ORCID Profile
0000-0003-2291-6952
Current Organisations
Institute of Psychiatry Psychology and Neuroscience
,
King's College London
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Publisher: Elsevier BV
Date: 2022
Publisher: Springer Science and Business Media LLC
Date: 11-11-2019
DOI: 10.1038/S41380-019-0558-2
Abstract: Multiplex families with a high prevalence of a psychiatric disorder are often examined to identify rare genetic variants with large effect sizes. In the present study, we analysed whether the risk for bipolar disorder (BD) in BD multiplex families is influenced by common genetic variants. Furthermore, we investigated whether this risk is conferred mainly by BD-specific risk variants or by variants also associated with the susceptibility to schizophrenia or major depression. In total, 395 in iduals from 33 Andalusian BD multiplex families (166 BD, 78 major depressive disorder, 151 unaffected) as well as 438 subjects from an independent, BD case/control cohort (161 unrelated BD, 277 unrelated controls) were analysed. Polygenic risk scores (PRS) for BD, schizophrenia (SCZ), and major depression were calculated and compared between the cohorts. Both the familial BD cases and unaffected family members had higher PRS for all three psychiatric disorders than the independent controls, with BD and SCZ being significant after correction for multiple testing, suggesting a high baseline risk for several psychiatric disorders in the families. Moreover, familial BD cases showed significantly higher BD PRS than unaffected family members and unrelated BD cases. A plausible hypothesis is that, in multiplex families with a general increase in risk for psychiatric disease, BD development is attributable to a high burden of common variants that confer a specific risk for BD. The present analyses demonstrated that common genetic risk variants for psychiatric disorders are likely to contribute to the high incidence of affective psychiatric disorders in the multiplex families. However, the PRS explained only part of the observed phenotypic variance, and rare variants might have also contributed to disease development.
Publisher: Massachusetts Medical Society
Date: 03-11-2022
Publisher: Wiley
Date: 02-2019
DOI: 10.1111/BDI.12748
Publisher: SAGE Publications
Date: 06-03-2023
DOI: 10.1177/02698811231158245
Abstract: Growing numbers of people are using psychedelics for personal psychotherapy outside clinical settings, but research on such use is scarce. This study investigated the patterns of use, self-reported outcomes and outcome predictors of psychedelic ‘self-treatment’ of mental health conditions or specific worries/concerns in life. We use data from the Global Drug Survey 2020, a large online survey on drug use collected between November 2019 and February 2020. In all, 3364 respondents reported their self-treatment experiences with lysergic acid diethylamide ( N = 1996) or psilocybin mushrooms ( N = 1368). The primary outcome of interest was the 17-item self-treatment outcome scale, items reflecting aspects of well-being, psychiatric symptoms, social-emotional skills, and health behaviours. Positive changes were observed across all 17 outcome items, with the strongest benefits on items related to insight and mood. Negative effects were reported by 22.5% of respondents. High intensity of psychedelic experience, seeking advice before treatment, treating with psilocybin mushrooms and treating post-traumatic stress disorder were associated with higher scores on the self-treatment outcome scale after averaging values across all 17 items. Younger age, high intensity of experience and treating with LSD were associated with increased number of negative outcomes. This study brings important insights into self-treatment practices with psychedelics in a large international s le. Outcomes were generally favourable, but negative effects appeared more frequent than in clinical settings. Our findings can help inform safe practices of psychedelic use in the community, and inspire clinical research. Future research can be improved with utilisation of prospective designs and additional predictive variables.
Publisher: Elsevier BV
Date: 05-2016
Publisher: Wiley
Date: 12-2020
DOI: 10.1111/BDI.13035
Abstract: To provide a succinct, clinically useful summary of the management of major depression, based on the 2020 Royal Australian and New Zealand College of Psychiatrists clinical practice guidelines for mood disorders (MDcpg To develop the MDcpg The depression summary provides a systematic approach to diagnosis, and a logical clinical framework for management. The latter begins with Actions, which include important strategies that should be implemented from the outset. These include lifestyle changes, psychoeducation and psychological interventions. The summary advocates the use of antidepressants in the management of depression as Choices and nominates seven medications that can be trialled as clinically indicated before moving to Alternatives for managing depression. Subsequent strategies regarding Medication include Increasing Dose, Augmenting and Switching (MIDAS). The summary also recommends the use of electroconvulsive therapy (ECT), and discusses how to approach non-response. The major depression summary provides up to date guidance regarding the management of major depressive disorder, as set out in the MDcpg
Publisher: Cambridge University Press (CUP)
Date: 15-07-2022
DOI: 10.1017/S1092852922000906
Abstract: This article is a clinical guide which discusses the “state-of-the-art” usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion—this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy—while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward “bridging” methods that may be used to transition simply and safely from other antidepressants to MAOIs.
