Decreased dopamine activity predicts relapse in methamphetamine abusers.

Studies in methamphetamine (METH) abusers showed that the decreases in brain dopamine (DA) function might recover with protracted detoxification. However, the extent to which striatal DA function in METH predicts recovery has not been evaluated. Here we assessed whether striatal DA activity in METH abusers is associated with clinical outcomes. Brain DA D2 receptor (D2R) availability was measured with positron emission tomography and [(11)C]raclopride in 16 METH abusers, both after placebo and after challenge with 60 mg oral methylphenidate (MPH) (to measure DA release) to assess whether it predicted clinical outcomes. For this purpose, METH abusers were tested within 6 months of last METH use and then followed up for 9 months of abstinence. In parallel, 15 healthy controls were tested. METH abusers had lower D2R availability in caudate than in controls. Both METH abusers and controls showed decreased striatal D2R availability after MPH and these decreases were smaller in METH than in controls in left putamen. The six METH abusers who relapsed during the follow-up period had lower D2R availability in dorsal striatum than in controls, and had no D2R changes after MPH challenge. The 10 METH abusers who completed detoxification did not differ from controls neither in striatal D2R availability nor in MPH-induced striatal DA changes. These results provide preliminary evidence that low striatal DA function in METH abusers is associated with a greater likelihood of relapse during treatment. Detection of the extent of DA dysfunction may be helpful in predicting therapeutic outcomes

Methylphenidate Attenuates Limbic Brain Inhibition after Cocaine-Cues Exposure in Cocaine Abusers

Dopamine (phasic release) is implicated in conditioned responses. Imaging studies in cocaine abusers show decreases in striatal dopamine levels, which we hypothesize may enhance conditioned responses since tonic dopamine levels modulate phasic dopamine release. To test this we assessed the effects of increasing tonic dopamine levels (using oral methylphenidate) on brain activation induced by cocaine-cues in cocaine abusers. Brain metabolism (marker of brain function) was measured with PET and 18FDG in 24 active cocaine abusers tested four times; twice watching a Neutral video (nature scenes) and twice watching a Cocaine-cues video; each video was preceded once by placebo and once by methylphenidate (20 mg). The Cocaine-cues video increased craving to the same extent with placebo (68%) and with methylphenidate (64%). In contrast, SPM analysis of metabolic images revealed that differences between Neutral versus Cocaine-cues conditions were greater with placebo than methylphenidate; whereas with placebo the Cocaine-cues decreased metabolism (p<0.005) in left limbic regions (insula, orbitofrontal, accumbens) and right parahippocampus, with methylphenidate it only decreased in auditory and visual regions, which also occurred with placebo. Decreases in metabolism in these regions were not associated with craving; in contrast the voxel-wise SPM analysis identified significant correlations with craving in anterior orbitofrontal cortex (p<0.005), amygdala, striatum and middle insula (p<0.05). This suggests that methylphenidate's attenuation of brain reactivity to Cocaine-cues is distinct from that involved in craving. Cocaine-cues decreased metabolism in limbic regions (reflects activity over 30 minutes), which contrasts with activations reported by fMRI studies (reflects activity over 2–5 minutes) that may reflect long-lasting limbic inhibition following activation. Studies to evaluate the clinical significance of methylphenidate's blunting of cue-induced limbic inhibition may help identify potential benefits of this medication in cocaine addiction

A Cross-Sectional Study of Prisoners in Mexico City Comparing Prevalence of Transmissible Infections and Chronic Diseases with That in the General Population.

ObjectivesTo describe patterns of transmissible infections, chronic illnesses, socio-demographic characteristics and risk behaviors in Mexico City prisons, including in comparison to the general population, to identify those currently needing healthcare and inform policy.Materials and methodsA cross-sectional study among 17,000 prisoners at 4 Mexico City prisons (June to December 2010). Participation was voluntary, confidential and based on informed consent. Participants were tested for HIV, Hepatitis B &amp; C, syphilis, hypertension, obesity, and, if at risk, glucose and cholesterol. A subset completed a questionnaire on socio-demographic characteristics and risk behaviors. Positive results were delivered with counseling and treatment or referral.Results76.8% (15,517/20,196) of men and 92.9% (1,779/1,914) of women participated. Complete data sets were available for 98.8%. The following prevalence data were established for transmissible infections: HIV 0.7%; syphilis: Anti-TP+/VDRL+ 2.0%; Hepatitis B: HBcAb 2.8%, HBsAg 0.15%; Anti-HCV 3.2%. Obesity: 9.5% men, 33.8% women. Compared with national age- and sex-matched data, the relative prevalence was greater for HIV and syphilis among women, HIV and Hepatitis C in men, and all infections in younger participants. Obesity prevalence was similar for women and lower among male participants. The prevalence of previously diagnosed diabetes and hypertension was lower. Questionnaire data (1,934 men, 520 women) demonstrated lower educational levels, increased smoking and substance use compared to national data. High levels of non-sterile tattooing, physical abuse and histories of sexual violence were found.ConclusionThe study identified that health screening is acceptable to Mexico City prisoners and feasible on a large-scale. It demonstrated higher prevalence of HIV and other infections compared to national data, though low rates compared to international data. Individual participants benefited from earlier diagnosis, treatment and support. The data collected will also enable the formulation of improved policy for this vulnerable group

