Physical Activity, Sleep, Body Mass Index, and Associated Risk of Behavioral and Emotional Problems in Childhood.

OBJECTIVE: Cross-sectional data indicate that physical activity, longer sleep duration, and normal body weight are associated with better mental health in childhood. It is less clear whether these factors protect against future emotional and behavioral problems. We investigated whether physical activity, sleep duration, and body mass index (BMI) at the age of 7 years are associated with emotional and behavioral problems at the age of 11 years. METHODS: Children born to European mothers enrolled in the prospective longitudinal Auckland Birthweight Collaborative Study (N = 871) were assessed at birth and ages 7 and 11 years. Physical activity and sleep duration were measured using accelerometer. BMI was calculated from height and weight measurement. Outcome variables assessed at the age of 11 years were parent and child self-report Strengths and Difficulties Questionnaire and parent and teacher Conners' Rating Scale scores. RESULTS: Physical activity, sleep duration, and BMI at the age of 7 years were not significantly associated with emotional and behavioral problems at the age of 11 years. In cross-sectional analysis at the age of 11 years, there was no significant association between physical activity or sleep duration and emotional and behavioral problems. Children with a BMI in the overweight or obese range were significantly more likely to have teacher-rated behavior problems and parent-rated emotional or behavioral problems after adjustment for potential confounders. CONCLUSION: Although physical activity and sleep have physical health benefits, they may not be protective against future emotional and behavioral problems in childhood in the general population. BMI in the obese or overweight range was significantly associated with current emotional and behavioral problems at the age of 11 years.

Discovery of GSK345931A: An EP(1) receptor antagonist with efficacy in preclinical models of inflammatory pain.

Herein we describe the medicinal chemistry programme to identify a potential back-up compound to the EP(1) receptor antagonist GW848687X. This work started with the lipophilic 1,2-biaryl benzene derivative 4 which displayed molecular weight of 414.9g/mol and poor in vivo metabolic stability in the rat and resulted in the identification of compound 7i (GSK345931A) which demonstrated good metabolic stability in the rat and lower molecular weight (381.9g/mol). In addition, 7i (GSK345931A) showed measurable CNS penetration in the mouse and rat and potent analgesic efficacy in acute and sub-chronic models of inflammatory pain.

Striatal contributions to reward and decision making: making sense of regional variations in a reiterated processing matrix.

The striatum is the major input nucleus of the basal ganglia. It is thought to play a key role in learning on the basis of positive reinforcement and in action selection. One view of the striatum conceives it as comprising a reiterated matrix of processing units that perform common operations in different striatal regions, namely synaptic plasticity according to a three-factor rule, and lateral inhibition. These operations are required for reinforcement learning and selection of previously reinforced actions. Analysis of the behavioral effects of circumscribed lesions of the striatum, however, suggests regional specialization of learning and decision-making operations. We consider how a basic processing unit may be modified by regional variations in neurochemical parameters, for example, by the gradient in density of dopamine terminals from dorsal to ventral striatum. These variations suggest subtle differences between dorsolateral and ventromedial striatal regions in the temporal properties of dopamine signaling, which are superimposed on regional differences in connectivity. We propose that these variations make sense in relation to the temporal structure of activity in striatal inputs from different regions, and the requirements of different learning operations. Dorsolateral striatal (DLS) regions may be subject to brief, precisely timed pulses of dopamine, whereas ventromedial striatal regions integrate dopamine signals over a longer time course. These differences may be important for understanding regional variations in the contribution to reinforcement of habits, versus incentive processes that are sensitive to the value of expected rewards.