Association analyses reveal gender-specific associations of DAT1 40-bp VNTR and -839C/T polymorphisms with obsessive-compulsive disorder and obsessive-compulsive symptoms.

The dopamine transporter (DAT) is involved in dopamine signaling and distribution, controlling dopamine concentrations and contributing to several central nervous system disorders. The purpose of this study was to determine the association between two functional polymorphisms in DAT1 gene, the 40-base pair Variable Number of Tandem Repeats (VNTR) and the Single Nucleotide Polymorphism (SNP) -839C/T and obsessive-compulsive disorder (OCD) and/or its clinical features. To do so, 199 OCD patients and 201 healthy controls were genotyped using Polymerase Chain Reaction (PCR). Genotype distribution of both polymorphisms was in Hardy-Weinberg equilibrium. Although OCD and controls did not differ in terms of polymorphisms distribution, we observed that the presence of 10R-allele protected men of having OCD (P = 0.03). We also observed a significant association between the presence of 10R and checking in women (P = 0.02; OR = 3.14; 95%CI 1.08-9.11), and between the 9/9 genotype and neutralization in men (P = 0.04; OR = 3.38; 95%CI 1.03-11.11). Finally, the T-allele of -839C/T was significantly associated with the "obsession" score (P = 0.02; OR = 2.66; 95%CI 1.15-6.13). Our results demonstrate an important influence of dopaminergic pathways, particularly DAT1 polymorphisms, in OCD.

[A clinical and genetic study of impulsive-compulsive disorders in patients with Parkinson's disease]. / Kliniko-geneticheskoe issledovanie impul'sivno-kompul'sivnykh rasstroistv u bol'nykh bolezn'iu Parkinsona.

AIM: To evaluate the frequency and spectrum of impulsive-compulsive disorders (ICDs) in patients with Parkinson's disease (PD) without dopaminergic medication and among patients receiving dopaminergic replacement therapy, depending on personality type, genetic factors, and to determine the influence of ICDs on the development of other non-motor manifestations of the disease. MATERIAL AND METHODS: Three hundred and eighty-six consecutive patients with idiopathic PD, including untreated patients with PD (de novo) and patients receiving dopaminergic replacement therapy during one year, were examined. ICDs were evaluated with QUIP and diagnostic criteria. Personality type and temperament features were assessed by the Eysenck personality inventory. Genotyping for the single nucleotide polymorphism rs141116007 in the DBH gene involved in the pathogenesis of PD and ICDs was performed. RESULTS AND CONCLUSION: ICDs were identified in 20.2% patients with PD and in 4% patients of the de novo group. The most common (10.36%) behavioral disorder was a binge eating. The frequency of ICDs among patients with PD before the onset of dopamine replacement therapy increased by 1.03 times after one year treatment. Smoking and young age were risk factors for ICDs (p<0.05). The results of the study allowed the determination of social and neuropsychological risk factors for ICDs in patients with PD. The account of these features, as well as early detection of ICDs using screening questionnaires may help to personalize treatment of patients with PD and to prevent the risk of developing comorbid non-motor manifestations of the disease.

OBSESSIVE-COMPULSIVE PERSONALITY DISORDER: EVIDENCE FOR TWO DIMENSIONS.

BACKGROUND: To determine possible dimensions that underlie obsessive-compulsive personality disorder (OCPD) and to investigate their clinical correlates, familiality, and genetic linkage. METHODS: Participants were selected from 844 adults assessed with the Structured Instrument for the Diagnosis of DSM-IV Personality Disorders (SIDP) in the OCD Collaborative Genetics Study (OCGS) that targeted families with obsessive-compulsive disorder (OCD) affected sibling pairs. We conducted an exploratory factor analysis, which included the eight SIDP-derived DSM-IV OCPD traits and the indecision trait from the DSM-III, assessed clinical correlates, and estimated sib-sib correlations to evaluate familiality of the factors. Using MERLIN and MINX, we performed genome-wide quantitative trait locus (QTL) linkage analysis to test for allele sharing among individuals. RESULTS: Two factors were identified: Factor 1: order/control (perfectionism, excessive devotion to work, overconscientiousness, reluctance to delegate, and rigidity); and Factor 2: hoarding/indecision (inability to discard and indecisiveness). Factor 1 score was associated with poor insight, whereas Factor 2 score was associated with task incompletion. A significant sib-sib correlation was found for Factor 2 (rICC = .354, P < .0001) but not Factor 1 (rICC = .129, P = .084). The linkage findings were different for the two factors. When Factor 2 was analyzed as a quantitative trait, a strong signal was detected on chromosome 10 at marker d10s1221: KAC LOD = 2.83, P = .0002; and marker d10s1225: KAC LOD = 1.35, P = .006. CONCLUSIONS: The results indicate two factors of OCPD, order/control and hoarding/indecision. The hoarding/indecision factor is familial and shows modest linkage to a region on chromosome 10.

