Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior.

Effects of Chronic D-Serine Elevation on Animal Models of Depression and Anxiety-Related Behavior.

PLoS One. 2013; 8(6): e67131
Otte DM, Barcena de Arellano ML, Bilkei-Gorzo A, Albayram O, Imbeault S, Jeung H, Alferink J, Zimmer A

NMDA receptors are activated after binding of the agonist glutamate to the NR2 subunit along with a co-agonist, either L-glycine or D-serine, to the NR1 subunit. There is substantial evidence to suggest that D-serine is the most relevant co-agonist in forebrain regions and that alterations in D-serine levels contribute to psychiatric disorders. D-serine is produced through isomerization of L-serine by serine racemase (Srr), either in neurons or in astrocytes. It is released by astrocytes by an activity-dependent mechanism involving secretory vesicles. In the present study we generated transgenic mice (SrrTg) expressing serine racemase under a human GFAP promoter. These mice were biochemically and behaviorally analyzed using paradigms of anxiety, depression and cognition. Furthermore, we investigated the behavioral effects of long-term administration of D-serine added to the drinking water. Elevated brain D-serine levels in SrrTg mice resulted in specific behavioral phenotypes in the forced swim, novelty suppression of feeding and olfactory bulbectomy paradigms that are indicative of a reduced proneness towards depression-related behavior. Chronic dietary D-serine supplement mimics the depression-related behavioral phenotype observed in SrrTg mice. Our results suggest that D-serine supplementation may improve mood disorders. HubMed – depression


Self-Help for Depression via E-mail: A Randomised Controlled Trial of Effects on Depression and Self-Help Behaviour.

PLoS One. 2013; 8(6): e66537
Morgan AJ, Jorm AF, Mackinnon AJ

Self-help or self-management strategies are commonly used to deal with depression, but not all are thought to be helpful. A previous study found that sub-threshold depression symptoms were improved by an e-mail intervention that encouraged the use of evidence-based self-help strategies.To investigate whether these e-mails were effective for adults with a range of depression symptomatology including major depression.The study was a parallel-group randomised controlled trial. Adult participants with any level of depressive symptoms were recruited over the internet from the United Kingdom, Australia, Canada, Ireland, New Zealand and the United States. Participants were randomised to receive a series of e-mails either promoting the use of evidence-based self-help strategies or containing depression information as a control. E-mails were sent automatically twice a week for six weeks. Depression symptoms were assessed with the self-rated Patient Health Questionnaire depression scale (PHQ-9).1736 participants with a wide range of symptom severity were recruited and assigned to active (n?=?862) and control (n?=?874) groups. However, there was a significant attrition rate, with 66.9% lost to follow-up at post-intervention. Both groups showed large improvements in depression symptoms overall, with no significant difference in improvement at the end of the study (mean difference in improvement 0.35 points, 95% CI: -0.57 to 1.28, d?=?0.11, 95% CI: -0.06 to 0.27), although there was a small effect at the study mid-point. Results were similar for the sub-group of participants with major depression. The active group showed small to moderate improvements in self-help behaviour (d?=?0.40, 95% CI: 0.23 to 0.56).These results suggest that the e-mails were able to increase participants’ use of evidence-based self-help, but that this did not improve depression more than an attention control.NCT01399502. HubMed – depression


Mapping acute systemic effects of inhaled particulate matter and ozone: multi-organ gene expression and glucocorticoid activity.

Toxicol Sci. 2013 Jun 26;
Thomson EM, Vladisavljevic D, Mohottalage S, Kumarathasan P, Vincent R

Recent epidemiological studies have demonstrated associations between air pollution and adverse effects that extend beyond respiratory and cardiovascular disease, including low birth weight, appendicitis, stroke, and neurological/neurobehavioural outcomes (e.g. neurodegenerative disease, cognitive decline, depression, suicide). To gain insight into mechanisms underlying such effects, we mapped gene profiles in the lungs, heart, liver, kidney, spleen, cerebral hemisphere, and pituitary of male Fischer-344 rats immediately and 24 h after a 4 h exposure by inhalation to particulate matter (0, 5, 50 mg/m(3) EHC-93 urban particles) and ozone (0, 0.4, 0.8 ppm). Pollutant exposure provoked differential expression of genes involved in a number of pathways, including antioxidant response, xenobiotic metabolism, inflammatory signalling, and endothelial dysfunction. The mRNA profiles, while exhibiting some inter-organ and pollutant-specific differences, were remarkably similar across organs for a set of genes, including increased expression of redox/glucocorticoid-sensitive genes and decreased expression of inflammatory genes, suggesting a possible hormonal effect. Pollutant exposure increased plasma levels of adrenocorticotropic hormone and the glucocorticoid corticosterone, confirming activation of the hypothalamic-pituitary-adrenal axis, and there was a corresponding increase in markers of glucocorticoid activity. Although effects were transient and presumably represent an adaptive response to acute exposure in these healthy animals, chronic activation and inappropriate regulation of the hypothalamic-pituitary-adrenal axis is associated with adverse neurobehavioural, metabolic, immune, developmental, and cardiovascular effects. The experimental data are consistent with epidemiological associations of air pollutants with extrapulmonary health outcomes, and suggest a mechanism through which such health effects may be induced. HubMed – depression


The Evaluation of Electrocardiogram Findings in Acute Abdominal Pain Patients Admitted to the Emergency Department.

J Prim Care Community Health. 2011 Jul 1; 2(3): 163-166
Oguzturk H, Turtay MG, Tekin YK, Tekin G

The aim of this study was to determine the diagnostic value of electrocardiogram in differential diagnosis of patients with nonspecific abdominal pain. This prospective observational study was conducted in a university emergency department over 2 weeks. One hundred twenty patients with complaints of abdominal pain were admitted to the emergency department. During the study period, a total of 120 cases were evaluated. The final emergency department disposition status of the 120 patients was 1 (0.8%) died in the emergency department, 28 (23.3%) were admitted to the general ward, 27 (22.5%) were admitted to other services, and 10 (8.3%) were admitted to the cardiology service and coronary care unit. The examination indicated that 38 (31.7%) patients with abdominal pain showed cardiac pathologies on their electrocardiograms; 3 (2.5%) patients with abdominal pain admitted to cardiology service had ST elevation, and 2 (1.6%) had electrocardiogram depression on their electrocardiograms. According to the results, the authors claim that the electrocardiogram played an important role in the treatment and diagnosis of patients presenting with abdominal pain in emergency medicine. For this reason, it was thought that emergency medicine specialists should understand the basis of the perception of abdominal pain and develop a focused approach to the initial evaluation of these patients. HubMed – depression