Reductions in cholesterol and synaptic markers in association cortex in mood disorders

Objectives: Cholesterol forms an integral part of cell membranes and is a major component of myelin. Furthermore, cholesterol also plays a vital role in the development, function and stability of synapses. While low serum cholesterol has previously been associated with mood disorders, cholesterol levels have yet to be quantified within the brain in these disorders. The aim of this study was to quantify sterol levels in the brains of patients with major psychiatric disorders and further to relate these levels to markers of myelin and synapses. Methods: Samples of visual association cortex were obtained postmortem from subjects with bipolar disorder (BPD), major depressive disorder (MDD) and schizophrenia (SCZ) and from controls (all n = 15). Concentrations of brain cholesterol, its precursors lathosterol, desmosterol and lanosterol and its metabolite 24S-hydroxycholesterol were determined by gas-liquid chromatography. Immunoreactivity for myelin basic protein (MBP), synaptophysin and VAMP was quantified by enzyme-linked immunosorbent assay. Results: Cholesterol levels were 13% lower in MDD (p = 0.018) and 10% lower in BPD (p = 0.052) compared with controls. Cholesterol precursor or metabolite concentrations did not differ between groups. Synaptophysin immunoreactivity was 20% lower in BPD (p = 0.025) and VAMP immunoreactivity 37% lower in MDD (p = 0.032) and 45% lower in BPD (p = 0.009). MBP immunoreactivity was not altered in any disorder. Conclusions: Our data suggest that lower brain cholesterol levels and a reduction in synapses may be features of mood disorders.