[Prevalence of pathological gambling in the general population around Paris: preliminary study]. / Prévalence du jeu pathologique en Île de France. Étude préliminaire.

INTRODUCTION: Pathological gambling is characterized in the DSM IV-TR as one of the disorders of impulse control. Problem gambling is also part of what is considered as behavioural addictions, the criteria of which have been defined by Goodman, with intrusive thoughts about the game, spending more and more to play, unable to control, reduce or stop gambling despite negative consequences, etc. AIM OF THE STUDY: There is no epidemiological study in France on the prevalence of pathological gambling. We wanted to study the prevalence of pathological gambling in a sample of 529 persons: 368 gamblers of Pari Mutuel Urbain and La Française des Jeux, and 161 persons in the general population. The study took place between January 2008 and June 2009. METHODS: As instruments, we used: the South Oaks Gambling Scale (SOGS) for screening of pathological gambling and the BIS-10 for impulsiveness' evaluation, the HAD scale to assess anxiety and depression and the ASRS for the evaluation of attention deficit disorder/hyperactivity disorder (ADHD). RESULTS: The rate of pathological gambling in the general population is 1.24% (this result is similar to those found in other places, such as in Quebec). In the general population, the rate of play at risk is of 5.59%. Among the population of gamblers, the rate for pathological gambling (JP) amounted to 9.23% and risk gambling to 10.86%. Men are overrepresented in the group of pathological gamblers (88.9%), also with consumption of alcohol and tobacco. Suicide attempts are more important than in the general population, but the difference was statistically significant. Depression and anxiety are particularly high, 40% of gamblers with an anxiety score significantly higher. DISCUSSION: The results indicate rates close to those of other countries, such as Canada. It would be necessary to establish follow-up studies of populations and patients, as well as specific studies on people who frequent casinos, racetracks and internet gambling. The importance of the phenomenon is obvious, because almost 20% of players have a gambling problem or risk and these people do not consult despite their psychological problems, family, work, debts.

[Psychometric properties of the French version of the Wender Utah Rating Scale and Brown's Attention Deficit Disorders Scale for adults]. / Propriétés psychométriques des versions françaises des échelles d'hyperactivité de Wender (WURS) et de l'Échelle de déficit d'attention de Brown (ADD).

OBJECTIVES: The objective of this work was to analyse the factorial structure of the two following instruments: (1) the Wender Utah Rating Scale (WURS) evaluates the Attention Deficit Hyperactivity Disorders (ADHD) for adults, with 25 items: the subjects describe their own childhood behaviour when they were 7 years old, (from few to very much, 0 to 4). The items are grouped in four clusters: affects and emotional problems; impulsivity and conduct disorders; impulsivity-hyperactivity; and difficulties in attention. A score of 46 or more strongly suggests diagnosis of a hyperactivity disorder during infancy; (2) Brown's (1996) Attention Deficit Disorders Scale (ADD) is a 40-item self-report. This scale is composed of a range of symptoms beyond the DSM-IV inattention criteria for ADHD. A score of 50 or more is strongly suggestive of ADD. The five clusters of this scale are: organizing and activating work; sustaining attention and concentration; sustaining energy and effort; managing affective interference; utilizing "working memory" and accessing recall. METHODS: For comparative purpose, we also used the Adult Self-Report Scale (ASRS), which evaluates ADHD with six items and accepts a cut-off of four or more; the Barratt Impulsivity Scale, and the Personality Inventory Revised, essentially with the neuroticism cluster. A total of 259 adult subjects were enrolled in this study and allocated to three groups: healthy subjects, depressive patients and alcoholic patients. RESULTS: This study indicates that the internal consistency for the French version of the ADD and WURS scales is adequate (α=0.8-0.9). The WURS and ADD scales are not fully validated, as both sensitivity to change and concurrent validity for all groups are missing. However, these adapted versions are interesting because they facilitate the use of the questionnaires for research and clinical assessment within healthy general and clinical populations. The study confirmed the psychometric properties of the two scales evaluating ADHD: Wender's Hyperactivity Scale during childhood and Brown's Attention Deficit Disorder Scale for adults (ADD). A larger patient sample would permit clearer conclusions. Nevertheless, the obtained results are very encouraging. DISCUSSION: The ASRS has already been validated. It has shown its utility as a screening tool (well correlated with the Brown's ADD Scale) and gives us a better understanding of the nature of difficulties met by patients in terms of attention. We would like to complete this study in the short-term by increasing the patient sample size and harmonizing evaluation instruments by applying the three scales (ADD, WURS and ASRS) within the three groups. Our results support the idea that the clinical population showed an elevated presence of ADD and this disorder needs to be assessed.

