Effects of starvation and short-term refeeding on gastric emptying and postprandial blood glucose regulation in adolescent girls with anorexia nervosa.

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 2 wk of acute refeeding compared with healthy controls (HCs). Twenty-two female adolescents with AN and 17 age-matched female HCs were assessed after a 4-h fast. Patients were commenced on a refeeding protocol of 2,400 kcal/day. Gastric emptying (13C-octanoate breath test), glucose absorption (3-O-methylglucose), blood glucose, plasma glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, C-peptide, and glucagon responses to a mixed-nutrient test meal were measured on admission and 1 and 2 wk after refeeding. HCs were assessed once. On admission, patients had slower gastric emptying, lower postprandial glucose and insulin, and higher glucagon and GLP-1 than HCs ( P < 0.05). In patients with AN, the rise in glucose (0-30 min) correlated with gastric emptying ( P < 0.05). With refeeding, postprandial glucose and 3-O-methylglucose were higher, gastric emptying faster, and baseline insulin and C-peptide less ( P < 0.05), compared with admission. After 2 wk of refeeding, postprandial glucose remained lower, and glucagon and GLP-1 higher, in patients with AN than HCs ( P < 0.05) without differences in gastric emptying, baseline glucagon, or postprandial insulin. Delayed gastric emptying may underlie reduced postprandial glucose in starved patients with AN; however, postprandial glucose and glucoregulatory hormone changes persist after 2 wk of refeeding despite improved gastric emptying. Future research should explore whether reduced postprandial glucose in AN is related to medical risk by examining associated symptoms alongside continuous glucose monitoring during refeeding.

Practitioner characteristics and the treatment of children and adolescents with attention deficit hyperactivity disorder.

AIM: 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. METHODS: Data from the 2007 Special Review on Attention Deficit Hyperactivity Disorder in Children and Adolescents in New South Wales (NSW) were examined. RESULTS: Two hundred seven approved stimulant prescribers in NSW responded to a detailed survey on treatment practice (including 121 paediatricians and 67 psychiatrists). Overall, the practice identified in this survey of NSW approved stimulant prescribers was consistent with that recommended in the draft NHMRC guidelines. Paediatricians were more likely to inform families of developmental therapies. Most prescribers (67%) considered stimulants to be the first line of treatment for at least half of their patients. Psychiatrists were more likely to use stimulants as first-line treatments, while those recently qualified were less likely to prescribe. Half of the prescribers were willing to consider prescribing for children 4 years of age and younger. Paediatricians were more likely to consider prescribing to this age group, while those recently qualified were less likely. There were no significant differences in prescribing practice between child and adult psychiatrists. Most prescribers (67-97%) routinely monitored patients on stimulants for weight, height, blood pressure and academic progress. Psychiatrists were less likely to review these parameters than paediatricians, with this difference being largely due to adult psychiatrists. CONCLUSIONS: There are significant differences in prescribing practice between paediatricians and psychiatrists. These variations may reflect differing training programs and patient populations, and merit close consideration in any review arising from the publication of the recent NHMRC guideline.

Refeeding in anorexia nervosa: increased safety and efficiency through understanding the pathophysiology of protein calorie malnutrition.

PURPOSE OF REVIEW: 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. RECENT FINDINGS: A number of recent reviews and original publications have highlighted important differences from the assumptions underpinning the current refeeding guidelines for patients with anorexia nervosa. The notion of 'starting low and going slow' with the prescription of daily calories seems unlikely to be important in preventing refeeding syndrome. Recent publications suggest this approach does not necessarily add to safety in the refeeding process but rather the contrary. It typically results in weight loss and protracts hospitalization and nutritional recovery. Rather, the composition of macronutrients, in particular avoiding a high proportion of calories from carbohydrates, appears to be more important than the absolute number of calories. The means of initial refeeding appears increasingly important in this process, particularly following descriptions of postprandial hypoglycemia. SUMMARY: The study supports a review of the current guidelines. Evidence for the use of continuous feeding strategies with less than 40% of calories from carbohydrates is presented. This approach has important implications for the prevention of the refeeding syndrome as well as the safety and efficiency with which refeeding may occur for children and adolescents with anorexia nervosa in hospital.

A Signature of Attention-Elicited Electrocortical Activity Distinguishes Response From Non-Response to the Non-Stimulant Atomoxetine in Children and Adolescents With ADHD.

