MRAP2 regulates energy homeostasis by promoting primary cilia localization of MC4R.

The G protein-coupled receptor melanocortin-4 receptor (MC4R) and its associated protein melanocortin receptor-associated protein 2 (MRAP2) are essential for the regulation of food intake and body weight in humans. MC4R localizes and functions at the neuronal primary cilium, a microtubule-based organelle that senses and relays extracellular signals. Here, we demonstrate that MRAP2 is critical for the weight-regulating function of MC4R neurons and the ciliary localization of MC4R. More generally, our study also reveals that GPCR localization to primary cilia can require specific accessory proteins that may not be present in heterologous cell culture systems. Our findings further demonstrate that targeting of MC4R to neuronal primary cilia is essential for the control of long-term energy homeostasis and suggest that genetic disruption of MC4R ciliary localization may frequently underlie inherited forms of obesity.

Low availability, long wait times, and high geographic disparity of psychiatric outpatient care in the US.

OBJECTIVE: To identify potential barriers to care, this study examined the general psychiatry outpatient new appointment availability in the US, including in-person and telepsychiatry appointments, comparing results between insurance types (Medicaid vs. private insurance), states, and urbanization levels. METHOD: This mystery shopper study investigated 5 US states selected according to Mental Health America Adult Ranking and geography to represent the US mental health care system. Clinics across five selected states were stratified sampled by county urbanization levels. Calls were made during 05/2022-07/2022. Collected data included contact information accuracy, appointment availability, wait time (days), and related information. RESULTS: Altogether, 948 psychiatrists were sampled in New York, California, North Dakota, Virginia, and Wyoming. Overall contact information accuracy averaged 85.3%. Altogether, 18.5% of psychiatrists were available to see new patients with a significantly longer wait time for in-person than telepsychiatry appointments (median = 67.0 days vs median = 43.0 days, p < 0.01). The most frequent reason for unavailability was provider not taking new patients (53.9%). Mental health resources were unevenly distributed, favoring urban areas. CONCLUSION: Psychiatric care has been severely restricted in the US with low accessibility and long wait times. Transitioning to telepsychiatry represents a potential solution for rural disparities in access.