Does hair zinc predict amphetamine improvement of ADD/hyperactivity?

In 18 boys with ADHD (ages 6-12) in a balanced crossover design, parent and teacher hyperactivity rating differences between one month of dextroamphetamine and one month of placebo correlated significantly (p less than .05, 2 tailed) on Pearson's r with baseline hair zinc levels and nonsignificantly with 24-hour urinary zinc excretion. The signs of the correlations were such that a higher baseline zinc predicted a better placebo-controlled response to amphetamine. Patient baseline urinary zinc was significantly (p less than .02) lower than 7 normal controls. These findings are compatible with the possibility that some ADHD children may be mildly deficient in zinc and constitute poorer stimulant responders. Correlations of zinc levels with 24-hour urinary MHPG were in the expected direction but nonsignificantly by 2-tailed test.     

Clinical,endocrine and neurochemical effects of moclobemide in depressed patients

The clinical efficacy of the monoamine oxidase A inhibitor moclobemide and its effect on the dexamethasone suppression test (DST) and plasma and urine methoxyhydroxyphenylglycol (MHPG) were investigated in 26 depressed patients during a 4-week clinical trial. Fourteen patients (54%) responded favourably to the treatment (50% or more reduction of the Hamilton Rating Scale for Depression score). All (8) patients with an abnormal DST responded to treatment; 11 of 16 patients with a normal DST did not respond. Patients with low pretreatment MHPG excretion, according to the median value, were more frequently treatment responders. Plasma and urine MHPG were significantly decreased by treatment. The results indicate that low excretion of MHPG and cortisol nonsuppression may be considered as predictors of favourable clinical response to moclobemide treatment.     

Offspring of schizophrenics. III. Hyperactivity and neurological soft signs.

Twenty-nine male offspring of "continuous schizophrenics" (chronic, borderline, and chronic schizoaffective schizophrenics), plus controls, were given neurological and psychological examinations at age 7. Eight of the 29 were found to have high ratings on a factor score that was termed "hyperactive" (increased activity, impulsivity, distractibility, and emotional lability), and three of these boys had high ratings for neurological signs as well. These frequencies were significantly greater than the control values. Mild incoordination, such as awkwardness in performing rapidly alternating movements, was the neurological soft sign most elevated in the index group. Fifteen female offspring of schizophrenics were not found to differ from their controls on these measures. Previous studies of the childhood of male schizophrenics have found behavior patterns similar to the behavior of the boys who scored high on our hyperactive factors. It is thus likely that the "hyperactive cases" in this sample are even more at risk for developing schizophrenia in later life than the other offspring of schizophrenic parents.     

Lithium carbonate treatment of mania. Cerebrospinal fluid and urinary monoamine metabolites and treatment outcome

Treatment of manic patients with lithium carbonate was associated with significant decreases in cerebrospinal fluid (CSF) 3-methoxy-4-hydroxyphenylglycol (MHPG) and urinary norepinephrine excretion. These measures, before treatment, were higher in manic patients than in either depressed or normal subjects and correlated significantly with severity of mania. Levels in CSF of homovanillic acid and 5-hydroxyindoleacetic acid did not correlate with severity or with change during lithium carbonate treatment. Responders (about 70% of the patients) did not differ from nonresponders in pretreatment mania ratings or neurotransmitter measures. The CSF MHPG and urinary norepinephrine excretion were reduced during lithium carbonate treatment in both responders and nonresponders. Unlike the case before treatment, urinary MHPG excretion was higher during treatment in nonresponders than in responders and correlated with several indexes of symptom severity. These results support a relationship between mania and increased noradrenergic function. Treatment outcome, however, was not related exclusively to the reduction of noradrenergic indexes by lithium carbonate since reductions were similar in both responders and nonresponders. Reduced noradrenergic activity may therefore be necessary but not sufficient for successful outcome during lithium carbonate treatment.     

Diurnal variation of urinary MHPG in unipolar and bipolar depressives

In eight bipolar depressives, 11 unipolar depressives, and 15 healthy controls urinary excretion of MHPG was measured at 3-h intervals over one 24-h period. Bipolars excreted smaller amounts of MHPG than unipolars and controls, especially at night. MHPG excretion was significantly dependent on time of day in the control group only. In the patients maximum excretion showed a tendency to occur earlier in the day than in controls. Minima were unaffected. There were indications that tricyclic antidepressants advance MHPG phases.     

