The validity of DSM-III-R hypochondriasis.

BACKGROUND: Because of the uncertainty about the status of hypochondriasis, the disorder is rarely diagnosed. To address this problem we examined the validity of DSM-III-R hypochondriasis as identified by structured interview. METHODS: Patients in a general medicine clinic were screened for hypochondriacal attitudes and symptoms. Those patients who scored above an established cutoff had a structured diagnostic interview, and 50 patients who met DSM-III-R criteria for hypochondriasis and 50 age- and sex-matched controls were thus identified. Information was obtained from both groups on health perceptions, health care utilization, and level of functioning using self-report and physician-rated measures. Additional information on diagnoses and treatment recommendations was obtained from record audits. RESULTS: Clinic physicians rated hypochondriacal subjects as having more unrealistic fear of illness (hypochondriasis) and diagnosed psychiatric and functional somatic syndromes more frequently in hypochondriacal than in control subjects. Hypochondriacal subjects viewed their health as worse, had more health worries, and had more severe psychiatric symptoms than control subjects. They also reported poorer physical functioning and work performance, greater health care utilization, poorer response to medical treatment, and less satisfaction with the care received than controls. CONCLUSIONS: Results show that, although the diagnosis of hypochondriasis is rarely made, physician recognition is high. They also show that several indicators of internal and external validity of this diagnostic category exist. Findings suggest that if physicians are to reduce the functional impairment and nonproductive health care utilization of these patients, they will need to make the diagnosis of hypochondriasis and intervene appropriately. However, for this to occur, research demonstrating predictive validity and treatment responsiveness of the disorder will be required.

Enhanced adrenal sensitivity to exogenous cosyntropin (ACTH alpha 1-24) stimulation in major depression. Relationship to dexamethasone suppression test results.

ACTH alpha 1-24 (cosyntropin) (250 micrograms by intravenous bolus) was given to 38 medicated patients with major depressive disorder (MDD) and to 34 normal control subjects. Patients with MDD had significantly higher plasma cortisol concentrations and significantly higher increases in plasma cortisol levels 60 minutes after cosyntropin infusion than did control subjects. Patients who were nonsuppressors in the dexamethasone suppression test had significantly higher 60-minute cortisol concentrations and cortisol increases than did normal subjects and patients with MDD who were suppressors. There were significant, strongly positive correlations between cortisol secretory responses to cosyntropin and postdexamethasone cortisol concentrations in patients with MDD. These findings confirm that adrenal sensitivity to corticotropin (ACTH) is enhanced in MDD and suggest that this endocrine abnormality may be related pathophysiologically to the resistance of cortisol secretion to dexamethasone suppression.

Differentiation of depressive subtypes by insulin insensitivity in the recovered phase.

The glucose response to a standard insulin tolerance test (ITT) has been reported to be blunted in the acute phase of heterogeneous depressive disorders and to be normal in the recovered phase. We studied the glucose response to ITT in the recovered phase depression in patients who had previously been subclassified according to familial and clinical characteristics. All patients with depressive spectrum disease had an adequate glucose response to the ITT, whereas only 40% of patients with familial pure depressive disease and 56% of patients with bipolar illness had an adequate hypoglycemic response. There was also a trend toward a decrease in insulin sensitivity in patients who had been nonsuppressors to dexamethasone when depressed. These findings suggest that the glucose response to ITT may be a useful tool in differentiating among the heterogeneous depressive disorders.

Propranolol in chronic anxiety disorders. A controlled study.

In a double-blind crossover study the beta-adrenergic blocking drug propranolol hydrochloride reduced symptoms in 17 of 26 patients with chronic anxiety disorders. Both somatic and psychic symptoms improved as judged by patient and observer ratings. The most frequent side effects (dizziness, fatigue, and insomnia) were difficult to distinguish from anxiety symptoms and were, for the most part, mild. The therapeutic and side effects observed suggested CNS activity of the drug. Although propranolol is of benefit to patients with anxiety, its efficacy, compared with that of other antianxiety drugs, has not been established.

Analysis of the specificity of physostigmine stimulation of adrenocorticotropin in man.

Five normal men were given infusions of saline and three doses (6, 12, and 18 micrograms/kg) of physostigmine, a centrally acting anticholinesterase, after pretreatment with glycopyrrolate, a peripheral cholinergic antagonist. There was no increase in basal ACTH or cortisol concentrations in any of the subjects after saline or the two smaller doses of physostigmine. However, each subject had a marked increase in ACTH and cortisol levels after the largest dose of physostigmine. These changes were preceded in each subject by the occurrence of noxious side effects and were accompanied by a rise in PRL levels in four of the subjects. Four subjects who received physostigmine (12 micrograms/kg) without glycopyrrolate pretreatment also experienced noxious side effects; these symptoms were followed by elevations in ACTH, cortisol, and PRL levels. These findings suggest that physostigmine stimulates ACTH and cortisol secretion through a stress-mediated effect rather than through a specific cholinergic mechanism. Consequently, physostigmine is not a reliable tool for investigating the cholinergic regulation of ACTH and cortisol.

