Microtubule associated protein 2 in bipolar depression: Impact of pregnenolone

Abstract

Background: Pregnenolone, and related neurosteroids, may have antidepressant properties. Preclinical research proposes that microtubule associated protein 2 (MAP2) binding may be a mechanism for antidepressant properties of pregnenolone. Thus, MAP2 might be a novel target for antidepressant therapy. This clinical study is the first to examine serum MAP2 levels in people with bipolar depression and controls, and whether pregnenolone treatment is associated with a change in MAP2 levels.

Methods: Blood samples from a previously published clinical trial of pregnenolone for adult bipolar depression were analyzed at baseline and week 6 of treatment with pregnenolone or placebo for serum MAP2 levels using Western Blot. MAP2 levels from healthy controls were also obtained.

Results: MAP2 levels in the bipolar depressed patients (n=11) tended to be higher than in controls (n=4) (p=0.062). MAP2 levels decreased non-significantly from baseline to week 6 in placebo (n=5) and pregnenolone-treated patients (n=6). MAP2 level changes correlated positively with change in self-reported depressive symptom scores in the pregnenolone group (r=0.771, p=0.072) but not in the placebo group (r=0.000, p=1.000).

Limitations: This study, exploring relationships between MAP-2 in humans with mood disorders, is limited by the small sample size. Thus, the findings must be viewed with great caution.

Conclusion: These findings suggest possible differences in serum MAP-2 levels between bipolar depressed persons and controls and a relationship between changes in depressive symptoms and MAP-2 levels during pregnenolone therapy. Findings suggest additional research is needed on MAP-2 in mood disorders.

Keywords: Bipolar disorder; Depression; Microtubule associated protein 2; Pregnenolone.