Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Mocking, Roel J. T.; Assies, Johanna; Ruhé, Henricus G.; Schene, Aart H.

doi:10.1007/s10545-018-0158-3

Cited by 38 publications

(28 citation statements)

References 152 publications

(236 reference statements)

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“…The mechanisms linking deficits in n-3 PUFA with psychopathology in the UHR group are only partially understood but likely include effects on serotonergic and dopaminergic neurotransmission through the modulation of membrane fluidity and ion channel function (42), PUFA effects on HPA axis regulation and the regulation of antioxidative defense (43), as well as the production of pro- and anti-inflammatory derivatives of PUFA (14, 44, 45). EPA rapidly beta-oxidized once in the brain (46, 47), and oxidation products are not specific for EPA.…”

Section: Discussionmentioning

confidence: 99%

Relationship Between Polyunsaturated Fatty Acids and Psychopathology in the NEURAPRO Clinical Trial

et al. 2019

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Background Deficiencies in membrane polyunsaturated fatty acids (PUFA) such as omega-3 (n-3) fatty acids are thought to contribute to the pathophysiological processes underlying psychotic disorders. Emerging evidence suggests that the levels of PUFA are related to clinical symptoms but significant heterogeneity exists between studies. Here, we investigated associations of membrane PUFA with clinical symptoms and functioning in a large sample of individuals at ultra-high risk (UHR) for psychosis. Methods A total of 285 participants of the NEURAPRO clinical trial were investigated for erythrocyte PUFA levels, including the n-3 index, n-6/n-3 PUFA ratio, docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA). Severity of general psychopathology [Brief Psychiatric Rating Scale (BPRS)], psychotic symptoms (BPRS psychosis subscale), negative symptoms [Scale for the Assessment of Negative Symptoms (SANS)], manic symptoms [Young Mania Rating Scale (YMRS)], depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS)], and functioning [Social and Occupational Functioning Scale (SOFAS), Global Functioning Social (GF-S) and Role (GF-R) scales] were assessed concurrently. Partial correlation taking into account the effects of gender, age, and smoking was used to examine the relationship between PUFAs and symptoms severity. Results The n-3 index negatively correlated with the severity of general psychopathology, psychotic symptoms, depressive symptoms, and manic symptoms. The n-6/n-3 PUFA ratio positively correlated with severity of psychotic and depressive symptoms. The n-3 PUFA DHA negatively correlated with the severity of general psychopathology, positive, manic, and depressive symptoms. EPA negatively correlated with manic symptoms. Nervonic acid, an n-9 monounsaturated fatty acid, positively correlated with general psychopathology, positive and negative symptoms, depressive symptoms, and manic symptoms. The long-chain saturated fatty acid tetracosanoic acid positively correlated with general psychopathology, positive, manic, and depressive symptoms. Conclusions Partially consistent with a previous study, psychotic symptoms, depressive symptoms, and symptoms of mania were associated with several classes of FAs in the present study. These findings support the relevance of membrane fatty acids for the onset of psychotic symptoms and indicate that FAs should be further evaluated as biomarkers in the UHR for psychosis group. Clinical Trial Registration ANZCTR, identifier: 12608000475347

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Section: Discussionmentioning

confidence: 99%

Relationship Between Polyunsaturated Fatty Acids and Psychopathology in the NEURAPRO Clinical Trial

et al. 2019

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“…The mechanism of action of ADs includes effects on PUFAs of cell membranes [70,71] and it has also been hypothesized that the structure of the membranes influences the efficacy of these drugs [72,73]. PUFAs also act as regulators of inflammation and of the HPA axis activity [74]. In humans, de novo synthesis of PUFAs is not possible; thus, their availability depends on dietary intake, mainly in the form of omega-3 and omega-6 [69].…”

Section: Recent Hypotheses: the Role Of Fatty Acids And The Gut Micromentioning

confidence: 99%

Blues in the Brain and Beyond: Molecular Bases of Major Depressive Disorder and Relative Pharmacological and Non-Pharmacological Treatments