Publisher: Wiley
Date: 12-2020
DOI: 10.1111/BDI.13036
Publisher: Springer Science and Business Media LLC
Date: 02-05-2017
DOI: 10.1038/MP.2017.73
Publisher: Royal College of Psychiatrists
Date: 17-04-2023
DOI: 10.1192/BJO.2023.36
Abstract: There is mounting interest in the potential efficacy of low carbohydrate and very low carbohydrate ketogenic diets in various neurological and psychiatric disorders. To conduct a systematic review and narrative synthesis of low carbohydrate and ketogenic diets (LC/KD) in adults with mood and anxiety disorders. MEDLINE, Embase, PsycINFO and Cochrane databases were systematically searched for articles from inception to 6 September 2022. Studies that included adults with any mood or anxiety disorder treated with a low carbohydrate or ketogenic intervention, reporting effects on mood or anxiety symptoms were eligible for inclusion. PROSPERO registration CRD42019116367. The search yielded 1377 articles, of which 48 were assessed for full-text eligibility. Twelve heterogeneous studies (stated as ketogenic interventions, albeit with incomplete carbohydrate reporting and measurements of ketosis diet duration: 2 weeks to 3 years n = 389 age range 19 to 75 years) were included in the final analysis. This included nine case reports, two cohort studies and one observational study. Data quality was variable, with no high-quality evidence identified. Efficacy, adverse effects and discontinuation rates were not systematically reported. There was some evidence for efficacy of ketogenic diets in those with bipolar disorder, schizoaffective disorder and possibly unipolar depression/anxiety. Relapse after discontinuation of the diet was reported in some in iduals. Although there is no high-quality evidence of LC/KD efficacy in mood or anxiety disorders, several uncontrolled studies suggest possible beneficial effects. Robust studies are now needed to demonstrate efficacy, to identify clinical groups who may benefit and whether a ketogenic diet (beyond low carbohydrate) is required and to characterise adverse effects and the risk of relapse after diet discontinuation.
Publisher: Wiley
Date: 18-03-2022
DOI: 10.1111/BDI.13198
Abstract: Bipolar disorder (BD) is a complex and dynamic condition with a typical onset in late adolescence or early adulthood followed by an episodic course with intervening periods of subthreshold symptoms or euthymia. It is complicated by the accumulation of comorbid medical and psychiatric disorders. The etiology of BD remains unknown and no reliable biological markers have yet been identified. This is likely due to lack of comprehensive ontological framework and, most importantly, the fact that most studies have been based on small nonrepresentative clinical s les with cross‐sectional designs. We propose to establish large, global longitudinal cohorts of BD studied consistently in a multidimensional and multidisciplinary manner to determine etiology and help improve treatment. Herein we propose collection of a broad range of data that reflect the heterogenic phenotypic manifestations of BD that include dimensional and categorical measures of mood, neurocognitive, personality, behavior, sleep and circadian, life‐story, and outcomes domains. In combination with genetic and biological information such an approach promotes the integrating and harmonizing of data within and across current ontology systems while supporting a paradigm shift that will facilitate discovery and become the basis for novel hypotheses.
