Psychiatry-Developmental DisorderReviewImaging phenotypes of major depressive disorder: genetic correlates
Section snippets
The amygdala: an emotional processing bias
Patients with MDD have repeatedly demonstrated increased amygdala reactivity to negative stimuli as evinced by functional magnetic resonance imaging (fMRI) (Table 1). (Siegle et al., 2002) found that amygdalar responses to negative words were no longer visible after 10 s in healthy controls but persisted in depressed patients for a mean of 25 s. Similarly, depressed individuals reportedly remember negative words better than positive words (Watkins et al., 1992), a finding that correlates with
Phenotypic heterogeneity
A great deal of genetic and phenotypic variation is encompassed within current nosological categories, and it is thus likely that the exact pattern of MDD-associated neuropathology will vary across subgroups of affectively ill patients. The relatively embryonic state of the field has unfortunately meant that these issues have thus far been largely neglected.
For example, there is some evidence that patients who are recurrently ill and those subjects who have experienced one lifetime episode of
Gene–gene interactions
Assuming the veracity of the common disease–common variant (CDCV) hypothesis, analyzing the additive effects of common polymorphisms on imaging phenotypes, and by extension, genetic risk for MDD, is an important project. Evidence for gene–gene interactions is beginning to emerge in the literature. The SLC6A4 gene has been reported to interact with BDNF to impact amygdala and anterior cingulate cortex volume (Pezawas et al., 2008); TPH2 (Canli et al., 2008), and COMT (Smolka et al., 2007), to
Conclusion
We have discussed seven (MRI and PET) imaging phenotypes which appear to be strongly associated with MDD. Strictly speaking, an endophenotype is a heritable trait present in periods of illness and remission that should be found in biological relatives of affected individuals at a greater frequency than the general population (Gottesman and Gould, 2003). The extant literature is not mature enough to allow us to evaluate whether the neurophysiological markers discussed above qualify as
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