Genome-wide association analysis of eating disorder-related symptoms, behaviors, and personality traits.

Eating disorders (EDs) are common, complex psychiatric disorders thought to be caused by both genetic and environmental factors. They share many symptoms, behaviors, and personality traits, which may have overlapping heritability. The aim of the present study is to perform a genome-wide association scan (GWAS) of six ED phenotypes comprising three symptom traits from the Eating Disorders Inventory 2 [Drive for Thinness (DT), Body Dissatisfaction (BD), and Bulimia], Weight Fluctuation symptom, Breakfast Skipping behavior and Childhood Obsessive-Compulsive Personality Disorder trait (CHIRP). Investigated traits were derived from standardized self-report questionnaires completed by the TwinsUK population-based cohort. We tested 283,744 directly typed SNPs across six phenotypes of interest in the TwinsUK discovery dataset and followed-up signals from various strata using a two-stage replication strategy in two independent cohorts of European ancestry. We meta-analyzed a total of 2,698 individuals for DT, 2,680 for BD, 2,789 (821 cases/1,968 controls) for Bulimia, 1,360 (633 cases/727 controls) for Childhood Obsessive-Compulsive Personality Disorder trait, 2,773 (761 cases/2,012 controls) for Breakfast Skipping, and 2,967 (798 cases/2,169 controls) for Weight Fluctuation symptom. In this GWAS analysis of six ED-related phenotypes, we detected association of eight genetic variants with P < 10(-5) . Genetic variants that showed suggestive evidence of association were previously associated with several psychiatric disorders and ED-related phenotypes. Our study indicates that larger-scale collaborative studies will be needed to achieve the necessary power to detect loci underlying ED-related traits.

Etiology of obsessive-compulsive symptoms and obsessive-compulsive personality traits: common genes, mostly different environments.

BACKGROUND: Little is known about the etiologic relationship between obsessive-compulsive (OC) symptoms and traits of OC personality disorder. The traits include perfectionism and rigidity. Some theorists have proposed that OC personality disorder is one of several disorders falling within an OC spectrum. This implies that OC personality traits and symptoms should have etiologic factors in common, and this should not be simply because symptoms and traits are both shaped by nonspecific etiological influences, such as those shaping negative emotionality (neuroticism). METHODS: To investigate these issues, a community sample of 307 pairs of monozygotic and dizygotic adult twins provided scores on six types of OC-related symptoms, two markers of negative emotionality, and a measure of OC personality traits. RESULTS: Analyses indicated that symptoms and traits arose from a combination of genetic and nonshared environmental factors. A matrix of genetic correlations was computed among the variables, which represented the correlations between the genetic components of pairs of variables. A matrix of environmental correlations was similarly computed. Each matrix was factor analyzed. One genetic factor was obtained, indicating that all variables were influenced by a common genetic factor. Three environmental factors were obtained, with salient loadings on either (a) all six OC symptoms, (b) negative emotionality and obsessing, or (c) OC personality traits and ordering. CONCLUSIONS: OC symptoms and traits were etiologically related primarily because they are shaped by the same nonspecific genetic factor that influenced negative emotionality. Implications for the concept of the OC spectrum are discussed.

Association between a serotonin transporter promoter polymorphism (5HTTLPR) and personality disorder traits in a community sample.

