Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response.
Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under- or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in antidepressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-α receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.
a Department of Biomedical and Neuromotor Sciences , University of Bologna , Bologna , Italy.
Chiara
C
Fabbri
b Department of Psychiatrics , Charles University, Faculty of Medicine and University Hospital, Hradec Králové , Czech Republic.
Ladislav
L
Hosak
c Department of Psychiatry and Psychotherapy , University of Tübingen , Tübingen , Germany.
Rainald
R
Mössner
d Department of Psychiatry, Psychotherapy and Psychosomatics , Martin Luther University of Halle-Wittenberg , Halle , Germany.
Ina
I
Giegling
a Department of Biomedical and Neuromotor Sciences , University of Bologna , Bologna , Italy.
Laura
L
Mandelli
e Fondation Fondamental, Créteil, France AP-HP , GH Saint-Louis-Lariboisière-Fernand-Widal, Pôle Neurosciences , Paris , France.
Frank
F
Bellivier
f GRASP-Research Group, Department of Neuroscience , University of Leuven , Leuven , Belgium.
Stephan
S
Claes
g Social, Genetic and Developmental Psychiatry Centre , Institute of Psychiatry, King's College London , London , UK.
David A
DA
Collier
h National University (UNT) Argentina, Argentinean Association of Biological Psychiatry , Buenos Aires , Argentina.
Alejo
A
Corrales
i VA Boston Health Care System , Brockton , MA , USA.
Lynn E
LE
Delisi
j Departamento de Ciencias Celulares y Moleculares, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía , Universidad Peruana Cayetano Heredia , Lima , Peru.
Carla
C
Gallo
k Neuropsychiatric Genetics Research Group, Department of Psychiatry , Trinity College Dublin , Dublin , Ireland.
Michael
M
Gill
l Neurogenetics Section, Centre for Addiction and Mental Health , Toronto , Ontario , Canada.
James L
JL
Kennedy
m Faculté de Médecine , Université Paris-Est Créteil, Inserm U955, Equipe Psychiatrie Translationnelle , Créteil , France.
Marion
M
Leboyer
l Neurogenetics Section, Centre for Addiction and Mental Health , Toronto , Ontario , Canada.
Amanda
A
Lisoway
n Department of Psychiatry , University of Bonn , Bonn , Germany.
Wolfgang
W
Maier
o Director of ADINEU (Asistencia, Docencia e Investigación en Neurociencia) , Buenos Aires , Argentina.
Miguel
M
Marquez
p UNI - ULB Neurosciences Institute, ULB , Bruxelles , Belgium.
Isabelle
I
Massat
q Department P , Aarhus University Hospital , Risskov , Denmark.
Ole
O
Mors
r UCB Biopharma , Belgium.
Pierandrea
P
Muglia
s Institute of Human Genetics , University of Bonn , Bonn , Germany.
Markus M
MM
Nöthen
t MRC Centre for Neuropsychiatric Genetics and Genomics , Institute of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University , Cardiff , UK.
Michael C
MC
O'Donovan
u Grupo de Investigación en Psiquiatría, Departamento de Psiquiatría, Facultad de Medicina , Universidad de Antioquia , Medellín , Colombia.
Jorge
J
Ospina-Duque
v University of Bonn , Germany.
Peter
P
Propping
w Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education , Shanghai Jiao Tong University , Shanghai , China.
Yongyong
Y
Shi
x University of Aberdeen, Institute of Medical Sciences , Aberdeen , UK.
David
D
St Clair
y University Hospital Cochin (Site Tarnier), University Sorbonne Paris Cité (Faculty of Medicine Paris Descartes), INSERM U 894 Centre Psychiatry and Neurosciences , Paris , France.
Florence
F
Thibaut
z Division of Medical Genetics, Department of Biomedicine , University of Basel , Basel , Switzerland.
Sven
S
Cichon
aa Laboratoire de Psychologie Medicale, Centre Européen de Psychologie Medicale , Université Libre de Bruxelles and Psy Pluriel , Brussels , Belgium.
Julien
J
Mendlewicz
d Department of Psychiatry, Psychotherapy and Psychosomatics , Martin Luther University of Halle-Wittenberg , Halle , Germany.
Dan
D
Rujescu
a Department of Biomedical and Neuromotor Sciences , University of Bologna , Bologna , Italy.
Alessandro
A
Serretti
D000928:Antidepressive Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics*; D044127:Epigenesis, Genetic; D005819:Genetic Markers; D006801:Humans; D009473:Neuronal Plasticity; D016032:Randomized Controlled Trials as Topic; D059467:Transcriptome
D000928:Antidepressive Agents; D005819:Genetic Markers
Major depression; antidepressant; genetics-epigenetics; transcriptomics-proteomics