Stable adrenocorticotropin-stimulated 11-beta-hydroxylase activity but loss of age-related changes in patients with hypercortisolemia.

Eleven-beta-hydroxylase activity was measured before and after acute adrenocorticotrophic hormone (ACTH) stimulation in 28 controls, 25 depressed Dexamethasone Suppression Test (DST) suppressors, 13 DST nonsuppressor patients, and 8 patients with Cushing's syndrome to investigate changes in states of cortisol hypersecretion. Eleven-beta-hydroxylase activity was equivalent among groups both before and after stimulation. Such 11-beta-hydroxylase stability, however, resulted in higher cortisol and 11-deoxycortisol poststimulation levels in both depressed DST nonsuppressors and Cushing's patients than in controls. Basal 11-beta-hydroxylase activity is positively correlated and 11-deoxycortisol is negatively correlated with age in controls and DST suppressors, but not in the patients tested with evidence of cortisol hypersecretion. These findings suggest that in vivo basal 11-beta-hydroxylase activity rises gradually with age, but does not rise after acute administration of exogenous ACTH. The age relationship is lost in states of cortisol hypersecretion, but the lack of response to acute exogenous ACTH is not affected.

The HPA axis response to insulin hypoglycemia in depression.

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis, demonstrated by failure to suppress cortisol secretion after dexamethasone, is found in approximately 50% of patients with major depression (MD). In this study, we examined the response of adrenocorticotrophic hormone (ACTH) and cortisol to insulin-induced hypoglycemia in 20 healthy controls and 18 inpatients with MD [12 dexamethasone suppressors (S) and 5 dexamethasone nonsuppressors (NS)]. After the administration of 0.15 U/kg of regular insulin, both controls and patients with MD showed an increase in plasma ACTH and cortisol levels. Controls had a significantly higher ACTH peak (p less than 0.01) and ACTH increment (p less than 0.01) than MD patients. There were no statistically significant differences between patients who were S and NS. Although baseline plasma cortisol levels were significantly higher in MD patients, there were no significant differences in the peak cortisol or increment in plasma cortisol after hypoglycemia between patients with MD and controls or between patients who were S and those who were NS. These findings suggest that a defect exists in the regulation of the HPA axis at the pituitary level in MD and that this defect is not necessarily reflected in the dexamethasone suppression status of the patient.

Direct comparison of urinary free cortisol excretion in patients with depression and panic disorder.

Urinary free cortisol (UFC) excretion in 31 patients with major depression is directly compared to UFC levels in 65 patients with panic disorder and 36 controls. Patients with depression demonstrated significantly higher UFC excretion [43 +/- 37 micrograms/g creatinine (cr)] than patients with panic disorder (29 +/- 13 micrograms/g-cr) or controls (22 +/- 10 micrograms/g-cr) (F = 8.5, df = 129, p less than 0.001). Panic patients with a secondary depression (35 +/- 17 micrograms/g-cr) or those with agoraphobia (34 +/- 14 micrograms/g-cr) had UFC levels that were in-between patients with primary major depression and panic patients without these complications (25 +/- 11 micrograms/g-cr). These findings support the hypothesis that patients with major depression, whether primary or secondary, and those with agoraphobia excrete more UFC than patients with uncomplicated panic disorder. This occurs despite the fact that panic disorder might also be expected to raise the stress-responsive hormone cortisol.

Elevated CSF protein in male patients with depression.

Elevation of total protein is the most frequent pathologic finding in the cerebrospinal fluid (CSF) examination. It occurs in a variety of situations, such as inflammation or tumors of the central nervous system (CNS), degenerative disorders, and subarachnoid hemorrhage, or as a result of traumatic taps. It has also been reported, for unknown reasons, in patients with psychiatric disease. In a study of hormone changes in depression, 9 of 24 (38%) patients (13 male, 11 female) were found to have elevated CSF protein levels (greater than 45 mg/dl), whereas no elevations were found in healthy controls (8 male, 9 female). Eight of the patients with the elevated CSF protein levels were male (62%) and one was female (9%). Depressed patients had significantly higher CSF protein levels (44.7 +/- 18.0 mg/dl) than controls (31.5 +/- 6.0 mg/dl) (t = 3.32, df = 30.37, p = 0.002). No relationship was found between CSF protein levels and (1) the use of medication (tricyclic antidepressants, lithium carbonate, or monoamine oxidase inhibitors) or (2) post-dexamethasone suppression test cortisol levels. Female controls, however, tended to have lower protein levels than male controls, whereas female patients had significantly lower levels than male patients. Protein electrophoresis was performed on 21 of the 41 subjects (13 patients, 8 controls). Male patients had nonsignificantly higher absolute concentrations of CSF albumin and the globulin fractions when compared to male controls. These differences in CSF protein do not suggest monoclonal CSF protein production, nor are they the result of this elevated peripheral protein.(ABSTRACT TRUNCATED AT 250 WORDS)

CRH challenge test in anxious depression.

