Last updated: 27-NOV-2008
Welcome to the GENDEP RESULTS page. Please follow the links below to jump to specific GENDEP RESULTS topics.
The Genome-based Therapeutic Drugs for Depression (GENDEP) research project has aimed to find a way to use information about patients genes to help doctors decide which antidepressant treatment will work best with the least side-effects. This 4.5 year project, involving scientists, clinicians, and industrial partners from ten countries* has been led by researchers at the UK Medical Research Councils (MRC) Social, Genetic, and Developmental Psychiatry Centre (SGDP) at the Institute of Psychiatry, Kings College London.
One in five people at some point in their lives suffer from an episode of depression severe enough to warrant antidepressant treatment. Although, currently there is plenty of evidence for efficacy of antidepressants, a substantial minority of patients show an unsatisfactory response to medication, and cessation of taking prescriptions is common because of adverse side-effects. At present doctors do not have enough information to know how well patients will respond to one antidepressant over another. The choice of what drug to prescribe for optimal response with minimum unwanted effects is largely a matter of taking an educated guess. It was hoped that the Genome-Based Therapeutic Drugs for Depression (GENDEP) project would lead to the development of a genetic test to assist doctors in choosing the right antidepressants for their patients and that it would advance understanding of the biological mechanisms responsible for an antidepressant being effective, which is important for the development of new and better treatments for depression.
GENDEP had three closely interconnected major themes aimed to address these issues. The first was a large-scale multi-centre human pharmacogenomics study focused on the prediction of therapeutic response to antidepressants and adverse effects. The second was a set of basic science studies using animal models and in vitro experiments, and the third was a programme of work to address the relevant ethical, social, and legal issues. This project was to culminate in an integrative analysis of the results of the transcriptomics and proteomics on the samples from the human, the rodent, and the in vitro studies, in order to identify biomarkers consistently identified across all of these experimental methodologies.
In the patient based part of the project, patients with depression were randomly assigned to one of two antidepressant treatments (escitalopram or nortriptyline), which represent the two major mechanisms of action of all antidepressants currently on the market, with an option to change to the other drug. Their clinical progress, and the development of any side-effects, was monitored during a 6 month follow-up period. Analysis was undertaken to compare how the patients responded to their assigned treatment, with information about their genetic make-up being determined by taking a blood sample. This identified particular genetic markers associated with good and bad responses to treatment. It is hoped that through further integrative analysis and biomarker validation, that genomics-based diagnostics assay will be developed, which will enhance the ability of clinicians to predict which treatments are likely to be most effective and best tolerated for a given individual.
In the basic science studies, research was conducted using cells grown in the laboratory and rodent models to find out more about how antidepressants work at the cellular level and how they affect the nervous system. Data from these areas of work has led to the addition of candidate genes into the human pharmacogenomics genetic association study.
In considering the key ethical issues associated with genetically tailored treatment for depression, such as, how genetic data should be held, whether and when a patient should be allowed access to that information, and how the process should be regulated, the research team has interviewed key stakeholders, including patients and the general public.
This integrated project has led to progress towards validated pharmacogenomic methods for symptom improvement, the prediction of response to psychiatric drug treatment and the reduction of adverse effects, greater basic understanding of the neurobiological mechanisms of depression, and identified methodological improvements that could be made relevant to drug discovery for depression.
*Countries involved: UK, Ireland, Belgium, Germany, Sweden, Italy, Denmark, Slovenia, Poland, Croatia
The GENDEP consortium is made up of eighteen contractors or partners: CR1 (Institute of Psychiatry), CR2 (University of Wales College of Medicine), CR3 (London School of Economics and Political Science), CR4 (The Provost Fellows and Scholars of the College of the Holy and Undivided Trinity of Queen Elizabeth, near Dublin), CR5 (Université Libre de Bruxelles, Hôpital Erasme, Département de Psychiatrie), CR6 (Zentralinstitut fr Seelische Gesundheit), CR7 (University of Bonn), CR8 (Karolinska Insitute), CR9 (Univeristy of Milan), CR10 (Provincia Lombardo-Veneta - Ordine Ospedaliero di San Giovanni di Dio Fatebenefratelli), CR11 (Afdeling for Psykiatrisk Demografi, Institut for Psykiatrisk Grundforskning), CR12 (Institut za varovanje zdravja Republike Slovenije), CR13 (University of Medical Sciences in Poznan), CR14 (University of Zagreb), CR15 (Proteome Sciences plc), CR17 (GlaxoSmithKline Research and Development Ltd), CR18 (GlaxoSmithKline SpA) & CR19 (GABO mbH & Co. KG).
