Simon D Clarke

The University of Sydney · Discipline of Paediatric, Adolescent and Young Adult medicine Medicine

Plain English Summary A large proportion of individuals with eating disorders (ED) or ED symptomatology within the community do not seek treatment or professional help. Low rates of detection and early intervention, low treatment uptake, stigma, shame and lack of motivation to seek help can lead to significant physical and psychological impairment....

Plain English summary Our understanding of the prevalence and impact of eating disorders has improved significantly over the past 20-years. Research highlights that rates of eating disorders are increasing. To inform the development of the Eating Disorder Research and Translation Strategy 2021–2031 this review aimed to better understand the global...

Plain English summary Research into the risk factors associated with eating disorders (EDs) is necessary in order to better understand the reasons why people develop EDs and to inform programs which aim to reduce these risk factors. In the current study we reviewed studies published between 2009 and 2021 which had researched risk factors associated...

Background Delayed diagnosis, gaps in services and subsequent delays in specialist care and treatment lead to poorer health outcomes for individuals with eating disorders (EDs) and drive significant government healthcare expenditure. Given the significant disease burden associated with EDs, it is imperative that current implementation research is s...

Background Limited screening practices, minimal eating disorder training in the healthcare professions, and barriers related to help-seeking contribute to persistent low rates of eating disorder detection, significant unmet treatment need, and appreciable associated disease burden. The current review sought to broadly summarise the literature and i...

Neuroimaging studies have revealed neurobiological differences in ADHD, particularly studies examining connectivity disruption and anatomical network organization. However, the underlying pathophysiology of ADHD types remains elusive as it is unclear whether dysfunctional network connections characterize the underlying clinical symptoms distinguish...

Background Eating disorders (EDs) are highly complex mental illnesses associated with significant medical complications. There are currently knowledge gaps in research relating to the epidemiology, aetiology, treatment, burden, and outcomes of eating disorders. To clearly identify and begin addressing the major deficits in the scientific, medical,...

Plain English Summary Patients hospitalised with anorexia nervosa require nutrition support as part of their treatment, whilst refeeding complications are prevented. Of particular concern, is the reintroduction of carbohydrate to malnourished patients, which has been proposed to cause a surge in insulin levels and disturbance in electrolytes, parti...

Objective The trail making task is used to assess executive functioning in ADHD youth, yet has only been validated in adult populations. We compare the relative contributions of various cognitive measures to performance on a trail making task analog, the Switching of Attention (SoA) task, in typically-developing and ADHD adolescents. Method Partic...

PurposeAnorexia nervosa (AN) affects approximately 2.9% of females and has the highest mortality rate among all psychiatric disorders. Despite several advances, the neurobiology of this disorder is still not well understood. Several studies have reported abnormalities in the white matter, but it is not know if these are disease-related or secondary...

Importance: Transgender and nonbinary youths have a higher incidence of a range of health conditions and may paradoxically face limited access to health care. Objective: To describe the perspectives and needs of transgender youths in accessing health care. Evidence review: MEDLINE, Embase, PsycInfo, and the Cumulative Index to Nursing and Alli...

To compare neural responses to high and low-energy food images in patients with Anorexia Nervosa (AN) and an age-matched Healthy Control (HC) group. 25 adolescents with AN and 21 HCs completed a diagnostic interview, self-report questionnaires and fMRI, during which they viewed food images evoking responses of disgust, happiness, or fear. Following...

Evidence from functional neuroimaging studies support neural differences between the Attention Deficit Hyperactivity Disorder (ADHD) presentation types. It remains unclear if these neural deficits also manifest at the structural level. We have previously shown that the ADHD combined, and ADHD inattentive types demonstrate differences in graph prope...

Behavioural disturbances in attention deficit hyperactivity disorder (ADHD) are thought to be due to dysfunction of spatially distributed, interconnected neural systems. While there is a fast-growing literature on functional dysconnectivity in ADHD, far less is known about the structural architecture underpinning these disturbances and how it may c...

Introduction: Providing effective nutritional rehabilitation to patients hospitalised with anorexia nervosa (AN) is challenging, partly due to conservative recommendations that advocate feeding patients at low energy intakes. An 'underfeeding syndrome' can develop when patients are not provided with adequate nutrition during treatment, whereby mal...

