Increased CNS levels of apolipoprotein D in schizophrenic and bipolar subjects: Implications for the pathophysiology of psychiatric disorders

Chronic administration of the atypical antipsychotic drug, clozapine, to ro dents has been shown to increase the concentration of apolipoprotein D (apo D) in several area of the brain, suggesting that apoD could be involved in the therapeutic effects of antipsychotic drugs and/or the pathology of psyc hotic illnesses. Here, we measured a significant decrease in the concentrat ion of apoD in serum samples from schizophrenic patients. In contrast, apoD levels were significantly increased (92-287%) in dorsolateral prefrontal c ortex (Brodmann's area 9) of schizophrenic and bipolar subjects. Elevated l evels of apoD expression were also observed in the caudate of schizophrenic and bipolar subjects (68-89%), No differences in apoD immunoreactivity wer e detected in occipital cortex (Brodmann's area 18) in either group, or in the hippocampus, substantia nigra, or cerebellum of the schizophrenic group . The low serum concentrations of apoD observed in these patients supports recent hypotheses involving systemic insufficiencies in lipid metabolism/si gnaling in schizophrenia. Elevation of apoD expression selectively within c entral nervous system regions implicated in the pathology of these neuropsy chiatric disorders suggests a focal compensatory response that neuroleptic drug regimens may augment.