations in the cerebello-thalamo-cortical network. Correlational analyses showed that negative symptoms severity was significantly correlated with the cerebello-thalamo-cortical structural network, but not with the DMN network in schizophrenia patients with PNS.Our findings highlight the important role of the cerebello-thalamo-cortical structural network underpinning the neuropathology of negative symptoms in schizophrenia. Future research should recruit a large sample and schizophrenia patients without PNS, and apply adjustments for multiple comparison, to verify our preliminary findings.

Early-onset psychosis is linked to adverse long-term outcomes, recurrent disease course, and prolonged periods of untreated illness; thus highlighting the urgency of improving early identification and intervention. This paper discusses three cases where initial emphasis on psychosocial treatments led to diagnostic and therapeutic delays: (1) a 15-year-old misdiagnosed with emotionally unstable personality disorder and autism, who improved on bipolar medication and antipsychotics; (2) another 15-year-old misdiagnosed with autism, who stabilized on lithium and antipsychotics, subsequently allowing for gender dysphoria evaluation; (3) a 9-year-old autistic boy incorrectly treated for ADHD, who recovered with appropriate antipsychotic treatment. These cases illuminate the vital importance of adhering to a diagnostic hierarchy, prioritizing diagnostic utility, and conducting longitudinal evaluations to facilitate early targeted treatment of psychotic symptoms in early-onset psychosis. Adherence to such strategies can minimize delays in managing early-onset psychosis and improve long-term prognoses.

Disorders of gambling are more common among the mentally ill, including in people with psychotic disorders. The aim of this study was to conduct a systematic review of the literature regarding the prevalence and correlates of gambling disorders in people with psychotic disorders. We systematically reviewed English-language literature through searches of six bibliographic databases, all run on 11 November 2022: Medline ALL, Embase, Emcare, APA PsycINFO, CINAHL and the Cochrane Library. Observational studies that reported the prevalence of gambling in psychotic disorders or psychosis among gamblers were included. Studies were critically appraised using the Joanna Briggs Institute Critical Appraisal Tools. Sixteen studies, including 1,116,103 participants, from across a range of settings, were included. Most studies were done on males and recruited participants with a mean age of 40 years. Most of the studies (n = 12) were cross-sectional, and the remaining were case control in design. Most of the studies rated fair in quality. The prevalence of gambling among psychotic population ranged from 0.32 to 19.3%, with the majority of the studies reporting rates between 6.4 and 17%. The rates were 5–25 times higher than in the general population. While there were no consistent associations found with socio-demographic indices, several studies reported an association between gambling behaviours and substance use disorder among those with psychotic illnesses. Our research suggests that clinicians should assess for comorbid gambling among those with psychotic illness, particularly in those with mood symptoms, impulsivity, and substance use disorders. Gambling can negatively impact on their financial and social situations. Future research should study specific strategies or therapies among those with comorbid gambling and psychotic disorders.

Serum neuropeptide levels may be linked to schizophrenia (SCZ) pathogenesis. This study aims to examine the relation between five serum neuropeptide levels and the cognition of patients with treatment-resistant schizophrenia (TRS), chronic stable schizophrenia (CSS), and in healthy controls (HC). Three groups were assessed: 29 TRS and 48 CSS patients who were hospitalized in regional psychiatric hospitals, and 53 HC. After the above participants were enrolled, we examined the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the blood serum levels of α-melanocyte stimulating hormone (α-MSH), β-endorphin (BE), neurotensin (NT), oxytocin (OT) and substance.P (S.P). Psychiatric symptoms in patients with SCZ were assessed with the Positive and Negative Syndrome Scale. SCZ patients performed worse than HC in total score and all subscales of the RBANS. The levels of the above five serum neuropeptides were significantly higher in SCZ than in HC. The levels of OT and S.P were significantly higher in CSS than in TRS patients. The α-MSH levels in TRS patients were significantly and negatively correlated with the language scores of RBANS. However, the BE and NT levels in CSS patients were significantly and positively correlated with the visuospatial/constructional scores of RBANS. Moreover, the interaction effect of NT and BE levels was positively associated with the visuospatial/constructional scores of RBANS. Therefore, abnormally increased serum neuropeptide levels may be associated with the physiology of SCZ, and may cause cognitive impairment and psychiatric symptoms, especially in patients with TRS.