Influence of the serotonin transporter gene polymorphism, cannabis and childhood sexual abuse on phenotype of bipolar disorder: a preliminary study.

OBJECTIVE: The gene coding for the 5-HT transporter (5-HTT) is considered as a candidate gene for bipolar disorder, either as a "vulnerability" or as a "modifying the phenotype" gene. Psychotic symptoms occur at least once in one bipolar patient out of two, the relevant risk factors being insufficiently understood. The gene × environment interaction approach offers the opportunity to disentangle the latter, including childhood sexual abuse and cannabis abuse. METHODS: We investigated the 5-HTTLPR of the 5-HTT gene (G) and the presence of childhood sexual abuse and cannabis comorbidity (E) in 137 bipolar patients with (versus without) lifetime psychotic symptoms. RESULTS: The short allele and cannabis abuse were significantly more frequent among patients with psychotic symptoms than in those without (p=0.01 and p=0.004, respectively), while childhood sexual abuse was not. Complex interactions were found between presence of the short allele, cannabis abuse or dependence and childhood sexual abuse. CONCLUSIONS: The short allele of the 5-HTTLPR polymorphism of the 5-HTT gene was a risk factor for psychotic symptoms in bipolar disorder in the present sample, directly but also indirectly, through the presence of cannabis abuse or dependence, as an exacerbating factor heightening psychotic symptoms.

Descriptive study of the occupational outcome of bipolar patients.

INTRODUCTION: The purpose of this study was to describe the occupational outcome of bipolar patients 3 years after being hospitalized in a psychiatry department, and the determinants of this outcome. METHODS: One hundred and one bipolar patients consecutively hospitalized between 1st January 2002 and 31st December 2003, were recruited. Their occupations and medical items were assessed at baseline from the medical records and reassessed 3 years later, using a questionnaire on their work and treatment, and a quality of life scale. Occupational outcome was compared by univariate and multivariate analyses. RESULTS: Of the 101 patients initially recruited, 36 were excluded and 34 were lost to follow-up. Among the 31 bipolar patients included in the study, 58.1% were working in 2003 and 54.8% were working in 2006. The presence of a personality disorder was significantly associated with a poorer occupational outcome and a lower rate of "return to work". CONCLUSION: More than half of a population of hospitalized bipolar patients was employed. The presence of a personality disorder appeared to be a pejorative factor for "return to work", although other studies are needed to define the factors that determine the occupational outcome of bipolar patients.

Switching to the bingeing/purging subtype of anorexia nervosa is frequently associated with suicidal attempts.

OBJECTIVE: Anorexia nervosa has the highest suicide mortality ratio of psychiatric disorders, suicide being associated with many factors. We assessed the first lifetime occurrence of these factors taking into account their possible overlap. METHOD: Three hundred and four in- and out-patients with anorexia nervosa (DSM-IV) were systematically recruited in three hospitals of Paris suburbs, between December 1999 and January 2003. Patients were assessed by a face-to-face interview (DIGS). Current eating disorder dimensions were measured, and patients interviewed by a trained clinician to assess minimal BMI and, retrospectively, the age at which anorexia nervosa, major depressive disorder, anxiety disorders and switch to bingeing/purging type occurred for the first time, if applicable. RESULTS: Major depressive disorder (p<0.001) and subtype switch from the restrictive to the bingeing/purging type (p<0.001) were the two factors significantly more frequently occurring before suicidal attempts, and remained involved when a multivariate analysis is performed, whether syndromic or dimensional measures are being used. Taking into account lifetime occurrence with a survival analysis, the switch to bingeing/purging type of anorexia appears as a major predictive factor, with a large increase of the frequency of suicidal attempts (OR=15) when compared to patients with neither major depressive disorder nor bingeing/purging type. CONCLUSIONS: Bingeing/purging type of anorexia nervosa is largely associated with suicidal attempts, and may deserve specific attention. If confirmed on a prospectively designed study, these results would argue for early detection and/or more intensive and specific therapeutic intervention on this aspect of bingeing and purging behaviors.

