Evidence for Locus Coeruleus-Norepinephrine System Abnormality in Military Posttraumatic Stress Disorder Revealed by Neuromelanin-Sensitive Magnetic Resonance Imaging.

BACKGROUND: The complex neurobiology of posttraumatic stress disorder (PTSD) calls for the characterization of specific disruptions in brain functions that require targeted treatment. One such alteration could be an overactive locus coeruleus (LC)-norepinephrine system, which may be linked to hyperarousal symptoms, a characteristic and burdensome aspect of the disorder. METHODS: Study participants were Canadian Armed Forces veterans with PTSD related to deployment to combat zones (n = 34) and age- and sex-matched healthy control participants (n = 32). Clinical measures included the Clinician-Administered PTSD Scale for DSM-5, and neuroimaging measures included a neuromelanin-sensitive magnetic resonance imaging scan to measure the LC signal. Robust linear regression analyses related the LC signal to clinical measures. RESULTS: Compared with control participants, the LC signal was significantly elevated in the PTSD group (t62 = 2.64, p = .010), and this group difference was most pronounced in the caudal LC (t56 = 2.70, Cohen's d = 0.72). The caudal LC signal was also positively correlated with the severity of Clinician-Administered PTSD Scale for DSM-5 hyperarousal symptoms in the PTSD group (t26 = 2.16, p = .040). CONCLUSIONS: These findings are consistent with a growing body of evidence indicative of elevated LC-norepinephrine system function in PTSD. Furthermore, they indicate the promise of neuromelanin-sensitive magnetic resonance imaging as a noninvasive method to probe the LC-norepinephrine system that has the potential to support subtyping and treatment of PTSD or other neuropsychiatric conditions.

Association of locus coeruleus integrity with Braak stage and neuropsychiatric symptom severity in Alzheimer's disease.

The clinical and pathophysiological correlates of locus coeruleus (LC) degeneration in Alzheimer's disease (AD) could be clarified using a method to index LC integrity in vivo, neuromelanin-sensitive MRI (NM-MRI). We examined whether integrity of the LC-norepinephrine system, assessed with NM-MRI, is associated with stage of AD and with neuropsychiatric symptoms (NPS), independent of cortical pathophysiology (amyloid-ß and tau burden). Cognitively normal older adults (n = 118), and individuals with mild cognitive impairment (MCI, n = 44), and AD (n = 28) underwent MR imaging and tau and amyloid-ß positron emission tomography (with [18F]MK6240 and [18F]AZD4694, respectively). Integrity of the LC-norepinephrine system was assessed based on contrast-to-noise ratio of the LC on NM-MRI images. Braak stage of AD was derived from regional binding of [18F]MK6240. NPS were assessed with the Mild Behavioral Impairment Checklist (MBI-C). LC signal contrast was decreased in tau-positive participants (t186 = -4.00, p = 0.0001) and negatively correlated to Braak stage (Spearman ρ = -0.31, p = 0.00006). In tau-positive participants (n = 51), higher LC signal predicted NPS severity (ρ = 0.35, p = 0.019) independently of tau burden, amyloid-ß burden, and cortical gray matter volume. This relationship appeared to be driven by the impulse dyscontrol domain of NPS, which was highly correlated to LC signal (ρ = 0.44, p = 0.0027). NM-MRI reveals loss of LC integrity that correlates to severity of AD. However, LC preservation in AD may also have negative consequences by conferring risk for impulse control symptoms. NM-MRI shows promise as a practical biomarker that could have utility in predicting the risk of NPS or guiding their treatment in AD.

Thinking about the future: Comparing children's forced-choice versus "generative" responses in the "spoon test".

One of the most popular methods to assess children's foresight is to present children with a problem (e.g., locked box with no key) in one room and then later, in another room, give them the opportunity to select the item (e.g., key) that will solve it. Whether or not children choose the correct item to bring back to the first room is the dependent measure of interest in this "spoon test." Although children as young as 3 or 4 years typically succeed on this test, whether they would pass a more stringent version in which they must verbally generate (vs. select) the correct item in the absence of any cues is unknown. This is an important point given that humans must often make decisions about the future without being explicitly "prompted" by the future-oriented option. In Experiment 1, using an adapted version of the spoon test, we show that as the "generative" requirements of the task increase, 3-, 4-, and 5-year-olds' (N = 99) performance significantly decreases. We replicate this effect in Experiment 2 (N = 48 3-, 4-, and 5-year-olds) and also provide preliminary evidence that the capacity to verbally generate the correct item in a spoon test may draw more heavily on children's category fluency skills than does their capacity to select this item among a set of distracters. Our findings underscore the importance of examining more generative forms of future thought in young children.

The effects of nitrogen and phosphorus fertilizer application on herbage yield of natural pastures.

This study was carried out in a natural pasture in Van province of Turkey between the years of 2004 and 2005 to determine the effects of nitrogen and phosphorus fertilization on herbage yield. The study was performed in randomized block with three replications. 0, 4, 8, 16 kg da(-1) nitrogen and 0, 6, 12 kg da(-1) phosphorus applications were examined. The effects of different nitrogen and phosphorus fertilizer applications on plant height, green herbage and crude protein yield were significant for both years. Depending on the increasing nitrogen and phosphorus applications, significant increases were in green herbage, hay and crude protein yields. According to results, differences between 8 and 16 kg da(-1) doses of nitrogen and 6 and 12 kg da(-1) doses of phosphorus applications were insignificant. In the first year, in terms of nitrogen applications, the highest green herbage, hay and crude protein yield (1423.1, 263.3 and 29.2 kg da(-1)) were obtained from 8 kg N da(-1), in the second year, the highest values (1426.1, 602.7 and 67.8 kg da(-1)) were obtained from 16 kg N da(-1) application. As for the phosphorus applications, in the first year, the highest green herbage yield was 1142.2 kg da(-1) at the 6 kg P2O5/da application, hay and crude protein yields (218.2, 23.1 kg da(-1)) were recorded from 12 kg P2O5/da application. In the second year, the highest green herbage, hay and crude protein yields were (1335.8, 549.6 and 66.1 kg da(-1)) determined at the 12 kg P2O5/da application.