BMAL1 knockout macaque monkeys display reduced sleep and psychiatric disorders.

Circadian disruption is a risk factor for metabolic, psychiatric and age-related disorders, and non-human primate models could help to develop therapeutic treatments. Here, we report the generation of BMAL1 knockout cynomolgus monkeys for circadian-related disorders by CRISPR/Cas9 editing of monkey embryos. These monkeys showed higher nocturnal locomotion and reduced sleep, which was further exacerbated by a constant light regimen. Physiological circadian disruption was reflected by the markedly dampened and arrhythmic blood hormonal levels. Furthermore, BMAL1-deficient monkeys exhibited anxiety and depression, consistent with their stably elevated blood cortisol, and defective sensory processing in auditory oddball tests found in schizophrenia patients. Ablation of BMAL1 up-regulated transcriptional programs toward inflammatory and stress responses, with transcription networks associated with human sleep deprivation, major depressive disorders, and aging. Thus, BMAL1 knockout monkeys are potentially useful for studying the physiological consequences of circadian disturbance, and for developing therapies for circadian and psychiatric disorders.

Task-Based and Questionnaire Measures of Inhibitory Control Are Differentially Affected by Acute Food Restriction and by Motivationally Salient Food Stimuli in Healthy Adults.

Adaptive eating behaviors are dependent on an interaction between motivational states (e.g., hunger) and the ability to control one's own behavior (inhibitory control). Indeed, behavioral paradigms are emerging that seek to train inhibitory control to improve eating behavior. However, inhibitory control is a multifaceted concept, and it is not yet clear how different types (e.g., reactive motor inhibition, proactive motor inhibition, reward-related inhibition) are affected by hunger. Such knowledge will provide insight into the contexts in which behavioral training paradigms would be most effective. The present study explored the impact of promoting a "need" state (hunger) together with motivationally salient distracting stimuli (food/non-food images) on inhibitory control in 46 healthy adults. Participants attended two study sessions, once after eating breakfast as usual and once after acute food restriction on the morning of the session. In each session, participants completed questionnaires on hunger, mood and inhibitory control, and undertook task-based measures of inhibitory control, and had physiological measurements (height, weight, and blood glucose) obtained by a researcher. Acute food restriction influenced task-based assessments but not questionnaire measures of inhibitory control, suggesting that hunger affects observable behavioral control but not self-reported inhibitory control. After acute food restriction, participants showed greater temporal discounting (devaluation of future rewards), and subjective hunger and these were inversely correlated with stop accuracy on the stop signal task. Finally, participants generally responded faster when food-related distractor images were presented, compared to non-food images, independent of state. This suggests that although food stimuli motivate approach behavior, stimulus relevance does not impact inhibitory control in healthy individuals, nor interact with motivational state. These findings may provide some explanation for poorer inhibitory control often reported in studies of individuals who practice restraint over eating.

Increased temporal discounting in bulimia nervosa.

OBJECTIVE: There is evidence that people with eating disorders display altered intertemporal choice behavior (the degree of preference for immediate rewards over delayed rewards). Compared to healthy controls (HC), individuals with anorexia nervosa and binge-eating disorder show decreased and increased rates of temporal discounting (TD; the devaluation of delayed rewards), respectively. This is the first study to investigate TD in people with bulimia nervosa (BN). METHOD: Thirty-nine individuals with BN (2 men) and 53 HC (9 men) completed a hypothetical monetary TD task. Over 80 binary choices, participants chose whether they would prefer to receive a smaller amount of money available immediately or a larger amount available in 3 months. Self-reported ability to delay gratification (the behavioral opposite of TD) was also measured. RESULTS: Individuals with BN showed greater TD (i.e., a preference for smaller-sooner rewards) and a decreased self-reported capacity to delay gratification relative to HC. Experimental groups did not differ in age, gender ratio, or BMI. DISCUSSION: Increased rates of TD may contribute to some of the core symptoms of BN that appear to involve making choices between immediate and delayed rewards (i.e., binge-eating and compensatory behaviors). Altered intertemporal choice behavior could therefore be a relevant target for intervention in this patient group. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1077-1081).