Strongly reduced number of parvalbumin-immunoreactive projection neurons in the mammillary bodies in schizophrenia further evidence for limbic neuropathology

The mammillary bodies (MB) are important relay nuclei within limbic and extralimbic connections. They are known to play important roles in memory formation and are affected in alcoholism and vitamin B1 deficiency. Their strategic position linking temporo-limbic to cortico-thalamic brain structures make the MB a candidate brain structure for alterations in schizophrenia. We studied 15 postmortem brains of schizophrenics and 15 matched control brains. Brain sections were stained either with Heidenhain-Woelcke, glutamic acid decarboxylase (GAD), calretinin, or parvalbumin. We determined the volumes of the MB and performed cell countings using stereological principles and a computerized image analysis system. The volumes of NIB do not differ between schizophrenics and controls. However, in schizophrenia the number of neurons as well as the resulting neuronal densities was significantly reduced on both sides (on left side by 38.9%, on right side by 22%). No changes were seen in the number of GAD-expressing or calretinin-containing neurons, whereas the number of parvalbumin-immunoreactive MB neurons was reduced by more than 50% in schizophrenia. This cell loss (as a result of developmental malformation and/or neurodegeneration) points to a prominent involvement of the MB in the pathomorphology of schizophrenia. Parvalbumin-immunoreactive GABAergic interneurons have been reported to be diminished in schizophrenia. However, in the MB parvalbumin labels a subpopulation of glutamate/aspartate-containing neurons projecting mainly to the anterior thalamus. Thus, our data provide new evidence for impaired limbic circuits in schizophrenia.