Publications by authors named "Daqiang Sun"

28 Publications

  • Page 1 of 1

A narrative review of prognosis prediction models for non-small cell lung cancer: what kind of predictors should be selected and how to improve models?

Ann Transl Med 2021 Oct;9(20):1597

Graduate School, Tianjin Medical University, Tianjin, China.

Objective: To discover potential predictors and explore how to build better models by summarizing the existing prognostic prediction models of non-small cell lung cancer (NSCLC).

Background: Research on clinical prediction models of NSCLC has experienced explosive growth in recent years. As more predictors of prognosis are discovered, the choice of predictors to build models is particularly important, and in the background of more applications of next-generation sequencing technology, gene-related predictors are widely used. As it is more convenient to obtain samples and follow-up data, the prognostic model is preferred by researchers.

Methods: PubMed and the Cochrane Library were searched using the items "NSCLC", "prognostic model", "prognosis prediction", and "survival prediction" from 1 January 1980 to 5 May 2021. Reference lists from articles were reviewed and relevant articles were identified.

Conclusions: The performance of gene-related models has not obviously improved. Relative to the innovation and diversity of predictors, it is more important to establish a highly stable model that is convenient for clinical application. Most of the prevalent models are highly biased and referring to PROBAST at the beginning of the study may be able to significantly control the bias. Existing models should be validated in a large external dataset to make a meaningful comparison.
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http://dx.doi.org/10.21037/atm-21-4733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576716PMC
October 2021

Let-7a targets Rsf-1 to modulate radiotherapy response of non-small cell lung cancer cells through Ras-MAPK pathway.

J BUON 2021 Jul-Aug;26(4):1422-1431

Graduate School, Tianjin Medical University, Tianjin, China.

Purpose: Radiotherapy is the most commonly selective medical treatment for non-small cell lung cancer (NSCLC) and the multiple underlying mechanisms are considered as the effectively theoretical foundation. Herein, we investigated the effects of let-7a targets Rsf-1 on modulating the radiotherapy response in NSCLC cells by Ras-MAPK pathway.

Methods: A549 cells were divided into different groups to investigate the role of let-7a and Rsf-1 on the radiotherapy response. The expression of let-7a and Rsf-1 were detected by RT-PCR. Bioinformatic analysis indicated that Rsf-1 is the target of let-7a. The binding site of let-7a in the Rsf-1 3'UTR was detected based on double luciferase reporter assay and Western blot. The cell variability and proliferation were assessed by MTT and colony formation assay. The expression levels of Ras-MARK signaling pathway related proteins were assessed by RT-PCR.

Results: RT-PCR results showed that radiotherapy could up-regulate the expression of let-7a, thereby reducing the expression of Rsf-1, and the correlation between the two factors was negatively correlated. At the same time, let-7a overexpression and Rsf-1 silencing could further reduce the activity of A549 cells after radiotherapy, have an inhibitory effect on cell proliferation and inhibit the expression of related proteins in the Ras-MAPK pathway.

Conclusions: Rsf-1 is the target of Let-7a. The present study provides evidence that let-7a targeting Rsf-1 can modulate radiotherapy response in NSCLC cells through Ras-MAPK pathway.
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September 2021

Safety and efficacy of lobectomy combined with off-pump coronary artery bypass grafting for lung cancer.

J Thorac Dis 2021 Jul;13(7):4438-4447

Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin, China.

Background: This study sought to assess the safety and efficacy of a lobectomy combined with off-pump coronary artery bypass grafting (OPCABG) among patients with lung cancer.

Methods: Patients who underwent a simultaneous pulmonary lobectomy combined with OPCABG at Tianjin Chest Hospital from December 2010 to June 2019 and patients who underwent pulmonary lobectomy during the same period were selected at a ratio of 1:2 using a multi-factor propensity score for this study. The clinical data of each group during the operation and perioperative period were analyzed and compared, and the survival curves were drawn using the Kaplan-Meier method to compare the long-term survival of the patients.

Results: In the simultaneous-surgery group, no patients required a secondary thoracotomy for hemostasis and there were no perioperative deaths; however, 2 patients underwent a second intubation, 2 patients underwent a second debridement and suturing due to wound infection, 28 patients (76.3%) had pulmonary complications, and 10 patients (26.3%) had circulatory complications. The operation time, intraoperative blood loss, postoperative drainage volume, postoperative hospital stay, and complication rate were all higher in the simultaneous-surgery group than the lobectomy group. No significant difference was observed in the long-term survival rates between the 2 groups.

Conclusions: The simultaneous surgery was safe and effective. Some differences existed in the data between the 2 groups during the perioperative period; however, the risk of complications after surgery was controllable.
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http://dx.doi.org/10.21037/jtd-21-788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8339769PMC
July 2021

Perioperative outcomes of combined heart surgery and lung tumor resection: a systematic review and meta-analysis.

J Cardiothorac Surg 2021 Aug 9;16(1):227. Epub 2021 Aug 9.

Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin, 300222, China.

Objective: The prevalence of patients with concomitant heart and lung lesions requiring surgical intervention is increasing. Simultaneous cardiac surgery and pulmonary resection avoids the need for a second operation. However, there are concerns regarding the potentially increased mortality and complication rates of simultaneous surgery and the adequacy of lung exposure during heart surgery. Therefore, we performed a meta-analysis to evaluate the perioperative mortality and complication rates of combined heart surgery and lung tumor resection.

Methods: A comprehensive literature search was performed in July 2020. The PubMed, Embase, and Web of Science databases were searched to identify studies that reported the perioperative outcomes of combined heart surgery and lung tumor resection. Two reviewers independently screened the studies, extracted data, and assessed the risk of bias of included studies. Pooled proportions and 95% confidence intervals (95% CI) were calculated by R version 3.6.1 using the meta package.