Plasma free homovanillic acid (HVA) as a predictor of clinical response in acute psychosis

The relationship of plasma free homovanillic acid (HVA) and methoxyhydroxyphenylglycol (MHPG) to early clinical response was prospectively studied in a new series of acutely psychotic inpatients given a fixed dose of perphenazine elixir for 10 days. Elevated pretreatment plasma HVA but not MHPG was significantly associated with good response. Change in HVA was correlated with a favorable response and a significant decline in MHPG was found in responders. Results suggest that HVA can provide a useful clinical predictor of response, and that both dopamine metabolism and noradrenergic functioning, as measured by plasma HVA and MHPG, are reduced in effective neuroleptic treatment.     

Neurologic Status in Hyperactive,Enuretic, Encopretic,and Normal Boys

The neurological status of 30 hyperactive, 40 enuretic, and 22 normal boys was investigated using the physical and neurological examination for soft signs (PANESS), a structured 44-item neurological exam with a 4-point scale for each item. There was a strong negative correlation between age and the PANESS score, indicating that the examination is also a kind of developmental scale. Age-adjusted mean PANESS score of hyperactive children was significantly higher than both the normal and enuretic groups, but there was no significant difference between the latter two groups in PANESS scores adjusted for age. PANESS scores correlated significantly with other measures of higher central nervous system function such as IQ, number of errors on the Bender test, and abnormal electroencephalograms (available in the hyperactive boys). Reliability of the examination as a whole by two independent raters was significant. Use of the PANESS in this study demonstrated a lag in neurodevelopmental maturity not necessarily specific to diagnostic category.     

Neurologic soft signs in borderline personality disorder

OBJECTIVE: Borderline personality disorder is a disabling and dramatic psychiatric condition. To date, its pathophysiology remains unclear. Scientific evidence seems to have found underlying, nonfocal, central nervous system dysfunction in borderline personality disorder. Neurologic soft signs are anomalies only evidenced by specific motor, sensory, or integrative testing when no other sign of a neurologic lesion is present. Neurologic soft signs have been proposed to be nonfocal in origin and to reflect central nervous system failure. The assessment of neurologic soft signs now appears reliable and stable. Assuming that neurologic soft signs reflect nonfocal central nervous system dysfunction, we hypothesized that patients with borderline personality disorder should have an increased frequency of neurologic soft signs, therefore enhancing the possibility of the existence in borderline personality disorder of a nonlocalized brain dysfunction. METHOD: To test this hypothesis, we compared 29 neurologic soft signs in 20 drug-free patients with DSM-III-R borderline personality disorder and 20 controls, using an examination adapted from the literature on neurologic soft signs. The study was conducted from February 1991 to March 1993. RESULTS: Thirteen neurologic soft signs were significantly more frequent in the borderline group. Patients with borderline personality disorder showed more left side, right side, and total neurologic soft signs than controls (p = .0001). All patients in the borderline group exhibited at least 1 neurologic soft sign, while only 7 controls did (p = .0001). CONCLUSION: Our hypothesis was confirmed. These results add evidence to the possibility of the existence of a nonfocal central nervous system failure in borderline personality disorder.     

Urinary 3-methoxy-4-hydroxyphenylglycol sulfate excretion in seventy-three schoolchildren with minimal brain dysfunction syndrome

Although many authors have studied the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) of minimal brain dysfunction (MBD) children to explore a possible mechanism for this disorder, the mechanism remains unclear. The present study extends the determinations of urinary MHPG X SO4 in MBD schoolchildren to a larger sample to determine whether or not the function of central norepinephrine (NE) of MBD children is normal. 24-hr urinary excretion of MHPG X SO4 was determined in 73 schoolchildren with MBD and 57 normal controls. MGPG X SO4 level was significantly lower in the MBD children than in the control group. 38 of these children received an open trial of methylphenidate and the urine specimen was examined blindly. The children with marked improvement showed significant decrease in urinary MHPD X SO4 while the nonresponders showed no change, but rather a slight increase. This was also demonstrated in a second drug trial in which eight MBD children received Chinese herbal medicine. The authors compare the clinical data with the biochemical findings and point out that the MBD children developed hypoactivity of central NE, especially those with positive genetic factors in their family history.     

