Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis

PLOS ONE, Dec 2019

Background Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders. Methods We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55) with healthy controls (HC n = 25) and first episode schizophrenia patients (FEP n = 25) treated with atypical antipsychotics. Results Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA), but positively correlated with phospholipase A2 (inPLA2) activity, a marker of membrane lipid repair/remodelling. Conclusions Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a “pro-inflammatory state”, whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated.

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Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis

February Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis Gregor E. Berger 0 1 Stefan Smesny 0 1 Miriam R. Schäfer 0 1 Berko Milleit 0 1 Kerstin Langbein 0 1 Uta-Christina Hipler 0 1 Christine Milleit 0 1 Claudia M. Klier 0 1 Monika Schlögelhofer 0 1 Magdalena Holub 0 1 Ingrid Holzer 0 1 Michael Berk 0 1 Patrick D. McGorry 0 1 Heinrich Sauer 0 1 G. Paul Amminger 0 1 0 Editor: F. Markus Leweke, Central Institute of Mental Health, Heidelberg University , GERMANY 1 1 University Hospital of Child and Adolescent Psychiatry, University of Zurich , Neumünsterallee 9, 8032 Zurich , Switzerland , 2 Department of Psychiatry, Jena University Hospital , Philosophenweg 3, D-07743 Jena, Germany , 3 Orygen Youth Health Research Centre, The University of Melbourne , Locked Bag 10, 35 Poplar Road Parkville, Victoria 3052, Melbourne , Australia , 4 Department of Child and Adolescent Psychiatry, Medical University of Vienna , Währingergürtel 18-20, A-1090 Vienna , Austria , 5 Department of Dermatology, University Hospital Jena , Erfurter Straße 35, D-07743 Jena, Germany , 6 Department of Nutritional Sciences, University of Vienna , Althanstrasse 14, A-1090 Vienna , Austria , 7 Deakin University of Melbourne, School of Medicine , Barwon Health, Geelong , Australia , 8 Florey Institute for Neuroscience and Mental Health , Parkville , Australia Contrary to our hypothesis niacin sensitivity of the entire UHR group was not attenuated, but significantly increased compared to the HC group, whereas no difference could be found between the UHR-T and UHR-NT groups. As expected, niacin sensitivity of FEP was attenuated compared to HC group. In UHR individuals niacin sensitivity was inversely correlated with omega-6 and -9 fatty acids (FA), but positively correlated with phospholipase A2 (inPLA2) activity, a marker of membrane lipid repair/remodelling. Conclusions Increased niacin sensitivity in UHR states likely indicates an impaired balance of eicosanoids and omega-6/-9 FA at a membrane level. Our findings suggest that the emergence of Most studies provide evidence that the skin flush response to nicotinic acid (niacin) stimulation is impaired in schizophrenia. However, only little is known about niacin sensitivity in the ultra-high risk (UHR) phase of psychotic disorders. We compared visual ratings of niacin sensitivity between adolescents at UHR for psychosis according to the one year transition outcome (UHR-T n = 11; UHR-NT n = 55) with healthy controls (HC n = 25) and first episode schizophrenia patients (FEP n = 25) treated with atyp Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The study was supported by Stanley Medical Research Institute, grant 03T-315. Dr. G. Paul Amminger was supported by grant 566529 from the National Health and Medical Research Council, Australia. The sponsor of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Competing Interests: The authors have declared that no competing interests exist. Background Methods ical antipsychotics. Results psychosis is associated with an increased mobilisation of eicosanoids prior to the transition to psychosis possibly reflecting a “pro-inflammatory state”, whereas thereafter eicosanoid mobilisation seems to be attenuated. Potential treatment implications for the UHR state should be further investigated. Introduction The observation that human kind responds with a red flush reaction of the upper body after intake of large doses of nicotinic acid (niacin, vitamin B3) goes back to the early fifties of the last century [1] a time when nicotinic acid was introduced as possible treatment of schizophrenia [2] While controlled studies failed to demonstrate a sustained clinical benefit of niacin in schizophrenia treatment [3] the clinical observation of an attenuated or even absent niacin flush reaction of the upper body in patients with schizophrenia compared to healthy controls caught the attention of some researchers [ 4,5 ]. The latter observation combined with other clinical observations such as that patients with schizophrenia are less sensitive to pain [6], have a lower temperature sensitivity [ 7 ] and a markedly decreased risk of rheumatoid arthritis [ 8 ], led to the proposal that schizophrenia might be associated with a deficiency or dysfunction of prostaglandin metabolism [ 9 ]. Prostaglandins are metabolites of arachidonic acid (AA), a key modulator of signal transduction [ 10 ]. The latter in conjunction with the observation that in particular AA levels are reduced in post mortem and peripheral red blood cell membranes in schizophrenia [ 11 ] lead to the formulation of the membrane and phospholipid hypothesis of schizophrenia [ 12,13 ]. The pathway underlying the niacin skin reaction includes the activation of G protein-coupled nicotinic acid receptors on skin ma (...truncated)


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Gregor E. Berger, Stefan Smesny, Miriam R. Schäfer, Berko Milleit, Kerstin Langbein, Uta-Christina Hipler, Christine Milleit, Claudia M. Klier, Monika Schlögelhofer, Magdalena Holub, Ingrid Holzer, Michael Berk, Patrick D. McGorry, Heinrich Sauer, G. Paul Amminger. Niacin Skin Sensitivity Is Increased in Adolescents at Ultra-High Risk for Psychosis, PLOS ONE, 2016, Volume 11, Issue 2, DOI: 10.1371/journal.pone.0148429