Body mass index, residual psychotic symptoms, and inflammation associated with brain volume reduction in older patients with schizophrenia

Tsai, Shang Ying; Sajatovic, Martha; Hsu, Jung Lung; Chung, Kuo Hsuan; Chen, Pao Huan; Huang, Yu Jui

doi:10.1002/gps.5291

Cited by 11 publications

(5 citation statements)

References 44 publications

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“…These included anterior cingulate, temporal pole, and key parts of frontal lobe, that is areas which are considered integral to neuroanatomy of major psychiatric disorders. This is in keeping with previous studies which also demonstrated additive effects of obesity and psychiatric disorders on brain structure [ 20 , 23 , 25 , 26 , 32 ]. We would expect changes in the regions associated with both conditions to be inflated in studies which did not control for BMI.…”

Section: Discussionsupporting

confidence: 93%

“…With 3021 individuals, this is the largest study investigating associations between schizophrenia, BMI and brain structure, and one of only 2 such studies [ 25 , 26 ]. We benefited from the significant methodological refinements and harmonization in the ENIGMA study and from access to a highly generalizable, multi-site sample of individuals with schizophrenia from around the world, thus representing a broad spectrum of individuals with this disorder.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated that in people with first episode of psychosis, obesity was associated with advanced brain age and lower cerebellar volume [ 23 , 24 ] and that BMI was a predictor of future neurostructural alterations [ 20 ]. The single previous study in 32 older individuals with schizophrenia found that higher BMI was significantly associated with lower volume of total gray matter, orbitofrontal and prefrontal cortices, and hippocampus [ 25 ]. Another study suggested that in schizophrenia, structural brain volume reductions, especially in areas of the reward circuitry, appeared to be related to comorbid metabolic syndrome [ 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals

et al. 2022

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Schizophrenia is frequently associated with obesity, which is linked with neurostructural alterations. Yet, we do not understand how the brain correlates of obesity map onto the brain changes in schizophrenia. We obtained MRI-derived brain cortical and subcortical measures and body mass index (BMI) from 1260 individuals with schizophrenia and 1761 controls from 12 independent research sites within the ENIGMA-Schizophrenia Working Group. We jointly modeled the statistical effects of schizophrenia and BMI using mixed effects. BMI was additively associated with structure of many of the same brain regions as schizophrenia, but the cortical and subcortical alterations in schizophrenia were more widespread and pronounced. Both BMI and schizophrenia were primarily associated with changes in cortical thickness, with fewer correlates in surface area. While, BMI was negatively associated with cortical thickness, the significant associations between BMI and surface area or subcortical volumes were positive.Lastly, the brain correlates of obesity were replicated among large studies and closely resembled neurostructural changes in major depressive disorders. We confirmed widespread associations between BMI and brain structure in individuals with schizophrenia. People with both obesity and schizophrenia showed more pronounced brain alterations than people with only one of these conditions. Obesity appears to be a relevant factor which could account for heterogeneity of brain imaging findings and for differences in brain imaging outcomes among people with schizophrenia.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals

et al. 2022

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“…Janney et al also pointed out that there was no association between obesity and PANSS psychiatric symptoms 45 . However, other studies have shown the opposite conclusion that obesity was a risk factor for cognitive impairment or rich psychiatric symptoms in schizophrenia [46][47][48][49][50] . Therefore, the relationship between obesity and cognitive and mental symptoms needs to be further studied.…”

Section: Discussionmentioning

confidence: 94%

APOE E4 is associated with hyperlipidemia and obesity in elderly schizophrenic patients

