Scott Richard Clark

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University of Adelaide · Discipline of Psychiatry

In the past two decades, significant progress has been made in the development of polygenic scores (PGSs). One specific application of PGSs is the development and potential use of pharmacogenomic-scores (PGx-scores) to identify patients who can benefit from a specific medication or are likely to experience side effects. This systematic review compr...

The concept of ultra-high risk for psychosis (UHR) has been at the forefront of psychiatric research for several decades, with the ultimate goal of preventing the onset of psychotic disorder in high-risk individuals. Orygen (Melbourne, Australia) has led a range of observational and intervention studies in this clinical population. These datasets h...

Introduction Anxiety and depression are major causes of disability in Arab countries, yet resources for mental health services are insufficient. Mobile devices may improve mental health care delivery (mental m-Health), but the Arab region's mental m-Health app landscape remains under-documented. This study aims to systematically assess the features...

Background Almost 40% of individuals at ultra-high risk (UHR) for psychosis experience persistent attenuated psychotic symptoms (APS) yet it is unclear (1) whether they share overlapping clinical and functional outcomes compared to individuals who transition to psychosis, (2) when symptom and functioning trajectories begin to diverge between UHR in...

Background: UK Biobank (UKB) is a large-scale, prospective resource including genetic and biological data, healthcare linkage, and mental health enhancements, offering significant opportunities for mental health research. However, challenges arise from incomplete linkage and selective enhancements occurring at different times post-baseline. This st...

Objectives: In this study, the trends and current situation of the injury burden as well as attributable burden to injury risk factors at global, regional, and national levels based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 are presented. Study design: To assess the attributable burden of injury risk factors, th...

Background and Hypothesis The clinical-high-risk (CHR) approach was developed to prevent psychosis through the detection of psychosis-risk. CHR services are transdiagnostic in nature, therefore the appropriate management of comorbidity is a central part of care. Differential diagnosis is particularly challenging across three common comorbidities, s...

Background Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the in...

Background: The Australian population aged 70 and above is increasing and imposing new challenges for policy makers and providers to deliver accessible, appropriate and affordable health care. We examine pre-COVID patterns of health loss between 1990 and 2019 to inform policies and practices. Methods: Using the standardised methodology framework an...

Aim Cognitive impairments are a core feature of first‐episode psychosis (FEP) and one of the strongest predictors of long‐term psychosocial functioning. Cognition should be assessed and treated as part of routine clinical care for FEP. Cognitive screening offers the opportunity to rapidly identify and triage those in most need of cognitive support....

In the past two decades, significant progress has been made in the development of polygenic scores (PGSs). One specific application of PGSs is the development and potential use of pharmacogenomic- scores (PGx-scores) to identify patients who can benefit from a specific medication or are likely to experience side effects. This systematic review comp...

The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we performed an exploratory study of the contributions of immune-relevant genetic factors to the response to l...

Individual and societal factors influencing the formation of long-term recreational exercise habits during the transition from adolescence to young adulthood are not well explored. Using data from the Longitudinal Survey of Australian Youth (LSAY), a population-representative cohort study of Young People followed from age 15 to 25, we aimed to (1)...

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of...

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extra...

Background. Mental illnesses mostly occur before 25 years of age when early identification and intervention could delay, ameliorate, or prevent lifelong disability. However, several challenges hinder optimal psychiatric care in youth due to the diversity of presentations, comorbidities, illness courses, and treatment responses. It is increasingly c...

Background: Pharmacogenomic studies on psychiatric drugs have slowly identified genetic variations that influence drug metabolism and treatment effectiveness in patients with mental illness. Because most of these studies predominantly centered on people of European descent, there remains a substantial knowledge gap on the clinical implications of c...

Background: Multimodal modelling that combines biological and clinical data shows promise in predicting transition to psychosis in individuals at ultra high risk (UHR). Individuals who transition to psychosis are known to have deficits at baseline in cognitive function and reductions in grey matter volume in multiple brain regions identified by mag...

Background: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the i...

