NPJ Schizophrenia最新文献

Quantification of treatment response is crucial to optimize outcomes for patients with schizophrenia. In this study, we evaluated the relationship between quantitative measures of clinician-rated symptom severity and self-rated side effects, well-being, and functioning among inpatients with schizophrenia using the six-item version of the Positive and Negative Syndrome Scale (PANSS-6), the Glasgow Antipsychotic Side-effect Scale (GASS), the WHO-Five Well-being Index (WHO-5), and the Sheehan Disability Scale (SDS). All measurements were conducted as close to admission and discharge as possible. Well-being and functioning were found to be most strongly associated with the additive effect of symptoms and side effects, while changes in side effects, well-being, and functioning appeared to be relatively independent from changes in symptom severity. The use of both symptom and side effect measures should inform clinical decision-making in the treatment of schizophrenia, as it has the potential to optimize functioning and well-being.

Neuroimaging studies have revealed that patients with schizophrenia exhibit disrupted resting-state functional connectivity. However, the inconsistent findings across these studies have hindered our comprehensive understanding of the functional connectivity changes associated with schizophrenia, and the molecular mechanisms associated with these alterations remain largely unclear. A quantitative meta-analysis was first conducted on 21 datasets, involving 1057 patients and 1186 healthy controls, to examine disrupted resting-state functional connectivity in schizophrenia, as measured by whole-brain voxel-wise functional network centrality (FNC). Subsequently, partial least squares regression analysis was employed to investigate the relationship between FNC changes and gene expression profiles obtained from the Allen Human Brain Atlas database. Finally, gene enrichment analysis was performed to unveil the biological significance of the altered FNC-related genes. Compared with healthy controls, patients with schizophrenia show consistently increased FNC in the right inferior parietal cortex extending to the supramarginal gyrus, angular gyrus, bilateral medial prefrontal cortex, and right dorsolateral prefrontal cortex, while decreased FNC in the bilateral insula, bilateral postcentral gyrus, and right inferior temporal gyrus. Meta-regression analysis revealed that increased FNC in the right inferior parietal cortex was positively correlated with clinical score. In addition, these observed functional connectivity changes were found to be spatially associated with the brain-wide expression of specific genes, which were enriched in diverse biological pathways and cell types. These findings highlight the aberrant functional connectivity observed in schizophrenia and its potential molecular underpinnings, providing valuable insights into the neuropathology of dysconnectivity associated with this disorder.

Psychotic symptoms typically emerge in adolescence. Age-associated thalamocortical connectivity differences in psychosis remain unclear. We analyzed diffusion-weighted imaging data from 1254 participants 8–23 years old (typically developing (TD):N = 626, psychosis-spectrum (PS): N = 329, other psychopathology (OP): N = 299) from the Philadelphia Neurodevelopmental Cohort. We modeled thalamocortical tracts using deterministic fiber tractography, extracted Q-Space Diffeomorphic Reconstruction (QSDR) and diffusion tensor imaging (DTI) measures, and then used generalized additive models to determine group and age-associated thalamocortical connectivity differences. Compared to other groups, PS exhibited thalamocortical reductions in QSDR global fractional anisotropy (GFA, p-values range = 3.0 × 10^–6–0.05) and DTI fractional anisotropy (FA, p-values range = 4.2 × 10^–4–0.03). Compared to TD, PS exhibited shallower thalamus-prefrontal age-associated increases in GFA and FA during mid-childhood, but steeper age-associated increases during adolescence. TD and OP exhibited decreases in thalamus-frontal mean and radial diffusivities during adolescence; PS did not. Altered developmental trajectories of thalamocortical connectivity may contribute to the disruptions observed in adults with psychosis.