The Coordinator of the project is Professor Peter McGuffin, and the Deputy Coordinator is Dr Kathy J Aitchison, contact via: firstname.lastname@example.org Kings College, London, Institute of Psychiatry, MRC SGDP Centre, Internal Box PO 80, 16 De Crespigny Park, London, SE5 8AF, UK.
1. Human pharmacogenomics study:
This aspect of the study had a 9 month lead time before commencement of recruitment for the following reasons: delayed receipt of funding, delays incurred on processing of ethical committee and EU Clinical Trials Directive documentation, and on making arrangements for insurance where necessary. CR14 made a detailed submission to satisfy local regulations (compatible with Good Clinical Practice under the EU Clinical Trials Directive) and made this available to other sites. Many supporting documents have been generated to facilitate smooth running of this study, and a secure web-based data entry system with accompanying sample tracking system has been designed. At just over a year after our real start date for this aspect of the work (September 2005), we met our first milestone (recruitment of 360 subjects into the study) and by the close of the study (June 2008), approximately 900 subjects have been recruited into the study, with over 10% crossovers (i.e., subjects who have received both study medications), giving approximately 1000 informative treatment paths. The results of data analysis from GENDEP have been most encouraging and have seen considerable international interest when presented. Indeed, the methodology described in Uher et al, (2008) could be translated to clinical trials in medicine in general and enhance the drug discovery pipeline. Longitudinal analysis of change in symptom dimensions over time by drug shows that escitalopram is more effective on mood and anxiety and cognitive dimensions, while nortriptyline more effective on physical symptoms accompanying depression (Uher et al,., under review). In addition, a novel analytical approach has been applied to suicidal ideation data, which shows that overall, in both drug treatment groups, suicidal ideation reduces over the course of the study, with those who have suicidal ideation at entry into the study having a greater risk of suicidal ideation, and a very low percentage experiencing treatment-emergent suicidal ideation (Perroud et al,., under review). Proteomic analyses (2D PAGE and SELDI ToF MS) have been conducted on a subset of samples, and will be integrated with other data from other GENDEP components.
We have genotyped markers across the ten original selected genes and other relevant candidates added since the initiation of the project (HTR2A, TPH2, ABCB1, NR3C1, FKBP5), fulfilling the requirements of the 2nd wave of genotyping. Across these genes we have genotyped a total of 158,730 single nucleotide polymorphisms (SNPs), 19,266 short sequence repeat markers, and over 800 subjects have been processed using the AmpliChip CYP450 Test (Roche Diagnostics) for an additional 33 alleles in two cytochrome P450 genes, CYP2D6 and CYP2C19,. On overall genetic association analysis, HTR2A, (serotonin2A receptor) markers predicted response to escitalopram, and SLC6A2, (noradrenaline transporter) and ADRA2A, (adrenergic2A receptor) genotypes predicted response to nortriptyline (Uher et al,., under review). We also found an 5-HTTLPR, (in SLC6A2, the serontonin transporter) by drug interaction (mood and anxiety symptom dimension, with individuals in the escitalopram-treated group carrying the long form of this polymorphism responding better, Huezo-Diaz et al,, under review). Subjects homozygous for CYP2C19*17 (ultrarapid metabolisers) had a significantly lower mean logarithm week 8 escitalopram than those homozygous for CYP2C19 poor metaboliser alleles (Huezo-Diaz et al,, under review). An association between BDNF and an increase in treatment-emergent or treatment-worsening suicidality (defined in Perroud et al., under review) has also been found, with a significant interaction between NTRK2 (the BDNF receptor) and BDNF .