Results: A total of 536 patients from 29 studies were included. Overall, the pooled proportion of operative mortality was 0.01 (95% CI: 0.00, 0.03) and the pooled proportion of postoperative complications was 0.40 (95% CI: 0.24, 0.57) for patients who underwent combined cardiothoracic surgery. Subgroup analysis by lung pathology revealed that, for patients with lung cancer, the pooled proportion of anatomical lung resection was 0.99 (95% CI: 0.95, 1.00) and the pooled proportion of systematic lymph node dissection or sampling was 1.00 (95% CI: 1.00, 1.00). Subgroup analysis by heart surgery procedure found that the pooled proportion of postoperative complications of patients who underwent coronary artery bypass grafting (CABG) patients using the off-pump method was 0.17 (95% CI: 0.01, 0.43), while the pooled proportion of complications after CABG using the on-pump method was 0.61 (95% CI: 0.38, 0.82).

Conclusion: Combined heart surgery and lung tumor resection had a low mortality rate and an acceptable complication rate. Subgroup analyses revealed that most patients with lung cancer underwent uncompromised anatomical resection and mediastinal lymph node sampling or dissection during combined cardiothoracic surgery, and showed off-pump CABG may reduce the complication rate compared with on-pump CABG. Further researches are still needed to verify these findings.
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http://dx.doi.org/10.1186/s13019-021-01607-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8351083PMC
August 2021

Prioritizing Genetic Contributors to Cortical Alterations in 22q11.2 Deletion Syndrome Using Imaging Transcriptomics.

Cereb Cortex 2021 06;31(7):3285-3298

Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Los Angeles, CA 90095, USA.

22q11.2 deletion syndrome (22q11DS) results from a hemizygous deletion that typically spans 46 protein-coding genes and is associated with widespread alterations in brain morphology. The specific genetic mechanisms underlying these alterations remain unclear. In the 22q11.2 ENIGMA Working Group, we characterized cortical alterations in individuals with 22q11DS (n = 232) versus healthy individuals (n = 290) and conducted spatial convergence analyses using gene expression data from the Allen Human Brain Atlas to prioritize individual genes that may contribute to altered surface area (SA) and cortical thickness (CT) in 22q11DS. Total SA was reduced in 22q11DS (Z-score deviance = -1.04), with prominent reductions in midline posterior and lateral association regions. Mean CT was thicker in 22q11DS (Z-score deviance = +0.64), with focal thinning in a subset of regions. Regional expression of DGCR8 was robustly associated with regional severity of SA deviance in 22q11DS; AIFM3 was also associated with SA deviance. Conversely, P2RX6 was associated with CT deviance. Exploratory analysis of gene targets of microRNAs previously identified as down-regulated due to DGCR8 deficiency suggested that DGCR8 haploinsufficiency may contribute to altered corticogenesis in 22q11DS by disrupting cell cycle modulation. These findings demonstrate the utility of combining neuroanatomic and transcriptomic datasets to derive molecular insights into complex, multigene copy number variants.
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http://dx.doi.org/10.1093/cercor/bhab008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196250PMC
June 2021

Effects of copy number variations on brain structure and risk for psychiatric illness: Large-scale studies from the ENIGMA working groups on CNVs.

Hum Brain Mapp 2021 Feb 21. Epub 2021 Feb 21.

Center for Neuroimaging, Genetics and Genomics, School of Psychology, NUI Galway, Galway, Ireland.

The Enhancing NeuroImaging Genetics through Meta-Analysis copy number variant (ENIGMA-CNV) and 22q11.2 Deletion Syndrome Working Groups (22q-ENIGMA WGs) were created to gain insight into the involvement of genetic factors in human brain development and related cognitive, psychiatric and behavioral manifestations. To that end, the ENIGMA-CNV WG has collated CNV and magnetic resonance imaging (MRI) data from ~49,000 individuals across 38 global research sites, yielding one of the largest studies to date on the effects of CNVs on brain structures in the general population. The 22q-ENIGMA WG includes 12 international research centers that assessed over 533 individuals with a confirmed 22q11.2 deletion syndrome, 40 with 22q11.2 duplications, and 333 typically developing controls, creating the largest-ever 22q11.2 CNV neuroimaging data set. In this review, we outline the ENIGMA infrastructure and procedures for multi-site analysis of CNVs and MRI data. So far, ENIGMA has identified effects of the 22q11.2, 16p11.2 distal, 15q11.2, and 1q21.1 distal CNVs on subcortical and cortical brain structures. Each CNV is associated with differences in cognitive, neurodevelopmental and neuropsychiatric traits, with characteristic patterns of brain structural abnormalities. Evidence of gene-dosage effects on distinct brain regions also emerged, providing further insight into genotype-phenotype relationships. Taken together, these results offer a more comprehensive picture of molecular mechanisms involved in typical and atypical brain development. This "genotype-first" approach also contributes to our understanding of the etiopathogenesis of brain disorders. Finally, we outline future directions to better understand effects of CNVs on brain structure and behavior.
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http://dx.doi.org/10.1002/hbm.25354DOI Listing
February 2021

Identification of Key circRNAs in Non-Small Cell Lung Cancer.

Am J Med Sci 2021 01 10;361(1):98-105. Epub 2020 Aug 10.

Department of Thoracic Surgery, Tianjin First Central Hospital, Tianjin, China.

Background: Our work aimed to identify the key differentially expressed circular RNAs (circRNAs) (DECs) in non-small cell lung cancer (NSCLC).

Materials And Methods: An integrated analysis based on public NSCLC datasets obtained from Gene Expression Omnibus was performed. DECs in NSCLC were subsequently identified. Bioinformatics analyses were utilized for describing the predictable functions of DECs including circRNA-miRNA network construction and pathway enrichment. The diagnostic value of candidate DECs among NSCLC and healthy individuals were preliminarily evaluated in GSE101586, GSEE101684, GSE112214 datasets.

