Brain metabolism in teenagers with attention-deficit hyperactivity disorder.

OBJECTIVES: We sought to obtain and compare values of cerebral glucose metabolism in normal minors and minors with Attention Deficit Hyperactivity Disorder (ADHD). We also sought to confirm our earlier findings of reduced brain metabolism in adults with ADHD, and to examine whether these results might be diagnostically useful. DESIGN: Case-control study. SETTING: Adolescents were recruited to National Institutes of Health Clinical Center/Research Facility through advertisement at local high schools and ADHD organizations. PATIENTS: Subjects were 10 normal adolescents and 10 adolescents with ADHD diagnosed with structured interviews using DSM-III-R criteria. MAIN OUTCOME MEASURES: Positron emission tomography and fludeoxyglucose F18 were used to study cerebral glucose metabolism in minors while they performed an auditory-attention task. RESULTS: Global or absolute measures of metabolism did not statistically differ between groups, although hyperactive girls had a 17.6% lower absolute brain metabolism than normal girls. As compared with the values for the controls, normalized glucose metabolism was significantly reduced in six of 60 specific regions of the brain, including an area of the left anterior frontal lobe (P < .05). Lower metabolism in that specific region of the left anterior frontal lobe was significantly inversely correlated with measures of symptom severity (P < .001-.009, r = -.56 to -.67). CONCLUSIONS: Global or absolute measures of metabolism using positron emission tomography and fludeoxyglucose F18 did not statistically differentiate between normal adolescents with ADHD. Positron emission tomography scans can be performed and are well tolerated by normal teenagers and teenagers with ADHD. The feasibility of normal minors participating in research involving radiation was established.

Cerebral glucose metabolism in adults with attention deficit hyperactivity disorder after chronic stimulant treatment.

OBJECTIVE: The authors examined the effects of chronic stimulant treatment on cerebral glucose metabolism in adults diagnosed with attention deficit hyperactivity disorder (ADHD), who were studied by means of positron emission tomography (PET) with [18F]fluorodeoxyglucose as the tracer. METHOD: Each subject received two PET scans, the first before drug treatment and the second after treatment with daily oral doses, individually titrated for clinical effect, of either methylphenidate (N = 19) or d-amphetamine (N = 18) for a minimum of 6 weeks. The subjects completed behavioral self-report measures before and at the end of the medication period. RESULTS: Neither stimulant medication changed global, or whole-brain, metabolism, although both drugs increased systolic blood pressure. Metabolism in only two of the 60 brain regions sampled was changed by methylphenidate, while d-amphetamine exhibited no effect on regional metabolism. Both drugs were associated with significant improvement in behavior, as evidenced by improved ratings for restlessness and ability to maintain attention. CONCLUSIONS: While the present study does not demonstrate any robust metabolic effects of chronic stimulant treatment, the behavioral data strongly indicate that methylphenidate and d-amphetamine are effective agents for the treatment of adults with ADHD.

Intravenous dextroamphetamine and brain glucose metabolism.

This study reports the effects of intravenous dextroamphetamine on cerebral glucose metabolism assayed by positron emission tomography (PET) and [fluorine-18]fluorodeoxyglucose (FDG) in 13 healthy adults during the performance of a continuous visual attention task. Two FDG PET scans were performed within a single experimental session. The first scan was preceded by the injection of placebo and the second scan by the injection of 0.15 mg/kg dextroamphetamine. Global and normalized regional glucose metabolic rates (rCMRglc) were examined as a function of pharmacological challenge and subjective experience. Subcortical, limbic, frontal, and cerebellar rCMRglc significantly increased after dextroamphetamine, whereas rCMRglc of the temporal cortex significantly decreased. Physiological and self-report measures of subjective states showed the expected alterations. These rCMRglc changes reflect both the direct pharmacological effect of dextroamphetamine on monoaminergic neurotransmitter systems as well as enhancement of the activation of the neural network mediating the performance of the continuous attention task.

