Nucleus accumbens volume is related to obesity measures in an age-dependent fashion.

Motivation theories of obesity suggest that one of the brain mechanisms underlying pathological eating and weight gain is the dysregulation of dopaminergic circuits. Although these dysregulations likely occur at the microscopic level, studies on grey matter volume report macroscopic differences associated with obesity. One region suggested to play a key role in the pathophysiology of obesity is the nucleus accumbens (NAcc). We performed a meta-analysis of findings regarding NAcc volume and overweight/obesity. We additionally examined whether grey matter volume in the NAcc and other mesolimbic areas depends on the longitudinal trajectory of obesity, using the UK Biobank dataset. To this end, we analysed the data using a latent growth model, which identifies whether a certain variable of interest (eg, NAcc volume) is related to another variable's (body mass index [BMI]) initial values or longitudinal trajectories. Our meta-analysis showed that, overall, NAcc volume is positively related to BMI. However, further analyses revealed that the relationship between NAcc volume and BMI is dependent on age. For younger individuals, such a relationship is positive, whereas, for older adults, it is negative. This was corroborated by our analysis in the UK Biobank dataset, which includes older adults, where we found that a higher BMI was associated with a lower NAcc and thalamus volume. Overall, the present study suggests that increased NAcc volume at a young age might be a vulnerability factor for obesity, whereas, at an older age, decreased NAcc volume with increased BMI might be an effect of prolonged influences of neuroinflammation on the brain.

Pathological glutamatergic neurotransmission in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome is a hereditary, neuropsychiatric movement disorder with reported abnormalities in the neurotransmission of dopamine and γ-aminobutyric acid (GABA). Spatially focalized alterations in excitatory, inhibitory and modulatory neurochemical ratios within specific functional subdivisions of the basal ganglia, may lead to the expression of diverse motor and non-motor features as manifested in Gilles de la Tourette syndrome. Current treatment strategies are often unsatisfactory thus provoking the need for further elucidation of the underlying pathophysiology. In view of (i) the close spatio-temporal synergy exhibited between excitatory, inhibitory and modulatory neurotransmitter systems; (ii) the crucial role played by glutamate (Glu) in tonic/phasic dopaminergic signalling; and (iii) the interdependent metabolic relationship exhibited between Glu and GABA via glutamine (Gln); we postulated that glutamatergic signalling is related to the pathophysiology of Gilles de la Tourette syndrome. As such, we examined the neurochemical profile of three cortico-striato-thalamo-cortical regions in 37 well-characterized, drug-free adult patients and 36 age/gender-matched healthy control subjects via magnetic resonance spectroscopy at 3 T. To interrogate the influence of treatment on metabolite concentrations, spectral data were acquired from 15 patients undergoing a 4-week treatment with aripiprazole. Test-retest reliability measurements in 23 controls indicated high repeatability of voxel localization and metabolite quantitation. We report significant reductions in striatal concentrations of Gln, Glu + Gln (Glx) and the Gln:Glu ratio, and thalamic concentrations of Glx in Gilles de la Tourette syndrome in comparison to controls. ON-treatment patients exhibited no significant metabolite differences when compared to controls but significant increases in striatal Glu and Glx, and trends for increases in striatal Gln and thalamic Glx compared to baseline measurements. Multiple regression analysis revealed a significant negative correlation between (i) striatal Gln and actual tic severity; and (ii) thalamic Glu and premonitory urges. Our results indicate that patients with Gilles de la Tourette syndrome exhibit an abnormality in the flux of metabolites in the GABA-Glu-Gln cycle, thus implying perturbations in astrocytic-neuronal coupling systems that maintain the subtle balance between excitatory and inhibitory neurotransmission within subcortical nuclei.