Cortisol and white matter integrity relationship disrupted in bipolar disorder

By Lucy Piper, Senior medwireNews Reporter

Researchers have found evidence in support of hypercortisol-induced glial dysfunction affecting periventricular white matter integrity in patients with bipolar disorder.

Among mentally healthy individuals participating in the study, there was an inverse relationship between evening cortisol levels and periventricular white matter integrity, as measured using fractional anisotropy; however, this relationship was disrupted in patients with bipolar disorder.

Possible explanations for this finding include periventricular osmoregulatory dysfunction, the researchers comment, or the effects of lithium therapy or past substance misuse.

"In the current analysis, there were signals that periventricular MD [mean diffusivity] correlated with evening salivary cortisol levels in the small sub-group of patients not on lithium and those with no history of substance misuse," the team notes in the Journal of Affective Disorders.

Karine Macritchie, from Imperial College London in the UK, and colleagues carried out diffusion tensor magnetic resonance imaging on 23 mentally healthy individuals and 25 euthymic patients with bipolar disorder to obtain fractional anisotropy and mean diffusivity data for regions of white matter.

Hyperintensities were observed in deep white matter in 11 of the mentally healthy individuals and 12 of the bipolar disorder patients, while periventricular hyperintensities were seen in a respective six and 10 individuals.

Mean diffusivity was increased in all frontal and periventricular regions in patients with bipolar disorder compared with mentally healthy individuals, whereas there were no significant differences in fractional anisotropy.

Participants with and without bipolar disorder had similar salivary cortisol levels, at respective averages of 12.3 and 10.9 nmol/L in the morning and 1.6 and 1.9 nmol/L in the evening.

The researchers report that there were very few partial correlations between fractional anisotropy and mean diffusivity and cortisol levels, but in healthy individuals mean evening cortisol levels correlated negatively and significantly with fractional anisotropy in all periventricular regions.

By contrast, evening cortisol levels did not correlate significantly with periventricular fractional anisotropy in patients with bipolar disorder.

There were no correlations between cortisol levels and periventricular mean diffusivity in either group.

"Increased MD in the anterior periventricular white matter in the bipolar group is consistent with an excess of extracellular fluid in this region," say Macritchie et al. "This excess fluid may disrupt the relationship between FA [fractional anisotropy] and evening SCLs [salivary cortisol levels], previously observed in the control group."

They call for further investigation of the effects of cortisol, lithium, and substance misuse on oligodendrocyte function and brain osmoregulation.

"These factors may be key influences on the aetiology of periventricular osmoregulatory and structural abnormalities in bipolar disorder," the team concludes.

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