3. Functional genomics using rat models of depression:
Transcriptomic analysis on FSL/FRL rats treated with escitalopram or nortriptyline (CR17, CR8, CR9) suggests that there are significant and consistent gene expression differences between FRL and FSL animals in both the hippocampus and the cortex. Amongst the genes 2 showing consistent differences in expression are cholinergic and serotinergic receptors. Little effect was seen with early-life stress or drug treatments. A large number of protein, belonging to specific functional classes, altered in the different animal models and by different experimental paradigms have been identified, suggesting new molecular correlates of vulnerability to depression, and of response to antidepressant treatment. The proteins have highlighted specific pathways which are affected by the genetic, environmental or pharmacological components. Functional proteomic data suggest new molecular correlates of vulnerability to depression, and of response to antidepressant treatment. Hippocampal synaptic plasticity studies (CR4, CR6, CR8, CR9) revealed that hippocampal NMDA receptor-dependent plasticity of AMPA receptor-mediated synaptic transmission was impaired in the FSL rats. Furthermore the inhibition of long-term potentiation in this rodent model of depression was somewhat resistant to reversal using the selected pharmacological agents, escitalopram and nortriptyline. Chronic escitalopram treatment inhibited long-term potentiation in the rat hippocampus; whereas, nortriptyline tended to rescue synaptic plasticity in the Flinders model of depression. The learned helplessness protocol had a persistent inhibitory effect. Further studies explored the mechanisms of synaptic plasticity disruption in these models of depression and how antidepressant response was regulated
4. Functional genomics using inbred mouse strains:
Simple dose response curves using acute IP administration were completed. The behavioural testing, including another paradigm (resident-intruder) at no additional cost, was completed and the analysis is being finalised. The most interesting observation from this work is that the maternal separation has a long lasting effect on the Porsolt test performance, and the sensitivity of the strains to this effect differs in the following order: FVB/NJ < DBA/2J< C57BL/6J < 129SvemJ. Furthermore this effect was reversed by nortriptyline, once again in a strain-dependent manner. These observations are of such interest that follow up work is already being conducted, in which we hope to replicate these results and also obtain cortisol measurements at key times and epigenetic measurements. The quality of the transcriptomic data is high. Strain differences are numerous and some of them are very large, notably Snrpn. The environmental stresses applied had a substantial number of long lasting effects on transcription. Quantitative proteomic analyses were undertaken on hippocampal tissue from a mouse model of depression to assess antidepressant effect. No protein changes were found to correlate to drug treatment. Ten proteins were identified that showed differences between maternal deprivation and the control group.
5. In vitro studies:
Data from the housekeeping gene study (Sugden et al., under review) showed that many genes previously used as reference genes changed their expression level on antidepressant treatment. Three genes (B2microglobulin, B2m; Cyclin1, Cyc1; and Atp binding protein subunit 5, Atpb5) were relatively stable, however, and were used for normalisation in the Q-PCR studies. Q-PCR analysis suggested that both Fkbp5 and Abcb1b show biphasic expression in the presence of antidepressant treatment: Fkbp5 was significantly up-regulated after 24 hours treatment with either escitalopram, whilst Abcb1b was significantly up-regulated after 24 hours treatment with 1µM nortriptyline. Using a combination of cellular fractionation, western blotting and mass spectrometry for protein characterisation we have optimised the detection of FK-506 binding protein 5 (FKBP51; Fkbp5) in total cell lysate. Detection of the serotonin transporter (5-Htt) has been assessed and the level of expression of this protein in mouse fibroblasts was found to be below the detectable limits of the techniques used; the protein was however detected in the positive control (hippocampal tissue lysate), and the serotonin transporter was therefore not taken forward for further analysis. Cells treated with escitalopram and nortriptyline (10µm) for 30mins and 24hr and the corresponding saline control were analysed for FKBP51 quantitation (six replicates will be analysed/group), which did not reveal differential protein expression by treatment condition.
6. Integrative analysis and biomarker generation:
Submitted papers include reports of replication of findings in genetic markers, including in a CYP450 locus for which we have used the AmpliChip CYP450 Test. Initial integrative analysis across GENDEP reveals YWHAZ as a potential protein biomarker (Aitchison et al., oral presentation at British Association of Psychopharmacology Summer Meeting), suitable for validation. The GENDEP project as a whole has generated more data with greater complexity than had originally envisaged, partly due to technological and scientific advances, e.g. newer methods of rapid genotyping using SNPlex, and partly due to additional funding (from the UK Medical Research Council and GlaxoSmithKline) for whole genome single nucleotide polymorphism (SNP) genotyping. Thus, thorough integration of all the GENDEP datasets and related datasets will be a very substantial but ultimately fruitful task for which we are seeking additional funding.
