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

Abstract

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.

Dietary Linoleic Acid Lowering Reduces Lipopolysaccharide-Induced Increase in Brain Arachidonic Acid Metabolism

“…This study demonstrates that dietary LA lowering can be used to target upregulated brain AA metabolism, which has been associated with progressive neurodegenerative disorders [1–3, 5]. Supporting this suggestion is evidence of reduced headache frequency in chronic migraine patients who reduced their LA intake from 7 to 2 % energy and increased EPA and DHA intake to 1.5 g/day for 12 weeks [64].…”

Systemic Biomarkers of Accelerated Aging in Schizophrenia: A Critical Review and Future Directions

“…Group Differences Free androgen index (FAI), an indicator of androgen activity, was significantly lower in individuals with psychosis, with a medium effect size. 77 Brain levels of BDNF did not differ between schizophrenia and HCs, 56 although other reviews suggest that BDNF is reduced in schizophrenia. 78 Age Relationships Age was negatively correlated with FAI in patients with psychosis, with a medium-to-large effect size, but not in HCs.…”

“…whereas 29% examined systemic markers in postmortem brain tissue. 22,[53][54][55][56][57][58][59][60][61][62][63] Most studies investigated a mixed-age sample of adults, 2 included only older participants. 55,58 All reviewed studies had at least one comparison group: 34 compared schizophrenia patients to a nonpsychiatric HC group; 4 involved at least one psychiatric comparison group in addition to an HC group; 32,53,61,63 one included only psychiatric comparison groups 40 ; one compared subtypes of patients with schizophrenia.…”

Prenatal exposure to ketamine in rats: Implications on animal models of schizophrenia

“…Furthermore, from a physiological standpoint, this disorder causes dysregulation of the neurotransmission systems and gradual neurodegeneration. Consequently, the symptoms normally worsen over time, with a concomitant deterioration of the mental health of patients suffering from schizophrenia (Rao et al, ). Hence, patients have their life expectancies reduced on average by 12–15 years, mainly attributed to suicide and a higher chance of developing risk routines (smoking, drinking, drug consumption, poor feeding, sedentary lifestyle) (Saha et al, ).…”