406. Prefrontal cell pathology distinguishes bipolar disorder from schizophrenia

Abstract

Bipolar disorder (BPD) is a mental illness in which depression and psychosis are present in an alternating course, and therefore the symptomatology of the disease resembles both major depressive disorder (MDD) and schizophrenia (SCHZ). Neuroimaging evidence has implicated the prefrontal cortex as a site of common morphological and metabolic abnormalities in all three disorders. Recent morphometric studies have demonstrated changes in prefrontal cell architecture in SCHZ (Selemon et al., 1995; 1998; Rajkowska et al., 1998) and MDD (Rajkowska et al., 1999). In contrast, cellular neuropathology in BPD has not been described. In this postmortem study, we analyzed area 9 of the dorsolateral prefrontal cortex in 10 subjects with BPD and 11 matched nonpsychiatric controls using a 3-D morphometric method. In comparison to nonpsychiatric controls, the prefrontal cortex in BPD was characterized by significant, lamina-specific reductions in the density of neurons with predominantly pyramidal shape, reductions in the density of glial cells, enlargement of glial nuclei and changes in their shape. These findings imply that the morphologic signature of BPD, i.e. glial hypertrophy in association with decreased neuronal and glial density, is distinct from our previously described elevations in neuronal density in SCHZ and more closely resembles the reductions in cell density found in MDD. Both SCHZ and BPD cortices, however, exhibit atrophy of neuronal cytoplasm in cortical layer III. Thus, the prefrontal cortex in BPD manifests a unique pattern of neuropathology that may reflect underlying neurochemical imbalances specific to this mental illness and distinct from SCHZ.