[Heritability and candidate genes in tobacco use]. / Héritabilité et gènes candidats dans le tabagisme.

HERITABILITY INDICATORS: Genetic studies of tobacco use can be useful to understand the physiopathology of nicotine dependence and potentially to prevent it. Twin and adoption studies have clearly shown the role of genetic factors in tobacco use at different stages. Genetic factors account for 55% (range: 11-84%) of the smoking initiation and 61% (range: 52-71%) for persistence. Age at onset and intensity of smoking are also influenced by genetic factors. Estimation of the heritability of initiation/persistence of smoking varies by gender. It is estimated as 66%/61% for women and 49%/61% for men respectively. In adolescent twin studies, heritability estimated the liability of lifetime or current use of tobacco to be more than 80%, while the heritability for initiation being between 11% and 59%. Heavy smoking is also influenced by genetic factors, especially when patients are co-abusing alcohol or coffee. Genetics findings - Advances in molecular genetics identified different candidate genes for tobacco use mainly involving neurotransmission of neuromodulators. Because of the brain reward effects of nicotine on the mesolimbic system, the genes involved in the dopaminergic transmission receive specific attention. Genetic polymorphisms of the dopamine D1, D2, D4 and D5 receptors, dopamine transporter (DAT1) and dopamine B-hydroxylase (DBH) have been associated at least once with clinical aspects of tobacco use (initiation, dependence and intensity) and temperament traits as novelty seeking, the latter being lower in smokers and thus considered as a vulnerable marker in accordance with the reinforcement effect of nicotine. Regarding interaction between nicotine use and anxiety and depression, the gene encoding for the serotonin transporter (5-HTT) may constitute a candidate gene. Because of interindividual bioavailability of nicotine, genetic polymorphisms of metabolism enzymes have also been analysed. Some variants of the cytochrome P450 seem to be more frequent among dependent smokers than controls or ever smokers (CYP2A6) and heavier smokers (CYP2D6). Genetic research might be suitable for a therapeutic approach and identify subjects at high risk for nicotine dependence.

Association between dopamine receptor D3 gene BalI polymorphism and cognitive impulsiveness in alcohol-dependent men.

The gene coding for the dopamine receptor D3 (DRD3) is considered as a major candidate gene in various addictive disorders. Association studies in alcohol-dependence for this gene are nevertheless controversial. We made the hypothesis that phenotypical heterogeneity of alcohol-dependence (i.e. the DRD3 gene is a vulnerability gene in a specific subgroup of patients only) could explain these spurious findings, focusing on a core dimension of addictive disorders, namely impulsiveness. In our sample of 108 French alcohol-dependent patients, patients above the median value for cognitive impulsiveness (one of the three dimensions of the Barratt scale) were more frequently heterozygous than both alcohol-dependent patients with lower impulsiveness (OR = 2.51, P = 0.019) and than 71 healthy controls (OR = 2.32, P = 0.025). Age at interview, antisocial personality disorder, other comorbid addictive disorder, age at onset of alcohol-dependence, and lifetime mood disorders did not constitute confusing intermediate factors.

Meta-analysis of family-based association studies between the dopamine transporter gene and attention deficit hyperactivity disorder.

