Philippe Hubain

Frontal and parietal metabolic disturbances in unipolar depression

The authors investigated brain glucose utilization using positron emission tomography (PET) in 12 normal volunteers and 12 unipolar unmedicated depressed patients (six endogenous; six nonendogenous) following injection of [18F]fluoro-deoxyglucose (FDG). Compared by analyses of variance, absolute and relative regional glucose metabolic rates appeared different in depressed patients and control subjects, especially in parietal and frontal lobes. In patients with unipolar depression, metabolic rates were increased in the orbital part of the frontal lobe and decreased in a frontal dorsolateral area. The metabolic supero-basal gradient calculated in the frontal cortex was significantly lower in depressed patients than in normal subjects. Decreased glucose metabolism was also observed in the parietal cortex of depressed patients. No differences in glucose metabolic rates have been detected between endogenous and nonendogenous patients. No correlation has been found between the metabolic data and the Hamilton Rating Scale.

Haloperidol plasma levels and clinical response in paranoid schizophrenics

SummaryThe relationship between haloperidol plasma levels, plasma prolactin, and therapeutic efficacy was evaluated in 20 paranoid schizophrenics in a fixed-dose study for 6 weeks. We found a significant intrapatient cross-correlation of therapeutic efficacy, as measured by decrease in MSS and BPRS rating scales and time-dependent haloperidol and pro lactin changes, which were tested at weekly intervals. However, no significant curvilinear relationship was present between steady-state haloperidol plasma levels and MSS and BPRS improvement scores. Our data do not furnish clear-cut evidence in favor of the existence of a therapeutic window for haloperidol plasma levels in paranoid schizophrenia.

Major depression in males: Effects of age, severity and adaptation on sleep variables

Sleep abnormalities have been repeatedly demonstrated in major depression. However, the respective influences of age, severity, adaptation and gender have never been clearly disentangled. In a retrospective study, full polysomnograms of 67 male depressive patients and 67 carefully age-matched male healthy control subjects were analyzed. The usual differences associated with the sleep of depressed patients were observed. However, in contrast to most reports, REMS was also found to be reduced; although no comparisons between sexes can be made in this all-male study, one interpretation of this finding is that reduction of REMS is a marker of male depression. Age was found to influence most sleep variables, but not the order of their association with depression. Depression severity was found to be associated with Wake After Sleep Onset (WASO), REMS, and Non-REMS (NREMS). No residual adaptation effect was observed. One of the main markers of depression was in fact the absence of sleep, whether observed as long delays prior to entering sleep, or excessive intermittent awakenings. This sleep reduction affected both REMS and NREMS, in comparable percentages. This supports the hypothesis of a hyperarousal possibly linked to stress.

Shortened REM latency as a psychobiological marker for psychotic depression? an age-, gender-, and polarity-controlled study

BACKGROUND Previous reports suggest that the clinical dichotomy separating psychotic and nonpsychotic depression corresponds to different neurobiological profiles. The aim of the present study is to further investigate the psychobiological correlates of these two particular depressive subtypes. METHODS Thyroid-stimulating hormone response to thyrotropin-releasing hormone postdexamethasone cortisol levels, and electroencephalgraphic sleep characteristics of 44 psychotic major depressive patients were compared to those of 44 nonpsychotic depressives matched for age, gender, and polarity. RESULTS Some biological disturbances usually associated with depression (increased wakefulness, diminished rapid eye movement latency, hypercortisolism, blunted thyroid-stimulating hormone response to thyrotropin-releasing hormone stimulation) seemed to be significantly more pronounced in the psychotic depressed group as a reflection of greater illness severity; however, shortened REM latency was not influenced by severity and seemed to be more specifically related to the co-occurrence of psychotic and depressive symptoms. CONCLUSIONS Our data provide further support for the validity of the clinical dichotomy separating psychotic and nonpsychotic major depression independently of severity.

