Patient's therapeutic skill acquisition and response to psychotherapy, alone or in combination with medication.

BACKGROUND: We tested the hypotheses that the addition of medication to psychotherapy enhances participation in the latter by: (1) speeding the acquisition of the psychotherapy's targeted skill; and (2) facilitating higher skill level acquisition. METHOD: Participants were 431 chronically depressed patients who received Cognitive Behavioral Analysis System of Psychotherapy (CBASP), alone (N=214) or in combination with nefazodone (N=217), as part of a randomized chronic depression study (Keller et al. 2000). CBASP, developed specifically to treat chronic depression, uses a specific procedure, 'situational analysis' to help patients engage in more effective goal-oriented interpersonal behaviours. At the end of each session, therapists rated patients on their performance of situational analysis. Outcome on depressive symptoms was assessed with the 24-item Hamilton Rating Scale for Depression. RESULTS: Although reductions in depression were significantly greater in combined treatment compared to CBASP alone, there were no between-group differences in either the rate of skill acquisition or overall skill level at the end of treatment. Proficiency in the use of the main skill taught in psychotherapy at treatment midpoint predicted outcome independently of medication status and of baseline depressive severity. CONCLUSIONS: Effective participation in CBASP, as reflected by proficiency in the compensatory skill taught in psychotherapy, is not enhanced by the addition of medication and does not mediate the between-group difference in depression outcome.

Preliminary examination of sex differences in depressive symptoms among adolescent psychiatric inpatients: the role of anxious symptoms and generalized negative affect.

Assessed the emerging view that generalized negative affect and anxious symptoms are important in understanding sex differences in depressive symptoms. Sixty-three adolescent psychiatric inpatients (32 boys, 31 girls), ages 12 to 16 (M = 13.87, SD = 1.36), completed measures of positive and negative affect and anxious and depressive symptoms. Results demonstrated, as predicted, that depressive and anxious symptoms were more highly associated in adolescent girls than boys. Furthermore, girls with depressive symptoms were more likely to have comorbid anxious symptoms than boys with depressive symptoms. Sex differences were not found for adolescents with specific depressive symptoms and specific anxious symptoms (i.e., the absence of comorbidity). Our findings supported the possibility that sex differences in pure forms of depression are overestimated and that comorbid internalizing conditions may be more prevalent in adolescent girls than boys.

The role of altered tissue norepinephrine concentration in the hereditary obese-hyperglycemic syndrome of mice.

The purpose of this study was to determine if the elevated concentration of norepinephrine in the hypothalamus of the obese-hyperglycemic mouse plays a role in the development of this syndrome. We treated normal and obese mice with the monoamine oxidase inhibitors pargyline or clorgyline for 25 weeks. This resulted in significant inhibition of monoamine oxidase in their hypothalamus, cerebral cortex, kidney, heart and epididymal fat. There was a significant increase in the norepinephrine concentration of the hypothalamus of the normal mice and the cerebral cortex of the obese mice. The obese mice receiving clorgyline had an increase in plasma glucose (313 +/- 9 mg/dl). However, the increase in tissue norepinephrine concentration did not result in increased weight gain or alterations in organ weights in the mice. Thus, the elevated hypothalamic norepinephrine concentration in obese mice is probably not the cause of their obesity.

Urinary free cortisol excretion in patients with metastatic cancer.

Many patients with metastatic carcinoma have an increase in urinary excretion of 17-hydroxycorticosteroids (17-OHCS), plasma concentrations of 17-OHCS, plasma total cortisol, plasma nonprotein-bound cortisol, or cortisol production rate. A small portion of circulating cortisol is excreted in the urine as unaltered or free cortisol. This urinary free cortisol, which is believed to reflect the average unbound plasma cortisol circulating during the day, is an excellent measure of adrenal cortical function. In this study, we compared the urinary free cortisol of 35 patients with metastastic cancer (10 small cell carcinomas of the lung, 8 other types of carcinoma of the lung, 8 breast carcinomas, and a miscellaneous carcinomas) with a group of 15 healthy age-matched volunteers. There were no significant changes in urinary free cortisol excretion in the patients with cancer.

Elevated hypothalamic norepinephrine content in mice with the hereditary obese-hyperglycemic syndrome.

There is evidence that hypothalamic norepinephrine (NE) plays a role in the control of appetite in the rat. Using specific and sensitive radioenzymatic assays, we determined if there was a difference in the tissue (hypothalamus, cerebral cortex and kidney) concentration of NE or of dopamine (DA) in mice with the hereditary obese-hyperglycemic syndrome (ob/ob) and their normal weight littermates, both when they were in the rapid growth phase (2--3 months of age) and when they were mature (6--7 months of age). The concentration of NE was similar in the cerebral cortex of obese and normal mice and in the kidneys of obese and normal mice. The concentration of DA was similar in the hypothalamus of obese and normal mice. The concentration of DA was similar in the hypothalamus of obese and normal mice and in the cerebral cortex of obese and normal mice. These observations support the concept that alterations in hypothalamic NE may play a role in the obesity of ob/ob mice.

