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Biomedical subjects

J Adès

Publications and source records attributed to J Adès.

At least 19 recordsLinked to original sources
PubMed2002

5-HT(2A) gene promoter polymorphism as a modifying rather than a vulnerability factor in anorexia nervosa.

The A allele of the 5-HT(2A) gene (-1438A/G polymorphism) has been associated with anorexia nervosa in four studies, but not in three others. One possibility to explain such a discrepancy is that the A allele acts as a modifying rather than a vulnerability allele. To test this hypothesis, we increased our initial sample of 102 trios left open bracket Mol. Psychiatry 7 (2002) 90 right open bracket with 43 new patients with anorexia nervosa and 98 healthy controls. In addition to confirming the absence of association on the global sample of 145 patients, we found that patients with the A allele had a significantly later age at onset of the disease (P = 0.032). Furthermore, the A allele was also transmitted with an older age at onset (P = 0.023) using a quantitative-trait TDT approach. The A allele may thus act as a modifying factor (delaying onset), potentially explaining variations of allele frequency across samples, in which differences in average age at onset are not only possible, but also expected. Taking into account vulnerability genes, but also genes modifying the expression of the disorder, will help to disentangle the complexity of the etiological factors involved in anorexia nervosa.

Adult↗
PubMed2002

The 5-HT(2A) -1438G/A polymorphism in anorexia nervosa: a combined analysis of 316 trios from six European centres.

Several case-control association studies have raised the possibility that the A allele of a -1438 G/A polymorphism in the type 2A serotonin receptor (HTR2A) gene may be a risk factor for anorexia nervosa. However the absence of linkage and the existence of negative association studies raise the possibility of false positive findings, resulting from population stratification or lack of statistical power. To address this controversy we recruited a sample of 316 patients with anorexia nervosa from six European centres, and utilised a family-based transmission disequilibrium (TDT) approach to analyse the HTR2A-1438 G/A polymorphism. Age at onset and minimal BMI were also taken into consideration in order to detect clinical heterogeneity or a quantitative trait effect. The TDT approach showed that the A allele was transmitted 133 times and not transmitted 148 times (McNemar chi(2) = 0.29, df = 1, P = 0.59). Also, the haplotype-based haplotype relative risk method showed no evidence for association of the A allele, in samples from each centre (chi(2) < 2.15, df = 1, P > 0.14) and in the total sample (chi(2) = 0.55, df = 1; P = 0.46). Furthermore, we found no evidence for heterogeneity of the A allele frequency between samples (chi(2) = 2.54, df = 4, P = 0.64), either according to minimal-BMI (F1/242 = 2.14, P = 0.45) or age at onset (F1/224 = 2.39; P = 0.12). QTL-TDT analyses also showed no direct role of the A allele on these traits. We thus found no evidence for a significant role of the 5-HT(2A) gene in anorexia nervosa. Previous results may have been exposed to stratification bias (which we controlled by the TDT method) and/or the risk of type 1 error (from which we were less exposed because of the sample size).

Adolescent↗
PubMed2001

Association and excess of transmission of a DRD2 haplotype in a sample of French schizophrenic patients.

The gene which codes for dopamine receptor D2 (DRD2) is considered as one of the most relevant candidate genes in schizophrenia. Previous genetic studies focusing on this gene gave conflicting results, potentially because of the differences in methodology (linkage versus association studies), and the different loci analyzed (the DRD2 gene having many polymorphisms). We used a progressive strategy with three different approaches (case/control, haplotype relative risk and transmission disequilibrium test) and investigated two genetic polymorphisms (TaqI B1/B2 and TaqI A1/A2, spanning the coding region of the DRD2 gene) in 50 patients with DSM-IV diagnoses of schizophrenia, in their 100 parents and in 50 healthy, matched controls. Firstly, we found a significant excess of the two alleles (B2 and A2) in the schizophrenic group compared to unaffected controls. Secondly, we found an excess of transmission from the parents to their affected children, using the haplotype relative risk design applied to the B2A2 haplotype. Finally, the transmission disequilibrium test showed evidence for linkage between B2A2 haplotype and schizophrenia. The significant excess of the B2A2 haplotype in schizophrenic patients is specifically observed in a subsample of patients with a disease onset occurring after 20 years of age. As the haplotype contains nearly the entire DRD2 gene, we found convergent evidence in our sample for a significant role of the DRD2 gene in the risk for schizophrenia. This haplotype may be more specifically involved in the disorder's onset at a later age in some patients, or, alternatively, may be implicated as a modifying factor acting on age of onset.

