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R F Haskett

Publications and source records attributed to R F Haskett.

71 records · Page 4Linked to original sources

Escape from dexamethasone suppression: possible role of an impaired inhibitory opioid mechanism.

Several lines of evidence indicate that the activity of the hypothalamus-pituitary-adrenal (HPA) axis in depression is disinhibited. Escape from dexamethasone suppression, although not limited to is more frequent in patients with endogenous depression compared to normals or patients with other psychiatric diagnoses. Norepinephrine, serotonin and acetylcholine have been implicated in the pathophysiology of this neuroendocrine abnormality. Morphine, 5 mg intravenously, suppressed cortisol secretion in healthy volunteers (n = 4) and the majority of 32 psychiatric inpatients. However, patients with endogenous depression and abnormal dexamethasone suppression test results show early resumption (escape) of cortisol secretion following the initial suppression induced by morphine. It is concluded that the pathophysiology of this neuroendocrine abnormality is not limited to classical neurotransmitter-HPA axis interaction but that it also involves opioid inhibitory mechanisms.

Depressive Disorder↗

Postnatal gonadal steroid effects on human behavior.

Gonadal steroid hormones, active during fetal life, continue after the birth of a fetus to influence the central nervous system and affect behavior. The characteristically different circulating concentrations of male and female steroid hormones in men and women appear to be partial determinants of certain sexually dimorphic behaviors, interacting in a complex way with psychological and sociocultural factors as well as with other biological factors. This interaction is highlighted in research on testosterone and aggression in men, mood and the menstrual cycle in women, and pubertal sex role reversal in pseudohermaphrodites.

Affect↗

A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility.

Four hundred thirty-eight subjects underwent an overnight dexamethasone suppression test (DST) to standardize the test for the diagnosis of melancholia (endogenous depression). Abnormal plasma cortisol concentrations within 24 hours after dexamethasone administration occurred almost exclusively in melancholic patients. The best plasma cortisol criterion concentration, above which a DST result may be considered abnormal, was 5 microgram/dL. The optimal dose of dexamethasone was 1 rather than 2 mg. Two blood samples obtained at 4 and 11 PM after dexamethasone administration detected 98% of the abnormal test results. This version of the DST identified melancholic patients with a sensitivity of 67% and a specificity of 96%. Baseline nocturnal plasma cortisol concentrations were not useful. Abnormal DST results were found with similar frequency among outpatients and inpatients with melancholia; but they were not related to age, sex, recent use of psychotropic drugs, or severity of depressive symptoms. Extensive evidence validates this practical test for the diagnosis of melancholia.

Adolescent↗

Diagnosis of endogenous depression. Comparison of clinical, research and neuroendocrine criteria.

Eighty-nine depressed outpatients were studied by clinical criteria, Research Diagnostic Criteria (RDC), and the dexamethasone suppression test (DST) of neuroendocrine regulation. A simple outpatient version of the DST, requiring only one blood sample, correctly identified 40% of patients diagnosed clinically as endogenous depression (ED), with a specificity of 98% and a diagnostic confidence of 95%. Differences in age, sex, or severity of symptoms between endogenous and non-endogenous depressives did not account for these results. By comparison, the diagnostic performance of the DST was weaker for the RDC categories Major Depressive Disorder (MDD) and primary MDD. These were less selective and more heterogeneous than the clinical category ED. The clinical diagnoses of ED were supported in 98% of cases by the RDC, but 22% of RDC endogenous MDD diagnoses were not supported by the clinical diagnoses. Abnormal DST results were found only in patients with both the clinical diagnosis of ED and the RDC diagnosis of endogenous MDD. Patients with definite endogenous MDD had a significantly higher frequency of abnormal DST results (42%) than those with probable endogenous MDD (14%), or those with other RDC diagnoses (3%). A significant association was found between positive DST results and a positive family history of depression. These results support other evidence for use of a positive DST result as an external validating criterion for ED. The category MDD contained all cases diagnosed clinically as ED, but was diluted by cases diagnosed clinically as non-endogenous depression who had no neuroendocrine disturbance. The results also confirmed that the endogenous/non-endogenous and primary/secondary classifications of depression are not identical. We conclude: (1) that the DST can be used in the differential diagnosis of depressed outpatients as well as inpatients; (2) that the RDC category primary MDD and the Washington University category primary depression are more heterogeneous and probably less valid than the clinical category ED; (3) that the RDC for endogenous MDD have only moderate validity; (4) that RDC diagnoses cannot substitute for careful clinical diagnoses in research studies; (5) that the best use of the RDC is to support clinical diagnoses, but not to generate diagnoses independently as a free-standing system; (6) that the concept of endogenous or endogenomorphic depression has validity and should be retained in research studies of depression.