BACKGROUND: The serotonin transporter (SERT) polymorphism (5HTTLPR) has been reported to be associated with several psychiatric conditions. Specific personality disorders could be intermediate factors in the known relationship between 5HTTLPR and psychiatric disorders. This is the first study to test the association between this polymorphism and dimensions of all DSM-IV personality disorders in a community sample. METHODS: 374 white participants were assessed by clinical psychologists using the International Personality Disorder Examination (IPDE). Associations between dimensions of each DSM-IV personality disorder and the long (l) and short (s) alleles of the 5HTTLPR were evaluated using non-parametric tests and regression models. RESULTS: The s allele of the 5HTTLPR polymorphism was significantly associated with higher avoidant personality trait scores in the whole sample. Males with the s allele had a significantly lower likelihood of higher obsessive-compulsive personality disorder (OCPD) trait scores, whereas females with the s allele were likely to have higher OCPD personality trait scores. CONCLUSION: This paper provides preliminary data on the relationship between personality disorders and the 5HTTLPR polymorphism. The relationship of the s allele and avoidant PD is consistent with findings of a nonspecific relationship of this polymorphism to anxiety and depressive disorders. Concerning the unusual sexual dimorphic result with OCPD, several hypotheses are presented. These findings need further replication, including a more detailed study of additional variants in SERT.

Comorbid obsessive-compulsive personality disorder in obsessive-compulsive disorder (OCD): a marker of severity.

INTRODUCTION: Comorbid obsessive-compulsive personality disorder (OCPD) is well-described in obsessive-compulsive disorder (OCD). It remains unclear, however, whether OCPD in OCD represents a distinct subtype of OCD or whether it is simply a marker of severity in OCD. MATERIALS AND METHODS: The aim of this study was to compare a large sample of OCD subjects (n=403) with and without OCPD on a range of demographic, clinical and genetic characteristics to evaluate whether comorbid OCPD in OCD represents a distinct subtype of OCD, or is a marker of severity. RESULTS: Our findings suggest that OCD with and without OCPD are similar in terms of gender distribution and age at onset of OC symptoms. Compared to OCD-OCPD (n=267, 66%), those with OCD+OCPD (n=136, 34%) are more likely to present with the OC symptom dimensions which reflect the diagnostic criteria for OCPD (e.g., hoarding), and have significantly greater OCD severity, comorbidity, functional impairment, and poorer insight. Furthermore there are no differences in distribution of gene variants, or response to treatment in the two groups. CONCLUSION: The majority of our findings suggest that in OCD, patients with OCPD do not have a highly distinctive phenomenological or genetic profile, but rather that OCPD represents a marker of severity.

[To know more about the Prader-Willi syndrome. Multidisciplinary support]. / Wiedziec wiecej o zespole Pradera-Williego. Opieka wielospecjalistyczna.

Prader-Willi syndrome, induced by a loss of function of paternal genes in the subcentrometric region of the chromosome 15 (q11.2q13), is a complex neurodevelopmental disorder with characteristic obesity resulting from hyperphagia. In addition behavioural disturbancies with obsessive-compulsive features, aggression, temper tantrums included, are relatively frequently seen and they often require psychiatric intervention. In this part of the paper we reviewed the recent data of behavioural phenotype the correlations of phenotype-genotype and possibilities of the multidisciplinary support for the affected persons and theirs families.

Preliminary evidence for an association between a dopamine D3 receptor gene variant and obsessive-compulsive personality disorder in patients with major depression.

We have previously reported that the Ser9Gly dopamine D3 receptor (DRD3) polymorphism was associated with increased rates of obsessive-compulsive personality disorder (OCPD) symptomology. We tested the replicability of this association within a further two independent groups of individuals with a history of depression, from a clinical sample (n = 149) and a family study (n = 213). The data from the replication samples and the original sample, within which the association was found, were compiled within a meta-analysis. Although the independent samples did not replicate the original finding, the meta-analysis elucidated significant evidence supporting the association. An individual with Gly/Gly genotype is 2.4 (P = 0.017) times more likely to be diagnosed with OCPD. Male gender was also found to be a significant predictor of OCPD diagnosis (OR = 2.82, P = 0.001). An exploration of an association of DRD3 with Axis I anxiety disorder diagnoses and Temperament and Character Inventory (TCI) traits, in particular persistence, revealed no support for an association. We conclude that DRD3 may contribute to the development of OCPD.

Differentiation of obsessive-compulsive-, panic-, obsessive-compulsive personality-, and non-disordered individuals by variation in the promoter region of the serotonin transporter gene.