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.EURONEURO.2022.05.007
Abstract: Depression is an invalidating disorder, marked by phenotypic heterogeneity. Clinical assessments for treatment adjustments and data-collection for pharmacological research often rely on subjective representations of functioning. Better phenotyping through digital applications may add unseen information and facilitate disentangling the clinical characteristics and impact of depression and its pharmacological treatment in everyday life. Researchers, physicians, and patients benefit from well-understood digital phenotyping approaches to assess the treatment efficacy and side-effects. This review discusses the current possibilities and pitfalls of wearables and technology for the assessment of the pharmacological treatment of depression. Their applications in the whole spectrum of treatment for depression, including diagnosis, treatment of an episode, and monitoring of relapse risk and prevention are discussed. Multiple aspects are to be considered, including concerns that come with collecting sensitive data and health recordings. Also, privacy and trust are addressed. Available applications range from questionnaire-like apps to objective assessment of behavioural patterns and promises in handling suicidality. Nonetheless, interpretation and integration of this high-resolution information with other phenotyping levels, remains challenging. This review provides a state-of-the-art description of wearables and technology in digital phenotyping for monitoring pharmacological treatment in depression, focusing on the challenges and opportunities of its application in clinical trials and research.
Publisher: SAGE Publications
Date: 22-10-2020
Abstract: Randomized controlled clinical trials that have investigated minocycline as an adjunctive treatment for major depressive disorder have proved promising. Data from two studies were pooled to evaluate more definitively whether the addition of minocycline to standard treatment for major depressive disorder leads to an improvement of depressive symptoms when compared with placebo. Both studies were multi-site, double-blinded, placebo-controlled trials of minocycline 200 mg/day added to treatment as usual during a 12-week period. The primary outcome measure was change in depressive symptoms (Montgomery–Asberg Depression Rating Scale in Dean et al. and Hamilton Depression Rating Scale in Husain et al.). Secondary outcomes were change in depression severity (Montgomery–Asberg Depression Rating Scale for Dean et al. and 9-item Patient Health Questionnaire in Husain et al.), anxiety severity (Hamilton Anxiety Rating Scale in Dean et al. and Generalized Anxiety Disorder 7-item scale in Husain et al.) and functional status, which were also evaluated as potential mediators on the primary outcome. A total of 112 participants were included in the pooled data (Dean et al., n = 71 Husain et al., n = 41). A significant change from baseline to week 12 was noted in depressive symptoms – differential change (Placebo vs Minocycline): 9.0, 95% confidence interval = [4.2, 13.9], Cohen’s D (95% confidence interval): 0.71 [0.29, 1.14], p 0.001 – anxiety severity – differential change (Placebo vs Minocycline): 0.38, confidence interval = [0.00, 0.75], Cohen’s D (95% confidence interval): 0.41 [0.00, 0.82], p = 0.050) and functional status – differential change (Placebo vs Minocycline): 1.0, 95% confidence interval = [0.4, 1.5], Cohen’s D (95% confidence interval): 0.76 [0.34, 1.19], p = 0.001). Duration of illness, current use of benzodiazepine and pain medication were identified as moderators, whereas functional status as a mediator redictor. The improvement of depressive symptoms, anxiety severity and functional status is promising and suggests that minocycline has potential as an adjunctive treatment for major depressive disorder. However, further studies are warranted to confirm therapeutic effects of minocycline in major depressive disorder. NCT02263872, registered October 2014, and ACTRN12612000283875, registered March 2012.
Publisher: SAGE Publications
Date: 10-05-2021
Publisher: Public Library of Science (PLoS)
Date: 04-04-2013
Publisher: SAGE Publications
Date: 07-06-2022
DOI: 10.1177/02698811221099650
Abstract: Recreational lysergic acid diethylamide (LSD) use is growing in popularity amid increasing research interest on psychedelics and their possible therapeutic potential yet the potent psychotropic effects of LSD may result in adverse reactions and behaviour. This study aimed to investigate the 12-month incidence and nature of LSD-related adverse experiences resulting in emergency medical treatment (EMT) seeking in an international s le of people reporting LSD use. We use data from the 2017 Global Drug Survey – a large anonymous online survey on patterns of drug use conducted between November 2016 and January 2017. Out of 10,293 past-year LSD users, 102 (1.0%) reported seeking EMT, with a per-event risk estimate of 0.2%. Younger age, comorbid mental health conditions and higher frequency of use were associated with increased risk of EMT seeking. The most common symptoms were psychological, including anxiety, panic and confusion, with the most common explanatory factors cited by respondents being poor ‘setting’ and ‘mindset’. Most responders reported feeling back to normal within 24 h, but 11 participants experienced persistent issues after 4 weeks. The results suggest that LSD is a relatively safe drug in recreational settings. Adverse reactions are typically short-lived, self-limiting and psychological in nature. Sub-optimal set and setting were commonly reported as suspected contributory factors. Within clinical settings, patient screening, preparatory sessions and supervision should reduce these acute risks considerably.
