Functional domains of the ATPase inhibitor protein from bovine heart mitochondria.

A study is presented of the activity and temperature dependence of the ATPase inhibitor protein (IF(1)) from bovine heart mitochondria and of synthetic partial IF(1) peptides. The results show that the IF(1)-(42-58) peptide is the most potent inhibitory domain of IF(1).

Tryptophan depletion in SSRI-recovered depressed outpatients.

RATIONALE: Recently, a number of studies have challenged the finding that acute tryptophan depletion (TD) increases depressive symptoms in medicated, formerly depressed patients. The present study examined the effects of acute nutritional TD on remitted depressed patients currently treated with selective serotonin reuptake inhibitors. In an attempt to clarify conflicting earlier findings, the effects of a number of clinical variables on outcome were also investigated. METHODS: Ten patients underwent TD in a double-blind, controlled, balanced crossover fashion. The control session followed the procedure of Krahn et al. (1996 Neuropsychopharmacology 15:325-328). Sessions were 5-8 days apart. RESULTS: TD was significantly related to increased scores on clinician-rated depression and anxiety scales, and on self-rated depression, anxiety, and somatic symptoms. The control challenge had no effect, despite the fact that the reductions in plasma tryptophan during the control session were unexpectedly high. Some evidence was found for a threshold in the relationship between reduction of plasma tryptophan and mood response. CONCLUSIONS: The mood effect of TD in medicated, formerly depressed patients was confirmed. A threshold may exist for mood effects following TD, implying that recent negative findings may have been caused by insufficient depletion. No other predicting or mediating factors were identified, although the variable "history of response pattern to medication" deserves further study.

Fenfluramine challenge in unipolar depression with and without anger attacks.

We have previously hypothesized that patients with major depression and anger attacks may have a greater central serotonergic dysregulation than depressed patients without such attacks. We wanted to compare the prolactin response to fenfluramine challenge, as an indirect measure of central serotonergic function, in depressed patients with and without anger attacks. We recruited 37 outpatients (22 men and 15 women; mean age: 39.5+/-10.5) with DSM-III-R major depressive disorder, diagnosed with the SCID-P. Their initial 17-item Hamilton Rating Scale for Depression score was >/=16. Patients were classified as either having or not having anger attacks with the Anger Attacks Questionnaire. All patients received a single-blind placebo challenge followed by a fenfluramine challenge (60 mg orally) the next day. Plasma prolactin measurements were obtained with double antibody radioimmunoassay before and after both placebo and fenfluramine challenges, and fenfluramine and norfenfluramine blood levels after each challenge were determined by gas chromatography. Of the 37 study participants, 17 (46%) were classified as having anger attacks. There were no significant differences in age, gender, fenfluramine, or norfenfluramine blood levels between depressed patients with and without anger attacks. Depressed patients with anger attacks showed a significantly blunted prolactin response to fenfluramine challenge compared to patients without anger attacks. As previous studies have shown blunted prolactin responses to fenfluramine in impulsive aggression among patients with personality disorders, our results support our hypothesis that depressed patients with anger attacks may have a relatively greater serotonergic dysregulation than depressed patients without these attacks.

Management of major depression in the primary care setting.

BACKGROUND: Patients treated in community clinics, particularly those of minority status, may rely more heavily on primary care physicians (PCPs) for the diagnosis and management of depression. We wished to determine how PCPs in a community clinic setting initially manage patients newly diagnosed with major depression. METHODS: 698 patients were screened for major depression by the Structural Clinical Interview for DSM-III-R in a community-based primary care health center. Forty outpatients (29 Hispanic) were found to suffer from major depression. A letter explaining positive findings was sent to the patients' PCPs. Medical record charts were reviewed 3 months later to determine the PCP's management following the diagnosis. RESULTS: Of the 38 patients who remained in the study at 3 months, 20 (53%) received no intervention from the PCP by the end of 3 months after diagnosis, and of these, 14 were Hispanic. Five (13%) were prescribed an antidepressant by the PCP. Nine (24%) were referred to mental health services for medication, psychotherapy or combination treatment. Four (11%) were prescribed an antidepressant and then referred to mental health services. Differences between management of Hispanic and non-Hispanic patients were not statistically significant. CONCLUSIONS: Independent screening by psychiatrists in primary care settings may not be adequate enough to ensure appropriate management of depression by PCPs. Possible explanations may include time constraints during primary care visits, patient and/or physician reticence, and insufficient education of PCPs about depression.