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Biomedical subjects

L Grunhaus

Publications and source records attributed to L Grunhaus.

At least 37 records · Page 2Linked to original sources

[Brain imaging and its clinical application in psychiatry].

The common structural and functional brain imaging techniques are described from a practical, clinical point of view. The clinical indications for brain imaging in psychiatry are reviewed in relation to the specific limitations and advantages of each technique. The clinical applications of computerized tomography (CT), magnetic resonance imaging (MRI) and single photon emission computerized tomography (SPECT) are discussed in relation to the differential diagnosis between organic and functional psychiatric disorders. In a 55-year-old man with late onset of behavioral changes but without neurological signs the application of structural brain imaging (CT and MRI) in case management was demonstrated. The imaging findings involved the differential diagnosis between depression and focal brain lesions. In a 38-year-old man with personality changes and depression following a traumatic brain injury, time interval repeated functional brain imaging (SPECT) was used. Brain imaging reflected improvement in clinical status following treatment and was able to differentiate between reversible and permanent traumatic brain injuries. The superior yield of time interval repeated functional imaging in diagnosis and management of postconcussion syndrome is discussed.

Adult↗

Sleep-onset rapid eye movement after electroconvulsive therapy is more frequent in patients who respond less well to electroconvulsive therapy.

The response to electroconvulsive therapy (ECT) was monitored with sleep polysomnography studies (SPS) performed pre- and post-ECT, in 25 patients with major depressive disorder (MDD). Patients included in this study met research diagnostic criteria for MDD and had been free of psychotropic medication for at least 10 days before SPS were performed. We compared ECT responders and nonresponders on SPS, demographic, and clinical parameters. Many SPS parameters, regardless of the clinical response, changed significantly with ECT. The presence of delusions was significantly associated with SOREM post-ECT. The presence of sleep-onset REM periods post-ECT was associated with poor response to ECT. SPS performed during a course of ECT may help identify patients at risk of responding less well to this modality of treatment.

Adult↗

Vitamin E treatment in tardive dystonia.

Tardive dystonia is a disorder characterized by abnormally sustained posturing associated with the use of dopamine-receptor blocking agents such as antipsychotic drugs. However, the structural pathologic and pathophysiologic features of this disorder are unknown, and no consistently effective pharmacologic treatment is available. Patients with tardive dystonia mostly are young men. We present the case of one substantially improved with treatment by 1200 mg/d (IU) of vitamin E.

Adult↗

ECT in patients with major depressive disorder and low cardiac output.

Electroconvulsive therapy (ECT) in patients with impaired cardiac output may be associated with significant cardiovascular morbidity and mortality because of its hemodynamic effects. Many clinicians are reluctant to treat these patients with ECT because of the high risk associated with the treatment. In this report, we present a clinically appropriate protocol for ECT treatment of patients with impaired cardiac output and major depressive disorder. Three patients, ages 59-78 years, with resistant major depression and impaired cardiac output (ejection fraction 20-25%), were successfully treated with ECT according to this protocol.

Aged↗

Polysomnographic studies in patients referred for ECT: pre-ECT studies.

Forty-one patients referred for electroconvulsive therapy (ECT) were evaluated with a standardized clinical protocol and had polysomnographic studies performed pre-ECT after 10 or more days drug free. Clinical evaluations were performed by blind investigators and included the Research Diagnostic Criteria and the Hamilton Rating Scale for Depression (HRSD). Patients were categorized according to the clinical response. Thirty patients (73%) reached a post-ECT HRSD < or = 10, whereas 21 of them (51.2%) reached a post-ECT HRSD score < or = 6. Sleep-onset rapid eye movement (SOREM) periods were present in 27 (66%) of the patients. Few polysomnographic variables differentiated between excellent responders and patients with residual symptoms. Older patients had significantly more disrupted polysomnographic study parameters. Although present in a significant proportion of patients, baseline SOREM was not a factor in outcome.

Adult↗

Shortened REM latency PostECT is associated with rapid recurrence of depressive symptomatology.