Adult↗
PubMed2001

[Precocious and polymorphic factitious disorder].

OBJECTIVE: Pathomimia is a mental disease more frequently diagnosed in women, characterised by a wide range of somatic or psychiatric symptoms, and a chronic course with severe complications. CASE REPORT: A 22-year-old woman was suffering from severe factitious disorders with thermopathomimia, dermopathomimia, self-injuries with induced abscess, Lasthenie de Ferjol syndrome, and psychiatric factitious disorder. A very precocious age at onset and a previous history of 37 surgical operations were found. DISCUSSION: This case history is particularly relevant in showing the clinical multiplicity of factitious disorders.

Adult↗
PubMed2001

The genetics of addiction: alcohol-dependence and D3 dopamine receptor gene.

Alcohol-dependence is a complex phenotype, with behavioral, psychological, pharmacological, medical and social dimensions. Aggregation studies, adoption and twin researches have demonstrated that the vulnerability to alcohol-dependence is at least in part linked to genetic factors, the genetic vulnerability to alcoholism being mainly not substance-specific. There are numerous candidate genes, but the D3 dopamine receptor is specifically located in the limbic area, and in particular in the nucleus accumbens, which are involved in reward and reinforcement behavior. Furthermore, a previous collaborative study showed that homozygosity for the Ball DRD3 locus was more frequently observed in opiate dependent patients with high sensation seeking scores. In this study, we analyzed the distribution of Ball DRD3 polymorphism in a new sample of 131 French male alcoholic-patients (DSM III-R criteria) and 68 healthy controls matched for sex and origins. Although we replicated the higher sensation seeking score in alcohol-dependent patients with comorbid dependence, we found no significant difference in the DRD3 gene polymorphism between controls and alcoholic patients, regardless of sensation seeking score, addictive or psychiatric comorbidity, alcoholism typology, and clinical specificities of alcoholism. There is good evidence that gene coding for the dopamine receptor D3 does not play a major role in the genetic vulnerability to alcoholism.

Adult↗
PubMed2001

Clinical characteristics of familial versus sporadic alcoholism in a sample of male and female patients.

Presence of a family history of alcoholism may predict clinical characteristics in affected subjects, such as an earlier age at onset. More frequent and severe social maladjustment and somatic complications are also regularly cited for familial alcoholism, although subject to many other confusing factors. We analysed the clinical specificities of 79 alcohol-dependent inpatients according to the absence versus presence of family history of alcoholism. Patients were evaluated for lifetime psychiatric morbidity with the Diagnostic Interview for Genetic Studies (DIGS), for somatic complications with a systematic screening list, and first-degree relatives (N = 428) were assessed with the Family Inventory Schedule and Criteria (FISC). Age at onset and social complications were predicting familial versus sporadic alcoholism, even when considering censored data and/or interaction between variables. But differences became non-significant when excluding patients with antisocial personality. If age at onset effectively appears to be the most informative characteristic for predicting familial versus sporadic alcoholism, it seems that it may be necessary in future studies to systematically take into account antisocial personality diagnosis, because of a probable contamination.

Adult↗
PubMed2001

Comparison of alcohol-dependent patients with and without physiological dependence.

Sociodemographic and clinical characteristics of alcohol-dependent patients with or without physiological dependence (e.g. tolerance to alcohol or withdrawal) were compared. 186 consecutive alcohol-dependent patients hospitalized for alcohol detoxification were assessed. Diagnosis of alcohol dependence, tolerance and withdrawal was determined according to DSM-IV criteria. Assessment also included modalities of alcohol consumption and the Michigan Alcohol Screening Test (MAST). All patients presented alcohol dependence, 124 presented tolerance, 116 alcohol withdrawal and 146 (78.5%) tolerance and/or withdrawal. Patients with physiological dependence were older (51.4 vs. 46.9 years), drank more alcohol each day (20.3 vs. 11.3 drinks/day) and began alcohol consumption more often in the morning (67 vs. 37.5%). MAST scores were significantly higher in patients with physiological dependence (28.8 vs. 24.5), as was the mean corpuscular volume of erythrocytes (108 vs. 83 fl). No difference was found in terms of age, marital status, rate of unemployment, level of education and psychiatric comorbidity between the patients with and without physiological dependence.

Adult↗
PubMed2000

Serotonin transporter gene polymorphisms, alcoholism, and suicidal behavior.

