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Biomedical subjects

E Giller

Publications and source records attributed to E Giller.

At least 19 recordsLinked to original sources
PubMed1990

The dexamethasone suppression test and thyrotropin-releasing hormone stimulation test in posttraumatic stress disorder.

Male veterans with posttraumatic stress disorder (PTSD) (n = 11), including 6 with concurrent major depressive disorder (MDD), were compared to veterans with MDD alone (n = 18) and to 28 controls in their response to the dexamethasone suppression test (DST) and thyrotropin-releasing hormone (TRH) stimulation tests. We found higher levels of 4 PM serum cortisol and lower peak thyroid-stimulating hormone (TSH) response to TRH in the MDD patients than in either the PTSD patients or controls, in spite of equivalent levels of depression for MDD and PTSD. DST suppression (cortisol less than 5 mg/dl) occurred in 90% of control, 90% of PTSD, and 78% of MDD subjects, whereas TRH blunting (dTSHmax less than 7 microU/ml) occurred in 28% of control, 27% of PTSD, and 67% of MDD subjects. Rather than blunting, four PTSD patients (36%) and only 10% of the control and MDD subjects had high TSH responses (13-24 microU/ml), which may be linked to high noradrenergic activity, since subclinical hypothyroidism seemed unlikely.

Adult↗
PubMed1989

Serum concentrations of circulating thyroid hormones in a group of depressed men.

Levels of circulating total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine TT3 and thyrotropin (TSH) were determined in 27 men with unipolar major depressive disorder ages 24-50, mean +/- SEM 36.9 +/- 2.9 years, and 38 healthy controls (HC) ages 20-50, mean +/- SEM 34.2 +/- 3.1 years. No significant differences were observed between HC and depressed men with regard to TT4 and FT4. Mean TT3 levels were lower, and mean TSH levels higher in depressed patients than in HC, p less than 0.05 for both, compatible with possible subclinical primary hypothyroidism in depressed patients. Consistent with this, an inverse correlation between basal TSH values and TT3 (r = -0.38, p less than 0.05) was noted in depressed but not in HC subjects.

Adult↗
PubMed1988

Platelet monoamine oxidase activity and tardive dyskinesia.

A few studies of chronic psychiatric inpatients have reported an inverse association between platelet monoamine oxidase (MAO) activity level and tardive dyskinesia (TD). In contrast to these earlier findings, we found no significant or consistent association between platelet MAO activity level and TD occurrence when we controlled for other TD predictors in a case-control study of 80 outpatients maintained on neuroleptic medications. We did find, however, that black subjects had significantly lower levels of MAO activity than did whites in an analysis controlling for age, sex, and neuroleptic dose.

Adult↗
PubMed1988

Neuroendocrine aspects of suicidal behavior.

To assess biologic risk factors in suicidal behavior accurately, it is necessary to distinguish prospective from retrospective design. The former studies are more likely to elicit information concerning possible risk factors in suicide, whereas the latter may be better indicators of biologic traits. In both types of investigations, measures taken close to the suicide attempt are more likely to reflect the biologic state of the individual at the time of the behavior. Although the abnormalities present in suicidal individuals are not entirely clear, most evidence to date suggests an overactivity of the hypothalamic-pituitary-adrenal axis and a dysregulation of both serotonin and adrenergic metabolism. These systems are interrelated. Both animal and human studies have established that a multivariate biologic approach is necessary to the understanding of the pathophysiology of suicide.

Dexamethasone↗
PubMed1988

Neuroendocrine aspects of suicidal behavior.

To assess biologic risk factors in suicidal behavior accurately, it is necessary to distinguish prospective from retrospective designs. The former studies are more likely to elicit information concerning possible risk factors in suicide, whereas the latter may be better indicators of biologic traits. In both types of investigations, measures taken close to the suicide attempt are more likely to reflect the biologic state of the individual at the time of the behavior. Although the abnormalities present in suicidal individuals are not entirely clear, most evidence to date suggests an overactivity of the hypothalamic-pituitary-adrenal axis and a dysregulation of both serotonin and adrenergic metabolism. These systems are interrelated. Both animal and human studies have established that a multivariate biologic approach is necessary to the understanding of the pathophysiology of suicide.

Adrenal Cortex Hormones↗
PubMed1985

The norepinephrine-to-epinephrine ratio in patients with a history of suicide attempts.

Norepinephrine and epinephrine were measured serially in 24-hour urine collections from 99 male psychiatric inpatients with mixed diagnoses. The group was blindly divided into those with a previous history of at least one suicide attempt (N = 38) and those without such a history (N = 61). The ratio of norepinephrine-to-epinephrine levels was significantly lower in the group with a history of suicide attempts. The authors discuss the possibility that a low norepinephrine-to-epinephrine ratio is a risk factor for suicidal behavior.

Adult↗
PubMed1985

Long-term amitriptyline in chronic depression.

