Relationship between Erythrocyte Fatty Acid Composition and Psychopathology in the Vienna Omega-3 Study

PLOS ONE, Dec 2019

This study investigated the relationship between erythrocyte membrane fatty acid (FA) levels and the severity of symptoms of individuals at ultra-high risk (UHR) for psychosis. Subjects of the present study consisted of 80 neuroleptic-naïve UHR patients. Partial correlation coefficients were calculated between baseline erythrocyte membrane FA levels, measured by gas chromatography, and scores on the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning Scale, and Montgomery–Asberg Depression Rating Scale (MADRS) after controlling for age, sex, smoking and cannabis use. Subjects were divided into three groups according to the predominance of positive or negative symptoms based on PANSS subscale scores; membrane FA levels in the three groups were then compared. More severe negative symptoms measured by PANSS were negatively correlated with two saturated FAs (myristic and margaric acids), one ω-9 monounsaturated FA (MUFA; nervonic acid), and one ω-3 polyunsaturated FA (PUFA; docosapentaenoic acid), and were positively correlated with two ω-9 MUFAs (eicosenoic and erucic acids) and two ω-6 PUFAs (γ-linolenic and docosadienoic acids). More severe positive symptoms measured by PANSS were correlated only with nervonic acid. No associations were observed between FAs and MADRS scores. In subjects with predominant negative symptoms, the sum of the ω-9 MUFAs and the ω-6:ω-3 FA ratio were both significantly higher than in those with predominant positive symptoms, whereas the sum of ω-3 PUFAs was significantly lower. In conclusion, abnormalities in FA metabolism may contribute to the neurobiology of psychopathology in UHR individuals. In particular, membrane FA alterations may play a role in negative symptoms, which are primary psychopathological manifestations of schizophrenia-related disability.

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Relationship between Erythrocyte Fatty Acid Composition and Psychopathology in the Vienna Omega-3 Study

March Relationship between Erythrocyte Fatty Acid Composition and Psychopathology in the Vienna Omega-3 Study Sung-Wan Kim 1 2 3 Min Jhon 1 2 3 Jae-Min Kim 1 2 3 Stefan Smesny 0 1 3 Simon Rice 1 3 Michael Berk 1 3 Claudia M. Klier 1 3 Patrick D. McGorry 1 3 Miriam R. Schäfer 1 3 G. Paul Amminger 1 3 0 Department of Psychiatry, University Hospital Jena , Jena, Germany, 3 Orygen , The National Centre of Excellence in Youth Mental Health, Centre for Youth Mental Health, The University of Melbourne , Parkville, Victoria 3052 , Australia , 4 IMPACT Strategic Research Centre, School of Medicine, Deakin University , Geelong , Australia , 5 Department of Child and Adolescent Medicine, Medical University of Vienna , Vienna , Austria 1 Funding: This study was supported by grant 03T- 315 from the Stanley Medical Research Institute. SWK was supported by Basic Science Research Program through the National Research Foundation 2 Department of Psychiatry, Chonnam National University Medical School , Gwangju , Republic of Korea 3 Editor: David O. Carpenter, Institute for Health & the Environment , UNITED STATES This study investigated the relationship between erythrocyte membrane fatty acid (FA) levels and the severity of symptoms of individuals at ultra-high risk (UHR) for psychosis. Subjects of the present study consisted of 80 neuroleptic-naïve UHR patients. Partial correlation coefficients were calculated between baseline erythrocyte membrane FA levels, measured by gas chromatography, and scores on the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning Scale, and Montgomery-Asberg Depression Rating Scale (MADRS) after controlling for age, sex, smoking and cannabis use. Subjects were divided into three groups according to the predominance of positive or negative symptoms based on PANSS subscale scores; membrane FA levels in the three groups were then compared. More severe negative symptoms measured by PANSS were negatively correlated with two saturated FAs (myristic and margaric acids), one ω-9 monounsaturated FA (MUFA; nervonic acid), and one ω-3 polyunsaturated FA (PUFA; docosapentaenoic acid), and were positively correlated with two ω-9 MUFAs (eicosenoic and erucic acids) and two ω-6 PUFAs (γ-linolenic and docosadienoic acids). More severe positive symptoms measured by PANSS were correlated only with nervonic acid. No associations were observed between FAs and MADRS scores. In subjects with predominant negative symptoms, the sum of the ω-9 MUFAs and the ω-6:ω-3 FA ratio were both significantly higher than in those with predominant positive symptoms, whereas the sum of ω-3 PUFAs was significantly lower. In conclusion, abnormalities in FA metabolism may contribute to the neurobiology of psychopathology in UHR individuals. In particular, membrane FA alterations may play a role in negative symptoms, which are primary psychopathological manifestations of schizophrenia-related disability. - OPEN ACCESS of Korea (NRF) funded by the Ministry of Science, ICT and future Planning (NRF2014R1A1A4A01005245). MB was supported by National Health and Medical Research Council Australia (NHMRC) Senior Principal Research Fellowship 1059660. SR was supported by an Early Career Fellowship from the Society for Mental Health Research. GPA was supported by NHMRC Senior Research Fellowship 1080963. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Introduction Schizophrenia is a severe mental illness that typically begins in adolescence or early adult life. It is a heterogeneous disorder with diverse symptoms which are generally characterised as positive or negative [ 1,2 ]. Positive symptoms, such as delusions and hallucinations, are considered to be more transient; negative symptoms, such as blunting of affect and passive withdrawal, are regarded as more persistent and contribute more to impairment [3]. The dopamine hypothesis is one of the most influential theories about the etiology of schizophrenia. Initially, the hypothesis emphasised an etiologic role of hyperdopaminergia, but this was subsequently reconceptualised to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia [ 4 ]. Normally, the prefrontal dopamine system suppresses the limbic dopamine system; however, in schizophrenia, this suppression seems to be reduced due to disturbed prefrontal dopaminergic activity, leading to elevated limbic dopaminergic activity [ 5 ]. The dopamine hypothesis is concordant with both the negative symptoms of schizophrenia, likely linked with prefrontal hypodopaminergia, and the positive symptoms, strongly related to enhanced limbic dopaminergic activity [ 6 ]. While psychopathology is traditionally explained by disturbed neurotransmitter function, polyunsaturated fatty acids (PUFAs) gained interest in terms of the etiology of structural and functional abnormalities of the developing nervous system in schizophrenia. (...truncated)


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Sung-Wan Kim, Min Jhon, Jae-Min Kim, Stefan Smesny, Simon Rice, Michael Berk, Claudia M. Klier, Patrick D. McGorry, Miriam R. Schäfer, G. Paul Amminger. Relationship between Erythrocyte Fatty Acid Composition and Psychopathology in the Vienna Omega-3 Study, PLOS ONE, 2016, Volume 11, Issue 3, DOI: 10.1371/journal.pone.0151417