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Journal of Affective Disorders Aug 2023The consumption of ultra-processed foods and drinks (UPF) has been associated with depression and inflammation and preclinical studies showed that some UPF components...
BACKGROUND
The consumption of ultra-processed foods and drinks (UPF) has been associated with depression and inflammation and preclinical studies showed that some UPF components disrupt the amygdala-hippocampal complex. We combine diet, clinical and brain imaging data to investigate the relationship between the UPF consumption, depressive symptoms, and brain volumes in humans, considering interactions with obesity, and the mediation effect of inflammation biomarkers.
METHODS
One-hundred fifty-two adults underwent diet, depressive symptoms, anatomic magnetic resonance imaging assessments and laboratory tests. Relationships between the % of UPF consumption (in grams) of the total diet, depressive symptoms, and gray matter brain volumes were explored using several adjusted regression models, and in interaction with the presence of obesity. Whether inflammatory biomarkers (i.e., white blood cell count, lipopolysaccharide-binding protein, c-reactive protein) mediate the previous associations was investigated using R mediation package.
RESULTS
High UPF consumption was associated with higher depressive symptoms in all participants (β = 0.178, CI = 0.008-0.261) and in those with obesity (β = 0.214, CI = -0.004-0.333). Higher consumption was also associated with lower volumes in the posterior cingulate cortex and the left amygdala, which in the participants with obesity also encompassed the left ventral putamen and the dorsal frontal cortex. White blood count levels mediated the association between UPF consumption and depressive symptoms (p = 0.022).
LIMITATIONS
The present study precludes any causal conclusions.
CONCLUSIONS
UPF consumption is associated with depressive symptoms and lower volumes within the mesocorticolimbic brain network implicated in reward processes and conflict monitoring. Associations were partially dependent on obesity and white blood cell count.
Topics: Adult; Humans; Food, Processed; Depression; Fast Foods; Diet; Obesity; Inflammation; Biomarkers
PubMed: 37207947
DOI: 10.1016/j.jad.2023.05.009 -
Bone Research Jul 2023In this study, we aimed to investigate the causal associations of brain structure with bone mineral density (BMD). Based on the genome-wide association study (GWAS)...
In this study, we aimed to investigate the causal associations of brain structure with bone mineral density (BMD). Based on the genome-wide association study (GWAS) summary statistics of 1 325 brain imaging-derived phenotypes (BIDPs) of brain structure from the UK Biobank and GWAS summary datasets of 5 BMD locations, including the total body, femoral neck, lumbar spine, forearm, and heel from the GEFOS Consortium, linkage disequilibrium score regression (LDSC) was conducted to determine the genetic correlations, and Mendelian randomization (MR) was then performed to explore the causal relationship between the BIDPs and BMD. Several sensitivity analyses were performed to verify the strength and stability of the present MR outcomes. To increase confidence in our findings, we also performed confirmatory MR between BIDPs and osteoporosis. LDSC revealed that 1.93% of BIDPs, with a false discovery rate (FDR) < 0.01, were genetically correlated with BMD. Additionally, we observed that 1.31% of BIDPs exhibited a significant causal relationship with BMD (FDR < 0.01) through MR. Both the LDSC and MR results demonstrated that the BIDPs "Volume of normalized brain," "Volume of gray matter in Left Inferior Frontal Gyrus, pars opercularis," "Volume of Estimated Total Intra Cranial" and "Volume-ratio of brain segmentation/estimated total intracranial" had strong associations with BMD. Interestingly, our results showed that more left BIDPs were causally associated with BMD, especially within and around the left frontal region. In conclusion, a part of the brain structure causally influences BMD, which may provide important perspectives for the prevention of osteoporosis and offer valuable insights for further research on the brain-bone axis.
Topics: Humans; Bone Density; Genome-Wide Association Study; Correlation of Data; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Osteoporosis; Femur Neck; Prefrontal Cortex
PubMed: 37474577
DOI: 10.1038/s41413-023-00270-z -
BMJ (Clinical Research Ed.) Aug 2023To investigate the associations between exposure to antenatal corticosteroids and serious infection in children during the first three, six, and 12 months of life.
OBJECTIVE
To investigate the associations between exposure to antenatal corticosteroids and serious infection in children during the first three, six, and 12 months of life.
DESIGN
Nationwide cohort study.
SETTING
National Health Insurance Research Database, Birth Reporting Database, and Maternal and Child Health Database, 1 January 2008 to 31 December 2019, to identify all pregnant individuals and their offspring in Taiwan.
PARTICIPANTS
1 960 545 pairs of pregnant individuals and their singleton offspring. 45 232 children were exposed and 1 915 313 were not exposed to antenatal corticosteroids.
MAIN OUTCOME MEASURES
Incidence rates were estimated for overall serious infection, sepsis, pneumonia, acute gastroenteritis, pyelonephritis, meningitis or encephalitis, cellulitis or soft tissue infection, septic arthritis or osteomyelitis, and endocarditis during the first three, six, and 12 months of life in children exposed versus those not exposed to antenatal corticosteroids. Cox proportional hazards models were performed to quantify adjusted hazard ratios with 95% confidence intervals for each study outcome.