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-cortical activity in 52 youth with ADHD. Baseline event-related potentials (ERP) were compared between those who subsequently responded to 6 weeks of atomoxetine versus those who did not. RESULTS: Responders were distinguished by significantly lower auditory oddball N2 amplitudes than both non-responders and typically developing controls, particularly in the right frontocentral region ( p = .002, Cohen's d = 1.1). Leave-one-out cross validation determined that N2 amplitude in this region was able to accurately predict non-responders with a specificity of 80.8%. There were no P3 differences between responders and non-responders. CONCLUSION: The N2 amplitude is a biomarker that may have utility in predicting response to atomoxetine for youth with ADHD.

Understanding the neural mechanisms of lisdexamfetamine dimesylate (LDX) pharmacotherapy in Binge Eating Disorder (BED): a study protocol.

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 neural mechanisms by which LDX improves symptoms of BED. We hypothesise that LDX will act by normalising connectivity within neural circuits responsible for reward and impulse control, and that this normalisation will correlate with reduced binge eating episodes. METHODS: This is an open-label Phase 4 clinical trial of LDX in adults with moderate to severe BED. Enrolment will include 40 adults with moderate to severe BED aged 18-40 years and Body Mass Index (BMI) of 20-45 kg/m2, and 22 healthy controls matched for age, gender and BMI. Clinical interview and validated scales are used to confirm diagnosis and screen for exclusion criteria, which include comorbid anorexia nervosa or bulimia nervosa, use of psychostimulants within the past 6 months, and current use of antipsychotics or noradrenaline reuptake inhibitors. Baseline assessments include clinical symptoms, multimodal neuroimaging, cognitive assessment of reward sensitivity and behavioural inhibition, and an (optional) genetic sample. A subset of these assessments are repeated after eight weeks of treatment with LDX titrated to either 50 or 70 mg. The primary outcome measures are resting-state intrinsic connectivity and the number of binge eating episodes. Analyses will be applied to resting-state fMRI data to characterise pharmacological effects across the functional connectome, and assess correlations with symptom measure changes. Comparison of neural measures between controls and those with BED post-treatment will also be performed to determine whether LDX normalises brain function. DISCUSSION: First enrolment was in May 2018, and is ongoing. This study is the first comprehensive investigation of the neurobiological changes that occur with LDX treatment in adults with moderate to severe BED. TRIAL REGISTRATION: ACTRN12618000623291, Australian and New Zealand Clinical Trials Registry URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374913&isReview=true. Date of Registration: 20 April 2018.

Event-related wave activity in the EEG provides new marker of ADHD.

OBJECTIVE: This study examines the utility of new measures of event-related spatio-temporal waves in the EEG as a marker of ADHD, previously shown to be closely related to the P3 ERP in an adult sample. METHODS: Wave activity in the EEG was assessed during both an auditory Oddball and a visual continuous performance task (CPT) for an ADHD group ranging in age from 6 to 18 years and comprising mostly Combined and Inattentive subtypes, and for an age and gender matched control group. RESULTS: The ADHD subjects had less wave activity at low frequencies ( approximately 1 Hz) during both tasks. For auditory Oddball targets, this effect was shown to be related to smaller P3 ERP amplitudes. During CPT, the approximately 1 Hz wave activity in the ADHD subjects was inversely related to clinical and behavioral measures of hyperactivity and impulsivity. CPT wave activity at approximately 1 Hz was seen to "normalise" following treatment with stimulant medication. CONCLUSIONS: The results identify a deficit in low frequency wave activity as a new marker for ADHD associated with levels of hyperactivity and impulsivity. SIGNIFICANCE: The marker is evident across a range of tasks and may be specific to ADHD. While lower approximately 1 Hz activity partly accounts for reduced P3 ERPs in ADHD, the effect also arises for tasks that do not elicit a P3. Deficits in behavioral inhibition are hypothesized to arise from underlying dysregulation of cortical inhibition.

Total body protein in healthy adolescent girls: validation of estimates derived from simpler measures with neutron activation analysis.