Liu

et al. 2021

Sci Rep

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Obesity is a critical issue in patients with schizophrenia, which is considered to be brought about by both environmental and genetic factors. Apolipoprotein E (APOE) gene polymorphisms might be involved in the pathogenesis of schizophrenia, however, the effect of APOE gene polymorphism on obesity has never been investigated in Chinese aging with schizophrenia. This cross-sectional study was to investigate the effect of obesity on cognitive and psychiatric symptoms in elderly participants with schizophrenia. At the same time, we also discussed the inner link between APOE E4 and obesity. 301 elderly participants with schizophrenia and 156 normal controls were included in the study. Their cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS), and APOE gene polymorphism was determined by polymerase chain reaction (PCR). The prevalence of obesity in elderly schizophrenic patients and healthy controls accounted for 15.9% (48/301) and 10.3% (16/156), respectively, with no statistically significant difference. By using stepwise linear regression analysis, we found that elevated fasting blood glucose, hypertension, and hyperlipidemia were risk factors for obesity in elderly schizophrenic patients. Although there was no direct correlation between APOE E4 and obesity in patients with schizophrenia, it was significantly correlated with hyperlipemia(r = − 0.154, p = 0.008), suggesting that APOE E4 may induce obesity in elderly patients with schizophrenia through hyperlipemia, However, the above conclusions do not apply to the normal elderly. What’s more, we did not find a link between obesity and cognitive function or mental symptoms for both patients with schizophrenia and normal controls. APOE E4 is associated with hyperlipidemia in elderly schizophrenic patients, which may be a risk factor for obesity, however, the above conclusion does not apply to the normal elderly.

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“…One study (48) found elevated levels of osteoprotegerin-a tumor necrosis factor receptor-associated with smaller total hippocampal volume, though no correlations with other cytokines, including TNF-α, nor IL-6, were found in the same study. Kudo et al (50) observed negative association between sTNF-R2 and hippocampal volume while Tsai et al (53) found sTNF-R1 was positively associated with right amygdala volume. Bossù et al reported an association between lower levels of pro-inflammatory cytokine IL-18 and smaller hippocampal volumes (44).…”

Section: Association Between Inflammatory and Neuroimaging Markersmentioning

confidence: 99%

The Role of Peripheral Inflammation in Clinical Outcome and Brain Imaging Abnormalities in Psychosis: A Systematic Review

et al. 2021

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Promising research investigating the association between inflammatory biomarkers and response to antipsychotic and/or adjunctive therapy, observed by improvement in psychiatric assessment, is emerging. Increased inflammation has been suggested to contribute to higher severity of symptoms/treatment resistance through the effects that this has on brain structure and function. The present systematic review aims to clarify the potential role of peripheral inflammatory markers as predictors of clinical outcomes and their association with neuroimaging markers in patients with psychosis. Systematic searches of the literature using the databases PsychInfo, OVID Medline, and Embase were conducted to collate studies investigating the association of inflammatory biomarkers with clinical outcome in patients with psychotic disorders and studies examining the relationships between inflammatory biomarkers and neuroimaging data. Seventeen studies on predictors of clinical outcome and 14 on associations between neuroimaging data and inflammatory biomarkers in psychosis were identified, and risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). The main inflammatory markers associated with clinical outcome in psychosis were interleukin (IL)-6, IL-10, and C-reactive protein (CRP). High levels of CRP and IL-6 were associated with worse clinical outcome and deterioration of symptoms over time; in contrast, increased levels of IL-10 were associated with greater symptoms improvement. Smaller hippocampal volume and reduced cortical thickness were the main neuroimaging markers associated with increased peripheral inflammation. The heterogeneity across the studies (i.e., treatments strategies, duration) suggests that potential prediction power of inflammatory biomarkers could partially depend on the methodologies, supported by the overall NOS ratings of the studies. Future studies may need to consider whether a combination of these inflammatory and neuroimaging markers could further improve our ability of predicting clinical outcome in patients with psychosis.

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Body mass index, residual psychotic symptoms, and inflammation associated with brain volume reduction in older patients with schizophrenia

Cited by 11 publications

References 44 publications

Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals

Obesity and brain structure in schizophrenia – ENIGMA study in 3021 individuals

APOE E4 is associated with hyperlipidemia and obesity in elderly schizophrenic patients

The Role of Peripheral Inflammation in Clinical Outcome and Brain Imaging Abnormalities in Psychosis: A Systematic Review

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