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1. Reply to 'Comments on Kullback-Leibler and renormalized entropies: Applications to electroencephalograms of epilepsy patients'

Author

Quiroga, R. Quian, Arnhold, J., Lehnertz, K., and Grassberger, P.

Subjects
Condensed Matter - Statistical Mechanics, Nonlinear Sciences - Chaotic Dynamics, Physics - Biological Physics, Quantitative Biology
Abstract

Kopitzki et al (preceeding comment) claim that the relationship between Renormalized and Kullback-Leibler entropies has already been given in their previous papers. Moreover, they argue that the first can give more useful information for e.g. localizing the seizure-generating area in epilepsy patients. In our reply we stress that if the relationship between both entropies would have been known by them, they should have noticed that the condition on the effective temperature is unnecessary. Indeed, this condition led them to choose different reference segments for different channels, even if this was physiologically unplausible. Therefore, we still argue that it is very unlikely that renormalized entropy will give more information than the conventional Kullback-Leibler entropy., Comment: 4 pages, 1 figure. Phys. Rev. E, in press

Published
2002

2. Kullback-Leibler and Renormalized Entropy: Applications to EEGs of Epilepsy Patients

Author

Quiroga, R. Quian, Arnhold, J., Lehnertz, K., and Grassberger, P.

Subjects
Physics - Biological Physics, Condensed Matter, Nonlinear Sciences - Chaotic Dynamics, Physics - Computational Physics, Physics - Data Analysis, Statistics and Probability, Physics - Medical Physics, Quantitative Biology
Abstract

Recently, renormalized entropy was proposed as a novel measure of relative entropy (P. Saparin et al., Chaos, Solitons & Fractals 4, 1907 (1994)) and applied to several physiological time sequences, including EEGs of patients with epilepsy. We show here that this measure is just a modified Kullback-Leibler (K-L) relative entropy, and it gives similar numerical results to the standard K-L entropy. The latter better distinguishes frequency contents of e.g. seizure and background EEGs than renormalized entropy. We thus propose that renormalized entropy might not be as useful as claimed by its proponents. In passing we also make some critical remarks about the implementation of these methods., Comment: 15 pages, 4 Postscript figures. Submitted to Phys. Rev. E, 1999

Published
1999
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3. A Robust Method for Detecting Interdependences: Application to Intracranially Recorded EEG

Author

Arnhold, J., Grassberger, P., Lehnertz, K., and Elger, C. E.

Subjects
Nonlinear Sciences - Chaotic Dynamics, Quantitative Biology
Abstract

We present a measure for characterizing statistical relationships between two time sequences. In contrast to commonly used measures like cross-correlations, coherence and mutual information, the proposed measure is non-symmetric and provides information about the direction of interdependence. It is closely related to recent attempts to detect generalized synchronization. However, we do not assume a strict functional relationship between the two time sequences and try to define the measure so as to be robust against noise, and to detect also weak interdependences. We apply our measure to intracranially recorded electroencephalograms of patients suffering from severe epilepsies., Comment: 29 pages, 5 figures, paper accepted for publication in Physica D

Published
1999
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4. Learning Driver-Response Relationships from Synchronization Patterns

Author

Quiroga, R. Quian, Arnhold, J., and Grassberger, P.

Subjects
Nonlinear Sciences - Chaotic Dynamics, Condensed Matter, Physics - Computational Physics
Abstract

We test recent claims that causal (driver/response) relationships can be deduced from interdependencies between simultaneously measured time series. We apply two recently proposed interdependence measures which should give similar results as cross predictabilities used by previous authors. The systems which we study are asymmetrically coupled simple models (Lorenz, Roessler, and Henon models), the couplings being such as to lead to generalized synchronization. If the data were perfect (noisefree, infinitely long), we should be able to detect, at least in some cases, which of the coupled systems is the driver and which the response. This might no longer be true if the time series has finite length. Instead, estimated interdependencies and mutual cross predictabilities depend strongly on which of the systems has a higher effective dimension at the typical neighborhood sizes used to estimate them, and causal relationships are more difficult to detect. We also show that slightly different variants of the interdependence measure can have quite different sensitivities., Comment: LaTex, 26 pages with 6 ps figures. Subm. to Phys. Rev. E

