Urinary MHPG and HVA excretion in boys with attention deficit disorder and hyperactivity treated with d-amphetamine.

The authors examined the excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in nine hyperactive and nine control boys admitted to a clinical research center. The hyperactives excreted lower 24 hr MHPG and HVA levels than controls. d-Amphetamine 0.5 mg/kg body weight daily for 2 weeks decreased MHPG and increased HVA. These data replicate the authors' previous findings on MHPG and HVA and on the effect of d-amphetamine in hyperactive children. The data suggest the involvement of norepinephrine and dopamine in the etiology of hyperactivity. It further suggests d-amphetamine may achieve its clinical effects in hyperactivity by inhibiting NE and potentiating DA activity.

alpha 2-Adrenergic receptor binding in human platelets: alterations during the menstrual cycle.

We studied the effect of several clinically important variables on the characteristics of alpha 2-adrenergic receptors in human platelet membranes. The number and affinity of the receptor binding sites were determined from radioligand binding experiments, with [3H]yohimbine being the radioligand of choice. Platelets from female subjects had a cyclic variation in the number of alpha 2-adrenergic receptors that coincided with their menstrual cycles. The number of alpha 2-receptors was highest at the onset of menses and dropped to 74% to 79% of that value during the middle of the cycle. In concurrent experiments we did not observe comparable cyclic changes in receptor binding sites in platelets from male subjects. There was no age-dependent alteration in receptor number in a sample of 39 subjects ranging in age from 8 to 80 yr, but the number of alpha 2-receptors in platelets from male and female subjects differed. We also tested the possibility of a circadian rhythm in alpha 2-receptor number but found no cyclic changes as a function of time of day. There was no alteration in alpha 2-adrenergic receptor binding in the platelets from five subjects with Parkinson's disease. Finally, there was no change in receptor affinity as a function of any of the variables tested. These data should apply to the design of further studies on the clinical importance of platelet alpha 2-adrenergic receptors.

Urinary MHPG excretion in minimal brain dysfunction and its modification by d-amphetamine.

The authors studied the excretion of 3-methoxy-4-hydroxyphenlyglycol (MHPG) in 15 hyperactive boys and 13 controls. They further examined soft neurologic signs and clinical drug response to d-amphetamine administration for two weeks in the hyperactive boys. MHPG excretion was significantly lower in the hyperactive boys than in the controls. d-Amphetamine decreased MHPG excretion significantly in the drug responders only. Pretreatment MHPG excretion did not predict clinical drug response. The responders had more soft neurologic signs than the nonresponders. Furthermore, soft neurologic signs were not related to pretreatment MHPG levels.

Urinary catecholamine metabolites in hyperkinetic boys treated with d-amphetamine.

The authors studied the excretion of 3-methoxy-4-hydroxyphenyl glycol (MHPG), normetanephrine (NM), metanephrine, and homovanillic acid in 7 hyperactive and 12 control children. MHPG was lower but NM was significantly higher in hyperactive children than in controls. Administration of d-amphetamine for 2 weeks depressed the levels of MHPG, NM, and metanephrine. The authors suggest a decreased central norepinephrine activity, which may be secondary to the interruption of norepinephrine fibers in the medial forebrain bundle.

Current perspectives on childhood depression: an overview.

The rapidly increasing research interest in childhood depression indicates that it has become a recognized disorder. The authors review the literature on depression in children, focusing on epidemiology, various diagnostic criteria, classification schemes, assessment instruments, and intervention studies that have been applied to childhood depression. Given that there are many etiological factors, it will be important to study the disorder from various conceptual frameworks, including biochemical, genetic learned helplessness, life stresses, cognitive distortion, behavioral reinforcement, and sociological models.

Platelet MAO in children with attention deficit disorder and hyperactivity: a pilot study.

The authors examined platelet MAO activity in 8 hyperactive and 18 control children who were admitted to a clinical research center and placed on a low monoamine diet. After 5 days, their blood was analyzed; the hyperactive children were discharged on day 7, placed on d-amphetamine for 2 weeks, and readmitted for repeat blood analysis. The hyperactive children initially had significantly lower levels of platelet MAO than the controls. After the hyperactive children were treated with d-amphetamine for 2 weeks, their platelet MAO levels were comparable to those of the control children. The authors suggest an association between low platelet MAO activity and a behavioral state of overactivity, short attention span, and impulsivity.

Effects of d-amphetamine on urinary metabolites of dopamine and norepinephrine in hyperactive boys.

The authors measured the urinary metabolites 3-methoxy-4-hydroxyphenylglycol (MHPG) and homovanillic acid (HVA) in 21 hyperactive boys and 12 matched healthy boys. The hyperactive boys excreted lower amounts of MHPG than control boys. Hyperactive drug responders excreted lower amounts of HVA than control boys and hyperactive nonresponders. Drug responders with normal MHPG excreted low amounts of HVA and those with normal HVA excreted low amounts of MHPG. d-Amphetamine decreased MHPG in all drug responders and HVA in drug responders with normal HVA levels, although it tended to increase HVA in those with low HVA levels. The authors discuss their data in terms of the possible involvement of norepinephrine and dopamine in the etiology of hyperactivity in children.

Effects of diet on urinary excretion of MHPG in normal preadolescent boys.

