[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.

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.

[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.

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.

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.

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 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.

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.

Lack of association between anorexia nervosa and D3 dopamine receptor gene.

BACKGROUND: Evidence from family and twin studies suggests a genetic contribution to the etiology of anorexia nervosa. Different genes could contribute to the vulnerability to anorexia nervosa, but dopamine could be more specifically implicated in anorexia nervosa because of pharmacologic, endocrine, and neurobiological specificities. The dopamine receptor D3 (DRD3) may be of additional interest, since it is specifically located in the limbic area, an area implicated in reward and reinforcement behavior. METHODS: We performed an association study between 39 patients with severe (requiring hospitalization and with young age at onset) anorexia nervosa (DSM-III-R), and 42 controls, with the Bal I polymorphism in exon I of the DRD3 gene. RESULTS: There was no significant difference between patients with anorexia nervosa and controls in allele frequencies or genotype count. The association was still negative between subgroups separated according to family history of anorexia nervosa or comorbid mood disorders. CONCLUSIONS: Despite the fact that the number of patients tested is small, there is good evidence that the Bal I DRD3 polymorphism does not play a major role in the genetic component of anorexia nervosa. It would be useful to test polymorphisms of the other genes coding for dopamine receptors.

Panic disorder in cardiac outpatients.

OBJECTIVE: Continuing the long history of interest in the relation of anxiety disorders to cardiovascular function and symptoms, this study investigated the level of anxiety and prevalence of panic disorder in cardiac patients and the possible associations between specific abnormal ECG results and a diagnosis of panic disorder. METHOD: Consecutive patients referred for ambulatory ECG recordings were assessed with the seven anxiety items of the Hospital Anxiety and Depression Scale. Then, 50 patients with scores higher than 8 (the anxious group) were interviewed with the Schedule for Affective Disorders and Schizophrenia--Lifetime Version Modified for the Study of Anxiety Disorders (SADS-LA). RESULTS: Of the 50 anxious patients (26 male and 24 female) interviewed with the SADS-LA, 62% (N = 31) met the DSM-III-R criteria for panic disorder. Patients with panic disorder had a higher mean maximal heart rate and a shorter P-R interval than patients without panic disorder. Unlike the patients without panic disorder, the patients with panic disorder showed no correlation between maximal heart rate and minimal P-R interval. CONCLUSIONS: The rate of panic disorder was high in the patients referred for ECG. Moreover, the prevalence of panic disorder was similar in the patients with and without ECG abnormalities, indicating that in anxious patients the presence of panic disorder does not rule out organic cardiac disease. On the other hand, the higher maximal heart rate and shorter P-R interval of the panic patients may be attributable to hypersensitivity of beta-adrenergic receptors in panic disorder.

Phenomenology and psychopathology of uncontrolled buying.

OBJECTIVE: Uncontrolled buying, defined by the presence of repetitive impulsive and excessive buying that leads to personal and familial distress, is a psychiatric disorder that has only recently been recognized. This review focuses on the prevalence, clinical features, and etiology of this disorder. METHOD: All published articles on the topic were collected and reviewed. The literature concerning the typology of normal consumerism was also reviewed. RESULTS: The prevalence of the disorder in the general population is reported to be 1.1%. The main clinical features of uncontrolled buying are impulsivity and repetition of buying, the invasive need to buy, unsuccessful attempts to control spending, and the existence of tangible negative consequences of buying (marked distress, interference with social or occupational functioning, or financial problems). Uncontrolled buying may be related to obsessive-compulsive disorder, depression, addiction, or impulsivity. CONCLUSIONS: In most cases, uncontrolled buying can be understood as "compensatory buying" that temporarily alleviates depressive symptoms and can thus be associated with the results of antidepressant treatment in cases in which uncontrolled buying is symptomatically associated with depression.

Meta-analysis of DRD3 gene and schizophrenia: ethnic heterogeneity and significant association in Caucasians.

