Biomedical subjects

Jean-Paul Macher

Publications and source records attributed to Jean-Paul Macher.

10 recordsLinked to original sources

PubMed2005

Facial expressiveness in patients with schizophrenia compared to depressed patients and nonpatient comparison subjects.

OBJECTIVE: Blunted affect is a major symptom in schizophrenia, and affective deficits clinically encompass deficits in expressiveness. Emotion research and ethological studies have shown that patients with schizophrenia are impaired in various modalities of expressiveness (posed and spontaneous emotion expressions, coverbal gestures, and smiles). Similar deficits have been described in depression, but comparative studies have brought mixed results. Our aim was to study and compare facial expressive behaviors related to affective deficits in patients with schizophrenia, depressed patients, and nonpatient comparison subjects. METHOD: Fifty-eight nondepressed inpatients with schizophrenia, 25 nonpsychotic inpatients with unipolar depression, and 25 nonpatient comparison subjects were asked to reproduce facial emotional expressions. Then the subjects were asked to speak about a specific emotion for 2 minutes. Each time, six cross-cultural emotions were tested. Facial emotional expressions were rated with the Facial Action Coding System. The number of facial coverbal gestures (facial expressions that are tied to speech) and the number of words were calculated. RESULTS: In relation to nonpatient comparison subjects, both patient groups were impaired for all expressive variables. Few differences were found between schizophrenia and depression: depressed subjects had less spontaneous expressions of other-than-happiness emotions, but overall, they appeared more expressive. Fifteen patients with schizophrenia were tested without and with typical or atypical antipsychotic medications: no differences could be found in study performance. CONCLUSIONS: The patients with schizophrenia and the patients with depression presented similar deficits in various expressive modalities: posed and spontaneous emotional expression, smiling, coverbal gestures, and verbal output.

Adult↗

PubMed2005

Neuroendocrine predictors of the evolution of depression.

Depression is both clinically and biologically a heterogeneous entity. Despite advances in psychopharmacology, a significant proportion of depressed patients either continue to have residual symptoms or do not respond to antidepressants. It has therefore become essential to determine parameters (or predictors) that would rationalize the therapeutic choice, taking into account not only the clinical features, but also the "biological state," which is a major determinant in the antidepressant response. Such predictors can derive from bioclinical correlates and, in this context, the neuroendocrine strategy appears particularly suited. Numerous studies have investigated neuroendocrine parameters--derived mainly from dynamic challenge tests--in order to (i) determine the predictive profiles of good clinical responders to given antidepressants; (ii) monitor the progression of markers in parallel with the clinical outcome; and (iii) evaluate "in vivo" in humans the mechanisms of action of antidepressant compounds (before, during, and after treatment). This article does not attempt to be exhaustive, but rather uses selected examples to illustrate the usefulness of the investigation of the adrenal and thyroid axes and the assessment of central serotonergic, noradrenergic, and dopaminergic systems by means of neuroendocrine tests. Given methodological constraints, most of these investigations--except for baseline hormone values and the dexamethasone suppression test--cannot be used routinely in psychiatry. Despite these limitations, the neuroendocrine strategy still offers new insights in biology and the treatment of depression. Its possible expansion depends mainly on the development of specific agonists or antagonists for better investigation of the receptors supposedly involved in the pathophysiology of depression. These investigations will help define more homogeneous subgroups from a bioclinical and therapeutic viewpoint.

Antidepressive Agents↗

PubMed2005

[Phenotypes].

Explore the source record for details and available documents.

Biomarkers↗

PubMed2004

Increased adrenocorticotropin suppression following dexamethasone administration in sexually abused adolescents with posttraumatic stress disorder.

Evidence suggests that individuals with posttraumatic stress disorder (PTSD) have an enhanced sensitization of the hypothalamic--pituitary--adrenocortical (HPA) axis. However, few studies in adolescents have been performed. Fourteen sexually abused adolescent inpatients with DSM-IV PTSD (12 female, two male; mean +/- SD age, 16.2 +/- 1.9 years) were compared with 14 adolescent hospitalized controls (11 female, three male; mean age, 15.7 +/- 2.0 years). All subjects underwent a standard dexamethasone suppression test (DST, 1 mg given orally at 2300 h) five days after admission. Baseline blood samples were obtained at 0800 h, and the following day, adrenocorticotropin (ACTH) and cortisol levels were measured at 0800, 1600, and 2300 h. Clinical assessment included the Impact of Event Scale, Stanford Acute Stress Reaction Questionnaire, Beck Depression Inventory, and Coping Inventory for Stressful Situations. Post-DST ACTH levels were significantly lower in PTSD than in control adolescents (at 0800 h: P < 0.005; at 1600 h: P < 0.001; at 2300 h: P < 0.05). In patients, post-DST cortisol levels were reduced but not significantly. No correlations were found between ACTH and cortisol levels and time elapsed since trauma. These results demonstrate that sexually abused adolescents with PTSD show ACTH hypersuppression to DST suggesting enhanced glucocorticoid receptor sensitivity in the pituitary.

