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Biomedical subjects

D L Murphy

Publications and source records attributed to D L Murphy.

At least 397 records · Page 22Linked to original sources
PubMed1982

The sleep of patients with obsessive-compulsive disorder.

Fourteen patients with obsessive-compulsive disorder (OCD) were studied with all-night sleep EEG recordings. Nine of these patients reported abnormal sleep patterns before the polygraphic study. Analysis of the sleep records disclosed significantly decreased total sleep time with more awakenings, less stage 4 sleep, decreased rapid-eye-movement (REM) efficiency, and shortened REM latency compared with those of a group of age- and sex-matched normal subjects. These abnormalities generally resembled those of an age-matched group of depressed patients, although significant differences remained. These findings suggest that such sleep abnormalities as shortened REM latency may not be entirely specific for primary affective illness. They also point to a possible biological link between OCD and affective illness.

Adult↗
PubMed1982

REM sleep suppression induced by selective monoamine oxidase inhibitors.

The effects of 4 weeks of treatment with the selective monoamine oxidase (MAO) inhibiting antidepressant clorgyline and pargyline on the sleep of affectively disordered patients were studied. Both inhibitors resulted in near total suppression of REM sleep, a decrease in total sleep time, and an increase in the percent of stage 2 sleep. Clorgyline also increased awake time and decreased total recording period and sleep latency. In general, changes were greater for clorgyline than for pargyline and were about 50% slower to return to baseline after clorgyline compared to pargyline discontinuation. The results were consistent with the hypothesis that selective inhibition of the MAO type A, as produced by clorgyline, is sufficient to induce marked sleep changes. MAO inhibitor-induced receptor changes are proposed to account for the time course of the REM suppression and the REM rebound observed upon withdrawal.

Adult↗
PubMed1982

Localization of monoamine oxidases A and B in primate brains relative to neuron-specific and non-neuronal enolases.

Using serotonin and phenylethylamine deamination as measures of MAO A and MAO B activity respectively, positive correlations were observed between the activities of MAO A and MAO B in different areas of rhesus monkey and human brains. When the activities of MAO A and MAO B were compared with those of neuron-specific enolase and nonneuronal enolase (isozymes which are markers for neurons and glia), a slight but non-significant correlation was observed, suggesting that a simple distribution of MAO A in neurons and MAO B in glia is unlikely. This conclusion is supported by studies using synaptosomes, but contrasts with that from investigations of MAO from peripheral tissues, where experiments indicate that MAO A is predominantly localized in neurones.

Animals↗
PubMed1982

Changes in alpha- and beta-receptor densities in rat brain as a result of treatment with monoamine oxidase inhibiting antidepressants.

The effects of chronic administration of the nonselective monoamine oxidase (MAO) inhibitor, phenelzine, and two selective inhibitors, clorgyline, and pargyline on adrenergic receptor binding and MAO activity were studied in the rat brain. Chronic but not acute administration of both phenelzine and the MAO-A inhibitor, clorgyline, resulted in significant decreases in cortical beta-adrenoreceptor binding ([3H]dihydroalprenolol) of 47 and 24% respectively. In contrast pargyline, which only partially inhibited MAO-A, caused only a nonsignificant (7%) change in rat cortical beta-receptor binding. In a more detailed study, chronic administration of clorgyline also caused changes in alpha-adrenergic receptor binding: by day 3 of treatment, significant changes were already observable in alpha-2-adrenergic receptor binding ([3H]clonidine), although changes in alpha-1 ([3H]WB4101)- and beta ([3H]dihydroalprenolol)-cortical receptor binding were not present until day 10. After 21 days of clorgyline treatment, the Bmax's of alpha-2-, alpha-1- and beta-adrenergic cortical receptors were reduced by 62, 36 and 34% respectively. In brainstem, alpha-2- and beta-receptors were reduced by 60 and 74%. The magnitude of these changes and particularly the rapidity of the alpha-2 changes suggest that clorgyline-induced alpha-2 autoreceptor changes may precede and contribute to the changes in postsynpatic alpha-1- and beta-receptors. These sequential alterations in adrenergic receptors may be pertinent to the efficacy and delay in onset of the clinical changes which follow treatment with these antidepressants.

Adrenergic alpha-Antagonists↗
PubMed1982

Lifetime monoamine oxidase inhibition and sleep.