Predicting Fluid Intelligence of Children using T1-weighted MR Images and a StackNet

In this work, we utilize T1-weighted MR images and StackNet to predict fluid intelligence in adolescents. Our framework includes feature extraction, feature normalization, feature denoising, feature selection, training a StackNet, and predicting fluid intelligence. The extracted feature is the distribution of different brain tissues in different brain parcellation regions. The proposed StackNet consists of three layers and 11 models. Each layer uses the predictions from all previous layers including the input layer. The proposed StackNet is tested on a public benchmark Adolescent Brain Cognitive Development Neurocognitive Prediction Challenge 2019 and achieves a mean squared error of 82.42 on the combined training and validation set with 10-fold cross-validation. In addition, the proposed StackNet also achieves a mean squared error of 94.25 on the testing data. The source code is available on GitHub.Comment: 8 pages, 2 figures, 3 tables, Accepted by MICCAI ABCD-NP Challenge 2019; Added ND

Addiction to Highly Pleasurable Food as a Cause of the Childhood Obesity Epidemic: A Qualitative Internet Study

An interactive, open-access website was launched as an overweight intervention for teens and preteens, and was generally unsuccessful. An understanding was needed of the reasons for weight loss failures versus successes in youth using the site. Bulletin board posts, chat room transcripts, and poll responses were prospectively gathered and qualitatively and quantitatively analyzed over a ten-year period. Many respondents, ages 8 to 21, exhibited DSM-IV substance dependence (addiction) criteria when describing their relationship with highly pleasurable foods. Further research is needed on possible addiction to highly pleasurable foods in youth. Incorporating substance dependence methods may improve the success rate in combating the childhood obesity epidemic

Electronic gaming machine characteristics: it's the little things that count

A range of gamblers, from low-frequency social gamblers through to problem gamblers in treatment, participated in focus groups discussing the characteristics of Electronic Gaming Machines (EGMs) that they found attractive. Analyses of the resulting transcripts resulted in two groups of EGM characteristics being identified as important, one group associated with winning and one with betting. Overall, free spin features were identified in all groups as the most attractive characteristic of EGMS. Beyond that it was smaller win-related characteristics, and low-denomination machines with multiple playable lines that were associated with increased duration and intensity of gambling behaviour. The important characteristics were consistent across different levels of gamblers, with the key behavioural difference being a self-reported ‘expertise’, and ‘strategic’ approach to gambling amongst higher-frequency gamblers and problem gamblers in treatment. The key characteristics all occur frequently and result in more wins and extended gambling sessions. The patterns identified resonated with established behavioural principles, and with models describing the development of problem gambling and addictions more generally

