Structural dysconnectivity in schizophrenia: A subnetwork analysis of probabilistic tractography

Background: The structural network of schizophrenia is characterized by the increased segregation and decreased integration. However, a local deficit in a specific region of interest (ROI) is not sufficient to explain the pathophysiology of schizophrenia. Considering the human brain consists of small-worlds with different connectivity characteristics, the aberrant network structure in schizophrenia should be investigated at a smaller subnetwork level. Objective: To investigate structural dysconnectivity in two subnetworks of schizophrenia. Methods: A total of 189 patients and 213 healthy controls were recruited from four different neuroimaging sites. T1 and diffusion-weighted images were used to perform probabilistic tractography, which in turn led to the association matrices of all participants. Network analysis based on graph theoretical approach was then proceeded. Nodal betweenness centrality was used in the k-means clustering algorithm to distinguish two subnetworks from the whole network. Global network properties of schizophrenia and healthy controls were compared in each subnetwork and robustness simulation as well as clinical correlation with network measures were performed. Results: The subnetwork 1 comprised 75 ROIs with lower betweenness centrality and the subnetwork 2 comprised 12 ROIs with higher betweenness centrality. Patients had an increased level of local efficiency, clustering coefficient, and overall connectivity in the subnetwork 1 whereas these properties as well as global efficiency were decreased in the subnetwork 2. The subnetwork 1 was more robust to sequential nodal damages in patients than controls. The increased network measures in the subnetwork 1 was negatively associated with disease duration. Conclusions: The central subnetwork (subnetwork 2) was less integrated and segregated whereas the non-central subnetwork (subnetwork 1) was more segregated, stronger, and vulnerable to targeted damages. The disrupted connectivity in the non-central subnetwork became less prominent while the disease duration increased. We conclude that the integration, segregation, and robustness of structural network in schizophrenia are differently manifested between central and non-central subnetworks. |배경: 조현병의 연결성 장애는 네트워크 분석을 통해 증명할 수 있다. 뇌가 작은 세상 네트워크의 집합체라는 점과 특정 뇌 구역에 국한된 이상 소견이 조현병의 발생 기전을 설명할 수 없다는 점 때문에 구조연결성은 더 작은 서브네트워크 단위에서 연구되어야 한다. 목표: 조현병의 구조연결성 장애를 두 개의 서브네트워크 단위에서 분석하고자 한다. 방법: 공공 데이터베이스를 이용해 뇌확산 영상으로 구조 네트워크를 구성한다. 노드 단위에서의 매개 중심성을 기준으로 k-means 알고리즘으로 두 개의 서브네트워크를 구성한다. 각 서브네트워크에서 환자군과 대조군의 네트워크 지표를 비교하고 견고성 시뮬레이션과 임상 지표와의 관련성을 분석한다. 결과: 1번 서브네트워크는 75개의 ROI로 구성되고 2번 서브네트워크는 중심성이 높은 12개의 ROI로 구성되었다. 로컬 효율성, 클러스터링 계수, 전반적 연결성은 1번 서브네트워크에서 환자가 더 높았는데 이들 지표와 글로벌 효율성이 2번 서브네트워크에서는 환자가 더 낮았다. 조현병 환자의 1번 서브네트워크가 연속적 데미지에는 더 견고하였고 1번 서브네트워크에서 상승한 3개의 지표는 유병 기간과 음의 상관을 보였다. 결론: 높은 중심성 서브네트워크는 분리와 통합 정도가 낮았으며 낮은 중심성 서브네트워크는 분리와 연결 정도가 높고 데미지에 견고했다. 낮은 중심성 네트워크의 구조연결성 장애는 유병 기간과 연관되어 있다. 따라서, 조현병 환자의 구조 연결성은 높은 중심성과 낮은 중심성 서브네트워크에서 다르게 나타난다.Docto

Shared and distinct white matter abnormalities in schizophrenia and bipolar disorder

While white matter impairments play an integral part in the pathophysiology of schizophrenia and bipolar disorder, the literature on white matter abnormality differences between the two disorders is insufficient. The University of California Los Angeles Consortium for Neuropsychiatric Phenomic LA5c public dataset, including 47 patients with schizophrenia, 47 with bipolar disorder, and 115 healthy controls, was obtained via OpenNeuro. Whole-brain tractography was performed using Unscented Kalman filter-based two-tensor tractography and White Matter Query Language. Diffusion indices, including fractional anisotropy (FA), axial diffusivity, radial diffusivity (RD), and trace (TR), were used to compare subject groups. Spearman?s partial correlation with a covariate of age was used for correlation with clinical variables. Both patient groups exhibited significantly higher RD in the left external capsule and TR in the right extreme capsule. Significantly lower FA in the left external capsule, right thalamo-occipital and thalamo-parietal tracts were found in the schizophrenia group in comparison with bipolar disorder and healthy control groups. Compared with healthy controls, patients with schizophrenia had significantly lower FA in the left-to-right lateral orbitofrontal commissural tract. There were possible associations of the FA and RD of the left external capsule with the anxiety-depression score of the Brief Psychiatric Rating Scale in patients with schizophrenia. The white matter alterations identified in schizophrenia and bipolar disorder may be a neurobiological basis contributing to characterization of the two disorders

