Can neural network instability in schizophrenia be improved with a very low carbohydrate ketogenic diet?
精神分裂症的神经网络不稳定可以通过极低碳水化合物的生酮饮食来改善吗?
基本信息
- 批准号:10471918
- 负责人:
- 金额:$ 19.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAddressAdultAgeAgingAnhedoniaAntidotesAntipsychotic AgentsBody Weight decreasedBrainCarbohydratesCardiovascular systemCase StudyChronicClinicalClinical ResearchCognitionCognitiveCognitive deficitsConsumptionDataDelusionsDementiaDiagnosisDietDiseaseEatingEnergy-Generating ResourcesFatty acid glycerol estersFree EnergyFunctional Magnetic Resonance ImagingGlucoseHallucinationsHomeostasisHumanImpaired cognitionInflammationInflammatoryInsulinInsulin ResistanceInterventionKetone BodiesKetonesKetosisLinkLipidsLiteratureLongevityMagnetic Resonance ImagingMeasuresMediatingMeta-AnalysisMetabolicMetabolic DiseasesMetabolic syndromeMetabolismMitochondriaModernizationMorbidity - disease rateNeurocognitive DeficitNeuropsychologyNon-Insulin-Dependent Diabetes MellitusNutrientObesityOccupationalOutcomeOverweightPaperParticipantPatientsPeripheralPersonsPharmaceutical PreparationsPilot ProjectsPredispositionProductionProteinsPsychiatryRandomizedReactive Oxygen SpeciesReducing dietReportingRestRiskRoleSchizophreniaSymptomsTimeVisceral fatWeight GainWorkanti agingbaseblood glucose regulationbody volumebrain dysfunctioncomorbiditydeprivationdiagnostic criteriaexperiencefirst episode schizophreniafunctional MRI scanfunctional declineglucose metabolismhuman old age (65+)improvedindexinginsulin sensitivityketogenic dietmortalityneural networkpreventprospectiverelating to nervous systemsexsocialsymptomatic improvementsystemic inflammatory response
项目摘要
Wide ranging cognitive deficits are major drivers of functional decline and poor outcomes in people with
schizophrenia (SZ). Antipsychotic medications do not target pathophysiological mechanisms thought to underlie
these deficits. In the search for interventions targeting underlying cognitive impairment in schizophrenia, we
look comprehensively beyond just the brain and to the potential role of dysfunctional systemic metabolism.
Disrupted insulin and glucose metabolism are seen in medication-naïve first-episode SZ, suggesting that
SZ itself, and not just the medications used to treat it, is associated with risk of Type 2 diabetes, cardiovascular
morbidity and mortality, and more generally, accelerated aging. Even young people with SZ have increased risk
of metabolic disease and cognitive deficits. Sadly, their life span is shortened by 15–20 years.
Although the human brain is 2% of the body’s volume, it consumes over 20% of its energy, and accordingly,
the brain is particularly vulnerable to the dysregulation of glucose metabolism seen in SZ. While glucose is
considered to be the brain’s default fuel, ketones provide 27% more free energy and are a major source of
energy for the brain. Ketones prevent or improve various age-associated diseases, and a ketogenic diet (70%
fat, 20% protein, 10% carbohydrates) has been posited as an anti-aging and dementia antidote.
The premise of the work is based on recent evidence that ketogenic diets improve dynamic neural network
instability, related to cognitive deficits, aging, and Type 2 diabetes. The rigor of the work rests on findings of (1)
poor glucose homeostasis in SZ, (2) neural network instability in SZ, and (3) direct effects of ketosis on network
instability. Unknown is whether ketogenic diets can improve network instability in people with SZ.
We propose a mechanistic, prospective, clinical pilot study of a 4-week ketogenic diet on neural network
instability in overweight/obese SZ, at risk for insulin resistance. Seventy SZ (40-65 years old) will be randomized
to a ketogenic diet (n=35) or diet-as-usual (n=35). Resting state 7Tesla fMRI scans will be acquired before and
after the 4-week diets. Cognitive data at baseline will be used to determine if its relationship with network
instability, seen in neurotypicals, is also seen in SZ. We will compare network stability following the two diets
and consider the role of metabolic and inflammatory mechanisms in improvement of neural network instability.
This work brings together cardiovascular metabolism and psychiatry to address two problems experienced
by people with schizophrenia: (1) neural network instability associated with cognitive deficits, and (2) insulin
resistance associated with morbidity and mortality. A controlled ketogenic diet has never been tried in people
with SZ, who suffer from both cognitive deficits and insulin resistance. At the end of this 2-year project, we will
know if deficient glucose metabolism, at least partially mediated by primary or secondary insulin-resistance,
contributes to network instability in schizophrenia, a pathophysiological mechanism underlying accelerated
aging and cognitive impairment in the disorder.