BACKGROUND: Little recent and accurate information about body protein content in healthy adolescent girls is available. OBJECTIVE: The objective was to assess the total body nitrogen (TBN) and total body protein (TBPr) contents of fat-free mass (P:FFM) in a group of healthy adolescent girls and to validate previously published TBN prediction equations. DESIGN: TBN was measured with in vivo neutron activation analysis (TBNNAA). Bone mineral density and FFM were measured with dual-energy X-ray absorptiometry (FFMDXA), total body water and FFM were measured with bioimpedance analysis, and FFM was assessed by measuring skinfold thicknesses in 51 girls with a mean (+/- SD) age of 14.7 +/- 0.7 y. The validity of the TBN prediction equations was assessed with Bland-Altman analysis. RESULTS: TBNNAA in our adolescent group was higher (1.49 kg) than values reported in earlier studies of women (1.25 and 1.31 kg), and P:FFM was slightly higher (23%) than that documented in adults (19-21%). Previously published TBN equations showed either systematic bias or wide limits of agreement. CONCLUSION: A predictive equation derived from the present study population based on FFMDXA improves the prediction of TBN for groups of young girls but may not be helpful for individuals in clinical settings.

An integrative approach to determine the best behavioral and biological markers of methylphenidate.

AIMS: To distinguish the most sensitive markers of methylphenidate (MPH) effects on behavior and underlying biology using an integrated cognitive and brain function test battery. METHODS: A randomized placebo-controlled trial with 32 healthy adult males. Subjects were tested on MPH doses across 18 sessions with subjective mood, objective behavioral and biological endpoints. From a computerized battery of tests, behavioral measures were cognitive performance scores, while biological measures of brain function included electroencephalographs (EEG) and event-related potentials (ERPs) with complementary measures of autonomic arousal. Using mixed modeling analyses; we determined which measures were most affected by MPH dose and correlation analyses determined the associations among them. RESULTS: MPH dose had the most pronounced effect on cognitive performance (sustained attention/vigilance), baseline autonomic arousal (heart rate, blood pressure) and baseline brain activity (EEG theta power). The faster reaction time, reduced errors, increased autonomic arousal and reductions in theta showed strong to moderate inter-correlations. MPH least affected subjective mood measures and early sensory ERP components. DISCUSSION: These findings suggest that MPH increases cortical and autonomic arousal, facilitating vigilance. The combination of behavioral and biological measures may provide an objective set of markers of MPH response. INTEGRATIVE SIGNIFICANCE: This approach has provided additional insight into the mechanism of the stimulant medication, MPH, which would not be achieved by using such measures in isolation.

Hospital based care of young people in Australia.

Australia has developed a unique model of hospital-based care for adolescents with Adolescent Inpatient Units developing within most tertiary Australian paediatric hospitals. These units provide developmentally appropriate health care with routine psychosocial screening and support for young people admitted with a diverse range of conditions. A supportive ward environment for adolescents offers privacy, respects confidentiality and fosters the development of young people's self-management skills in order to support their emerging independence with health care and facilitate a smooth transition to adult care. When linked to broader Adolescent Medicine programs, these Adolescent Inpatient Units have helped drive a wider education, training and research agenda in adolescent health, and act as a focus for advocacy around hospitalised young people's health care needs.

Distinguishing symptom profiles in adolescent ADHD using an objective cognitive test battery.

UNLABELLED: Currently diagnosis and assessment of ADHD relies on clinical interview and subjective ratings. Standardized objective cognitive tests can provide additional information about ADHD and help distinguish symptom profiles. OBJECTIVE: To assess the cognition of adolescent ADHD subtypes using a standardized cognitive test battery. STUDY GROUP: Seventy-two ADHD combined subtype, 58 ADHD predominantly inattentive subtype and 130 age- and sex-matched healthy controls. METHODS: Cognitive differences between ADHD subtypes were examined according to 1. symptom dimensions (inattentive versus hyperactivity/impulsivity scores) and 2. category (ADHDcom vs. ADHDin). We examined whether cognitive performance would discriminate symptom profiles (from each other and from healthy controls), and whether these profiles could predict test performance. All subjects completed the standardized and fully computerized IntegNeuro test battery using a touch-screen protocol. These tests span the domains of sensori-motor, attention, executive function, language and memory, and have robust construct validity compared to traditional paper-and-pencil tests. The results highlighted the consistency with which performance varied across symptom profiles, irrespective of categorical or dimensional definitions. ADHDcom was primarily distinguished from ADHDin by increased errors and response variability in response inhibition and (to a lesser extent) selective attention tasks. Inattentive symptoms were more likely to predict cognitive performance and there is an indication that despite the same criteria, these symptoms may be more severe in the ADHDcom subtype. CONCLUSIONS: These findings highlight the specificity of cognitive deficits, which differentiate ADHD subtypes in adolescence. This study provides consistent evidence that accuracy and response variability in an executive function (response inhibition) task may best distinguish the common ADHD subtypes.

