Is schizophrenia a neurodegenerative disease? Evidence from age-related decline of brain-derived neurotrophic factor in the brains of schizophrenia patients and matched nonpsychiatric controls.

BACKGROUND Brain-derived neurotrophic factor (BDNF) protein levels decline in the brain during senescence and are also shown to be reduced in schizophrenia patients. BDNF is present in both the gray and white matters of the brain. It is unclear whether BDNF abnormalities in schizophrenia are specific to gray and/or white matter. OBJECTIVE We hypothesized that the age-related BDNF decline is abnormal and contributes to the reduced BDNF in schizophrenia. METHODS We tested this hypothesis by measuring BDNF protein levels in postmortem gray and white matter, using the prefrontal cortex (PFC) and the genu of the corpus callosum as regions of interests, from 20 schizophrenia patients and 20 matched nonpsychiatric controls. Samples were selected across the adult lifespan--from 20 to 80 years of age. RESULTS PFC gray matter BDNF protein levels were significantly lower in older age in both nonpsychiatric comparisons and patients, while BDNF in white matter did not decrease significantly with age in either group. PFC BDNF was linearly lower from 20 to 80 years of age in nonpsychiatric comparisons. In schizophrenia, the age effect was similarly linear in younger patients but a decline did not occur in older patients. CONCLUSION PFC BDNF does not follow a normative linear age effect in schizophrenia patients as they grow older, which may represent a 'floor effect' due to earlier decline or a survivor cohort of older patient donors who are less susceptible to a schizophrenia-related pathological aging process.