Results: A total of 43 up-regulated and 78 down-regulated DECs in NSCLC were identified. The mTOR signaling pathway, ErbB signaling pathway and cell cycle were significantly enriched from the originated genes of DECs in NSCLC. In the circRNA-miRNA network, hsa-circ-0002702, hsa-circ-0049271, hsa-circ-0009150 and hsa-circ-0053958 had high connectivity with miRNAs, which respectively interacted with 122, 42, 41, and 39 miRNAs. hsa_circ_0003028, hsa_circ_0015278, hsa_circ_0043256, hsa_circ_0049657 and hsa_circ_0074930 could distinguish NSCLC patients from healthy individuals in GSE101586, GSEE101684, GSE112214 datasets.

Conclusions: DECs including hsa_circ_0003028, hsa_circ_0015278, hsa_circ_0043256, hsa_circ_0049657 and hsa_circ_0074930 had diagnostic value in NSCLC. These DECs might play key roles in NSCLC pathogenesis through the mTOR signaling pathway, ErbB signaling pathway and cell cycle.
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http://dx.doi.org/10.1016/j.amjms.2020.08.008DOI Listing
January 2021

Survival prediction model for non-small cell lung cancer based on somatic mutations.

J Gene Med 2020 09 11;22(9):e3206. Epub 2020 Jun 11.

Graduate School, Tianjin Medical University, Tianjin, China.

Background: The 5-year survival rate of non-small cell lung cancer (NSCLC) is only 15%. Screening some combined gene mutations could predict the survival of NSCLC patients and also provide new ideas for the diagnosis and treatment of NSCLC. The present study aimed to identify signature mutations for survival prediction of NSCLC.

Methods: Clinical and gene mutation information for 949 NSCLC patients was downloaded from TCGA. High frequency mutation and common mutation genes were analyzed based on 1000 cancer related genes. The LASSO-COX model was used to screen gene mutation points and analyze their survival, and then a survival prediction model was established. Fifty NSCLC patients were collected and 1000 targeted genes were enriched by targeted next generation sequencing. The results were used to verify the combination of common mutation genes and the function of the survival model, and then to clarify their clinical significance.

Results: Ten variables were screened out after LASSO-COX analysis, including age, tumor stage, EGFR c.[2,573 T>G], PIK3CA c.[1624G>A], TP53 c.[375G>T], TP53 c.[527G>T], TP53 c.[733G>T], TP53 c.[734G>T], TP53 c.[743G>T], NFE2L2 c.[100C>G]. Except for TP53 c.[743G>T] and NFE2L2 c.[100C>G], the residual six hot spot mutations of EGFR, PIK3CA and TP53 could be regarded as a signature mutations for forecasting the survival time of NSCLC.

Conclusions: The combination of six hot spot mutations of EGFR, PIK3CA and TP53 is expected to be used for predicting the survival time of NSCLC.
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http://dx.doi.org/10.1002/jgm.3206DOI Listing
September 2020

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

Transl Psychiatry 2020 03 20;10(1):100. Epub 2020 Mar 20.

Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors.
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http://dx.doi.org/10.1038/s41398-020-0705-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083923PMC
March 2020

Mapping Subcortical Brain Alterations in 22q11.2 Deletion Syndrome: Effects of Deletion Size and Convergence With Idiopathic Neuropsychiatric Illness.

Am J Psychiatry 2020 07 12;177(7):589-600. Epub 2020 Feb 12.

Imaging Genetics Center, Mark and Mary Stevens Institute for Neuroimaging and Informatics, Keck School of Medicine, Los Angeles (Ching, Villalon Reina, Zavaliangos-Petropulu, Thompson); Department of Biomedical Engineering, Armour College of Engineering, Illinois Institute of Technology, Chicago (Gutman); Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, Los Angeles (Ching, Sun, Lin, Jonas, Pacheco-Hansen, Vajdi, Forsyth, Bearden); Department of Psychology, UCLA, Los Angeles (Ching, Forsyth, Bearden); Department of Biomedical Engineering, Oregon Health and Science University, Portland (Ragothaman); Department of Biomedical Engineering, Duke University, Durham, N.C. (Isaev); Graduate Interdepartmental Program in Neuroscience, UCLA School of Medicine, Los Angeles (Lin, Jonas); Department of Psychiatry, University of Pittsburgh, Pittsburgh (Jalbrzikowski); Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, the Netherlands (Bakker, van Amelsvoort); Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Amsterdam (Bakker); Department of Psychology, Syracuse University, Syracuse, N.Y. (Antshel); Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse (Fremont, Kates); School of Psychology, University of Newcastle, Newcastle, Australia (Campbell, McCabe); MIND Institute and Department of Psychiatry and Behavioral Sciences, University of California Davis, Davis (McCabe, Durdle, Goodrich-Hunsaker, Simon); Institute of Psychiatry, Psychology, and Neuroscience, Sackler Institute for Translational Neurodevelopment, and Department of Forensic and Neurodevelopmental Sciences, King's College London (Craig, Daly, Gudbrandsen, C.M. Murphy, D.G. Murphy); Bethlem Royal Hospital, National Institute for Health Research Maudsley Biomedical Research Centre, and SLaM NHS Foundation Trust, National Autism Unit, London (Craig); Behavioural Genetics Clinic, Adult Autism Service, Behavioural and Developmental Psychiatry Clinical Academic Group, South London and Maudsley NHS Foundation Trust, London (C.M. Murphy, D.G. Murphy); Department of Psychiatry, Royal College of Surgeons in Ireland, and Education and Research Centre, Beaumont Hospital, Dublin (K.C. Murphy); Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands (Fiksinski, Koops, Vorstman); Clinical Genetics Research Program (Bassett, Fiksinski, Chow), Clinical Genetics Service (Chow), Campbell Family Mental Health Research Institute (Bassett), Centre for Addiction and Mental Health, Toronto; Dalglish Family 22q Clinic (Bassett, Fiksinski), Department of Mental Health, and Toronto General Hospital Research Institute (Bassett); University Health Network, Toronto (Fiksinski, Bassett); Department of Psychiatry, University of Toronto, Toronto (Bassett, Vorstman, Chow); Program in Genetics and Genome Biology, Research Institute, and Department of Psychiatry, Hospital for Sick Children, Toronto (Vorstman); Division of Human Genetics and 22q and You Center, Children's Hospital of Philadelphia, Philadelphia (Crowley, Emanuel, McDonald-McGinn, Zackai); Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia (Emanuel, McDonald-McGinn, Zackai); Department of Psychiatry, University of Pennsylvania Perelman School of Medicine and Children's Hospital of Philadelphia, Philadelphia (Gur); Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia (Roalf, Ruparel); Departments of Radiology and Psychiatry, Hospital of the University of Pennsylvania, Philadelphia (Schmitt); Department of Psychological and Brain Sciences, University of California, Santa Barbara (Durdle); Department of Neurology, University of Utah, Salt Lake City (Goodrich-Hunsaker); Child Health Evaluative Sciences, Hospital for Sick Children Research Institute, Toronto (Butcher); Department Psychiatry, University of British Columbia, Vancouver (Vila-Rodriguez); MRC Centre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, U.K. (Cunningham, Doherty, Linden, Moss, Owen, van den Bree); Cardiff University Brain Research Imaging Centre, Cardiff, U.K. (Doherty, Linden); Department of Psychiatry, Pontificia Universidad Católica de Chile, Santiago (Crossley); Clinica Alemana, Universidad del Desarrollo, Centro de Genética y Genomica, Facultad de Medicina, Santiago (Repetto); Departments of Neurology, Psychiatry, Radiology, Engineering, Pediatrics, and Ophthalmology, University of Southern California, Los Angeles (Thompson).