BACKGROUND: Dysfunction of serotoninergic transmission could predispose to excessive alcohol consumption and dependence. The functional polymorphism of the serotonin transporter gene (5-HTTLPR) has been associated with different disorders, including alcoholism. Considering the likelihood of heterogeneity in the "alcohol dependence" phenotype, 5-HTTLPR may be more specifically implicated in subsamples of patients or in related traits of alcoholism, such as impulsivity. METHODS: We analyzed the role of this functional polymorphism in the risk for suicide attempt in a population of male alcohol-dependent subjects. One hundred ten male alcohol-dependent patients (DSM-III-R criteria), French for at least two generations, were personally interviewed with the Diagnostic Interview for Genetic Studies and compared with 61 unaffected blood donors. RESULTS: The "short" (S) allele of the 5-HTTLPR appeared to be unrelated to alcohol dependence and comorbid depression in our sample, but was found associated with an increased risk for suicide attempts. This association was predominantly observed in severe and repetitive suicide attempts, with a significant dose effect of the S allele (0, 1, or 2) on the number and the severity of suicide attempts. CONCLUSIONS: Mood disorders and alcohol dependence may interact with a genetic (relative) deficiency in serotonin reuptake, thereby increasing the risk for aggressive/impulsive behaviors such as suicide attempts.

Adult↗
PubMed2000

Epidemiology of behavioral dependence: literature review and results of original studies.

The extension of the definition of dependence leads to the consideration of some impulsive disorders as a form of dependence disorder. This pathological condition is characterized by the repetitive occurrence of impulsive and uncontrolled behaviors. Other clinical characteristics are failure to resist an impulse, drive or temptation to perform some act harmful to oneself and/or others, an increasing sense of tension or excitement before acting out, and a sense of pleasure, gratification or release at the time of the behavior or shortly thereafter. Behavioral dependences most often described are pathological gambling, kleptomania, trichotillomania and compulsive buying. Studies using a specific assessment scale, the South Oaks Gambling Screen, distinguished problem gambling from pathological gambling. Social gamblers spend 5% of their money and pathological gamblers 14 to 45%. Prevalence of 'problem gambling' is 4% and pathological gambling 2%. Several studies have suggested that the incidence of pathological gambling is eight to ten times greater in alcohol-dependent patients than in the general population. No systematic study has assessed the prevalence of kleptomania. Data come from case reports. Among subjects arrested after a theft, prevalence of kleptomania varied between 0 and 24%. Trichotillomania prevalence rate is 0.6% among students. Studies using less restrictive diagnostic criteria found a prevalence rate of 3.4% in women and 1.5% in men. The disorder is often unrecognized; 40% of the cases are not diagnosed and 58% of the patients have never been treated. Prevalence studies of compulsive buying found a rate between 1 and 6% in the general population. Compulsive buying is significantly more frequent among women (90% of the cases). Study of family history of compulsive buyers showed a high frequency of alcohol-dependence disorder (20%) and depression (18%). In all cases of behavioral dependence disorders, a high level of impulsivity and sensation-seeking could determine an increased risk.

Adult↗
PubMed2000

Relationships between antisocial personality and alcoholism: genetic hypotheses.

Genetic factors explain a non-negligible part of the vulnerability to alcohol dependence, the genetic influence in males being estimated at around 60%. The search for gene(s) potentially implicated in alcoholism is counteracted by the clinical heterogeneity of alcoholism, but also by heterogeneity of the etiologic factors involved. It is thus necessary to redefine more specific phenotypes with more simple determinism, and to focus on more specific subsets of candidate genes. In this view, the existence of co-occurrence (presence at the same time, whatever the cause) between antisocial personality and alcoholism is frequently reported. Three hypotheses have been previously proposed to explain this co-occurrence. Firstly, it could be a pure artefact or contamination, due to common items in diagnostic manuals widely used, such as the DSM or ICD. Secondly, antisocial personality and alcoholism could share common etiologic factor(s), and determine a 'real' co-morbidity. Finally, common genetic factors between these two disorders may exist, with the observation of a co-transmission of both disorders more often than expected by chance alone, meaning the existence of co-aggregation. Each of these three hypotheses will be reviewed and discussed.

Alcoholism↗
PubMed2000

The DRD2 gene and the risk for alcohol dependence in bipolar patients.

