"Neuropsychiatric disorders and suicidal behaviour represent major contributions to mortality in Canada. Among the many factors associated with psychiatric disorders and suicide, alterations in lipids and cholesterol have been demonstrated both peripherally and centrally, supporting their roles as mediating variables in the underlying neuropathology. Cholesterol (CHL) regulation is a complex and dynamic system, and while animal studies also support a mediating role of CHL on brain function, efforts to determine a biological association in humans have achieved only modest gains. While mechanisms governing cholesterol regulation are not entirely understood, cholesterol is well accepted to have important impacts on a variety of brain functions from neurotransmission to synaptic plasticity and neurodegeneration, with unique contributions from neurons, astrocytes, and oligodendrocytes. Given the extensive regulatory feedback mechanisms and the implications in neurological function, determining a biological basis for the association of cholesterol with neuropsychiatric disorders remains an important area of research. This research aimed to explore the neurobiological mechanism whereby alterations in CHL may relate to neuropsychiatric phenotypes. The results presented in chapter 3 suggest, while no clear differences were found in suicide completers with major depressive disorder, expression of several CHL related genes associate more strongly with white matter CHL levels compared to grey matter, suggesting a potential contribution of SORT1, LPL, and ABCA2, in the regulation of white matter CHL. The results of chapter 4 suggest altered phospholipid levels and expression of lysosomal acid lipase A gene in violent suicides in the prefrontal cortex, which would have important consequences for inhibitory neurotransmission. The results of chapter 4 suggest an increase in 24-hydroxycholesterol in the prefrontal cortex of suicide completers and this could have implications for synapse maintenance and loss in the neuropathology of suicide. In regards to CHL levels, however, little evidence in support of alterations in CNS CHL in neuropsychiatric disorders and suicidal behaviour was noted." --