Objective: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group.

Methods: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6-56 years; 49% female).

Results: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, -0.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, -0.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder.

Conclusions: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.
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http://dx.doi.org/10.1176/appi.ajp.2019.19060583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7419015PMC
July 2020

Altered white matter microstructure in 22q11.2 deletion syndrome: a multisite diffusion tensor imaging study.

Mol Psychiatry 2020 11 29;25(11):2818-2831. Epub 2019 Jul 29.

Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.

22q11.2 deletion syndrome (22q11DS)-a neurodevelopmental condition caused by a hemizygous deletion on chromosome 22-is associated with an elevated risk of psychosis and other developmental brain disorders. Prior single-site diffusion magnetic resonance imaging (dMRI) studies have reported altered white matter (WM) microstructure in 22q11DS, but small samples and variable methods have led to contradictory results. Here we present the largest study ever conducted of dMRI-derived measures of WM microstructure in 22q11DS (334 22q11.2 deletion carriers and 260 healthy age- and sex-matched controls; age range 6-52 years). Using harmonization protocols developed by the ENIGMA-DTI working group, we identified widespread reductions in mean, axial and radial diffusivities in 22q11DS, most pronounced in regions with major cortico-cortical and cortico-thalamic fibers: the corona radiata, corpus callosum, superior longitudinal fasciculus, posterior thalamic radiations, and sagittal stratum (Cohen's d's ranging from -0.9 to -1.3). Only the posterior limb of the internal capsule (IC), comprised primarily of corticofugal fibers, showed higher axial diffusivity in 22q11DS. 22q11DS patients showed higher mean fractional anisotropy (FA) in callosal and projection fibers (IC and corona radiata) relative to controls, but lower FA than controls in regions with predominantly association fibers. Psychotic illness in 22q11DS was associated with more substantial diffusivity reductions in multiple regions. Overall, these findings indicate large effects of the 22q11.2 deletion on WM microstructure, especially in major cortico-cortical connections. Taken together with findings from animal models, this pattern of abnormalities may reflect disrupted neurogenesis of projection neurons in outer cortical layers.
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http://dx.doi.org/10.1038/s41380-019-0450-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986984PMC
November 2020

[Systemic Therapy for Low-grade Pulmonary Neuroendocrine Tumor].

Zhongguo Fei Ai Za Zhi 2019 Jan;22(1):34-39

Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin 300000, China.

The lung is the second most common site of neuroendocrine tumors (NETs). Typical and atypical carcinoids are low-grade NETs of the lung. These rare tumors have received little attention and education is needed for treating physicians. The article describes the classifcation of lung NETs, the epidemiology and pathological characteristics. When lung NETs are diagnosed at an early stage, surgical intervention is often curative. For advanced lung NETs patients, different treatment methods including chemotherapy, somatostatin analogs, m-TOR inhibition, peptide receptor radioligand therapy, and biologic systemic therapy are discussed. The conclusions are generally extrapolated from the outcome of extra-pulmonary carcinoids. Prospective randomized well-designed trials are urgently needed to inform current recommendations on systemic treatment.
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http://dx.doi.org/10.3779/j.issn.1009-3419.2019.01.07DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348159PMC
January 2019

Large-scale mapping of cortical alterations in 22q11.2 deletion syndrome: Convergence with idiopathic psychosis and effects of deletion size.

Mol Psychiatry 2020 08 13;25(8):1822-1834. Epub 2018 Jun 13.

