Mendelian randomization analyses identify bidirectional causal relationships of obesity with psychiatric disorders

Journal of Affective Disorders, Journal Year: 2023, Volume and Issue: 339, P. 807 - 814

Published: July 19, 2023

Language: Английский

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Genetic influences on circulating retinol and its relationship to human health

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Feb. 19, 2024

Retinol is a fat-soluble vitamin that plays an essential role in many biological processes throughout the human lifespan. Here, we perform largest genome-wide association study (GWAS) of retinol to date up 22,274 participants. We identify eight common variant loci associated with retinol, as well rare-variant signal. An integrative gene prioritisation pipeline supports novel retinol-associated genes outside main transport complex (RBP4:TTR) related lipid biology, energy homoeostasis, and endocrine signalling. Genetic proxies circulating were then used estimate causal relationships almost 20,000 clinical phenotypes via phenome-wide Mendelian randomisation (MR-pheWAS). The MR-pheWAS suggests may exert effects on inflammation, adiposity, ocular measures, microbiome, MRI-derived brain phenotypes, amongst several others. Conversely, be causally influenced by factors including lipids serum creatinine. Finally, demonstrate how polygenic score could individuals more likely fall normative range for given age. In summary, this provides comprehensive evaluation genetics revealing traits which should prioritised further investigation respect therapies or nutritional intervention.

Language: Английский

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Microbiome and immuno-metabolic dysregulation in patients with major depressive disorder with atypical clinical presentation

Neuropharmacology, Journal Year: 2023, Volume and Issue: 235, P. 109568 - 109568

Published: May 12, 2023

Depression is highly prevalent (6% 1-year prevalence) and the second leading cause of disability worldwide. Available treatment options for depression are far from optimal, with response rates only around 50%. This most likely related to a heterogeneous clinical presentation major disorder (MDD), suggesting different manifestations underlying pathophysiological mechanisms. Poorer outcomes first-line antidepressants were reported in MDD patients endorsing an "atypical" symptom profile that characterized by preserved reactivity mood, increased appetite, hypersomnia, heavy sensation limbs, interpersonal rejection sensitivity. In recent years, evidence has emerged immunometabolic biological dysregulation important mechanism depression, which maps more consistently atypical features. last few years human microbial residents have as key influencing variable associated dysregulations depression. The microbiome plays critical role training development components host's innate adaptive immune systems, while system orchestrates maintenance features host-microbe symbiosis. Moreover, being metabolically active ecosystem commensal microbes may huge impact on signaling pathways, involved mechanisms depressive symptoms. this review, we discuss interplay between imbalance context Although research field its infancy, targeting determinants homogeneous presentations offer new avenues novel therapeutic strategies treatment-resistant article part Special Issue "Microbiome & Brain: Mechanisms Maladies".

Language: Английский

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Increased prefrontal cortical cells positive for macrophage/microglial marker CD163 along blood vessels characterizes a neuropathology of neuroinflammatory schizophrenia

Brain Behavior and Immunity, Journal Year: 2023, Volume and Issue: 111, P. 46 - 60

Published: March 25, 2023

Language: Английский

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The missing hallmark of health: psychosocial adaptation

Cell Stress, Journal Year: 2024, Volume and Issue: 8, P. 21 - 50

Published: Jan. 1, 2024

The eight biological hallmarks of health that we initially postulated (Cell. 2021 Jan 7;184(1):33-63) include features spatial compartmentalization (integrity barriers, containment local perturbations), maintenance homeostasis over time (recycling & turnover, integration circuitries, rhythmic oscillations) and an array adequate responses to stress (homeostatic resilience, hormetic regulation, repair regeneration). These affect all somatic strata the human body (molecules, organelles, cells, supracellular units, organs, organ systems, systemic circuitries meta-organism). Here postulate mental socioeconomic factors must be added this 8×8 matrix as additional hallmark (“psychosocial adaptation”) stratum interactions”), hence building a 9×9 matrix. Potentially, perturbation each affects psychosocial vice versa. Finally, discuss (patho)physiological bases these interactions their implications for improvement.

Language: Английский

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Schizophrenia and obesity: May the gut microbiota serve as a link for the pathogenesis?

iMeta, Journal Year: 2023, Volume and Issue: 2(2)

Published: April 4, 2023

Abstract Schizophrenia (SZ) places a tremendous burden on public health as one of the leading causes disability and death. SZ patients are more prone to developing obesity than general population from clinical practice. The development frequently poor psychiatric outcomes in patients. In turn, maternal during pregnancy has been associated with an increased risk offspring, suggesting that these two disorders may have shared neuropathological mechanisms. gut microbiota is well known serve major regulator bidirectional interactions between central nervous system gastrointestinal tract. It also plays critical role maintaining physical mental humans. Recent studies shown dysbiosis intimately onset through pathophysiological mechanisms, particularly stimulation immune inflammation. Therefore, common biological basis for etiology both obesity, perturbed gut–brain axis therefore account high prevalence SZ. On findings, this review provides updated perspectives intervention approaches etiology, prevention, management by summarizing recent findings pathogenesis highlighting gut‐derived

Language: Английский

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Mega-analysis of association between obesity and cortical morphology in bipolar disorders: ENIGMA study in 2832 participants

Psychological Medicine, Journal Year: 2023, Volume and Issue: 53(14), P. 6743 - 6753

Published: Feb. 27, 2023

Abstract Background: Obesity is highly prevalent and disabling, especially in individuals with severe mental illness including bipolar disorders (BD). The brain a target organ for both obesity BD. Yet, we do not understand how cortical alterations BD interact. Methods: We obtained body mass index (BMI) MRI-derived regional thickness, surface area from 1231 1601 control 13 countries within the ENIGMA-BD Working Group. jointly modeled statistical effects of BMI on structure using mixed tested interaction mediation. also investigated impact medications BMI-related associations. Results: additively impacted many same regions. Both were negatively associated but area. In most regions number used psychiatric medication classes remained lower thickness when controlling BMI. single region, fusiform gyrus, about third negative association between was mediated by higher Conclusions: confirmed consistent associations area, across cerebral mantle, which Higher people indicated more pronounced alterations. important understanding neuroanatomical changes brain.

Language: Английский

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Comorbid health outcomes in patients with schizophrenia: an umbrella review of systematic reviews and meta-analyses

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 18, 2024

Language: Английский

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Investigating the shared genetic architecture between schizophrenia and body mass index

Molecular Psychiatry, Journal Year: 2023, Volume and Issue: 28(6), P. 2312 - 2319

Published: May 18, 2023

Language: Английский

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Effects of obesity on aging brain and cognitive decline: a cohort study from the UK Biobank

IBRO Neuroscience Reports, Journal Year: 2025, Volume and Issue: 18, P. 148 - 157

Published: Jan. 5, 2025

Language: Английский

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