Molecular Aging of the Brain, Neuroplasticity, and Vulnerability to Depression and Other Brain-Related Disorders.

Molecular aging of the brain, neuroplasticity, and vulnerability to depression and other brain-related disorders.

Dialogues Clin Neurosci. 2013 Mar; 15(1): 53-65
Sibille E

The increased risk for neurodegenerative and neuropsychiatric disorders associated with extended lifespan has long suggested mechanistic links between chronological age and brain-related disorders, including depression, Recent characterizations of age-dependent gene expression changes now show that aging of the human brain engages a specific set of biological pathways along a continuous lifelong trajectory, and that the same genes that are associated with normal brain aging are also frequently and similarly implicated in depression and other brain-related disorders. These correlative observations suggest a model of age-by-disease molecular interactions, in which brain aging promotes biological changes associated with diseases, and additional environmental factors and genetic variability contribute to defining disease risk or resiliency trajectories. Here we review the characteristic features of brain aging in terms of changes in gene function over time, and then focus on evidence supporting accelerated molecular aging in depression. This proposed age-by-disease biological interaction model addresses the current gap in research between “normal” brain aging and its connection to late-life diseases. The implications of this model are profound, as it provides an investigational framework for identifying critical moderating factors, outlines opportunities for early interventions or preventions, and may form the basis for a dimensional definition of diseases that goes beyond the current categorical system. HubMed – depression


Aging and neuroplasticity.

Dialogues Clin Neurosci. 2013 Mar; 15(1): 3-5
Smith GS

Neuroplasticity can be defined as a final common pathway of neurobiological processes, including structural, functional or molecular mechanisms, that result in stability or compensation for age- or disease-related changes. The papers in this issue address the aging process, as well as depression, dementia, and stroke and a range of interventions, including manipulations in behavior (physical and cognitive activity/exercise), physiological factors (caloric restriction, cholesterol), pharmacologic treatments (AMPA receptors) and manipulation of brain magnetic fields and electrical activity (transcranial magnetic stimulation, magnetic seizure therapy, and deep brain stimulation).This editorial will address different facets of neuroplasticity, the need for translational research to interpret neuroimaging data thought to reflect neuroplasticity in the human brain, and the next steps for testing interventions in aging and in disease. HubMed – depression


Superior antidepressant effect occurring 1 month after rTMS: add-on rTMS for subjects with medication-resistant depression.

Neuropsychiatr Dis Treat. 2013; 9: 397-401
Chen SJ, Chang CH, Tsai HC, Chen ST, Lin CCh

Depression is a major psychiatric disorder. The standard treatment for depression is antidepressant medication, but the responses to antidepressant treatment are only partial, even poor, among 30%-45% of patients. Refractory depression is defined as depression that does not respond to antidepressant therapy after 4 weeks of use. There is evidence that repetitive transcranial magnetic stimulation (rTMS) may exert effects in treating psychiatric disorder through moderating focal neuronal functions. High-frequency rTMS on the left prefrontal area and low-frequency rTMS on the right prefrontal area were shown to be effective in alleviating depressive symptoms. Given the statistically significant antidepressant effectiveness noted, the clinical application of rTMS as a depression treatment warrants further studies. Application of rTMS as an add-on therapy would be a practical research model. High-frequency (5-20 Hz) rTMS over the left dorsolateral prefrontal cortex was found to have a significant effect on medication-resistant depression. In the present study, we not only measured the acute antidepressant effect of rTMS during treatment and immediately after its completion but also evaluated participants 1 month after completion of the treatment protocol. Study participants were divided into two groups: an active rTMS group (n = 10) and a sham group (n = 10). The active rTMS group was defined as participants who received the rTMS protocol, and the sham group was defined as participants who received a sham rTMS procedure. A significant Hamilton Depression Rating Scale score reduction was observed in both groups after the fifth and tenth treatments. However, those in the active rTMS group maintained their improvement as measured one month after completion of the rTMS protocol. Participants who received active rTMS were more likely to have persistent improvement in depression scores than participants who received sham rTMS. HubMed – depression


Crossmodal emotional integration in major depression.

Soc Cogn Affect Neurosci. 2013 Apr 10;
Müller VI, Cieslik EC, Kellermann TS, Eickhoff SB

Major depression goes along with affective and social-cognitive deficits. Most research on affective deficits in depression has, however, only focused on unimodal emotion processing, whereas in daily life emotional perception is often highly dependent on the evaluation of multimodal inputs. We thus investigated emotional audiovisual integration in patients with depression and healthy subjects. Subjects rated the expression of happy, neutral and fearful faces while concurrently being exposed to emotional or neutral sounds. Results demonstrated group differences in left inferior frontal gyrus and inferior parietal cortex when comparing incongruent to congruent happy facial conditions, mainly due to a failure of patients to deactivate these regions in response to congruent stimulus pairs. Moreover, healthy subjects decreased activation in right posterior superior temporal gyrus/sulcus and middle cingulate cortex when an emotional stimulus was paired with a neutral rather than another emotional one. In contrast, patients didn’t show such deactivation when neutral stimuli were integrated. These results demonstrate aberrant neural response in audiovisual processing in depression, indicated by failure to deactivate regions involved in inhibition and salience processing when congruent and neutral audiovisual stimuli pairs are integrated, providing a possible mechanism of constant arousal and readiness to act in this patient group. HubMed – depression



New Drug Used To Treat Depression – Dr. Sidney Zisook, a professor at UC San Diego, discusses the causes of depression and new ways of treating it on KPBS Television’s “Evening Edition.”