Published
1999
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5. Capacity of ceruloplasmin to scavenge products of the respiratory burst of neutrophils is not altered by the products of reactions catalyzed by myeloperoxidase

Author

Sokolov, A.V., Kostevich, V.A., Varfolomeeva, E.Y., Grigorieva, D.V., Gorudko, I.V., Kozlov, S.O., Kudryavtsev, I.V., Mikhalchik, E.V., Filatov, M.V., Cherenkevich, S.N., Panasenko, O.M., Arnhold, J., and Vasilyev, V.B.

Subjects
Peroxidase -- Health aspects, Neutrophils -- Health aspects, Biological sciences
Abstract

CP is a copper-containing ferroxidase of blood plasma, which acts as an acute phase reactant during inflammation. The effect of oxidative modification of CP induced by oxidants produced by MPO, such as HOCl, HOBr, and HOSCN, on its spectral, enzymatic, and anti-inflammatory properties was studied. We monitored the chemiluminescence of lucigenin and luminol along with fluorescence of hydroethidine and scopoletin to assay the inhibition by CP of the neutrophilic respiratory burst induced by PMA or fMLP. Superoxide dismutase activity of CP and its capacity to reduce the production of oxidants in respiratory burst of neutrophils remained virtually unchanged upon modifications caused by HOC1, HOBr, and HOSCN. Meanwhile, the absorption of type I copper ions at 610 nm became reduced, along with a drop in the ferroxidase and amino oxidase activities of CP. Likewise, its inhibitory effect on the halogenating activity of MPO was diminished. Sera of either healthy donors or patients with Wilson disease were co-incubated with neutrophils from healthy volunteers. In these experiments, we observed an inverse relationship between the content of CP in sera and the rate of [H.sub.2][O.sub.2] production by activated neutrophils. In conclusion, CP is likely to play a role of an anti-inflammatory factor tempering the neutrophil respiratory burst in the bloodstream despite the MPO-mediated oxidative modifications. Key words: ceruloplasmin, myeloperoxidase, superoxide dismutase, neutrophils, respiratory burst. Resume : La ceruloplasmine (CP) est une ferroxidase du plasma sanguin comportant du cuivre, qui agit comme proteine de phase aigue durant l'inflammation. L'effet de la modification oxydative de la CP induite par les oxydants produits par la myeloperoxydase (MPO), comme le HOCl, le HOBr et le HOSCN, sur ses proprietes spectrale, enzymatique et anti-inflammatoire a ete etudie. Les auteurs ont suivi la chimiluminescence de la lucigenine et du luminol parallelement a la fluorescence de l'hydroethidine et de la scopoletine, afin de mesurer l'inhibition par la CP de la flambee oxydative des neutrophiles induite par le phorbol 12-myristate 13-acetate (PMA) ou la formyl-methionyl-leucyl-phenylalanine (fMLP). L'activite superoxyde dismutase de la CP et sa capacite de reduire la production d'oxydants dans la flambee oxydative des neutrophiles demeuraient pratiquement inchangees a la suite des modifications causees par le HOCl, le HOBr et le HOSCN. En meme temps, l'absorption d'ions cuivre de type I a 610 nm etait reduite parallelement a une chute des activites ferroxidase et amino-oxydase de la CP. De la meme facon, son effet inhibiteur sur l'activite d'halogenation de la MPO etait diminue. Les serums de donneurs sains ou de patients atteints de la maladie de Wilson ont ete co-incubes avec les neutrophiles de donneurs sains. Lors de ces experiences, les auteurs ont observe une correlation inverse entre le contenu en CP dans le serum et le taux de production de [H.sub.2][O.sub.2] par les neutrophiles actives. En conclusion, la CP joue probablement un role de facteur anti-inflammatoire en temperant la flambee oxydative des neutrophiles dans la circulation sanguine malgre les modifications oxydatives provoquees par la MPO. [Traduit par la Redaction] Mots-cles: ceruloplasmine, myeloperoxydase, superoxyde dismutase, neutrophiles, flambee oxydative., Introduction One of the effector links of innate immunity is represented by polymorphonuclear leukocytes (neutrophils). The primary response to alien microorganisms is stimulation of neutrophils, which is accompanied by changes [...]

