We agree with David et al that the key problem, which we have highlighted, in in vivo MRI studies of the amygdala, is anatomical definition. The ability to define anatomical boundaries at the cellular level means that post-mortem samples set the gold standard for anatomical delineation. Indeed, the generally smaller volumes of the amygdala (uncorrected for tissue shrinkage in Reference Chance, Esiri and CrowChance et al, 2002) reported in post-mortem studies are indicative of more conservative estimates when the precise boundaries can be seen. This is consistent with Brierley et al's (Reference Brierley, Shaw and David2002) conclusion in their meta-analysis that anatomical definition is the most prominent contributor to variance in MRI volume estimates of the amygdala.

Our criticism is not of meta-analysis per se, but of the inclusion of some studies, which owing to low scan resolution use only very approximate anatomical definitions. Particularly problematic in schizophrenia is the use of landmarks, which may be systematically shifted with respect to the boundary of the amygdala, owing to other changes in the temporal lobe. While MRI studies have the obvious advantages of an in vivo assessment and larger sample size, post-mortem studies are also important as a check on the possibility of systematic bias which may enter the MRI literature (Reference Walker, Highley and EsiriWalker et al, 2002).

We agree with the importance of consensus criteria for anatomical definitions which take full advantage of the improvements in up-to-date MRI visualisation. Our paper concludes with some references to studies attempting to tackle this issue for the amygdala, to which the paper of Brierley et al (Reference Brierley, Shaw and David2002) should be added.