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Biomedical subjects

Frédéric Rouillon

Publications and source records attributed to Frédéric Rouillon.

At least 19 recordsLinked to original sources
PubMed2007

Family trios analysis of common polymorphisms in the obestatin/ghrelin, BDNF and AGRP genes in patients with Anorexia nervosa: association with subtype, body-mass index, severity and age of onset.

Anorexia nervosa (AN) affects 0.3% of young girls with a mortality of 6%/decade and is strongly familial with genetic factors. Ghrelin is an upstream regulator of the orexigenic peptides NPY and AgRP and acts as a natural antagonist to leptin's effects on NPY/AgRP-expressing neurons, resulting in an increase in feeding and body weight. Obestatin which counteracts ghrelin action on feeding is derived from the same propeptide than ghrelin. BDNF has been involved in body weight regulation and its Val66Met polymorphism associated with AN. We therefore re-investigated the association between AN and the Leu72Met and Gln90Leu polymorphisms of the prepro-ghrelin/obestatin gene, the Ala67Thr polymorphism of AgRP and the Val66Met polymorphism of BDNF taking into account clinical subtypes (restrictive--ANR--and bingeing/purging--ANB--subtypes). Family trios study of these 4 single nucleotide polymorphisms were performed in 114 probands with AN and both their parents recruited in two specialized French centres. A transmission disequilibrium was observed for the Leu72Met SNP of the preproghrelin gene and for the Ala67Thr SNP of the AgRP gene. When stratified by clinical subtype, these two polymorphisms were preferentially transmitted for the trios with a bingeing/purging proband. An excess of transmission of the Gln90Leu72 preproghrelin/obestatin haplotype in patients with AN was observed. These results do not provide evidence for a preferential transmission of the 66Met allele of BDNF but support the hypothesis that ghrelin and AGRP polymorphisms confers susceptibility to AN. Further simultaneous analysis of genetic variants of the biological determinants of energy metabolism and feeding behaviour in very large populations should contribute to the understanding of the high degree of heritability of eating disorders and to the description of pathophysiological patterns leading to life-threatening conditions in a highly redundant system.

Adolescent↗
PubMed2006

Determinants of early identification of suicidal ideation in patients treated with antidepressants or anxiolytics in general practice: a multilevel analysis.

BACKGROUND: General practitioners (GPs) play a key role in identifying and managing patients with suicidal tendencies. Few studies, however, examine both GP and patient characteristics and GP practices associated with suicide assessment. This article aims to evaluate 1) GPs' success in early identification of suicidal ideation (SI) in patients starting antidepressant or anxiolytic treatment, and 2) patient- and GP-related factors associated with this success. METHODS: Survey of 144 GPs practising in southeastern France and of consecutive adults consulting them during June-October 2004 and prescribed antidepressant or anxiolytic treatment. Data were collected from GPs (consultation-questionnaires focusing on their prescription, diagnosis and detection of SI) and patients (self-administered questionnaires including the Hospital Anxiety and Depression scale and social and demographic characteristics). We used multilevel logistic regression to analyse factors associated with SI detection. RESULTS: GPs completed consultation-questionnaires for 713 patients, 405 of whom completed self-administered questionnaires. Eighty-nine patients (22%) reported SI; in 43 cases (48%) SI had not been detected by the GP. GPs detected SI more frequently when they had completed continuing medical education about depression, when patients had higher depressive symptom scores, and when consultations were relatively long. LIMITATIONS: Study limited to patients receiving initial prescriptions for antidepressants or anxiolytics. CONCLUSIONS: The percentage of undetected SI in this study population was high. Additional training of GPs increases the chances of detecting SI. Medical training and continuing medical education should include better instruction about SI risk factors and diagnosis, including non-major depressions, and stress that screening requires sufficient consultation time.

Adolescent↗
PubMed2006

Prevalence of mental disorders in French prisons for men.

BACKGROUND: Psychiatric surveys conducted in prison populations find high prevalence rates, but diagnoses may be difficult in this particular context. None of these surveys have been conducted in France. METHODS: 800 incarcerated male were sampled at random. Each prisoner was interviewed by a group of 2 clinicians, at least one of them being a senior psychiatrist. One of the clinicians used a structured clinical interview which generated DSM IV diagnosis (MINI plus); the second completed the procedure with an open clinical interview. RESULTS: Prevalence rates for a diagnosis given independently by both clinicians and for a consensual diagnosis were respectively: 3.8% (6.2%) for schizophrenia, 17.9% (24%) for major depressive disorder, 12.0% (17.7%) for generalized anxiety and 10.8% (14.6%) for drug dependence. CONCLUSION: Psychiatric diagnosis can be difficult to interpret in prison, especially using traditional standardized interviews. The approach proposed here, with good reliability and closer to a day-to-day clinical practice, yields high prevalence rates.