Age and gender effects on the diagnostic power of the DST

Among 365 major and 158 minor depressive inpatients, the dexamethasone suppression test (DST) yielded an overall diagnostic sensitivity of 50%, a specificity of 85%, and a confidence level of 88%. Age was significantly correlated with the post-dexamethasone cortisol levels in the whole sample (r = 0.11; P less than 0.01); however, this low relationship disappeared when all subgroups defined by gender or diagnostic were considered. Gender did not appear to influence DST results; however, among the patients between 30 and 39 years, the diagnostic performance of the DST was significantly lower among female as compared to male patients, suggesting possible interferences with endocrine variables.

Neuroendocrine and sleep variables in major depressed inpatients: role of severity

To evaluate the reliability of the endogenous concept of depressive illness according to the Newcastle Endogenous Depression Diagnostic Index (NEDDI), 155 major depressive inpatients with NEDDI scores > or = 6 (endogenous) were matched for gender and age (+/- 5 years) to 155 major depressive inpatients with NEDDI scores < 6 (nonendogenous). When sleep polygraphic variables, neuroendocrine parameters (dexamethasone suppression and thyrotropin-releasing hormone tests), and various clinical variables (unipolar/bipolar status, psychotic/nonpsychotic subtype, and severity of the depressive episode) were examined, statistically significant differences between endogenous and nonendogenous patients emerged for three variables: the thyroid-stimulating hormone response to the thyrotropin-releasing hormone test, the dexamethasone suppression test response at 16:00 h, and the percentage of time awake during the night. However, when the effects of age and severity of depression were controlled, those differences disappeared.

The Dexamethasone Suppression Test in Affective Illnesses and Schizophrenia: Relationship with Psychotic Symptoms

The authors studied the dexamethasone suppression test (DST) on a series of 112 inpatients including 65 patients with major depressive disorder (21 bipolars: 4 with, 17 without psychotic symptoms; 44 unipolars: 13 with, 31 without psychotic symptoms), 15 patients with depressive disorder, 10 schizoaffective and 22 schizophrenic patients. Using different diagnostic criteria, they confirm the best performances of the DST in depression for the diagnosis of a major depressive disorder, primarily endogenous. They also examined the potential influence of psychotic symptoms, suicidal behavior and family history of affective illness on the DST. The only significant difference found is in the cortisol plasma level at 4 p.m. in bipolar patients with psychotic symptoms. That fact and the high rate of abnormality of the DST in schizoaffective and schizophrenic patients indicate that psychotic symptoms per se may play a role in a dysregulation of the hypothalamo-pituitary adrenal axis.

Cimetidine-Induced Mania

The authors report a case of a typical manic syndrome following the administration of cimetidine. They discuss the risk factors related to the neuropsychiatric toxicity of cimetidine and suggest a pos

Alprazolam and amitriptyline in the treatment of major depressive disorder: a double-blind clinical and sleep EEG study

This study was designed to compare the antidepressant effects of alprazolam and amitriptyline in a group of 30 inpatients suffering from a severe major endogenous depression, diagnosed by Research Diagnostic Criteria and the Newcastle Rating scale, and to examine the effects of alprazolam and amitriptyline on two biological markers of depression, the dexamethasone suppression test and sleep EEG parameters. The 6-week study was double-blind with a random allocation of treatment. Patients were treated with flexible doses of 4-9 mg of alprazolam and 100-225 mg of amitriptyline. After 4 weeks of treatment the antidepressant effects of amitriptyline significantly exceeded those of alprazolam, as measured on the Hamilton Rating Scale for Depression. There was a high drop-out rate in the alprazolam group because of ineffectiveness of treatment. Alprazolam showed similar effects on sleep parameters as amitriptyline: lengthening of the REM latency and a tendency to shorten stages 3 and 4 and stage REM. These negative clinical results should be interpreted with caution, because of the severity of our selection criteria, and should not be extended to all depressive disorders.

Tetany due to hypomagnesaemia with secondary hypocalcaemia

The case is described of a 5-month-old boy who had convulsions and persistent tetany, associated with hypomagnesaemia and hypocalcaemia. Vitamin D treatment corrected the hypocalcaemia without modifying the clinical status; parenteral magnesium was given, but the child died shortly thereafter. The pathological examination showed calcinosis of the myocardium, kidneys and in one of the cerebral arteries.