Schizophrenia is a chronic mental disorder primarily treated with antipsychotics, which have limited efficacy for negative symptoms. This study aims to evaluate the effectiveness and feasibility of exercise interventions as adjuncts to pharmacotherapy through a meta-analysis, providing valuable insights for rational intervention design. Four databases were searched, and randomized controlled trials with no language restrictions published up to March 27, 2023, were included. The primary outcome indicator was the Positive and Negative Symptom Scale (PANSS) total score along with its three sub-scales. Secondary outcomes included the Scale for Assessment of Negative Symptoms (SANS) and Body Mass Index (BMI), which were used to assess the efficacy of aerobic exercise interventions in patients with schizophrenia. Subgroup analyses were conducted to explore the impact of intervention duration and total weekly exercise time, while treatment feasibility was assessed through adherence rates. A total of 17 publications involving 973 patients with schizophrenia were deemed eligible and included in the analysis. Compared to other forms of adjunctive interventions, the network meta-analysis of 12 PANSS-based studies revealed that adjunctive aerobic exercise interventions were the most effective in reducing overall PANSS scores in patients with schizophrenia, with statistically significant pooled results (MD = −4.84, 95% CI: −5.72, −3.96). Both the PANSS negative symptom subscale (MD = −2.11, 95% CI: −3.26, −0.95) and SANS (MD = −9.11, 95% CI: −11.94, −6.27) indicated that adjunctive aerobic exercise interventions effectively alleviate negative symptoms. Subgroup meta-analysis indicated that 2-3 month interventions involving 100–220 min of exercise per week were the most effective. Additionally, adherence to the adjunctive aerobic exercise regimen was found to be comparable to that of conventional treatment alone. Aerobic exercise interventions, as adjunctive therapy, are an effective measure for reducing PANSS scores in patients with schizophrenia, contributing to the alleviation of both the positive and negative symptoms, and patients demonstrated strong adherence to aerobic exercise.

Investigation of the choroid plexus in schizophrenia has seen growing interest due to its role in the interaction between neuroinflammation and brain dysfunction. Most previous studies included treated and long-term ill patients, while antipsychotics and illness course might both affect the choroid plexus. Here, we recruited first-episode antipsychotic-naïve schizophrenia patients, performed high-resolution structural brain scan and manually extracted choroid plexus volume. Choroid plexus volume was compared between patients and healthy controls after controlling for age, sex and intracranial volume. Age and sex effects were examined on choroid plexus volume in patient and healthy control groups respectively. In patients, we also examined the correlation of choroid plexus volume with volume measures of cortical and subcortical gray matter, white matter, lateral ventricular as well as symptom severity and cognitive function. Schizophrenia patients showed significantly enlarged choroid plexus volume compared with healthy controls. Choroid plexus volume was positively correlated with age in only patient group and we found significantly larger choroid plexus volumes in males than females in both patient and healthy control groups, while the sex effects did not differ between groups. Choroid plexus volume was only found correlated with lateral ventricular volume among the brain volume measures. No significant correlation between choroid plexus volume and clinical ratings or cognitive performance was observed. Without potential confounding effects of pharmacotherapy or illness course, our findings indicated the enlargement of choroid plexus in schizophrenia might be an enduring trait for schizophrenia.

Since the 1970s, famines have been widely invoked as natural experiments in research into the long-term impact of foetal exposure to nutritional shocks. That research has produced compelling evidence for a robust link between foetal exposure and the odds of developing schizophrenia. However, the implications of that research for the human cost of famines in the longer run have not been investigated. We address the connection between foetal origins and schizophrenia with that question in mind. The impact turns out to be very modest—much less than one per cent of the associated famine death tolls—across a selection of case studies.

There is substantial cognitive heterogeneity among patients with schizophrenia (SZ) and bipolar disorders (BD). More knowledge about the magnitude and clinical correlates of performance variability could improve our understanding of cognitive impairments. Using double generalized linear models (DGLMs) we investigated cognitive mean and variability differences between patients with SZ (n = 905) and BD spectrum disorders (n = 522), and healthy controls (HC, n = 1170) on twenty-two variables. The analysis revealed significant case-control differences on 90% of the variables. Compared to HC, patients showed larger intra-individual (within subject) variability across tests and larger inter-individual (between subject) variability in measures of fine-motor speed, mental processing speed, and inhibitory control (SZ and BD), and in verbal learning and memory and intellectual functioning (SZ). In SZ, we found that lager intra -and inter (on inhibitory control and speed functions) individual variability, was associated with lower functioning and more negative symptoms. Inter-individual variability on single measures of memory and intellectual function was additionally associated with disorganized and positive symptoms, and use of antidepressants. In BD, there were no within-subject associations with symptom severity. However, greater inter-individual variability (primarily on inhibitory control and speeded functions) was associated with lower functioning, more negative -and disorganized symptoms, earlier age at onset, longer duration of illness, and increased medication use. These results highlight larger individual differences in patients compared to controls on various cognitive domains. Further investigations of the causes and correlates of individual differences in cognitive function are warranted.