Published
2018
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6. Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Author

Velthorst E., Mollon J., Murray R. M., de Haan L., Germeys I. M., Glahn D. C., Arango C., van der Ven E., Di Forti M., Bernardo M., Guloksuz S., Delespaul P., Mezquida G., Amoretti S., Bobes J., Saiz P. A., Garcia-Portilla M. P., Santos J. L., Jimenez-Lopez E., Sanjuan J., Aguilar E. J., Arrojo M., Carracedo A., Lopez G., Gonzalez-Penas J., Parellada M., Atbasoglu C., Saka M. C., Ucok A., Alptekin K., Akdede B., Binbay T., Altinyazar V., Ulas H., Yalincetin B., Gumus-Akay G., Beyaz B. C., Soygur H., Cankurtaran E. S., Kaymak S. U., Maric N. P., Mihaljevic M. M., Petrovic S. A., Mirjanic T., Del-Ben C. M., Ferraro L., Gayer-Anderson C., Jones P. B., Jongsma H. E., Kirkbride J. B., La Cascia C., Lasalvia A., Tosato S., Llorca P. -M., Menezes P. R., Morgan C., Quattrone D., Menchetti M., Selten J. -P., Szoke A., Tarricone I., Tortelli A., McGuire P., Valmaggia L., Kempton M. J., van der Gaag M., Riecher-Rossler A., Bressan R. A., Barrantes-Vidal N., Nelson B., McGorry P., Pantelis C., Krebs M. -O., Ruhrmann S., Sachs G., Rutten B. P. F., van Os J., Alizadeh B. Z., van Amelsvoort T., Bartels-Velthuis A. A., Bruggeman R., van Beveren N. J., Luykx J. J., Cahn W., Simons C. J. P., Kahn R. S., Schirmbeck F., van Winkel R., Calem M., Tognin S., Modinos G., Pisani S., Kraan T. C., van Dam D. S., Burger N., Amminger G. P., Politis A., Goodall J., Borgwardt S., Studerus E., Gadelha A., Brietzke E., Asevedo G., Asevedo E., Zugman A., Dominguez-Martinez T., Monsonet M., Cristobal-Narvaez P., Racioppi A., Kwapil T. R., Kazes M., Daban C., Bourgin J., Gay O., Mam-Lam-Fook C., Nordholm D., Rander L., Krakauer K., Glenthoj L. B., Glenthoj B., Gebhard D., Arnhold J., Klosterkotter J., Lasser I., Winklbaur B., Reichenberg A., Velthorst E., Mollon J., Murray R.M., de Haan L., Germeys I.M., Glahn D.C., Arango C., van der Ven E., Di Forti M., Bernardo M., Guloksuz S., Delespaul P., Mezquida G., Amoretti S., Bobes J., Saiz P.A., Garcia-Portilla M.P., Santos J.L., Jimenez-Lopez E., Sanjuan J., Aguilar E.J., Arrojo M., Carracedo A., Lopez G., Gonzalez-Penas J., Parellada M., Atbasoglu C., Saka M.C., Ucok A., Alptekin K., Akdede B., Binbay T., Altinyazar V., Ulas H., Yalincetin B., Gumus-Akay G., Beyaz B.C., Soygur H., Cankurtaran E.S., Kaymak S.U., Maric N.P., Mihaljevic M.M., Petrovic S.A., Mirjanic T., Del-Ben C.M., Ferraro L., Gayer-Anderson C., Jones P.B., Jongsma H.E., Kirkbride J.B., La Cascia C., Lasalvia A., Tosato S., Llorca P.-M., Menezes P.R., Morgan C., Quattrone D., Menchetti M., Selten J.-P., Szoke A., Tarricone I., Tortelli A., McGuire P., Valmaggia L., Kempton M.J., van der Gaag M., Riecher-Rossler A., Bressan R.A., Barrantes-Vidal N., Nelson B., McGorry P., Pantelis C., Krebs M.-O., Ruhrmann S., Sachs G., Rutten B.P.F., van Os J., Alizadeh B.Z., van Amelsvoort T., Bartels-Velthuis A.A., Bruggeman R., van Beveren N.J., Luykx J.J., Cahn W., Simons C.J.P., Kahn R.S., Schirmbeck F., van Winkel R., Calem M., Tognin S., Modinos G., Pisani S., Kraan T.C., van Dam D.S., Burger N., Amminger G.P., Politis A., Goodall J., Borgwardt S., Studerus E., Gadelha A., Brietzke E., Asevedo G., Asevedo E., Zugman A., Dominguez-Martinez T., Monsonet M., Cristobal-Narvaez P., Racioppi A., Kwapil T.R., Kazes M., Daban C., Bourgin J., Gay O., Mam-Lam-Fook C., Nordholm D., Rander L., Krakauer K., Glenthoj L.B., Glenthoj B., Gebhard D., Arnhold J., Klosterkotter J., Lasser I., Winklbaur B., Reichenberg A., RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience, Neurosciences, Psychiatry, Clinical Developmental Psychology, World Health Organization (WHO) Collaborating Center, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Adult Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, and Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep

