Abstract
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.
Highlights
Schizophrenia is a severe mental illness that typically begins in adolescence or early adult life
The ω-6:ω-3 FA ratio was positively correlated with Positive and Negative Syndrome Scale (PANSS) total and negative symptom scores and sum of the ω 3 fatty acids was negatively associated with PANSS negative symptom scores
Linolenic and docosadienoic acids), and the ω-6:ω-3 FA ratio were all significantly higher in the negative-symptoms-dominant as compared to the positive-symptoms-dominant group. In this exploratory study of individuals at ultra-high risk (UHR) for psychosis, the PE fraction of erythrocyte membrane FAs were associated with severity of psychopathology
Summary
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]. The dopamine hypothesis is one of the most influential theories about the etiology of schizophrenia. The hypothesis emphasised an etiologic role of hyperdopaminergia, but this was subsequently reconceptualised to specify subcortical hyperdopaminergia with prefrontal hypodopaminergia [4]. 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]
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