Search PubMed⌕ Search

Biomedical subjects

J P Boulenger

Publications and source records attributed to J P Boulenger.

At least 19 recordsLinked to original sources
PubMed2002

[Impact of psychiatric disturbances on the outcome of coronary bypass surgery].

The influence of anxiety and depression on the development and prognosis of coronary disease seems to be well established but there are few studies of the effects of these disturbances on the postoperative outcome of coronary surgery. The object of this review of the literature was to present recent data on this subject and to suggest therapeutic strategies for patients referred for coronary bypass surgery to improve their quality of life and even cardiovascular prognosis.

Anxiety Disorders↗
PubMed2001

The influence of Type A behavior pattern on the response to the panicogenic agent CCK-4.

OBJECTIVES: Review of the literature equivocally suggests that subjects with Type A behavioral pattern (TABP) compared to subjects with Type B behavioral pattern display an increased sympathetic activity, a condition associated with sudden cardiac death. The objective of this study was to determine whether healthy subjects classified as Type A or Type B differed in their reactivity to the beta 1 and beta 2 receptor agonist isoproterenol and to the panicogenic agent cholecystokinin-tetrapeptide (CCK-4). By comparing reactivity to CCK-4 after pretreatment with placebo or propranolol, a beta 1 and beta 2 receptor antagonist, the role of the beta adrenergic system in the hypothesized increased response of Type A subjects to CCK-4 was also assessed. METHODS: The study used a randomized, double-blind, placebo-controlled design. Twenty-seven Type A or B subjects were included in the study. The reactivity to isoproterenol was assessed with the CD25 of isoproterenol (i.e., the intravenous dose of isoproterenol necessary to increase the heart rate of 25 bpm). The panic symptom response and the cardiovascular response to bolus injection of 50 microg of CCK-4 was assessed in subjects pretreated with either propranolol or placebo infusions prior to the CCK-4 challenge. An additional group of subjects was recruited and these subjects received a placebo infusion pretreatment before an injection of placebo. RESULTS: The CD25 was significantly greater in Type A subjects than in Type B subjects. No difference was found among the groups on behavioral sensitivity to the CCK-4 challenge. However, CCK-4-induced maximum increase in heart rate was greater in Type A subjects. CONCLUSION: Our finding that Type A subjects exhibited greater CD25 of isoproterenol and greater increases in heart rate following CCK-4 administration compared to Type B subjects suggests that peripheral beta-receptor sensitivity may be increased in individuals with TABP.

Adrenergic beta-Agonists↗
PubMed2001

Suicide attempts and the tryptophan hydroxylase gene.

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synthesis. In this case-control study, we investigated whether the TPH gene was a susceptibility factor for suicidal behavior. Seven polymorphisms spanning the entire gene were studied in a case-control study including 231 individuals who had attempted suicide and 281 controls. Significant associations were found between variants in introns 7, 8 and 9 (chi(2) = 11.2, df = 1, P< 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3' noncoding region (chi(2) = 30.94, P = 0.0014) and suicide attempt. The association was strongest for subjects who had attempted suicide by violent means and who had a history of major depression. No significant association was observed between suicide attempts and polymorphisms in the promoter, intron 1 and intron 3. The results presented here, and those of previous studies, suggest that a genetic variant of the 3' part of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression.

Adult↗
PubMed2001

Association between violent suicidal behavior and the low activity allele of the serotonin transporter gene.

There is compelling evidence that serotonin system dysfunction is associated with certain behavioral disorders, such as suicidal behavior and impulsive aggression. A functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) was recently identified and the presence of the short allele found to be associated with a lower level of expression of the gene, lower levels of 5-HT uptake, suicidal behavior and anxiety-related traits. We genotyped 51 West European Caucasians who had made violent suicide attempts and 139 controls of the same ethnic origin, with no history of suicidal behavior. The frequencies of the S allele and the SS genotype were significantly higher in the violent suicide attempters than in the controls. The odds ratio for the SS genotype vs the LL genotype was 3.63 (95% CI (1.27--10.40)). This suggests that a change in expression of the gene encoding the 5-HT transporter may be involved in violent suicidal behavior.