The high co-morbidity between bipolar disorder and alcohol dependence may have different explanations, one of them being the existence of common genetic factors for the two disorders. Several candidate genes may be involved but the genes acting in the dopaminergic pathway may be more specifically involved. We have thus tested the role of the gene encoding the D2 dopamine receptor (TaqI A1 allele) in the potentially shared vulnerability to alcohol dependence and bipolar disorder. One hundred and twenty-two French (for at least two generations) patients were recruited on the basis of hospital or outpatient files and were interviewed with the DIGS. The A1 allele frequencies were compared between four groups, namely, with bipolar patients and co-morbid alcohol dependence (N = 21), with bipolar patients without alcohol morbidity (N = 31), with alcohol dependence without mood disorder (N = 35) and unaffected controls (N = 35). The Hardy Weinberg equilibrium for the DRD2 Taq1 A1 genotypes was respected for the sample as a whole, and for each subsample. We observed that 42.9% of control subjects have at least one A1 allele, a frequency which is not significantly different from the one observed in the affected sample as a whole (39.1%), neither from patients with alcohol dependence (37.1%), patients with bipolar disorder (48.4%) nor patients with alcohol dependence and bipolar disorder (28.6%). The regression analysis based on the three variables (bipolar disorder, alcohol dependence and interaction between these two disorders) does not explain the presence of the A1 allele of the DRD2 gene. We thus found no evidence for a significant role of the A1 allele of the D2 dopamine receptor gene in the specific association between bipolar disorder and alcohol dependence in our sample.

Adult↗
PubMed2000

Reappraisal of the association between the DRD2 gene, alcoholism and addiction.

We analysed the impact of the TaqI A1 allele of the D2 dopamine receptor gene on the risk for alcoholism, trying to depict three explanations frequently proposed to explain discrepancies in association and linkage studies: that the A1 allele may act as a marker rather than as a vulnerability factor, that stratification biases and unevaluated controls may explain positive results, and that the A1 allele is modifying the phenotype rather than increasing the risk for alcoholism. We thus tested another (dinucleotide STRP) marker within the DRD2 gene, selected a new homogenous sample of 113 alcoholic patients and 49 unaffected controls strictly matched for ethnic origins, and systematically assessed both samples with a semi-structured interview to detect (in both samples) alcohol dependence, but also such related traits as specificities of complications. The frequency of the A1 allele was not significantly different between alcoholics and controls but when comparing different subgroups of alcoholics, the A1 allele was significantly more frequent in alcoholic patients with somatic complications (OR = 3.00, CI[1.37-6.62]), social and professional complications (OR = 2. 72, CI[1.25-5.90]), or with co-morbid dependence (OR = 2.88, 95% IC [1.16-7.15]). The association for co-morbid dependence and somatic complications was also positive when taking into consideration both STRP and TaqIA polymorphisms. The A1 allele does not increase the risk for alcoholism per se in our sample, but may be involved in a related trait which is partially dependent on the diagnosis of alcoholism, through a disequilibrium with another close mutation.

Adult↗
PubMed1999

[Behçet's disease and factitious manic-depressive psychosis: a case of Münchausen syndrome].

BACKGROUND: Munchausen syndrome is frequently observed in men unlike other factitious conditions. The patient presents a characteristic triad: apparently acute but factitious disorders, migration from hospital to hospital resulting in unnecessary explorations and treatments, and fabulated medical history. CASE REPORT: A 57-year-old man was hospitalized in the psychiatric unit for alleged insomnia, psychomotor excitation and multiple hallucinatory phenomena. The factitious nature of the patientís condition was rapidly suspected in light of the large number of previous unconfirmed medical conditions and a rather unbelievable history. DISCUSSION: Unlike the classical description of Munchausen's syndrome, this patient had no history of surgery. This unusual aspect should not exclude the clinical diagnosis as for some patients, the invasive nature of certain explorations may be a valid substitute for surgery.

Behcet Syndrome↗
PubMed1999

Genetic factors in anorexia nervosa.

Anorexia nervosa is a severe and complex disorder with incompletely known vulnerability factors. It is generally recognized that anorexia nervosa is a familial disorder, but the majority of twin studies have shown that the concordance rate for monozygotic twins is higher (on average 44%) than for dizygotic twins (on average 12.5%). This difference in concordance rates shows that genetic factors, more than common familial environment, may explain why the 'anorexia nervosa' phenotype runs in families. In order to estimate the heritability in the broad sense of anorexia nervosa according to published familial and twin studies, we first assessed the intrapair correlation between monozygotic and dizygotic twins, and secondly calculated the deviation threshold of relatives of affected probands from the relative mean. In this review, we obtained an estimation of the heritability at 0.72 according to all published controlled familial studies (six references quoted in MEDLINE(R)), and 0.71 for all published twin studies (59 references quoted in MEDLINE(R)). This estimation is close to the ones previously proposed, between 0. 5 and 0.8. Familial and twin studies may also help to define the boundaries of the phenotype, shedding light on the complex relationship between anorexia nervosa on the one hand, and bulimia nervosa, mood disorders, and alcoholism on the other. Demonstrating the importance of genetic factors in anorexia nervosa, and more specifically for anorexia of the restrictive type, requires not only prospective and adoption studies (which are still lacking), but also genetic polymorphisms analyses, which began very recently.