Maffioletti

Minelli

Tardito

et al. 2020

Genes

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Despite the extensive research conducted in recent decades, the molecular mechanisms underlying major depressive disorder (MDD) and relative evidence-based treatments remain unclear. Various hypotheses have been successively proposed, involving different biological systems. This narrative review aims to critically illustrate the main pathogenic hypotheses of MDD, ranging from the historical ones based on the monoaminergic and neurotrophic theories, through the subsequent neurodevelopmental, glutamatergic, GABAergic, inflammatory/immune and endocrine explanations, until the most recent evidence postulating a role for fatty acids and the gut microbiota. Moreover, the molecular effects of established both pharmacological and non-pharmacological approaches for MDD are also reviewed. Overall, the existing literature indicates that the molecular mechanisms described in the context of these different hypotheses, rather than representing alternative ones to each other, are likely to contribute together, often with reciprocal interactions, to the development of MDD and to the effectiveness of treatments, and points at the need for further research efforts in this field.

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“…Certain nutritional components, including specific B vitamins and docosahexaenoic acid (DHA) are essential for the biosynthesis and absorption of neurotransmitters [22] and may thereby affect mood and behavior. Particularly important in preventing perinatal depression/anxiety are omega-3 long-chain polyunsaturated fatty acids (n-3 FA) due to their anti-inflammatory effects and their important influence on brain physiology, including their effect on neuronal membrane structure, hypothalamic-pituitary-adrenal-axis activity, and oxidative stress vulnerability [23]. Pregnancy and lactation are associated with higher demands for n-3 FA [24,25], particularly during the third trimester when existing maternal depots of n-3 are depleted for fetal development [26].…”

Section: Introductionmentioning

confidence: 99%

Levels of n-3 and n-6 Fatty Acids in Maternal Erythrocytes during Pregnancy and in Human Milk and Its Association with Perinatal Mental Health

et al. 2020

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Omega-3 long-chain polyunsaturated fatty acid (n-3 FA) status may be associated with mood disorders. Here, we evaluated the potential association between antenatal depression/anxiety and n-3/n-6 FA in (a) maternal erythrocytes and (b) human milk. In addition, we explored associations between n-3/n-6 FA in erythrocytes and in human milk and postpartum depression, while controlling for antenatal depression. Twenty-seven pregnant women diagnosed with a current major depressive disorder (MDD; n = 9), anxiety disorder (AD; n = 10) or a mixed anxiety-depression disorder (MADD; n = 8), and 40 healthy controls were included. n-3/n-6 FA were determined in maternal erythrocytes in gestational week 32 and in human milk in postpartum week 1. In the first week postpartum, the Edinburgh-Postnatal-Depression-Questionnaire was used to assess postpartum depression. Results show that women with M(A)DD had significantly lower erythrocyte levels of total n-3 FA, EPA, DHA and DGLA, and significantly higher n-6 DPA, and n-6:n-3, AA:EPA and n-6 DPA:DHA ratios compared to healthy controls. No significant associations between antenatal depression or anxiety and n-3/n-6 FA in human milk were found. After controlling for antenatal mental health, n-3/n-6 FA in maternal erythrocytes or in human milk were not significantly associated with postpartum depression. In conclusion, antenatal depression, alone or with an anxiety disorder, was associated with lower n-3 FA levels and higher n-6:n-3 FA ratios in maternal erythrocytes during gestation. This study provides some insights into the associations between n-3/n-6 FA levels during pregnancy and lactation and perinatal mental health.

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Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders

Cited by 38 publications

References 152 publications

Relationship Between Polyunsaturated Fatty Acids and Psychopathology in the NEURAPRO Clinical Trial

Relationship Between Polyunsaturated Fatty Acids and Psychopathology in the NEURAPRO Clinical Trial

Blues in the Brain and Beyond: Molecular Bases of Major Depressive Disorder and Relative Pharmacological and Non-Pharmacological Treatments

Levels of n-3 and n-6 Fatty Acids in Maternal Erythrocytes during Pregnancy and in Human Milk and Its Association with Perinatal Mental Health

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