Amitriptyline and nortriptyline plasma levels, urinary 3-methoxy-4-hydroxyphenylglycol and clinical response in depressed women

Thirty-eight depressed female inpatients, treated intramuscularly with 100 mg/day amitriptyline (AMT), were monitored to investigate the relationships between plasma levels of the drug and its metabolite nortriptyline (NT), the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG), side effects and clinical response. Considering the whole group, the clinical improvement was better within an intermediate range of AMT plus NT plasma concentrations (100-200 ng/ml). A more favorable outcome was also observed at NT plasma levels below 55 ng/ml. No significantly different percent clinical response among the patient clinical subgroups was observed as well as no significant correlations between MHPG decrease and drug plasma levels.     

Stimulants, urinary catecholamines, and indoleamines in hyperactivity. A comparison of methylphenidate and dextroamphetamine

Children with attention deficit disorder with hyperactivity were given either methylphenidate hydrochloride or dextroamphetamine sulfate to compare the effects on urinary excretion of catecholamines, indoleamines, and phenylethylamine (PEA). Methylphenidate's effects were distinctly different from those of dextroamphetamine. After methylphenidate administration, both norepinephrine (NE) and normetanephrine (NMN) concentrations were significantly elevated, and there was a 22% increase in excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG). In contrast, after dextroamphetamine treatment, MHPG excretion was significantly reduced and NE and NMN values were unchanged. Excretion of dopamine and metabolites was unchanged by either drug. Urinary PEA excretion was not significantly changed after methylphenidate treatment, but increased 1,600% in response to dextroamphetamine. Methylphenidate treatment did not significantly alter serotonin or 5-hydroxyindoleacetic acid excretion. Effects of dextroamphetamine were not tested.     

Response to amitriptyline and urinary MHPG in bipolar depressive patients.

This investigation was done in order to test the hypothesis that urinary MHPG levels provide a predictor of response to therapy in depressed patients. 15 elderly biopolar depressives were included in this study. Their depressive state was estimated by the Hamilton Depressive Scale and their urinary MHPG levels were simultaneously measured before and after 5 weeks of amitriptyline therapy. When comparing amitriptyline responders to nonresponders by parametric techniques, the responders excreted significantly higher mean MHPG levels before the treatment than the nonresponders. During treatment MHPG levels rose significantly in both groups.     

Neurological soft signs and psychopathology: incidence in diagnostic groups.

In earlier studies the authors have reported impairments of cortical function in the parietal and frontal lobes of schizophrenic patients. In this study these results are pursued. The performance of different groups of psychiatric patients with respect to individual neurological soft signs rather than combined cortical function scores, was studied. The potential influence of psychotropic drugs on the significant findings was also analyzed. The results show that specific individual neurologic soft signs are significantly more frequently present in schizophrenics than in either controls or in other psychiatric groups. Additionally, there was no statistical evidence of psychotropic drug effects on the findings.     

Maternal characteristics and perceptions of pervasive and situational hyperactives and normal controls

Thirty 6- to 9-year-old boys were rated by their mothers and teachers as being pervasively hyperactive, situationally hyperactive, or not hyperactive at home or school. Maternal characteristics and perceptions of their children's behavior problems were collected. Children's global and molecular social skills were also assessed in a role-play format. Mothers of pervasive hyperactive boys reported significantly more overall stress in their relationship with their child and perceived their sons as displaying more behavioral problems compared to mothers of situational hyperactive and nonhyperactive children. Mothers of pervasive hyperactive boys also rated themselves as more depressed, less competent, more restricted, and frustrated compared to control mothers. Mothers of situational hyperactive children indicated that their sons displayed more behavior problems and reported more maternal stress compared to mothers of normal controls. Normal controls were rated as overall more socially skilled than situational hyperactive boys. The utility of the pervasive and situational hyperactivity distinction is discussed.     