Adult↗
PubMed2006

Night eating syndrome and winter seasonal affective disorder.

Night eating syndrome (NES) and winter seasonal affective disorder (SAD) share some features such as snacking for high-carbohydrate/high-fat food with increased weight, emotional distress, circadian disturbances, good response to serotoninergic antidepressants (SSRIs) and bright-light therapy. This study assessed the prevalence and socio-demographical and clinical correlates of the NES in a sample of 62 consecutive depressed outpatients with winter seasonal features (DSM-IV criteria). Depression was assessed with the 29 item-HDRS and Sigh-SAD version and with the 7-item depression subscale of the Hospital Anxiety and Depression scale. The prevalence of NES was low (4.8%). Patients suffering from NES were significantly older with a greater duration of the illness. NES was not related to depression and to Body Mass Index. NES and winter SAD are not overlapping disorders.

Adult↗
PubMed2006

Mortality in schizophrenia.

PURPOSE: The purpose of this article is to describe the current status of knowledge on excess mortality in schizophrenia and its causative factors, and to expand upon previous work evaluating approaches that may reduce mortality rates. METHODS: Literature available since 1995 was identified in a computerized search of the bibliographical databases Medline and Embase, using the topics 'mortality' and 'schizophrenia', and in a cross-reference search for articles that were particularly relevant. RESULTS: Schizophrenia is associated with mortality rates that are two to three times higher than those expected or observed in the general population. This excess of mortality is accounted for by a combination of an increased risk of suicide, in particular in young male patients soon after diagnosis, and more importantly, a higher number of natural deaths. In order to diminish the level of suicide among people with schizophrenia, the majority of research has focused on the identification of risk factors that predispose patients to attempt or commit suicide, while unhealthy styles, polypharmacy and inadequate healthcare have been shown to contribute to the high natural mortality. The link between the use of antipychotics and mortality has not been yet clarified. CONCLUSION: Dramatically increased mortality of schizophrenia patients is well established. It is time to move beyond this topic, and work towards interventions that aim at reducing the mortality risk in such patients.

Antipsychotic Agents↗
PubMed2006

[Epidemiology of schizophrenic disorders].

The prevalence of schizophrenic disorders in the general population is 1%, that is, in France, approximately 40000 people, given the age group concerned. The sex ratio is one. The first episode occurs between the ages of 15 and 25 years in men, a little later in women. 90% of patients treated for schizophrenia are aged from 15 to 55 years. The short-term course is marked by a relapse rate after the first episode estimated at 20-40%. The long-term evolution is marked by substantial excess mortality, a suicide rate of 10-20% and an overall decrease of approximately 10 years in life expectancy. Only 10% of patients will have an outcome including full autonomy. The socioeconomic impact is therefore considerable, with a mean cost of management estimated at 15000 Euros per year. Genetic factors affect vulnerability or predisposition to schizophrenia. Accordingly a first-degree relative of a schizophrenic patient has a risk 5 to 10 times higher of developing the disease than does a person with no affected relatives. This risk is not one of simple Mendelian transmission but rather vulnerability, which implies the intervention of several genes. Some environmental factors have also been identified, including exposure to influenza virus during the gestational period (between the 4th and 7th month of pregnancy). This finding reinforces the hypothesis of a neurodevelopmental origin of schizophrenia. Finally, among other associated factors, regular cannabis use appears to quadruple the risk of disease.

Adolescent↗
PubMed2006

Assessing and interpreting personality change and continuity in patients treated for major depression.

Structural, mean- and individual-level, differential, and ipsative personality continuity were examined in 599 patients treated for major depression assigned to 1 of 6 forms of a 6-month pharmaco-psychotherapy program. Covariation among traits from the Five Factor model remained invariant across treatment, and patients described themselves as slightly more extraverted, open to experience, agreeable and conscientious, and substantially more emotional stable after treatment. Trait changes were only to a small extent explained by changes in depression severity. There was evidence for differential, individual-level, and ipsative stability, with stable personality profiles in terms of shape and to a lesser extent in terms of scatter and elevation. Traits remain relatively stable, except for emotional stability, despite the depressive state and the psychopharmacological interventions.