Electroconvulsive therapy (ECT) is highly effective in the treatment of major depressive disorder (MDD). The 1-year relapse rates are reported to be high and in the 30%-60% range, however. To test whether polysomnography (PS) can identify patients with a propensity for relapse we studied 20 patients, responders to a course of ECT, with PS studies. All patients met baseline diagnostic criteria for MDD, were treated with ECT following standardized protocols, had PS studies performed after the course of ECT in a medication-free state, received maintenance antidepressants postECT, and were followed periodically with phone interviews. The recurrence of depressive symptoms was determined at 3 months and 6 months after discharge. Fifty-five percent of the patients were symptomatic when evaluated 6 months after the ECT. Sleep Onset rapid eye movement (REM) periods were identified in 55% of the patients. As a group, patients who had experienced a recurrence of depressive symptoms by 6 months after discharge, had significantly shorter REM latencies after the course of ECT. A shorter REM latency after ECT identified patients who at six months demonstrated significant depressive symptomatology. Shortened REM latency after ECT in patients with MDD appears to be a correlate of vulnerability for relapse.

Adult↗

Increased evening activation of the hypothalamic-pituitary-adrenal axis in depressed patients.

OBJECTIVE: To determine whether depressed patients demonstrate hypothalamic-pituitary-adrenal (HPA) axis activation during the late afternoon and evening, a time when the HPA axis is usually quiescent in normal subjects. METHODS: We administered metyrapone, an 11-beta-hydroxylase inhibitor of cortisol synthesis, to normal controls and depressed patients between 4 and 10 PM. Metyrapone blockade of cortisol secretion would amplify any HPA axis secretion. RESULTS: In 10 normal control subjects, administration of metyrapone lowered plasma cortisol levels to a mean of 36 nmol/L. No rebound corticotropin or beta-endorphin secretion was seen in these normal controls between 4 and 10 PM, supporting the existence of a period of minimal endogenous corticotropin releasing factor drive. Compared with a group of placebo-treated depressed patients (n = 10), metyrapone-treated depressed subjects (n = 17) had significantly decreased plasma cortisol concentrations. However, in contrast to normal controls treated with metyrapone, metyrapone-treated depressed patients demonstrated rebound corticotroph secretion, particularly between 7:30 and 10 PM (P = .036 for patients vs normal controls for beta-endorphin secretion from 4:30 to 10 PM). CONCLUSION: These data support the hypothesis of increased corticotropin releasing factor drive in the evening in depressed subjects and are in agreement with the longstanding observation of "early escape" from dexamethasone suppression between 4 and 11 PM in depressed patients.

Adrenocorticotropic Hormone↗

Clinical characteristics of patients with concurrent major depressive disorder and panic disorder.

OBJECTIVE: This study was designed to test the hypothesis that patients with both major depressive disorder and panic disorder exhibit more clinical symptoms and have a more protracted course of illness than patients with major depressive disorder only. METHOD: The authors compared standardized clinical evaluations (from Schedule for Affective Disorders and Schizophrenia interviews) of 119 patients with major depressive disorder only and 57 patients with major depressive disorder and concurrent panic disorder. Clinical and demographic variables were included. RESULTS: The patients with both disorders reported symptoms of major depressive disorder earlier in life and also required treatment and hospital admission earlier in life. Many clinical features during the index episode were significantly more severe in the patients with both disorders. A logistic regression identified a "panic index" consisting of the symptoms of somatic anxiety, phobia, indecisiveness, and feelings of inadequacy. Scores on this index allowed proper classification of patients to either of the two diagnostic groups with high reliability. CONCLUSIONS: In major depressive disorder, the presence of panic disorder is suggestive of a more severe and precocious form of illness.

Adult↗

Noradrenergic response to intravenous yohimbine in patients with depression and comorbidity of depression and panic.