Effects of food restriction on mice with the hereditary obese-hyperglycemic syndrome.

The purpose of this study was to compare the organ weights of obese-hyperglycemic (ob/ob) mice with the organ weights of their normal litter-mates. The absolute weights of the epididymal fat pads (white fat), interscapular fat pads (brown fat) and liver were greater in ob/ob mice than in normal mice. The weights of the kidneys and heart were similar in the 2 groups. The weights of the brain and testes were decreased in ob/ob mice when compared with normal mice. The weight gain of a second group of ob/ob mice was decreased by chronic food restriction resulting in a 26% reduction in weight when compared with ob/ob mice having unrestricted access to food. This substantially reduced the weight of the liver, but resulted in a minimal reduction in the weight of the epididymal fat pad. Food restriction did not alter the weight of the interscapular fat pads. It caused a relative reduction in kidney weight and a further absolute and relative reduction in testis weight.

Plasma norepinephrine response to standing in patients with pheochromocytoma or medullary carcinoma of the thyroid.

We determined the effect of a lying/standing test on 22 patients with medullary carcinoma of the thyroid (MCT), seven patients with pheochromocytoma (six of whom also had MCT), six healthy first-degree family members of patients with MCT, and nine normal subjects who did not have a family history of MCT. The purpose of the study was to determine if the patients with MCT had an altered noradrenergic response to standing and to determine if this test would be useful in screening MCT patients for the presence of pheochromocytoma. All of the patients with MCT, as well as all of the healthy family members, had normal urinary excretion of catecholamines and their metabolites. Plasma norepinephrine (NE) concentrations, plasma cortisol levels, and blood pressure (BP) were determined during the lying/standing test. The plasma NE concentration showed the expected increase with a change in posture; the plasma cortisol concentration did not change. There was no significant difference in the plasma NE, plasma cortisol, and BP response in the four study groups. Only one of the seven patients with pheochromocytoma had a hypertensive episode in response to standing. We conclude that there is probably a normal noradrenergic response to standing in patients with MCT, and the standing/lying test, as performed in this study, is of limited value in screening for the presence of pheochromocytoma.

Alterations in plasma norepinephrine concentration during surgical resection of pheochromocytoma.

Using a sensitive and specific radioenzymatic assay, the plasma norepinephrine (NE) concentration was measured in seven patients with pheochromocytoma, one patient with bilateral adrenal medullary hyperplasia, one patient with a retroperitoneal paraganglioma, and two patients undergoing bilateral adrenalectomies for palliation of metastatic breast carcinoma. Surgical manipulation of the pheochromocytomas resulted in striking increases in plasma NE concentration with concomitant increases in blood pressure. There were either small changes or no changes in the patients' plasma NE and blood pressure during resection of the normal adrenal glands, the adrenal glands with medullary hyperplasia, or the retroperitoneal paraganglioma. Plasma dopamine-beta-hydroxylase (DBH) was measured in one patient with pheochromocytomas and the patient with medullary hyperplasia. There was no change in plasma DBH in either patient, supporting the concept that exocytosis is not the primary mechanism for catecholamine secretion from pheochromocytomas. It was also noted that enflurane is an excellent general anesthetic for the resection of pheochromocytomas, and that sodium nitroprusside (rather than phentolamine) may be the agent of choice for the management of the hypertensive episodes that occur during surgical manipulation of pheochromocytomas.

Plasma and tumor dopamine-beta-hydroxylase activity in patients with familial pheochromocytomas.

The majority of patients with sporadic pheochromocytomas (pheos) have been noted to have normal plasma dopamine-beta-hydroxylase (DBH) activity. We determined the activity of DBH in the plasma of 8 patients with pheos, secondary to multiple endocrine neoplasia Type 2 (MEN II) (medullary carcinoma of the thyroid [MCT], pheochromocytoma(s), and parathyroid hyperplasia). We also determined the activity of DBH in the pheos of six of the patients. Three of the eight patients (38%) had elevated plasma DBH in the preoperative period. After surgical resection of their pheos, the plasma DBH of two of the subjects, in whom it could be measured, returned to normal. Although two of the other patients had bilateral pheos containing large amounts of DBH and norepinephrine (NE), their plasma DBH was normal in the preoperative and postoperative periods. Despite elevated urinary vanillylmandelic acid (VMA) excretion in all eight patients, their homovanillic acid (HVA) excretion was normal. VMA reflects NE plus epinephrine (E) excretion, while HVA reflects dopamine (DA) excretion. We conclude that the majority of patients with pheos, associated with MEN II, have normal plasma DBH activity.