Potential therapeutic effects of ritanserin in Cushing's disease.
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Biomedical subjects
Publications and source records attributed to G A Fava.
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The majority of 20 patients suffering from panic disorder with agoraphobia reported experiencing agoraphobic avoidance, generalized anxiety, and/or hypochondriacal fears and beliefs before the first panic attack. The results replicated those of a previous investigation and are in accordance with an increasing number of studies concerned with prodromal symptoms, epidemiologic surveys, and analysis of mechanisms of change upon treatment.
Controversy continues over the characteristics of beta-endorphin secretion in depression. Beta-endorphin plasma levels were measured in 30 drug-free male patients with a DSM-III-R major depressive disorder and 21 healthy controls. Depressed patients displayed significantly lower beta-endorphin plasma levels in baseline conditions, after the single dose metyrapone test, and after the dexamethasone suppression test. The activation of hypothalamic-pituitary-adrenal (HPA) axis in depression might be due, at least in part, to low levels of beta-endorphin. These results suggest that HPA axis dysregulation in depression may involve peptides other than ACTH.
The clinical concepts related to the assessment of psychosocial factors in the medically ill are reviewed, with particular reference to the DSM-III-R categories of adjustment disorders, psychological factors affecting physical conditions, and somatoform disorders. The clinical and heuristic value of the concepts of psychosomatic disorder and abnormal illness behavior is underscored.
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Three self-rating personality inventories were administered to 33 patients who had recovered from panic disorder associated with agoraphobia and to 33 healthy subjects matched for sociodemographic variables. The personality inventories comprised the Tridimensional Personality Questionnaire (TPQ), which provides three major dimensions (novelty seeking, harm avoidance and reward dependence), the Anxiety Sensitivity Index (ASI) and the Emotional Inhibition Scale (EIS). Agoraphobic patients reported significantly more TPQ harm avoidance and anxiety sensitivity than controls. Although these findings might have been influenced by residual anxiety symptoms in panic-free patients and could also apply to patients with other anxiety disorders, they suggest that harm avoidance and anxiety sensitivity may be risk factors for developing agoraphobia and panic disorder. There may be overlap between this characterologic cluster and prodromal symptoms of panic disorder with agoraphobia, such as anxiety, phobias and hypochondriasis.
There has been very little interest in research on prodromal symptoms of mood disorders. This paper reviews the literature concerned with bipolar disorder and unipolar depression. In both illnesses, recent preliminary studies would suggest that within each patient there is a striking consistency in prodromal symptoms preceding each episode. Since the appearance of prodromal symptoms generally precedes the full syndrome by weeks or months, the findings pave the way for the intermittent use of medications (antidepressants and lithium) in mood disorders.
Any undue concern with bodily function is often labeled as hypochondriacal. Kellner's Illness Attitude Scales, self-rating instruments, distinguish between generic worry about illness, concern about pain, health habits, hypochondriacal beliefs, thanatophobia, disease phobia, and bodily preoccupations. The Illness Attitude Scales have been used in a number of studies concerned with patients suffering from DSM-III-R hypochondriasis, panic disorder, melancholia, in the medically ill, in pregnant women, during medical procedures such as mammography, and in experiments in therapeutics, such as drug trials. The results of these studies and of clinical investigations suggest that the differential diagnosis between hypochondriacal beliefs (characterized by resistance to reassurance), disease phobia, thanatophobia, and the other less specific illness attitudes, is worthy of clinical attention and may entail prognostic and therapeutic implications. Pilowsky's concept of abnormal illness behavior, unlike the DSM-III-R, provides a framework for such differentiation.
OBJECTIVE: The aim of this paper was to review the clinical and conceptual implications of the studies investigating prodromal symptoms of mania, depression, and panic disorder. METHOD: Twenty-four studies specifically addressing the issue of prodromal symptoms in mood and anxiety disorders were selected by computer search (Medline) and manual search of Index Medicus and the psychiatric literature. RESULTS: Most of the studies have described a prodromal phase in the development of mania, depression, and panic attacks. CONCLUSIONS: The appearance of prodromal symptoms may precede the full syndrome by weeks or months; if these symptoms are detected, recurrences of affective disorders (bipolar illness, unipolar depression, panic disorder) could be treated earlier and perhaps more effectively. DSM-III has emphasized the traditional clinical syndromes and cross-sectional descriptions. Appraisal of prodromal and residual phases may complement this approach. The longitudinal study of prodromes, the fully developed disorder, and residual states calls for an assessment of personality, neurotic traits, and their interaction in the evolution of affective disorders.
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Prodromal symptomatology was investigated, by means of a modified version of Paykel's Clinical Interview for Depression, in 15 outpatients at their first episode of primary major depressive disorder. Compared to normals, generalized anxiety and irritability were significantly more frequent. Impaired work and interests, fatigue, initial and delayed insomnia were also reported. Four patients who relapsed upon discontinuation of antidepressant treatment displayed the same prodromal symptomatology as in the initial episode.
There is current controversy over the mechanisms underlying hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in depression. Pro-gamma-melanocyte-stimulating hormone (MSH), a portion of the N-terminal region of pro-opiomelanocortin, has been shown to act synergistically with adrenocorticotropic hormone (ACTH) in stimulating corticosteroid secretion both in vitro and in vivo. Pro-gamma-MSH and ACTH plasma levels were measured in 30 drug-free male patients with a DSM-IIIR major depressive disorder and 21 healthy controls. The baseline levels were similar in the two groups. After single-dose metyrapone stimulation, both hormones increased, but pro-gamma-MSH was significantly higher in control subjects than in depressives. After overnight 1-mg dexamethasone, ACTH was significantly less suppressed in depressives than controls. These results suggest that HPA axis dysregulation in depression may involve peptides other than ACTH and be more complex than previously reported.
There is current controversy over the mechanisms underlying hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in depression. Pro-gamma-MSH, a portion of the N-terminal region of POMC, has been shown to act synergistically with ACTH in stimulating corticosteroid secretion in vitro and in vivo. Pro-gamma-MSH and ACTH plasma levels were measured in 30 drug-free male patients with a DSM-III-R major depressive disorder and 21 healthy controls. The baseline levels were similar in the two groups. After single-dose metyrapone stimulation, both hormones increased, but pro-gamma-MSH was significantly higher in control subjects than in depressives. After overnight 1 mg dexamethasone, ACTH was significantly less suppressed in depressives than controls. These results suggest that HPA axis dysregulation in depression may involve peptides other than ACTH and be more complex than previously reported.
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Illness attitudes were evaluated in 26 pregnant women and 26 control subjects matched for sociodemographic variables, by means of a self-rating scale, on 3 different occasions. For each trimester of pregnancy, women displayed more hypochondriacal fears and beliefs and conviction of disease (disease phobia) than normal controls. In the third trimester, they also reported more fear of dying and bodily preoccupations. The findings should alert physicians to ask their pregnant patients whether they are preoccupied with fear of dying, or are concerned that they suffer from an undiagnosed physical illness, or dread a specific illness such as cancer or heart disease. Hypochondriacal fears and beliefs are liable to affect well-being and the health attitudes of pregnant women. If properly recognized, they may effectively be treated.
Research on quality of life may herald a welcome psychosomatic change in biomedical research and clinical practice. The many promising horizons available, however, do not prevent miscommunication, random effort and faulty reasoning. An illusion of simplicity has caused many investigators to believe that the measurement of quality of life is simple and feasible, whereas only the psychosocial variables affecting quality of life can be assessed by current, reliable psychometric methods. The areas concerned with biomedical research on quality of life are reviewed and some methodological issues are discussed.