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- Schwarz, E, et al.
(author)
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Reproducible grey matter patterns index a multivariate, global alteration of brain structure in schizophrenia and bipolar disorder
- 2019
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In: Translational psychiatry. - : Springer Science and Business Media LLC. - 2158-3188. ; 9:1, s. 12-
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Journal article (peer-reviewed)abstract
- Schizophrenia is a severe mental disorder characterized by numerous subtle changes in brain structure and function. Machine learning allows exploring the utility of combining structural and functional brain magnetic resonance imaging (MRI) measures for diagnostic application, but this approach has been hampered by sample size limitations and lack of differential diagnostic data. Here, we performed a multi-site machine learning analysis to explore brain structural patterns of T1 MRI data in 2668 individuals with schizophrenia, bipolar disorder or attention-deficit/ hyperactivity disorder, and healthy controls. We found reproducible changes of structural parameters in schizophrenia that yielded a classification accuracy of up to 76% and provided discrimination from ADHD, through it lacked specificity against bipolar disorder. The observed changes largely indexed distributed grey matter alterations that could be represented through a combination of several global brain-structural parameters. This multi-site machine learning study identified a brain-structural signature that could reproducibly differentiate schizophrenia patients from controls, but lacked specificity against bipolar disorder. While this currently limits the clinical utility of the identified signature, the present study highlights that the underlying alterations index substantial global grey matter changes in psychotic disorders, reflecting the biological similarity of these conditions, and provide a roadmap for future exploration of brain structural alterations in psychiatric patients.
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| 3. |
- Elvsashagen, T, et al.
(author)
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The genetic architecture of human brainstem structures and their involvement in common brain disorders
- 2020
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In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4016-
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Journal article (peer-reviewed)abstract
- Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson’s disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.
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| 4. |
- Malmqvist, Anna, et al.
(author)
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Increased peripheral levels of TARC/CCL17 in first episode psychosis patients
- 2019
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In: Schizophrenia Research. - : ELSEVIER. - 0920-9964 .- 1573-2509. ; 210, s. 221-227
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Journal article (peer-reviewed)abstract
- Background: Evidence for a link between the pathophysiology of schizophrenia and the immune system is mounting. Altered levels of chemokines in plasma have previously been reported in patients with schizophrenia under antipsychotic medication. Here we aimed to study both peripheral and central chemokine levels in drugnaive or short-time medicated first episode psychosis (FEP) patients. Method: We analyzed nine chemokines in plasma and CSF from 41 FEP patients and 22 healthy controls using electrochemiluminescence assay. Results: In plasma four chemokines; TARC/CCL17, eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 and in CSF one chemokine; IP-10/CXCL10 showed reliable detection in N50% of the cases. FEP patients displayed increased levels of TARC/CCL17 in plasma compared to healthy controls, 89.6 (IQR 66.2-125.8) pg/mL compared to 48.6 (IQR 28.0-71.7) pg/mL (p = 0.001). The difference was not attributed to confounding factors. Plasma TARC/CCL17 was not associated with PANSS, CGI or GAF scores, neither with cognitive functions. The chemokines eotaxin/CCL11, MDC/CCL22, IP-10/CXCL10 in plasma and IP-10/CXCL10 in CSF did not differ between FEP patients and controls. Conclusion: In line with a previous study showing that chronic patients with schizophrenia display increased plasma TARC/CCL17 levels, we here found an elevation in FEP patients suggesting a role of TARC/CCL17 in early stages of schizophrenia. The exactmechanism of this involvement is still unknown and future longitudinal studies as well as studies of central and peripheral chemokine levels would be of great interest. (C) 2018 Elsevier B.V. All rights reserved.
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| 8. |
- Orhan, F., et al.
