Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders

Opel, Nils; Thalamuthu, Anbupalam; Milaneschi, Yuri; Grotegerd, Dominik; Flint, Claas; Leenings, Ramona; Goltermann, Janik; Richter, Maike; Hahn, Tim; Woditsch, Georg; Berger, Klaus; Hermesdorf, Marco; McIntosh, Andrew M.; Whalley, Heather C.; Harris, Mathew A.; MacMaster, Frank P.; Walter, Henrik; Veer, Ilya M.; Frodl, Thomas; Carballedo, Angela; Krug, Axel; Nenadić, Igor; Kircher, Tilo; Alemán, André; Groenewold, Nynke A.; Stein, Dan J.; Soares, Jair C.; Zunta-Soares, Giovana; Mwangi, Benson; Wu, Mon Ju; Walter, Martín; Li, Meng; Harrison, Ben J; Davey, Christopher G.; Cullen, Kathryn R.; Klimes‐Dougan, Bonnie; Mueller, Bryon A.; Sämann, Philipp G.; Penninx, Brenda W.J.H.; Nawijn, Laura; Veltman, Dick J.; Aftanas, Lyubomir I.; Brak, Ivan V.; Filimonova, Elena; Osipov, Evgeniy A.; Reneman, Liesbeth; Schrantee, Anouk; Grabe, Hans J.; Auwera, Sandra Van der; Wittfeld, Katharina; Hosten, Norbert; Völzke, Henry; Sim, Kang; Gotlib, Ian H.; Sacchet, Matthew D.; Lagopoulos, Jim; Hatton, Sean N.; Hickie, Ian B.; Pozzi, Elena; Thompson, Paul M.; Jahanshad, Neda; Schmaal, Lianne; Baune, Bernhard T.; Dannlowski, Udo

doi:10.1038/s41380-020-0774-9

Cited by 95 publications

(64 citation statements)

References 60 publications

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“…Another animal study showed that there is astrogliosis in paraventricular and arcuate nucleus of hypothalamus and in hippocampus of obese rats and that this fact is probably associated with memory deficits in these rats [ 193 ]. A recent human study used MRI imaging to investigate if brain structure alterations in obese patients compared to normal weight controls are similar with those in patients with neuropsychiatric disorders [ 194 ]. The results support the notion that obesity affects cortical thickness in a similar way that major depression does, as previous studies reported [ 194 , 195 ].…”

Section: Presumed Role Of Hypothalamic Inflammation In Cognitive Amentioning

confidence: 99%

“…A recent human study used MRI imaging to investigate if brain structure alterations in obese patients compared to normal weight controls are similar with those in patients with neuropsychiatric disorders [ 194 ]. The results support the notion that obesity affects cortical thickness in a similar way that major depression does, as previous studies reported [ 194 , 195 ]. Another recent cross-sectional study used diffusion tensor imaging, an MRI technique, to correlate hypothalamic damage in middle-aged obese individuals with cognitive defects.…”

Section: Presumed Role Of Hypothalamic Inflammation In Cognitive Amentioning

confidence: 99%

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The Role of Hypothalamic Inflammation in Diet-Induced Obesity and Its Association with Cognitive and Mood Disorders

et al. 2021

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Obesity is often associated with cognitive and mood disorders. Recent evidence suggests that obesity may cause hypothalamic inflammation. Our aim was to investigate the hypothesis that there is a causal link between obesity-induced hypothalamic inflammation and cognitive and mood disorders. Inflammation may influence hypothalamic inter-connections with regions important for cognition and mood, while it may cause dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and influence monoaminergic systems. Exercise, healthy diet, and glucagon-like peptide receptor agonists, which can reduce hypothalamic inflammation in obese models, could improve the deleterious effects on cognition and mood.

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Section: Presumed Role Of Hypothalamic Inflammation In Cognitive Amentioning

confidence: 99%

Section: Presumed Role Of Hypothalamic Inflammation In Cognitive Amentioning

confidence: 99%

The Role of Hypothalamic Inflammation in Diet-Induced Obesity and Its Association with Cognitive and Mood Disorders

et al. 2021

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“…Whereas the negative association between obesity and cortical measures appears relatively uniform and replicated, there is less consistency in the direction and location of obesity-associated subcortical alterations [16,[19][20][21]24]. Therefore, more research specifically focusing on obesity and subcortical regions is needed in general, but especially in psychiatric disorders.…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, more research specifically focusing on obesity and subcortical regions is needed in general, but especially in psychiatric disorders. Relative to cortical measures, subcortical volumes are generally less linked to the genetic mechanisms of major psychiatric disorders [24][25][26]. Yet, subcortical changes are associated with BD [23] and are sensitive to other BD-related factors, such as medications [8] and metabolic alterations [19,27].…”