Department of Radiology, Division of Neuroradiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

The 22q11.2 deletion (22q11DS) is a common chromosomal microdeletion and a potent risk factor for psychotic illness. Prior studies reported widespread cortical changes in 22q11DS, but were generally underpowered to characterize neuroanatomic abnormalities associated with psychosis in 22q11DS, and/or neuroanatomic effects of variability in deletion size. To address these issues, we developed the ENIGMA (Enhancing Neuro Imaging Genetics Through Meta-Analysis) 22q11.2 Working Group, representing the largest analysis of brain structural alterations in 22q11DS to date. The imaging data were collected from 10 centers worldwide, including 474 subjects with 22q11DS (age = 18.2 ± 8.6; 46.9% female) and 315 typically developing, matched controls (age = 18.0 ± 9.2; 45.9% female). Compared to controls, 22q11DS individuals showed thicker cortical gray matter overall (left/right hemispheres: Cohen's d = 0.61/0.65), but focal thickness reduction in temporal and cingulate cortex. Cortical surface area (SA), however, showed pervasive reductions in 22q11DS (left/right hemispheres: d = -1.01/-1.02). 22q11DS cases vs. controls were classified with 93.8% accuracy based on these neuroanatomic patterns. Comparison of 22q11DS-psychosis to idiopathic schizophrenia (ENIGMA-Schizophrenia Working Group) revealed significant convergence of affected brain regions, particularly in fronto-temporal cortex. Finally, cortical SA was significantly greater in 22q11DS cases with smaller 1.5 Mb deletions, relative to those with typical 3 Mb deletions. We found a robust neuroanatomic signature of 22q11DS, and the first evidence that deletion size impacts brain structure. Psychotic illness in this highly penetrant deletion was associated with similar neuroanatomic abnormalities to idiopathic schizophrenia. These consistent cross-site findings highlight the homogeneity of this single genetic etiology, and support the suitability of 22q11DS as a biological model of schizophrenia.
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http://dx.doi.org/10.1038/s41380-018-0078-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292748PMC
August 2020

Sclerosing thymoma: A rare case report and brief review of literature.

Medicine (Baltimore) 2018 Apr;97(16):e0520

Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin, China.

Rationale: Sclerosing thymoma is an extremely rare mediastinal neoplasm; it was recognized for the first time in 1994 and to date only 15 cases have been reported.

Patient Concerns: The present study report a case of a 65-year-old man who was incidentally found to have an anterior mediastinal nodule, without clinical symptoms including fever, chest pain, and myasthenia gravis.

Diagnoses: The chest computed tomography (CT) revealed the nodule was 4.9 × 4.2 × 3.0 cm in size. And the microscopic and immunohistochemical findings indicated that the final diagnosis was sclerosing thymoma.

Interventions: The anterior mediastinal nodule was completely removed.

Outcomes: No evidence of recurrence or complication was found in the second year after surgery.

Lessons: The biologic behavior of the rare sclerosing thymoma is still largely mysterious; it is utmost importance to classify the sclerosing thymoma from other mediastinal tumors. Its prognosis is favorable and thymectomy is currently the mainstay of treatment.
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http://dx.doi.org/10.1097/MD.0000000000010520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5916703PMC
April 2018

Correlation Between Tumor Necrosis Factor-α and Interleukin-1β in Exhaled Breath Condensate and Pulmonary Function.

Am J Med Sci 2017 10 12;354(4):388-394. Epub 2017 Jun 12.

Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin, China. Electronic address:

Background: Exhaled breath condensate (EBC) has emerged as a noninvasive method for assessing inflammation in lung diseases. Our aim is to investigate the correlation between tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) in EBC and in lung tissue, and between these values in EBC with pulmonary function tests in patients with chronic obstructive pulmonary disease (COPD).

Materials And Methods: To ensure the availability of lung tissue, 60 patients undergoing resection for early lung cancer were divided into 3 groups: a COPD treatment group, a COPD control group and a non-COPD group. Patients in the COPD treatment group received what was termed "lung-protective treatment" including ambroxol, budesonide and ipratropium bromide in addition to chest physiotherapy. Patients underwent pulmonary function testing and EBC collection, and TNF-α and IL-1β were detected by enzyme-linked immunosorbent assay (ELISA). TNF-α and IL-1β in lung tissues were evaluated by immunoflorescense. Correlations were analyzed by Pearson correlation coefficients.

Results: The TNF-α and IL-1β levels in EBC were significantly higher in the COPD groups compared with the non-COPD group before surgery (all P < 0.01), and the levels were significantly decreased after lung-protective treatment was received before surgery (all P < 0.01). TNF-α and IL-1β levels in EBC were significantly decreased in all patients after surgery with lung-protective treatment (P = 0.027, P = 0.004). TNF-α and IL-1β content in lung tissues was significantly higher in the COPD groups (all P < 0.05), and the histologic analysis showed similar results. Negative correlations between FEV1/FVC and expression of TNF-α and IL-1β were observed. There was a positive correlation between TNF-α and IL-1β in lung tissues and in EBC.

Conclusions: TNF-α and IL-1β in EBC are potential biomarkers for evaluating pulmonary function and inflammation in patients with COPD. Furthermore, lung-protective treatment is effective in reducing inflammation in patients with COPD.
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http://dx.doi.org/10.1016/j.amjms.2017.06.004DOI Listing
October 2017

Correlation analysis of surfactant protein A and surfactant protein D with lung function in exhaled breath condensate from lung cancer patients with and without COPD.

Mol Med Rep 2017 Oct 7;16(4):4948-4954. Epub 2017 Aug 7.

Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin 300222, P.R. China.