Eating disorders in adolescents.

BACKGROUND: The overall prevalence of eating disorders among children and adolescents is rising - the younger age group are more likely to present with anorexia nervosa (AN), while the older adolescent can present with either AN or bulimia nervosa (BN). However, eating disorders exist as part of a spectrum and general practitioners will encounter many adolescents that have an eating disorder that do not yet fulfil diagnostic criteria for either AN or BN. OBJECTIVE: This article aims to provide an overview of assessment and principles of management of eating disorders in the adolescent patient. DISCUSSION: General practitioners are key in recognising and offering early intervention in cases of incipient eating disorders or problem dieting behaviour. The physical findings of AN are those of protein calorie malnutrition, while in BN, they reflect chronic purging. Failure of outpatient management requires hospitalisation for nutritional rehabilitation with close monitoring of fluid and electrolyte status to prevent the development of refeeding syndrome. Family involvement is vital, particularly in the younger patient, with ongoing family therapy offering the best outcomes.

Higher Caloric Refeeding Is Safe in Hospitalised Adolescent Patients with Restrictive Eating Disorders.

Introduction. 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 included in a 3-year retrospective chart review. Results. The mean (SD) age of the 162 adolescents was 16.7 years (0.9), admission % median BMI was 80.1% (10.2), and discharge % median BMI was 93.1% (7.0). The mean (SD) starting caloric intake was 2611.7 kcal/day (261.5) equating to 58.4 kcal/kg (10.2). Most patients (92.6%) were treated with nasogastric tube feeding. The mean (SD) length of stay was 3.6 weeks (1.9), and average weekly weight gain was 2.1 kg (0.8). No patients developed cardiac signs of RFS or delirium; complications included 4% peripheral oedema, 1% hypophosphatemia (<0.75 mmol/L), 7% hypomagnesaemia (<0.70 mmol/L), and 2% hypokalaemia (<3.2 mmol/L). Caloric prescription on admission was associated with developing oedema (95% CI 1.001 to 1.047; p = 0.039). No statistical significance was found between electrolytes and calories provided during refeeding. Conclusion. A rapid refeeding protocol with the inclusion of phosphate supplementation can safely achieve rapid weight restoration without increased complications associated with refeeding syndrome.

Sex differences in adolescent ADHD: findings from concurrent EEG and EDA.

OBJECTIVE: Attention Deficit Hyperactivity Disorder (ADHD) occurs more frequently in male children and adolescents than in females, with a ratio of approximately 3 to 1. We determined whether psychophysiological differences are associated with the expression of ADHD in males and females, using simultaneously recorded electroencephalography (EEG) and electrodermal activity (EDA). METHODS: Quantitative EEG and EDA measures were acquired simultaneously and continuously (2min) during an eyes closed resting condition for 70 ADHD adolescents (48 males, 22 females) and their age- and sex-matched controls. RESULTS: Males and females with ADHD were differentiated by both EEG theta activity and EDA. ADHD males showed increased theta (widespread), whereas ADHD females showed a localised frontal enhancement of theta with reduced rate of EDA decrement. These sex differences were unrelated to ADHD subtype. CONCLUSIONS: These findings suggest that different psychophysiological processes may underlie ADHD in each sex. The profile of theta enhancement in ADHD males is consistent with a developmental deviation model of ADHD, whereas ADHD in females may be better understood within an arousal model, which emphasizes both central and autonomic function. SIGNIFICANCE: These findings highlight the potential for concurrent EDA measures to inform EEG studies of ADHD, particularly in regard to sex differences.

Resting EEG theta activity predicts cognitive performance in attention-deficit hyperactivity disorder.