Publisher: Elsevier BV
Date: 2010
Publisher: Springer Science and Business Media LLC
Date: 30-03-2010
DOI: 10.1038/MP.2009.107
Publisher: Springer Science and Business Media LLC
Date: 09-02-2016
DOI: 10.1038/MP.2015.227
Publisher: Springer Science and Business Media LLC
Date: 06-2023
DOI: 10.1038/S41591-023-02365-W
Abstract: Urban-living in iduals are exposed to many environmental factors that may combine and interact to influence mental health. While in idual factors of an urban environment have been investigated in isolation, no attempt has been made to model how complex, real-life exposure to living in the city relates to brain and mental health, and how this is moderated by genetic factors. Using the data of 156,075 participants from the UK Biobank, we carried out sparse canonical correlation analyses to investigate the relationships between urban environments and psychiatric symptoms. We found an environmental profile of social deprivation, air pollution, street network and urban land-use density that was positively correlated with an affective symptom group ( r = 0.22, P perm 0.001), mediated by brain volume differences consistent with reward processing, and moderated by genes enriched for stress response, including CRHR1 , explaining 2.01% of the variance in brain volume differences. Protective factors such as greenness and generous destination accessibility were negatively correlated with an anxiety symptom group ( r = 0.10, P perm 0.001), mediated by brain regions necessary for emotion regulation and moderated by EXD3 , explaining 1.65% of the variance. The third urban environmental profile was correlated with an emotional instability symptom group ( r = 0.03, P perm 0.001). Our findings suggest that different environmental profiles of urban living may influence specific psychiatric symptom groups through distinct neurobiological pathways.
Publisher: Elsevier BV
Date: 12-2021
Publisher: Springer Science and Business Media LLC
Date: 11-08-2202
DOI: 10.1038/NG.2711
Publisher: AME Publishing Company
Date: 16-02-2017
Publisher: Elsevier BV
Date: 10-2019
Publisher: Springer Science and Business Media LLC
Date: 05-2019
Publisher: SAGE Publications
Date: 24-07-2013
Abstract: The aim of this paper is to increase awareness of the prevalence and cost of psychiatric and neurological disorders (brain disorders) in the UK. UK data for 18 brain disorders were extracted from a systematic review of European epidemiological data and prevalence rates and the costs of each disorder were summarized (2010 values). There were approximately 45 million cases of brain disorders in the UK, with a cost of €134 billion per annum. The most prevalent were headache, anxiety disorders, sleep disorders, mood disorders and somatoform disorders. However, the five most costly disorders (€ million) were: dementia: €22,164 psychotic disorders: €16,717 mood disorders: €19,238 addiction: €11,719 anxiety disorders: €11,687. Apart from psychosis, these five disorders ranked amongst those with the lowest direct medical expenditure per subject ( €3000). The approximate breakdown of costs was: 50% indirect costs, 25% direct non-medical and 25% direct healthcare costs. The prevalence and cost of UK brain disorders is likely to increase given the ageing population. Translational neurosciences research has the potential to develop more effective treatments but is underfunded. Addressing the clinical and economic challenges posed by brain disorders requires a coordinated effort at an EU and national level to transform the current scientific, healthcare and educational agenda.
Publisher: Springer Science and Business Media LLC
Date: 24-05-2016
DOI: 10.1038/MP.2016.72
Publisher: Springer Science and Business Media LLC
Date: 17-05-2021
Publisher: Informa UK Limited
Date: 11-2021
DOI: 10.2147/NSS.S266240
Publisher: Elsevier BV
Date: 07-2020
Publisher: Informa UK Limited
Date: 08-12-2020
Publisher: Wiley
Date: 14-10-2021
DOI: 10.1111/JEP.13631
Abstract: Sturmberg and Martin's application of systems and complexity theory to understanding Universal Health Care (UHC) and Primary Health Care (PHC) is evaluated in the light of the influence of political economy on health systems. Furthermore, the role that neoliberal approaches to governance have had in creating increased inequities is seen as a key challenge for UHC. COVID‐19 has emphasized long standing discrepancies in health and these disadvantages require government will and cooperation together with adequate social services to redress these discrepancies in UHC.