Medication was discontinued under a placebo-controlled, double-blind, six-month protocol with 17 chronically depressed patients who had been taking an average daily dose of 138 mg amitriptyline (AMI) for an average of 3.7 years. Only one of nine patients became depressed on active medication, while of the 15 patients receiving a placebo trial, 11 had a depressive recurrence at an average time of 9.3 weeks. These 11 were subsequently restarted on AMI, and responded similarly to the way in which acutely depressed patients respond, although the patients showed either a need for less AMI or decreased symptoms, compared to entry. Tolerance did not develop to anticholinergic side-effects during long-term medication. Twelve of the 15 patients on placebo showed a withdrawal reaction during the first few weeks of tapered AMI discontinuation which could be distinguished from recurrence of depression. This study suggests that the majority of patients on long-term antidepressant will suffer a recurrence of depressive symptoms when the medication is discontinued.

Amitriptyline↗
PubMed1984

Platelet and fibroblast monoamine oxidase in alcoholism.

Monoamine oxidase (MAO) activity has been reported to be low in platelets (MAO B) and brain (MAO A and B) of some patients with alcoholism compared to control subjects. Whether the decreased platelet MAO activity found in alcoholism is secondary to the effect of alcohol or exists before alcohol abuse is not clear. The hypothesis that altered MAO A activity is determined by an abnormality in the genetic regulation of the enzyme can be tested by measuring MAO A activity in human fibroblasts cultured under controlled conditions. We first studied the kinetic parameters of platelet MAO B activity in patients hospitalized for treatment of alcoholism. Vmax was 38% lower in the patients (n = 14) than in normal controls (n = 22), but the enzyme affinity (Km) for the substrate tyramine was unchanged. Patients with the five lowest levels of platelet MAO activity had MAO activity measured from fibroblasts cultured from skin punch biopsies. Their fibroblast MAO activity was within the normal range, showing a dissociation between platelet MAO B and fibroblast MAO A activities and suggesting that MAO A activity is not low for genetic reasons in alcoholic subjects who do have low platelet MAO B activity.

Alcoholism↗
PubMed1984

Cross-national reliability study of a schedule for assessing personality disorders.

The inter-rater reliability of a schedule used to assess personality disorders was examined. The Personality Assessment Schedule (PAS) involves an interview with both the patient and a close informant and the ratings for the informant are given most weight in the final scoring. Videotaped interviews with 23 psychiatric patients, most of whom had a clinical diagnosis of personality disorder, and a close informant were scored by seven raters, four in the United Kingdom and three in the United States. Overall inter-rater reliabilities (using the intraclass correlation coefficient, RI) were generally good to excellent for each of the 24 personality variables tested, ranging between .66 and .94 for informants and between .51 and .91 for subjects. Corresponding reliability coefficients for overall mean PAS scores were .82 and .75, respectively. Consistent with these findings, there was little bias between the scores of American and British raters, although there was some tendency for American raters to score higher for the trait of eccentricity and lower for the trait of conscientiousness than was true for British raters. There was less bias for informants' ratings than for those of subjects. In a second set of analyses, it was shown that inter-rater reliability levels (using the Kappa statistic) were also good to excellent (.6 to .8) for the categorical diagnosis of personality disorder. These results, taken together, demonstrate that abnormal personality can be reliably assessed by both British and American raters.

Adolescent↗
PubMed1984

Poor outcome and low platelet MAO activity in chronic schizophrenia.

Platelet monoamine oxidase (MAO) activity was significantly lower among 21 chronic schizophrenic patients, 19 of whom were receiving stable doses of antipsychotic medication, than among 16 control subjects. Poor ego functioning and poor outcome were significantly correlated with low MAO activity; current dose of major tranquilizer was negatively but not significantly correlated. The degree of psychopathology, rather than presence or absence of specific symptom constellations, was the significant characteristic of patients with low enzyme levels. This finding is in accordance with those of earlier studies of schizophrenic patients as well as with recent findings in nonschizophrenic samples.

Adult↗
PubMed1984

Clinical research: a key to clinical training.

Rational clinical decision making is at the core of any medical field, including psychiatry. Although clinical decision making should be based on reasoning logically from sufficient hard data, the process is often short-circuited; hypotheses are considered fact or causality is inferred where only association exists. This report describes how clinical research protocols provide a structure that helps train clinicians to reduce these errors. A good research design forces articulation and evaluation of hypotheses and prevents premature assumption of causality. The authors present case examples which show that clinical research can serve as in-service training for staff clinicians.

Adult↗
PubMed1984

Assessing treatment response to the monoamine oxidase inhibitor isocarboxazid.

The response to the MAOI isocarboxazid was investigated in a two-phase protocol. Phase 1 was a double-blind, placebo-controlled study; Phase 2 was an open active medication trial for Phase 1 placebo patients who still met symptom criteria. In Phase 1, 60 male outpatients were randomly divided into placebo or active medication groups. Mean platelet MAO inhibition was 86% by Week 1, while significant symptomatic improvement was not seen until Week 3. In Phase 2, 16 of the symptomatic placebo patients were given an open trial on isocarboxazid; thus, 43 patients received a trial of active medication. Separation of responders (N = 26) from nonresponders (N = 17) by discriminant function analysis using 3 entry variables (platelet MAO activity, standing diastolic blood pressure, and psychomotor irregularity) accounted for 28% of the variance, with correct classification of 32 of the 43 patients.

