Laboratory for Structural Neuroscience, McLean Hospital, Belmont, Massachusetts, USA, and Program in Neuroscience and Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA
This chapter reviews recent postmortem studies of schizophrenic
brain and discusses the potential role of the amygdala in the
induction of hippocampal abnormalities in this disorder. Based
on available evidence, sectors CA4, CA3, and CA2, but not CA1,
show preferential changes in schizophrenic subjects, although
the most pronounced changes have been found in CA3 and CA2.
It seems likely that the amygdala would contribute in some way
to the induction of abnormalities along the trisynaptic pathway
via its direct input to sectors CA3 and CA2, as well as an indirect
one that involves the entorhinal cortex and its perforant path
projection to the area dentata. The postmortem findings reported
to date have been integrated into a working model in which decreases
of inhibitory GABAergic modulation are invoked to explain the
observation from a recent PET scan study (Heckers
et al., 1999)
that baseline metabolic activity in the hippocampus of schizophrenics
is increased. In addition, however, the apparent inability of
schizophrenics to increase metabolic activity in the hippocampus
when challenged with a memory retrieval task may reflect a disturbance
of disinhibitory modulation postulated herein to occur in sector
CA3, a key relay point along the trisynaptic pathway. Overall,
it seems plausible that an increase of excitatory activity entering
the hippocampus from the basolateral complex via both direct
and indirect pathways may make a significant contribution to
the pathophysiology of schizophrenia.