Publisher: SAGE Publications
Date: 31-10-2018
Abstract: To derive new criteria sets for defining manic and hypomanic episodes (and thus for defining the bipolar I and II disorders), an international Task Force was assembled and termed AREDOC reflecting its role of Assessment, Revision and Evaluation of DSM and other Operational Criteria. This paper reports on the first phase of its deliberations and interim criteria recommendations. The first stage of the process consisted of reviewing Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and recent International Classification of Diseases criteria, identifying their limitations and generating modified criteria sets for further in-depth consideration. Task Force members responded to recommendations for modifying criteria and from these the most problematic issues were identified. Principal issues focussed on by Task Force members were how best to differentiate mania and hypomania, how to judge ‘impairment’ (both in and of itself and allowing that functioning may sometimes improve during hypomanic episodes) and concern that rejecting some criteria (e.g. an imposed duration period) might risk false-positive diagnoses of the bipolar disorders. This first-stage report summarises the clinical opinions of international experts in the diagnosis and management of the bipolar disorders, allowing readers to contemplate diagnostic parameters that may influence their clinical decisions. The findings meaningfully inform subsequent Task Force stages (involving a further commentary stage followed by an empirical study) that are expected to generate improved symptom criteria for diagnosing the bipolar I and II disorders with greater precision and to clarify whether they differ dimensionally or categorically.
Publisher: Elsevier BV
Date: 06-2018
Publisher: SAGE Publications
Date: 19-04-2016
Abstract: The off-label use of medicines for children and adolescents remains a common and important issue for prescribing practice across child and adolescent psychiatry, paediatrics and primary care. This editorial focusses on psychotropic drug treatment, which plays an essential part in the comprehensive management of a range of child and adolescent psychiatric disorders. Despite a growing evidence base for drug treatment in child and adolescent psychiatric disorders, much psychotropic medication continues to be prescribed off-label (i.e. outside the limits of the marketing authorisation or product license). The reasons for and implications of off-label prescribing, including the potential clinical benefits/risks and medico-legal implications, are often poorly understood by both patients and prescribers. An important unintended consequence of the uncertainties and confusion surrounding the status of off-label prescribing for children and adolescents may be that effective drug treatments are being withheld or underused. This BAP Position Statement aims to clarify these issues, challenge some of the myths surrounding off-label prescribing for children and adolescents and offer practical guidance for prescribers.
Publisher: Springer Science and Business Media LLC
Date: 07-05-2020
Publisher: SAGE Publications
Date: 07-04-2022
DOI: 10.1177/02698811221084063
Abstract: Psilocybin-containing mushrooms are used for recreational, spiritual, self-development and therapeutic purposes. However, physiologically relatively nontoxic, adverse reactions are occasionally reported. This study investigated the 12-month prevalence and nature of magic mushroom-related adverse reactions resulting in emergency medical treatment seeking in a global s le of people reporting magic mushroom use. We use data from the 2017 Global Drug Survey – a large anonymous online survey on patterns of drug use conducted between November 2016 and January 2017. Out of 9233 past year magic mushroom users, 19 (0.2%) reported having sought emergency medical treatment, with a per-event risk estimate of 0.06%. Young age was the only predictor associated with higher risk of emergency medical presentations. The most common symptoms were psychological, namely anxiety anic and paranoia/suspiciousness. Poor ‘mindset’, poor ‘setting’ and mixing substances were most reported reasons for incidents. All but one respondent returned back to normality within 24 h. The results confirm psilocybin mushrooms are a relatively safe drug, with serious incidents rare and short lasting. Providing harm-reduction information likely plays a key role in preventing adverse effects. More research is needed to examine the detailed circumstances and predictors of adverse reactions including rarer physiological reactions.