Ambulatory Care↗
PubMed1984

Haloperidol inhibition of monoamine oxidase in vivo and in vitro.

Haloperidol was found to inhibit monoamine oxidase (MAO) activity in sonicated platelets by 50% (IC50) at a concentration of 10(-4) M. Preincubation of the sonicated platelets with haloperidol before the assay did not shift the dose-response curve. When cultured human skin fibroblast MAO was assayed along with haloperidol, MAO activity was only slightly affected (estimated IC50 = 3 X 10(-2) M), even with 1 hr of preincubation. When fibroblasts were cultured with medium containing haloperidol, however, the haloperidol IC50 for MAO activity was 3 X 10(-7) M after 3 days, 2 X 10(-8) M after 7 days, and 3 X 10(-9) M after 14 days. We conclude that haloperidol alters MAO enzyme activity acutely in vitro and that the inhibition increases at lower concentrations with chronic treatment in vivo.

Blood Platelets↗
PubMed1982

Monoamine oxidase inhibitor-responsive depression.

Double-blind, placebo-controlled trials have documented the efficacy of some monoamine oxidase (MAO) inhibitors in treating certain depressed patients. This preliminary report of a 6-week, double-blind, placebo-controlled study of the MAO inhibitor isocarboxazid (Marplan) examines the time course of platelet MAO inhibition and treatment response, and describes symptoms that distinguish markedly improved from slightly improved responders. Thirty male outpatients, ages 28-64, randomly divided into placebo (n = 15) and active medication (n = 15) groups, were followed weekly. Medication was started at 20 mg daily and increased to achieve 90% platelet MAO inhibition. Data were analyzed for 24 patients who completed at least 3 weeks of the study. A clinician's global change rating at the study's conclusion showed that 12 of 13 patients (92%) in the active medication group improved, while 3 of 11 (27%) patients in the placebo group improved. Significant symptomatic improvement occurred in the active treatment group by week 3. Trends suggest that anxiety improved first (week 2), followed by depression (week 3), and finally cognitive outlook (week 6). Only minimal difficulties were observed with orthostatic hypotension, hypertensive crises, or other side effects. At baseline, the only significant difference between the markedly improved and slightly improved groups was greater psychomotor retardation in the markedly improved group. Trends suggest that the markedly improved group showed less depression, anxiety, sleep disturbance, and weight loss, fewer gastrointestinal complaints, and more helplessness and worthlessness.

Adult↗
PubMed1982

Steady-state plasma concentrations of cis- and trans-10-OH amitriptyline metabolites.

Plasma concentrations of the geometric isomers of 10-OH amitriptyline (10-OH AT) and 10-OH nortriptyline (10-OH-NT) were determined by reversed-phase high-pressure liquid chromatography. Steady-state concentrations of At, NT, and the four 10-OH metabolites were measured in 27 patients taking AT for depression. All of the unconjugated hydroxylated metabolites were usually detectable and trans-10-OH NT always predominated. Mean concentrations, expressed as percentage of the sum of all six compounds, were: AT 30%, NT 27%, cis-10-OH AT 1.1%, trans-10-OH AT 4.0%, cis-10-OH NT 4.0%, and trans-10-OH NT 33%. Repeated measurements on 10 patients over several weeks indicated that interindividual variations in absolute and relative 10-OH metabolite concentrations are much greater than day-to-day variations. Five patients who also received a phenothiazine had a lower proportion of 10-OH metabolites.

Adult↗
PubMed1982

Neuroendocrine risk factors of suicidal behavior.

Three of 22 subjects in a study of neuroendocrine correlates of clinical change made serious suicide attempts, 2 of which were lethal. The suicidal subjects had significantly higher 24-hour urinary cortisol levels and significantly lower 24-hour urinary norepinephrine-to-epinephrine ratios than the nonsuicidal patients had. Although the cortisol finding confirms earlier reports, the norepinephrine-to-epinephrine ratio finding is new. The results support the concept that the clinical utility of neuroendocrine measures is enhanced by using a multihormonal profile.

Adult↗
PubMed1982

Recurrence of depression after discontinuation of long-term amitriptyline treatment.

In this study 10 of 17 patients receiving long-term amitriptyline treatment (average duration: 3.7 years, average dose: 138 mg) had their medication tapered and discontinued under double-blind conditions. Eight became depressed within 3 to 15 weeks. None of the 7 control subjects became depressed during the 6 months of the study. Those who became depressed also showed psychomotor retardation and sleep disturbance. Relief of longstanding anticholinergic side effects followed medication discontinuation. Some patients whose amitryptyline was discontinued experienced a mild withdrawal syndrome within the first 2 weeks, consisting of irritability, dream and sleep disturbance, and restlessness during the first few weeks.

Adult↗