The effects of clorgyline, a type A monoamine oxidase (MAO) inhibitor, on the sleep of the rat were examined after subacute and lifetime administration. When 2 mg/kg 24 hours were given for 60 hours, type A MAO was inhibited by 92% and a significant reduction in REM sleep time was noted. When fetal rats were exposed to maternal dosage of 1 mg/kg/24 hours and then received this dose from one to 6 weeks postnatally, type A MAO was inhibited by 99%, but there were no alterations in the EEG sleep stages. In summary, subacute administration of clorgyline resulted in decreases in both Type A MAO and REM sleep; during chronic administration in a developing animal, Type A MAO was again decreased, but there was no corresponding change in REM sleep.

Animals↗
PubMed1982

Cerebrospinal fluid hydroxylase cofactor in schizophrenia.

Cerebrospinal fluid levels of pterin cofactor were measured in off-medication schizophrenic patients and normal control subjects as one aspect of monoamine physiology in schizophrenia. Pterin cofactor is essential for the hydroxylation of several substances including tyrosine, the rate-limiting step in the synthesis of dopamine and norepinephrine. No significant differences were found. Platelet monoamine oxidase activity correlated significantly with pterin levels in male schizophrenic and in female control subjects.

Adult↗
PubMed1982

The dexamethasone suppression test in patients with primary obsessive-compulsive disorder.

The dexamethasone suppression test (DST) was administered to 16 obsessive-compulsive disorder (OCD) patients. Six of these patients (37.5%) had an abnormal DST response. There was a trend for patients with the DST abnormality to have higher depression rating scale scores and a higher incidence of family history of affective illness compared to DST suppressors. Although 7 of the 16 OCD patients met DSM-III criteria for major depressive disorder, in every case the affective symptoms were secondary to the primary obsessional illness. The relationship of the DST to the specificity of psychiatric diagnoses is discussed.

Adolescent↗
PubMed1982

Growth hormone response to clonidine as a probe of noradrenergic receptor responsiveness in affective disorder patients and controls.

The growth hormone (GH) response to the alpha-adrenergic agonist clinidine was blunted in 19 depressed patients compared to 20 controls. The difference remained significant when age- and sex-matches pairs of patients and controls were compared from this sample, either including or excluding subjects with elevated GH baseline levels. Plasma levels of free 3-methoxy-4-hydroxyphenyl-glycol (MHPG) were assayed in blood samples drawn just before the clonidine infusion. A modest negative correlation was found between the plasma MHPG values and the magnitude of the GH responses to clonidine, although baseline plasma MHPG levels were not significantly different between patients and controls. The diminished GH response to clonidine observed suggests that many depressed patients may have decreased alpha-adrenoreceptor responsiveness. Decreased responsiveness may in some cases be associated with relatively increased indices of presynaptic noradrenergic availability. Such a model might have implications for understanding the functional status of the noradrenergic neurotransmitter system in depressed patients and the possible subtyping of affective disorder patients.

Clonidine↗
PubMed1982

Possible subsensitization of alpha 2-adrenergic receptors by chronic monoamine oxidase inhibitor treatment in psychiatric patients.

Clonidine was administered to nine psychiatric patients before and after chronic treatment (3 to 4 weeks) with clorgyline, a selective monoamine oxidase type A inhibitor with antidepressant efficacy. The hypotensive response to clonidine, believed to be mediated by brain alpha 2-adrenergic receptors, was significantly attenuated by chronic but not acute (2 to 3 days) clorgyline treatment, with a time course similar to the onset of its clinical efficacy. This study supports the hypothesis that subsensitization of alpha 2-adrenergic receptors plays an important role in clorgyline's antidepressant effects and may constitute a key contribution to the mode of action of other antidepressant treatments as well.

Adult↗
PubMed1982

Growth hormone response to clonidine unchanged by chronic clorgyline treatment.

The growth hormone (GH) response to the alpha 2-adrenergic agonist, clonidine, was determined before and after chronic clorgyline treatment in 10 psychiatric patients. No significant differences emerged in the magnitude of the GH response to clonidine before as compared to after clorgyline. These results do not support the hypothesis that postsynaptic alpha 2-adrenergic responsiveness is enhanced following chronic antidepressant treatment.

Adult↗
PubMed1982

Plasma steady-state concentrations of hydroxylated metabolites of clomipramine.

Plasma clomipramine, desmethylclomipramine, 8-hydroxyclomipramine, and 8-hydroxydesmethylclomipramine concentrations were measured in nine obsessive-compulsive outpatients. The mean dose of clomipramine at steady state was 237.5 +/- 51.8 (SD) mg/24 hr. The mean concentrations at steady state were: clomipramine, 147.5 +/- 57.5; desmethylclomipramine, 313.0 +/- 170.0; 8-hydroxyclomipramine, 56.1 +/- 20.9; and 8-hydroxydesmethylclomipramine, 152.7 +/- 83.2 ng/ml. In vitro, the hydroxymetabolites of clomipramine and desmethylclomipramine exhibited serotonin reuptake potency of the same order as that of the parent compounds.