Adult↗
PubMed2000

Outcomes in a referral cohort of patients with anxiety disorders.

This study describes 6- and 12-month outcomes in a referral cohort with anxiety disorders and identifies treatment and prognostic factors related to these outcomes. Patients were recruited at three general hospital clinics, two psychologist-run clinics, and one psychiatric hospital clinic. Outcomes included severity of symptoms, physical and mental health status, and subjective global change in problem severity. Of 254 patients eligible for follow-up, 165 (65.0%) completed a follow-up questionnaire. Methods of treatment included consultation with return to the primary care physician (38.2%); or continued treatment at the clinic, with medications (16.4%), psychotherapy (22.4%), or both (23.0%). Both severity of symptoms and mental health status improved but remained abnormal at follow-up. In multiple logistic regression, subjective global improvement was related to a diagnosis of panic disorder only, treatment with psychotherapy, and type of referral. Change over time in symptom severity was related to clinic type, and change over time in mental health was related to clinic type and duration of previous treatment.

Adult↗
PubMed1999

CCK4-induced panic in healthy subjects I: psychological and cardiovascular effects.

Sixteen healthy subjects participated in a crossover, double blind, and placebo-controlled study, designed to assess simultaneously the psychological and cardiovascular effects of cholecystokinin tetrapeptide (CCK4). Following an i.v. injection of 25 microg of CCK4, 44 percent of subjects experienced symptoms that fulfilled the DSM-IV criteria for a panic attack while no one panicked with placebo. CCK4 induced a significantly greater number and higher intensity of panic-like symptoms than placebo. A significant increase in state anxiety was observed in the period after CCK4 injection; this increase was significantly larger than the non-specific anxious reaction to placebo. CCK4 also affected cardiovascular signs. Both heart rate and mean blood pressure significantly increased after administration of CCK4. Again, these increases were significantly higher than those seen after placebo injection. We conclude that, in healthy subjects, CCK4 induces panic-like reaction characterized by a number of somatic, cognitive and emotional symptoms, which are accompanied by increases in heart rate and blood pressure.

Adult↗
PubMed1999

CCK4-induced panic in healthy subjects II: neurochemical correlates.

Cholecystokinin tetrapeptide (CCK4) induces symptoms similar to those of panic attack. The present study investigated the effects of CCK4 administration on catecholaminergic system. In this double blind, randomised, crossover experiment, 16 healthy subjects received injections of either 25 microg of CCK4 or placebo on two separate occasions. Platelet and plasma catecholamine concentrations were assessed before the administration and compared to post-injection values. The results clearly show that both plasma and platelet concentrations of catecholamines are significantly affected by CCK4. Plasma norepinephrine (NE) and epinephrine (EPI) raised significantly above baseline in the immediate post-CCK4 period, while in plasma dopamine (DA), the significant increases were delayed. In the platelets, significant post-CCK4 increases of NE and EPI concentrations were observed with a delay of several minutes. In summary, we have demonstrated that, in healthy subjects, CCK4 increases peripheral concentrations of catecholamines in both plasma and platelets, with the most consistent changes occurring in platelet NE and plasma EPI concentrations.

Adult↗
PubMed1999

Relationships between trait and state anxiety and the central benzodiazepine receptor: a PET study.