Anorexia Nervosa↗
PubMed1999

Study of impulse-control disorders among alcohol-dependent patients.

BACKGROUND: Impulse-control disorders (ICDs) include intermittent explosive disorder, kleptomania, trichotillomania, pyromania, and pathological gambling. Several studies have suggested that the incidence of pathological gambling is substantially higher in alcoholics than in the general population. The rate of co-occurrence of other ICDs and alcohol dependence has never been systematically investigated. In our study, we assessed the frequency of all ICDs in a population of alcohol-dependent patients. We also examined the possibility that the presence of an ICD can correspond to earlier onset and more severe forms of alcoholism, which have a greater association with antisocial personality. METHOD: All patients hospitalized at our psychiatric unit for detoxification between January and August 1997 met DSM-IV criteria for alcohol dependence and were included in this study. Diagnosis of alcohol dependence was confirmed with the Mini-International Neuropsychiatric Interview. ICDs were investigated using the Minnesota Impulsive Disorders Interview. All patients completed the Michigan Alcoholism Screening Test. RESULTS: Among the 79 patients included in the study, 30 (38.0%) met criteria for an ICD. Included in the study were 19 cases of intermittent explosive disorder, 7 cases of pathological gambling, 3 cases of kleptomania, and 1 case of trichotillomania. Patients with co-occurring ICDs were significantly younger than patients without an ICD (mean age = 40.7 vs. 44.5 years; p = .03). Patients with co-occurring pathological gambling were significantly younger at the onset of alcohol dependence than patients without ICDs (mean age = 19.5 vs. 25.9 years; p = .0008). Pathological gamblers had significantly longer duration of alcohol dependence compared with patients without ICDs (26.0 vs. 17.9 years; p = .02). Patients with co-occurring intermittent explosive disorder had the shortest duration of alcohol dependence of all patients (9.9 years). Prevalence of antisocial personality disorder was no different in patients with or without co-occurring ICDs. CONCLUSION: Thirty-eight percent of the alcohol-dependent patients studied presented with an ICD. Patients with ICDs were younger than those without an ICD. The presence of an ICD was not associated with a specific form of alcohol dependence or with antisocial personality. Co-occurrence of pathological gambling, however, was associated with lower age at onset of alcohol dependence, a higher number of detoxifications, and a longer duration of alcohol dependence than was absence of an ICD.

Adult↗
PubMed1998

Impulse-control disorders in alcoholics are related to sensation seeking and not to impulsivity.

Impulse-control disorders (ICD) include intermittent explosive disorder, kleptomania, trichotillomania, pyromania and pathological gambling. Several studies have suggested that the incidence of pathological gambling and impulsive violent behavior is substantially higher in alcohol-dependent patients than in the general population. The association between ICD and alcoholism, as well as personality characteristics such as sensation seeking and impulsivity, has never been systematically studied. The present study compared the levels of impulsivity and sensation seeking in age- and sex-matched groups of alcohol-dependent patients with concomitant ICD (ICD+, n = 30), alcohol-dependent patients without ICD (ICD-; n = 30) and control subjects (n = 30). All the alcohol-dependent patients (ICD+ and ICD-) were hospitalized for alcohol detoxification. Diagnoses of ICD were based on DSM-IV criteria and the Minnesota Impulsive Disorders Interview. All patients completed the Zuckerman Sensation-Seeking Scale (SSS) and the Barratt Impulsiveness Rating Scale (BIS). Mean scores on the SSS general factor, the SSS disinhibition subscale, and the SSS experience-seeking scale were significantly higher in ICD+ patients than in either ICD- patients or control subjects. By contrast, total scores and subscale scores on the BIS showed no significant differences among the three groups. Thus, it appears that measures of sensation seeking, rather than impulsivity, are relevant in distinguishing between alcohol-dependent patients with and without concomitant impulse control disorders.

Adult↗