Selegiline in ADHD adults: plasma monoamines and monoamine metabolites.

Plasma monoamines and monoamine metabolites were assessed before and during selegiline treatment in adults with attention deficit/hyperactivity disorder (ADHD). Selegiline, at low dose, is a selective monoamine oxidase inhibitor type B (MAOI-B). After 2-week placebo baseline, 36 ADHD adults were randomized to 6-week placebo or 20 mg/day or 60 mg/day selegiline, followed by 2-week posttreatment placebo. Twenty-seven subjects continued into a 6-week 20-mg/day or 60-mg/day selegiline period. Behavioral variables included self-rated scores on the Conners' Abbreviated Teacher Rating Scale (Conners-ATRS) and performance on a Continuous Performance Task (CPT). Plasma samples were assayed for amines (dopamine, norepinephrine, epinephrine), precursor (DOPA), and metabolites (HVA, DOPAC, DHPG, normetanephrine, metanephrine, 5-HIAA). Selegiline produced dose-dependent changes in monoamine metabolites and DOPA plasma levels. Dopaminergic indices were associated with ADHD symptom severity (Conners-ATRS) and noradrenergic indices with CPT performance. Serotonergic metabolism, challenged by selegiline, correlated with clinical changes. These findings support a multisystem dysfunction underlying ADHD pathophysiology.

Effects of a multicomponent intervention on functional outcomes and process of care in hospitalized older patients: a randomized controlled trial of Acute Care for Elders (ACE) in a community hospital.

BACKGROUND: Older persons frequently experience a decline in function following an acute medical illness and hospitalization. OBJECTIVE: To test the hypothesis that a multicomponent intervention, called Acute Care for Elders (ACE), will improve functional outcomes and the process of care in hospitalized older patients. DESIGN: Randomized controlled trial. SETTING: Community teaching hospital. PATIENTS: A total of 1,531 community-dwelling patients, aged 70 or older, admitted for an acute medical illness between November 1994 and May 1997. INTERVENTION: ACE includes a specially designed environment (with, for example, carpeting and uncluttered hallways); patient-centered care, including nursing care plans for prevention of disability and rehabilitation; planning for patient discharge to home; and review of medical care to prevent iatrogenic illness. MEASUREMENTS: The main outcome was change in the number of independent activities of daily living (ADL) from 2 weeks before admission (baseline) to discharge. Secondary outcomes included resource use, implementation of orders to promote function, and patient and provider satisfaction. RESULTS: Self-reported measures of function did not differ at discharge between the intervention and usual care groups by intention-to-treat analysis. The composite outcome of ADL decline from baseline or nursing home placement was less frequent in the intervention group at discharge (34% vs 40%; P = .027) and during the year following hospitalization (P = .022). There were no significant group differences in hospital length of stay and costs, home healthcare visits, or readmissions. Nursing care plans to promote independent function were more often implemented in the intervention group (79% vs 50%; P = .001), physical therapy consults were obtained more frequently (42% vs 36%; P = .027), and restraints were applied to fewer patients (2% vs 6%; P = .001). Satisfaction with care was higher for the intervention group than the usual care group among patients, caregivers, physicians, and nurses (P < .05). CONCLUSIONS: ACE in a community hospital improved the process of care and patient and provider satisfaction without increasing hospital length of stay or costs. A lower frequency of the composite outcome ADL decline or nursing home placement may indicate potentially beneficial effects on patient outcomes.

Cerebral glucose metabolism in adolescent girls with attention-deficit/hyperactivity disorder.

