How can drug discovery for psychiatric disorders be improved? (original) (raw)

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Author notes

  1. Emmanuel Canet: IDRS, 11 Rue des Moulineaux, 92150 Suresnes, France.
  2. Graham Collingridge: Department of Anatomy, Medical School, University of Bristol, University Walk, Bristol, BS8 1TD, UK.
  3. André Delacourte: 75 Rue Gambetta, 59045 Falmes Thumesnil, France.
  4. Ray Dolan: Wellcome Department of Imaging Neuroscience, Institute of Neurology, 12 Queen Square, London, WC1N 3BG, UK.
  5. Philippe Fossati: Service de Psychiatrie d'Adultes, Hôpital Pitié Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.
  6. Therese Jay: INSERM E0117, 2 Ter Rue d'Alésia, 75014 Paris, France.
  7. Jean-Pierre Lepine: Hôpital Fernand Widal, Psychiatrie Adultes (CS), 200 Faubourg St Denis, 75475 Paris Cedex 10, France.
  8. Pierre Lestage: IDRS, 11 Rue des Moulineaux, 92150 Suresnes, France.
  9. Bernard Marchand: IRIS, 6 Place des Pléiades, 92415 Courbevoie, France.
  10. Mark J. Millan: IDRS, 11 Rue des Moulineaux, 92150 Suresnes, France.
  11. Laurent Perret: IRIS, 6 Place des Pléiades, 92415 Courbevoie, France.
  12. Léon Tremblay: Neurologie et Thérapeutique expérimentale, INSERM U 289, Hôpital Pitié Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.
  13. Stéphane Vandenabeele: IDRS, 11 Rue des Moulineaux, 92150 Suresnes, France.

Authors and Affiliations

  1. Yves Agid: Physiologie and Pathogénie des Maladies Neurodégénératives, INSERM U 289, Hôpital Salpêtrière, 47 Boulevard de l'Hôpital, 75651 Paris Cedex 13, France.,
    Yves Agid
  2. György Buzsáki: Center for Molecular and Behavioural Neuroscience, Rutgers University, 197 University Avenue, Newark, New Jersey 07102, USA.,
    György Buzsáki
  3. David M. Diamond: Medical Research Division, Departments of Psychology and Pharmacology, Veterans Hospital and University of South Florida, 4202 East Fowler Avenue (PCD 4118G) Tampa, Florida 33620-8200, USA.,
    David M. Diamond
  4. Richard Frackowiak: Wellcome Department of Imaging Neuroscience, Institute of Neurology, 12 Queen Square, London, WC1N 3BG, UK.,
    Richard Frackowiak
  5. Jay Giedd: Department of Health and Human Services, National Institute of Mental Health, National Institutes of Health (NIMH/NIH), Room 4C110, 10 Center Drive, MSC 1367, Bethesda, Maryland 20892, USA.,
    Jay Giedd
  6. Jean-Antoine Girault: INSERM U 536, Institut du Fer à Moulin, 17 Rue du Fer à Moulin, 75005 Paris, France.,
    Jean-Antoine Girault
  7. Department of Neuroscience, Anthony Grace: University of Pittsburgh, 458 Crawford Hall, Pittsburgh, Pennsylvania 15260, USA.,
    Anthony Grace
  8. Division of Pathology and Neuroscience, Jeremy J. Lambert: Neurosciences Institute, University of Dundee, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK.,
    Jeremy J. Lambert
  9. Husseini Manji: Mood and Anxiety Disorders Program, DIRP/NIMH/NIH, Building 15K, Room 102, 15K Northdrive Bethesda, Maryland 20892 2670, USA.,
    Husseini Manji
  10. Helen Mayberg: Emory University School of Medicine, 101 Woodruff Circle, WMB 4-313, Atlanta, Georgia 30322, USA.,
    Helen Mayberg
  11. Center of Neuropharmacology-Department of Pharmacological Sciences, Maurizio Popoli: University of Milan, Via Balzaretti 9, 20133 Milano, Italy.,
    Maurizio Popoli
  12. Alain Prochiantz: Ecole Normale Supérieure, CNRS UMR 8542, 46 Rue d'Ulm, Paris 75005, France.,
    Alain Prochiantz
  13. Gal Richter-Levin: Brain and Behaviour Research Center, University of Haifa, Haifa 31905, Israel.,
    Gal Richter-Levin
  14. Department of Pharmacology, Peter Somogyi: MRC Anatomical Neuropharmacology Unit, University of Oxford, Mansfield Road, Oxford, OX1 3TH, UK.,
    Peter Somogyi
  15. Michael Spedding: IDRS, 11 Rue des Moulineaux, 92150 Suresnes, France.,
    Michael Spedding
  16. Per Svenningsson: Karolinska Institute, Section of Molecular Neuropharmacology, Nanna Svartz Väg 2-4, 171 77 Stockholm, Sweden.,
    Per Svenningsson
  17. Daniel Weinberger: Clinical Brain Disorder Branch, NIH/NIMH 900 Rockville Pike, Building 10, Room 4S237B, Bethesda, Maryland 20892, USA.,
    Daniel Weinberger