RESULTS
The study cohort was 1 960 545 singleton children: 45 232 children were exposed to one course of antenatal corticosteroids and 1 915 313 children were not exposed to antenatal corticosteroids. The adjusted hazard ratios for overall serious infection, sepsis, pneumonia, and acute gastroenteritis among children exposed to antenatal corticosteroids were significantly higher than those not exposed to antenatal corticosteroids during the first six months of life (adjusted hazard ratio 1.32, 95% confidence interval 1.18 to 1.47, P<0.001, for overall serious infection; 1.74, 1.16 to 2.61, P=0.01, for sepsis; 1.39, 1.17 to 1.65, P<0.001, for pneumonia; and 1.35, 1.10 to 1.65, P<0.001, for acute gastroenteritis).Similarly, the adjusted hazard ratios for overall serious infection (P<0.001), sepsis (P=0.02), pneumonia (P<0.001), and acute gastroenteritis (P<0.001) were significantly higher from birth to 12 months of life. In the sibling matched cohort, the results were comparable with those observed in the whole cohort, with a significantly increased risk of sepsis in the first six (P=0.01) and 12 (P=0.04) months of life.
CONCLUSIONS
This nationwide cohort study found that children exposed to one course of antenatal corticosteroids were significantly more likely to have an increased risk of serious infection during the first 12 months of life. These findings suggest that before starting treatment, the long term risks of rare but serious infection associated with antenatal corticosteroids should be carefully weighed against the benefits in the perinatal period.
Topics: Humans; Pregnancy; Child; Female; Cohort Studies; Adrenal Cortex Hormones; Taiwan; Premature Birth
PubMed: 37532264
DOI: 10.1136/bmj-2023-075835 -
Molecular Neurobiology Mar 2024Previous in vitro and post-mortem studies have reported the role of inflammation in neurodegenerative disorders. However, the association between inflammation and brain...
Previous in vitro and post-mortem studies have reported the role of inflammation in neurodegenerative disorders. However, the association between inflammation and brain structure in vivo and the transcriptome-driven functional basis with relevance to neurodegenerative disorders remains elusive. The aim of the present study is to identify the association among inflammation, brain structure, and neurodegenerative disorders at genetic and transcriptomic levels. Genetic variants associated with inflammatory cytokines were selected from the latest and largest genome-wide association studies of European ancestry. Neurodegenerative disorders including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and dementia with Lewy bodies (DLB) and brain structure imaging measures were selected as the outcomes. Two-sample Mendelian randomization analyses were conducted to identify the causal associations. Single-nucleus transcriptome data of the occipitotemporal cortex was further analyzed to identify the differential expressed genes in AD, which were tested for biological processes and protein interaction network. MR analysis indicated that genetically predicted TREM2 and sTREM2 were significantly associated with AD (TREM2: z-score = -9.088, p-value = 1.02 × 10; sTREM2: z-score = -7.495, p-value = 6.61 × 10). The present study found no evidence to support the causal associations between other inflammatory cytokines and the risks of AD, PD, ALS, or DLB. Genetically predicted TREM2 was significantly associated with the cortical thickness of inferior temporal (z-score = -4.238, p-value = 2.26 × 10) and pole temporal (z-score = -4.549, p-value = 5.40 × 10). In the occipitotemporal cortex samples, microglia were the main source of TREM2 gene and showed increasing expression of genes associated with inflammation and immunity. The present study has leveraged genetic and transcriptomic data to identify the association among TREM2, temporal lobe, and AD and the underlying cellular and molecular basis, thus providing a new perspective on the role of TREM2 in AD and insights into the complex associations among inflammation, brain structure, and neurodegenerative disorders, particularly AD.
Topics: Humans; Alzheimer Disease; Amyotrophic Lateral Sclerosis; Genome-Wide Association Study; Mendelian Randomization Analysis; Neurodegenerative Diseases; Parkinson Disease; Brain; Inflammation; Cytokines; Encephalitis
PubMed: 37736795
DOI: 10.1007/s12035-023-03648-6 -
Behavioral and Brain Functions : BBF Oct 2023Emerging evidence suggests bidirectional causal relationships between sleep disturbance and psychiatric disorders, but the underlying mechanisms remain unclear....
BACKGROUND
Emerging evidence suggests bidirectional causal relationships between sleep disturbance and psychiatric disorders, but the underlying mechanisms remain unclear. Understanding the bidirectional causality between sleep traits and brain imaging-derived phenotypes (IDPs) will help elucidate the mechanisms. Although previous studies have identified a range of structural differences in the brains of individuals with sleep disorders, it is still uncertain whether grey matter (GM) volume alterations precede or rather follow from the development of sleep disorders.
