Behavioral Association And Neural Links Between Dietary Intake Pattern And Physical And Mental Health

Part 1.Study on the Post-oral Mechamisms of Glucose PreferencesObjectives: Previous studies have shown that obesity or metabolic syndrome caused by excessive glucose intake could increase the risk of mental disorders.The purpose of this study was to explore the possible mechanisms underlying the formation of glucose preference,providing cues to develop effective prevention or intervention strategies to rescue glucose preference behaviors,as well as the follwing adverse consequences.Methods: This study was conduct on mice.By putting intra-gastric catheter,we successfully setup a mouse post-oral feeding model;in combination with flavor-nutrition conditioning paradigm,we first compared the intake of glucose and non-metabolizable glucose analog a-methyl-D-glucopyranoside(MDG)at several sugar concentrations.Then by inserting catheter into the portal-mesenteric vein and infusing glucose or MDG through it,we detected the changes of dopamine release in both the ventral striatum and dorsal striatum via dopamine microdialysis.Then,we empolyed mice with dopamine transporter knockdown(DAT+/-)and low-dose haloperidol i.p.injection,to explore whether hyperdopaminergia associated with impared learning and memory,symptoms obeseved in mental disorders.Results: Through nutrition-flavor conditioning paradigm,mice formed stronger preference for glucose solution over MDG solution at both concentrations(p < 0.05),and this glucose preference was difficult to reverse through reverse learning.GLU infusion throught portal venous catheters produced sustained dopamine increase in both the dorsal striatum and ventral striatum,whereas an equivalent infusion of MDG failed to raise dopamine release above baseline levels(dorsal striatum: p < 0.001;ventral striatum: p = 0.001).Mice with modest increased dopamine showed impared trace conditioned fear memory and spatial working memory(all p <0.05).Conclusions: The formation of glucose preference mainly attribute to the effect after glucose absorption into the blood rather than the activation of intestinal glucose receptors.After glucose is absorbed,it is glucose or its metabolites might activate the mesenteric-portal system,which then activate the midbrain reward system,increasing dopamine release.Meanwhile,hyperdopaminergic activities are associated with some learning and memory impairment.Part 2.Study on the Relationships between Chinese Dietary Patterns and Depressive Symption during Preconception and PregnancyObjectives: previous researches in pregnancy women mainly focused on single nutrient.Given the complex interactions among various nutrients that make up habitual diet,to explore the association between habitual dietary patterns and mental health could be a more reliable approach.Therefore,we set up the present study with the aim to identify and describe specific Chinese dietary patterns for women from preconception to pregnancy in Shanghai,as well as to exam the association between specific Chinese habitual dietary patterns and the depressive symptoms.Mehods: This is a corss-sectional study,based on the Shanghai Birth Cohort.Women at their preconception or the prenatal stage,and met the inclusion criteria were included in study.First,the presence of depressive symptoms was assessed by the Center for Epidemiologic Studies Depression Scale,with a cutoff of 16.Then,Chinese dietary patterns were determined via principal component analysis,using information obtained from food frequency questionnaire;and scores for each dietary pattern were categorized into quartiles(Q1-Q4),and the first quartile(Q1)was used as a reference category.Then,logistic regression analysis with adjustment was employed to study the relationship between dietary patterns and depressive symptoms.Results: 1,160 women was included at the preconception stage,among them four Chinese dietary patterns were identified(Modern Convenient,Traditional Balanced,Traditional Meat-rich and Modern Diary-rich)and 351 subjects(27.2%)were classified as having depressiive symptoms.Traditional Balanced Pattern was associated with the lower OR of depression,with a significant level achieved for the second quartile(OR = 0.547,95% CI = 0.338~0.885);and a significant U-shape association between Modern Convenient Pattern and depression was observed(p for quadratic trend = 0.004),with lowest OR in the third quartile(OR = 0.450,95%CI = 0.273~0.742).Meanwhile,during prenatal stage,2,722 women took part.Among them,three dietary patterns were identified(Traditional Vegetarian,Modern Convenient,and Traditional Meat-rich dietary pattern)and 594 subjects(21.8%)were classified as having suspicious depression.Only the third quartile of the Traditional Vegetarian Pattern was associated with lower OR of depression(OR = 0.645,95%CI = 0.454~0.917).Conclusions: With this large-scale cross-sectional study,our study supports a relationship between maternal dietary patterns and depression at both prenatal and preconception periods;further large-scale prospective and dietary intervention studies are required to confirm this finding.Part 3.Study on the Relationship between Abnormal Eating Behaviors and Clinical Symptoms/Brain Structure in ASDObjectives: Children with ASD often co-morbid with eating problem,in this section,we would focused on the ASD children,to assess the prevalence and types of abnormal eating behaviors among them;and to investigate the relationship between abnormal eating behaviors and individuals' growth and development,clinical symptoms and brain structures.Methods: This is a corss-sectional study,based on the Shanghai Xinhua ASD Cohort.Children met the inclusion criteria were included in study,recuited from October 2016 to September 2018.First,for ASD children,their demographic information,clinical symptoms and eating behaviors information were collected;ASD children were grouped into ASD with/without abnormal eating bahviors,according to the presence of eating problem(i.e.poor appetite,limited food repertoire,severe food preferences or rejecting novel food)or not.We compared the clinical phenotypes between these two groups of ASD children.Meanwhile,T1 structural imagings were collected at both ASD with/without abnormal eating bahviors,and children without ASD.We compared brain structures among the above three groups.Results: A total of 272 ASD children were included in this study;of them,123 children have abnormal eating behavior,with an incidence of 45.22%,and the most frequent symptoms are limited food repertoire(92,33.82%)and rejecting novel food(84,30.88%).Focusing on behaviors,we found that there is no significant difference at BMI zscore,developmental quotient/intelligence quotient,or ASD overall severity bwtween ASD with and without eating problem.Meanwhile,we found that ASD children with eating problems surfered more from gastrointestinal problems,and sensory hyperresponsiveness and repetitive and stereotyped problems(all p < 0.05)than ASD children without eating problem.When comparing the gray matter volume,we found significat volume differences at Frontal_Med_Orb_L,Precentral_R,Temporal_Pole_Sup_R,Frontal_Mid_R and Frontal_Inf_Oper_R(alphasim correction,voxel-wise p<0.001,cluster-wise p<0.05).Post-hoc analysis further revelled that the difference identified above were occurred mostly between ASD children and children without ASD;only the Temporal_Pole_Sup_R showed volumetric difference between ASD children with and without eating problems.Conclusions: As eating problem is common in children diagnosed with autism,and it is with associated with worse clinical and behavioral phenotypes,therefore it is worthy to pay more attention to eating problem in ASD and make target intervention strategy.