ARDC Research Link Australia

ORCID Profile
Orcid icon. 0000-0002-2511-0682

Current Organisations
King's College London , Institute of Psychiatry Psychology and Neuroscience , Central and North West London NHS Foundation Trust , Imperial College London , Higher Education Academy , University of Cambridge , Royal College of Psychiatrists , NHS Leadership Academy & Open University

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Publications

Publication

Pharmacogenetics of antidepressant response: a polygenic approach

Publisher: Cold Spring Harbor Laboratory

Date: 14-12-2016

DOI: 10.1101/093799

Abstract: Major depressive disorder (MDD) has a high personal and socio-economic burden and more than 60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait. Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n=736) to the STAR*D study (n=1409) and vice-versa, including the whole s le or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n=3756). No significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in in idual studies or a meta-analysis. Stratifying by antidepressant did not alter the results. We identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response.

Publication

Multidisciplinary healthcare teams' challenges and strategies in supporting people with type 1 diabetes to recover from disordered eating

Publisher: Wiley

Date: 23-12-2019

DOI: 10.1111/DME.14207

Abstract: To examine the challenges healthcare teams face when treating people with type 1 diabetes and disordered eating and the strategies these teams have developed to facilitate effective treatment. Four semi-structured focus groups were conducted including two tertiary diabetes specialist teams and three tertiary eating disorders specialist teams between July and December 2018. Thematic analysis of the transcripts followed a six-phase process. Twenty-nine experienced healthcare professionals (16 diabetes and 13 eating disorder specialists, 16±12 years' professional experience) were interviewed. The challenges identified in treating people with type 1 diabetes and disordered eating included subthemes the 'challenges specific to the healthcare professional' (feeling not competent enough and perceived emotional burden), 'challenges pertaining to patient factors' (e.g. difficulties with engaging in therapy) and 'challenges created by the healthcare system' (time pressure and staff shortage). Healthcare professionals expressed the need for a consensus on diagnosis and the definition of disordered eating in type 1 diabetes, as well as the need for training and educational resources specific to type 1 diabetes and disordered eating. Healthcare professionals gave practical ex les of strategies of communication for better patient engagement and felt that multidisciplinary working in joint clinics with the other specialty were facilitators for recovery from disordered eating. Healthcare professionals require multidisciplinary team support when treating people with type 1 diabetes and to improve their own competencies. The development of effective screening and assessment tools, educational resources and training for healthcare professionals, and developing multidisciplinary treatment pathways will be key to improving outcomes for their service users with type 1 diabetes and disordered eating.

Publication

Correction: Genome-wide gene-environment analyses of major depressive disorder and reported lifetime traumatic experiences in UK Biobank

Publisher: Springer Science and Business Media LLC

Date: 18-05-2020

DOI: 10.1038/S41380-020-0779-4

Publication

Developing a theoretical maintenance model for disordered eating in Type 1 diabetes

Publisher: Wiley

Date: 16-07-2015

DOI: 10.1111/DME.12839

Abstract: According to the literature, eating disorders are an increasing problem for more than a quarter of people with Type 1 diabetes and they are associated with accentuated diabetic complications. The clinical outcomes in this group when given standard eating disorder treatments are disappointing. The Medical Research Council guidelines for developing complex interventions suggest that the first step is to develop a theoretical model. To review existing literature to build a theoretical maintenance model for disordered eating in people with Type 1 diabetes. The literature in diabetes relating to models of eating disorder (Fairburn's transdiagnostic model and the dual pathway model) and food addiction was examined and assimilated. The elements common to all eating disorder models include weight/shape concern and problems with mood regulation. The predisposing traits of perfectionism, low self-esteem and low body esteem and the interpersonal difficulties from the transdiagnostic model are also relevant to diabetes. The differences include the use of insulin mismanagement to compensate for breaking eating rules and the consequential wide variations in plasma glucose that may predispose to 'food addiction'. Eating disorder symptoms elicit emotionally driven reactions and behaviours from others close to the in idual affected and these are accentuated in the context of diabetes. The next stage is to test the assumptions within the maintenance model with experimental medicine studies to facilitate the development of new technologies aimed at increasing inhibitory processes and moderating environmental triggers.

Publication

Genome-wide gene-environment analyses of depression and reported lifetime traumatic experiences in UK Biobank

Publisher: Cold Spring Harbor Laboratory

Date: 12-01-2018

DOI: 10.1101/247353

Abstract: Depression is more frequently observed among in iduals exposed to traumatic events. The relationship between trauma exposure and depression, including the role of genetic variation, is complex and poorly understood. The UK Biobank concurrently assessed depression and reported trauma exposure in 126,522 genotyped in iduals of European ancestry. We compared the shared aetiology of depression and a range of phenotypes, contrasting in iduals reporting trauma exposure with those who did not (final s le size range: 24,094-92,957). Depression was heritable in participants reporting trauma exposure and in unexposed in iduals, and the genetic correlation between the groups was substantial and not significantly different from 1. Genetic correlations between depression and psychiatric traits were strong regardless of reported trauma exposure, whereas genetic correlations between depression and body mass index (and related phenotypes) were observed only in trauma exposed in iduals. The narrower range of genetic correlations in trauma unexposed depression and the lack of correlation with BMI echoes earlier ideas of endogenous depression.

Publication

Genetic overlap between type 2 diabetes and depression in Swedish and Danish twin registries

Publisher: Springer Science and Business Media LLC

Date: 29-03-2016

DOI: 10.1038/MP.2016.28

Publication

Pharmacogenetics of antidepressant response: A polygenic approach

Publisher: Elsevier BV

Date: 04-2017

DOI: 10.1016/J.PNPBP.2017.01.011

Abstract: Major depressive disorder (MDD) has a high personal and socio-economic burden and >60% of patients fail to achieve remission with the first antidepressant. The biological mechanisms behind antidepressant response are only partially known but genetic factors play a relevant role. A combined predictor across genetic variants may be useful to investigate this complex trait. Polygenic risk scores (PRS) were used to estimate multi-allelic contribution to: 1) antidepressant efficacy 2) its overlap with MDD and schizophrenia. We constructed PRS and tested whether these predicted symptom improvement or remission from the GENDEP study (n=736) to the STAR*D study (n=1409) and vice-versa, including the whole s le or only patients treated with escitalopram or citalopram. Using summary statistics from Psychiatric Genomics Consortium for MDD and schizophrenia, we tested whether PRS from these disorders predicted symptom improvement in GENDEP, STAR*D, and five further studies (n=3756). No significant prediction of antidepressant efficacy was obtained from PRS in GENDEP/STAR*D but this analysis might have been underpowered. There was no evidence of overlap in the genetics of antidepressant response with either MDD or schizophrenia, either in in idual studies or a meta-analysis. Stratifying by antidepressant did not alter the results. We identified no significant predictive effect using PRS between pharmacogenetic studies. The genetic liability to MDD or schizophrenia did not predict response to antidepressants, suggesting differences between the genetic component of depression and treatment response. Larger or more homogeneous studies will be necessary to obtain a polygenic predictor of antidepressant response.