Subjects
0301 basic medicine, validity, medicine.medical_treatment, CHILDHOOD, Neuropsychological Tests, FAMÍLIA, episode, Cognition, 0302 clinical medicine, DEFICITS, Settore MED/48 -Scienze Infermierist. e Tecn. Neuro-Psichiatriche e Riabilitat, Medicine, Cognitive impairment, Psychiatry, Symptom severity, Cannabis use, IMPAIRMENT, ABILITY, Psychiatry and Mental health, Schizophrenia, RELIABILITY, Neuropsychological Test, Life Sciences & Biomedicine, Human, Clinical psychology, Adult, Biochemistry & Molecular Biology, impairment, schizophrenia-patients, ability, GENETIC RISK, Psychotic Disorder, SCHIZOPHRENIA-PATIENTS, 03 medical and health sciences, Cellular and Molecular Neuroscience, SDG 3 - Good Health and Well-being, Settore M-PSI/08 - Psicologia Clinica, Humans, In patient, Cognitive skill, VALIDITY, Antipsychotic, Molecular Biology, Settore MED/25 - Psichiatria, Aged, Cross-Sectional Studie, DECLINE, Science & Technology, reliability, business.industry, Working memory, Siblings, Neurosciences, Diagnostic markers, medicine.disease, Cross-Sectional Studies, 030104 developmental biology, deficits, Psychotic Disorders, PSYCHOSIS, COGNITION, MULTICENTRIC STUDY, Neurosciences & Neurology, business, EPISODE, 030217 neurology & neurosurgery
Abstract