The central benzodiazepine receptor (cBZr) has long been implicated in anxiety disorders on the basis of: (i) the well-known anxiolytic and anxiogenic properties of cBZr agonists and inverse agonists, respectively; (ii) a possibly reduced sensitivity to benzodiazepines in anxious subjects; and (iii) a putative endogenous ligand. Thus, two main hypothesis have been advanced, namely changes in the concentration or properties of the latter, and changes in the GABAA complex conformation, which contains the cBZr. Neither postmortem studies nor appropriate animal models are available to investigate these ideas. We have used positron emission tomography (PET) to measure both the density and affinity of the cBZr in multiple brain regions in unmedicated patients and age- and sex-matched healthy volunteers, and have looked for differences between groups as well as correlations between cBZr parameters and state and trait anxiety scores. We studied 10 unmedicated patients (sex ratio 1 : 1; mean age: 39 years), prospectively recruited using DSM III-R criteria, and 10 age- and gender-matched healthy unmedicated volunteers. Thanks to a PET procedure using two successive administrations of 11C-flumazenil (at high and low specific radioactivity) and previously validated by us, we estimated the Bmax, Kd and bound : free (B/F) ratios in 11 neocortical areas and in the cerebellum. Before and after the PET session, anxiety scores from Spielberger's and Covi's scales were obtained. There was no statistically significant difference in Bmax, Kd or B/F-values between the two groups for any region. Across the two groups, there were only a few marginally significant anxiety-score-PET correlations, suggesting chance findings. This is the first fully quantitative study to report on the relationships between cBZr parameters and anxiety. Using two independent approaches (i.e. group comparison and across-group correlations), we found no evidence for a link between anxiety trait or state and the cBZr in neocortex or cerebellum in this sample. These findings, if confirmed by studies on larger samples, have implications for the pharmacotherapy of anxiety disorders, and will need to be considered when designing new neurobiological models of anxiety.

Adolescent↗
PubMed1998

Effect of aging on cholecystokinin-induced panic.

OBJECTIVE: Epidemiologic surveys have found that the incidence and prevalence of panic disorder decline in later life. The goal of this study was to determine whether aging has an effect on healthy subjects' responses to the panicogenic agent cholecystokinin tetrapeptide (CCK-4). METHOD: The study used a double-blind, placebo-controlled design: 40 subjects 20-35 years old and 40 subjects 65 years old or older were randomly assigned to receive an intravenous bolus of either 50 micrograms of CCK-4 or normal saline. RESULTS: When given CCK-4, older subjects had significantly fewer and less intense symptoms of panic, shorter duration of symptoms, and less of an increase in heart rate than did younger subjects. CONCLUSIONS: This study found an age-related change in responsiveness to CCK-4. Further research to delineate the mechanism of this change is warranted.

Adult↗
PubMed1998

Pharmacologic treatments effective in both generalized anxiety disorder and major depressive disorder: clinical and theoretical implications.

OBJECTIVE: To review the efficacy of anxiolytics (alprazolam and azapirones) in major depressive disorder (MDD) and that of antidepressants in generalized anxiety disorder (GAD), thereby exploring the possible theoretical and clinical implications of this efficacy. METHOD: A Medline literature search was performed for the period January 1980 to September 1997 of randomized, double-blind comparison studies between anxiolytics and antidepressants in the acute treatment of adult patients with either MDD or GAD. RESULTS: Alprazolam, at doses double those generally recommended for anxiety disorders, appears to be as effective as tricyclic antidepressants (TCAs) in the acute treatment of mild to moderate MDD. Alprazolam was also found to have a more rapid onset of action than to TCAs, particularly for the improvement of anxiety, somatization, and insomnia. Two azapirones (buspirone and gepirone) also have demonstrated a modest acute antidepressant effect in preliminary studies, albeit only in a depressed outpatient sample with considerable anxiety at baseline. Finally, various antidepressant drugs (imipramine, trazodone, paroxetine) were shown to have, at the least, comparable efficacy to benzodiazepines (BZDs) in the acute treatment of GAD. CONCLUSIONS: The nonspecificity of treatment response suggests that GAD and MDD are 1) different expressions of a similar disorder with a common neurobiological substrate, 2) discrete diagnostic entities that respond to independent pharmacological effects of the same drugs, or 3) a combination of the two (heterogeneity hypothesis). The most relevant clinical finding is the efficacy of antidepressants in the acute treatment of GAD.

Adult↗
PubMed1997

Use of health services for anxiety disorders: a multisite study in Quebec.