Adult↗

Neuroendocrine dysfunction in genetic subtypes of primary unipolar depression.

Disinhibited activity of the hypothalamic-pituitary-adrenocortical (HPA) neuroendocrine system, characterized most specifically by abnormal responses to the dexamethasone suppression test (DST), is observed in 40-50% of patients with endogenous depression. The heterogeneity of endogenous depressives with respect to this neuroendocrine marker is so far unexplained. A recent report from Iowa suggested that genetic factors could account for this heterogeneity, since abnormal DST reponses were found with widely differing frequencies among primary unipolar depressives subtyped by the genetic criteria of Winokur. We studied 14 patients with primary endogenous delusional unipolar depression. Abnormal DST responses were found in 79% of the entire group, and with similar frequencies among each of the Winokur subtypes. In particular, five of six patients (83%) with depression spectrum disease had abnormal DST results. This contrasts with a frequency of 4% reported by the Iowa group. We conclude that disinhibited HPA activity does occur in depression spectrum disease when a delusional endogenous depression is present. Our results and those of the Iowa study could both be consistent with a threshold model of HPA activation. The high frequency of positive DST results in delusional endogenous depressives may be determined by disinhibited central pain mechanisms. Variations in this clinical dimension, combined with variations in threshold for HPA activation by pain mechanisms, could account for the heterogeneity of DST responses among endogenous depressives.

Delusions↗

Treatment of premenstrual tension with lithium carbonate. A pilot study.

Some previous reports have suggested that lithium treatment is of benefit to women with the premenstrual tension syndrome (PMTS). In this study 15 women carefully selected for severe PMTS were given lithium carbonate (600-900 mg/day) continuously for three menstrual cycles. Lithium did not affect physical premenstrual symptoms and was ineffective in most women against behavioral premenstrual symptoms. Despite the low dosage most women also experienced significant drug-related side effects. Although a statistically significant improvement was recorded by several symptom rating instruments, this benefit was of no practical clinical value. The three women who responded best to lithium, and who requested continued treatment beyond 3 months, met diagnostic criteria for subsyndromal affective (cyclothymic) disorder. Lithium is not recommended for the average woman with PMTS.

Adult↗

Premenstrual tension syndrome: the development of research diagnostic criteria and new rating scales.

Research diagnostic criteria for premenstrual tension syndrome (PMTS) are developed using data collected from a study of 42 women who were suffering from severe PMTS but were well at other times. Two specific scales are also devised for rating the severity of PMTS, a 36-item self-report questionnaire and a 10-item scale for use by therapist/researcher. It is proposed that after further evaluation and validation, these instruments may permit more useful comparisons of data on the etiology and treatment of this disorder.

Adult↗

Severe premenstrual tension: delineation of the syndrome.

Forty-two women with severe premenstrual tension syndrome (PMTS) were studied to define the clinical phenomenology and examine its resemblance to common psychiatric disorders. They were mature, adult women suffering severe emotional and physical symptoms in the premestruum but well at other times. Their mean premenstrual score on the Menstrual Distress Questionnaire (MDQ) was twice as high as in the study of Moos. Symptoms showed a marked On--Off phenomenon between premenstrual and follicular evaluations with all rating instruments (p less than 0.001). Existing scales for depression, anxiety, and hostility did not demonstrate that the core disturbance of PMTS is any of these dimensions alone. Item analysis of the MDQ revealed that irritability, mood lability, tension, and restlessness were the most prominent emotional descriptors of this specific syndrome. Several indicators of impaired intellectual and physical functioning were also noted. In most of these women PMTS occurred in the absence of other psychopathology. Subclinical characterological and neurotic disturbances when present were probably exacerbated in the premenstrual period. PMTS is not a clinical model for recurrent affective disorders.