The European Community’s Seventh Framework Programme under grant agreement No. HEALTH-F2-2010-241909 (EUGEI); The Spanish sample was supported by the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III (SAM16PE07CP1, PI16/02012, PI19/024) (...), Velthorst, E., Mollon, J., Murray, R.M., de Haan, L., Germeys, I.M., Glahn, D.C., Arango, C., van der Ven, E., Di Forti, M., Bernardo, M., Guloksuz, S., Delespaul, P., Mezquida, G., Amoretti, S., Bobes, J., Saiz, P.A., García-Portilla, M.P., Santos, J.L., Jiménez-López, E., Sanjuan, J., Aguilar, E.J., Arrojo, M., Carracedo, A., López, G., González-Peñas, J., Parellada, M., Atbaşoğlu, C., Saka, M.C., Üçok, A., Alptekin, K., Akdede, B., Binbay, T., Altınyazar, V., Ulaş, H., Yalınçetin, B., Gümüş-Akay, G., Beyaz, B.C., Soygür, H., Cankurtaran, E.Ş., Kaymak, S.U., Maric, N.P., Mihaljevic, M.M., Petrovic, S.A., Mirjanic, T., Del-Ben, C.M., Ferraro, L., Gayer-Anderson, C., Jones, P.B., Jongsma, H.E., Kirkbride, J.B., La Cascia, C., Lasalvia, A., Tosato, S., Llorca, P.-M., Menezes, P.R., Morgan, C., Quattrone, D., Menchetti, M., Selten, J.-P., Szöke, A., Tarricone, I., Tortelli, A., McGuire, P., Valmaggia, L., Kempton, M.J., van der Gaag, M., Riecher-Rössler, A., Bressan, R.A., Barrantes-Vidal, N., Nelson, B., McGorry, P., Pantelis, C., Krebs, M.-O., Ruhrmann, S., Sachs, G., Rutten, B.P.F., van Os, J., Alizadeh, B.Z., van Amelsvoort, T., Bartels-Velthuis, A.A., Bruggeman, R., van Beveren, N.J., Luykx, J.J., Cahn, W., Simons, C.J.P., Kahn, R.S., Schirmbeck, F., van Winkel, R., Calem, M., Tognin, S., Modinos, G., Pisani, S., Kraan, T.C., van Dam, D.S., Burger, N., Amminger, G.P., Politis, A., Goodall, J., Borgwardt, S., Studerus, E., Gadelha, A., Brietzke, E., Asevedo, G., Asevedo, E., Zugman, A., Domínguez-Martínez, T., Monsonet, M., Cristóbal-Narváez, P., Racioppi, A., Kwapil, T.R., Kazes, M., Daban, C., Bourgin, J., Gay, O., Mam-Lam-Fook, C., Nordholm, D., Rander, L., Krakauer, K., Glenthøj, L.B., Glenthøj, B., Gebhard, D., Arnhold, J., Klosterkötter, J., Lasser, I., Winklbaur, B., Reichenberg, A., EU-GEI High Risk Study

Published
2021

13. Association of Adverse Outcomes With Emotion Processing and Its Neural Substrate in Individuals at Clinical High Risk for Psychosis

Author

Modinos, G, Kempton, MJ, Tognin, S, Calem, M, Porffy, L, Antoniades, M, Mason, A, Azis, M, Allen, P, Nelson, B, McGorry, P, Pantelis, C, Riecher-Rossler, A, Borgwardt, S, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Glenthoj, B, Ruhrmann, S, Sachs, G, Rutten, B, van Os, J, de Haan, L, Velthorst, E, van der Gaag, M, Valmaggia, LR, McGuire, P, Kraan, TC, van Dam, DS, Burger, N, Amminger, GP, Politis, A, Goodall, J, Rapp, C, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Dominguez-Martinez, T, Monsonet, M, Hinojosa, L, Racioppi, A, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, LB, Gebhard, D, Arnhold, J, Klosterkotter, J, Lasser, I, Winklbaur, B, Delespaul, PA, Modinos, G, Kempton, MJ, Tognin, S, Calem, M, Porffy, L, Antoniades, M, Mason, A, Azis, M, Allen, P, Nelson, B, McGorry, P, Pantelis, C, Riecher-Rossler, A, Borgwardt, S, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Glenthoj, B, Ruhrmann, S, Sachs, G, Rutten, B, van Os, J, de Haan, L, Velthorst, E, van der Gaag, M, Valmaggia, LR, McGuire, P, Kraan, TC, van Dam, DS, Burger, N, Amminger, GP, Politis, A, Goodall, J, Rapp, C, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Dominguez-Martinez, T, Monsonet, M, Hinojosa, L, Racioppi, A, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, LB, Gebhard, D, Arnhold, J, Klosterkotter, J, Lasser, I, Winklbaur, B, and Delespaul, PA

