Serum BDNF as a peripheral biomarker of treatment-resistant depression and the rapid antidepressant response: A comparison of ketamine and ECT.
BACKGROUND
Ketamine is associated with rapid antidepressant efficacy but the biological mechanisms underpinning this effect are unclear. Serum brain-derived neurotrophic factor (sBDNF) is a potential circulating biomarker of treatment-resistant depression (TRD) and ketamine response but it is unclear if this is a common target of both ketamine and electroconvulsive therapy (ECT), the current gold standard for TRD. Moreover, the impact of multiple ketamine infusions on sBDNF has not yet been established.


METHODS
Thirty five TRD patients with a current DSM-IV diagnosis of recurrent depressive disorder received up to 12 ECT sessions (N=17) or up to three intravenous infusions of low-dose (0.5mg/kg) ketamine (N=18). Blood samples were taken over the course of the study for assessment of sBDNF. Symptom severity and response were monitored using the 17-item Hamilton Depression Rating Scale (HDRS). sBDNF was assessed in 20 healthy controls to allow comparison with TRD patients.


RESULTS
As expected, sBDNF was lower in TRD patients at baseline compared to healthy controls. Ketamine and ECT treatment were both associated with significant reductions in depressive symptoms. However, sBDNF was significantly elevated only at one week following the first ketamine infusion in those classified as responders one week later. sBDNF was not elevated following subsequent infusions. ECT reduced depressive symptoms, as expected, but was not associated with an enhancement in BDNF.


CONCLUSIONS
Patients continued with their psychotropic medications throughout this trial.


CONCLUSIONS
SBDNF normalisation does not appear to be a prerequisite for symptomatic improvement in TRD following ketamine or ECT treatment.
Department of Psychiatry, University College Cork, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
A P
AP
Allen
Department of Psychiatry, University College Cork, Cork, Ireland.
M
M
Naughton
Department of Anaesthesia and Intensive Care Medicine, University College Cork, Cork, Ireland.
J
J
Dowling
Department of Anaesthesia and Intensive Care Medicine, University College Cork, Cork, Ireland.
A
A
Walsh
Department of Psychiatry, University College Cork, Cork, Ireland.
F
F
Ismail
Department of Anaesthesia and Intensive Care Medicine, University College Cork, Cork, Ireland.
G
G
Shorten
Department of Psychiatry, University College Cork, Cork, Ireland.
L
L
Scott
St. Patrick's University Hospital, Dublin 8, Ireland; Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland.
D M
DM
McLoughlin
Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
J F
JF
Cryan
Department of Psychiatry, University College Cork, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Electronic address: t.dinan@ucc.ie.
T G
TG
Dinan
Department of Psychiatry, University College Cork, Cork, Ireland; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
G
G
Clarke
D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage; D015415:Biomarkers / Q000097:blood; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D016022:Case-Control Studies; D061218:Depressive Disorder, Treatment-Resistant / Q000097:blood / Q000628:therapy*; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004565:Electroconvulsive Therapy / Q000379:methods*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D016896:Treatment Outcome
D000928:Antidepressive Agents; D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; C579455:BDNF protein, human
Biomarker; Brain-derived neurotrophic factor; ECT; Ketamine; Treatment-resistant depression