The authors examined the effect of diets with low and high monoamine content on the 24-hour urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) and creatinine in eight healthy preadolescent boys. The subjects were admitted to a clinical research center and were placed on a diet low in monoamines--the vanillylmandelic acid (VMA)-exclusion diet--for 5 consecutive days. They were switched on the 6th day to a diet rich in monoamines, and urine specimens were collected for 4 more consecutive days. There were no differences in MHPG or creatinine excretion between the urine taken on the low and high monoamine diet days.

Psychoeducational and impulsivity correlates of platelet MAO in normal children.

The authors examined the relationship between the activity of platelet monoamine oxidase (MAO) and a variety of psychoeducational measures, as well as the scores on the Matching Familiar Figures Test (MFF), a psychological test of reflection-impulsivity, in 21 normal children (12 boys, 9 girls) who were admitted to a clinical research center and placed on a low monoamine diet. The children were divided into three equal groups (n = 7) based on their values of platelet MAO. There were no significant differences among the three groups in the psychoeducational measures. However, the high and low MAO groups made significantly more errors and had shorter latency periods on the MFF than the middle MAO group. These findings suggest that normal children with platelet MAO activity values in the high and low ends of the MAO distribution are more impulsive than the children with platelet MAO values in the middle range on the MFF Test of Impulsivity. The findings further suggest that there is no relationship between platelet MAO levels and intellectual abilities or scholastic achievement in normal children.

Platelet MAO activity and personality variations in normals.

The authors examined platelet MAO activity and several personality variables in 58 non-clinic-referred healthy adult males. The psychological tests administered consisted of the Minnesota Multiphasic Personality Inventory, the Personality Research Form-E, and the Zuckerman Sensation Seeking Scale. The findings replicated previous findings in the literature.

Platelet alpha 2-adrenergic receptor binding to 3H-yohimbine and personality variations in normals.

The authors examined platelet alpha 2-adrenergic receptor binding to 3H-yohimbine and several personality variables in 58 adult males in a campus community. Subjects with high receptor Bmax levels exhibited personality traits of less social inhibition and more sensation seeking and thrill seeking behavior, were more playful and autonomous, and came from healthier, more intact families. The results also suggested that high affinity states of platelet alpha 2-adrenergic receptors (low Kd) correlate with traits suggestive of stability, i.e., Autonomy, Dominance, Nurturance, Order, Succorance, and General Sensation Seeking Scale of Zuckerman, while low affinity states (high Kd) of platelet alpha 2-receptors correlate with psychopathological traits of Dependence, Exhibitionism, and Paranoia.

Platelet MAO and measures of attention and impulsivity in boys with attention deficit disorder and hyperactivity.

Platelet monoamine oxidase (MAO) activity was studied in 22 boys diagnosed as having attention deficit disorder with hyperactivity and 12 healthy control boys admitted to a clinical research center and placed on a diet low in monoamines. The hyperactive boys had lower platelet MAO activity than controls, and MAO activity was related to performance on the Matching Familiar Figures Test (MFF) and the Continuous Performance Test (CPT), which yield scores sensitive to impulsivity and inattention. Furthermore, it was negatively related, in hyperactive boys only, to two tests of reading and spelling achievement. Administration of d-amphetamine and placebo in a double-blind crossover design did not significantly raise MAO levels above baseline and was minimally related to improved performance on the MFF and CPT.

Norepinephrine and dopamine metabolites and educational variables in boys with attention deficit disorder and hyperactivity.

The present study evaluated the biochemical measures of urinary homovanillic acid (HVA) and 3-methoxy-4-hydroxy-phenylglycol (MHPG) in relation to functioning on selected psychoeducational tests in a group of boys with attention deficit disorder and hyperactivity. The Wechsler Intelligence Scale for Children-Revised (WISC-R), the Wide Range Achievement Test (WRAT), and the Peabody Picture Vocabulary Test were administered to 28 hyperactive and 23 control subjects. The findings suggest subtle differences in psychoeducational test performance in relation to specific levels of homovanillic acid and MHPG.

Prediction of discharges against medical advice from an alcohol and drug misuse treatment program.

A discriminant function method of data analysis revealed that statistically significant predictions could be made regarding AMA discharge, and that certain variables emerge consistently as predictors: a diagnosis involving personality disorder, admission after regular hours, age 20-29, intoxicated on admission, and less likely to have been referred by relatives or legal authorities.

Congenital sensory neuropathy with anhydrosis-a case report and investigation of autonomic nervous system abnormalities.

A review of the clinical profile of congenital sensory neuropathy with anhydrosis is presented. It is stressed that major diagnostic criteria of this recessively inherited condition should be limited to insensitivity to pain with normal tactile perception, anhydrosis, recurrent unexplained fever, self-mutilation, mental retardation, hypotonia, histologically normal sweat glands and variable autonomic abnormality. A case conforming to this description is reported and compared with 13 published cases. Special investigations of the autonomic nervous system through measurement of urinary catecholamine metabolites and psychophysiologic variables were conducted on this patient. Based on the analysis of 5 X 24-hour urine, values of metabolites of dopamine and epinephrine were normal. Metabolites of norepinephrine, such as 3-methoxy-4-hydroxy phenylglycol and normetanephrine, however, were significantly low when compared with those of four controls, suggesting decreased peripheral and central norepinephrine activity. Polygraph recording and evaluation of some orienting response components revealed no obvious signs of autonomic perturbation and, specifically, no phasic electrodermal activity. These two findings (biochemical and electrodermal) strongly suggest an autonomic imbalance, specifically component, both central and peripheral. It is suggested that autonomic disorder is an integral part of the syndrome and may be demonstrated by special investigations.