Authors

  1. Yves Agid
  2. György Buzsáki
  3. David M. Diamond
  4. Richard Frackowiak
  5. Jay Giedd
  6. Jean-Antoine Girault
  7. Anthony Grace
  8. Jeremy J. Lambert
  9. Husseini Manji
  10. Helen Mayberg
  11. Maurizio Popoli
  12. Alain Prochiantz
  13. Gal Richter-Levin
  14. Peter Somogyi
  15. Michael Spedding
  16. Per Svenningsson
  17. Daniel Weinberger

Corresponding author

Correspondence toMichael Spedding.

Ethics declarations

Competing interests

David Diamond has received funding from Institute de Recherches Servier. Helen Mayberg is a consultant for Advanced Neuromodulation System (ANS), has intellectual property licensed to ANS, and has served on the scientific advisory committee for Cyberonics. Michael Spedding is deputy director of research at Institute de Recherches Servier.

Supplementary information

Glossary

Deep brain stimulation

Continuous therapeutic electric stimulation of subcortical areas at high frequencies (130 Hz) using chronically implanted electrodes.

Neuronal plasticity

The capacity of the nervous system to modify its organization. Such changes can occur as a consequence of many events, including the normal development and maturation of the organism, the acquisition of new skills ('learning') in immature and mature organisms, and after damage to the nervous system.

Long-term potentiation (LTP)

The prolonged strengthening of synaptic communication, which is induced by patterned input and is thought to be involved in learning and memory formation.

Long-term depression (LTD)

An enduring weakening of synaptic strength that is thought to interact with long-term potentiation (LTP) in the cellular mechanisms of learning and memory in structures such as the hippocampus and cerebellum. Unlike LTP, which is produced by brief high-frequency stimulation, LTD can be produced by long-term, low-frequency stimulation.

T1- weighted structural brain scans

MRI scans can be acquired with various types of contrast. T1-weighted images are weighted according to the so-called spin-lattice relaxation time (T1) of the protons that give rise to the MRI signals; such images provide good contrast between grey and white matter.

Transcranial magnetic stimulation (TMS)

A technique that is used to induce a transient interruption of normal activity in a relatively restricted area of the brain. It is based on the generation of a strong magnetic field near the area of interest, which, if changed rapidly enough, will induce an electric field that is sufficient to stimulate neurons

Vagus nerve stimulation

Vagus nerve stimulation uses a commercially available device for treating both refractory seizure disorders and treatment-resistant depression. The procedure involves the surgical implantation of a small pacemaker-like device into the left chest wall with a wire running under the skin leading to coils wrapped around the left vagus nerve. The device delivers continual electrical pulses, in 30 seconds-on and

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Agid, Y., Buzsáki, G., Diamond, D. et al. How can drug discovery for psychiatric disorders be improved?.Nat Rev Drug Discov 6, 189–201 (2007). https://doi.org/10.1038/nrd2217

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