Review: No Reliable Evidence of the Effect of Psychotherapy Upon Suicide Risk in People With Depression.
Review: no reliable evidence of the effect of psychotherapy upon suicide risk in people with depression.
Evid Based Ment Health. 2013 Apr 13;
Fowler JC
Metabolomics identifies pyrimidine starvation as the mechanism of 5-aminoimidazole-4-carboxamide-1-?-riboside (AICAr) induced apoptosis in multiple myeloma cells.
Mol Cancer Ther. 2013 Apr 12;
Bardeleben C, Sharma S, Reeve JR, Bassilian S, Frost PJ, Hoang B, Shi Y, Lichtenstein A
To investigate the mechanism by which AICAr induces apoptosis in multiple myeloma (MM) cells, we performed an unbiased metabolomics screen. AICAr had selective effects on nucleotide metabolism, resulting in an increase in purine metabolites and a decrease in pyrimidine metabolites. The most striking abnormality was a 26 x fold increase in orotate associated with a decrease in UMP levels, indicating an inhibition of UMP synthetase (UMPS), the last enzyme in the de novo pyrimidine biosynthetic pathway, which produces UMP from orotate and PRPP. As all pyrimidine nucleotides can be synthesized from UMP, this suggested the decrease in UMP would lead to pyrimidine starvation as a possible cause of AICAr-induced apoptosis. Exogenous pyrimidines uridine, cytidine and thymidine, but not purines adenosine or guanosine, rescued MM cells from AICAr-induced apoptosis, supporting this notion. In contrast, exogenous uridine had no protective effect on apoptosis resulting from bortezomib, melphalan or metformin. Rescue resulting from thymidine add-back indicated apoptosis was induced by limiting DNA synthesis rather than RNA synthesis. DNA replicative stress was identified by associated H2A.X phosphorylation in AICAr-treated cells, which was also prevented by uridine add-back. Although phosphorylation of AICAr by adenosine kinase was required to induce MM cell death, apoptosis was not associated with AMP-activated kinase activation or mTORC1 inhibition. A possible explanation for inhibition of UMP synthase activity by AICAr was a depression in cellular levels of PRPP, a substrate of UMP synthase. These data identify pyrimidine biosynthesis as a potential molecular target for future therapeutics in MM cells. HubMed – depression
[Analysis of (1)H-MRS in patients with depression after basal ganglia infarction].
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2013 Mar; 42(2): 205-11
Zhou L, Lou M, Zheng SH, Li J
To investigate the metabolic changes on proton magnetic resonance spectroscopy ((1)H-MRS) in patients with first left basal ganglia infarction and their relationship with depression.Twenty-two patients with first left basal ganglia infarction and 10 matched healthy controls were recruited in the study. Patients and controls underwent (1)H MRS scan and the spectrum of N-acetyl aspartic acid (NAA), choline (Cho) and creatinine (Cr) was recorded at the first week (D7) and 1 month after onset (M1), respectively. National Institutes of Health Stroke Scale (NIHSS), Ability of daily life (ADL), Hamilton Depression Scale (HAMD) were evaluated at D7, M1 and M6 after onset. The patients were classified into two groups: post-stroke depression (PSD) and non-post-stroke depression (NPSD) according to the result of HAMD.The differences of (1)H-MRS between these two groups were compared and their relationship with NIHSS and ADL was analyzed.Among 22 patients 10 were diagnosed as PSD and 12 were NPSD. Compared to controls, NAA/Cr was significantly lower and Cho/Cr was significantly higher (P <0.05)in left prefrontal white matter and left basal ganglia in patients with infarct. Patients with PSD showed a lower NAA/Cr and higher Cho/Cr than NPSD patients (P <0.05). At M1 after onset, NAA/Cr in the left prefrontal white matter was significantly correlated with NIHSS (r=-0.551, P =0.032), while Cho/Cr was correlated with ADL (r=0.682, P=0.005)in PSD patients.Metabolic changes shown on (1)H-MRS in patients with basal ganglia infarction may predict the occurrence of PSD. HubMed – depression
[Comparison of skin sympathetic reaction in patients with generalized anxiety disorder and with major depression disorder].
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2013 Mar; 42(2): 192-6
Jiang H, Wang L, Wang XL, Feng R, Zhang YC, Tu LL, Chen W
To compare skin sympathetic response(SSR) between patients with generalized anxiety disorder(GAD) and patients with major depression disorder(MDD).The latency and amplitude of SSR wave were measured in 30 GAD patients and 30 MDD patients, before and after 8-week treatment of anti-anxiety or anti-depression drugs. Thirty age and sex-matched healthy subjects served as healthy controls (HC).Before the treatment, the latency of SSR in GAD patients was significantly shorter than that in HC group, while the amplitude was significantly higher than that in the HC (P<0.05). In MDD group, the latency before the treatment was significantly longer than that in the HC,while the amplitude was significantly lower than that in the HC (P <0.05). After treatment,the latency of SSR in GAD group was extended compared to the baseline level, and close to the level of the HC. The amplitude of SSR in GAD group became lower after treatment, but still higher than that of control group. The latency of SSR in MDD patients was significantly shorter after treatment compared to baseline level (P <0.05). In addition, the latency of SSR in MDD group was still longer than that in GAD group (P<0.05); meanwhile,the amplitude of SSR in MDD group was significantly lower that in GAD group (P<0.001). SSR parameters were positively correlated with HAMA and HAMD scores with a correlation coefficient of 0.57 and 0.73, respectively.There are significant differences in SSR parameters between patients with GAD and patients with MDD,indicating that SSR can be used as an objective index to distinguish anxiety from depression. HubMed – depression
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