Publisher: Royal College of Psychiatrists
Date: 03-2021
DOI: 10.1192/BJO.2021.34
Abstract: Although no drugs are licensed for the treatment of personality disorder, pharmacological treatment in clinical practice remains common. This study aimed to estimate the prevalence of psychotropic drug use and associations with psychological service use among people with personality disorder. Using data from a large, anonymised mental healthcare database, we identified all adult patients with a diagnosis of personality disorder and ascertained psychotropic medication use between 1 August 2015 and 1 February 2016. Multivariable logistic regression models were constructed, adjusting for sociodemographic, clinical and service use factors, to examine the association between psychological services use and psychotropic medication prescribing. Of 3366 identified patients, 2029 (60.3%) were prescribed some form of psychotropic medication. Patients using psychological services were significantly less likely to be prescribed psychotropic medication (adjusted odds ratio 0.48, 95% CI 0.39–0.59, P .001) such as antipsychotics, benzodiazepines and antidepressants. This effect was maintained following several sensitivity analyses. We found no difference in the risk for mood stabiliser (adjusted odds ratio 0.79, 95% CI 0.57–1.10, P = 0.169) and multi-class psychotropic use (adjusted odds ratio 0.80, 95% CI 0.60–1.07, P = 0.133) between patients who did and did not use psychological services. Psychotropic medication prescribing is common in patients with personality disorder, but significantly less likely in those who have used psychological services. This does not appear to be explained by differences in demographic, clinical and service use characteristics. There is a need to develop clear prescribing guidelines and conduct research in clinical settings to examine medication effectiveness for this population.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.JAD.2014.09.035
Abstract: It remains uncertain whether schizoaffective disorder (SAD) is a discrete diagnostic entity, is a variant of either a psychotic mood disorder such as bipolar disorder (BDP) or schizophrenia (SCZ), or exists on a spectral continuum between these disorders. The present study examined whether SCZ, SAD, and BDP differed qualitatively on demographic and clinical variables based on a large Australian dataset. This study examined data from the Australian Survey of High Impact Psychosis (SHIP), in which 1469 of the 1825 participants in who had an ICD-10 diagnosis of SCZ (n=857), SAD (n=293), and BDP (n=319) were assessed across a broad range of variables. When compared to patients with SCZ, those with SAD reported more current delusional and thought disorder symptoms, a greater number of lifetime depression, mania, and positive symptoms, and fewer negative symptoms. Relative to the BPD group, the SAD group were younger, endorsed more current positive, delusional, and thought disorder symptoms, fewer lifetime mania symptoms, more lifetime psychotic, hallucination, and delusional symptoms, and recorded lower premorbid IQ scores. Compared to patients with BPD, those with SCZ were significantly younger, endorsed more current psychotic and hallucination symptoms, fewer lifetime depression and mania symptoms, more lifetime psychotic, hallucination, and delusional symptoms, reported more negative symptoms and had lower premorbid IQ and psychosocial functioning scores. Validated psychometric measures of psychotic or mood symptoms were not used. This pattern of results is consistent with the conceptualisation of a spectrum of disorders, ranging from BDP at one end, to SAD in the middle, and SCZ at the other end.
Publisher: Elsevier BV
Date: 12-2020
Publisher: Springer Science and Business Media LLC
Date: 17-06-2021
DOI: 10.1038/S41380-021-01148-4
Abstract: As millions of patients have been infected by SARS-CoV-2 virus a vast number of in iduals complain about continuing breathlessness and fatigue even months after the onset of the disease. This overwhelming phenomenon has not been well defined and has been called “post-COVID syndrome” or “long-COVID” [1]. There are striking similarities to myalgic encephalomyelitis also called chronic fatigue syndrome linked to a viral and autoimmune pathogenesis. In both disorders neurotransmitter receptor antibodies against ß-adrenergic and muscarinic receptors may play a key role. We found similar elevation of these autoantibodies in both patient groups. Extracorporeal apheresis using a special filter seems to be effective in reducing these antibodies in a significant way clearly improving the debilitating symptoms of patients with chronic fatigue syndrome. Therefore, such a form of neuropheresis may provide a promising therapeutic option for patients with post-COVID-19 syndrome. This method will also be effective when other hitherto unknown antibodies and inflammatory mediators are involved.
