Dissociation between pituitary and adrenal suppression to dexamethasone in depression.

OBJECTIVE: To determine if corticotroph nonsuppression, as reflected by beta-endorphin nonsuppression, occurs before cortisol nonsuppression (defined as a cortisol level of > 140 nmol/L) when examining multiple time points in a day. SETTING: The General Medical Clinical Research Center and Inpatient Depression Research Unit, Ann Arbor, Mich. DESIGN: Multiple blood samples were obtained through an intravenous catheter around the time points of 8 AM, noon, and 4 PM and assayed for beta-endorphin and cortisol. PATIENTS: Patients meeting Research Diagnostic Criteria for the diagnosis of major depressive disorder, primary and simple. A total of 73 subjects, both inpatients and outpatients, were studied. INTERVENTION: Samples were obtained both at baseline and 1 day after administration of 1 mg of dexamethasone at 11:30 PM. MEASUREMENTS AND RESULTS: Overall 39 patients (53%) demonstrated beta-endorphin nonsuppression after administration of dexamethasone at any of the three time points, while only eight patients (11%) demonstrated cortisol nonsuppression at any of these time points. Cortisol nonsuppression, but not beta-endorphin nonsuppression, was associated with lower concentrations of dexamethasone in plasma. Baseline cortisol and menopausal status were significantly associated with beta-endorphin nonsuppression in women.

Multiple HPA profiles in endogenous depression: effect of age and sex on cortisol and beta-endorphin.

We have previously shown that a number of depressed patients demonstrated a failure to suppress corticotrophic secretion, as measured by beta-Endorphin/beta-Lipotropin (beta-End/beta-LPH levels), following dexamethasone challenge. The current study is an extension and replication of these findings, as well as an analysis of some of the biological variables which may contribute to the variance in beta-End/beta-LPH nonsuppression. We continue to observe a high rate of beta-End/beta-LPH nonsuppression in depressed patients following dexamethasone; this escape at the pituitary level is even observed in a number of patients who demonstrate normal cortisol suppression. Advancing age, particularly in women, led to higher baseline cortisol, lower baseline beta-End/beta-LPH, and a greater likelihood of being a nonsuppressor on one or both measures.

Abnormal premovement brain potentials in schizophrenia.

We assessed scalp-recorded movement related potentials (MRPs) generated prior to voluntary movements in chronic, medicated schizophrenics (n = 9) and age matched normal controls (n = 9). MRPs were recorded in a self-paced button press task in which subjects pressed a button with either their right, left or both thumbs (experimental condition I, II and III respectively). Controls generated a slowly rising readiness potential (RP) at about 1000 ms, a negative shift (NS') at about 450 ms and a motor potential (MP) at about 100 ms prior to movement. The initial MRP components (RP and NS') were reduced in schizophrenics indicating an impairment of the voluntary preparatory process in schizophrenia. Results of the present study indicate a similarity of MRP findings in schizophrenics and reported MRPs (Singh and Knight, 1990) in patients with unilateral lesions of the dorsolateral prefrontal cortex. These findings provide further support for frontal lobe dysfunction in schizophrenia.

Beta-lipotropin-beta-endorphin response to low-dose ovine corticotropin releasing factor in endogenous depression. Preliminary studies.

Studies in depression using a maximal stimulatory dose of corticotropin releasing factor have concluded that elevated resting cortisol levels in depressed patients exert a negative feedback effect on the corticotroph, resulting in a decreased corticotropin response. In this preliminary report, we examine the effects of a submaximal dose of corticotropin releasing factor on the release of another corticotroph secretory product, beta-lipotropin-beta-endorphin. We observed a decreased beta-lipotropin-beta-endorphin response in depressed subjects, but a normal adrenal cortisol response. Although the total beta-lipotropin-beta-endorphin response was decreased, the initial secretory response did not differ between patients and normal controls. Rather, the patients appeared to turn off secretion faster. This rapid shutoff was seen in all patients regardless of resting cortisol levels, suggesting that resting cortisol levels alone do not explain the decreased response seen in depressed patients.

Circadian symptom fluctuations in people with anxiety disorders.

Circadian rhythm abnormalities have been demonstrated in people with depression, including a tendency toward maximal symptom severity in the morning. Although a few studies have suggested that symptoms in people with anxiety are worse later in the day, no detailed study of this observation has been reported. In 86 patients with anxiety disorders (63 with panic disorder or agoraphobia with panic attacks), anxiety symptoms tended to be more severe in the afternoon or evening than in the morning, with no abnormalities of heart rate or oral temperature. This is the first systematic demonstration of a circadian fluctuation of mood in any disorder other than depression.