Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial

Cheng, Nicholas; McLaverty, Alison; Nelson, Barnaby; Markulev, Connie; Schäfer, Miriam R.; Berger, Maximus; Mossaheb, Nilufar; Schlögelhofer, Monika; Smesny, Stefan; Hickie, Ian B.; Berger, Gregor; Chen, Eric; Haan, Lieuwe de; Nieman, Dorien H.; Nordentoft, Merete; Riecher‐Rössler, Anita; Verma, Swapna; Street, Rebekah; Thompson, Andrew; Yuen, Hok Pan; Hester, Robert; Yung, Alison R.; McGorry, Patrick; Allott, Kelly; Amminger, G. Paul

doi:10.1192/bjo.2022.572

Cited by 2 publications

(1 citation statement)

References 43 publications

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“…Omega-3 supplementation has shown promising results in reducing clinical symptoms associated with a range of brain conditions, including MDD [9, 10], anxiety disorders [11], schizophrenia [12, 13], attention-deficit/hyperactivity disorder (ADHD) [14], autism spectrum disorder [15] and Alzheimer’s disease (ALZ) [16]. However, several randomized controlled trials reported small or no effects of PUFAs on schizophrenia [5], depression [17], ALZ [18] and psychosis [19, 20]. Consequently, the overall impact of PUFAs on human brain disorders remains inconclusive, necessitating further investigation to establish their therapeutic potential.…”

Section: Introductionmentioning

confidence: 99%

Shared genetic basis informs the roles of polyunsaturated fatty acids in brain disorders

Xu,

Sun,

Francis

et al. 2023

Preprint

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The neural tissue is rich in polyunsaturated fatty acids (PUFAs), components that are indispensable for the proper functioning of neurons, such as neurotransmission. PUFA nutritional deficiency and imbalance have been linked to a variety of chronic brain disorders, including major depressive disorder (MDD), anxiety, and anorexia. However, the effects of PUFAs on brain disorders remain inconclusive, and the extent of their shared genetic determinants is largely unknown. Here, we used genome-wide association summary statistics to systematically examine the shared genetic basis between six phenotypes of circulating PUFAs (N = 114,999) and 20 brain disorders (N = 9,725-762,917), infer their potential causal relationships, identify colocalized regions, and pinpoint shared genetic variants. Genetic correlation and polygenic overlap analyses revealed a widespread shared genetic basis for 77 trait pairs between six PUFA phenotypes and 16 brain disorders. Two-sample Mendelian randomization analysis indicated potential causal relationships for 16 pairs of PUFAs and brain disorders, including alcohol consumption, bipolar disorder (BIP), and MDD. Colocalization analysis identified 40 shared loci (13 unique) among six PUFAs and ten brain disorders. Twenty-two unique variants were statistically inferred as candidate shared causal variants, including rs1260326 (GCKR), rs174564 (FADS2) and rs4818766 (ADARB1). These findings reveal a widespread shared genetic basis between PUFAs and brain disorders, pinpoint specific shared variants, and provide support for the potential effects of PUFAs on certain brain disorders, especially MDD, BIP, and alcohol consumption.

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Section: Introductionmentioning

confidence: 99%

Shared genetic basis informs the roles of polyunsaturated fatty acids in brain disorders

Xu,

Sun,

Francis

et al. 2023

Preprint

View full text Add to dashboard Cite

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N-Acetylcysteine and a Specialized Preventive Intervention for Individuals at High Risk for Psychosis: A Randomized Double-Blind Multicenter Trial

Wasserthal,

Muthesius,

Hurlemann

et al. 2024

Schizophrenia Bulletin Open

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Background and Hypothesis Clinical high risk for psychosis (CHR-P) offers a window of opportunity for early intervention and recent trials have shown promising results for the use of N-acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention (IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of CHR-P patients. Study Design In this double-blind, randomized, controlled multicenter trial, a 2 × 2 factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI compared to psychological stress management (PSM). The primary endpoint was the transition to psychosis or deterioration of CHR-P symptoms after 18 months. Study Results While insufficient recruitment led to early trial termination, a total of 48 participants were included in the study. Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI + NAC: 72.7 ± 13.4%, PSM + NAC: 72.7 ± 13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ± 15.3%, PSM + PLC: 39.0 ± 17.4%). However, a log-rank chi-square test in Kaplan–Meier analysis revealed no significant difference of survival probability for NAC vs control (point hazard ratio: 0.879, 95% CI 0.281–2.756) or IPPI vs control (point hazard ratio: 0.827, 95% CI 0.295–2.314). The number of adverse events (AE) did not differ significantly between the four groups. Conclusions The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P compared to controls could not be statistically validated in this trial. However, results indicate a consistent pattern that warrants further testing of NAC as a promising and well-tolerated intervention for CHR patients in future trials with adequate statistical power.

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Effects of omega-3 polyunsaturated fatty acid supplementation on cognitive functioning in youth at ultra-high risk for psychosis: secondary analysis of the NEURAPRO randomised controlled trial

Cited by 2 publications

References 43 publications

Shared genetic basis informs the roles of polyunsaturated fatty acids in brain disorders

Shared genetic basis informs the roles of polyunsaturated fatty acids in brain disorders

N-Acetylcysteine and a Specialized Preventive Intervention for Individuals at High Risk for Psychosis: A Randomized Double-Blind Multicenter Trial

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