OBJECTIVE: Low cerebral metabolic rates for glucose (CMRglc) have been reported in a small sample of girls with attention-deficit/hyperactivity disorder (ADHD). This study was an effort to replicate this finding in a larger independent sample. METHOD: Using positron emission tomography and [18F]fluorodeoxyglucose, CMRglc were compared between 10 girls with ADHD (14.10 +/- 1.91 years) and 11 normal girls (14.3 +/- 1.70 years). RESULTS: Global CMRglc was similar between ADHD and control girls. Lateralization of normalized CMRglc differed significantly between ADHD and control girls in parietal and subcortical regions, with rCMRglc lower on the left than on the right side in girls with ADHD, and conversely in control girls. The sylvian area of the parietal region and the anterior putamen of the subcortical region were the main contributors to this effect. Normalized rCMRglc of the hippocampus was higher in ADHD than in control girls. Sexual maturation was the only clinical characteristic that differed between present and previous samples, and it correlated with global CMRglc. CONCLUSIONS: Although failing to confirm abnormally low CMRglc in girls with ADHD, this study suggested that (1) functional interactions between sex and brain development may contribute to ADHD pathophysiology, and (2) sexual maturation should be controlled in future CMRglc studies of adolescent girls.

Reduced brain metabolism in hyperactive girls.

OBJECTIVE: This study assesses the effect of attention-deficit hyperactivity disorder (ADHD) and gender on cerebral glucose metabolism (CMRglu), using positron emission tomography and 18F-fluorodeoxyglucose. METHOD: Nineteen normal (6 females; 14.3 +/- 1.3 years old) and 20 ADHD adolescents (5 females; 14.7 +/- 1.6 years old) participated in the study. An auditory continuous performance task was used during the 30-minute uptake of 18F-fluorodeoxyglucose. RESULTS: There were no statistically significant differences in global or regional CMRglu between ADHD (N = 20) and normal (N = 19) adolescents. However, the global CMRglu in ADHD girls (N = 5) was 15.0% lower than in normal girls (N = 6) (p = .04), while global CMRglu in ADHD boys was not different than in normal boys. Furthermore, global CMRglu in ADHD girls was 19.6% lower than in ADHD boys (p = .02) and was not different between normal girls and normal boys. Clinical rating scales did not differentiate ADHD girls from ADHD boys, nor normal girls from normal boys. CONCLUSIONS: The greater brain metabolism abnormalities in females than males strongly stress that more attention be given to the study of girls with ADHD.

Social organization and aggression in a group of olfactory bulbectomized male mice.

Olfactory bulbectomized and control male CF-1 strain mice were housed in separate, large, seminatural environments over a 30-day observation period. Control mice engaged in vigorous fighting behavior before a dominant animal emerged. The alpha mouse established the floor area as its territory and vigorously attacked all other mice that ventured from the second tier of the enclosure to the floor. Lower ranking mice had numerous body scars, were much less aggressive, and engaged in a variety of nonaggressive social interactions. In contrast, bulbectomized mice did not fight and roamed freely through all areas of the environment. These mice largely ignored one another, engaged in little or no social behavior, and had no body scars. When two anosmic mice came into physical contact, they appeared startled and moved away from one another. These results, together with those of prior studies, indicate that olfaction plays a critical role in virtually all aspects of social behavior in male mice.

Selegiline in adults with attention deficit hyperactivity disorder: clinical efficacy and safety.

Clinical effects of high-dose and low-dose selegiline treatment were examined in 24 adults with attention deficit hyperactivity disorder (ADHD). The study used a double-blind randomized three-arm parallel-groups design with a 2-week placebo baseline followed by 6 weeks of treatment (placebo, 20 mg/day, or 60 mg/day selegiline) and then by 2 weeks of placebo post-treatment. A two-way repeated measures analysis of variance (ANOVA) showed no Drug x Time interaction and no main effect of Drug on severity of ADHD symptoms as self-rated by the subjects on the Conners Abbreviated Teacher Rating Scale (Conners ATRS). There was a significant effect of Time, indicating decreased ADHD symptom severity scores in all three groups. Selegiline treatment was not more effective than placebo. Side effects were more severe in the high-dose selegiline group than in either of the other groups. These preliminary results must be interpreted with caution because of methodological limitations in terms of sample size, patient population selection, and measurement tools.