Amygdala-liver signaling orchestrates rapid glycemic responses to stress and drives stress-induced metabolic dysfunction.

Behavioral adaptations to environmental threats are crucial for survival and necessitate rapid deployment of energy reserves. The amygdala coordinates behavioral adaptations to threats, but little is known about its involvement in underpinning metabolic adaptations. Here, we show that acute stress activates medial amygdala (MeA) neurons that innervate the ventromedial hypothalamus (MeAVMH neurons), which precipitates hyperglycemia and hypophagia. The glycemic actions of MeAVMH neurons occur independent of adrenal or pancreatic glucoregulatory hormones. Instead, using whole-body virus tracing, we identify a polysynaptic connection from MeA to the liver, which promotes the rapid synthesis of glucose by hepatic gluconeogenesis. Repeated stress exposure disrupts MeA control of blood glucose and appetite, resulting in diabetes-like dysregulation of glucose homeostasis and weight gain. Our findings reveal a novel amygdala-liver axis that regulates rapid glycemic adaptations to stress and links recurrent stress to metabolic dysfunction.

Impact of Illness Severity Tools on Adolescent Psychiatric Managed Care in California.

Youth with mental illness struggle to receive essential behavioral health care. One obstacle is denial of coverage by insurance. In California, managed care consumers may apply for independent medical review (IMR) which potentially overturns an insurance denial through the California Department of Managed Healthcare (CDMHC). The authors aim to analyze IMR appeals for psychiatric treatment among adolescents and elucidate factors associated with obtaining coverage of care. We performed an analysis to identify factors that are associated with depression and substance use disorder (SUD) treatment claim denials in 11-20-year-olds from 2001 to 2022 using CDMHC data. Logistic regression modeling was used to identify specific factors related to claim characteristics and medical society instruments that are significantly associated with overturning a denial by IMR. Behavioral health IMRs are overturned at a higher rate than non-behavioral health claims. 54.5% of those with depression and 36.3% of those with SUD initially denied care coverage were overturned by IMR. For those seeking depression treatment, we found a significantly greater odds of overturn by IMR if there was a reference of CALOCUS [1.64, 95%CI (1.06-2.5)]. The odds of a SUD treatment denial being overturned was significantly greater if referencing CALOCUS [3.85 (1.54-9.62)] or ASAM [2.47, [4.3 (1.77-10.47)]. After the standardized implementation of illness severity tools in IMRs, the odds of a medically necessary claim being overturned was 2.5 times higher than before the standards. With a high percentage of claims being overturned after IMR, the findings suggest that health plans inappropriately deny medically necessary behavioral health treatment. The use of medical society instruments was associated with higher odds of overturning a denial. The recent decision of CDMHC to implement standard use of CALOCUS and similar illness severity criteria is supported by our findings and may facilitate more equitable care.

Repeated hypoglycemia remodels neural inputs and disrupts mitochondrial function to blunt glucose-inhibited GHRH neuron responsiveness.

Hypoglycemia is a frequent complication of diabetes, limiting therapy and increasing morbidity and mortality. With recurrent hypoglycemia, the counterregulatory response (CRR) to decreased blood glucose is blunted, resulting in hypoglycemia-associated autonomic failure (HAAF). The mechanisms leading to these blunted effects are only poorly understood. Here, we report, with ISH, IHC, and the tissue-clearing capability of iDISCO+, that growth hormone releasing hormone (GHRH) neurons represent a unique population of arcuate nucleus neurons activated by glucose deprivation in vivo. Repeated glucose deprivation reduces GHRH neuron activation and remodels excitatory and inhibitory inputs to GHRH neurons. We show that low glucose sensing is coupled to GHRH neuron depolarization, decreased ATP production, and mitochondrial fusion. Repeated hypoglycemia attenuates these responses during low glucose. By maintaining mitochondrial length with the small molecule mitochondrial division inhibitor-1, we preserved hypoglycemia sensitivity in vitro and in vivo. Our findings present possible mechanisms for the blunting of the CRR, significantly broaden our understanding of the structure of GHRH neurons, and reveal that mitochondrial dynamics play an important role in HAAF. We conclude that interventions targeting mitochondrial fission in GHRH neurons may offer a new pathway to prevent HAAF in patients with diabetes.

Assessing the efficacy and experience of in-person versus telephonic psychiatric evaluations for asylum seekers in the U.S.

Psychiatric evaluations of asylum seekers in the U.S. play an important role in asylum cases; however, there are significant barriers to assessing asylum seekers' psychological trauma. Telephonic psychiatric evaluations provide an opportunity to access important resources to bolster their case. In this retrospective study, we considered the efficacy of telephonic psychiatric evaluations and assessed their potential as a solution to meet the needs of asylum seekers. Ten affidavits produced from telephonic evaluations were compared to twenty produced from in-person evaluations using a standardized scoring rubric. Providers who conducted telephonic evaluations also completed a structured interview and a qualitative assessment of themes was conducted. Overall, there was a small, but non-significant difference in overall score. The presence of descriptions of cognitive complaints, appearance, motor activity and use of checklists were, however, all significantly lower in telephonic compared to in-person affidavits. Providers agreed that despite limitations, the ability to diagnose and advocate for asylum seekers is equivalent regardless of format. This study identifies that telephonic psychiatric evaluations produce comparable results to in-person evaluations with the benefit of reaching a hard to reach population. Evaluators, lawyers, and judges should consider these results in weighing the risk-benefits of a telephonic evaluation of an asylum seeker.