Quantitative electroencephalography has contributed significantly to elucidating the neurobiologic mechanisms of attention-deficit hyperactivity disorder. The most consistent and robust electroencephalographic disturbance in attention-deficit hyperactivity disorder has been abnormally increased theta band during resting conditions. Separate research using attention-demanding tests has elucidated cognitive disturbances that differentiate attention-deficit hyperactivity disorder. This study attempts to integrate electroencephalographic and neuropsychological indices to determine whether cognitive performance is specifically related to increased theta. Theta activity was recorded during a resting condition for 46 children/adolescents with attention-deficit hyperactivity disorder and their sex- and age-matched control subjects. Accuracy and reaction time during an auditory oddball and a visual continuous performance test were then recorded. Compared with control subjects, the attention-deficit hyperactivity disorder group manifested significantly increased (primarily left) frontal theta. Furthermore, the attention-deficit hyperactivity disorder group scored significantly delayed reaction time and decreased accuracy in both tasks. Correlation analysis revealed a significant relationship between frontal (primarily left) theta and oddball accuracy for the attention-deficit hyperactivity disorder group compared with a significant relationship between posterior (primarily right) theta and reaction time in the continuous performance test for the control group. These results indicate that spatial neurophysiologic deficits in attention-deficit hyperactivity disorder may be related to disturbances in signal detection. This observation has important implications for the role of trait-like biologic deficits in attention-deficit hyperactivity disorder predicting performance in information processing.

Anxiety in young people with ADHD: clinical and self-report outcomes.

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 report (Conners' Parent Rating Scale-Revised: Long version) and self-report (State-Trait Anxiety Inventory and Brain Resource Inventory for Screening Cases-Child version) scales were used to assess anxiety. The ADHD-Rating Scale IV was used to measure ADHD symptoms. RESULTS: Of 134 participants (11.0 ± 2.6 years), 31.3% had comorbid anxiety disorder. Comorbid anxiety disorder was associated with greater severity of ADHD. Anxiety symptoms from parent reports (p < .05) but not from child/self-report (p > .05) correlated with clinician assessment. CONCLUSION: Assessment for comorbid anxiety disorder and inclusion of parent rating in this assessment are important components of ADHD treatment in children and adolescents.

Body composition in adolescents with anorexia nervosa.

BACKGROUND: Malnourished patients with anorexia nervosa have altered body composition characterized by depletion of fat and fat-free mass. OBJECTIVES: The objectives of this study were to assess the body composition of adolescents with anorexia nervosa compared with that of control subjects and to investigate the relation between simple anthropometric measures and reference techniques for measuring body composition. DESIGN: Twenty-three adolescent females with anorexia nervosa aged 15.46 +/- 1.34 y (x +/- SD) were studied. Body composition was measured by anthropometry, dual-energy X-ray absorptiometry (DXA) (for body fat), and prompt gamma in vivo neutron activation analysis [for total body nitrogen (TBN)]. Twenty-five female subjects provided the control DXA data. TBN measurements were compared with prediction equations based on sex, height, age, and weight. RESULTS: Anorexia nervosa patients had significantly lower weight (40.2 +/- 4.6 kg), body mass index (in kg/m(2): 15.3 +/- 1.2), percentage of body fat (DXA) (13.8 +/- 5.8%), percentage of TBN predicted for age (73 +/- 10%), trunk fat (2.1 +/- 1.0 kg), leg fat (2.6 +/- 1.1 kg), and trunk-to-leg fat ratio than did control subjects (P < 0.05). In anorexia nervosa patients, significant correlations were found between triceps skinfold thickness and percentage of body fat (r = 0.83), body mass index and percentage of body fat (r = 0.46), and body weight and TBN (r = 0.84, P < 0.05). CONCLUSIONS: Hospitalized adolescent females with anorexia nervosa are depleted of total body fat and protein. We identified 3 simple anthropometric measures (triceps skinfold thickness, BMI, and body weight) that can be used to assess body composition and nutritional status in malnourished adolescents with anorexia nervosa.

Efficacy and safety of atomoxetine in the treatment of children and adolescents with attention deficit hyperactivity disorder.

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 studies as well as in recent large longitudinal studies. This paper provides an updated summary of the literature on atomoxetine, particularly in relation to findings on the short- and long-term safety of atomoxetine in children and adolescents arising from recent large longitudinal cohort studies. Information is presented about the efficacy, safety, and tolerability of this medication.

A randomized controlled trial investigation of a non-stimulant in attention deficit hyperactivity disorder (ACTION): rationale and design.