7. Training activities:
CR1 has provided training for all sites recruiting for the human pharmacogenomics study (CR1, CR5, CR6, CR7, CR10, CR11, CR12, CR13, and CR14). Researchers from CR9 and CR18 have spent time in the laboratory of CR8, and in addition a researcher from CR9 has spent time in the laboratory of CR18, exchanging knowledge, which has led to the establishment of reproducible methods across sites. Two researchers from Poland (CR16) have attended the SGDP, IoP, Summer School to train in genetic association. Interrater reliability audio and video files were generated for the HDRS, MADRS, UKU, ASEC, and SCAN (10 for each measure) and interrater reliability analysis for the clinical response measures has been completed and shown to be of a high standard.
8. Ethical, Legal, and Social Policy Implications Research
The dominant theme emerging from interviews conducted by the Service Users Research Enterprise with GENDEP subjects from the UK, Germany, Poland, and Denmark is the importance of the weekly contact with the researcher. For the cost-effectiveness analysis, relevant health and social care unit costs were obtained and the costing for the novel aspect of this study, the genotyping test, was undertaken in the form of a literature review in this area. The economic evidence (widely interpreted) in relation to mental health and pharmacogenomic testing was reviewed. The impact on the pharmaceutical industry, health care insurers, 3 health care providers and individuals were considered. It was clear from the limited evidence available that using genetic information (again, widely interpreted) in relation to a complex disorder such as depression is a novel process and, therefore, predicting the impact that it will have on these various stakeholders is difficult. A report on this topic was prepared. Data from the focus groups showed that members of some user organisations were in general opposed to pharamacogenetics, while members of other organisations were in general not. There was a mixed response from participants at all levels, including surveys.
9. Management activities:
A Consortium Agreement was drawn up and negotiated (CR17 and CR1), with all contractors signing up to this. Contracts were negotiated (CR1) with Lundbeck for the supply of study medication and with Roche Molecular Systems for the supply of the AmpliChip CYP450 Test. A one year no-cost extension with the Commission was successfully negotiated with the European Commission. All Periodic Activity Reports and Management Reports have been completed and delivered on time. CR1 and CR19 have organized Consortium Meetings. Telephone and web-conference meetings of the Project Executive Board and Governing Board have been coordinated by CR1, and Task Force Groups have met or communicated to refine relevant aspects of study design.
D1.1 Results of data analysis for the clinical pharmacogenomics study (Uher et al. 2008; Uher et al., under review; Perroud et al., under review).
D2.1 Creation of a resource for future analysis in the form of lymphocyte pellets/cell lines.
D2.2 Completion of the first wave of genotyping.
D2.3 Results of genetic association analysis (Gupta et al., in press; Uher et al., under review; Huezo-Diaz et al., 2008a, under review; Huezo-Diaz et al., 2008b, under review; Aitchison et al., oral presentation to International Congress of Genetics, Berlin, 2008).
D3.1 No robust proteomic changes were found on analysis of the clinical pharmacogenomics samples.
D3.2 No robust gene expression changes that could predict the response of subjects to escitalopram or nortryptiline were detected.
D4.2 Proteins differentially regulated in rat model groups: expression levels of a number of proteins were altered in the different animal models, belonging to specific functional classes, suggesting new molecular correlates of vulnerability to depression, and of response to antidepressant treatment
D4.3 Functional proteomic data in rat models of depression.
D4.4 Data on hippocampal synaptic plasticity.
D5.1 Dose-response curves in inbred mouse strains.
D5.2 Behavioural testing in inbred mouse strains revealed that maternal separation had a lasting effect, moderated by genetic background (i.e., strain).
D5.3 Transcriptomics in mouse models: numerous strain differences, some very large, e.g. Snrpn. The environmental stresses applied had a substantial number of long lasting transcription effects.
D5.4 Proteomic studies in mouse models: 10 proteins were identified that showed differences between maternal deprivation and control groups.
