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Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group.

ABSTRACT: Emerging evidence suggests that obesity impacts brain physiology at multiple levels. Here we aimed to clarify the relationship between obesity and brain structure using structural MRI (n = 6420) and genetic data (n = 3907) from the ENIGMA Major Depressive Disorder (MDD) working group. Obesity (BMI > 30) was significantly associated with cortical and subcortical abnormalities in both mass-univariate and multivariate pattern recognition analyses independent of MDD diagnosis. The most pronounced effects were found for associations between obesity and lower temporo-frontal cortical thickness (maximum Cohen´s d (left fusiform gyrus) = -0.33). The observed regional distribution and effect size of cortical thickness reductions in obesity revealed considerable similarities with corresponding patterns of lower cortical thickness in previously published studies of neuropsychiatric disorders. A higher polygenic risk score for obesity significantly correlated with lower occipital surface area. In addition, a significant age-by-obesity interaction on cortical thickness emerged driven by lower thickness in older participants. Our findings suggest a neurobiological interaction between obesity and brain structure under physiological and pathological brain conditions.

SUBMITTER: Opel N

PROVIDER: S-EPMC8589644 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundObservational studies have shown associations between psychiatric disorders and osteoarthritis (OA). However, the causal impact of different psychiatric disorder types on specific sites of osteoarthritis remains unclear. This study aimed to comprehensively understand the potential causal associations between psychiatric disorders and osteoarthritis using Mendelian randomization (MR) analysis.MethodsWe collected data from genome-wide association studies of knee osteoarthritis (KOA) (n = 403,124), hip osteoarthritis (HOA) (n = 393,873), osteoarthritis of the knee or hip (KHOA) (n = 417,596), as well as three psychiatric disorders: bipolar disorder (n = 41,917), major depressive disorder (n = 170,756), and schizophrenia (n = 76,755) among European populations. We applied bidirectional univariate and multivariate MR analyses, including inverse variance weighted, Mendelian randomization-Egger, weighted median, simple mode, and weighted mode. We considered p < .05 as a criterion for identifying potential evidence of association. Bonferroni correction was used for multiple tests.ResultsOur univariate MR analysis results demonstrated that bipolar disorder is a protective factor for KOA (OR = 0.90, 95% CI = 0.83 to 0.97, p = 0.0048) and may also be protective for KHOA (p = 0.02). Conversely, major depression has a positive causal effect on both KOA (OR = 1.27; 95% CI = 1.08 to 1.49; p = 0.0036) and KHOA (OR = 1.24; 95% CI = 1.12 to 1.37; p = 3.62×10-05 ). Furthermore, our analysis suggested that KHOA may be a risk factor for major depression (OR = 1.06; 95% CI = 1.00 to 1.12; p = 0.0469) in reverse MR. After adjusting smoking (OR = 1.46; 95% CI = 1.19 to 1.65; p = 0.0032) and body mass index (OR = 1.44; 95% CI = 1.09 to 1.81; p = 8.56×10-04 ), the casual association between major depression and KHOA remained.ConclusionOur study indicates that major depression is a great risk factor for KHOA, increasing the likelihood of their occurrence. However, further in-depth studies will be required to validate these results and elucidate the underlying molecular mechanisms.

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Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders : Evidence through univariate and multivariate mega-analysis including 6420 participants from the ENIGMA MDD working group.

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