Association of the First Antipsychotic Treatment Duration With the Re-Initiation of Treatment in Schizophrenia: A National Health Insurance Data-Based Study

Objectives The optimal duration of maintenance treatment for patients with first-episode schizophrenia (FES) remains unclear. We examined the first antipsychotic treatment duration and its association with re-initiation of treatment using a nationwide claim database. Methods Data from the Health Insurance Review and Assessment Service database in South Korea for 2007-2016 were used. Linear regression analysis and Cox proportional hazard models were used to evaluate the associations between the duration of the first antipsychotic treatment, time to re-initiation of treatment, and occurrence of treatment re-initiation. Results Of 30,143 patients with FES, 80.4% (n=24,231) received <2 years of the first antipsychotic treatment. In patients who discontinued treatment (n=23,030), the rate of treatment re-initiation was 74.2% (n=17,086). As the duration of the first antipsychotic treatment increased, the time to re-initiation of treatment decreased (β=-0.146, p<0.001); however, the rate of treatment re-initiation was relatively constant (hazard ratio=1.001, p<0.001). Conclusion Long-term antipsychotic treatment was not significantly associated with the rate of treatment re-initiation but showed a negative association with the time to re-initiation of treatment. Further research is needed to better understand the optimal treatment duration for FES

Antipsychotic treatment and risk of discontinuation and hospitalization in first-episode schizophrenia: a nationwide population-based study

------EPUB (22.1.12)----- 2021 Apr 15;1-8. doi: 10.1017/S0033291721001379. Online ahead of print. Background: Current evidence on antipsychotic treatment and risk of psychiatric hospitalization in first-episode schizophrenia (FES) is largely based on the findings from randomized clinical trials (RCTs). However, the generalization of the findings to real-world patients is limited due to inherent caveats of the RCT. We aimed to investigate the treatment discontinuation and risk of psychiatric hospitalization using a nationwide population database. Methods: The Health Insurance Review Agency database in South Korea was obtained, and the observation period started from 1 January 2009 to 31 December 2016. We defined the maintenance period as the period from 6-month after the diagnosis of schizophrenia, which is utilized for the main results. For a total of 44 396 patients with FES, a within-individual Cox regression model was used to compare the risk of the treatment discontinuation and psychiatric hospitalization. Results: In group comparison, a long-acting injectable (LAI) antipsychotic group was associated with the lowest risk of the treatment discontinuation (0.64, 0.55-0.75) and psychiatric hospitalization (0.29, 0.22-0.38) in comparison with a typical antipsychotic group and no use, respectively. Among individual antipsychotics, the lowest risk of the treatment discontinuation was observed in LAI paliperidone (0.46, 0.37-0.66) compared to olanzapine. Clozapine was found to be the most effective antipsychotic in lowering the risk of psychiatric hospitalization as monotherapy compared to no use (0.23, 0.18-0.31). Conclusions: In real-world patients with FES, LAI paliperidone and clozapine were associated with low treatment discontinuation and better effectiveness in lowering the risk of psychiatric hospitalization. Keywords: Antipsychotic; discontinuation; hospitalization; nationwide population

Effects of comorbid alcohol use disorder on the clinical outcomes of first-episode schizophrenia: a nationwide population-based study

Background: Alcohol use disorder (AUD) is a common psychiatric comorbidity in schizophrenia, associated with poor clinical outcomes and medication noncompliance. Most previous studies on the effect of alcohol use in patients with schizophrenia had limitations of small sample size or a cross-sectional design. Therefore, we used a nationwide population database to investigate the impact of AUD on clinical outcomes of schizophrenia. Methods: Data from the Health Insurance Review Agency database in South Korea from January 1, 2007 to December 31, 2016 were used. Among 64,442 patients with first-episode schizophrenia, 1598 patients with comorbid AUD were selected based on the diagnostic code F10. We performed between- and within-group analyses to compare the rates of psychiatric admissions and emergency room (ER) visits, and medication possession ratio (MPR) between the patients with comorbid AUD and control patients matched for the onset age, sex, and observation period. Results: The rates of psychiatric admissions and ER visits in both groups decreased after the time point of diagnosis of AUD; however, the decrease was significantly greater in the patients with comorbid AUD compared to the control patients. While the comorbid AUD group showed an increase in MPR after the diagnosis of AUD, MPR decreased in the control group. The rates of psychiatric admissions, ER visits, and MPR were worse in the comorbid AUD group both before and after the diagnosis of AUD. Conclusions: The results emphasize an importance of psychiatric comorbidities, especially AUD, in first-episode schizophrenia and the necessity of further research for confirmative findings of the association of AUD with clinical outcomes of schizophrenia