Abstract

IMPORTANCE: The development of adverse clinical outcomes in patients with psychosis has been associated with behavioral and neuroanatomical deficits related to emotion processing. However, the association between alterations in brain regions subserving emotion processing and clinical outcomes remains unclear. OBJECTIVE: To examine the association between alterations in emotion processing and regional gray matter volumes in individuals at clinical high risk (CHR) for psychosis, and the association with subsequent clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS: This naturalistic case-control study with clinical follow-up at 12 months was conducted from July 1, 2010, to August 31, 2016, and collected data from 9 psychosis early detection centers (Amsterdam, Basel, Cologne, Copenhagen, London, Melbourne, Paris, The Hague, and Vienna). Participants (213 individuals at CHR and 52 healthy controls) were enrolled in the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) project. Data were analyzed from October 1, 2018, to April 24, 2019. MAIN MEASURES AND OUTCOMES: Emotion recognition was assessed with the Degraded Facial Affect Recognition Task. Three-Tesla magnetic resonance imaging scans were acquired from all participants, and gray matter volume was measured in regions of interest (medial prefrontal cortex, amygdala, hippocampus, and insula). Clinical outcomes at 12 months were evaluated for transition to psychosis using the Comprehensive Assessment of At-Risk Mental States criteria, and the level of overall functioning was measured through the Global Assessment of Functioning [GAF] scale. RESULTS: A total of 213 individuals at CHR (105 women [49.3%]; mean [SD] age, 22.9 [4.7] years) and 52 healthy controls (25 women [48.1%]; mean [SD] age, 23.3 [4.0] years) were included in the study at baseline. At the follow-up within 2 years of baseline, 44 individuals at CHR (20.7%) had developed psychosis and 169 (79.3%) had n

Published
2020

14. From Speech Illusions to Onset of Psychotic Disorder: Applying Network Analysis to an Experimental Measure of Aberrant Experiences

Author

Boyette, L-L, Isvoranu, A-M, Schirmbeck, F, Velthorst, E, Simons, CJP, Barrantes-Vidal, N, Bressan, R, Kempton, MJ, Krebs, M-O, McGuire, P, Nelson, B, Nordentoft, M, Riecher-Rössler, A, Ruhrmann, S, Rutten, BP, Sachs, G, Valmaggia, LR, van der Gaag, M, Borsboom, D, de Haan, L, van Os, J, Calem, M, Tognin, S, Modinos, G, Kraan, TC, van Dam, DS, Burger, N, McGorry, P, Amminger, GP, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Studerus, E, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Domínguez-Martínez, T, Cristóbal-Narváez, P, Kwapil, TR, Monsonet, M, Hinojosa, L, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthøj, L, Glenthøj, B, Gebhard, D, Arnhold, J, Klosterkötter, J, Lasser, I, Winklbaur, B, Delespaul, PA, Boyette, L-L, Isvoranu, A-M, Schirmbeck, F, Velthorst, E, Simons, CJP, Barrantes-Vidal, N, Bressan, R, Kempton, MJ, Krebs, M-O, McGuire, P, Nelson, B, Nordentoft, M, Riecher-Rössler, A, Ruhrmann, S, Rutten, BP, Sachs, G, Valmaggia, LR, van der Gaag, M, Borsboom, D, de Haan, L, van Os, J, Calem, M, Tognin, S, Modinos, G, Kraan, TC, van Dam, DS, Burger, N, McGorry, P, Amminger, GP, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Studerus, E, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Domínguez-Martínez, T, Cristóbal-Narváez, P, Kwapil, TR, Monsonet, M, Hinojosa, L, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthøj, L, Glenthøj, B, Gebhard, D, Arnhold, J, Klosterkötter, J, Lasser, I, Winklbaur, B, and Delespaul, PA

