Obesidade e neuroprogressão : estudos de associação com enfoque na funcionalidade

Transtorno bipolar (TB) e esquizofrenia (SZ) são transtornos psiquiátricos graves e persistentes (TMGP) com curso muitas vezes progressivo associado a significativo prejuízo funcional para as atividades diárias. Indivíduos com esses transtornos também apresentam prevalências muito aumentadas de sobrepeso e obesidade e têm como principal causa de morte eventos cardiovasculares, morrendo entre 10 e 20 anos mais cedo do que o restante da população. Os mecanismos fisiopatológicos comuns à obesidade e TMGP são ainda muito pouco estudados para uma comorbidade tão prevalente e de morbimortalidade tão elevada. O objetivo desta tese foi estudar a obesidade em TMGP a partir da perspectiva da neuroprogressão. O primeiro estudo apresentado consiste na revisão dos achados clínicos e biológicos que corroboram os modelos de neuroprogressão e neurodesenvolvimento em SZ. A partir dessa perspectiva, foram propostos dois estudos experimentais, um analisando a associação do índice de massa corporal (IMC) com um marcador de conectividade cerebral em TB e o outro com a funcionalidade na SZ, ambos comparados a um grupo controle sem transtornos psiquiátricos (CTR). O IMC está associado a alterações microestruturais do giro do cíngulo direito em indivíduos com TB (AdjR²=0,312 F(3)=5,537 p=0,004; β=-0,340 p=0,034), mas não em CTR, sugerindo que a interação entre TB e obesidade esteja associada à diminuição de conectividade límbica. Já no outro estudo, cerca de 22% da variação dos escores funcionais em CTR (AdjR²= 0,225 F(3,284)=28,79 p<0,001) foi descrito por um modelo com efeito do IMC (β=0,509 t=9,240 p<0,001) e da idade (β=0,174 t=3,118 p=0,002), enquanto que em indivíduos com SZ foram apenas os anos vividos com a doença que se associaram a pior funcionamento (β=0,197 t=2,615 p=0,009). Em conjunto, demonstramos uma área cerebral possivelmente envolvida na interação deletéria entre obesidade e TB, além de evidenciar que a obesidade traz prejuízos ao funcionamento diário na população em geral. Ambas embasam a importância de estratégias de combate à obesidade para a promoção da saúde mental na comunidade. Além disso, dada a inquestionável associação do excesso de peso com aumento da morbimortalidade, sua identificação e manejo devem ser prioridades dos profissionais de saúde.Bipolar disorder (BD) and schizophrenia (SZ) are severe mental illnesses (SMI), often with a progressive course leading to functioning impairment. This population also deals with at least a 2-fold increase in the prevalence of obesity. The main cause of death among patients with SMI are cardiovascular events, resulting in a reduction in life expectancy of more than 10 years, reaching an alarming gap of 20 years in TB and SZ. There is still scarce research focused on the pathophysiological mechanisms common to obesity and SMI considering its morbidity and mortality. The aim of this thesis was to study obesity in SMI from the perspective of neuroprogression. The first study is a review of the biological findings that endorse neuroprogression and neurodevelopmental models in SZ. From this perspective, two experimental studies were proposed, one analyzing the association of body mass index (BMI) with a white matter integrity marker and the other with SZ functioning, both compared to a control group without psychiatric disorders (CTR). BMI is associated with the microstructure of the right cingulate gyrus fibers in BD (AdjR²=.312 F(3)=5.537 p=.004; β=-.034), but not among CTR. It suggests that the interaction between TB and obesity may be associated with decreased limbic connectivity. In the other study, about 22% of the functioning performance of CTR (AdjR²= .225F(3.284)=28.79 p<.001) was described by a model with significant main effect of BMI (β=.540 p <.001) and age (β=.174 t=3,118 p=.002). Among SZ, only years lived with the disease were associated with daily functioning (β=.197 t=2.615 p=.009). Taken together, these findings demonstrate a possible brain area related to the deleterious interaction between obesity and TB, in addition to functioning impairment associated with obesity in the general population. Both support the importance of strategies to oppose obesity targeting promotion of mental health in the community. Furthermore, given the unquestionable association of increased BMI with increased morbidity and mortality, its identification and management should be a priority for health professionals

Country-level gender inequality is associated with structural differences in the brains of women and men

男女間の不平等と脳の性差 --男女間の不平等は脳構造の性差と関連する--. 京都大学プレスリリース. 2023-05-10.Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7, 876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality

Country-level gender inequality is associated with structural differences in the brains of women and men

Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women's worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women's brains and provide initial evidence for neuroscience-informed policies for gender equality