Publisher: Elsevier BV
Date: 10-2019
Publisher: Wiley
Date: 15-04-2022
DOI: 10.1111/BDI.13208
Abstract: Persistent functional impairment is common in bipolar disorder (BD) and is influenced by a number of demographic, clinical, and cognitive features. The goal of this project was to estimate and compare the influence of key factors on community function in multiple cohorts of well‐characterized s les of in iduals with BD. Thirteen cohorts from 7 countries included n = 5882 in iduals with BD across multiple sites. The statistical approach consisted of a systematic uniform application of analyses across sites. Each site performed a logistic regression analysis with empirically derived “higher versus lower function” as the dependent variable and selected clinical and demographic variables as predictors. We found high rates of functional impairment, ranging from 41 to 75%. Lower community functioning was associated with depressive symptoms in 10 of 12 of the cohorts that included this variable in the analysis. Lower levels of education, a greater number of prior mood episodes, the presence of a comorbid substance use disorder, and a greater total number of psychotropic medications were also associated with low functioning. The bipolar clinical research community is poised to work together to characterize the multi‐dimensional contributors to impairment and address the barriers that impede patients' complete recovery. We must also identify the core features which enable many to thrive and live successfully with BD. A large‐scale, worldwide, prospective longitudinal study focused squarely on BD and its heterogeneous presentations will serve as a platform for discovery and promote major advances toward optimizing outcomes for every in idual with this illness.
Publisher: Wiley
Date: 16-10-2019
DOI: 10.1111/BDI.12834
Abstract: Impairments in affective cognition are part of the neurocognitive profile and possible treatment targets in bipolar disorder (BD), but the findings are heterogeneous. The International Society of Bipolar Disorder (ISBD) Targeting Cognition Task Force conducted a systematic review to (i) identify the most consistent findings in affective cognition in BD, and (ii) provide suggestions for affective cognitive domains for future study and meta-analyses. The review included original studies reporting behavioral measures of affective cognition in BD patients vs controls following the procedures of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) statement. Searches were conducted on PubMed/MEDLINE, EMBASE, and PsychInfo from inception until November 2018. A total of 106 articles were included (of which nine included data for several affective domains) 41 studies assessed emotional face processing 23 studies investigated reactivity to emotional words and images 3 investigated explicit emotion regulation 17 assessed implicit emotion regulation 31 assessed reward processing and affective decision making. In general, findings were inconsistent. The most consistent findings were trait-related difficulties in facial emotion recognition and implicit emotion regulation, and impairments in reward processing and affective decision making during mood episodes. Studies using eye-tracking and facial emotion analysis revealed subtle trait-related abnormalities in emotional reactivity. The ISBD Task Force recommends facial expression recognition, implicit emotion regulation, and reward processing as domains for future research and meta-analyses. An important step to aid comparability between studies in the field would be to reach consensus on an affective cognition test battery for BD.
Publisher: Springer Science and Business Media LLC
Date: 07-03-2018
DOI: 10.1038/S41467-017-02769-6
Abstract: Genomic prediction has the potential to contribute to precision medicine. However, to date, the utility of such predictors is limited due to low accuracy for most traits. Here theory and simulation study are used to demonstrate that widespread pleiotropy among phenotypes can be utilised to improve genomic risk prediction. We show how a genetic predictor can be created as a weighted index that combines published genome-wide association study (GWAS) summary statistics across many different traits. We apply this framework to predict risk of schizophrenia and bipolar disorder in the Psychiatric Genomics consortium data, finding substantial heterogeneity in prediction accuracy increases across cohorts. For six additional phenotypes in the UK Biobank data, we find increases in prediction accuracy ranging from 0.7% for height to 47% for type 2 diabetes, when using a multi-trait predictor that combines published summary statistics from multiple traits, as compared to a predictor based only on one trait.
Publisher: Springer Science and Business Media LLC
Date: 08-10-2018
DOI: 10.1038/S42003-018-0155-Y
Abstract: Psychiatric disorders are thought to have a complex genetic pathology consisting of interplay of common and rare variation. Traditionally, pedigrees are used to shed light on the latter only, while here we discuss the application of polygenic risk scores to also highlight patterns of common genetic risk. We analyze polygenic risk scores for psychiatric disorders in a large pedigree ( n ~ 260) in which 30% of family members suffer from major depressive disorder or bipolar disorder. Studying patterns of assortative mating and anticipation, it appears increased polygenic risk is contributed by affected in iduals who married into the family, resulting in an increasing genetic risk over generations. This may explain the observation of anticipation in mood disorders, whereby onset is earlier and the severity increases over the generations of a family. Joint analyses of rare and common variation may be a powerful way to understand the familial genetics of psychiatric disorders.