D6.1 Transcripts and proteins in mouse fibroblasts: housekeeping gene expression is affected by antidepressant treatment (Sudgen et al., under review); QPCR analysis revealed biphasic expression changes for Fkbp5 and Abcb1b, with the former not, however, being confirmed by proteomic analysis.
D7.1 Loci consistently differentially regulated: Initial integrative analysis across GENDEP reveals YWHAZ as a potential protein biomarker (Aitchison et al., oral presentation at British Association of Psychopharmacology Summer Meeting).
D8.1 Views of service users on consent in the clinical pharmacogenomics study: dominant emergent theme of the importance of weekly contact with the researcher.
D8.2 Data on pharmacogenomics cost-effectiveness analysis: reviews and reports conducted.
D8.3 Patient and public attitudes to treatments: mixed response.
D9.1 Establishment of interrater reliability: completed.
D10.1 Training in molecular genetics: Polish researchers attended the CR1s Summer School in 2006.
D11.1 Training in preclinical research: completed.
D12.1 Development of predictive assays for medical services: submitted papers include reports of replication of findings in genetic markers. As we have conducted the CYP450 genotyping using the AmpliChip CYP450 Test, which is already approved for clinical diagnostic use, our positive association with CYP2C19 would be readily translatable. YWHAZ is our first proteomic biomarker, suitable for validation.
D13.1 Training in proteomic research: completed.
D14.1.2, and D14.1.3, D14.1.4, D14.1.5, D14.1.6: Reports to the Commission all delivered.
D14.2.1 Exploitation plan: Data on genetic markers associated with response to treatment and serum levels of antidepressants have been written up for publication, including an association found with CYP2C19. The latter included genotyping with the AmpliChip CYP450 Test.
D14.2.2 Implementation of the Gender Action Plan: implemented.
D14.2.3 Actions taken to raise public awareness: many completed (see below).
Novel analytical approaches applied to the clinical data from GENDEP have yielded highly interested results, of relevance to the conduct and analysis of all clinical trials. Analysis of the genetic data from the clinical trial is generating information regarding appropriate markers for bioassays applicable to medical services for the prediction of response to antidepressants, which, if subjected to a further prospective evaluation, could result in validated clinical pharmacogenomics assays. These would enable clinicians to make pharmacogenomically informed choices regarding which type of antidepressant might be most efficacious and be associated with minimal adverse effects. Data 4 on the functional characterisation of the molecular mechanisms involved in depression and the effects of antidepressant treatment has been provided. These achievement represent significant advances in clinical and preclinical psychopharmacology, as applied to depression, and of potential translatability to other therapeutic areas.
The project has enabled European SMEs to work in a collaborative and integrated fashion with leading academic centres, a large industrial partner, and industrial collaborators. The multicentre pan-European collaborative nature of this research project has necessitated a unique mobilisation of resources and expertise across Europe, in an integrated project that is generating data of high scientific import, with the ultimate aim of facilitating sustained pan-European research in this field to be conducted in an internationally competitive manner.
The exploitable knowledge created includes know-how about how to conduct a large-scale multicentre human pharmacogenomics study, knowledge of biomarkers associated with clinical response to antidepressants in various model systems and the human pharmacogenomics study, and druggable targets for pharmaceutical drug discovery.
An editorial has also been written in the British Journal of Psychiatry (2005; 286: 91-92). CR1 and CR9 have had contact with the media in their countries, including GENDEP being featured on Channel 4 News (24th July 2004), and an article in Nature's News and Views section (2004; 428: 791). A number of papers have been published. Pharmacological Reviews (2006; 58: 115-134). Progress in Neuro-Psychopharmacology and Biological Psychiatry (2006; 30: 535-540), an article in the Pharmacogenomics Reporter, outlining GENDEP project in lay terms. (European Research group Tries to Pinpoint PGx Basis for Drug Response in Depression. Pharmacogenomics Reporter, 22 April 2004; 2(17): 1, 4), and articles in lay terms: interview of Dr Aitchison by a reporter from Business Weekly, March 2005, contribution by Dr Aitchison to the Roche Diagnostics response to the Royal Society Report, Personalised Medicines: Hopes & Realities, released on newswires 22nd September 2005; contribution by Dr Aitchison to news story in Chemistry World, Cheerful news for antidepressant research, 9th August 2007, http://www.rsc.org/chemistryworld/News/2007/August/09080702.asp; contribution to A Single Step, Magazine for Supporters of Depression Alliance, Autumn 2007 (pages 9-10), Studies in Depression: Thanks, News, and Opportunities(Gupta, Gunasinghe, Aitchison, & Farmer); contribution to Psychiatry Research Trust Newsletter, Issue 41, Winter 2007, Antidepressants (Gupta & Aitchison).