Adaptation, Psychological↗

PubMed2004

Increased adrenocorticotropin suppression after dexamethasone administration in sexually abused adolescents with posttraumatic stress disorder.

Evidence suggests that individuals with posttraumatic stress disorder (PTSD) have enhanced sensitization of the hypothalamic-pituitary-adrenocortical (HPA) axis. Fourteen adolescent inpatients with DSM-IV PTSD were compared with 14 adolescent hospitalized controls without current axis I diagnoses. All patients were drug-naive. The causative trauma had been sexual abuse in all cases. Dexamethasone, 1 mg orally, was given at 11 PM, 5 days after admission. Baseline blood samples were obtained at 8 AM, and on the following day, adrenocorticotropin (ACTH) and cortisol levels were measured at 8 AM, 4 PM, and 11 PM. Clinical assessment included the Impact of Event Scale, Stanford Acute Stress Reaction Questionnaire, Beck Depression Inventory, and Coping Inventory for Stressful Situations. Post-DST ACTH levels were significantly lower in PTSD than in control adolescents (at 8 AM, P <0.005; at 4 PM, P <0.001; and at 11 PM, P <0.05). In patients, post-DST cortisol levels were reduced but not significantly. No correlations were found between ACTH and cortisol levels and time elapsed since trauma. These results demonstrate that sexually abused adolescents with PTSD show ACTH hypersuppression to DST, suggesting enhanced glucocorticoid receptor sensitivity in the pituitary.

Adaptation, Psychological↗

PubMed2003

Dopamine and serotonin function in untreated schizophrenia: clinical correlates of the apomorphine and d-fenfluramine tests.

This study examined the prolactin (PRL), adrenocorticotropin (ACTH) and cortisol responses to the direct DA receptor agonist apomorphine (APO) and the selective 5HT-releasing agent d-fenfluramine (d-FEN) in 20 untreated inpatients with DSM-IV schizophrenia and without a history of suicide attempt, compared to 23 hospitalized healthy controls. We hypothesized that different patterns of responsiveness of the DA and 5-HT systems might be associated with specific schizophrenic symptom clusters. A positive correlation was observed between pituitary-adrenal response to APO and d-FEN tests (i.e. deltaACTH and deltacortisol) in the overall population and in schizophrenic patients. Pituitary-adrenal response to APO was lower in patients than in normal controls. Moreover, lower pituitary-adrenal response to APO and d-FEN was associated with increased severity of BPRS thought disturbance score. Lower pituitary-adrenal responses to APO (and to a lesser degree to d-FEN) differentiated paranoid from disorganized schizophrenic patients. Neither PRL suppression to APO, nor PRL stimulation to d-FEN were altered in schizophrenic patients. Our results suggest that decreased hypothalamic DA receptor activity (possibly secondary to increased presynaptic DA release) together with relatively decreased 5-HT tone characterize paranoid SCH, while normal hypothalamic DA receptor activity together with relatively increased 5-HT tone characterize the disorganized SCH subtype.

Adrenocorticotropic Hormone↗

PubMed2003

Sleep microstructure around sleep onset differentiates major depressive insomnia from primary insomnia.

In the present study we investigate whether alterations of sleep propensity or of wake propensity are implicated in sleep initiation disturbances encountered in major depressive insomnia and in primary insomnia. For this purpose, the time course of electroencephalogram (EEG) power density during the period preceding sleep onset and during the first non-rapid eye movement (REM) period was examined in three age and gender matched groups of 10 women and 11 men (healthy controls, primary insomniacs and depressive insomniacs). In contrast to healthy controls and depressive insomniacs, patients with primary insomnia did not experience a gradual decrease of their alpha and beta1 power during the sleep onset period and had a lower delta activity in the 5 min preceding sleep onset. Compared with the two other groups, depressive patients exhibit less dynamic changes in slow wave activity during the first non-REM period. The present results suggest that hyperarousal (high 'Process W') may mainly be implicated in the sleep initiation difficulties of primary insomniacs whereas the homeostatic sleep regulation process seems to be partially maintained. In our major depressed patients, the sleep initiation disturbances appeared to relate to a lower sleep pressure (low 'Process S') rather than to hyperarousal. This study supports the idea that different mechanisms are implicated in sleep disturbances experienced by primary insomniacs and major depressive insomniacs.