广泛的认知缺陷是患有这种疾病的人功能下降和不良结果的主要驱动因素
精神分裂症(SZ)。抗精神病药物并不针对被认为是潜在的病理生理机制。
在寻找针对精神分裂症潜在认知障碍的干预措施时,我们。
不仅要全面关注大脑,还要关注系统代谢功能失调的潜在作用。
在首次接受药物治疗的 SZ 患者中观察到胰岛素和葡萄糖代谢紊乱,这表明
SZ 本身,而不仅仅是用于治疗它的药物,与 2 型糖尿病、心血管疾病的风险相关。
发病率和死亡率,更普遍的是,加速衰老,即使是年轻人,患有精神分裂症的风险也会增加。
不幸的是,他们的寿命缩短了 15-20 年。
人脑虽然只占身体体积的2%,但却消耗了身体20%以上的能量,因此,
大脑特别容易受到 SZ 中葡萄糖代谢失调的影响。
酮被认为是大脑的默认燃料,可提供 27% 以上的自由能,并且是大脑的主要来源
酮可以预防或改善各种与年龄相关的疾病,以及生酮饮食(70%)
脂肪、20% 蛋白质、10% 碳水化合物)已被认为是抗衰老和痴呆症的解毒剂。
这项工作的前提是基于生酮饮食改善动态神经网络的最新证据
不稳定,与认知缺陷、衰老和 2 型糖尿病有关。这项工作的严谨性取决于 (1) 的发现。
SZ 的葡萄糖稳态较差,(2) SZ 的神经网络不稳定,以及 (3) 酮症对网络的直接影响
生酮饮食是否可以改善精神分裂症患者的网络不稳定尚不清楚。
我们提出了一项基于神经网络的 4 周生酮饮食的机械性、前瞻性、临床试点研究
超重/肥胖 SZ 不稳定,有胰岛素抵抗风险的 70 名 SZ(40-65 岁)将被随机分组。
生酮饮食 (n=35) 或照常饮食 (n=35) 之前和之前采集静息状态 7Tesla fMRI 扫描。
4 周节食后,基线认知数据将用于确定其与网络的关系。
在神经典型中出现的不稳定性在 SZ 中也出现过,我们将比较两种饮食后的网络稳定性。
并考虑代谢和炎症机制在改善神经网络不稳定性中的作用。
这项工作将心血管代谢和精神病学结合起来,以解决所遇到的两个问题
精神分裂症患者:(1) 与认知缺陷相关的神经网络不稳定,以及 (2) 胰岛素
与发病率和死亡率相关的抵抗力从未在人类中尝试过。
与同时患有认知缺陷和胰岛素抵抗的 SZ 一起,在这个为期 2 年的项目结束时,我们将
了解葡萄糖代谢缺陷是否至少部分由原发性或继发性胰岛素抵抗介导,
导致精神分裂症的网络不稳定,这是加速潜在的病理生理机制
该疾病中的衰老和认知障碍。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Judith M Ford其他文献
Judith M Ford的其他文献
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{{ truncateString('Judith M Ford', 18)}}的其他基金
CSRD Research Career Scientist Award Application
CSRD研究职业科学家奖申请
- 批准号:
10657600 - 财政年份:2022
- 资助金额:
$ 19.16万 - 项目类别:
Neural and cognitive consequences of COVID-19 survival.
COVID-19 生存对神经和认知的影响。
- 批准号:
10595562 - 财政年份:2021
- 资助金额:
$ 19.16万 - 项目类别:
Can neural network instability in schizophrenia be improved with a very low carbohydrate ketogenic diet?
精神分裂症的神经网络不稳定可以通过极低碳水化合物的生酮饮食来改善吗?
- 批准号:
10517239 - 财政年份:2021
- 资助金额:
$ 19.16万 - 项目类别:
Can neural network instability in schizophrenia be improved with a very low carbohydrate ketogenic diet?
精神分裂症的神经网络不稳定可以通过极低碳水化合物的生酮饮食来改善吗?
- 批准号:
10689440 - 财政年份:2021
- 资助金额:
$ 19.16万 - 项目类别:
Secondary data analysis of auditory steady-state response to explore the RDoC cognitive system constructs across the psychosis spectrum
听觉稳态反应的二次数据分析,以探索整个精神病谱系的 RDoC 认知系统结构
- 批准号:
10333412 - 财政年份:2021
- 资助金额:
$ 19.16万 - 项目类别:
Neural and cognitive consequences of COVID-19 survival.
COVID-19 生存对神经和认知的影响。
- 批准号:
10368420 - 财政年份:2021
- 资助金额:
$ 19.16万 - 项目类别:
Can neural network instability in schizophrenia be improved with a very low carbohydrate ketogenic diet?
精神分裂症的神经网络不稳定可以通过极低碳水化合物的生酮饮食来改善吗?
- 批准号:
10288095 - 财政年份:2021
- 资助金额:
$ 19.16万 - 项目类别:
Secondary data analysis of existing data to explore the RDoC construct of agency across the psychosis spectrum using fMRI and EEG
使用 fMRI 和 EEG 对现有数据进行二次数据分析,探索整个精神病谱系的 RDoC 代理结构
- 批准号:
9884515 - 财政年份:2020
- 资助金额:
$ 19.16万 - 项目类别:
Predictive Coding Abnormalities in Psychosis: EEG and fMRI
精神病中的预测编码异常:脑电图和功能磁共振成像
- 批准号:
9482228 - 财政年份:2017
- 资助金额:
$ 19.16万 - 项目类别:
Rescuing the ruminating brain: Identifying biomarkers of rumination and mindfulness through concurrent EEG and fMRI studies of schizophrenia and depression
拯救沉思的大脑:通过精神分裂症和抑郁症的同步脑电图和功能磁共振成像研究来识别沉思和正念的生物标志物
- 批准号:
10291800 - 财政年份:2011
- 资助金额:
$ 19.16万 - 项目类别:
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