Response to antipsychotic medications (AP) is subjected to a wide and unpredictable variability and efforts were directed to discover predictive biomarkers to personalize treatment. Electroencephalography abnormalities in subjects with schizophrenia are well established, as well as a pattern of EEG changes induced by APs. The aim of this review is to provide a synthesis of the EEG features that are related to AP efficacy, including both pre-treatment signatures and changes induced by APs during treatment. A systematic review of English articles using PubMed, PsychINFO and the Cochrane database of systematic reviews was undertaken until july 2023. Additional studies were added by hand search. Studies having as an endpoint the relationship between AP-related clinical improvement and electroencephalographic features were included. Heterogeneity prevented a quantitative synthesis. Out of 1232 records screened, 22 studies were included in a final qualitative synthesis. Included studies evaluated resting-state and task-related power spectra, functional connectivity, microstates and epileptic abnormalities. At pre-treatment resting-state EEG, the most relevant predictors of a poor response were a change in theta power compared to healthy control, a high alpha power and connectivity, and diminished beta power. Considering EEG during treatment, an increased theta power, a reduced beta-band activity, an increased alpha activity, a decreased coherence in theta, alpha and beta-band were related to a favorable outcome. EEG is promising as a method to create a predictive biomarker for response to APs; further investigations are warranted to harmonize and generalize the contradictory results of reviewed studies.

We evaluated two models to link stressful life events (SLEs) with the psychopathology of schizophrenia spectrum disorders (SSD). We separated SLEs into independent (iSLEs, unlikely influenced by one’s behavior) and dependent (dSLEs, likely influenced by one’s behavior). Stress-diathesis and stress generation models were evaluated for the relationship between total, i- and d- SLEs and the severity of positive, negative, and depressive symptoms in participants with SSD. Participants with SSD (n = 286; 196 males; age = 37.5 ± 13.5 years) and community controls (n = 121; 83 males; 35.4 ± 13.9 years) completed self-report of lifetime negative total, i- and d- SLEs. Participants with SSD reported a significantly higher number of total SLEs compared to controls (B = 1.11, p = 6.4 × 10^–6). Positive symptom severity was positively associated with the total number of SLEs (β = 0.20, p = 0.001). iSLEs (β = 0.11, p = 0.09) and dSLEs (β = 0.21, p = 0.0006) showed similar association with positive symptoms (p = 0.16) suggesting stress-diathesis effects. Negative symptom severity was negatively associated with the number of SLEs (β = –0.19, p = 0.003) and dSLEs (β = −0.20, p = 0.001) but not iSLEs (β = –0.04, p = 0.52), suggesting stress generation effects. Depressive symptom severity was positively associated with SLEs (β = 0.34, p = 1.0 × 10^–8), and the association was not statistically stronger for dSLEs (β = 0.33, p = 2.7 × 10^–8) than iSLEs (β = 0.21, p = 0.0006), p = 0.085, suggesting stress-diathesis effects. The SLE – symptom relationships in SSD may be attributed to stress generation or stress-diathesis, depending on symptom domain. Findings call for a domain-specific approach to clinical intervention for SLEs in SSD.

Cognitive impairments are a core feature of schizophrenia that have negative impacts on functional outcomes. However, it remains challenging to assess these impairments in clinical settings. Smartphone apps provide the opportunity to measure cognitive impairments in an accessible way; however, more research is needed to validate these cognitive assessments in schizophrenia. We assessed the initial accessibility, validity, and reliability of a smartphone-based cognitive test to measure cognition in schizophrenia. A total of 29 individuals with schizophrenia and 34 controls were included in the analyses. Participants completed the standard pen-and-paper Trail Making Tests (TMT) A and B, and smartphone-based versions, Jewels Trail Tests (JTT) A and B, at the single in-lab visit. Participants were asked to complete the JTT remotely once per week for three months. We also investigated how subjective sleep quality and mood may affect cognitive performance longitudinally. In-lab and remote JTT scores moderately and positively correlated with in-lab TMT scores. Moderate test-retest reliability was observed across the in-lab, first remote, and last remote completion times of the JTT. Additionally, individuals with schizophrenia had significantly lower performance compared to controls on both the in-lab JTT and TMT. Self-reported mood had a significant effect on JTT A performance over time but no other significant relationships were found remotely. Our results support the initial accessibility, validity and reliability of using the JTT to measure cognition in schizophrenia. Future research to develop additional smartphone-based cognitive tests as well as with larger samples and in other psychiatric populations are warranted.