Past research investigating the role of the serotonin transporter gene in OCD has produced mixed findings. One possible reason for the mixed findings is comorbidity. In this study, non-comorbid OCD individuals were compared to non-disordered controls. A sample of panic disordered individuals was also compared to a non-disordered group. Finally, as an exploratory analysis, individuals were assessed for OCPD and their allelic frequencies were also compared to non-disordered individuals. Analyses revealed that there were higher frequencies of the s/s genotype among the OCD group when compared to non-disordered controls. There were no differences in allelic frequencies on the serotonin transporter gene between the panic disordered group, the OCPD group, and the non-disordered control group. This study found that non-comorbid OCD individuals tended to have a higher percentage of the homozygous short genotype than non-disordered individuals. The s/s genotype might serve as a contributory risk factor for OCD.

Perfectionism in anorexia nervosa: variation by clinical subtype, obsessionality, and pathological eating behavior.

OBJECTIVE: The purpose of this study was to examine the role of perfectionism as a phenotypic trait in anorexia nervosa and its relevance across clinical subtypes of this illness. METHOD: The Multidimensional Perfectionism Scale and the perfectionism subscale of the Eating Disorder Inventory were administered to 322 women with a history of anorexia nervosa who were participating in an international, multicenter genetic study of anorexia nervosa. All participants were additionally interviewed with the Yale-Brown Obsessive Compulsive Scale and the Yale-Brown-Cornell Eating Disorder Scale. Mean differences on dependent measures among women with anorexia nervosa and comparison subjects were examined by using generalized estimating equations. RESULTS: Persons who had had anorexia nervosa had significantly higher total scores on the Multidimensional Perfectionism Scale than did the healthy comparison subjects. In addition, scores of the anorexia subjects on the Eating Disorder Inventory-2 perfectionism subscale exceeded Eating Disorder Inventory-2 normative data. For the anorexia nervosa participants, the total score on the Multidimensional Perfectionism Scale and the Eating Disorder Inventory-2 perfectionism subscale score were highly correlated. Total score on the Multidimensional Perfectionism Scale was also significantly related to the total score and the motivation-for-change subscale score of the Yale-Brown-Cornell Eating Disorder Scale. CONCLUSIONS: These data show that perfectionism is a robust, discriminating characteristic of anorexia nervosa. Perfectionism is likely to be one of a cluster of phenotypic trait variables associated with a genetic diathesis for anorexia nervosa.

A family study of obsessive-compulsive disorder.

BACKGROUND: The causes of obsessive-compulsive disorder (OCD) are as yet unknown. Evidence of familial aggregation is one approach for investigating the role of genetics in the etiology of this condition. The current study was conducted to determine ifOCD is familial and to investigate possible familial subtypes. METHODS: Eighty case probands were identified in 5 specialty OCD clinics and 73 community control probands were identified by random-digit dialing. These probands and their first-degree relatives (343 case and 300 control relatives) were blinded to group and evaluated by psychiatrists and doctoral-level clinical psychologists using semistructured instruments. Final diagnoses were assigned by a blinded-consensus procedure. The results were analyzed using logistic regression by the method of generalized estimating equations. RESULTS: The lifetime prevalence of OCD was significantly higher in case compared with control relatives (11.7% vs 2.7%) (P<.001). Case relatives had higher rates of both obsessions and compulsions; however, this finding is more robust for obsessions. Age at onset of obsessive-compulsive symptoms in the case proband was strongly related to familiality (odds ratio, 0.92; confidence interval, 0.85-0.99) (P = .05); no case of OCD symptoms was detected in the relatives of probands whose age at onset of symptoms was 18 years or older. Probands with tics or obsessive-compulsive personality disorder were not more likely to have relatives with OCD than those without these features. CONCLUSIONS: Obsessive-compulsive disorder is a familial disorder. Obsessions are more specific to the phenotype than are compulsions. Age at onset of OCD is valuable in characterizing a familial subtype.

Segregation analysis of obsessive-compulsive disorder using symptom-based factor scores.