INTRODUCTION: Molecular genetic research has mainly focused on the D4 dopamine receptor (DRD4) and the dopamine transporter (DAT) genes in attention-deficit hyperactivity disorder (ADHD). A recent meta-analysis showed that the DRD4 gene has a significant role in the vulnerability to ADHD. OBJECTIVES: With an equal number of positive and negative association studies between the 10-repeat of the DAT gene and ADHD, a meta-analysis is required for this other candidate gene. METHODS: We re-analysed the 13 published family-based association studies between ADHD and the DAT gene. Following recent recommendations, different biases were specifically assessed, such as the sample-size effect and the time effect. RESULTS: The meta-analysis showed no significant association between ADHD and the DAT gene (P = 0.21), but an important between-samples heterogeneity (P = 0.0009). Odds ratios above 1 are mostly observed in studies with a small number of informative transmissions, and decrease with larger sample size. CONCLUSIONS: Contrary to what was found for the DRD4 gene, the 10-repeat allele of the DAT gene has at most a minor role in the genetic susceptibility of ADHD. The different biases detected herein probably explain the initial impression of a significant impact of the DAT gene on hyperactivity.

[Meta-analysis of candidate genes in attention-deficit hyperactivity disorder]. / Meta-analyse des gènes candidats dans le trouble déficit attentionnel avec hyperactivité (TDAH).

Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder observed during childhood, detected in 3% to 5% of school-age children. The disorder is characterised by marked inattention, hyperactivity, and impulsiveness. In most cases, symptoms can be treated by catecholamine-releasing drugs, such as methylphenidate. Children with ADHD are at higher risk for substance abuse and oppositional, conduct and mood disorders. Familial and adoption studies shed light on the genetic vulnerability of ADHD. Twin studies estimated the broad heritability to range between 40% and 90%. The mode of transmission is yet unknown, but is likely polygenic. Molecular genetic studies in ADHD should contribute to a greater understanding of the pathophysiology of the disorder (genetics of the vulnerability), and could help to select a more rational type of treatment (pharmacogenetic). Family-based association studies already performed are reviewed in this manuscript. Association studies, using haplotype relative risk (HRR) or transmission disequilibrium test (TDT) have focused on candidate genes which code for proteins potentially involved in the etiopathogenesis of the disorder. Genes involved in dopamine, serotonin, and noradrenalin systems have thus been assessed for their role in core features of ADHD, such as motor overactivity, inattention, and impulsiveness. According to a meta-analysis, the DAT1 gene, an obvious candidate gene in ADHD vulnerability, does not appear to be involved (OR = 1.13, p = 0.21). On the other hand, DRD4 (OR = 1.26, p = 0.01) and DRD5 (OR = 1.4, p = 0.01) are significantly associated to ADHD according to the present meta-analysis, confirming previous ones. Recent studies showed a trend for an association between one allele of the 5-HTT (considering case-control studies) and DBH (OR = 1.27, p = 0.06) genes and ADHD, but these positive findings have to be replicated. ADHD is a complex disorder with potentially many different risk factors. Genetic and phenotypic heterogeneity could explain why some association studies are positive, whereas others are negative. For instance, different developmental pathways are likely to lead to similar clinical outcomes. More clear-cut phenotypes, such as ADHD with conduct disorder, or ADHD with bipolar disorder, could be more homogenous, the genes involved being therefore more easy to detect. These phenotypes are beginning to be specifically studied in molecular genetics. In addition, the development of pharmacogenetics could help to identify predictors of clinical response for a specific type of treatment, which would be clearly helpful in clinical practice.

Family-based association studies between 5-HT5A receptor gene and schizophrenia.

BACKGROUND: Pharmacological and neurodevelopmental data support the idea that the gene, which codes for the 5-HT(5A) receptor is an important candidate gene for schizophrenia susceptibility. However, previous genetic studies focusing on this gene yielded conflicting results, potentially because of: (i) stratification biases of case-control association studies, (ii) genetic and phenotypic heterogeneity of schizophrenia, and (iii) variability in the loci analyzed (the 5-HT(5A) gene having many polymorphic sites). METHODS: A transmission disequilibrium test was used in the present study aimed at investigating two polymorphisms in exon 1 of the 5-HT(5A) gene, the A12T silent substitution and the C43T transversion leading to a 15Pro --> Ser substitution, in 103 patients with DSM-IV diagnosis of schizophrenia, and their 206 parents. RESULTS: We found an excess of transmission of the 12T allele from the parents to their affected children (P = 0.02), with evidence for linkage disequilibrium between the 12T-43C haplotype and schizophrenia (P = 0.002). Furthermore, patients with the 12T allele had a significantly later age at onset (P = 0.003), and the Q-TDT approach confirmed that this allele was transmitted with an older age at onset (P = 0.01). CONCLUSIONS: These data provided convergent evidence for a significant role of the 5-HT(5A) gene in schizophrenia and more specifically in patients with later age at onset.