BACKGROUND: 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 atomoxetine for improving cognition and emotional function in ADHD and whether any improvements in these outcomes are more pronounced in participants with comorbid anxiety; and to determine if changes in these outcomes after atomoxetine are more reliable than changes in diagnostic symptoms of ADHD. This manuscript will describe the methodology and rationale for the ACTION study. METHODS: Children and adolescents aged 6 - 17 y with ADHD will be enrolled. Clinical interview and validated scales will be used to confirm diagnosis and screen for exclusion criteria, which include concurrent stimulant use, and comorbid psychiatric or neurological conditions other than anxiety. Three assessment sessions will be conducted over the 13-week study period: Session 1 (Baseline, pre-treatment), Session 2 (six weeks, atomoxetine or placebo), and Session 3 (13 weeks, cross-over after one-week washout period). The standardized touch-screen battery, "IntegNeuro™", will be used to assess cognitive and emotional function. The primary measure of response will be symptom ratings, while quality of life will be a secondary outcome. Logistic regression will be used to determine predictors of treatment response, while repeated measures of analysis will determine any differences in effect of atomoxetine and placebo. RESULTS: The methodology for the ACTION study has been detailed. CONCLUSIONS: The ACTION study is the first controlled trial to investigate the efficacy of atomoxetine using objective cognitive and emotional function markers, and whether these objective measures predict outcomes with atomoxetine in ADHD with and without comorbid anxiety. First enrollment was in March 2008. The outcomes of this study will be a significant step towards a 'personalized medicine' (and therefore a more efficient) approach to ADHD treatment. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ANZCTRN12607000535471.

Different thermic effects of leptin in adolescent females with varying body fat content.

BACKGROUND & AIMS: Investigating the effect of leptin on energy expenditure in undernutrition might lead to a better understanding of the role of leptin in regulating body weight in humans. METHODS: 73 underweight female adolescents with anorexia nervosa (AN) were compared with 23 healthy normal weight (nwC), and 9 overweight girls (OW); 37 AN were followed during 7 months of weight recovery. Resting energy expenditure (REE, by indirect calorimetry), body composition (fat mass, FM; lean tissue mass, LTM; by Dual-Energy X-Ray Absorptiometry) and plasma hormones of leptin and 3,5,3'-Triiodothyronine (T(3)) were measured. RESULTS: In underweight, leptin, T(3) and REE adjusted for lean tissue mass (REE(LTM)) were decreased; in OW, FM and leptin were increased at unchanged T(3) and REE(LTM). There was a significant positive relation between FM and leptin at low and normal (AN, r(2) = 0.26; nwC, r(2) = 0.51, p < 0.001), but not at high adiposity. Leptin and REE(LTM) were positively associated in underweight (r(2) = 0.14, p = 0.001) but not in normal or overweight subjects. T(3) was linearly related to REE(LTM) over the whole range of adiposity (r(2) = 0.42, p < 0.001). With weight gain in AN (5.0 ± 3.5 kg) the relationship between leptin and REE(LTM) changed toward the conditions seen in normal weight controls. CONCLUSIONS: At low adiposity the interrelated fall of leptin and REE reflect an adaptive mechanism to preserve body weight. High leptin production associated with excessive adiposity was without effect on metabolic adaptation.

Alterations in theta activity associated with novelty and routinization processing in ADHD.

OBJECTIVE: Novelty and routinization-related information processing disturbances were examined in adolescent males with ADHD using an oddball paradigm and electrophysiological measurement of theta (4-7Hz) activity. METHODS: Fifty-four unmedicated adolescent males (12-18years) with Attention Deficit Hyperactivity Disorder (ADHD) and matched controls performed an auditory oddball task. Theta activity was sub-averaged, and Fourier Integrals with simultaneous measurement of electrodermal activity (EDA) was used to index response to stimulus novelty and routinization. RESULTS: ADHD participants showed an overall increase in theta activity to both novel and routine stimuli relative to controls. While controls showed increased theta activity in response to novel compared to routine targets across the brain, ADHD participants did not show this novelty-related increase in theta activity in the right anterior/frontal brain. CONCLUSIONS: The findings of this study are consistent with disturbances in theta activity and the brain substrates of novelty relative to routinization-related processing in ADHD. SIGNIFICANCE: These findings show that there are distinct alterations in theta activity related to stimulus novelty and routinization during an auditory oddball task in ADHD, and they highlight the value of using an event-related approach to elucidate the neural substrates of stimulus processing in ADHD.