The pathway to receiving specialty care for first episode psychosis (FEP) among Black youth in the US has received little attention despite documented challenges that negatively impact engagement in care and clinical outcomes. We conducted a systematic review of US-based research, reporting findings related to the pathway experiences of Black individuals with FEP and their family members. A systematic search of PubMed, PsycInfo, and Embase/Medline was performed with no date restrictions up to April 2021. Included studies had samples with at least 75% Black individuals and/or their family members or explicitly examined racial differences. Of the 80 abstracts screened, 28 peer-reviewed articles met the inclusion criteria. Studies were categorized into three categories: premordid and prodromal phase, help-seeking experiences, and the duration of untreated psychosis (DUP). Compounding factors such as trauma, substance use, and structural barriers that occur during the premorbid and prodromal contribute to delays in treatment initiation and highlight the limited use of services for traumatic childhood experiences (e.g., sexual abuse). Studies focused on help-seeking experiences demonstrated the limited use of mental health services and the potentially traumatic entry to services (e.g., law enforcement), which is associated with a longer DUP. Although the majority of studies focused on help-seeking experiences and predictors of DUP, findings suggests that for Black populations, there is a link between trauma and substance use in the pathway to care that impacts the severity of symptoms, initiation of treatment, and DUP. The present review also identifies the need for more representative studies of Black individuals with FEP.

Social cognitive impairment is a core feature of schizophrenia and plays a critical role in poor community functioning in the disorder. However, our understanding of the relationship between key biological variables and social cognitive impairment in schizophrenia is limited. This study examined the effect of sex on the levels of social cognitive impairment and the relationship between social cognitive impairment and social functioning in schizophrenia. Two hundred forty-eight patients with schizophrenia (61 female) and 87 healthy controls (31 female) completed five objective measures and one subjective measure of social cognition. The objective measures included the Facial Affect Identification, Emotion in Biological Motion, Self-Referential Memory, MSCEIT Branch 4, and Empathic Accuracy tasks. The subjective measure was the Interpersonal Reactivity Index (IRI), which includes four subscales. Patients completed measures of social and non-social functional capacity and community functioning. For objective social cognitive tasks, we found a significant sex difference only on one measure, the MSCEIT Branch 4, which in both patient and control groups, females performed better than males. Regarding the IRI, females endorsed higher empathy-related items on one subscale. The moderating role of sex was found only for the association between objective social cognition and non-social functional capacity. The relationship was stronger in male patients than female patients. In this study, we found minimal evidence of a sex effect on social cognition in schizophrenia across subjective and objective measures. Sex does not appear to moderate the association between social cognition and functioning in schizophrenia.

We computed intrinsic neural timescales (INT) based on resting-state functional magnetic resonance imaging (rsfMRI) data of healthy controls (HC) and patients with schizophrenia spectrum disorder (SZ) from three independently collected samples. Five clusters showed decreased INT in SZ compared to HC in all three samples: right occipital fusiform gyrus (rOFG), left superior occipital gyrus (lSOG), right superior occipital gyrus (rSOG), left lateral occipital cortex (lLOC) and right postcentral gyrus (rPG). In other words, it appears that sensory information in visual and posterior parietal areas is stored for reduced lengths of time in SZ compared to HC. Finally, we found that symptom severity appears to modulate INT of these areas in SZ.

This study analyzed the effectiveness of an integrative cognitive remediation program (REHACOP) in improving neurocognition, social cognition, creativity, functional outcome, and clinical symptoms in patients with schizophrenia. In addition, possible mediators predicting improvement in functional outcomes were explored. The program combined cognitive remediation with social cognitive training and social and functional skill training over 20 weeks. The sample included 94 patients, 47 in the REHACOP group and 47 in the active control group (occupational activities). Significant differences were found between the two groups in change scores of processing speed, working memory, verbal memory (VM), inhibition, theory of mind, emotion processing (EP), figural creative strengths, functional competence, disorganization, excitement, and primary negative symptoms. A mediational analysis revealed that changes in VM, inhibition, and EP partially explained the effect of cognitive remediation on functional competence improvement. This study provides initial evidence of the effect of integrative cognitive remediation on primary negative symptoms and creativity.