Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016.

The last quarter century witnessed significant population growth, aging, and major changes in epidemiologic trends, which may have shaped the state of chronic kidney disease (CKD) epidemiology. Here, we used the Global Burden of Disease study data and methodologies to describe the change in burden of CKD from 1990 to 2016 involving incidence, prevalence, death, and disability-adjusted-life-years (DALYs). Globally, the incidence of CKD increased by 89% to 21,328,972 (uncertainty interval 19,100,079- 23,599,380), prevalence increased by 87% to 275,929,799 (uncertainty interval 252,442,316-300,414,224), death due to CKD increased by 98% to 1,186,561 (uncertainty interval 1,150,743-1,236,564), and DALYs increased by 62% to 35,032,384 (uncertainty interval 32,622,073-37,954,350). Measures of burden varied substantially by level of development and geography. Decomposition analyses showed that the increase in CKD DALYs was driven by population growth and aging. Globally and in most Global Burden of Disease study regions, age-standardized DALY rates decreased, except in High-income North America, Central Latin America, Oceania, Southern Sub-Saharan Africa, and Central Asia, where the increased burden of CKD due to diabetes and to a lesser extent CKD due to hypertension and other causes outpaced burden expected by demographic expansion. More of the CKD burden (63%) was in low and lower-middle-income countries. There was an inverse relationship between age-standardized CKD DALY rate and health care access and quality of care. Frontier analyses showed significant opportunities for improvement at all levels of the development spectrum. Thus, the global toll of CKD is significant, rising, and unevenly distributed; it is primarily driven by demographic expansion and in some regions a significant tide of diabetes. Opportunities exist to reduce CKD burden at all levels of development.

Glutamatergic supramammillary nucleus neurons respond to threatening stressors and promote active coping.

Threat-response neural circuits are conserved across species and play roles in normal behavior and psychiatric diseases. Maladaptive changes in these neural circuits contribute to stress, mood, and anxiety disorders. Active coping in response to stressors is a psychosocial factor associated with resilience against stress-induced mood and anxiety disorders. The neural circuitry underlying active coping is poorly understood, but the functioning of these circuits could be key for overcoming anxiety and related disorders. The supramammillary nucleus (SuM) has been suggested to be engaged by threat. SuM has many projections and a poorly understood diversity of neural populations. In studies using mice, we identified a unique population of glutamatergic SuM neurons (SuMVGLUT2+::POA) based on projection to the preoptic area of the hypothalamus (POA) and found SuMVGLUT2+::POA neurons have extensive arborizations. SuMVGLUT2+::POA neurons project to brain areas that mediate features of the stress and threat responses including the paraventricular nucleus thalamus (PVT), periaqueductal gray (PAG), and habenula (Hb). Thus, SuMVGLUT2+::POA neurons are positioned as a hub, connecting to areas implicated in regulating stress responses. Here we report SuMVGLUT2+::POA neurons are recruited by diverse threatening stressors, and recruitment correlated with active coping behaviors. We found that selective photoactivation of the SuMVGLUT2+::POA population drove aversion but not anxiety like behaviors. Activation of SuMVGLUT2+::POA neurons in the absence of acute stressors evoked active coping like behaviors and drove instrumental behavior. Also, activation of SuMVGLUT2+::POA neurons was sufficient to convert passive coping strategies to active behaviors during acute stress. In contrast, we found activation of GABAergic (VGAT+) SuM neurons (SuMVGAT+) neurons did not alter drive aversion or active coping, but termination of photostimulation was followed by increased mobility in the forced swim test. These findings establish a new node in stress response circuitry that has projections to many brain areas and evokes flexible active coping behaviors.

Cortical midline structures associated with rumination in women with PTSD.

Elevated rumination, characterized by repetitive, negative self-focused cognition, is common in posttraumatic stress disorder (PTSD) and has been shown to predict the onset and maintenance of the disorder. Neuroimaging research has implicated cortical midline brain structures, including the rostral anterior cingulate cortex (rACC), posterior cingulate cortex (PCC), and isthmus cingulate (IsthCing), in rumination in healthy and depressed populations. While past research has revealed dysfunction in cortical midline regions in PTSD, no studies have yet investigated the structural and functional neural mechanisms underlying rumination in women with PTSD. In the current study, we used structural MRI and resting-state fMRI to examine relationships between rumination and brain volume, as well as resting-state functional connectivity (rsFC) of cortical midline structures in women with PTSD due to interpersonal trauma (N = 71). We performed multiple linear regression analyses to relate brain volume in rACC, PCC, and IsthCing regions to self-reported rumination, after controlling for age and total intracranial volume. We also conducted standard seed-based voxelwise rsFC analyses for significant regions identified in the structural analysis. We found a significant relationship between greater rumination and volume in the left IsthCing (p = .025). Results from the rsFC analyses revealed a significant relationship between greater rumination and diminished rsFC between the left IsthCing and left precuneus (pFWE < .05). These findings provide novel support for alterations in the neural substrates of ruminative thought in women with PTSD. More broadly, we discuss clinical implications for targeted interventions to reduce rumination through psychotherapy or non-invasive brain stimulation.