OBJECTIVE: We investigated patient characteristics and use of services for anxiety disorders among patients seeking care from participating clinicians at 7 anxiety clinics in Quebec: 3 general hospital clinics, 3 psychologist-run clinics, and one psychiatric hospital clinic. METHODS: Persons eligible for the study were those who were visiting the clinics for the first time, had a current diagnosis of an anxiety disorder, and could communicate in French or English. Subjects recruited through advertisements were excluded. Data, collected by a self-administered questionnaire, included demographics, treatment history, use of services for anxiety, and the Beck Anxiety Inventory (BAI). RESULTS: The sample comprised 235 subjects: 146 seen at 3 general hospital clinics, 54 at 3 psychologist-run clinics, and 35 at a psychiatric hospital clinic. There were statistically significant differences by clinic type in the prevalence of specific anxiety diagnoses, BAI score, referral source, antidepressant use, and use of services. High-intensity use (10 or more consultations during the previous year) was reported by 23.4% of the sample for medical services and 19.6% for mental health services. Multiple logistic regression identified variables associated with high-intensity use of medical services (higher BAI score, 1 to 4 years since first sought treatment, and less than 12 years of education) and high-intensity use of mental health services (clinic type, obsessive-compulsive disorder [OCD], and 5 or more years since first sought treatment). CONCLUSIONS: The patient populations seen at different types of anxiety clinics differ in several respects, including referral source, previous treatment, and severity of symptoms. Regardless of type of clinic, patients with a longer time since they first sought treatment use more services, particularly mental health services. Those with less education use more medical services than those with greater education.

Adult↗
PubMed1997

Mixed anxiety and depression: from theory to practice.

The 10th International Classification of Disease (ICD-10) introduced the concept of mixed anxiety-depression to define patients presenting both anxiety and depressive symptoms of limited number and/or intensity, not sufficiently severe to fulfill criteria for a specific diagnosis of depressive or anxiety disorder. Epidemiologic surveys have shown that these patients may display significant levels of functional impairment, have unexplained somatic symptoms and a high use of nonpsychiatric medical care, have long-lasting symptoms, and are at risk for more severe psychiatric disorders. A DSM-IV field trial concluded that patients with affective-symptoms not meeting thresholds for DSM-III-R disorders were at least as common as patients with anxiety or mood disorders, and that their symptoms were associated with significant distress or impairment. Although some of these patients present residual symptoms from previous psychiatric episodes and may request treatment specific to these conditions, it is not known if those without a psychiatric history could benefit from pharmacologic or psychological treatments usually used in mild outpatient cases.

Adult↗
PubMed1996

Elevated plasma levels of neuropeptide Y in patients with panic disorder.

OBJECTIVE: Neuropeptide Y is a pancreatic polypeptide closely associated with noradrenergic activity both in the central and peripheral nervous systems. The objective of this study was to assess plasma neuropeptide Y-like immunoreactivity in panic disorder. METHOD: Radioimmunoassays were performed in 12 patients with DSM-III-R panic disorder and two groups of normal comparison subjects (N = 22 and N = 16). RESULTS: Markedly higher plasma neuropeptide Y-like immunoreactivity was found in patients with panic disorder. CONCLUSIONS: Higher plasma neuropeptide Y-like immunoreactivity suggests that this peptide may be implicated in the etiology or expression of symptoms of panic disorder.

Female↗
PubMed1993

Mixed anxiety and depression: diagnostic issues.

Mixed anxiety and depression (MAD) is a new diagnostic category introduced in the ICD-10 classification for patients seen mainly in primary care settings. These patients are defined as those suffering from symptoms of anxiety and depression of limited and equal intensity accompanied by at least some autonomic features, who do not qualify for specific diagnosis of anxiety or depressive disorders and are independent of stressful life events. The validity of this clinical entity is presently under investigation in the DSM-IV-MAD field trial. Cases of mixed anxiety and depression, however, are not limited to those meeting the criteria of this new "subsyndromal" category. Many patients fulfilling criteria for either depressive or anxiety disorders may also respectively present symptoms, syndromes, or a diagnosis of anxiety or depression. It is still not known whether anxious and depressive symptoms are two different expressions of the same psychopathologic underlying process. Tyrer's recent description of a "general neurotic syndrome" is an attempt to reunify syndromes separated in our present classifications. In this comprehensive approach, anxiety, depression, or MAD states are associated at different times with specific personality features and considered as expressing different levels of overreactivity to various stressful situations. This hypothesis would explain the close relationship existing between these two categories of symptoms and the common efficacy of some psychopharmacologic agents for both anxiety and depressive disorders.

