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Richard Simmons. Cropped from a photo by Del F...Image via Wikipedia The Wall Street Journal just ran a piece on the growing use of electro-convulsive (“shock”) therapy in elderly patients suffering from severe depression. While the clinical evidence may show this approach is effective – albeit scary – it is notable that another study published on the same day by Hunsberger et al., entitled, “Antidepressant actions of the exercise-regulated gene VGF(DOI). This paper reveals that a number of genes possessing antidepressant-like properties are induced by exercise. Yes, good old fashioned walkin’ and sweatin’. A few clinical trials have shown that, in older people especially, exercise is just as effective as anti-depressant medications. Furthermore, exercise seems to increase neurogenesis in the hippocampus in a manner that is parallel to anti-depressants. One of the genes induced by exercise, a growth factor named VGF, produces anti-depressant responses when administered into the mouse brain, while +/- hemizygous VGF animals show increased physiological and behavioral signs of stress. The authors point to the role of structural synaptic changes in long-term relief of depression, rather than short term increases in serotonin, but -ironically – note that VGF would be a great candidate for drug development. Hmmm, seems like I’ll skip the meds and the electrodes, and get to sweatin’ with a Richard Simmons video.*

*For the record, I do not currently own a Richard Simmons video.

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Daniel Weinberger and company have a new installment in-press at Biological Psychiatry in their epic program to untangle the genetic basis of schizophrenia – “Heritability of Brain Morphology Related to Schizophrenia: A Large-Scale Automated Magnetic Resonance Imaging Segmentation Study.” Like all complex illness, schizophrenia is regulated by a variety of environmental sources (perinatal complications, stress & substance abuse are a few) and equally regulated by heritable factors. Although several specific genes for schizophrenia have been painstakingly identified, the genes are expressed widely throughout the brain – making it difficult to pinpoint where in the brain the gene interacts with the environment to exert its detrimental effects. To solve this problem, Weinberger and colleagues pioneered a method known as imaging-genetics where they look at how individual genetic differences correlate with differences in brain structure or functional activity (if you ever have a chance to volunteer for an fMRI brain imaging study – go for it – it’ll be one of the top 10 weirdest experiences of your life). In their latest report, the team pioneers a new “fully-automated whole brain segmentation” technique to show that the genetic factors that put individuals at risk may be functioning vis-a-vis the hippocampus and neocortex. This narrows the search space a lot! and is a major step forward in beginning to localize where in the brain the genetic risk originates.

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