A press briefing was drafted with the assistance of the UK Medical Research Council Press Office, and released in November 2004. TV and radio interviews have also been made: Professor P McGuffin and Dr KJ Aitchison by Science Correspondent from Channel Four News (in regard to the GENDEP project); featured in Channel 4 News, 24 July 2004; interview of Dr Aitchison by reporter in videotaped session for Roche Diagnostics (June 2005), for an educational CD program that will help psychiatrists better understand the role of Cytochrome P450 genotype analysis in the treatment of psychiatric disorders; TV interview of Prof J Perez, Prof M Gennarelli, and Dr M Popoli for a programme (Depressione: il male oscuro Depression, an obscure disease); interview of Dr Aitchison by a reporter on behalf of Roche Diagnostics for a press release (Roche Diagnostics unveils new diagnostic technology plans for personalized medicine within leukemia and cancer), June 2005 (release date 29th June 2005); interview of Prof J Perez for a Swiss TV channel (2007).
Many oral and poster presentations have been made at international conferences and published. A public access website was launched in July 2005 (www.gendep.iop.kcl.ac.uk). Reports to various key stakeholders will be delivered, and data submitted to other websites (e.g. genetic or pharmacogenomic websites) as appropriate.
Aitchison KJ, Basu A, McGuffin P, Craig I (2005).
Psychiatry and the 'new genetics': hunting for genes for behaviour and drug response
Tardito D et al (2006). Signaling pathways regulating gene expression, neuroplasticity and neurotrophic mechanisms in the actions of antidepressants. A critical overview. Pharmacol. Reviews 58: 115-134.
Gupta B, Gunasinghe CM, Aitchison KJ, Farmer A (2007).
Studies in Depression: Thanks, News, and
Opportunities, A Single Step (Magazine for Supporters of Depression Alliance (leading UK charity for
people affected by depression), Autumn 2007 (9-10).
Rose, N (2007)
Psycho-Pharmaceuticals In Europe. In Martin Knapp, David McDaid, Elias Mossialos and
Graham Thornicroft (eds), Mental Health Policy and Practice across Europe, pp. 146-187. Milton
Keynes: Open University Press.
Rose, N (2007)
Susceptibility as a Form of Life: Genetic Testing, Susceptibility and the Remit of Medicine. In
Regula Valeri Burri and Joseph Dumit (eds) Biomedicine as Culture, pp. 141-150. London: Routledge.
Rose, N (2007)
Pharmacogenomics in psychiatry: social and ethical aspects.
Rose, N (2007)
The Lancet 369: 700-701.
Uher R, Farmer A, Maier W, Rietschel M, Hauser J, Marusic A, Mors O, Elkin A, Williamson RJ, Schmael C, Henigsberg N, Perez J, Mendlewicz J, Janzing JGE, Zobel A, Skibinska M, Kozel D, Stamp AS, Bajs M, Placentino A, Barreto M, McGuffin P, Aitchison, KJ (2008).
Measuring depression: comparison and integration of three scales in the GENDEP study.
Asa Petersén, Gita Wörtwein, Susanne H.M. Gruber, Aleksander A. Mathé (2008). Escitalopram reducesincreased hippocampal cytogenesis in a genetic rat depression model. Neurosicence Letters 436: 305-308.
Barr, M and Rose D (2008). The great ambivalence: factors likely to affect service users and public acceptability of the pharmacogenomics of antidepressant medication. Sociology of Health and Illness Special Issue on Pharmaceuticals, Sept 2008. Also published in monograph form, see below.
Barr, M and Rose D (2008). The great ambivalence: factors likely to affect service users and public acceptability of the pharmacogenomics of antidepressant medication. Sociology of Health and Illness Special Issue Pharmaceuticals and Society: critical discourses and debates, 30: 944-958.