Adult↗
PubMed1982

2-year follow-up of subjects and their families defined as at risk for psychopathology on the basis of platelet MAO activities. 2-year follow-up of low platelet MAO.

College students hypothesized as being at risk for psychiatric dysfunction solely on the basis of their MAO platelet activities were briefly interviewed 2 years after completion of initial studies. These 33 low-MAO subjects reported more job instability than 30 high-MAO control subjects. Moreover, the low-MAO males had fallen about half a year behind their high-MAO counterparts in school. No differences in other aspects of social status or psychosocial problems had developed, although the low-MAO subjects smoked significantly more cigarettes and tended to report more major or minor medical problems. While the low-MAO subjects reported no significant decline in their own mental health status during this period, more low-MAO male subjects did report mental health problems in their families, especially depression, alcoholism, and suicide attempts, as well as significantly more mental health interventions among family members, such as psychiatric visits, prescription of psychotropic medication, and psychiatric hospitalization.

Achievement↗
PubMed1982

High plasma norepinephrine levels in patients with major affective disorder.

The authors found that patients with major affective disorder had higher levels of plasma norepinephrine and higher pulse rates (tachycardia) than healthy control subjects, but their blood pressures were normal. These measurements were similar in all three subgroups of patients with affective disorder--manic, bipolar depressed, and unipolar. Because norepinephrine is the primary neurotransmitter of the sympathetic nervous system, these data suggest sympathetic hyperactivity in the major affective disorders. This conclusion is compatible with recent speculation based on the effect of antidepressants on noradrenergic receptors and a failure of alpha-receptors to downregulate normally in patients with major affective disorder.

Adult↗
PubMed1982

Intellectual function in primary affective disorder.

The possible effects of clinical depression on intellectual function were investigated in unipolar and bipolar patients. Ninety-six hospitalized depressed patients completed the Wechsler Adult Intelligence Scale (WAIS) on admission and 34 were retested on remission. The high average full scale IQs found remained relatively stable throughout, consistent with earlier studies indicating a limited relationship between intellectual function and clinical severity of depression. No evidence was found for retarded psychomotor activity in bipolar groups or increased psychomotor activity in unipolar groups on three WAIS subtests of psychomotor function, but full scale IQ increased slightly in hypomania.

Affective Disorders, Psychotic↗
PubMed1982

Chronic effects of a monoamine oxidase-inhibiting antidepressant: decreases in functional alpha-adrenergic autoreceptors precede the decrease in norepinephrine-stimulated cyclic adenosine 3': 5'-monophosphate systems in rat brain.

Various antidepressant drugs (monoamine oxidase inhibitors and tricyclics) enhance norepinephrine availability and lead to adaptive changes in brain noradrenergic systems, namely, decreases in the number of beta receptors and in the responsiveness of adenylate cyclase to norepinephrine monamine oxidase inhibitor, but not after 3 days, there is an increase in norepinephrine release from rat brain microsacs in response to 43 mM KCl stimulation. Microsacs prepared from 21-day clorgyline-treated animals also show a marked decrease in the inhibition of norepinephrine release caused by the alpha 2-selective agonist clonidine. These functional changes in norepinephrine release mechanisms are accompanied by a 53% reduction in brainstem alpha 2 receptor density as measured by [3H]clonidine binding. At the same time, despite findings of a decrease in beta receptor number as determined by [3H]dihydroalprenolol binding data, no significant decrease in the responses of cyclic adenosine 3': 5'-monophosphate (cyclic AMP) systems to norepinephrine stimulation is observed. Decreases in the cyclic AMP response are observed by day 35 of clorgyline treatment. The results provide direct physiological support for a change in the norepinephrine release mechanism and an effect on autoreceptors, specifically, preceding postsynaptic adaptive changes in the instance of one antidepressant, clorgyline. Difficulties in observing such changes with other antidepressants may result from the multiple nature of alpha-adrenergic receptors, especially as measured by radioactive ligand techniques; the lack of a direct relationship between physiological changes and receptors as measured by radioligand techniques; the large doses of monoamine oxidase inhibitors used in some studies; and the possible multiplicity of antidepressant molecular mechanisms.

Animals↗