Recently, renewed interest has developed in the concept of anxious depression. Using an operational definition of "anxious depression" based on the SADS interview, 25 patients with major depressive disorder were separated into anxious (n = 14) and nonanxious (n = 11) subtypes. These two patient groups and normal control subjects received an intravenous corticotropin-releasing hormone challenge test. Adrenocorticotropic hormone (ACTH) and cortisol responses were compared among the three groups. Patients with anxious depression had significant attenuation of ACTH response when compared to nonanxious patients and normal control subjects.

Urinary free cortisol levels and dexamethasone suppression testing in organic affective disorder associated with hyperthyroidism.

Eleven of 32 newly diagnosed untreated patients with hyperthyroidism met DSM-III criteria for organic affective syndrome. Thirty of these patients submitted 24-hour urine specimens for measurement of urinary free cortisol levels, and 31 were given a 1-mg dexamethasone suppression test (DST) before antihyperthyroidism therapy was started. There was no difference in the mean +/- SD urinary free cortisol excretion levels between depressed and nondepressed hyperthyroid patients. One nondepressed patient demonstrated nonsuppression (greater than 5 micrograms/dl) at 8:00 a.m. These results suggest that cortisol abnormalities as reflected by urinary free cortisol levels and DST findings are uncommon in patients with hyperthyroidism whether they are depressed or nondepressed.

Diagnosis of major depression in cancer patients according to four sets of criteria.

Diagnoses of major depression in 152 cancer patients differed as much as 13% depending on the diagnostic system used. The Beck Depression Inventory and the Hamilton Rating Scale for Depression were useful tools for screening patients with depressive symptoms but frequently misclassified those who had no major depression according to one or more of the criteria-based diagnostic systems.

HPA axis abnormalities in depressed patients with normal response to the DST.

In order to identify depressed patients with hypothalamic-pituitary-adrenal (HPA) axis abnormalities who have a normal response to the dexamethasone suppression test (DST), the authors administered a series of neuroendocrine tests including insulin-induced hypoglycemia, arginine vasopressin challenge, and a DST. Using standard sensitivity measures, as well as logistic regression, they concluded that many patients with HPA abnormalities are not identified by the DST. These findings suggest that other neuroendocrine tests, which are sensitive to HPA axis abnormalities, may be helpful in subtyping depression on the basis of HPA axis functioning.

Pathophysiology of HPA axis abnormalities in patients with major depression: an update.

Four hypotheses have been proposed to explain why nonsuppression on the dexamethasone suppression test occurs in patients with major depression. These include 1) increased metabolism of dexamethasone, 2) decreased sensitivity of pituitary glucocorticoid receptors to dexamethasone, 3) hyperresponsivity of the adrenal gland to ACTH stimulation, and 4) increased central drive of the pituitary from hypothalamic/limbic structures that overrides the action of the dexamethasone. A critical review of the literature suggests that the last hypothesis is most closely supported by the data. Despite this conclusion, factors other than depression may be involved in hypothalamic-pituitary-adrenal axis dysfunction.

DSM-IV field trial: testing a new proposal for somatization disorder.

OBJECTIVE: The purpose of this study was to evaluate for APA a proposed strategy to diagnose somatization disorder for possible inclusion in DSM-IV. METHOD: Five sites--Washington University, University of Kansas, University of Iowa, University of Arkansas, and Mount Sinai Medical Center in New York--participated in a collaborative field trial. Female subjects (N = 353) were recruited from several different services (psychiatry, internal medicine, and family practice) and were evaluated for the presence or absence of the disorder. This assessment was performed with a new instrument constructed by combining all the criteria for somatization disorder from the proposed criteria for DSM-IV, DSM-III, DSM-III-R, Perley-Guze, and proposed criteria for ICD-10. RESULTS: A high level of concordance was found between the proposed diagnostic strategy for DSM-IV and the current criteria (DSM-III-R), as well as the earlier criteria (Perley-Guze and DSM-III). The ICD-10 criteria agreed poorly with all other criteria sets. The level of experience of the rater (expert versus novice) with the earlier (Perley-Guze, DSM-III) and current (DSM-III-R) criteria did not influence the identification of cases by use of DSM-IV criteria. No racial effect was introduced by any of the criteria sets. CONCLUSIONS: The strategy for DSM-IV is an accurate and simpler method of diagnosing somatization disorder that does not require special expertise for proper use.

