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Biomedical subjects

L J Siever

Publications and source records attributed to L J Siever.

At least 145 records · Page 8Linked to original sources
PubMed1984

Biological markers in obsessive-compulsive and affective disorders.

To explore the relationship between obsessive-compulsive disorder (OCD) and affective disorder, patients with OCD were studied using a series of biological markers which have been previously reported to be abnormal in patients with affective illness. These "markers" included the dexamethasone suppression test, sleep electroencephalography, the plasma growth hormone response to clonidine, and platelet 3H-imipramine binding. Results from each of these studies suggested similarities between patients with obsessional disorder and those with affective illness. Many of these biological abnormalities were evident in obsessional patients who did not manifest depressive symptoms. As a tricyclic antidepressant, clomipramine, has been found to reduce obsessional symptoms, the relationship between these "affective-like" laboratory findings and the clinical response to clomipramine was studied in a subgroup of OCD patients. Preliminary results suggest that none of the markers studied predict clomipramine response.

Blood Platelets↗
PubMed1984

Platelet alpha-adrenergic binding and biochemical responsiveness in depressed patients and controls.

In a study of platelet alpha 2-adrenergic receptor number in depressed patients, binding of tritiated dihydroergocriptine (3H-DHE) to platelet membranes was measured in 23 depressed patients and 51 controls. To examine the functional responsiveness of the platelet alpha 2-adrenergic receptor, basal cyclic adenosine 3',5'-monophosphate (cAMP) production, prostaglandin E1 (PGE1) stimulation of cAMP production, and norepinephrine (NE) inhibition of PGE1-stimulated cAMP production were measured in 23 depressed patients and 53 control subjects. Finally, plasma NE concentration was measured in 20 patients to explore the possible relationship between this endogenous agonist and platelet alpha 2-adrenergic receptor function. 3H-DHE binding to platelet membranes was significantly increased in the depressed patients compared to control subjects. Both the PGE1-stimulated cAMP response and the inhibition of this response by NE were significantly reduced in the depressed patients compared to the control subjects. Thus, an apparent dissociation between alpha 2-adrenergic receptor binding and functional responsiveness was observed. Plasma NE concentrations were neither significantly different in the depressed patients than in the controls nor correlated with any of the measures of cAMP responsiveness. They were, however, significantly negatively correlated with 3H-DHE binding in depressed patients with adequate PGE1 stimulation of cAMP production.

Adult↗
PubMed1984

The Genain Quadruplets: psychological studies.

A series of behavioral studies is reported on the Genain Quadruplets. These monozygous women, all of whom have suffered or are suffering from schizophrenia, were studied previously at the National Institute of Mental Health (1955-1958) and were the subject of an extensive report by Rosenthal (1963). Although the Genains are genetically identical, the expression of the schizophrenic disorder is unequal among the quads, and this circumstance has led to speculation about the relative contributions of nature and nurture (or diathesis and stress in Rosenthal's terminology) in the development of this disease. Two goals were pursued in this investigation: one concerned a comparison of the status of the Genains in 1981 as compared with 1958; the other concerned whether data from the armamentarium of newer behavioral and neurobiological techniques invented and employed since 1958 might shed some light on the unequal expression of schizophrenia among the quadruplets. We conclude that the Genains are functioning about as well as they ever have in their adult lives, and scores on attentional tests show improvement as compared to 1958 measures. This is probably attributable to the medication (primarily neuroleptics) and other supportive treatments they have received over the years. With respect to the varying degrees of illness seen in the Genains, scrutiny of the biochemical, physiological, neuroradiological, immunogenetic, and behavioral test data leads to speculation that certain unique biochemical findings interacting with differing types and amounts of cerebral pathology constitute a major cause of the variable expression of the schizophrenic diathesis.

Antipsychotic Agents↗
PubMed1984

Fear and anxiety: relationship to noradrenergic function.

The experiences of human fear and anxiety are discussed within the context of locus ceruleus function in animals. The rationale for studying correlates of noradrenergic function, such as 3-methoxy-4-hydroxyphenethylene glycol (MHPG), is reviewed, and data demonstrating a positive correlation between plasma free MHPG and state anxiety in normal volunteers is presented. The behavioral effects of oral caffeine (240-720 mg), intravenous clonidine (2 micrograms/kg), and oral yohimbine (20 mg) were studied in various psychiatric patients and normal volunteers. Caffeine and yohimbine had anxiogenic properties; conversely, clonidine reduced self-rated measures of anxiety across a wide spectrum of psychiatric conditions. These findings expand previous research indicating that noradrenergic hyperactivity may be associated with many types of human fear and anxiety.

Animals↗
PubMed1984

Impaired smooth pursuit eye movement: vulnerability marker for schizotypal personality disorder in a normal volunteer population.

