Brain-derived Neurotrophic Factor and Mood in Perimenopausal Depression

Jessica Harder, MD
Department of Psychiatry
Division of Neuropsychiatry
Poster Overview

Objectives: Assess whether molecules including brain-derived neurotrophic factor (BDNF) and cytokines (that cause inflammation) are associated with mood symptoms in different parts of the menstrual cycle in menopause-associated depression. Studies have found that inflammatory molecules affect mood. In regular depression, BDNF is low. With premenstrual mood symptoms, however, BDNF is higher when mood is better.

Methods: BDNF, cytokines, hormones, and mood were assessed at mid-cycle (before ovulation) and peri-menstrually (around menstruation) for 20 menstrual cycles at 49 time points. 14 perimenopausal women ages 38-52 with menstrual cycles 24-35 days long and normal ovulation participated. The study assessed impact of individual participant, molecules, cycle selected, and part of cycle on mood, irritability, and psychological distress as measured by Montgomery-├ůsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI), Kellner Symptom Questionnaire Anger-Hostility subscale (SQ), Profile of Mood States (POMS).

Results: Higher BDNF levels were associated with worse mood on MADRS (=0.00053; p=0.0004), POMS (=0.00153; p=0.0225), SQ (=0.00053; p=0.0019), BDI (=0.00039; p=0.0099). Time point in cycle (mid-cycle versus peri-menstruation) did not affect this relationship.

Conclusion: In menopause-associated depression, as with premenstrual mood symptoms, higher BDNF is associated with worse mood. This pattern suggests that hormonally-sensitive mood disorders are distinct from regular depression.

Scientific Abstract

Objectives: Evaluate whether brain-derived neurotrophic factor (BDNF) and inflammatory cytokines predict mood symptoms across the menstrual cycle in perimenopausal depression. Previous work implicates inflammatory biomarkers in mood disturbance and found low BDNF in major depression, whereas in premenstrual dysphoria, BDNF is higher when mood is worse. Perimenopausal depression has not been studied.

Methods: 20 menstrual cycles were assessed during mid-to-late follicular phase and peri-menstrually for mood, BDNF, cytokines, estradiol, and progesterone (n=49 time points). Subjects were 14 perimenopausal women ages 38-52 with ovulatory menstrual cycles 24-35 days long. Depression was assessed with Montgomery-├ůsberg Depression Rating Scale (MADRS), Beck Depression Inventory (BDI); irritability with Kellner Symptom Questionnaire Anger-Hostility subscale (SQ); psychological distress with Profile of Mood States (POMS). Mixed models were run for dependent variables MADRS, BDI, POMS, SQ, with independent variables biomarkers, cycle phase, cycle number, and participant.

Results: BDNF showed significant positive relationships to MADRS (=0.00053; p=0.0004), POMS (=0.00153; p=0.0225), SQ (=0.00053; p=0.0019), BDI (=0.00039; p=0.0099). Cycle phase had no effect. No other biomarker consistently predicted mood.

Conclusion: In hormonally-sensitive perimenopausal depression, higher BDNF is associated with worse mood, resembling the pattern in premenstrual dysphoria and suggesting that hormonally-sensitive mood disorder biomarker profiles differ from that of major depression.

Clinical Implications
Hormonally-sensitive perimenopausal depression shows a pattern of higher BDNF levels associated with worse mood, a biomarker profile similar to premenstrual dysphoria and distinct from major depression. Effective treatments for hormonally-sensitive depression may also diverge from those for major depression.
Research Areas
Authors
Jessica Harder, MD, Raina Fichorova, MD, PhD, Akanksha Srivastava, BA, Aleta Wiley, MPH, Joseph J. Locascio, PhD, Hadine Joffe, MD MSc
Principal Investigator
Hadine Joffe

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