Utilization of Whole Health and Longitudinal Outcomes After Screening Positive for Possible Depression Documented in Veterans Health Administration's Electronic Health Record.

Objectives: Depression is common among Veterans. Veterans Health Administration (VHA) is transforming into a Whole Health system of care that includes holistic treatment planning, well-being programs, and health coaching. This evaluation explores the impact of Whole Health on improving symptoms of depression among Veterans who screen positive for possible depression diagnosis. Materials and Methods: We examined a cohort of Veterans who started using Whole Health after screening positive for possible depression (having a PHQ-2 score ≥3) at 18 VA Whole Health sites. We compared Whole Health users with non-Whole Health users on their follow-up PHQ-2 scores (9-36 months after baseline), using propensity score matching with multivariable regression to adjust for baseline differences. Results: Of the 13,559 Veterans screening positive for possible depression on the PHQ-2 and having a follow-up PHQ-2, 902 (7%) began using Whole Health after their initial positive PHQ-2. Whole Health users at baseline were more likely than non-Whole Health users to have posttraumatic stress disorder or acute stress (43% vs. 29%), anxiety (22% vs. 12%), ongoing opioid use (14% vs. 8%), recent severe pain scores (15% vs. 8%), or obesity (51% vs. 40%). Both groups improved at follow-up, with mean PHQ-2 scores decreasing from 4.49 to 1.77 in the Whole Health group and 4.46 to 1.46 in the conventional care group, with the Whole Health group significantly higher at follow-up. Also, the proportion continuing to screen positive at follow-up trended higher in the Whole Health group (26% and 21%, respectively). Conclusions: After screening positive for depression, Veterans with more mental and physical health conditions were more likely to subsequently use Whole Health services, suggesting that Whole Health is becoming a tool used in VHA to address the needs of complex patients. Nevertheless, the Whole Health group did not improve compared to the Conventional Care group. Results add to the growing body of literature that Whole Health services may play an important role among patients with complex symptom presentations by promoting self-management of symptoms and targeting "what matters most" to Veterans.

Estradiol modulates translocator protein (TSPO) and steroid acute regulatory protein (StAR) via protein kinase A (PKA) signaling in hypothalamic astrocytes.

The ability of the central nervous system to synthesize steroid hormones has wide-ranging implications for physiology and pathology. Among the proposed roles of neurosteroids is the regulation of the LH surge. This involvement in the estrogen-positive feedback demonstrates the integration of peripheral steroids with neurosteroids. Within the female hypothalamus, estradiol from developing follicles stimulates progesterone synthesis in astrocytes, which activate neural circuits regulating gonadotropin (GnRH) neurons. Estradiol acts at membrane estrogen receptor-α to activate cellular signaling that results in the release of inositol trisphosphate-sensitive calcium stores that are sufficient to induce neuroprogesterone synthesis. The purpose of the present studies was to characterize the estradiol-induced signaling leading to activation of steroid acute regulatory protein (StAR) and transporter protein (TSPO), which mediate the rate-limiting step in steroidogenesis, ie, the transport of cholesterol into the mitochondrion. Treatment of primary cultures of adult female rat hypothalamic astrocytes with estradiol induced a cascade of phosphorylation that resulted in the activation of a calcium-dependent adenylyl cyclase, AC1, elevation of cAMP, and activation of both StAR and TSPO. Blocking protein kinase A activation with H-89 abrogated the estradiol-induced neuroprogesterone synthesis. Thus, together with previous results, these experiments completed the characterization of how estradiol action at the membrane leads to the augmentation of neuroprogesterone synthesis through increasing cAMP, activation of protein kinase A, and the phosphorylation of TSPO and StAR in hypothalamic astrocytes.