Adolescent↗
PubMed2006

Efficacy and tolerance profile of agomelatine and practical use in depressed patients.

Agomelatine is a new agent with a unique pharmacological profile, as the first melatonergic antidepressant. Its antidepressant efficacy has been demonstrated in the treatment of major depressive disorder (MDD) at a dose of 25 mg/day. Expectations from antidepressant therapies now go beyond efficacy alone, to include advantages in tolerability and safety. Due to its pharmacological profile, agomelatine does not induce the side-effects typical of other therapies, such as selective serotonin reuptake inhibitors (i.e. gastrointestinal disorders, weight gain, serotonergic syndrome and insomnia). Moreover, a placebo-controlled trial in MDD comparing the effects of agomelatine and venlafaxine on sexual dysfunction (another significant side-effect with current antidepressant medications) indicated the very favourable profile of agomelatine; in the same study, there was similar antidepressant efficacy in the same two groups. A double-blind, placebo-controlled trial investigating the effect of abrupt cessation of treatment demonstrated the absence of discontinuation symptoms with agomelatine, which was in contrast with the results observed with paroxetine. The ability of an antidepressant to relieve sleep complaints with no sedative effects is a key advantage because sleep complaints are a major presenting feature of depression. Again due to its unique pharmacological profile, agomelatine has been shown to positively influence disturbed circadian rhythms in depressed patients by significantly improving all phases of disturbed sleep and the overall quality of sleep, with a favourable impact on daytime alertness. In conclusion, experience with agomelatine across a range of clinical studies suggests that this compound offers a novel approach to the treatment of depression combining efficacy, even in severe depression, with an extremely favourable side-effect profile and sleep regulation. These properties give agomelatine a definite clinical advantage in the treatment of depression.

Acetamides↗
PubMed2005

A prospective study of the psychological effects of "person under train" incidents on drivers.

Previous studies have shown that person under train (PUT) accidents cause psychological distress to drivers during the first year following the incident. Our aims were to assess the psychological consequences of PUT accidents on drivers prospectively, and to identify risk factors for psychological effects. In this prospective, one-year, follow-up study, a consecutive series of PUT drivers (n=202) were compared with a group of matched control drivers (n=186). Psychological state was assessed 15 days, 3 months and 1 year after the event, using the GHQ-28 questionnaire and a standardised diagnostic interview (the v4.4 MINI). Fifteen days after the event, PUT drivers had significantly higher GHQ-28 scores (p<0.0001) and more acute stress disorder (p=0.008) than control drivers. No significant differences were found 3 months and 1 year after the accident. Significant explicative variables were the presence of acute and chronic psychosocial stressors (OR=3.30 and 3.68) and the availability of immediate help (OR=0.46). We thus confirm previous findings that train drivers who have experienced a PUT accident experience acute psychological disturbances. Our results also highlight the utility of the systematic prevention programme provided.

Accidents, Traffic↗
PubMed2005

Male-specific association between the 5-HTTLPR S allele and suicide attempts in alcohol-dependent subjects.

Changes in serotoninergic neurotransmission have been implicated in the pathogenesis of suicidal behavior and alcohol dependence. Previous studies have demonstrated an association between suicide attempts and the 5-HTTLPR S allele in alcohol-dependent subjects. We investigated the frequency of the S allele of 5-HTTLPR in a sample of 100 French Caucasian alcohol-dependent inpatients (48 men and 52 women) with and without a history of suicide attempts. The frequencies of 5-HTTLPR genotypes did not differ significantly between men and women. A history of at least one suicide attempt was more frequent in women than in men (57.5% versus 31.3%, respectively, p=0.008). Logistic regression analysis showed that the presence of the S allele of 5-HTTLPR was related to a life-time risk of suicide attempts, but only in male subjects (p=0.05). There seems to be an allelic association between the 5-HTTLPR S allele and suicidal behavior in alcohol-dependent subjects, but this relationship is restricted to male subjects.

Adult↗
PubMed2004

Continuing clozapine treatment despite neutropenia.