Abstract

Aberrant perceptional experiences are a potential early marker of psychosis development. Earlier studies have found experimentally assessed speech illusions to be associated with positive symptoms in patients with psychotic disorders, but findings for attenuated symptoms in individuals without psychotic disorders have been inconsistent. Also, the role of affect is unclear. The aim of this study was to use the network approach to investigate how speech illusions relate to individual symptoms and onset of a psychotic disorder. We estimated a network model based on data from 289 Clinical High-Risk (CHR) subjects, participating in the EU-GEI project. The network structure depicts statistical associations between (affective and all) speech illusions, cross-sectional individual attenuated positive and affective symptoms, and transition to psychotic disorder after conditioning on all other variables in the network. Speech illusions were assessed with the White Noise Task, symptoms with the BPRS and transition during 24-month follow-up with the CAARMS. Affective, not all, speech illusions were found to be directly, albeit weakly, associated with hallucinatory experiences. Hallucinatory experiences, in turn, were associated with delusional ideation. Bizarre behavior was the only symptom in the network steadily predictive of transition. Affective symptoms were highly interrelated, with depression showing the highest overall strength of connections to and predictability by other symptoms. Both speech illusions and transition showed low overall predictability by symptoms. Our findings suggest that experimentally assessed speech illusions are not a mere consequence of psychotic symptoms or disorder, but that their single assessment is likely not useful for assessing transition risk.

Published
2020

15. Clinical, cognitive and neuroanatomical associations of serum NMDAR autoantibodies in people at clinical high risk for psychosis

Author

Pollak, TA, Kempton, MJ, Iyegbe, C, Vincent, A, Irani, SR, Coutinho, E, Menassa, DA, Jacobson, L, de Haan, L, Ruhrmann, S, Sachs, G, Riecher-Roessler, A, Krebs, M-O, Amminger, P, Glenthoj, B, Barrantes-Vidal, N, van Os, J, Rutten, BPF, Bressan, RA, van der Gaag, M, Yolken, R, Hotopf, M, Valmaggia, L, Stone, J, David, AS, McGuire, P, Calem, M, Tognin, S, Modinos, G, Velthorst, E, Kraan, TC, van Dam, DS, Burger, N, Nelson, B, McGorry, P, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Rosa, A, Racioppi, A, Monsonet, M, Hinojosa-Marques, L, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, L, Nordentoft, M, Gebhard, D, Arnhold, J, Klosterkoetter, J, Lasser, I, Winklbaur, B, Delespaul, PA, Pollak, TA, Kempton, MJ, Iyegbe, C, Vincent, A, Irani, SR, Coutinho, E, Menassa, DA, Jacobson, L, de Haan, L, Ruhrmann, S, Sachs, G, Riecher-Roessler, A, Krebs, M-O, Amminger, P, Glenthoj, B, Barrantes-Vidal, N, van Os, J, Rutten, BPF, Bressan, RA, van der Gaag, M, Yolken, R, Hotopf, M, Valmaggia, L, Stone, J, David, AS, McGuire, P, Calem, M, Tognin, S, Modinos, G, Velthorst, E, Kraan, TC, van Dam, DS, Burger, N, Nelson, B, McGorry, P, Pantelis, C, Politis, A, Goodall, J, Borgwardt, S, Ittig, S, Studerus, E, Smieskova, R, Gadelha, A, Brietzke, E, Asevedo, G, Asevedo, E, Zugman, A, Rosa, A, Racioppi, A, Monsonet, M, Hinojosa-Marques, L, Kwapil, TR, Kazes, M, Daban, C, Bourgin, J, Gay, O, Mam-Lam-Fook, C, Nordholm, D, Randers, L, Krakauer, K, Glenthoj, L, Nordentoft, M, Gebhard, D, Arnhold, J, Klosterkoetter, J, Lasser, I, Winklbaur, B, and Delespaul, PA