Impaired smooth pursuit eye movement has been proposed as a possible biologic marker for schizophrenia. Preliminary studies have suggested that this impairment may be associated with social introversion and related psychopathology in a nonpsychiatric population. To evaluate the relationship between dysfunctional smooth pursuit eye movement and schizophrenia-related psychopathology, the authors screened a new, volunteer sample of 284 male college students for eye tracking accuracy. Volunteers identified as low-accuracy trackers were significantly more likely to be diagnosed (blindly) as having a schizotypal personality disorder by DSM-III criteria than those identified as high-accuracy trackers. The authors suggest that disordered smooth pursuit eye movement may reflect a vulnerability marker for schizotypal personality disorder.

Adult↗
PubMed1984

Differential inhibitory noradrenergic responses to clonidine in 25 depressed patients and 25 normal control subjects.

The authors measured plasma 3-methoxy-4-hydroxyphenylglycol (MHPG), plasma norepinephrine, blood pressure, and heart rate responses to the alpha 2-adrenergic agonist clonidine in 25 depressed patients and 25 normal control subjects. In the control subjects clonidine reduced plasma norepinephrine, blood pressure, and heart rate significantly more than placebo. In the depressed patients clonidine reduced blood pressure and the percent fall in plasma norepinephrine but not plasma MHPG or heart rate significantly more than placebo. The absolute and percent reductions in plasma MHPG and heart rate following clonidine were significantly less than in control subjects. These results raise the possibility that the sensitivity of the alpha 2-adrenergic receptors inhibitory to noradrenergic output may be reduced in depression.

Adult↗
PubMed1984

The psychopharmacologic treatment of personality disorders.

We have reviewed both the rationale for and approaches to the use of psychotropic medications in the treatment of personality disorders. Despite some studies that may provide the seeding crystals around which significant data bases regarding the drug treatment of personality disorders will develop, the pharmacologic treatment of personality disorder remains a clouded area governed more by opinion than fact. Clinicians must still be guided by basic clinical sense regarding the use of medications with these patients. Some questions to ask are the following: Has the patient responded to medications in the past? What are the risks for abuse or self-destructive acting out? What is the risk-to-benefit ratio for the introduction of a drug into a psychotherapeutic situation at a given time? Is hospitalization necessary to assess the potential benefits of medication to the patient while minimizing the potential to act out? Although these guidelines may seem inadequate, clinicians can take some solace in the fact that ongoing studies will lead to better informed psychopharmacologic choices for patients with personality disorders.

Anticonvulsants↗
PubMed1984

New studies and perspectives on the noradrenergic receptor system in depression: effects of the alpha 2-adrenergic agonist clonidine.

In an attempt to understand the dynamics of noradrenergic function in depression, we evaluated neuroendocrine, biochemical, cardiovascular, and behavioral responses to the acute intravenous administration of the alpha 2-adrenergic agonist, clonidine, in depressed patients and normal controls. Significantly more variance was observed in the depressed patients than the controls for most indices of basal noradrenergic output including plasma norepinephrine (NE) and 3-methoxy-4-hydroxyphenylglycol (MHPG). Growth hormone, plasma MHPG, and heart rate responses to clonidine were reduced in the depressed patients compared to the controls, all suggesting reduced responsiveness of alpha 2-adrenergic receptors in depression. Baseline levels of cortisol were elevated in the depressed patients compared to the controls. Clonidine decreased cortisol to normal levels in the depressed patients but had little effect in the controls. Thus the depressed patients manifested a significantly increased cortisol response to clonidine. These data raise the possibility that the hypercortisolemia of depression may be related to noradrenergic dysfunction. Clonidine also significantly reduced anxiety in the depressed patients, particularly those with elevated basal plasma MHPG, but not in controls. These results suggest that diminished alpha 2-adrenergic responsiveness as documented by decreased endocrine, biochemical, and physiological responses to clonidine may be related to the depressive and anxiety symptoms as well as the neuroendocrine disturbances characteristic of many depressed patients.

Adult↗
PubMed1983

The search for a schizotype. Crossing the border again.

We reexamined case records from the Danish Extended Family Study to find so-called borderline schizophrenic (B3) persons who were clustered in the biologic relatives of chronic schizophrenic adoptees. A syndrome can be identified in these B3 cases that is distinguishable from borderline personality disorder and other personality disorders. Its discriminating features suggest that current DSM III criteria for schizotypal personality disorder be revised to include new criteria for somatization and social role dysfunction and a shift away from the past emphasis on psychoticlike experiences. Although the methodological limitations in this and other studies that have searched for a schizotype necessitate further research on the criteria for this new category, there is growing evidence to support its validity as a psychiatric diagnosis.