RATIONALE: Approximately 1-2% of patients treated with the atypical antipsychotic clozapine develop severe neutropenia and agranulocytosis. The usual recommendation is to discontinue treatment with the drug when the peripheral neutrophil count drops below 1,500/mm3. METHODS: We have reviewed several reports describing procedures that allowed the patients to continue clozapine treatment despite the occurrence of these haematological side effects. RESULTS: The therapeutic procedures described (symptomatic treatment of neutropenia by co-administration of lithium or granulopoiesis-stimulating factors, management of the adjunctive medication) seem to be efficient strategies that allow continuation of clozapine treatment despite the occurrence of neutropenia. However, these types of therapy have only been used in a limited number of cases, and the evidence supporting their use remains anecdotal. CONCLUSION: Although the procedures adopted in the cases described in this review are uncommon, they potentially provide an alternative to the discontinuation of clozapine treatment in patients with complex symptomatologies for whom treatment with other antipsychotic medication is insufficient.

Antipsychotic Agents↗
PubMed2004

Admixture analysis of age at onset in schizophrenia.

In schizophrenia, clinical, familial and biological characteristics according to age at onset (AAO) suggest that AAO is a valid candidate symptom for genetic studies. However, none of the various thresholds used to define AAO subgroups in schizophrenia has been validated. We aim to define different AAO subtypes by admixture analysis in a sample of prospectively recruited subjects with schizophrenia. Consecutive inpatients and outpatients (N=141) meeting DSM IV criteria for schizophrenia were included. We used admixture analysis to investigate whether the observed AAO distribution consisted of a mixture of gaussian distributions and then compared clinical features and familial risks in the various groups of subjects. The model that best fitted the observed AAO distribution was a mixture of two gaussian distributions (mean+/-S.D.): (19.91+/-3.56 years) and (33.48+/-8.2 years), with a cutoff point at 28 years. The existence of two subgroups according to AAO was further confirmed by the different clinical and familial profiles of these subgroups. The early-onset group consisted predominantly of male patients, with non-paranoid subtypes and with a higher familial risk of schizophrenia spectrum disorders and affective disorders. The late-onset group of patients presented predominantly paranoid subtype, preponderance of females; they were more likely to be married and to have children. We identified two subgroups of schizophrenic subjects with different clinical and familial profiles. This study provides a mathematical validation of the existence of two subgroups defined by an onset of schizophrenia before or after 28 years. These results may have important implications for the search for schizophrenia susceptibility factors. Working with homogeneous subgroups defined on the basis of AAO may facilitate the identification of genetic vulnerability factors in schizophrenia.

Adult↗
PubMed2004

The A9 allele of the dopamine transporter gene increases the risk of visual hallucinations during alcohol withdrawal in alcohol-dependent women.

Previous studies have found an association between the A9 allele (nine-copy repeat) of the dopamine transporter (DAT) gene and two complications of alcohol withdrawal, namely delirium tremens (DT) and alcohol withdrawal seizures (AWS). Most of these studies only included male alcohol-dependent patients. Even those that included a small proportion of women did not look at the effect of gender. We compared the frequency of the A9 allele in 64 French Caucasian alcohol-dependent women with a history of alcohol withdrawal complications. Women carrying the A9 allele had more visual hallucinations during withdrawal than those without this allele (P = 0.03). However, women with the A9 allele were not more susceptible to DT or AWS than those without (P = 0.48 and P = 1.00, respectively). Our results suggest that the A9 allele of the DAT gene is involved in vulnerability to alcohol withdrawal complications in women, but that these complications differ from those associated with this polymorphism in alcohol-dependent men.

Adult↗
PubMed2004

Executive dysfunctions as potential markers of familial vulnerability to bipolar disorder and schizophrenia.

Attentional and executive impairments have been found both in patients with schizophrenia and in their unaffected first-degree relatives, suggesting that they might be considered as familial vulnerability markers. Several studies have shown that the performance of bipolar patients does not significantly differ from that of schizophrenic patients, so that executive and attentional deficits might not be specific to schizophrenia. In the present study, we aimed to identify executive dysfunctions in schizophrenia and bipolar disorder that might be vulnerability trait markers specific to one or common to both of these diseases. We assessed cognitive performance of euthymic bipolar and schizophrenic patients, their unaffected first-degree relatives and a healthy control group, using neuropsychological tasks to test different components of executive function: the Verbal Fluency Test, the Stroop Word Colour Test, the Wisconsin Card Sorting Test and the Trail Making Test. The two groups of patients and their unaffected relatives demonstrated disproportionately increased slowness on the Stroop test in comparison to the normal healthy group. Patients with schizophrenia performed poorly on all the tests in comparison to the normal healthy subjects, while no other impairment was observed in the bipolar patients and in the relatives of schizophrenic and bipolar patients. Enhanced susceptibility to interference and reduced inhibition could be transnosographical markers for a shared familial vulnerability common to schizophrenia and bipolar disorders.

