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D L Murphy

Publications and source records attributed to D L Murphy.

At least 37 records · Page 2Linked to original sources

Brain region differences and some characteristics of monoamine oxidase type A and B activities in the vervet monkey.

Monoamine oxidase in the vervet monkey showed greater variations in activity in six brain regions when tyramine or phenylethylamine was used as the substrate (3.8- to 4.1-fold differences) than when serotonin was the substrate (1.8-fold differences). With phenylethylamine and tyramine as substrates, the highest MAO specific activities were found in the hypothalamus and the lowest in the cerebellum and cortex. With serotonin as the substrate, the highest specific activities were in the mesencephalon and cortex. The inhibition of tyramine deamination by clorgyline and deprenyl yielded biphasic plots indicative of the presence of MAO-A and MAO-B enzyme forms in the vervet brain. On the basis of these inhibitor curves, the vervet brain could be estimated to contain approximately 85% MAO-B and 15% MAO-A, in contrast to rat brain which contains 45% MAO-B and 5% MAO-A. The inhibition of serotonin deamination by deprenyl in vervet brain yielded a biphasic plot, suggesting that some serotonin deamination in the vervet is accomplished by the MAO-B enzyme form. Estimations of the relative amounts of MAO-A and MAO-B based on inhibitor curves or based on substrate ratios yielded proportionate results which were in close agreement across the different brain regions, supporting the validity of these approaches to estimating MAO-A and MAO-B activities.

Animals

The central noradrenergic system and affective response to MAO inhibitors.

1. In humans, norepinephrine (NE) has been postulated to be involved in the regulation of mood and behavior and to be altered in patients with manic-depressive illness. 2. Recent methodological advances have made possible a more direct assessment of central noradrenergic activity by the accurate measurement of the small amounts of NE and of the enzyme responsible for the conversion of dopamine to NE, dopamine-beta-hydroxylase (DBH), found in cerebrospinal fluid (CSF). 3. Cerebrospinal fluid samples were obtained from depressed patients both before and after treatment with two monoamine oxidase-inhibiting antidepressant drugs, clorgyline and pargyline. 4. Patients were rated twice daily by nursing staff on a modified 15-point scale for severity of global depression and anxiety. Patients were also rated using the Hamilton depression rating scale. 5. High negative correlations were observed between the drug-related changes in CSF NE and the changes in depression ratings on both the global ratings (r = -.95, p less than .001) and the Hamilton rating scale (r = -.81, p less than .01). Changes in NE were also highly correlated with changes in global anxiety ratings (r = -.85, p less than .01) calculated on the basis of changes from baseline for each measurement. Drug-related changes in CSF DBH similarly showed negative correlations with clinical response (r = -.79, r = -.38, r = -.68 respectively). In contrast, no significant correlations were found when drug-related changes in CSF MHPG were compared to changes in clinical state.

Adult

Platelet monoamine oxidase activity correlates with social affiliative and agonistic behaviors in normal rhesus monkeys.

After a 4-mo study period, quantitative measures of stable behavioral traits in individual rhesus monkeys correlated significantly with platelet monoamine oxidase (MAO) activity. In particular, behavioral items reflecting social activity and social contact, both agonistic and affiliative, were inversely correlated with enzyme activity. Time spent alone was positively correlated. Since platelet MAO activity is generally stable and predominantly controlled by genetic factors, it might serve as a "genetic marker" for individual differences in "normal" behaviors possibly related to differences in MAO activity in the brain and other tissues.

Age Factors

Prediction of antidepressant responses to imipramine.

45 patients hospitalized for depression who had received double-blind trials with imipramine were examined for possible associations between pretreatment responses to the Minnesota Multiphasic Personality Inventory (MMPI) and their behaviorally-rated responses to this drug. Each patient was randomly assigned to one of two groups with the restriction that the number of responders and nonresponders be balanced for sex. Results from the group A patients suggest that responders and nonresponders to imipramine were best identified by using two sex-specific, empirically-derived, MMPI scales. In contrast, 12 of 13 regular validity and clinical scales and all 49 of the selected special scales of the MMPI failed to separate responders from nonresponders. In the cross-validation study with the group B patients, we were able to predict female and male responders from nonresponders by the new imipramine response scale with accuracy rates of 93 and 100%, respectively. The implications of these results are discussed.

