The relationship of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate cortex of bipolar disorder subjects: A post-mortem study.

Increased levels of inflammation markers have been found in the peripheral tissue of individuals with bipolar disorder (BD), especially during mood episodes. Previous studies found distinctive inflammatory profiles across different brain regions, but potential associations with clinical symptoms are still lacking. This study aims to evaluate the association of neuropsychiatric symptoms with inflammatory markers in the hippocampus and cingulate of individuals with BD. Levels of IL-1ß, IL-6, IL-17A, cortisol, and C-reactive protein (CRP) were measured in the hippocampus and anterior cingulate of 14 BD individuals and their non-psychiatric controls. Neuropsychiatric symptoms present in the three months before death were assessed using the Neuropsychiatric Inventory (NPI). In the BD group, greater NPI scores were associated with higher IL-6 in the hippocampus (p = 0.011) and cingulate (p = 0.038) and higher IL-1ß (p = 0.039) in the hippocampus. After adjusting for age, sex and CDR, IL-1ß and IL-6 were still associated with higher NPI in the hippocampus. In correlation analysis considering both BD and their controls, moderate positive associations were found between NPI and IL-6 and cortisol in the hippocampus (p < 0.001 and p = 0.006) and cingulate (p = 0.024 and p = 0.016), IL-1ß (p < 0.001) and IL-17A in the hippocampus (p = 0.002). No difference in inflammatory markers was found according to type of psychotropic medication used. Hence, in individuals with BD, neuropsychiatric symptoms were differently associated with specific inflammatory cytokines and CRP in the hippocampus and cingulate. These results suggest that the neuroinflammatory changes occurring in BD may be more complex than previously expected and could be associated with clinical manifestations.

Gene expression alterations in the postmortem hippocampus from older patients with bipolar disorder - A hypothesis generating study.

Bipolar disorder (BD) presents with a progressive course in a subset of patients. However, our knowledge of molecular changes in older BD is limited. In this study, we examined gene expression changes in the hippocampus of BD from the Biobank of Aging Studies to identify genes of interest that warrant further exploration. RNA was extracted from the hippocampus from 11 subjects with BD and 11 age and sex-matched controls. Gene expression data was generated using the SurePrint G3 Human Gene Expression v3 microarray. Rank feature selection was performed to identify a subset of features that can optimally differentiate BD and controls. Genes ranked in the top 0.1% with log2 fold change >1.2 were identified as genes of interest. Average age of the subjects was 64 years old; duration of disease was 21 years and 82% were female. Twenty-five genes were identified, of which all but one was downregulated in BD. Of these, CNTNAP4, MAP4, SLC4A1, COBL, and NEURL4 had been associated with BD and other psychiatric conditions in previous studies. We believe our findings have identified promising targets to inform future studies aiming to understand the pathophysiology of BD in later life.

Cause of Death Determined by Full-body Autopsy in Neuropathologically Diagnosed Dementias: The Biobank for Aging Studies of the University of Sao Paulo (BAS-USP), Brazil.

OBJECTIVE: This study aimed to compare causes of death in the most prevalent neuropathologically diagnosed dementias. METHODS: We analyzed causes of death in a community-based cohort of participants aged 50 or older, submitted to full-body autopsy and a comprehensive neuropathologic examination of the brain. Individuals with Alzheimer disease (AD), vascular dementia (VaD), mixed dementia (AD+VaD), or dementia with Lewy bodies (DLBs) were compared with individuals with no dementia. RESULTS: In a sample of 920 individuals, 456 had no dementia, 147 had AD, 120 had VaD, 53 had DLB, and 37 had AD+VaD. Pneumonia as the cause of death was more frequent in the AD (P=0.023), AD+VaD (P=0.046), and DLB (P=0.043) groups. In addition, VaD (P=0.041) and AD+VaD (P=0.028) groups had a higher frequency of atherosclerosis as detected by full-body autopsy. CONCLUSION: Our findings highlight the importance of preventive measures regarding atherosclerosis and pneumonia in patients with dementia. Moreover, because of cognitive impairment, these patients may not fully account for symptoms to make early detection and diagnosis possible. These results confirm findings from previous studies that were based on clinical data, with added accuracy provided by neuropathologic diagnosis and full-body autopsy reports.