Adult↗
PubMed2004

Long term therapy of generalized anxiety disorder.

Generalized anxiety disorder (GAD) is a common (lifetime prevalence: 5.1%), recurrent condition, which often heralds other psychiatric disorders, notably depression. As by definition it is a disorder progressing over months, treatment should be designed on a long term basis. And yet, few studies have been conducted beyond the classical 6-8 weeks characterizing the acute treatment phase. This is especially true of anxiolytics, but also of antidepressants, with the exception of paroxetine and venlafaxine, which are the only drugs approved in this indication in Western countries. The efficacy of psychotherapy, notably relaxation and cognitive-behavioral therapy, is established in the treatment of GAD, but its preferred indications and possible combination with antidepressants are still to be specified. Long term, not to say very long term studies of GAD, as well as depression, will still be required in the future to improve its management and specify therapeutic modalities (combination treatment, optimal duration, continuous or intermittent therapy, choice of psychotherapeutic techniques or agents, em leader ). Early and adequately prolonged treatment should not only result in more numerous remission periods, but also in decreased frequency of co-morbidities whether depressive, addictive, or of another nature, and should also reduce the social impact of GAD.

Anti-Anxiety Agents↗
PubMed2004

Platelet serotonergic predictors of clinical improvement in obsessive compulsive disorder.

OBJECTIVE: Serotonin reuptake inhibitors (SRIs) are the most efficient pharmacological treatment of obsessive-compulsive disorders (OCD). Previous studies have suggested that some peripheral serotonergic parameters can be used to predict the clinical outcome of the treatment of OCD patients with SRIs. We tried to identify further peripheral serotonergic parameters that could help predict the clinical outcome of SRI treatment in a sample of patients with OCD. METHODS: We compared 19 OCD patients before and after 8 weeks of SRI treatment with 19 sex-matched and age-matched controls. We assessed clinical improvement and whole-blood serotonin (5-HT) concentration, platelet 5-HT transporter (5-HTT) and 5-HT2A receptor binding characteristics and platelet IP3 content. RESULTS: Before treatment, OCD patients had higher platelet IP3 content and fewer 5-HTT binding sites than the controls. Treatment with SRIs further lowered the number of 5-HTT binding sites, normalized platelet IP3 contents, and lowered the number of platelet 5-HT2A binding sites and whole-blood 5-HT concentrations below control values. The patients who improved most following SRI treatment had higher whole-blood 5-HT concentrations before treatment. CONCLUSION: Our results confirm that whole-blood 5-HT concentration is a predictor for clinical improvement and indicate that abnormal intracellular mechanisms may be involved in OCD patients, in particular, the overstimulation of the phosphoinositide signaling system.

Adolescent↗
PubMed2004

The psychological impact of terrorism: an epidemiologic study of posttraumatic stress disorder and associated factors in victims of the 1995-1996 bombings in France.

OBJECTIVE: A wave of bombings struck France in 1995 and 1996, killing 12 people and injuring more than 200. The authors conducted follow-up evaluations with the victims in 1998 to determine the prevalence of and factors associated with posttraumatic stress disorder (PTSD). METHOD: Victims directly exposed to the bombings (N=228) were recruited into a retrospective, cross-sectional study. Computer-assisted telephone interviews were conducted to evaluate PTSD, per DSM-IV criteria, and to assess health status before the attack, initial injury severity and perceived threat at the time of attack, and psychological symptoms, cosmetic impairment, hearing problems, and health service use at the time of the follow-up evaluation. Factors associated with PTSD were investigated with univariate logistic regression followed by multiple logistic regression analyses. RESULTS: A total of 196 respondents (86%) participated in the study. Of these, 19% had severe initial physical injuries (hospitalization exceeding 1 week). Problems reported at the follow-up evaluation included attack-related hearing problems (51%), cosmetic impairment (33%), and PTSD (31%) (95% confidence interval=24.5%-37.5%). Results of logistic regression analyses indicated that the risk of PTSD was significantly higher among women (odds ratio=2.54), participants age 35-54 (odds ratio=2.83), and those who had severe initial injuries (odds ratio=2.79) or cosmetic impairment (odds ratio=2.74) or who perceived substantial threat during the attack (odds ratio=3.99). CONCLUSIONS: The high prevalence of PTSD 2.6 years on average after a terrorist attack emphasizes the need for improved health services to address the intermediate and long-term consequences of terrorism.

Adult↗