RESULTS
After Bonferroni correction, the forward MR analysis showed that insomnia complaint remained positively associated with the surface area (SA) of medial orbitofrontal cortex (β, 0.26; 95% CI, 0.15-0.37; P = 5.27 × 10). In the inverse MR analysis, higher global cortical SA predisposed individuals less prone to suffering insomnia complaint (OR, 0.89; 95%CI, 0.85-0.94; P = 1.51 × 10) and short sleep (≤ 6 h; OR, 0.98; 95%CI, 0.97-0.99; P = 1.51 × 10), while higher SA in posterior cingulate cortex resulted in a vulnerability to shorter sleep durations (β, - 0.09; 95%CI, - 0.13 to - 0.05; P = 1.21 × 10).
CONCLUSIONS
Sleep habits not only result from but also contribute to alterations in brain structure, which may shed light on the possible mechanisms linking sleep behaviours with neuropsychiatric disorders, and offer new strategies for prevention and intervention in psychiatric disorders and sleep disturbance.
Topics: Humans; Sleep Initiation and Maintenance Disorders; Mendelian Randomization Analysis; Brain; Sleep; Sleep Wake Disorders; Phenotype; Genome-Wide Association Study
PubMed: 37784181
DOI: 10.1186/s12993-023-00220-z -
Journal of Crohn's & Colitis Oct 2023To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and/or endoscopic outcomes in moderately-to-severely active ulcerative colitis... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and/or endoscopic outcomes in moderately-to-severely active ulcerative colitis [UC].
METHODS
Endoscopic remission [ER], histological improvement [HI], histological remission [HR], histological-endoscopic mucosal improvement [HEMI], and histological-endoscopic mucosal remission [HEMR] were assessed at Week [W]12 [LUCENT-1: N = 1162, induction] and W40 [LUCENT-2: N = 544, maintenance] for patients randomised to mirikizumab or placebo. Analyses were performed to evaluate predictors of: HEMI at W12 with mirikizumab and HEMR at W40 in patients re-randomised to subcutaneous [SC] mirikizumab; associations between W12 histological/endoscopic endpoints and W40 outcomes in mirikizumab responders re-randomised to mirikizumab SC; and associations between W40 endoscopic normalisation [EN] with/without HR.
RESULTS
Significantly more patients treated with mirikizumab achieved HI, HR, ER, HEMI, and HEMR vs placebo [p <0.001], irrespective of prior biologic/tofacitinib failure [p <0.05]. Lower clinical baseline disease activity, female sex, no baseline immunomodulator use, and no prior biologic/tofacitinib failure were predictors of HEMI at W12 [p <0.05]. Corticosteroid use and longer disease duration were negative predictors of achieving HEMR at W40 [p <0.05]. W12 HI, HR, or ER was associated with W40 HEMI or HEMR [p <0.05]; ER at W12 was associated with clinical remission [CR] [p <0.05] and corticosteroid-free remission [CSFR] at W40 [p = 0.052]. HR and HEMR at W12 were associated with CSFR, CR, and symptomatic remission at W40. Alternate HEMR [EN + HR] at W40 was associated with bowel urgency remission at W40 [p <0.05].
CONCLUSIONS
Early resolution of endoscopic and histological inflammation with mirikizumab is associated with better UC outcomes. Clinicaltrials.gov: LUCENT-1, NCT03518086; LUCENT-2, NCT03524092.
Topics: Humans; Female; Colitis, Ulcerative; Inflammation; Adrenal Cortex Hormones; Biological Products; Remission Induction; Sulfonamides; Antibodies, Monoclonal, Humanized
PubMed: 37057827
DOI: 10.1093/ecco-jcc/jjad050 -
Cerebral Cortex (New York, N.Y. : 1991) Oct 2023The potential causal association between dyslipidemia and brain structures remains unclear. Therefore, this study aimed to investigate whether circulating lipids are...
The potential causal association between dyslipidemia and brain structures remains unclear. Therefore, this study aimed to investigate whether circulating lipids are causally associated with brain structure alterations using Mendelian randomization analysis. Genome-wide association study summary statistics of blood lipids and brain structures were obtained from publicly available databases. Inverse-variance weighted method was used as the primary method to assess causality. In addition, four additional Mendelian randomization methods (MR-Egger, weighted median, simple mode, and weighted mode) were applied to supplement inverse-variance weighted. Furthermore, Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis were performed for sensitivity analyses. After Bonferroni corrections, two causal associations were finally identified: elevated non-high-density lipoprotein cholesterol level leads to higher average cortical thickness (β = 0.0066 mm, 95% confidence interval: 0.0045-0.0087 mm, P = 0.001); and elevated high-density lipoprotein cholesterol level leads to higher inferior temporal surface area (β = 18.6077 mm2, 95% confidence interval: 11.9835-25.2320 mm2, P = 0.005). Four additional Mendelian randomization methods indicated parallel results. Sensitivity tests demonstrated the stability. Overall, the present study showed causal relationships between several lipid profiles and specific brain structures, providing new insights into the link between dyslipidemia and neurological disorders.
Topics: Humans; Genome-Wide Association Study; Mendelian Randomization Analysis; Lipids; Brain; Cholesterol; Dyslipidemias
PubMed: 37718242
DOI: 10.1093/cercor/bhad334