Adrenergic response following infusions of yohimbine or normal saline was evaluated in 9 control subjects, 8 patients suffering from a major depressive episode (MDE), and 12 patients suffering from concurrent MDE and panic disorder (MDE + P). Blood was drawn at -20, 0, 5, 10, 20, 45, and 90 min following the infusions, and assayed for norepinephrine (NE) and 3-methoxy-4-hydroxy-phenyl glycol (MHPG). Although the patient groups exhibited higher baseline NE concentrations, and a greater NE area under the plasma concentration versus time curve (AUC0-90) during the yohimbine infusion, the differences were not statistically significant. Baseline NE was significantly correlated with the NE AUC0-90 in all three groups, suggesting that, although the NE system may be dysregulated in the MDE and MDE + P patients, the NE system still appears to respond somewhat predictably following a challenge, even though the actual magnitude of response may vary.

Adult↗

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.

Adrenocorticotropic Hormone↗

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.

Adult↗

The DST as a predictor of outcome in depression: a meta-analysis.

OBJECTIVE: The authors undertook a review of the literature on the dexamethasone suppression test (DST) as a predictor of course and outcome in major depression, to illustrate clinical and pathophysiological implications of studying the relation between biological measures and course of illness in psychiatry. METHOD: In computerized searches and cross-references, 144 articles were found that related DST results to prediction of treatment response or outcome. Meta-analysis was performed on pooled data from all of the studies and separately on data from selected studies that had used stricter methodology. RESULTS: 1) Baseline DST status did not predict response to antidepressant treatment or outcome after hospital discharge. 2) Non-suppression of cortisol on the baseline DST predicted poorer response to placebo. 3) Persistent nonsuppression of cortisol on the DST after treatment was associated with high risk of early relapse and poor outcome after discharge. CONCLUSIONS: Baseline DST results may be devoid of prognostic value, but posttreatment nonsuppression of cortisol on the DST is strongly associated with poor outcome. Persistent nonsuppression may reflect a partially treated index episode or identify sicker patients who are unresponsive to treatment. The findings reiterate the importance of studying biological measures in relation to multiple validators of psychiatric illness beyond cross-sectional diagnosis.

Antidepressive Agents↗

EEG sleep in Cushing's disease and Cushing's syndrome: comparison with patients with major depressive disorder.

Because patients with Cushing' syndrome (CS) and Major depressive disorder (MDD) share features of hypercortisolism and the depressive syndrome, we compared electro-encephalographic (EEG) sleep in patients with pituitary-ACTH-dependent Cushing's syndrome (Cushing's disease, CD), patients with ACTH-independent Cushing's syndrome (AICS), patients with major depressive disorder (MDD), and normal subjects. There were substantial similarities in the abnormal polysomnography profiles of patients with CD, AICS, and MDD. All three patient groups demonstrated poorer sleep continuity, shortened rapid eye movement (REM) latency, and increased first REM period density compared with normal subjects. In addition, AICS patients and MDD patients had elevated REM activity and density. These findings are discussed in terms of models of pathophysiology that relate abnormalities in sleep, mood, and hypothalamic-pituitary-adrenal function.

Adenoma↗

A longitudinal evaluation of dexamethasone pharmacokinetics in depressed patients and normal controls.

Ten depressed patients and eight control subjects received 1 mg of dexamethasone intravenously at two different time points. Depressed patients were studied when they were depressed and following an improvement in their depression. In control subjects the first and second studies were performed approximately 1 month apart. Dexamethasone and cortisol were determined at 0, 5, 15, and 30 minutes, then at 1, 1.2, 2, 3, 4, 5, 6, 7, 9, 12, 17, and 24 hours following dexamethasone administration. Data from each patient was fit using a computer to a two compartment pharmacokinetic model and area under the time versus plasma concentration curve, elimination half-life, and clearance were also determined. Depressed patients exhibited a slower dexamethasone clearance and a larger area under the curve than control subjects at the first time point, but not at the second time point. The groups did not differ significantly in any of the other pharmacokinetic parameters (including distribution half-life, elimination half-life, or volume of distribution) at either time point. The possible causes and implications of these findings are discussed.

Adult↗