Publisher: Wiley
Date: 18-07-2023
DOI: 10.1111/BDI.13366
Abstract: To understand treatment practices for bipolar disorders (BD), this study leveraged the Global Bipolar Cohort collaborative network to investigate pharmacotherapeutic treatment patterns in multiple cohorts of well‐characterized in iduals with BD in North America, Europe, and Australia. Data on pharmacotherapy, demographics, diagnostic subtypes, and comorbidities were provided from each participating cohort. In idual site and regional pooled proportional meta‐analyses with generalized linear mixed methods were conducted to identify prescription patterns. This study included 10,351 in iduals from North America ( n = 3985), Europe ( n = 3822), and Australia ( n = 2544). Overall, participants were predominantly female (60%) with BD‐I (60% vs. BD‐II = 33%). Cross‐sectionally, mood‐stabilizing anticonvulsants (44%), second‐generation antipsychotics (42%), and antidepressants (38%) were the most prescribed medications. Lithium was prescribed in 29% of patients, primarily in the Australian (31%) and European (36%) cohorts. First‐generation antipsychotics were prescribed in 24% of the European versus 1% in the North American cohort. Antidepressant prescription rates were higher in BD‐II (47%) compared to BD‐I (35%). Major limitations were significant differences among cohorts based on inclusion/exclusion criteria, data source, and time/year of enrollment into cohort. Mood‐stabilizing anticonvulsants, second‐generation antipsychotics, and antidepressants were the most prescribed medications suggesting prescription patterns that are not necessarily guideline concordant. Significant differences exist in the prescription practices across different geographic regions, especially the underutilization of lithium in the North American cohorts and the higher utilization of first‐generation antipsychotics in the European cohorts. There is a need to conduct future longitudinal studies to further explore these differences and their impact on outcomes, and to inform and implement evidence‐based guidelines to help improve treatment practices in BD.
Publisher: Springer Science and Business Media LLC
Date: 17-07-2019
DOI: 10.1038/S41598-019-46649-Z
Abstract: Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
Publisher: Springer Science and Business Media LLC
Date: 31-10-2012
DOI: 10.1038/NATURE11582
Publisher: Springer Science and Business Media LLC
Date: 04-2010
DOI: 10.1038/NATURE08979
Publisher: Elsevier BV
Date: 09-2019
DOI: 10.1016/J.JAD.2019.06.060
Abstract: Seasonal Affective Disorder (SAD) is a form of cyclic mood disorder that tends to manifest as winter depression. SAD has anecdotally been described as a hypocortisolemic condition. However, there are no systematic reviews on SAD and Hypothalamic-Pituitary-Adrenal (HPA) axis function. This review intends to summarize these findings. Using the PRISMA (2009) guideline recommendations we searched for relevant articles indexed in databases including MEDLINE, EMBASE, PsycINFO, and PsychArticles. The following keywords were used: "Seasonal affective disorder", OR "Winter Depression", OR "Seasonal depression" associated with: "HPA Axis" OR "cortisol" OR "CRH" OR "ACTH". Thirteen papers were included for qualitative analysis. Studies used both heterogeneous methods and populations. The best evidence comes from a recent study showing that SAD patients tend to demonstrate an attenuated Cortisol Awakening Response (CAR) in winter, but not in summer, compared to controls. Dexamethasone Suppression Test (DST) studies suggest SAD patients have normal suppression of the HPA axis. There is still insufficient evidence to classify SAD as a hypocortisolemic condition when compared to controls. Heterogeneous methods and s les did not allow replication of results. We discuss the limitations of these studies and provide new methods and targets to probe HPA axis function in this population. SAD can provide a unique window of opportunity to study HPA axis in affective disorders, since it is highly predictable and can be followed before, during and after episodes subsides.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Allan Young.