Pulmonary surfactant protein A (SP‑A) and pulmonary surfactant protein D (SP‑D) are associated with the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of the present study was to determine the correlation between SP‑A, SP‑D and lung function in patients with COPD. A total of 60 patients with lung cancer undergoing unilateral lobectomy were selected and divided into three groups, including a non‑COPD group (n=20), a COPD treatment group (n=20) and a COPD control group (n=20). The levels of SP‑A and SP‑D were detected in the exhaled breath condensate (EBC) using ELISA analysis. Tissue samples were obtained during lobectomy via resection of the adjacent lung tissues, located >5 cm from the nodule. Immunohistochemistry and reverse transcription‑quantitative polymerase chain reaction analysis was performed. The proportion of SP‑A+ alveolar type II (ATII) cells and the mRNA levels of SP‑A and SP‑D in lung tissue were measured. In addition, the correlation between SP‑A and SP‑D in EBC, SP‑A and SP‑D mRNA in lung tissue, forced expiratory volume in 1 sec (FEV1) and the ratio of SP‑A+ ATII, was evaluated. The expression levels of SP‑A and SP‑D were significantly increased in patients of the non‑COPD group compared with the other two groups (P<0.05). In addition, the expression levels of SP‑A were positively correlated with FEV1 and the ratio of SP‑A+ ATII (P<0.05). The expression levels of SP‑D exhibited no correlation with FEV1 and ratio of SP‑A+ ATII (P>0.05). The results of the present study indicated that the SP‑A and SP‑D levels in EBC were correlated with lung function, which contributed to COPD diagnosis. Future studies are required to further investigate the results of the present study.
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http://dx.doi.org/10.3892/mmr.2017.7182DOI Listing
October 2017

Mapping 22q11.2 Gene Dosage Effects on Brain Morphometry.

J Neurosci 2017 06 23;37(26):6183-6199. Epub 2017 May 23.

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California 90095,

Reciprocal chromosomal rearrangements at the 22q11.2 locus are associated with elevated risk of neurodevelopmental disorders. The 22q11.2 deletion confers the highest known genetic risk for schizophrenia, but a duplication in the same region is strongly associated with autism and is less common in schizophrenia cases than in the general population. Here we conducted the first study of 22q11.2 gene dosage effects on brain structure in a sample of 143 human subjects: 66 with 22q11.2 deletions (22q-del; 32 males), 21 with 22q11.2 duplications (22q-dup; 14 males), and 56 age- and sex-matched controls (31 males). 22q11.2 gene dosage varied positively with intracranial volume, gray and white matter volume, and cortical surface area (deletion < control < duplication). In contrast, gene dosage varied negatively with mean cortical thickness (deletion > control > duplication). Widespread differences were observed for cortical surface area with more localized effects on cortical thickness. These diametric patterns extended into subcortical regions: 22q-dup carriers had a significantly larger right hippocampus, on average, but lower right caudate and corpus callosum volume, relative to 22q-del carriers. Novel subcortical shape analysis revealed greater radial distance (thickness) of the right amygdala and left thalamus, and localized increases and decreases in subregions of the caudate, putamen, and hippocampus in 22q-dup relative to 22q-del carriers. This study provides the first evidence that 22q11.2 is a genomic region associated with gene-dose-dependent brain phenotypes. Pervasive effects on cortical surface area imply that this copy number variant affects brain structure early in the course of development. Probing naturally occurring reciprocal copy number variation in the genome may help us understand mechanisms underlying deviations from typical brain and cognitive development. The 22q11.2 genomic region is particularly susceptible to chromosomal rearrangements and contains many genes crucial for neuronal development and migration. Not surprisingly, reciprocal genomic imbalances at this locus confer some of the highest known genetic risks for developmental neuropsychiatric disorders. Here we provide the first evidence that brain morphology differs meaningfully as a function of reciprocal genomic variation at the 22q11.2 locus. Cortical thickness and surface area were affected in opposite directions with more widespread effects of gene dosage on cortical surface area.
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http://dx.doi.org/10.1523/JNEUROSCI.3759-16.2017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6705695PMC
June 2017

CT-guided I brachytherapy on pulmonary metastases after resection of colorectal cancer: A report of six cases.

Oncol Lett 2015 Jan 30;9(1):375-380. Epub 2014 Oct 30.

Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin 300051, P.R. China.

Colorectal cancer (CRC) is one of the most common malignancies in the world and distant metastasis is the main cause of cancer-related mortality. Percutaneous computed tomography (CT) guided radioactive I seed implantation (CTRISI) is a minimally invasive technique used to treat pulmonary metastases in CRC patients. In the present study, following colorectal cancer resection, six patients with pulmonary metastases were treated with computed tomography (CT)-guided percutaneous implantation of radioactive I seeds. At six months following seed implantation, CT examination was performed and compared with the images captured prior to the treatment. Of the total 13 lesions, four had disappeared, eight were reduced by >50% and one was enlarged, indicating that the local control rate was 92.3% (12/13). Overall, two patients developed intraoperative pneumothorax and one experienced hemoptysis subsequent to the procedure. Following a median follow-up period of 31 months, no local recurrence was observed in 12 of the metastatic lesions. The mean survival time was 32.7 months and the median survival time was 31 months.
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http://dx.doi.org/10.3892/ol.2014.2649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4247005PMC
January 2015

Progressive reduction in cortical thickness as psychosis develops: a multisite longitudinal neuroimaging study of youth at elevated clinical risk.

Biol Psychiatry 2015 Jan 12;77(2):147-57. Epub 2014 Jun 12.

Division of Treatment and Prevention Research, National Institute of Mental Health, Rockville, Maryland.

Background: Individuals at clinical high risk (CHR) who progress to fully psychotic symptoms have been observed to show a steeper rate of cortical gray matter reduction compared with individuals without symptomatic progression and with healthy control subjects. Whether such changes reflect processes associated with the pathophysiology of schizophrenia or exposure to antipsychotic drugs is unknown.

Methods: In this multisite study, 274 CHR cases, including 35 individuals who converted to psychosis, and 135 healthy comparison subjects were scanned with magnetic resonance imaging at baseline, 12-month follow-up, or the point of conversion for the subjects who developed fully psychotic symptoms.

Results: In a traveling subjects substudy, excellent reliability was observed for measures of cortical thickness and subcortical volumes. Controlling for multiple comparisons throughout the brain, CHR subjects who converted to psychosis showed a steeper rate of gray matter loss in the right superior frontal, middle frontal, and medial orbitofrontal cortical regions as well as a greater rate of expansion of the third ventricle compared with CHR subjects who did not convert to psychosis and healthy control subjects. Differential tissue loss was present in subjects who had not received antipsychotic medications during the interscan interval and was predicted by baseline levels of an aggregate measure of proinflammatory cytokines in plasma.

