Maria Giese1, Johannes Beck2, Serge Brand2, Flavio Muheim2, Ulrich Hemmeter3, Martin Hatzinger4, Edith Holsboer-Trachsler2, Anne Eckert5. 1. Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric Clinics of the University of Basel, Basel, Switzerland; Transfacultary Research Platform, Molecular & Cognitive Neuroscience, University of Basel, Basel, Switzerland. 2. Center for Affective, Stress and Sleep Disorders, Psychiatric Hospital of the University of Basel, Basel, Switzerland. 3. Psychiatric Service Center St. Gallen, Wil, Switzerland. 4. Psychiatric Services Solothurn, Department of Adult Psychiatry, Solothurn, Switzerland. 5. Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric Clinics of the University of Basel, Basel, Switzerland; Transfacultary Research Platform, Molecular & Cognitive Neuroscience, University of Basel, Basel, Switzerland. Electronic address: Anne.Eckert@upkbs.ch.
Abstract
OBJECTIVE: Preclinical and clinical studies support a role for brain-derived neurotrophic factor (BDNF) in the pathophysiology of stress-related mood disorders. Furthermore, BDNF seems to be linked to antidepressant action. Available pharmacological treatments for depression are characterized by significant limitations with low efficacy and a major delay until treatment response. This demonstrates the urgent need for more efficient and fast-acting antidepressants. Besides ketamine, sleep deprivation (SD) as well as partial sleep deprivation (PSD) are effective and fast-acting antidepressant methods. However, the underlying molecular mechanisms of SD are not well understood; especially possible mechanisms explaining the rapid, but transient antidepressant effect of SD are unknown. METHODS: We evaluated serum BDNF from 28 patients suffering from major depressive disorder (MDD), who were naïve to SD therapy at seven different time points within a 32 h time window before (day 0) and after PSD (day 1). PSD-response was assessed by 6-Items of the Hamilton Depression Rating Scale (HDRS) before (day 0) and at follow-up after 2 weeks (FU2). RESULTS: PSD induced a very fast increase in BDNF serum levels at day 1 which parallels clinical findings, since levels increased with decreasing depression scores in all participants. Notably, responders showed a significant diurnal BDNF serum variation not only after PSD but already before PSD treatment, while diurnal profile of serum BDNF from non-responders did not vary. CONCLUSIONS: The elasticity in diurnal serum BDNF variation is associated with favourable treatment response to PSD in patients suffering from MDD. Therefore, a normalized BDNF serum profile which oscillates in a circadian fashion seems to precede, rather than follow a favourable treatment outcome in depressed patients. Furthermore the fast increase of BDNF is comparable to effects seen with ketamine infusion.
OBJECTIVE: Preclinical and clinical studies support a role for brain-derived neurotrophic factor (BDNF) in the pathophysiology of stress-related mood disorders. Furthermore, BDNF seems to be linked to antidepressant action. Available pharmacological treatments for depression are characterized by significant limitations with low efficacy and a major delay until treatment response. This demonstrates the urgent need for more efficient and fast-acting antidepressants. Besides ketamine, sleep deprivation (SD) as well as partial sleep deprivation (PSD) are effective and fast-acting antidepressant methods. However, the underlying molecular mechanisms of SD are not well understood; especially possible mechanisms explaining the rapid, but transient antidepressant effect of SD are unknown. METHODS: We evaluated serum BDNF from 28 patients suffering from major depressive disorder (MDD), who were naïve to SD therapy at seven different time points within a 32 h time window before (day 0) and after PSD (day 1). PSD-response was assessed by 6-Items of the Hamilton Depression Rating Scale (HDRS) before (day 0) and at follow-up after 2 weeks (FU2). RESULTS: PSD induced a very fast increase in BDNF serum levels at day 1 which parallels clinical findings, since levels increased with decreasing depression scores in all participants. Notably, responders showed a significant diurnal BDNF serum variation not only after PSD but already before PSD treatment, while diurnal profile of serum BDNF from non-responders did not vary. CONCLUSIONS: The elasticity in diurnal serum BDNF variation is associated with favourable treatment response to PSD in patients suffering from MDD. Therefore, a normalized BDNF serum profile which oscillates in a circadian fashion seems to precede, rather than follow a favourable treatment outcome in depressedpatients. Furthermore the fast increase of BDNF is comparable to effects seen with ketamine infusion.
Authors: Jeanelle Portelli; Mehdi Farokhnia; Sara L Deschaine; Jillian T Battista; Mary R Lee; Xiaobai Li; Dorit Ron; Lorenzo Leggio Journal: Alcohol Date: 2020-08-13 Impact factor: 2.405
Authors: Brenda Cartmel; Meghan Hughes; Elizabeth A Ercolano; Linda Gottlieb; Fangyong Li; Yang Zhou; Maura Harrigan; Jennifer A Ligibel; Vivian E von Gruenigen; Radhika Gogoi; Peter E Schwartz; Harvey A Risch; Lingeng Lu; Melinda L Irwin Journal: Gynecol Oncol Date: 2021-03-26 Impact factor: 5.482