during pregnancy, further suggesting that exposure to cigarette smoke while in utero may have long-term consequences still measurable into adolescence. The BDNF gene contains several exons, the expression of which is crucial for proper functioning of BDNF protein and which have been shown to be differentially-regulated in an exon-specific manner. One additional preliminary study, for example, has noted that measurement of methylation upstream of BDNF exon I may have promise as a diagnostic blood biomarker for major depression (Fuchikami et al., 2011). Interestingly, exon 6 of the BDNF gene appears to be particularly sensitive to epigenetic modification from environmental factors related to depression. Specifically, chronic stress results in epigenetic changes in histones related to hippocampal BDNF that reduce expression whereas treatment with the antidepressant imipramine results in epigenetic changes of histones associated with the same exon that increase expression rates (Calabrese, Molteni, Racagni, & Riva, 2009). This example highlights the importance the various types of epigenetic modification that may increase (or decrease) risk for psychopathology by modifying the same gene in different ways and how such mechanisms may overlap with prenatal smoke exposure. Abnormal methylation upstream of one BDNF exon may change the ultimate expression of BDNF and thus play