Abstract Background Routine supplementation of thiamine in patients with restrictive eating disorders prior to initiation of nutritional rehabilitation, is an example of a clinical guideline based on expert opinion rather than evidence-based recommendations. This study investigates whether adolescents hospitalised with a restrictive eating disorder...

Background: The efficacy and safety of Lisdexamfetamine dimesylate (LDX) in the treatment of moderate to severe binge eating disorder (BED) has been demonstrated in multiple randomised clinical trials. Despite this, little is known about how LDX acts to improve binge eating symptoms. This study aims to provide a comprehensive understanding of the...

Purpose: Anorexia nervosa (AN) is a chronic and life-threatening eating disorder that can have a considerable negative impact on the growing skeleton. We hypothesized that the long-term impact on bone health may persist even after normalization of body weight. Methods: 41 females (mean age 21.2 ± 2.9 years) with a history of adolescent-onset AN...

Factors underlying disturbed appetite perception in anorexia nervosa (AN) are poorly characterized. We examined in patients with AN whether fasting and postprandial appetite perceptions, gastrointestinal (GI) hormones, GI symptoms and state anxiety (i) differed from healthy controls (HCs) and (ii) were modified by two weeks of refeeding. 22 female...

Objectives: To investigate emotional responses to food images in women with eating disorders (EDs) and healthy controls (HCs); and in underweight individuals post weight-restoration. Methods: Women (>14 years) with ( n = 139) and without ( n = 41) an ED rated food images evoking fear, disgust and happiness on a three-visual-analogue scale. Under...

Postprandial glucose is reduced in malnourished patients with anorexia nervosa (AN), but the mechanisms and duration for this remain unclear. We examined blood glucose, gastric emptying and glucoregulatory hormone changes in malnourished patients with AN, and during two weeks of acute refeeding, compared with healthy controls (HCs). 22 female adole...

The current study aimed to examine the temporal relationship between anxiety symptoms and weight gain for adolescents with anorexia nervosa over the course of an inpatient admission targeting weight restoration through rapid refeeding. Participants were 31 females presenting to a specialist inpatient unit. Psychometric assessments using standardize...

EEG biomarkers have shown promise in predicting non-response to stimulant medication in ADHD and could serve as translational biomarkers. This study aimed to replicate and extend previous EEG biomarkers. The international Study to Predict Optimized Treatment for ADHD (iSPOT-A), a multi-center, international, prospective open-label trial, enrolled 3...

Research on children and parents’ experiences of ADHD has grown in recent years, attracting attention to their subjective perception of ADHD as a disorder. Theoretical accounts of illness perception suggest that it is multi-dimensional, consisting of at least five core constructs (see the common-sense model of illness representations or CSM: Levent...

Background: Bone health and growth during adolescence require adequate total body protein (TBPr). Renutrition for patients with anorexia nervosa (AN) should aim to normalize body composition and to recover both fat mass and TBPr. Objective: We intended to analyze predictors of protein status, including exercise status, in adolescents with AN and...

Objective: Atomoxetine has several characteristics that make it an attractive alternative to stimulants for treating ADHD, but there are currently no tests identifying individuals for whom the medication should be a first-line option. Method: Within the ADHD Controlled Trial Investigation Of a Non-stimulant (ACTION) study, we examined neuro-cort...

Anorexia Nervosa (AN) is a mental health disorder of complex aetiology. Previous neuroimaging studies have found consistent global reductions in global grey matter volume of underweight girls with AN, however differences in regional grey matter volumes are less consistent. The aims of this study were to investigate grey matter regional volumes of a...

Supplementary material

Attention Deficit Hyperactivity Disorder (ADHD) is characterized clinically by hyperactive/impulsive and/or inattentive symptoms which determine diagnostic subtypes as Predominantly Hyperactive-Impulsive (ADHD-HI), Predominantly Inattentive (ADHD-I), and Combined (ADHD-C). Neuroanatomically though we do not yet know if these clinical subtypes refle...

Attention-Deficit/Hyperactivity Disorder (ADHD) is a heterogeneous disorder. Current subtypes lack longitudinal stability or prognostic utility. We aimed to identify data-driven biotypes using multiple cognitive measures, then to validate these biotypes using EEG, ECG, and clinical response to atomoxetine as external validators. Study design was a...

