Various neuropathological findings have been reported in bipolar disorder (BD). However, it is unclear which findings are well established. To address this gap, we carried out a systematic review of the literature. We searched over 5000 publications, identifying 103 data papers, of which 81 were eligible for inclusion. Our main findings can be summarised as follows. First, most studies have relied on a limited number of brain collections, and have used relatively small sample sizes (averaging 12 BD cases and 15 controls). Second, surprisingly few studies have attempted to replicate closely a previous one, precluding substantial meta-analyses, such that the latter were all limited to two studies each, and comprising 16-36 BD cases and 16-74 controls. As such, no neuropathological findings can be considered to have been established beyond reasonable doubt. Nevertheless, there are several replicated positive findings in BD, including decreased cortical thickness and glial density in subgenual anterior cingulate cortex, reduced neuronal density in some amygdalar nuclei, and decreased calbindin-positive neuron density in prefrontal cortex. Many other positive findings have also been reported, but with limited or contradictory evidence. As an important negative result, it can be concluded that gliosis is not a feature of BD; neither is there neuropathological evidence for an inflammatory process.

Background: Antihypertensive drugs, especially calcium channel blockers, have been associated with differential rates of a number of neuropsychiatric outcomes. Delirium is commonly attributed to medication, including antihypertensive drugs, but delirium incidence has not been compared directly between antihypertensive drug classes. Methods: Using a federated electronic health records network of 25.5 million people aged 50 years or older, we measured rates of delirium over a two-year period in patients prescribed calcium channel blockers compared to the other main antihypertensive drug classes. Extensive propensity score matching was used to create cohorts matched for a range of demographic factors and delirium risk factors. Negative control outcomes were also measured. Results: Cohort sizes ranged from 54,000–577,000. Delirium was more common with calcium channel blockers than with renin-angiotensin system agents (~40% higher) but less common than with beta-blockers (~20% lower). These differences remained when patients with a range of other delirium risk factors were excluded, and they were not paralleled by the negative control outcomes. Comparisons between calcium channel blockers and diuretics produced inconclusive results. Conclusions: Calcium channel blockers are associated with higher rates of delirium than renin-angiotensin system agents, but lower rates compared to beta-blockers. The findings add to the list of factors which may be considered when choosing antihypertensive drug class.