Conclusions: These findings demonstrate that the brain changes are not explained by exposure to antipsychotic drugs but likely play a role in psychosis pathophysiology. Given that the cortical changes were more pronounced in subjects with briefer durations of prodromal symptoms, contributing factors may predominantly play a role in acute-onset forms of psychosis.
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http://dx.doi.org/10.1016/j.biopsych.2014.05.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4264996PMC
January 2015

Video-assisted thoracoscopic right lower lobectomy: the Tianjin Chest Hospital experience.

J Thorac Dis 2013 Aug;5 Suppl 3:S282-4

Tianjin Medical College, Tianjin 300222;

Video-assisted thoracoscopic surgery (VATS) is now well established as an alternative to open thoracotomy for major pulmonary resections of bronchogenic carcinoma and benign disease. More than 900 VATS major pulmonary resections have been performed in our center over the last 5 years and we here describe our method for VATS right lower lobectomy. In our center, procedures is performed with 3 incisions. For right lower lobes, the patient is placed into the left lateral position. The inferior pulmonary vein is dissected and divided with an endoscopic vascular stapler. The pulmonary artery branches to right lower lobe are divided with endoscopic staplers, and the lower lobe bronchus is divided at last. Throughout the procedure, hilar and mediastinal lymph nodes are dissected and removed in NSCLC. According to our experience, VATS is safe and feasible in thoracotomy for major pulmonary resections.
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http://dx.doi.org/10.3978/j.issn.2072-1439.2013.08.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3771614PMC
August 2013

Phospholipids and insulin resistance in psychosis: a lipidomics study of twin pairs discordant for schizophrenia.

Genome Med 2012 Jan 18;4(1). Epub 2012 Jan 18.

VTT Technical Research Centre of Finland, Tietotie 2, Espoo, FI-02044 VTT, Finland.

Background: Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission.

Methods: Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 ± 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples.

Results: In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed.

Conclusions: Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins.
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http://dx.doi.org/10.1186/gm300DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3334549PMC
January 2012

Structural and Functional Brain Abnormalities in Schizophrenia.

Curr Dir Psychol Sci 2010 Aug;19(4):226-231

Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles ; Department of Psychology, University of California, Los Angeles.

Schizophrenia is associated with changes in the structure and functioning of a number of key brain systems, including prefrontal and medial temporal lobe regions involved in working memory and declarative memory, respectively. Imaging techniques provide an unparalleled window into these changes, allowing repeated assessments across pre- and post-onset stages of the disorder and in relation to critical periods of brain development. Here we review recent directions in structural and functional neuroimaging research on schizophrenia. The view emerging from this work is that schizophrenia is fundamentally a disorder of disrupted neural connectivity, the sources of which appear to be genetic and environmental risk factors influencing brain development both prenatally and during adolescence.
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http://dx.doi.org/10.1177/0963721410377601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4235761PMC
August 2010

Elucidating a magnetic resonance imaging-based neuroanatomic biomarker for psychosis: classification analysis using probabilistic brain atlas and machine learning algorithms.

Biol Psychiatry 2009 Dec 3;66(11):1055-60. Epub 2009 Sep 3.

Department of Psychology, University of California at Los Angeles, 90095, USA.

Background: No objective diagnostic biomarkers or laboratory tests have yet been developed for psychotic illness. Magnetic resonance imaging (MRI) studies consistently find significant abnormalities in multiple brain structures in psychotic patients relative to healthy control subjects, but these abnormalities show substantial overlap with anatomic variation that is in the normal range and therefore nondiagnostic. Recently, efforts have been made to discriminate psychotic patients from healthy individuals using machine-learning-based pattern classification methods on MRI data.

Methods: Three-dimensional cortical gray matter density (GMD) maps were generated for 36 patients with recent-onset psychosis and 36 sex- and age-matched control subjects using a cortical pattern matching method. Between-group differences in GMD were evaluated. Second, the sparse multinomial logistic regression classifier included in the Multivariate Pattern Analysis in Python machine-learning package was applied to the cortical GMD maps to discriminate psychotic patients from control subjects.

Results: Patients showed significantly lower GMD, particularly in prefrontal, cingulate, and lateral temporal brain regions. Pattern classification analysis achieved 86.1% accuracy in discriminating patients from controls using leave-one-out cross-validation.

Conclusions: These results suggest that even at the early stage of illness, psychotic patients present distinct patterns of regional cortical gray matter changes that can be discriminated from the normal pattern. These findings indicate that we can detect complex patterns of brain abnormality in early stages of psychotic illness, which has critical implications for early identification and intervention in individuals at ultra-high risk for developing psychosis/schizophrenia.
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http://dx.doi.org/10.1016/j.biopsych.2009.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192809PMC
December 2009

Progressive brain structural changes mapped as psychosis develops in 'at risk' individuals.

Schizophr Res 2009 Mar 12;108(1-3):85-92. Epub 2009 Jan 12.

Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Parkville, Victoria, Australia.

Background: Schizophrenia and related psychoses are associated with brain structural abnormalities. Recent findings in 'at risk' populations have identified progressive changes in various brain regions preceding illness onset, while changes especially in prefrontal and superior temporal regions have been demonstrated in first-episode schizophrenia patients. However, the timing of the cortical changes and their regional extent, relative to the emergence of psychosis, has not been clarified. We followed individuals at high-risk for psychosis to determine whether structural changes in the cerebral cortex occur with the onset of psychosis. We hypothesized that progressive volume loss occurs in prefrontal regions during the transition to psychosis.

Methods: 35 individuals at ultra-high risk (UHR) for developing psychosis, of whom 12 experienced psychotic onset by 1-year follow-up ('converters'), participated in a longitudinal structural MRI study. Baseline and follow-up T1-weighted MR images were acquired and longitudinal brain surface contractions were assessed using Cortical Pattern Matching.