The involvement of dopamine in the etiology of schizophrenia is suggested by a number of neurobiological and pharmacological data, the dopamine D3 receptor (DRD3) being selectively expressed in brain regions which may be specifically involved in the risk for schizophrenia. The gene coding for DRD3 has thus been extensively analyzed. Since the initial report providing substantial evidence for an association of homozygosity of either allele of the gene coding for DRD3 (BalI polymorphisms) with schizophrenia, a flurry of replicating studies has appeared, which have been split into confirmations and nonreplications in North European Caucasian, Mediterranean, Asian, American, and African populations. The involvement of DRD3 polymorphisms thus remains questionable, particularly as no linkage studies have favored a nonrandom segregation of DRD3 alleles and schizophrenia. We performed a metaanalysis from 29 independent samples, from 24 different association studies so far published, allowing the examination of 2,619 schizophrenic patients and 2,517 controls. No significant differences of genotype counts were noted between patients and controls for the whole sample, considering frequency of any genotype. Starting from the high variability of the genotypes in different geographical areas, the impact of ethnic heterogeneity was taken into account. When the studies were reorganized in five groups according to geographical origin of samples, both homozygosity and 1-1 genotype revealed significant heterogeneity (P < 0.05). We specifically found an excess of homozygosity and 1-1 genotype in schizophrenic patients only in the African and Caucasian groups (P < 0.05). The present analysis suggests a small but significant effect of DRD3 in the susceptibility to schizophrenia, at least in Caucasians.

Lack of association between alcohol-dependence and D3 dopamine receptor gene in three independent samples.

Numerous studies on the involvement of dopamine receptors in the genetics of alcoholism focused on associations between a polymorphism of the D2 dopamine receptor (DRD2) gene and alcohol dependence. However, the results of these studies are conflicting. Another receptor, the D3 dopamine receptor (DRD3), may be of additional interest since it is specifically located in the limbic area, and in particular in the nucleus accumbens which plays a significant role in the reward process of addiction behavior. We thus tested the association in three independent samples of alcoholic patients, with different origins and various inclusion criteria. No difference in the DRD3 gene polymorphism emerged between controls and alcoholic patients, regardless of their origin, inclusion criteria, or presence or absence of the DRD2 TaqI A1-allele. Despite the fact that more information could have been considered and that association studies provide limited information, there is good evidence that this DRD3 polymorphism does not play a major role in the genetic component of alcoholism.

Antidepressant discontinuation: a review of the literature.

Sudden or tapered withdrawal from treatment with antidepressants, including monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and serotonin selective reuptake inhibitors (SSRIs), can produce phenomena consisting of somatic and psychological symptoms. The literature about these discontinuation phenomena consists mainly of case reports and a limited number of controlled prospective studies. The symptoms are generally mild and transient for the TCAs and the SSRIs but may be serious for the MAOIs. They are much more common with a shorter acting SSRI, such as paroxetine, than with the longer acting agent fluoxetine. Because the symptoms of antidepressant discontinuation include changes in mood, affect, appetite, and sleep, they are sometimes mistaken for signs of a relapse into depression. Thus, it is important to directly question patients about new symptoms that occur during antidepressant discontinuation to optimally manage treatment discontinuation.

Study of compulsive buying in depressed patients.

BACKGROUND: Compulsive buying is defined by the presence of repetitive impulsive and excessive buying leading to personal and familial distress. Patients with this disorder also suffer from mood disorder in 50% to 100% of the cases studied, and antidepressants help to decrease the frequency and the severity of uncontrolled buying. To define the correlation between compulsive buying and depression, we assessed this behavior among 119 inpatients answering to DSM-III-R criteria for major depressive episode. Additionally, we evaluated for comorbidity in the patients suffering from compulsive buying and in those free from this disorder. Impulsivity and sensation seeking were also compared in the two groups. METHOD: Diagnosis of compulsive buying was made using standardized criteria and a specific rating scale. Diagnosis of depression and assessment of comorbidity were investigated using the Mini International Neuropsychiatric Interview and a modified version of the Minnesota Impulsive Disorders Interview. All patients answered the Zuckerman Sensation-Seeking Scale and the Barrat Impulsivity Rating Scale. RESULTS: The prevalence of the disorder was 31.9%; 38 of the 119 depressed patients were diagnosed as compulsive buyers. Patients from the compulsive buying group were younger in age, more often women than men, and more frequently unmarried. They presented more often than others with recurrent depression (relative risk = 1.4), disorders associated with deficits in impulse control such as kleptomania (relative risk = 8.5) or bulimia (relative risk = 2.8), benzodiazepine abuse or dependence disorder (relative risk = 4.7), and two or more dependence disorders (relative risk = 1.99). Subscores for experience seeking using the Zuckerman Sensation-Seeking Scale were significantly higher (p = .04) and scores of impulsivity were much higher (p < .0001) than corresponding scores in the group without compulsive buying behavior. CONCLUSION: Compulsive buying is frequent among depressed patients. In most cases, the behavior is associated with other impulse control disorders or dependence disorders and a high level of impulsivity.

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.

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.

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.