False positive results: a challenge for psychiatric screening in primary care.

OBJECTIVE: The goal of this study was to characterize primary care patients with false positive results on screens for mental disorders. METHOD: A sample of 1,001 primary care patients completed self-administered screens and structured interviews for DSM-IV diagnoses. RESULTS: A substantial proportion of the patients with false positive screen results for at least one diagnosis met the diagnostic criteria for other psychiatric disorders. They also had significantly greater functional impairment and higher rates of recent use of mental health services than the subjects with true negative results on the screens. CONCLUSIONS: Although the positive predictive values of screens for specific mental disorders are in line with those of other medical screens, false positive results are not uncommon. This may be due in part to the sensitivity of brief screening instruments to nonspecific symptoms. The results suggest that as with other screens used in primary care, patients with false positive results on screens for mental disorders should receive clinical attention.

Mental disorders and disability among patients in a primary care group practice.

OBJECTIVE: This article examines social and occupational disability associated with several DSM-IV mental disorders in a group of adult primary care outpatients. METHOD: The subjects were 1,001 primary care patients (aged 18-70 years) in a large health maintenance organization. Data on each patient's sociodemographic characteristics and functional disability, including scores on the Sheehan Disability Scale, were collected at the time of a medical visit. A structured diagnostic interview for current DSM-IV disorders was then completed by a mental health professional over the telephone within 4 days of the visit. RESULTS: The most prevalent disorders were phobias (7.7%), major depressive disorder (7.3%), alcohol use disorders (5.2%), generalized anxiety disorder (3.7%), and panic disorder (3.0%). A total of 8.3% of the patients met the criteria for more than one mental disorder. The proportion of patients with co-occurring mental disorders varied by index disorder from 50.0% (alcohol use disorder) to 89.2% (generalized anxiety disorder). Compared with patients who had a single mental disorder, patients with co-occurring disorders reported significantly more disability in social and occupational functioning. After adjustment for other mental disorders and demographic and general health factors, compared with patients with no mental disorder, only patients with major depressive disorder, bipolar disorder, phobias, and substance use disorders had significantly increased disability, as measured by the Sheehan Disability Scale. CONCLUSIONS: Primary care patients with more than one mental disorder are common and highly disabled. Individual mental disorders have distinct patterns of psychiatric comorbidity and disability.

Reduction in urinary free cortisol during benzodiazepine treatment of panic disorder.

Urinary free cortisol (UFC) levels were measured at baseline and at four and eight weeks after initiation of treatment in 66 patients who met DSM-III-R criteria for primary panic disorder (PD). Thirty-seven normal control subjects also had UFC levels measured three times at monthly intervals. Patients were randomly assigned to treatment with alprazolam, diazepam, or placebo. At baseline, complicated PD patients (those with agoraphobia and secondary depression) had significantly higher UFC levels than did normal controls. At four and eight weeks, complicated PD patients receiving alprazolam and diazepam had significant reductions in UFC excretion compared to baseline. Patients with uncomplicated PD maintained UFC levels comparable to controls at each sampling period. Treatment with benzodiazepines did not lower UFC levels in this group. These findings suggest that patients with complicated PD demonstrate hyperactivity of the hypothalamo-pituitary-adrenal axis that is decreased by treatment with benzodiazepines.

Provocative endocrine testing in recovered depressives.

Twenty-eight patients underwent a series of provocative endocrine tests an average of one year after their last admission for depression. Hypersecretion of cortisol, early escape of cortisol from dexamethasone suppression, diminished growth hormone response to insulin-induced hypoglycemia and altered thyrotropin response to thyrotropin-releasing hormone reported in acute primary depression were not observed after recovery. There were no differences in these measures after recovery between previous suppressors and nonsuppressors to dexamethasone. The cortisol response to insulin-induced hypoglycemia was less than expected in 6 of 16 recovered patients tested. There were significant differences in post-dexamethasone urinary free cortisol and in basal and early post-insulin serum cortisol levels between patients who had been suppressors and those who had been nonsuppressors to dexamethasone during acute depression. Further studies need to be done to substantiate these findings. These data indicate that hormone responses in recovered depressives are largely normal, suggesting that abnormalities during depression are "state" related phenomena.

Transition from bipolar affective disorder to intermittent Cushing's syndrome: case report.

A patient with a 6-year history of bipolar affective disorder who developed cushingoid features during an exacerbation of her psychiatric condition was found to have intermittent hypersecretion of cortisol. Close observation of this patient for 3 years has revealed that her medical and psychiatric symptoms are controlled by suppression of cortisol with bromocriptine.