Section: Introductionmentioning

confidence: 99%

Association between body mass index and subcortical brain volumes in bipolar disorders–ENIGMA study in 2735 individuals

McWhinney¹,

Abé²,

Alda³

et al. 2021

Mol Psychiatry

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Individuals with bipolar disorders (BD) frequently suffer from obesity, which is often associated with neurostructural alterations. Yet, the effects of obesity on brain structure in BD are under-researched. We obtained MRI-derived brain subcortical volumes and body mass index (BMI) from 1134 BD and 1601 control individuals from 17 independent research sites within the ENIGMA-BD Working Group. We jointly modeled the effects of BD and BMI on subcortical volumes using mixed-effects modeling and tested for mediation of group differences by obesity using nonparametric bootstrapping. All models controlled for age, sex, hemisphere, total intracranial volume, and data collection site. Relative to controls, individuals with BD had significantly higher BMI, larger lateral ventricular volume, and smaller volumes of amygdala, hippocampus, pallidum, caudate, and thalamus. BMI was positively associated with ventricular and amygdala and negatively with pallidal volumes. When analyzed jointly, both BD and BMI remained associated with volumes of lateral ventricles and amygdala. Adjusting for BMI decreased the BD vs control differences in ventricular volume. Specifically, 18.41% of the association between BD and ventricular volume was mediated by BMI (Z = 2.73, p = 0.006). BMI was associated with similar regional brain volumes as BD, including lateral ventricles, amygdala, and pallidum. Higher BMI may in part account for larger ventricles, one of the most replicated findings in BD. Comorbidity with obesity could explain why neurostructural alterations are more pronounced in some individuals with BD. Future prospective brain imaging studies should investigate whether obesity could be a modifiable risk factor for neuroprogression.

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“…Regarding the functional role of the OFC, previous work has highlighted it as a key area in evaluating food options and has been implicated in other psychiatric conditions with disturbed immunometabolic profiles such as anorexia nervosa [67]. Furthermore, as outlined above the OFC has repeatedly been linked to increased body-weight and obesity in large-scale mega-and meta-analyses [22,68]. Results from a recent study [38] that demonstrated an association between lower lateral OFC thickness and food addiction symptoms seem to further support the results presented here.…”

Section: Discussionmentioning

confidence: 99%

Evidence for a specific regional association between lateral orbitofrontal cortex morphometry and increased appetite in major depression

Mehler¹,

Repple²,

Kroemer³

et al. 2021

Preprint

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Increased appetite and body weight are core features of atypical depression. While previous research has consistently highlighted the presence of distinct immunometabolic profiles in atypical depression, little is still known about the neural correlates of atypical symptoms in major depression. Even though obesity and increased body-mass index have frequently been associated with prefrontal brain structural alterations first and foremost in the orbitofrontal cortex (OFC) in healthy and depressed subjects, it is unclear if conceptually related atypical depressive symptoms are associated with similar neural signatures. Here we aimed to investigate associations between appetite and weight change in major depression and OFC morphometry using a multimodal structural neuroimaging approach. We found that increased appetite was associated with significantly lower cortical thickness and lower gray matter density specifically in the right lateral OFC. Further, Bayesian model comparison showed that appetite change was a more informative predictor for changes in cortical thickness and gray matter density compared to body mass index. No conclusive association between appetite change and white matter tracts connected to the right lateral OFC was found. Our findings highlight the relevance of the right lateral OFC for future investigation of the neurobiological underpinnings of the atypical depressive symptom dimensions appetite and weight gain.

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Brain structural abnormalities in obesity: relation to age, genetic risk, and common psychiatric disorders

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

Cited by 95 publications

References 60 publications

The Role of Hypothalamic Inflammation in Diet-Induced Obesity and Its Association with Cognitive and Mood Disorders

The Role of Hypothalamic Inflammation in Diet-Induced Obesity and Its Association with Cognitive and Mood Disorders

Association between body mass index and subcortical brain volumes in bipolar disorders–ENIGMA study in 2735 individuals

Evidence for a specific regional association between lateral orbitofrontal cortex morphometry and increased appetite in major depression

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