The autonomic nervous system (ANS) plays an important role in attention and self-regulation by modulating physiological arousal to meet environmental demands. Core symptoms of ADHD such as inattention and behavioral disinhibition may be related to dysregulation of the ANS, however previous findings have been equivocal. We examined autonomic activit...

Although multiple studies have reported structural deficits in multiple brain regions in attention-deficit hyperactivity disorder (ADHD), we do not yet know if these deficits reflect a more systematic disruption to the anatomical organization of large-scale brain networks. Here we used a graph theoretical approach to quantify anatomical organizatio...

In this study, we aimed to examine the psychological experience over the course of an inpatient treatment implementing rapid-refeeding protocol for adolescent patients with anorexia nervosa (AN). Ten female participants were included in the study and interviews were conducted on a weekly basis over the course of their admissions. Interviews were au...

Background: Of the available treatment options for attention-deficit/hyperactivity disorder (ADHD), the use of medications remains the most controversial and it is often difficult for parents to make decisions about treatment. Provision of relevant, reliable information about treatment during consultations may help address parents' concerns about...

. This study examines weight gain and assesses complications associated with refeeding hospitalised adolescents with restrictive eating disorders (EDs) prescribed initial calories above current recommendations. Methods . Patients admitted to an adolescent ED structured “rapid refeeding” program for >48 hours and receiving ≥2400 kcal/day were includ...

The impact of severe malnutrition and medical instability in adolescent Anorexia Nervosa (AN) on immediate health and long-term development underscores the need for safe and efficient methods of refeeding. Current refeeding guidelines in AN advocate low initial caloric intake with slow increases in energy intake to avoid refeeding syndrome. This st...

Aim This study examines weight gain and assesses complications associated with refeeding adolescent inpatients admitted with a restrictive eating disorder (ED) who were provided with caloric intakes above current recommendations. Methods Patients admitted to an adolescent ED program for >48 hours were included in a 3-year retrospective chart review...

Gastric emptying (GE) is an important determinant of postprandial blood glucose (BG), yet GE is delayed in anorexia nervosa (AN). This study aimed to characterise relationships between GE (13C-octanoate breath test), and BG responses to, a mixed-nutrient semi-solid meal in 22 female adolescent AN inpatients on admission (BL) and following 1 (W1) an...

Avoidant/restrictive food intake disorder (ARFID) is a potentially lethal eating disorder. This case example of a male, G, aged 17 years with ARFID illustrates the multiplicity of health problems related to nutritional deficiencies which may develop in an adolescent of normal weight. Of particular concern was the diagnosis of subacute combined dege...

Despite advances in our understanding of ADHD as a neurodevelopmental disorder, robust biomarkers are yet to be established in clinical practice. More than 40 years of electroencephalography (EEG)-based research has culminated in the recent Food and Drug Administration (FDA) approval of the theta/beta (EEG power) ratio (TBR) as a diagnostic marker...

A parent's response to a young person's mental illness can influence their recovery and wellbeing. Many parents devote considerable time and energy to supporting a young person experiencing mental illness and engage in numerous different practices to do so. Yet little is known about why parents use particular practices. This article explores this q...

The family meal is an integral component of Maudsley family-based treatment for anorexia nervosa. The aim of this study was to determine whether there are different types of family meal, as suggested in the treatment manual, and whether within session processes differ according to meal type. Thirty video-recorded family meal sessions from a randomi...

Anorexia nervosa (AN) is a serious disorder incurring high costs due to hospitalization. International treatments vary, with prolonged hospitalizations in Europe and shorter hospitalizations in the USA. Uncontrolled studies suggest that longer initial hospitalizations that normalize weight produce better outcomes and fewer admissions than shorter h...

Parents of young people with mental illness use a variety of strategies to try to positively influence young people’s mental health-related behaviours. Evidence suggests that these parents can influence young people’s well-being and mental health trajectories. However little is known about how young people perceive and are affected by the strategie...

Aim To present data on outcomes including weight and BMI gain, length of stay and complications of a high caloric refeeding regimen. Methods A retrospective audit of 98 consecutive admissions over 36 months of medically unstable patients (Defined as bradycardic HR ≤50), who had a BMI of ≤18.5 kg/m2. Patients were prescribed a regimen of nasogastric...