Family-based association study of the serotonin-6 receptor gene (C267T polymorphism) in schizophrenia.

The expression of serotonin type 6 receptor (5-HT(6)) in limbic and cortical regions of the brain, and its high affinity for atypical antipsychotics suggest that its encoding gene may play a role in the pathogenesis of schizophrenia. We firstly performed a meta-analysis of the C267T polymorphism of the 5-HT(6) gene in schizophrenia, based on four different case/control studies, and showed that the allelic distribution is not significantly different between patients and controls, even when taking into account the role of between samples heterogeneity. We then recruited 103 trios (patients with Diagnostic and Statistical Manual Mental Disorders, 4th ed. (DSM-IV) diagnosis of schizophrenia and their parents), and investigated the C267T polymorphism of the 5-HT(6) receptor gene with regard to family-based association study approach (haplotype relative risk (HRR) and transmission disequilibrium test (TDT)). We found no excess of transmission of one allele from the parents to their affected children, using the HRR (P = 0.60), as well as no evidence for linkage between C267T polymorphism and schizophrenia, using the TDT (P = 0.71). Furthermore, the 267T allele frequency was comparable in the different subgroups defined on age at onset, family history of schizophrenia, treatment response, and subtypes of patients based on positive versus negative predominant symptoms. These data do not support the idea that the 5-HT(6) receptor gene plays a major role in the etiopathogenesis of schizophrenia.

Rheumatoid arthritis and schizophrenia: a negative association at a dimensional level.

There is wide evidence for a decreased risk of rheumatoid arthritis in patients with schizophrenia. Nevertheless, very few studies have looked at the risk of schizophrenia in a group of patients with rheumatoid arthritis. We prospectively investigated, with the SCL-90R, 220 consecutive outpatients with rheumatoid arthritis and 196 consecutive outpatients with various medical conditions, half of them suffering from psoriatic arthritis (a medical condition close to rheumatoid arthritis). The SCL-90R appears to be a valuable tool to distinguish patients with schizophrenia from the outpatients of our sample, the former having more "paranoid ideation" (p = 0.004) and more "psychoticism" (p < 0.001) than the latter. The "paranoid ideation" dimension was significantly lower (25% decrease) in the sample of patients with rheumatoid arthritis compared to the combined control group (p = 0.005), ratings under the median value being more frequent in the former group (p = 0.025). Confounding factors might not explain this difference according to the regression logistic analysis performed. As patients with rheumatoid arthritis have a lower score of paranoid ideation than controls in our sample, even after controlling for age, gender and severity of the disease, these data represent further evidence for a decreased risk of schizophrenia in individuals with rheumatoid arthritis.

Impulsiveness as the intermediate link between the dopamine receptor D2 gene and alcohol dependence.

OBJECTIVES: Reinforcement and reward processes have been proposed as being an intermediate link between the risk for alcohol dependence and the gene coding for the dopamine receptor D2 (DRD2). This hypothesis remains open to speculation, and personality traits such as impulsiveness, a core dimension in addictive disorders, should also be taken into account. For instance, recent evidence in rats showed that DRD2 antagonists might increase impulsivity in decreasing the value of delayed rewards. METHODS: Considering the pro-impulsiveness role of ethanol observed in clinical practice and epidemiological studies, we analysed the Barratt impulsiveness scores in a sample of 92 alcohol-dependent French patients (57 men and 35 women), according to the TaqI A polymorphism of the DRD2 gene. RESULTS: A2/A2 and A1/A2 genotypes were significantly associated with a higher global impulsiveness than A1/A1 genotype (P=0.02 and P=0.03, respectively). CONCLUSIONS: We propose that reward-related impulsiveness may constitute a risk factor for alcohol dependence, and that this core temperament could be partly mediated by the DRD2 gene.

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.

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).

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.

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.

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.

[Precocious and polymorphic factitious disorder]. / Pathomimie précoce et polymorphe.

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.