Adult↗

PubMed2002

Serotonergic function and suicidal behavior in schizophrenia.

Recent studies suggest that altered serotonergic (5-HT) function, as assessed by lower prolactin (PRL) response to fenfluramine (FEN), a specific 5-HT releaser and uptake inhibitor, is associated with suicidal behavior in either depressed and personality disordered patients. The purpose of this study was to investigate, in schizophrenic patients, the relationship between suicidal behavior and PRL response to D-fenfluramine (D-FEN). A D-FEN test was performed in 18 healthy controls and 33 drug-free DSM-IV schizophrenic patients (12 with a history of suicide attempts, 21 without it). Schizophrenic patients with a history of suicide attempts showed a lower PRL response to D-FEN (Delta PRL) compared to schizophrenic patients without such history (P<0.04) and also compared to healthy controls (P<0.0003). Delta PRL did not differentiate schizophrenic patients without suicide attempts and controls. These findings could not be explained by PRL basal hormonal levels, age, sex, menstrual status, demographic or clinical characteristics. These results suggest that PRL response to D-FEN is a marker of suicidal tendencies also in schizophrenia, supporting the hypothesis that a dysfunction in serotonergic function is associated with suicidal behavior regardless of the psychiatric diagnosis.

Adult↗

PubMed2002

Localized 2D correlation spectroscopy in human brain at 3 T.

The purpose of this study was to acquire a localized 2D (two-dimensional) 1H correlation spectrum, in a volume of interest reasonably small, and within an experiment time compatible with clinical applications. A modified PRESS technique has been used. The last 180 degrees pulse of the PRESS sequence has been converted into a 90 degrees pulse for both refocusing and coherence transfer. 2D correlation spectroscopy was performed on healthy volunteers in a clinical magnet, at 3 T, within 34 min, for a voxel size of 27 cm3. This result makes it possible to consider clinical applications.

Brain↗

PubMed2002

Efficacy and safety of hydroxyzine in the treatment of generalized anxiety disorder: a 3-month double-blind study.

BACKGROUND: The prevalence of generalized anxiety disorder (GAD) represents an important public health issue. Hydroxyzine, an antagonist of histamine receptors, showed both efficacy and safety in previous short-term double-blind studies over placebo in this pathology. The aim of the current study was to confirm those positive results over a 3-month period in adult outpatients. METHOD: This multicenter, parallel (hydroxyzine [50 mg/day]; bromazepam [6 mg/day]), randomized, double-blind, placebo-controlled trial included 2 weeks of single-blind run-in placebo, 12 weeks of double-blind randomized treatment, and 4 weeks of single-blind run-out placebo. Three hundred thirty-four of 369 selected outpatients with a diagnosis of GAD according to DSM-IV criteria and a Hamilton Rating Scale for Anxiety (HAM-A) total score >/= 20 were randomized before entering the double-blind period. The primary outcome criterion was the change in the HAM-A score from baseline to 12 weeks of double-blind treatment with hydroxyzine compared with placebo. RESULTS: In the intent-to-treat analysis, the mean +/- SD change in HAM-A scores from baseline to endpoint was -12.16 +/- 7.74 for hydroxyzine and -9.64 +/- 7.74 for placebo (p =.019). Results at endpoint for percentage of responders (p =.003) and remission rates (p =.028), Clinical Global Impressions-Severity scale score (p =.001), maintenance of efficacy (p =.022), and Hospital Anxiety and Depression scale score on day 84 (p =.008) also confirmed the efficacy of hydroxyzine over placebo. The study showed no statistically significant difference between hydroxyzine and bromazepam. Except for drowsiness, which was more frequent with bromazepam, safety results were comparable in the 3 groups. CONCLUSION: Hydroxyzine showed both efficacy and safety in the treatment of GAD and appears to be an effective alternative treatment to benzodiazepine prescription.

Adult↗