Inverse Association Between BMI and Prefrontal Metabolic Activity in Healthy Adults

National Institute on Drug Abuse, Bethesda, Maryland, USA.
Obesity (Impact Factor: 3.73). 11/2008; 17(1):60-5. DOI: 10.1038/oby.2008.469
Source: PubMed

ABSTRACT Obesity has been associated with a higher risk for impaired cognitive function, which most likely reflects associated medical complications (i.e., cerebrovascular pathology). However, there is also evidence that in healthy individuals excess weight may adversely affect cognition (executive function, attention, and memory). Here, we measured regional brain glucose metabolism (using positron emission tomography (PET) and 2-deoxy-2[(18)F]fluoro-D-glucose (FDG)) to assess the relationship between BMI and brain metabolism (marker of brain function) in 21 healthy controls (BMI range 19-37 kg/m(2)) studied during baseline (no stimulation) and during cognitive stimulation (numerical calculations). Statistical parametric mapping (SPM) revealed a significant negative correlation between BMI and metabolic activity in prefrontal cortex (Brodmann areas 8, 9, 10, 11, 44) and cingulate gyrus (Brodmann area 32) but not in other regions. Moreover, baseline metabolism in these prefrontal regions was positively associated with performance on tests of memory (California Verbal Learning Test) and executive function (Stroop Interference and Symbol Digit Modality tests). In contrast, the regional brain changes during cognitive stimulation were not associated with BMI nor with neuropsychological performance. The observed association between higher BMI and lower baseline prefrontal metabolism may underlie the impaired performance reported in healthy obese individuals on some cognitive tests of executive function. On the other hand, the lack of an association between BMI and brain metabolic activation during cognitive stimulation indicates that BMI does not influence brain glucose utilization during cognitive performance. These results further highlight the urgency to institute public health interventions to prevent obesity.

