Olanzapine and other atypical antipsychotics cause metabolic side effects leading to obesity and diabetes; while these continue to be an important public health concern, their underlying mechanisms remain elusive. Therefore, an animal model of these side effects was developed in male Sprague-Dawley rats. Chronic administration of olanzapine elevated fasting glucose, impaired glucose and insulin tolerance, increased fat mass but, in contrast to female rats, did not increase body weight or food intake. Acute studies were conducted to delineate the mechanisms responsible for these effects. Olanzapine markedly decreased physical activity without a compensatory decline in food intake. It also acutely elevated fasting glucose, and worsened oral glucose and insulin tolerance, suggesting these effects are adiposity independent. Hyperinsulinemic-euglycemic clamp studies measuring 14C-2-deoxyglucose (14C-DOG) uptake revealed tissue-specific insulin resistance. Insulin sensitivity was impaired in skeletal muscle, but either unchanged or increased in adipose tissue depots. Consistent with the olanzapine-induced hyperglycemia there was a tendency for increased 14C-DOG uptake into fat depots of fed rats and, surprisingly, free fatty acid (FFA) uptake into fat depots was elevated approximately 2-fold. The increased glucose and FFA uptake into adipose tissue was coupled with increased adipose tissue lipogenesis. Finally, olanzapine lowered fasting plasma FFA and whereas it had no effect on isoproterenol-stimulated rises in plasma glucose, it blunted isoproterenol-stimulated in vivo lipolysis in fed rats. Collectively, these results suggest olanzapine exerts several metabolic effects that together favor increased accumulation of fuel into adipose tissue, thereby increasing adiposity.

Objectives: To examine whether heightened vigilance partially explains associations between police brutality, depressed mood, and generalized anxiety among Black adults. Method: We used data from the cross-sectional Survey of the Health of Urban Residents (SHUR) in the United States (N = 623). Controlling for sociodemographic and health characteristics, we regressed depressed mood and generalized anxiety on police brutality. To assess whether heightened vigilance mediates the relationship between police brutality and mental health, we computed the direct effects of police brutality and indirect effects (through heightened vigilance) on depression and anxiety. Results: Over half of the sample reported experiencing police brutality. Both police brutality and heightened vigilance were associated with depressed mood and generalized anxiety. Heightened vigilance explained 11% of the total effect of police brutality on depressed mood and 21% of the total effect of police brutality on generalized anxiety. Conclusions: Police brutality is associated with negative mental health outcomes among Black people. As clinicians work to provide assessment, diagnosis, and treatment services, they should be aware that Black patients might face increased risk for depression and anxiety because of heightened vigilance and police brutality. Addressing how to manage these kinds of stressors is important, as is building a society where hypervigilance is unnecessary for the survival of Black people. Advocating for broad policy actions to reimagine policing is important for the mental health of Black adults.

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