Obsessive-compulsive disorder (OCD) is a complex psychiatric disorder characterized by recurring obsessions or compulsions that cause significant distress to the patient or significantly interfere with the patient's normal home, work, or social activities [Diagnostic and Statistical Manual of Mental Disorders, 4th Edition. Washington, DC: American Psychiatric Association, 1994]. Twin and family studies have suggested that OCD has a significant genetic component. We performed complex segregation analyses using POINTER with families ascertained through an OCD-affected proband. In an attempt to resolve the phenotypic heterogeneity observed among individuals with OCD these segregation analyses used four factor-analytic symptom dimensions to subset the family sample based upon probands' symptom factor scores. Analysis of the entire sample allowed rejection of only the no transmission model; that model was also rejected in all subsequent analyses. Limiting the analyses to families with at least one OCD-affected member in addition to the proband (the demonstrably familial form of OCD) allowed rejection of all models except the mixed model. Analyses limited to families of high-factor-3 (symmetry and ordering symptoms) probands led to rejection of the polygenic model, indicating the involvement of a major locus. Additionally, the relative risk of OCD or subclinical OCD was 1.7 for relatives of probands with a factor 3 score greater than zero compared with relatives of probands with a low factor score. The symptoms attributed to high factor 3 scores (symmetry and ordering) may constitute a genetically significant symptomatic subtype of OCD. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:669-675, 1999.

Withdrawn: Opitz oculo-genito-laryngeal syndrome: a rare cause of recurrent aspiration pneumonia in an adult.

This paper has been withdrawn for data protection reasons.

[Familial incidence of affective diseases in patients with anorexia nervosa]. / Familiäre Belastungen mit affektiven Erkrankungen von Patienten mit Anorexia nervosa.

Analysis of family history information about first-, second- and third-degree relatives of 45 anorectic patients and 38 control subjects with different types of neurosis showed significantly more depression and eating disorders in the families of the anorectic group. Our data revealed the same prevalence of psychiatric disorders in general for both groups; the alcoholism rate was higher in the anorectic group without a statistic significance. These findings might provide further evidence of a possible genetic relationship between anorexia nervosa and affective illness.

The oral, obsessive, and hysterical personality syndromes. A study of hereditary and environmental factors by means of the twin method.

Lazare et al have demonstrated a factor structure similar to the oral, obsessive, and hysterical personality syndromes in a female patient population. The factor structure has been replicated in a sample of 99 predominantly "normal" females and male twin pairs. Furthermore, it was found that hysterical traits in female subjects and oral traits in male subjects seemed to have a genetic component. The study also indicated that environmental factors from an early age influence the development of the personality structure.

Children of psychotic mothers. Performance of 3-year-old children on tests of attention.

Children of mentally ill mothers (N = 21), believed to be at risk for the subsequent development of psychopathology (high-risk group) were compared with children of well mothers (N = 21)(low-risk group) on the Embedded Figures Test (EFT) and the Peabody Picture Vocabulary Test (PPVT). Results indicated that children in the high-risk group perform less well than low-risk children on the EFT (particularly on the more difficult stimuli), but do not differ from low-risk children on the PPVT. These results are interpreted as showing greater impairment of attention among children of mentally ill mothers than among children of well mothers.

Gene interaction in the phenotypic expression of mental diseases.

A genealogical analysis is carried out on the pedigrees of 10 twin pairs with two or more psychoses. The probands' symptoms reveal some peculiar aspects, i.e., an atypical phenomenology possibly due to the interference of more pathological genes. Schizophrenia, depression, epilepsy, and obsessive neurosis, are found in the pedigrees in different combinations. The study of these pedigrees would lead to the conclusion that interaction of more than one psychosis gives rise to atypical forms as a result of an attempt to establish a state of balance between opposing dynamic actions, as in reversible chemical reactions. Probands' symptoms are less severe and with an often more favourable prognosis. Epilepsy tends to become independent and the major psychoses seem to be epistatic on it. As for obsessive-compulsive neurosis, probands may progress into schizophrenia or depression if one of these psychoses is present in the pedigree, or may represent the neurotic form of the major disease.

Lithium in treatment failures.

Thirty-five patients with chronic and incapacitating mental illness who had not responded to the usual pharmacological and interactional therapies were treated with lithium. None of these patients appeared to be suffering from manic-depressive illness. If a trial of lithium resulted in unexpected improvement, lithium's contribution was assessed by double blind substitution of a placebo followed by lithium in an A-B-A-B design in which the patient served as his own control. Five patients (14 per cent) improved dramatically; in retrospect, four of these five patients suffered from nonremitting forms of manic-depressive illness, and the fifth patient suffered from a severe obsessive compulsive neurosis. Six other chronically hospitalized patients improved to the point of unexpected discharge. A trial of lithium therapy is recommended for the "backward" or intractable patient.