Methylphenidate and atomoxetine normalise fronto-parietal underactivation during sustained attention in ADHD adolescents.

Problems with sustained attention are a key clinical feature of Attention Deficit/Hyperactivity Disorder (ADHD) which also manifests in poor performance and abnormal fronto-striato-parietal activation during sustained attention. Methylphenidate and atomoxetine improve attention functions and upregulate abnormal fronto-cortical activation during executive function tasks in ADHD patients. Despite this, no functional Magnetic Resonance Imaging (fMRI) study has compared the effects of methylphenidate and atomoxetine on the neurofunctional substrates of sustained attention in ADHD. This randomised, double-blind, placebo-controlled, cross-over study investigated the comparative normalisation effects of methylphenidate and atomoxetine on fMRI correlates and performance in 14 ADHD adolescents relative to 27 age-matched healthy controls during a parametric sustained attention/vigilance task with progressively increasing load of sustained attention. ADHD patients were scanned three times under a single clinical dose of either methylphenidate, atomoxetine, or placebo in pseudo-randomised order. Healthy controls were scanned once and compared to patients under each drug condition to test for potential drug-normalisation effects. Relative to controls, ADHD boys under placebo were impaired in performance and had underactivation in predominantly right-hemispheric fronto-parietal, and striato-thalamic regions. Both drugs normalised all underactivations, while only methylphenidate improved performance deficits. Within patients, methylphenidate had a drug-specific effect of upregulating left ventrolateral prefrontal/superior temporal activation relative to placebo and atomoxetine, while both drugs increased activation of right middle/superior temporal cortex, posterior cingulate, and precuneus relative to placebo. The study shows shared normalisation effects of methylphenidate and atomoxetine on fronto-striato-thalamo-parietal dysfunction in ADHD during sustained attention but a drug-specific upregulation effects of methylphenidate on ventral fronto-temporal regions.

Inverse fluoxetine effects on inhibitory brain activation in non-comorbid boys with ADHD and with ASD.

RATIONALE: Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are often comorbid and have both performance and brain dysfunctions during motor response inhibition. Serotonin agonists modulate motor response inhibition and have shown positive behavioural effects in both disorders. AIMS: We therefore used functional magnetic resonance imaging (fMRI) to investigate the so far unknown shared and disorder-specific inhibitory brain dysfunctions in these two disorders, as well as the effects of a single dose of the selective serotonin reuptake inhibitor fluoxetine. METHODS: Age-matched boys with ADHD (18), ASD (19) and healthy controls (25) were compared with fMRI during a stop task measuring motor inhibition. Patients were scanned twice, under either an acute dose of fluoxetine or placebo in a double-blind, placebo-controlled randomised design. Repeated measures analyses within patients assessed drug effects. To test for potential normalisation effects of brain dysfunctions, patients under each drug condition were compared to controls. RESULTS: Under placebo, relative to controls, ASD boys showed overactivation in left and right inferior frontal cortex (IFC), while ADHD boys showed disorder-specific underactivation in orbitofrontal cortex (OFC) and basal ganglia. Under fluoxetine, the prefrontal dysfunctions were no longer observed, due to inverse effects of fluoxetine on these activations: fluoxetine downregulated IFC and OFC activation in ASD but upregulated them in ADHD. CONCLUSIONS: The findings show that fluoxetine normalises frontal lobe dysfunctions in both disorders via inverse effects, downregulating abnormally increased frontal activation in ASD and upregulating abnormally decreased frontal activation in ADHD, potentially reflecting inverse baseline serotonin levels in both disorders.

Inverse Effect of Fluoxetine on Medial Prefrontal Cortex Activation During Reward Reversal in ADHD and Autism.

Attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) share brain function abnormalities during cognitive flexibility. Serotonin is involved in both disorders, and selective serotonin reuptake inhibitors (SSRIs) can modulate cognitive flexibility and improve behavior in both disorders. Thus, this study investigates shared and disorder-specific brain dysfunctions in these 2 disorders during reward reversal, and the acute effects of an SSRI on these. Age-matched boys with ADHD (15), ASD (18), and controls (21) were compared with functional magnetic resonance imaging (fMRI) during a reversal task. Patients were scanned twice, under either an acute dose of Fluoxetine or placebo in a double-blind, placebo-controlled randomized design. Repeated-measures analyses within patients assessed drug effects. Patients under each drug condition were compared with controls to assess normalization effects. fMRI data showed that, under placebo, ASD boys underactivated medial prefrontal cortex (mPFC), compared with control and ADHD boys. Both patient groups shared decreased precuneus activation. Under Fluoxetine, mPFC activation was up-regulated and normalized in ASD boys relative to controls, but down-regulated in ADHD boys relative to placebo, which was concomitant with worse task performance in ADHD. Fluoxetine therefore has inverse effects on mPFC activation in ASD and ADHD during reversal learning, suggesting dissociated underlying serotonin abnormalities.

Shared and drug-specific effects of atomoxetine and methylphenidate on inhibitory brain dysfunction in medication-naive ADHD boys.

