Decreased gray matter density in the thalamus was reported60 when MR images were compared using significance probability mapping. The reduced volume seen in our MRI studies combined with the reduced volume and neuronal number,2,16,19- 20 neuronal size,2 and reduced metabolic rate24 is consistent with the concept that the MDN in patients with schizophrenia is compromised and that smaller numbers of smaller (and presumably less active) neurons carry out a reduced amount of information processing. The reduction in size is seen with absolute data and those expressed relative to whole brain volume. This may reflect the removal of irrelevant body-size associated variance, because effect sizes were larger when data corrected for total brain size were examined; if the thalamus merely shrank along with all other brain structures, we might have anticipated a smaller effect size for relative than absolute data. The percentage reduction in absolute MDN volume we observed is small(6.7%) compared with the larger volume reductions seen in the postmortem studies by the research groups of Pakkenberg,16 Byne et al,2 Popken et al,19 and Young et al20 cited above (27%, 15%, 17%, and 24%, respectively). This may reflect a combination of factors, including statistically more variable measurement of volume in MRI than postmortem material, differential contributions to MRI density of different types of neurons, and characteristics of the parvocellular subregion that might shift the lateral edge of the entire MDN on MRI. Nevertheless, our findings match those of the 4 postmortem studies and provide data on a much larger and younger cohort without the confounding factor of old age, variation in postmortem interval, and fixation shrinkage. Since putatively atrophic changes have been described in 1 of the cortical targets of the MDN, these data are also consistent with our overarching hypothesis that schizophrenia-related pathology in a particular subdivision of the thalamus is etiologically related to pathology in its projection fields. The localization of schizophrenia-associated changes to thalamic subregions is a step in the understanding of neuronal circuit impairments that may be involved in the symptomatology of the schizophrenias. The finding of reduced PUL volume in the large sample used in the present study adds weight to our previous observations based on much smaller in vivo1 and postmortem samples.2 The PUL is a large, heterogeneous structure that occupies nearly a quarter of the total thalamic volume and consists of several subdivisions with unique patterns of connectivity.11 If our overarching hypothesis is correct, subsequent postmortem studies may find that the volume changes in the PUL disproportionately affect its medial portion, which may be further subdivided into a centrolateral subdivision with a preponderance of prefrontal connections similar to those of the MDN, and a medial subdivision (ie, the medial subdivision of the medial PUL) with a preponderance of temporal connections.