Results: Significantly greater brain contraction was found in the right prefrontal region in the 'converters' compared with UHR cases who did not develop psychosis ('non-converters').

Conclusions: These findings show cortical volume loss is associated with the onset of psychosis, indicating ongoing pathological processes during the transition stage to illness. The prefrontal volume loss is in line with structural and functional abnormalities in schizophrenia, suggesting a critical role for this change in the development of psychosis.
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http://dx.doi.org/10.1016/j.schres.2008.11.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2670732PMC
March 2009

Developmental disruptions in neural connectivity in the pathophysiology of schizophrenia.

Dev Psychopathol 2008 ;20(4):1297-327

Department of Psychology, 1285 Franz Hall Box 951563, University of California, Los Angeles, Los Angeles, CA 90095-1563, USA.

Schizophrenia has been thought of as a disorder of reduced functional and structural connectivity. Recent advances in neuroimaging techniques such as functional magnetic resonance imaging, structural magnetic resonance imaging, diffusion tensor imaging, and small animal imaging have advanced our ability to investigate this hypothesis. Moreover, the power of longitudinal designs possible with these noninvasive techniques enable the study of not just how connectivity is disrupted in schizophrenia, but when this disruption emerges during development. This article reviews genetic and neurodevelopmental influences on structural and functional connectivity in human populations with or at risk for schizophrenia and in animal models of the disorder. We conclude that the weight of evidence across these diverse lines of inquiry points to a developmental disruption of neural connectivity in schizophrenia and that this disrupted connectivity likely involves susceptibility genes that affect processes involved in establishing intra- and interregional connectivity.
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http://dx.doi.org/10.1017/S095457940800062XDOI Listing
February 2009

WITHDRAWN: Progressive brain structural changes mapped as psychosis develops in 'at risk' individuals.

Schizophr Res 2008 Feb 11. Epub 2008 Feb 11.

Melbourne Neuropsychiatry Centre, Department of Psychiatry, The University of Melbourne and Melbourne Health, Parkville, Victoria, Australia; Clinical Neuroscience Laboratory, Departments of Psychology and Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, USA.

This article has been withdrawn consistent with Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The Publisher apologizes for any inconvenience this may cause.
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http://dx.doi.org/10.1016/j.schres.2007.12.473DOI Listing
February 2008

Mapping cortical thickness in children with 22q11.2 deletions.

Cereb Cortex 2007 Aug 20;17(8):1889-98. Epub 2006 Oct 20.

Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA 90095, USA.

The 22q11.2 deletion syndrome (velocardiofacial/DiGeorge syndrome, 22q11.2DS) involves cardiac and craniofacial anomalies, marked deficits in visuospatial cognition, and elevated rates of psychosis. Although the mechanism is unknown, characteristic brain alterations may predispose to development of psychosis and cognitive deficits in 22q11DS. We applied cortical pattern matching and new methods for measuring cortical thickness in millimeters to structural magnetic resonance images of 21 children with confirmed 22q11.2 deletions and 13 demographically matched healthy comparison subjects. Thickness was mapped at 65 536 homologous points, based on 3-dimensional distance from the cortical gray-white matter interface to the external gray-cerebrospinal fluid boundary. A pattern of regionally specific cortical thinning was observed in superior parietal cortices and right parietooccipital cortex, regions critical for visuospatial processing, and bilaterally in the most inferior portion of the inferior frontal gyrus (pars orbitalis), a key area for language development. Several of the 30 genes encoded in the deleted segment are highly expressed in the developing brain and known to affect early neuronal migration. These brain maps reveal how haploinsufficiency for such genes can affect cortical development and suggest a possible underlying pathophysiology of the neurobehavioral phenotype.
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http://dx.doi.org/10.1093/cercor/bhl097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2819929PMC
August 2007

Structural brain imaging evidence for multiple pathological processes at different stages of brain development in schizophrenia.

Schizophr Bull 2005 Jul 14;31(3):672-96. Epub 2005 Jul 14.

Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Royal Melbourne Hospital, Sunshine Hospital, Victoria.

The underlying neurobiology of emerging psychotic disorders is not well understood. While there is evidence from structural imaging and other studies supporting the popular notion that schizophrenia arises as a consequence of an "early neurodevelopmental" lesion, more recent findings challenge this notion. Evidence, including our own data, suggests that dynamic brain changes occur during the earliest stages of a psychotic illness, including around the time of transition to illness. In this article we review the available longitudinal and relevant cross-sectional structural neuroimaging studies focusing on both the very early neurodevelopmental markers (pre- or perinatal origin) and the later markers (late neurodevelopmental) around the period of transition to illness. Based on our review of recent findings, we suggest that the onset of psychosis is a time of active brain changes, wherein, for a proportion of individuals, (i) an early (pre- and perinatal) neurodevelopmental lesion renders the brain vulnerable to anomalous late (particularly postpubertal) neurodevelopmental processes, as indicated by evidence for accelerated loss of gray matter and aberrant connectivity particularly in prefrontal regions; and (ii) these anomalous neurodevelopmental processes interact with other causative factors associated with the onset of psychosis (e.g., substance use, stress, and dysregulation of the hypothalamic-pituitary-adrenal axis function), which together have neuroprogressive sequelae involving medial temporal and orbital prefrontal regions, as suggested by imaging studies around transition to active illness. However, the pathological processes underlying such progressive changes during "late neurodevelopment" remain unclear but may reflect anomalies of synaptic plasticity, abnormal brain maturation, the adverse effects of stress, or other environmental factors. In this context, the features of schizophrenia, including the neuropsychological deficits and behavioral manifestations, can be understood as direct effects of these multiple pathological processes at various neurodevelopmental stages, including genetic and nongenetic etiological factors.
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http://dx.doi.org/10.1093/schbul/sbi034DOI Listing
July 2005
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