Depression Treatment: Neuronal Apoptosis and Synaptic Density in the Dentate Gyrus of Ischemic Rats’ Response to Chronic Mild Stress and the Effects of Notch Signaling.

Neuronal apoptosis and synaptic density in the dentate gyrus of ischemic rats’ response to chronic mild stress and the effects of notch signaling.

Filed under: Depression Treatment

PLoS One. 2012; 7(8): e42828
Wang S, Yuan Y, Xia W, Li F, Huang Y, Zhou Y, Guo Y

Our previous research highlighted an inconsistency with Notch1 signaling-related compensatory neurogenesis after chronic mild stress (CMS) in rodents suffering from cerebral ischemia, which continue to display post-stroke depressive symptoms. Here, we hypothesize that CMS aggrandized ischemia-related apoptosis injury and worsened synaptic integrity via gamma secretase-meditated Notch1 signaling. Adult rats were exposed to a CMS paradigm after left middle cerebral artery occlusion (MCAO). Open-field and sucrose consumption testing were employed to assess depression-like behavior. Gene expression of pro-apoptotic Bax, anti-apoptotic Bcl-2, and synaptic density-related synaptophysin were measured by western blotting and real-time PCR on Day 28 after MCAO surgery. CMS induced depressive behaviors in ischemic rats, which was accompanied by an elevation in Bax/bcl-2 ratio, TUNEL staining in neurons and reduced synaptophysin expression in the dentate gyrus. These collective effects were reversed by the gamma-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenyl-glycine t-butyl ester). We found that post-stroke stressors made neurons in the dentate gyrus vulnerable to apoptosis, which supports a putative role for Notch signaling in neural integrity, potentially in newborn cells’ synaptic deficit with regard to preexisting cells. These findings suggest that post-stroke depression therapeutically benefits from blocking gamma secretase mediated Notch signaling, and whether this signaling pathway could be a therapeutic target needs to be further investigated.
HubMed – depression


Taking the Perspective that a Depressive State Reflects Inflammation: Implications for the Use of Antidepressants.

Filed under: Depression Treatment

Front Psychol. 2012; 3: 297
Littrell JL

This paper reviews both the evidence that supports the characterization of depression as an inflammatory disorder and the different biochemical mechanisms that have been postulated for the connection between inflammation and depression. This association offers credible explanation for the short term efficacy of antidepressants, which have short term anti-inflammatory effects. Evidence for those anti-inflammatory effects is discussed. Evidence of the contrary long-term effects of antidepressants, which increase rather than decrease inflammation, is also reviewed. It is argued that this increase in inflammation would predict an increase in chronicity among depressed patients that have been treated with antidepressants drugs, which has been noted in the literature. A brief discussion of alternatives for decreasing inflammation, some of which have demonstrated efficacy in ameliorating depression, is presented.
HubMed – depression


A randomized double-blind sham-controlled study of transcranial direct current stimulation for treatment-resistant major depression.

Filed under: Depression Treatment

Front Psychiatry. 2012; 3: 74
Blumberger DM, Tran LC, Fitzgerald PB, Hoy KE, Daskalakis ZJ

Objectives: Transcranial direct current stimulation (tDCS) has demonstrated some efficacy in treatment-resistant major depression (TRD). The majority of previous controlled studies have used anodal stimulation to the left dorsolateral prefrontal cortex (DLPFC) and a control location such as the supraorbital region for the cathode. Several open-label studies have suggested effectiveness from anodal stimulation to the left DLPFC combined with cathodal stimulation to the right DLPFC. Thus, this study evaluated the efficacy of tDCS using anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC compared to sham tDCS. Methods: Subjects between the ages of 18 and 65 were recruited from a tertiary care university hospital. Twenty-four subjects with TRD and a 17-item Hamilton Rating Scale for Depression greater than 21 were randomized to receive tDCS or sham tDCS. The rates of remission were compared between the two treatment groups. Results: The remission rates did not differ significantly between the two groups using an intention to treat analysis. More subjects in the active tDCS group had failed a course of electroconvulsive therapy in the current depressive episode. Side effects did not differ between the two groups and in general the treatment was very well tolerated. Conclusion: Anodal stimulation to the left DLPFC and cathodal stimulation to the right DLPFC was not efficacious in TRD. However, a number of methodological limitations warrant caution in generalizing from this study. Ongoing, controlled studies should provide further clarification on the efficacy of this stimulation configuration in TRD. Identifier: NCT01078948.
HubMed – depression


Dealing with depression after a stroke? Doctor offers treatment options

Filed under: Depression Treatment

Simms said the presence of depression is also an important marker in the rehabilitation process and adjustment after stroke. “We will discuss the different symptoms as well as treatments available for this condition in the context of acute stroke or in …
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Patrick Kennedy: Rep. Jackson in 'deep' depression

Filed under: Depression Treatment

"I don't think people understand the depth of his depression. It's deep. He has a lot of work to continue to do to be able to learn how to treat this illness in the most effective way possible," Kennedy told The Associated Press. "Depression is a …
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More Evidence that Exercise May Help Treat Depression

Filed under: Depression Treatment

It's no surprise that upbeat, motivated people find it easier to get out and exercise. But exercise itself can actually improve mood and motivation as well, particularly for people with heart failure, a new study shows. The finding is exciting not only …
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