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Available from: Panayotis Thanos, Sep 26, 2015
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    • "The hypothesis regarding transfer of addiction seems more likely, following even longer periods post-bariatric surgery. While there is evidence for a decreased availability of D2R in obese subjects (Volkow et al., 2009), there is some controversy that argues this is only true for severe obesity (Eisenstein et al., 2013; Kessler, Zald, Ansari, Li & Cowan, 2014). Confounding variables include control cohorts from which other RDS behaviors have not been excluded, the use of BMI as a factor may not be appropriate as a phenotype and mild obesity may not indicate the real disorder. "
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    ABSTRACT: Background: Following the first association between the dopamine D2 receptor gene polymorphism and severe alcoholism, there has been an explosion of research reports in the psychiatric and behavioral addiction literature and neurogenetics. With this increased knowledge, the field has been rife with controversy. Moreover, with the advent of Whole Genome-Wide Studies (GWAS) and Whole Exome Sequencing (WES), along with Functional Genome Convergence, the multiple-candidate gene approach still has merit and is considered by many as the most prudent approach. However, it is the combination of these two approaches that will ultimately define real, genetic allelic relationships, in terms of both risk and etiology. Since 1996, our laboratory has coined the umbrella term Reward Deficiency Syndrome (RDS) to explain the common neurochemical and genetic mechanisms involved with both substance and non-substance, addictive behaviors. Methods: This is a selective review of peer-reviewed papers primary listed in Pubmed and Medline. Results: A review of the available evidence indicates the importance of dopaminergic pathways and resting-state, functional connectivity of brain reward circuits. Discussion: Importantly, the proposal is that the real phenotype is RDS and impairments in the brain's reward cascade, either genetically or environmentally (epigenetically) induced, influence both substance and non-substance, addictive behaviors. Understanding shared common mechanisms will ultimately lead to better diagnosis, treatment and prevention of relapse. While, at this juncture, we cannot as yet state that we have "hatched the behavioral addiction egg", we are beginning to ask the correct questions and through an intense global effort will hopefully find a way of "redeeming joy" and permitting homo sapiens live a life, free of addiction and pain.
    Journal of Behavioural Addictions 09/2014; 3(3):149-56. DOI:10.1556/JBA.3.2014.019 · 1.87 Impact Factor
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    • "Greater scores on TEFQ disinhibition are associated with impaired control of food intake [21] and have been linked with worse frontal executive function [21], [22]. They are also consistent with our prior findings showing a significant correlation between food restraint scores and striatal DA increases induced by exposure to food cues [23], thus supporting an association between decreased striatal DA signaling and impaired self-control [24]. "
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    ABSTRACT: Objective Dopamine mediates the rewarding effects of food that can lead to overeating and obesity, which then trigger metabolic neuroadaptations that further perpetuate excessive food consumption. We tested the hypothesis that the dopamine response to calorie intake (independent of palatability) in striatal brain regions is attenuated with increases in weight. Method We used positron emission tomography with [11C]raclopride to measure dopamine changes triggered by calorie intake by contrasting the effects of an artificial sweetener (sucralose) devoid of calories to that of glucose to assess their association with body mass index (BMI) in nineteen healthy participants (BMI range 21–35). Results Neither the measured blood glucose concentrations prior to the sucralose and the glucose challenge days, nor the glucose concentrations following the glucose challenge vary as a function of BMI. In contrast the dopamine changes in ventral striatum (assessed as changes in non-displaceable binding potential of [11C]raclopride) triggered by calorie intake (contrast glucose – sucralose) were significantly correlated with BMI (r = 0.68) indicating opposite responses in lean than in obese individuals. Specifically whereas in normal weight individuals (BMI <25) consumption of calories was associated with increases in dopamine in the ventral striatum in obese individuals it was associated with decreases in dopamine. Conclusion These findings show reduced dopamine release in ventral striatum with calorie consumption in obese subjects, which might contribute to their excessive food intake to compensate for the deficit between the expected and the actual response to food consumption.
    PLoS ONE 07/2014; 9(7):e101585. DOI:10.1371/journal.pone.0101585 · 3.23 Impact Factor
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    • "Obesity reduces regional cerebral blood flow, specifically to the prefrontal cortex, negatively impacting behaviors associated with that area thereby reducing executive functioning Pannacciulli et al., 2006; Walther et al., 2010; Willeumier et al., 2011. Reduced frontal lobe baseline metabolism correlates with body mass index (BMI), and negatively correlates with cognitive performance Mozley et al., 2001; Volkow et al., 2008. The extent of cognitive dysfunction seen in obese adults is highly variable Kanoski, 2012, perhaps caused by interactions or additive effects with related metabolic comorbidities. "
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    ABSTRACT: Despite 50 years of pharmacological and psychosocial interventions, schizophrenia remains one of the leading causes of disability. Schizophrenia is also a life-shortening illness, caused mainly by poor physical health and its complications. The end result is a considerably reduced lifespan that is marred by reduced levels of independence, with few novel treatment options available. Disability is a multidimensional construct that results from different, and often interacting, factors associated with specific types and levels of impairment. In schizophrenia, the most poignant and well characterized determinants of disability are symptoms, cognitive and related skills deficits, but there is limited understanding of other relevant factors that contribute to disability. Here we conceptualize how reduced physical performance interacts with aging, neurobiological, treatment-emergent, and cognitive and skills deficits to exacerbate ADL disability and worsen physical health. We argue that clearly defined physical performance components represent underappreciated variables that, as in mentally healthy people, offer accessible targets for exercise interventions to improve ADLs in schizophrenia, alone or in combination with improvements in cognition and health. And, finally, due to the accelerated aging pattern inherent in this disease – lifespans are reduced by 25 years on average – we present a training model based on proven training interventions successfully used in older persons. This model is designed to target the physical and psychological declines associated with decreased independence, coupled with the cardiovascular risk factors and components of the metabolic syndrome seen in schizophrenia due to their excess prevalence of obesity and low fitness levels.
    Schizophrenia Research: Cognition 06/2014; 1(2). DOI:10.1016/j.scog.2014.06.002
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