Objective: Major depressive disorder (MDD) remains difficult to treat, with many patients resistant to existing treatments or experiencing relapse. Cognitive dysfunction is associated with more severe clinical outcomes. Vortioxetine has shown efficacy in remediating depression-associated cognitive impairment. Anti-inflammatory augmentation of antid...

Low‐grade inflammation is considered as a pathophysiological mechanism in a subtype of patients with major depressive disorder (MDD). Anti‐inflammatory drugs have shown efficacy in treating MDD. However, it remains unclear how to identify suitable patients for anti‐inflammatory treatment of depression. This study investigates the predictive value o...

Lithium is the gold standard treatment for bipolar disorder (BD). However, its mechanism of action is incompletely understood, and prediction of treatment outcomes is limited. In our previous multi-omics study of the Pharmacogenomics of Bipolar Disorder (PGBD) sample combining transcriptomic and genomic data, we found that focal adhesion, the extra...

Background: A comprehensive understanding of temporal trends in the disease burden in Australia is lacking, and these trends are required to inform health service planning and improve population health. We explored the burden and trends of diseases and their risk factors in Australia from 1990 to 2019 through a comprehensive analysis of the Global...

Objective: Deliberate foreign body ingestion (DFBI) is characterised by recurrent presentations among patients with mental health conditions, intellectual disabilities and in prisoners. We aimed to profile the characteristics and evaluate the care of such patients in this study. Methods: Adult patients with an endoscopic record of attempted fore...

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar pa...

Background: Up to 1/2 of outpatients prescribed clozapine may be partially/fully non-adherent, based on therapeutic drug monitoring (TDM). Three indices for measuring partial/full non-adherence are proposed a: 1) clozapine concentration/dose (C/D) ratio which drops to half or more of what is expected in the patient; 2) clozapine/norclozapine ratio...

The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment...

During weak induction (from smoking and/or valproate co-prescription), clozapine ultrarapid metabolizers (UMs) need very high daily doses to reach the minimum therapeutic concentration of 350 ng/ml in plasma; clozapine UMs need clozapine doses higher than: 1) 900 mg/day in patients of European/African ancestry, or 2) 600 mg/day in those of Asian an...

The concept of anomalous self-experience, also termed Self-Disorder, has attracted both clinical and research interest, as empirical studies suggest such experiences specifically aggregate in and are a core feature of schizophrenia spectrum disorders. A comprehensive neurophenomenological understanding of Self-Disorder may improve diagnostic and th...

Speech carries essential information about the speaker’s physiology and possible pathophysiological conditions. Bio-acoustic voice qualities show promising value for characterizing mood disorders. Depression alters several bio-acoustic features of speech, and by measuring and analyzing those, conventional diagnostic tools could be enhanced, and cli...

Purpose/background: A recent article in this journal presented a US perspective regarding the modernization of clozapine prescription and proposed an escape from the long shadow cast by agranulocytosis. Methods: Here, an international group of collaborators discusses a point of view complementary to the US view by focusing on worldwide outcomes...

The individual and societal factors influencing long-term recreational exercise participation during the transition from adolescence to young adulthood are not well explored. We modelled latent longitudinal recreational exercise trajectories spanning 8 years from age 16 to 24, and examined demographic, socioeconomic, behavioural, academic, and psyc...

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients,...

Introduction The UK Biobank cognitive assessment data has been a significant resource for researchers looking to investigate predictors and modifiers of cognitive abilities and associated health outcomes in the general population. Given the diverse nature of this data, researchers use different approaches – from the use of a single test to composin...

Introduction The ability to perform optimally under pressure is critical across many occupations, including the military, first responders, and competitive sport. Despite recognition that such performance depends on a range of cognitive factors, how common these factors are across performance domains remains unclear. The current study sought to int...

Study objectives: To assess the association between psychotropic medications and sleep microstructure in large community-based cohorts of older people. Methods: We analyzed overnight polysomnograms of 381 women from the Study of Osteoporotic Fractures (SOF) and 2,657 men from the Osteoporotic Fractures in Men Sleep Study (MrOS), who either used...