(author)
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Increased number of monocytes and plasma levels of MCP-1 and YKL-40 in first-episode psychosis
- 2018
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In: Acta Psychiatrica Scandinavica. - : WILEY. - 0001-690X .- 1600-0447. ; 138:5, s. 432-440
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Journal article (peer-reviewed)abstract
- ObjectiveMethodAccumulating evidence implicates immune activation in the development of schizophrenia. Here, monocyte numbers, monocyte chemoattractant protein-1 (MCP-1) and chitinase-3-like protein 1 (YKL-40) were investigated in plasma and cerebrospinal fluid (CSF) in first-episode psychosis (FEP) patients. CSF and blood were sampled from 42 first-episode psychosis (FEP) patients and 22 healthy controls. The levels of YKL-40 and MCP-1 were measured using electrochemiluminescence assay, and blood monocytes were counted using an XN-9000-hematology analyzer. ResultsConclusionWe found higher plasma levels of MCP-1 and YKL-40 in FEP patients compared with healthy controls, a condition that was unrelated to antipsychotic and/or anxiolytic medication. This was combined with an increased number of blood monocytes and a borderline significant increase in YKL-40 levels in the CSF of tobacco-free FEP patients. Plasma or CSF chemokines or blood monocytes did not correlate with the severity of symptoms or the level of functioning. These data demonstrate activation of monocytes in FEP and strengthens the idea of an immune dysfunction of psychotic disorders. Further studies are required to perceive a role of YKL-40 and MCP-1 in the initiation and progression of schizophrenia.
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| 9. |
- Agewall, S, et al.
(author)
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Risk factors for myocardial infarction with normal coronary arteries and myocarditis compared with myocardial infarction with coronary artery stenosis
- 2012
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In: Angiology. - : SAGE Publications. - 1940-1574 .- 0003-3197. ; 63:7, s. 500-503
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Journal article (peer-reviewed)abstract
- The interest and awareness of myocardial infarction with normal coronary arteries (MINCA) have increased recently due to the frequent use of coronary angiography, the description of Takotsubo stress cardiomyopathy, and new sensitive troponin analyses. The prevalence of MINCA in all patients with myocardial infarction (MI) was registered during a 3-month period in the Stockholm metropolitan area in Sweden. The results showed that MINCA is more common than previously thought (7%) and affecting one third of every woman with MI. Patients with myocarditis were younger and more often presented with signs of inflammation such as elevated C-reactive protein and fever. Myocarditis constitutes an important differential diagnosis for coronary artery disease. There is a need for larger studies of MINCA, including investigation with cardiac magnetic resonance imaging, to establish prevalence and pathological process in this important subgroup of MI.
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| 10. |
- Collste, O., et al.
(author)
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Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study
- 2013
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In: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 273:2, s. 189-196
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Journal article (peer-reviewed)abstract
- Collste O, Sorensson P, Frick M, Agewall S, Daniel M, Henareh L, Ekenback C, Eurenius L, Guiron C, Jernberg T, Hofman-Bang C, Malmqvist K, Nagy E, Arheden H, Tornvall P (Sodersjukhuset, Stockholm; Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden; University of Oslo, Oslo, Norway; Sankt Goran Hospital Capio, Karolinska Institutet, Stockholm; Huddinge, Stockholm; Danderyd Hospital, Karolinska Institutet, Stockholm; and Skane University Hospital, Lund University, Lund, Sweden). Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study. J Intern Med 2013; 273: 189-196. Objectives Myocardial infarction with angiographically normal coronary arteries (MINCA) is an important subtype of myocardial infarction; however, the prevalence, underlying pathophysiology, prognosis and optimal management of this condition are still largely unknown. Cardiovascular magnetic resonance (CMR) imaging has the potential to clarify the underlying pathology in patients with MINCA. The objective of this study was to investigate the diagnostic value of CMR imaging in this group of patients. Design The prospective, multicentre, observational Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study. Setting Coronary care units in the Stockholm metropolitan area. Subjects Patients between 35 and 70 years of age with MINCA were consecutively included in the screening phase of the SMINC study. All patients had a typical clinical presentation, fulfilling the universal definition of myocardial infarction and had normal coronary angiography finding. Patients with known structural or coronary heart disease or other known causes of elevated troponin levels were excluded. Results In total, 176 patients with MINCA were screened from 2007 to 2011. Of these, 152 underwent CMR imaging. The investigation was performed a median of 12 (interquartile range 628) days after hospital admission; 67% of the findings were normal, whereas 19% of patients had signs of myocardial necrosis and 7% had signs of myocarditis. The remaining patients (7%) had either unrecognized hypertrophic cardiomyopathy or could not be classified. Conclusion In this consecutive series of patients with MINCA, CMR imaging may help to differentiate between those with myocarditis, myocardial necrosis and normal myocardium. The incidence of MINCA was higher than previously reported. After excluding cases of myocarditis, MINCA consists of a large group of patients with normal CMR imaging results and a smaller group with myocardial necrosis. The aetiologies of these different imaging findings need to be explored.
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