Adult↗

Normalization of dexamethasone suppression test: a laboratory index of recovery from endogenous depression.

Carroll et al. reported that an abnormal dexamethasone suppression test (DST) may identify approximately 50% of endogenous depressives and that normalization of the test occurs with clinical recovery. Brown et al. and Schlesser et al. have confirmed the diagnostic utility of the test. A preliminary study suggested that when the DST failed to normalize at discharge, patients were at high risk for early relapse. In this study, we compared ten unipolar or bipolar endogenous depressives who had an abnormal DST on admission and a normal DST at discharge, with four patients whose abnormal DST on admission failed to convert at discharge. On all measures, those whose DST fail to convert showed substantially less improvement. Patients whose DST fail to normalize may have incomplete resolution of their underlying depressive process. Despite clinical judgment that discharge may be appropriate these patients may require further active treatment. Use of the DST prior to discharge may help discriminate between patients whose remaining symptoms reflect situational or psychosocial problems and those with a continuing endogenomorphic process.

Adult↗

Serial dexamethasone suppression tests in depressed patients treated only with electroconvulsive therapy.

Several systematic studies have evaluated serial dexamethasone suppression tests (DST) in patients with major depression who were treated with antidepressant medications. DST changes were noted to parallel clinical improvement in most recovering patients. If serial DSTs are a valid state-related correlate of depressive pathophysiology, all types of effective antidepressant treatment should result in DST 'normalization'. However, no treatment modalities other than antidepressant medications have been studied serially with systematic assessments. To test whether serial DSTs reflect clinical progress in depressives treated solely with electroconvulsive therapy (ECT), we studied weekly DSTs and Hamilton Rating Scales for Depression (HRSD) in 22 drug-free depressed patients. We observed progressive DST 'normalization' in most patients and moderately high correlations between weekly DST and HRSD values throughout treatment. Most patients receiving ECT became DST suppressors. In most patients the DST appeared to reflect the severity of depressive pathophysiology, perhaps providing serial feedback to clinicians monitoring the progress of treatment with ECT.

Depressive Disorder↗

Fluoxetine versus placebo for the marijuana use of depressed alcoholics.

The aim of this analysis was to evaluate the efficacy of the SSRI antidepressant fluoxetine versus placebo for the marijuana use of depressed alcoholics. There are no previous reports involving and SSRI antidepressant for marijuana abuse. This analysis involved a subsample of 22 depressed alcoholic marijuana users out of a total of 51 depressed alcoholics. The entire sample was involved in a 12-week double-blind, placebo-controlled study evaluating the efficacy of fluoxetine versus placebo in depressed alcoholics. During the course of the trial, the cumulative number of marijuana cigarettes used was almost 20 times as high in the placebo group as in the fluoxetine group. Also, the number of days of marijuana use during the study was five times higher in the placebo group than in the fluoxetine group. These data suggest efficacy for fluoxetine in decreasing marijuana use of depressed alcoholics.

Adult↗

Fluoxetine versus placebo in depressed alcoholics: a 1-year follow-up study.

The authors conducted a first study to evaluate the long-term efficacy of fluoxetine for decreasing the depressive symptoms and the drinking of patients with comorbid major depressive disorder and alcohol dependence. This study consisted of a 1-year naturalistic follow-up of 31 patients who previously had completed a 3-month double-blind, placebo-controlled study of fluoxetine in depressed alcoholics. The fluoxetine group continued to demonstrate less depressive symptoms and less drinking than the placebo group at the 1-year follow-up evaluation. The results of the 1-year follow-up evaluation suggest persistent efficacy for fluoxetine for treating the depressive symptoms and the drinking of depressed alcoholics.

Adult↗