Abstract

Serum neuronal autoantibodies, such as those to the NMDA receptor (NMDAR), are detectable in a subgroup of patients with psychotic disorders. It is not known if they are present before the onset of psychosis or whether they are associated with particular clinical features or outcomes. In a case-control study, sera from 254 subjects at clinical high risk (CHR) for psychosis and 116 healthy volunteers were tested for antibodies against multiple neuronal antigens implicated in CNS autoimmune disorders, using fixed and live cell-based assays (CBAs). Within the CHR group, the relationship between NMDAR antibodies and symptoms, cognitive function and clinical outcomes over 24 month follow-up was examined. CHR subjects were not more frequently seropositive for neuronal autoantibodies than controls (8.3% vs. 5.2%; OR = 1.50; 95% CI: 0.58-3.90). The NMDAR was the most common target antigen and NMDAR IgGs were more sensitively detected with live versus fixed CBAs (p < 0.001). Preliminary phenotypic analyses revealed that within the CHR sample, the NMDAR antibody seropositive subjects had higher levels of current depression, performed worse on the Rey Auditory Verbal Learning Task (p < 0.05), and had a markedly lower IQ (p < 0.01). NMDAR IgGs were not more frequent in subjects who later became psychotic than those who did not. NMDAR antibody serostatus and titre was associated with poorer levels of functioning at follow-up (p < 0.05) and the presence of a neuronal autoantibody was associated with larger amygdala volumes (p < 0.05). Altogether, these findings demonstrate that NMDAR autoantibodies are detectable in a subgroup of CHR subjects at equal rates to controls. In the CHR group, they are associated with affective psychopathology, impairments in verbal memory, and overall cognitive function: these findings are qualitatively and individually similar to core features of autoimmune encephalitis and/or animal models of NMDAR antibody-mediated CNS disease. Overall the current

Published
2020

50. Inhibition of the heme-induced hemolysis of red blood cells by thechlorite-based drug WF10.

Author

Flemmig, J., Schlorke, D., Kühne, F.-W., and Arnhold, J.

Subjects
ERYTHROCYTES, CELL-mediated cytotoxicity, PROTOPORPHYRINS, HEMOLYSIS & hemolysins, ULTRAVIOLET-visible spectroscopy
Abstract

Excessive release of hemoglobin from red blood cells markedly disturbs the health status of patients due to cytotoxic effects of free hemoglobin and heme. The latter component is able to initiate novel hemolytic events in unperturbed red blood cells. We modeled this process by incubation of ferric protoporphyrin IX with freshly isolated red blood cells from healthy volunteers. The heme-induced hemolysis was inhibited in a concentration-dependent manner by the chlorite-based drug WF10, whereby the hemolysis degree was totally abolished at a molar ratio of 1:2 between chlorite and heme. Upon incubation of heme with WF10, the ultraviolet-visible spectrum changed, whereas the release of iron from heme and the appearance of fluorescent breakdown products of the porphyrin ring were negligible at this ratio, but increased with increasing excess of chlorite over heme. Thus, inhibition of hemolysis by WF10 takes already place at those chlorite concentrations, where no degradation of the porphyrin ring occurs. As WF10 is applied in form of an intravenous infusion to patients with severe inflammatory states, these data support the hypothesis that the beneficial WF10 effects are closely associated with inactivation of free heme. [ABSTRACT FROM PUBLISHER]

Published
2016
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