Adoption↗
PubMed1983

Effect of long-term clorgyline administration on human platelet alpha-adrenergic receptor binding and platelet cyclic AMP responses.

Platelet alpha 2-adrenergic receptor number and physiologic responsiveness, as well as plasma norepinephrine (NE), were evaluated in psychiatric patients with major depressive disorder before and during chronic clorgyline treatment. The alpha 2-adrenergic receptor number was determined by measuring the binding of tritiated dihydroergocriptine (3H-DHE) to platelet membranes. Physiologic responsiveness was determined by measuring the response of cyclic adenosine 3'-5'-monophosphate (cAMP) to prostaglandin E1 (PGE1), and the inhibition of the PGE1-stimulated cAMP response by NE in intact platelets. No significant differences from pretreatment values were observed in platelet alpha 2-adrenergic binding or responsiveness during clorgyline treatment. Baseline platelet cAMP production and plasma NE levels were significantly decreased after chronic clorgyline treatment. Previous studies on animals and humans have suggested that brain alpha 2-adrenergic receptor responsiveness decreases during chronic clorgyline treatment. The present findings therefore suggest that such changes may represent adaptations induced by long-term clorgyline administration which may differ between the brain and the platelet, thus illustrating potential limitations of the study of platelet alpha 2-adrenergic receptors as a model for central alpha 2-adrenergic receptor adaptation.

Adult↗
PubMed1983

Clinical studies of monoamine receptors in the affective disorders and receptor changes with antidepressant treatment.

Pre-clinical and clinical studies suggest that the responsiveness of monoamine and cholinergic receptors may be altered in the affective disorders and that antidepressants may modify the sensitivity of these receptors. The growth hormone response to clonidine is reduced in depressed patients compared to controls according to several independent studies, suggesting that post-synaptic alpha 2-adrenergic receptors may be less responsive in depressed patients. The cortisol response to clonidine is enhanced in depressed patients compared to controls in our study raising the possibility that cortisol hypersecretion in depressed patients may be related to noradrenergic dysfunction. The hypotensive response to clonidine is blunted in patients on chronic antidepressant treatment with either clorgyline or desipramine suggesting that pre-synaptic alpha 2-adrenergic receptors may subsensitize with chronic antidepressant treatment. The prolactin increase in response to fenfluramine is less in depressed patients compared to controls suggesting decreased functional activity of the serotonergic system in depression. Platelet alpha 2-adrenergic receptor number as measured by tritiated dihydroergocriptine (3H-DHE) binding is increased in depressed patients compared to controls, while cyclic 3'-5' adenosine monophosphate (cAMP) production in response to prostaglandin E1 (PGE1) and norepinephrine (NE) inhibition of PGE1-stimulated cAMP production are reduced in the platelets of depressed patients. Thus, it is not clear that increased 3H-DHE binding reflects increased functional responsiveness and might in fact be compensatory to decreases in functional responses of alpha 2-adrenergic receptors.

Clonidine↗
PubMed1983

Growth hormone response to clonidine in obsessive-compulsive patients.

We have observed a lesser growth hormone response to intravenous clonidine administration in nine obsessive-compulsive disorder patients meeting research diagnostic criteria than in nine matched controls. The obsessive-compulsive disorder patients had higher plasma free 3-methoxy-4-hydroxyphenylglycol and plasma norepinephrine levels before clonidine than the controls. As blunted growth hormone responses to clonidine are also characteristic of affective disorder patients, these results support other observations of a psychobiologic affinity between these two groups and are also compatible with an association between increased presynaptic noradrenergic activity and decreased post-synaptic receptor responsiveness.

Adolescent↗
PubMed1982

Smooth pursuit eye tracking impairment: relation to other 'markers' of schizophrenia and psychologic correlates.

Smooth pursuit eye tracking impairment has been observed in the major psychoses, particularly schizophrenia. To understand better the relationship of smooth pursuit disruption to personality dispositions linked to psychiatric syndromes and to two other "marker variables" associated with psychosis (low platelet monoamine oxidase [MAO] activity and poor performance on the continuous performance task [CPT]), we studied the psychologic, biochemical, and psychophysiologic correlates of impaired smooth pursuit tracking in two nonpsychiatric patient populations. One sample consisted of 67 volunteers screened for extreme values in a distribution of platelet MAO activities, and the second included 29 volunteers screened for extreme scores on the CPT. An aggregate of about 5% of both samples showed clearly dysfunctional smooth pursuit. Eye tracking dysfunction did not seem to be related to either MAO or CPT performance in either study. Both studies were consistent in showing that subjects with impaired smooth pursuit eye tracking had a psychologic profile characterized particularly by social introversion.

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↗