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Smoking remains the second leading cause of premature death in the United States among men and women combined [247, 248], and a recent study showed an association between tobacco use and severity of cardiomyopathy in DM1 patients [29]. There is some evidence for changes in smoking behavior in DM1. We have observed a high prevalence of smoking in our DM1 population [9]. However, smoking cessation was more effective in men than in women [249]. Altered metabolism of nicotine may underlie the differences in smoking behavior in male and female DM1 patients [250]. Research by Serano and colleagues suggests that there may be differences in brain activity in people with DM1 and healthy controls [251]. The most common symptoms in DM1 patients include cardiac and sensory nerve dysfunction [252]. DM1 patients may be at higher risk for cardiac arrhythmias than the general population [253], and cardiovascular disease is a major contributor to mortality [254]. Depression is common in DM1 [255, 256] and one can speculate that impaired cardiac function, sensory deficits and altered metabolism of nicotine may contribute to these symptoms.

Mutations in the FKBP12 gene occur in about 85% of cases with DM1 and result in a cellular dysfunction that may lead to chronic muscle wasting [257]. Experimental data indicate that brain-derived neurotrophic factor (BDNF) signaling is impaired in DM1 muscle [258]. BDNF is a neurotrophin which is involved in survival, growth and differentiation of neurons. The brain contains high levels of this protein. BDNF levels are also found in brain tumors [259]. BDNF and its high affinity receptor TrkB are dynamically expressed in muscle during post-natal growth and development [260]. While BDNF can be delivered directly to striated skeletal muscle [261], BDNF is also expressed in other organs including adipose tissue and skeletal muscle [262, 263], suggesting a paracrine autocrine action in different tissues. BDNF has also been shown to promote axon branching by an autocrine action in the dentate gyrus of the hippocampus and the olfactory bulb [264]. d2c66b5586

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