Understanding the genomic architecture and molecular mechanisms of cognitive functioning in healthy individuals is critical for developing tailored interventions to enhance cognitive functioning, as well as for identifying targets for treating impaired cognition. There has been substantial progress in uncovering the genetic composition of the gener...

BACKGROUND The efficacy of digital meditation is well established. However, the extent to which benefits remain after 12-weeks in real-world settings remains unknown. In addition, findings related to dosage and practice habits have been mixed, conducted on small and homogenous samples, and used a limited range of analysis procedures and meditation...

Background The efficacy of digital meditation is well established. However, the extent to which the benefits remain after 12 weeks in real-world settings remains unknown. Additionally, findings related to dosage and practice habits have been mixed, and the studies were conducted on small and homogeneous samples and used a limited range of analytica...

Background Response to lithium in patients with bipolar disorder is associated with clinical and transdiagnostic genetic factors. The predictive combination of these variables might help clinicians better predict which patients will respond to lithium treatment. Aims To use a combination of transdiagnostic genetic and clinical factors to predict l...

Defence personnel are among a host of occupations selected and trained to perform under pressure. The premium on optimized cognitive performance is set to increase in future operating environments characterized by information overload, uncertainty, and complex decisions under time pressure. Cognition is broadly recognised as a key driver of both ph...

Bio-acoustic properties of speech show evolving value in analyzing psychiatric illnesses. Obtaining a sufficient speech sample length to quantify these properties is essential, but the impact of sample duration on the stability of bio-acoustic features has not been systematically explored. We aimed to evaluate bio-acoustic features’ reproducibility...

Given the role of low-grade inflammation in the pathophysiology of major depressive disorder (MDD), anti-inflammatory strategies may improve treatment outcomes in some patients. However, it is controversial whether they can be used as adjunctive treatments and whether pre-treatment levels of inflammation can predict treatment outcomes. This study w...

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molec...

Response to lithium varies widely between individuals with bipolar disorder (BD). Polygenic risk scores (PRSs) can uncover pharmacogenomics effects and may help predict drug response. Patients ( N = 2,510) with BD were assessed for long-term lithium response in the Consortium on Lithium Genetics using the Retrospective Criteria of Long-Term Treatme...

The ability to perform optimally under pressure is critical across many occupations, including the military, first responders, and competitive sport, and depends on a range of cognitive factors. How common these key performance factors are across application domains remains unclear. The current study sought to integrate existing knowledge in the pe...

Autoimmune processes are suspected to play a role in the pathophysiology of psychotic disorders. Better understanding of the associations between auto-immunoglobulin G (IgG) repertoires and clinical features of mental illness could yield novel models of the pathophysiology of psychosis, and markers for biological patient stratification. We undertoo...

Bipolar affective disorder (BD) is a severe psychiatric illness, for which lithium (Li) is the gold standard for acute and maintenance therapies. The therapeutic response to Li in BD is heterogeneous and reliable biomarkers allowing patients stratification are still needed. A GWAS performed by the International Consortium on Lithium Genetics (ConLi...

Background Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. Aims To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristi...

Background No biological treatment has been firmly established for the at-risk stage of psychotic disorder. In this study we aim to test if subthreshold psychotic symptoms can be effectively treated with cannabidiol (CBD), a non-psychoactive compound of the plant Cannabis sativa. The question has taken on increased importance in the wake of evidenc...

Introduction There are no well-established biomedical treatments for the core symptoms of autism spectrum disorder (ASD). A small number of studies suggest that repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique, may improve clinical and cognitive outcomes in ASD. We describe here the protocol for a fund...

Introduction Immune system abnormalities exist across a range of psychiatric disorders. Autoimmunity, characterized by the production of antibodies against the body’s own antigens, is a feature of immune system dysfunction and could play a role in mental disorder pathophysiology. Better understanding of the associations of auto-immunoglobulin G (Ig...

Lithium is a first-line medication for bipolar disorder (BD), but only one in three patients respond optimally to the drug. Since evidence shows a strong clinical and genetic overlap between depression and bipolar disorder, we investigated whether a polygenic susceptibility to major depression is associated with response to lithium treatment in pat...