Gender Specific Associations Between Types of Childhood Maltreatment and the Onset,Escalation and Severity of Substance Use in Cocaine Dependent Adults

We examined associations between types of childhood maltreatment and the onset, escalation, and severity of substance use in cocaine dependent adults. In men (n = 55), emotional abuse was associated with a younger age of first alcohol use and a greater severity of substance abuse. In women (n = 32), sexual abuse, emotional abuse, and overall maltreatment was associated with a younger age of first alcohol use, and emotional abuse, emotional neglect, and overall maltreatment was associated with a greater severity of substance abuse. There was no association between childhood maltreatment and age of nicotine or cocaine use. However, age of first alcohol use predicted age of first cocaine use in both genders. All associations were stronger in women. Findings suggest that early intervention for childhood victims, especially females, may delay or prevent the early onset of alcohol use and reduce the risk for a more severe course of addiction.     

Biological mechanisms underlying the relationship between stress and smoking: state of the science and directions for future work

Theories of addiction implicate stress as a crucial mechanism underlying initiation, maintenance, and relapse to cigarette smoking. Examinations of the biological stress systems, including functioning of the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system (ANS), have provided additional insights into the relationship between stress and smoking. To date, convergent data suggests that chronic cigarette smoking is associated with alterations in HPA and ANS functioning; however, less is known about the role of HPA and ANS functioning in smoking initiation and relapse following cessation. In order to organize existing findings and stimulate future research, the current paper summarizes the available literature on the roles of HPA axis and ANS functioning in the relationship between stress and cigarette smoking, highlights limitations within the existing literature, and suggests directions for future research to address unanswered questions in the extant literature on the biological mechanisms underlying the relationship between stress and smoking.     

Circulating glucose levels modulate neural control of desire for high-calorie foods in humans

Obesity is a worldwide epidemic resulting in part from the ubiquity of high-calorie foods and food images. Whether obese and nonobese individuals regulate their desire to consume high-calorie foods differently is not clear. We set out to investigate the hypothesis that circulating levels of glucose, the primary fuel source for the brain, influence brain regions that regulate the motivation to consume high-calorie foods. Using functional MRI (fMRI) combined with a stepped hyperinsulinemic euglycemic-hypoglycemic clamp and behavioral measures of interest in food, we have shown here that mild hypoglycemia preferentially activates limbic-striatal brain regions in response to food cues to produce a greater desire for high-calorie foods. In contrast, euglycemia preferentially activated the medial prefrontal cortex and resulted in less interest in food stimuli. Indeed, higher circulating glucose levels predicted greater medial prefrontal cortex activation, and this response was absent in obese subjects. These findings demonstrate that circulating glucose modulates neural stimulatory and inhibitory control over food motivation and suggest that this glucose-linked restraining influence is lost in obesity. Strategies that temper postprandial reductions in glucose levels might reduce the risk of overeating, particularly in environments inundated with visual cues of high-calorie foods.     

Inhibitory control and emotional stress regulation: neuroimaging evidence for frontal-limbic dysfunction in psycho-stimulant addiction

This review focuses on neuroimaging studies that examined stress processing and regulation and cognitive inhibitory control in patients with psycho-stimulant addiction. We provide an overview of these studies, summarizing converging evidence and discrepancies as they occur in the literature. We also adopt an analytic perspective and dissect these psychological processes into their sub-components, to identify the neural pathways specific to each component process and those that are more specifically involved in psycho-stimulant addiction. To this aim we refer frequently to studies conducted in healthy individuals. Despite the separate treatment of stress/affect regulation, stress-related craving or compulsive drug seeking, and inhibitory control, neural underpinnings of these processes overlap significantly. In particular, the ventromedial prefrontal regions including the anterior cingulate cortex, amygdala and the striatum are implicated in psychostimulant dependence. Our overarching thesis is that prefrontal activity ensures intact emotional stress regulation and inhibitory control. Altered prefrontal activity along with heightened striatal responses to addicted drug and drug-related salient stimuli perpetuates habitual drug seeking. Further studies that examine the functional relationships of these neural systems will likely provide the key to understanding the mechanisms underlying compulsive drug use behaviors in psycho-stimulant dependence.     

Fungal dysbiosis predicts the diagnosis of pediatric Crohn's disease

AIM To investigate the accuracy of fungal dysbiosis inmucosa and stool for predicting the diagnosis of Crohn's disease(CD). METHODS Children were prospectively enrolled in two medical centers: one university hospital and one private gastroenterology clinic in the city of Riyadh, Kingdom of Saudi Arabia. The children with confirmed diagnosis of CD by standard guidelines were considered cases, and the others were considered non-inflammatory bowel disease controls. Mucosal and stool samples were sequenced utilizing Illumina MiSeq chemistry following the manufacturer's protocols, and abundance and diversity of fungal taxa in mucosa and stool were analyzed. Sparse logistic regression was used to predict the diagnosis of CD. The accuracy of the classifier was tested by computing the receiver operating characteristic curves with 5-fold stratified cross-validation under 100 permutations of the training data partition and the mean area under the curve(AUC) was calculated. RESULTS All the children were Saudi nationals. There were 15 children with CD and 20 controls. The mean age was 13.9(range: 6.7-17.8) years for CD children and 13.9(3.25-18.6) years for controls, and 10/15(67%) of the CD and 13/20(65%) of the control subjects were boys. CD locations at diagnosis were ileal(L1) in 4 and colonic(L3) in 11 children, while CD behavior was non-stricturing and non-penetrating(B1) in 12 and stricturing(B2) in 3 children. The mean AUC for the fungal dysbiosis classifier was significantly higher in stools(AUC = 0.85 ± 0.057) than in mucosa(AUC = 0.71 ± 0.067)(P 0.001). Most fungal species were significantly more depleted in stools than mucosal samples, except for Saccharomyces cerevisiae and S. bayanus, which were significantly more abundant. Diversity was significantly more reduced in stools than in mucosa. CONCLUSION We found high AUC of fungal dysbiosis in fecal samples of children with CD, suggesting high accuracy in predicting diagnosis of CD.