The stimulant methylphenidate (MPX) and the nonstimulant atomoxetine (ATX) are the most commonly prescribed medications for attention deficit hyperactivity disorder (ADHD). However, no functional magnetic resonance imaging (fMRI) study has as yet investigated the effects of ATX on inhibitory or any other brain function in ADHD patients or compared its effects with those of MPX. A randomized, double-blind, placebo-controlled, crossover pharmacological design was used to compare the neurofunctional effects of single doses of MPX, ATX, and placebo during a stop task, combined with fMRI within 19 medication-naive ADHD boys, and their potential normalization effects relative to 29 age-matched healthy boys. Compared with controls, ADHD boys under placebo showed bilateral ventrolateral prefrontal, middle temporal, and cerebellar underactivation. Within patients, MPX relative to ATX and placebo significantly upregulated right ventrolateral prefrontal activation, which correlated with enhanced inhibitory capacity. Relative to controls, both drugs significantly normalized the left ventrolateral prefrontal underactivation observed under placebo, while MPX had a drug-specific effect of normalizing right ventrolateral prefrontal and cerebellar underactivation observed under both placebo and ATX. The findings show shared and drug-specific effects of MPX and ATX on performance and brain activation during inhibitory control in ADHD patients with superior upregulation and normalization effects of MPX.

Neurofunctional effects of methylphenidate and atomoxetine in boys with attention-deficit/hyperactivity disorder during time discrimination.

BACKGROUND: The catecholamine agonists methylphenidate and atomoxetine effectively treat attention-deficit/hyperactivity disorder (ADHD). Furthermore, dopamine agonists have shown to improve time estimation in ADHD, a core cognitive deficit. However, few have compared the effects of methylphenidate and atomoxetine on brain function in ADHD, and none during time estimation. Using single dose challenges, we investigated shared and drug-specific effects in ADHD adolescents on the neural substrates of time discrimination (TD). METHODS: Twenty ADHD adolescent male subjects were compared in a randomized double-blind cross-over design after single doses of methylphenidate, atomoxetine, and placebo in functional magnetic resonance imaging during TD. Normalization effects were assessed by comparing brain activation under each drug condition with that of 20 healthy age-matched control subjects. RESULTS: Relative to control subjects, patients under placebo showed TD deficits and reduced activation of ventrolateral prefrontal cortex (VLPFC)/insula, inferior frontal cortex, and supplementary motor area. Performance differences were normalized only by methylphenidate, relative to both atomoxetine and placebo. Both medications, however, significantly upregulated right VLPFC/insula activation within patients and normalized its underactivation in ADHD boys under placebo relative to control subjects. The supplementary motor area and inferior frontal cortex activation differences that were observed under placebo were reduced by methylphenidate and atomoxetine, respectively, but neither survived rigorous testing for normalization. CONCLUSIONS: While only methylphenidate had a drug-specific effect of improving TD performance deficits, both drugs significantly upregulated and normalized right VLPFC underactivation in ADHD boys under placebo relative to control subjects, suggesting shared effects of stimulants and nonstimulants on a key prefrontal dysfunction during timing.

Use of psychotropics among looked after children: an audit in the Borough of Lambeth.

Background Looked after children and young people (LAC) have higher incidence of mental health problems than non-looked after children. Many mental health difficulties are missed in this group, in particular the effects of trauma and loss and the resulting depression. LAC often move between placements, which further disrupts their care and therapeutic interventions. NICE recommends that in most mental health disorders, children and adolescents should receive specific psychological therapies as first-line treatment, before medication. This standard should apply to LAC. Setting The audit was conducted in the Lambeth CLAMHS, a specialist mental health team working with LAC. Question To ascertain if Lambeth LAC (living in the borough) are receiving psychotropic medication without CLAMHS input and as their only treatment. (All LAC who are on psychotropic medication should have been offered psychological treatments first.) Methods A questionnaire was sent out to Lambeth general practice (GP) surgeries to find out what medications children were prescribed, if any. When children were prescribed psychotropic medication checks were made to ascertain whether they were receiving input from mental health services. Results LAC were seen in 67 different GP surgeries across Lambeth. Responses from 63 surgeries relating to 145 children (87.34% of the total number) were received. Conclusions There were no LAC in Lambeth who were prescribed psychotropic medication without a CAMHS service being involved. All the patients that were on psychotropic medication were known by CLAMHS or another child and adolescent mental health service within the South London and Maudsley NHS Foundation Trust. This is in accordance with NICE recommendations.

Alcohol-related problems in adolescents and adults with intellectual disabilities.

PURPOSE OF REVIEW: Alcohol is widely available and one of the most commonly used psychoactive substances. This review examined the recent literature for empirical research addressing the cause, prevalence and treatment of alcohol-related problems in adolescents and adults with intellectual disabilities. RECENT FINDINGS: Adequate controlled research has not been conducted, and most of the studies were epidemiological and inconclusive. Despite the high variation in the reported prevalence in alcohol use and misuse rates, most published studies document that adolescents and adults with intellectual disabilities consume alcohol at substantially lower rates than the general population. Few treatment interventions have been reported, but limitations in the study design outline the emphasis for future research. SUMMARY: Alcohol misuse affects the physical and mental health of people with intellectual disabilities, leading to behavioural and social difficulties. Assessment and treatment of alcohol-related problems pose ethical considerations. Uncertainty surrounds the ability of alcohol services, and services for individuals with intellectual disabilities respectfully, to meet the needs of this population. Modification of existing treatment approaches, further staff training and development of liaison approach between alcohol services and services for people with intellectual disabilities need further evaluation of their effectiveness.