Neurological soft signs as predictors of treatment response to selective serotonin reuptake inhibitors in obsessive-compulsive disorder

Neurological soft-sign abnormalities have been implicated in obsessive-compulsive disorder (OCD). This first comprehensive data analysis evaluated the association between baseline neurological soft signs and treatment response in 117 OCD patients treated with controlled-release fluvoxamine in a double-blind placebo-controlled trial. Total and right-sided soft signs for the responders and the nonresponders did not differ significantly. Left-sided visuospatial soft signs were significantly increased in treatment nonresponders compared to responders. These subtle neurological abnormalities may implicate a potential subgroup of OCD patients with poorer treatment response. This may have treatment implications and therefore serve as a screening tool in OCD.     

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.     

Stimulant drugs and activity level in hyperactive children.

This study of 14 hyperactive boys reports that activity and attention span appear to be affected by methylphenidate even in highly stimulating, informal settings. Comparison of the hyperactive boys with a group of 14 normal controls suggests that this drug induced reduction of activity and inattentiveness is not a "normalizing" effect. Implications of the findings are discussed.     

Urinary noradrenaline and serotonin metabolites in drug-free Parkinson patients and the effect of L-dopa treatment

3-methoxy-4-hydroxyphenylglycol (MHPG) and 5-hydroxyindoleacetic acid (5-HIAA) as well as homovanillic acid (HVA) and cyclic AMP were estimated in the morning urine of 41 drug-free parkinsonian patients and 25 hospitalized controls. In 29 patients, the estimations were repeated after 2 weeks treatment with L-dopa plus decarboxylase inhibitor. Drug-free patients excreted more MHPG and less 5-HIAA than controls. The difference from controls was significant for MHPG, only for the subgroup of patients with akinesia as the main symptom ( P = 0.001) and for 5-HIAA only for the tremor subgroup ( P = 0.03). 2 weeks treatment with L-dopa plus decarboxylase inhibitor, increased the MHPG excretion signficantly only for the akinesia subgroup, where the pretreatment MHPG values were high, while there was no change in MHPG excretion in the tremor and the rigidity subgroups. The treatment caused no change in the 5-HIAA excretion in the tremor subgroup, where the pretreatment values were low, while in the rigidity and akinesia subgroups 5-HIAA excretion was significantly decreased. These results, as well as our previous results on HVA and cyclic AMP, show that there are considerable differences among the subgroups of parkinsonian patients regarding the metabolism of dopamine, noradrenaline and serotonin.     

Noradrenergic output and clinical response in depressed women during amitriptyline therapy

The measurement of the urinary excretion of 3-methoxy-4-hydroxyphenylglycol (MHPG) in 59 unipolar depressed women before and during administration of 100 mg amitriptyline (AMT) i.m. daily for four weeks showed that the patients could be divided into high or low MHPG excretors. An analysis of the excretion course of MHPG and 3-methoxy-4-hydroxy mandelic acid during therapy showed, in most patients, a lower urinary excretion of both these noradrenaline (NA) metabolites in comparison with basal values. Therapy also decreased plasma noradrenaline concentrations and blood pressure values both at rest and on orthostatic challenge. Available evidence seems to suggest that AMT administration caused a lower overall noradrenergic output that might be partially responsible for a diminished sympathetic nervous activity. The authors were unable to confirm that the baseline MHPG level can predict the clinical response to antidepressant treatment and they found no significant correlations between changes in bio-chemical or physiological variables and drug plasma concentrations or clinical response. The possibility that depressed patients might be grouped according to their different NA metabolism needs to be validated in a larger patient sample.     

Disorders of noradrenergic pathways in anorexia nervosa. Results

Twelve patients suffering from mental anorexia were examined on clinical and biological grounds, based on the hypothesis of the functional depression of the noradrenergic track. The initial values of MHPG and of catecholamines were below normal. The quantitative results for depression and retardation were lessened significantly under beta-stimulant treatment. Only glucuro-conjugate MHPG excretion increased significantly, but the MHPG values were much lower than normal at the end of the treatment. The correlations between biochemical and behavioural parameters were worth noticing as far as the retardation scale was concerned. The present study shows the advantage of the dexamethasone suppression test and of the response of TSH under TRH.