Anxiety↗
PubMed1992

Central benzodiazepine receptors in human brain: estimation of regional Bmax and KD values with positron emission tomography.

Studies of central benzodiazepine receptors in the human brain in vivo are now possible using positron emission tomography (PET) and [11C]flumazenil. With the aim of measuring Bmax and Kd in brain regions, we used a two-injection [11C]flumazenil (at high and low specific radioactivity, respectively) pseudo-equilibrium paradigm to evaluate, in seven unmedicated healthy volunteers, the relative merits of three 'reference' structures (pons, hemispheric white matter and corpus callosum) in which the free radioligand concentration in brain tissue was estimated 15-40 min after i.v. injection of the radioligand. By means of high-resolution PET, the Bmax and Kd were calculated for each subject in 18 gray matter structures, based on a two-point Scatchard plot. We found that the use of the corpus callosum as reference often resulted in spurious Bmax and Kd values. The pons was the best reference structure because it provided satisfactory Bmax values (closest to in vitro data) and most consistent Kd values, and was the region easiest to sample on PET images. The pattern of regional Bmax was consistent with that expected from in vitro studies, with values highest in the cerebral cortex, intermediate in the cerebellum, and lowest in the striatum and the thalamus. The Kd values were uniform among regions and were consistent with earlier in vitro and in vivo data. This work documents the feasibility of estimating Bmax and Kd of central benzodiazepine receptors in multiple brain regions for clinical research.

Adult↗
PubMed1992

Evidence for hypothalamo-growth hormone dysfunction in panic disorder: profile of growth hormone (GH) responses to clonidine, yohimbine, caffeine, glucose, GRF and TRH in panic disorder patients versus healthy volunteers.

Given the abrupt and time-limited nature of daytime-awake and nocturnal-sleep panic attacks, several chemical and neuroendocrine challenge tests have been employed to investigate the neurobiology of "spontaneous" panic attacks. Previously we demonstrated that panic disorder patients have blunted growth hormone (GH) responses to clonidine, an alpha 2-adrenergic agonist. However, the mechanism of this blunted response and the role of hypothalamic-GH dysfunction, if any, remains unclear. To further delineate the status of hypothalamic-GH function in panic disorder, we review the literature and present original data on the GH responses to a number of different chemical and neuroendocrine challenge paradigms. Although stress-mediated increases in GH are thought to be a common correlate of stress in humans, our findings indicate that panic disorder patients have significantly blunted GH responses to clonidine, yohimbine, growth-hormone releasing factor, and caffeine compared to normal control subjects. A similar trend was noted in the delayed rise in GH after glucose challenge. There was no difference in the rate of abnormal GH responses to thyrotropin-releasing hormone in panic disorder compared to normal control subjects. No drug or neuroendocrine challenge, even if associated with marked increases in anxiety, produced a significantly enhanced GH response compared to normal control subjects. These findings provide support for a hyporesponsive hypothalamic-GH system in panic disorder. These observations, combined with preliminary observations from our clinic of short stature in several cases of prepubescent children with anxiety disorders, also underscore the need for assessing early growth patterns in individuals with panic disorder. Strategies for investigating the site(s) of possible neurotransmitter or hypothalamic-GH-somatomedin dysfunction are discussed.

Caffeine↗
PubMed1991

[Benzodiazepines in the treatment of anxiety].

During the last ten years, the treatment of anxiety disorders has changed considerably. Cognitive-behavioural therapies and new chemotherapies have been added to benzodiazepine therapy and psychotherapy which for a long time had been the only treatment of these frequent and invalidating disorders. Recent reports of possible drawbacks in prolonged benzodiazepine therapy provide another reason to reconsider the indications of these drugs now that other drugs are available. Benzodiazepines remain the treatment of choice for recent anxiety states requiring some degree of sedation and rapid relief, but their long-term administration should be reserved to patients who did not respond to other treatments. The authors propose several guidelines for a better prescription of these anxiolytic agents and for more rational indications taking into account the advantages of other available treatments.

Anxiety↗