Objective: To explore the utility of cognitive measures for predicting response of children and adolescents to methylphenidate (MPH). Method: Participants from the International Study to Predict Optimized Treatment-in ADHD (iSPOT-A) completed a cognitive test battery prior to receiving 6 weeks of MPH. The responder criterion was a 25% reduction...

Background: Anorexia nervosa (AN) is a serious disorder incurring high costs due to hospitalization. International treatments vary, with prolonged hospitalizations in Europe and shorter hospitalizations in the USA. Uncontrolled studies suggest that longer initial hospitalizations that normalize weight produce better outcomes and fewer admissions t...

Background / Purpose: Attention deficit hyperactivity disorder (ADHD) is the most common neuropsychiatric disorder in children and is commonly comorbid with other psychiatric conditions, such as anxiety, which has implications for the severity of impairments experienced. The aim of this analysis was to examine the efficacy and predictors of respo...

Purpose: There is growing evidence that siblings have a role to play in the recovery from adolescent anorexia nervosa (AN), yet we know very little about the effect that AN has on them and what they do to cope. This study aims to investigate the impact of AN on adolescent siblings. Method: Semi-structured interviews were conducted with 20 adolescen...

Objective: To evaluate skinfold anthropometry and dual-energy x-ray absorptiometry (DXA) to estimate percentage of body fat (%BF) in adolescent patients with anorexia nervosa (AN). Methods: We examined 80 female AN patients (age 15.6 ± 1.4 years) and 31 healthy, normal weight sex- and age-matched controls with DXA and skinfold anthropometry to e...

Objective: To investigate the growth and pubertal attainment of boys with attention deficit hyperactivity disorder (ADHD) on stimulant medication. Design, setting and participants: Longitudinal study of boys aged 12.00-15.99 years at recruitment in 2005-2011, with stimulant-treated ADHD for at least 3 years, attending three paediatric practices...

Several non-stimulant medications have been used in the treatment of attention deficit hyperactivity disorder (ADHD). Atomoxetine, was introduced in 2002. The safety and efficacy of atomoxetine in the treatment of ADHD for children, adolescents, and adults has been evaluated in over 4000 patients in randomized controlled studies and double blinded...

Objective: (a) To determine the prevalence of comorbid anxiety disorder in ADHD, defined by diagnostic criteria and (b) to compare anxiety as reported by parents and participants with clinician assessment. Method: Children with ADHD were assessed for comorbid anxiety disorder using the Anxiety Disorder Interview Schedule for Children. Parent rep...

Background / Purpose: Poor emotional function is characteristic of internalizing conditions, such as anxiety, that are comorbid with ADHD. Here, we present our behavioural and event-related potential (ERP) results recorded in facial emotion processing tasks from two separate studies, to classify ADHD and ADHD with anxiety, and to predict who will...

To investigate whether recent Australian practice conforms to the draft 2009 National Health and Medical Research Council (NHMRC) guidelines on the management of attention deficit hyperactivity disorder. Data from the 2007 Special Review on Attention Deficit Hyperactivity Disorder in Children and Adolescents in New South Wales (NSW) were examined....

This paper reviews recent publications about the physiology associated with adaptation to malnutrition and refeeding (including the refeeding syndrome) and clinical outcomes of refeeding paradigms. A number of recent reviews and original publications have highlighted important differences from the assumptions underpinning the current refeeding guid...

The ACTION study (Attention deficit hyperactivity disorder Controlled Trial Investigation Of a Non-stimulant) is a multi-center, double-blind, randomized cross-over trial of the non-stimulant medication, Atomoxetine, in children and adolescents with attention deficit hyperactivity disorder (ADHD). The primary aims are to examine the efficacy of ato...

Attention Deficit Hyperactivity Disorder (ADHD) is the most common disorder of childhood-adolescent brain health. Here, we take an integrative neuroscience approach to personalized medicine. The goal of this approach is: 1) to identify promising markers that bridge cognitive and brain measures, as well as genomics; these currently have value for su...

To examine resting awake EEG in adolescent AN participants before and after refeeding to determine if EEG abnormalities in Anorexia Nervosa (AN) are reversible. In 37 adolescent first admission AN patients and 45 healthy controls, EEG was recorded during short duration "eyes open" and "eyes closed" awake resting conditions. Repeat testing occurred...