Remembering the forgotten non-communicable diseases

The forthcoming post-Millennium Development Goals era will bring about new challenges in global health. Low- and middle-income countries will have to contend with a dual burden of infectious and non-communicable diseases (NCDs). Some of these NCDs, such as neoplasms, COPD, cardiovascular diseases and diabetes, cause much health loss worldwide and are already widely recognised as doing so. However, 55% of the global NCD burden arises from other NCDs, which tend to be ignored in terms of premature mortality and quality of life reduction. Here, experts in some of these 'forgotten NCDs' review the clinical impact of these diseases along with the consequences of their ignoring their medical importance, and discuss ways in which they can be given higher global health priority in order to decrease the growing burden of disease and disability.MerckUniv Melbourne, Sch Populat & Global Hlth, Melbourne, Vic 3053, AustraliaUniv London Imperial Coll Sci Technol & Med, St Marys Hosp, Dept Med, London W2 1NY, EnglandKEMRI Wellcome Trust Res Programme, Kilifi, KenyaUniv British Columbia, St Pauls Hosp, Vancouver, BC V6Z 1Y8, CanadaVA Med Ctr, Med Serv, Birmingham, AL USAVA Med Ctr, Ctr Surg Med Acute Care Res & Transit, Birmingham, AL USAUniv Alabama Birmingham, Sch Med, Dept Med, Birmingham, AL 35294 USAUniv Alabama Birmingham, Sch Publ Hlth, Div Epidemiol, Birmingham, AL 35294 USAMayo Clin, Coll Med, Dept Orthoped Surg, Rochester, MN 55905 USAUniv London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, EnglandCtr Addict & Mental Hlth, Toronto, ON, CanadaTech Univ Dresden, D-01062 Dresden, GermanyUniv Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, CanadaUniv Toronto, Dept Psychiat, Toronto, ON, CanadaUofT, Inst Med Sci, Toronto, ON, CanadaNIDA, NIH, Rockville, MD USANIAAA, NIH, Bethesda, MD 20892 USAHosp Alemao Oswaldo Cruz, Inst Educ & Hlth Sci, BR-01323903 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Psychobiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Psychobiol, BR-04023062 São Paulo, BrazilWeb of Scienc

Radionuclide Labeling and Evaluation of Candidate Radioligands for PET Imaging of Histone Deacetylase in the Brain

Histone deacetylases (HDACs) regulate gene expression by inducing conformational changes in chromatin. Ever since the discovery of a naturally occurring HDAC inhibitor, trichostatin A (TSA) stimulated the recent development of suberoylanilide (SAHA, Zolinza®), HDAC has become an important molecular target for drug development. This has created the need to develop specific in vivo radioligands to study epigenetic regulation and HDAC engagement for drug development for diseases including cancer and psychiatric disorders. 6-([18F]Fluoroacetamido)-1-hexanoicanilide ([18F]FAHA) was recently developed as a HDAC substrate and shows moderate blood–brain barrier (BBB) permeability and specific signal (by metabolic trapping/or deacetylation) but rapid metabolism. Here, we report the radiosynthesis of two carbon-11 labeled candidate radiotracers (substrate- and inhibitor-based radioligand) for HDAC and their evaluation in non-human primate brain. PET studies showed very low brain uptake and rapid metabolism of both labeled compounds but revealed a surprising enhancement of brain penetration by F for H substitution when comparing one of these to [18F]FAHA. Further structural refinement is needed for the development of brain-penetrant, metabolically stable HDAC radiotracers and to understand the role of fluorine substitution on brain penetration.Chemistry and Chemical Biolog

Dorsal Striatum and Its Limbic Connectivity Mediate Abnormal Anticipatory Reward Processing in Obesity

Obesity is characterized by an imbalance in the brain circuits promoting reward seeking and those governing cognitive control. Here we show that the dorsal caudate nucleus and its connections with amygdala, insula and prefrontal cortex contribute to abnormal reward processing in obesity. We measured regional brain glucose uptake in morbidly obese (n = 19) and normal weighted (n = 16) subjects with 2-[18F]fluoro-2-deoxyglucose ([18F]FDG) positron emission tomography (PET) during euglycemic hyperinsulinemia and with functional magnetic resonance imaging (fMRI) while anticipatory food reward was induced by repeated presentations of appetizing and bland food pictures. First, we found that glucose uptake rate in the dorsal caudate nucleus was higher in obese than in normal-weight subjects. Second, obese subjects showed increased hemodynamic responses in the caudate nucleus while viewing appetizing versus bland foods in fMRI. The caudate also showed elevated task-related functional connectivity with amygdala and insula in the obese versus normal-weight subjects. Finally, obese subjects had smaller responses to appetizing versus bland foods in the dorsolateral and orbitofrontal cortices than did normal-weight subjects, and failure to activate the dorsolateral prefrontal cortex was correlated with high glucose metabolism in the dorsal caudate nucleus. These findings suggest that enhanced sensitivity to external food cues in obesity may involve abnormal stimulus-response learning and incentive motivation subserved by the dorsal caudate nucleus, which in turn may be due to abnormally high input from the amygdala and insula and dysfunctional inhibitory control by the frontal cortical regions. These functional changes in the responsiveness and interconnectivity of the reward circuit could be a critical mechanism to explain overeating in obesity