Depression

Tyramine infusions in bipolar illness: behavioral effects and longitudinal changes in pressor sensitivity.

Steady state intravenous tyramine dose pressor-response tests were administered to a patient with bipolar illness during depressed and hypomanic phases of her illness. The greatest tyramine sensitivity while unmedicated occurred when the patient was hypomanic, and the least sensitivity when she was depressed before her first switch. The data raise the possibility that changes in peripheral alpha-adrenergic receptor sensitivity accompany spontaneous mood cycles. Tyramine produced a replicable mood and cognitive alteration only in the infusion closest to the switch from hypomania to depression, suggesting that the CNS may be particularly susceptible to peripheral noradrenergic inputs at specific points in bipolar illness.

Adult

Paranoia and platelet MAO in normals and nonschizophrenic psychiatric groups.

The authors compared the correlation between platelet monoamine oxidase (MAO) activity and the Paranoia (Pa) scale of the Minnesota Multiphasic Personality Inventory in several groups. The data suggest that there is a positive association between high MAO activity and high scores on the Pa scale but only in samples with psychopathology.

Affective Symptoms

The role of plasma amine oxidase, platelet monoamine oxidase, and red cell catechol-O-methyl transferase in severe behavioral reactions to disulfiram.

The authors assayed platelet monoamine oxidase (MAO), plasma amine oxidase (AO), and red cell catechol-O-methyl transferase (COMT) in 32 male alcoholics before they began disulfiram treatment. Seven subjects developed psychotic reactions to disulfiram; these 7 had significantly lower pretreatment MAO and AO levels and significantly higher COMT than the patients who had no adverse reactions to disulfiram, which suggests that severe behavioral reactions to disulfiram are associated with differences in enzyme activities.

Adolescent

Platelet MAO activity and evoked potentials in the identification of subjects biologically at risk for psychiatric disorders.

Individuals potentially at risk for psychiatric disorders were identified by screening 375 college student volunteers for low platelet monoamine oxidase (MAO) activity levels. The lower and upper 10% in MAO activity were administered a personal and family history interview, psychological tests and average evoked response (AER) electroencephalographic procedures. Results indicated that low MAO males and females were socially more active, had more psychiatric contact, and had relatives who were psychiatrically more disturbed than high MAO subjects. Low MAO males had more convictions, experimented more with illegal drugs and had elevated scores on the MMPI. AER criteria further defined a high risk group of low MAO-AER augmenters which had more suicides among their relatives and higher scores on the schizophrenia scale of the MMPI.

Adolescent

Platelet monoamine oxidase activity in schizophrenia: a review of the data.

The authors review studies of platelet and white cell monoamine oxidase (MAO) activity in schizophrenic patients. The data on acute schizophrenic patients remain inconclusive. Review of 26 reports of chronic schizophrenic patients leaves little doubt, however, that there is a subgroup in which the enzyme activity is decreased. Despite the strong association of decreased MAO activity and chronic schizophrenia, the etiological relationship of low platelet MAO activity to schizophrenia has not been demonstrated. More complete diagnostic descriptions will shed light on precisely which patients have lowered MAO activity. Further metabolic investigations with such patients are needed to determine the physiological significance of this phenomenon.

Acute Disease

Psychological characteristics corresponding to low versus high platelet monoamine oxidase activity.

From an original sample of 375 college students and employees studied for platelet MAO activity, 66 subjects representing the lower and upper deciles of the sample were contacted for further study, including administration of the booklet form of the MMPI. We analyzed what psychological characteristics might be associated with differences in MAO activity and attempted to cross-validate these characteristics by using them to predict the separability of low vs. high MAO subjects. Each subject was randomly assigned to one of two groups in which the low and high MAO subjects were balanced for sex. For 16 women in group A, a MAO scale discriminated low and high subjects with 100% accuracy. For 18 men in group A, a separate MAO scale discriminated with 94% accuracy. To cross-validate these results, the two scales were applied to another population; both discriminated low and high MAO women and men with a combined 97% accuracy. The thematic content of the two scales is discussed in the light of other reports on the psychological characteristics of low and high MAO subjects, including the apparent relationship between the scale content and the clinical features of bipolar affective disorder.

Adolescent