Rowan MJ et al (2008). Stress and plasticity at glutamatergic synapses in vivo. Proceedings of XXVI CINP Congress 2008, in press.
Ryan BK et al (2008). 5-HT(2) receptor-mediated reversal of the inhibition of hippocampal long-term potentiation by acute inescapable stress. Neuropharmacology, in press.
Sugden K, Pariante CM, McGuffin P, Aitchison KJ,* D'Souza UM.* *joint senior authors
Housekeeping gene expression is affected by antidepressant treatment in a mouse fibroblast cell line.
J Psychopharmacol first published on December 12, 2008 as doi:10.1177/0269881108099690
Mallei A et al (2008). Synaptoproteomics of existing and new animal models of depression. In Turck CW (Ed), "Biomarkers for psychiatric disorders," Springer, in press.
Gupta B,* Keers R,* Uher R, McGuffin P, Aitchison KJ. *joint first authors
Pharmacogenetics of antidepressant response.
In: Pariante CM, Nesse R, Nutt D, Wolpert L (eds). Depression: Translational approaches to
understanding and treating. Oxford University Press, in press.
Romeo R, Aitchison KJ, Capdevielle D (2008). Pharmacogenetic testing in psychiatry: pharmacoeconomic applications and considerations. Clin Neuropsychiatry, J Treatment Evaluation 5: 206-211.
Mallei A et al (2008). Synaptoproteomics of existing and new animal models of depression. In "Biomarkers for psychiatric disorders," (CW Turck Editor), Springer.
Ryan B et al (2008). Remodelling by early-life stress of NMDA receptor-dependent synaptic plasticity in a gene-environment rat model of depression. Int J Neuropsychopharmacol. Oct 31: 1-7. [Epub ahead of print]
Uher R, Maier W, Hauser J, Marusic A, Schmael C, Mors O, Henigsberg N, Souery D, Placentino A, Rietschel M, Zobel A, Dmitrzak-Weglarz M, Petrovic A, Jorgensen L, Kalember P, Giovannini C, Barreto M, Elkin A, Landau S, Farmer A, Aitchison KJ*, McGuffin P* (2009). *joint senior authors Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression. British Journal of Psychiatry 194: 252-259.
Huezo-Diaz P*, Uher R*, Smith R, Rietschel M, Henigsberg N, Marusic A, Mors O, Maier W, Hauser J, Souery D, Placentino A, Zobel A, Larsen ER, Czerski PM, Gupta B, Hoda F, Perroud N, Farmer A, Craig I, Aitchison KJ, McGuffin P (2009). *joint first authors Moderation of antidepressant response by the serotonin transporter gene. British Journal of Psychiatry, in press.
Uher R, Mors O, Hauser J, Rietschel M, Maier W, Kozel D, Henigsberg N, Souery D, Placentino A, Perroud N, Dernovsek MZ, Strohmaier J, Larsen ER, Zobel A, Leszczynska-Rodziewicz A, Kalember P, Pedrini L, Linotte S, Gunasinghe C, Aitchison KJ, McGuffin P, Farmer A (2009). Body weight as a predictor of antidepressant efficacy in the GENDEP project. J Affective Disorders, doi:10.1016/j.jad2009.02.013.
Uher R, Farmer AE, Henigsberg N, Rietschel M, Mors O, Maier W, Kozel D, Hauser J, Souery D, Placentino A, Strohmaier J, Perroud N, Zobel A, Rajewska-Rager A, Drnovsek MZ, Larsen ER, Kalember P, Giovannini C, Barreto M, McGuffin P, Aitchison KJ (2009). Adverse drug reactions to antidepressants in the GENDEP study. British Journal of Psychiatry, in press (includes the ASEC measure).
Perroud N*, Aitchison KJ*, Uher R, Smith R, Huezo-Diaz P, Marusic A, Maier W, Mors O, Placentino A, Henigsberg N, Rietschel M, Hauser J, Souery D, Kapelski P, Bonvicini C, Zobel A, Jorgensen L, Petrovic A, Kalember P, Schulze TG, Gupta B, Gray J, Lewis CM, Farmer AE, McGuffin P, Craig I (2009). *joint first authors Genetic predictors of increase in suicidal ideation during antidepressant treatment in the GENDEP project. Neuropsychopharmacology, in press.