Julio Vallejo

Met66 in the brain-derived neurotrophic factor (BDNF) precursor is associated with anorexia nervosa restrictive type

Several lines of evidence support a role for brain-derived neurotrophic factor (BDNF) alterations in the etiology of eating disorders (EDs). BDNF heterozygous knockout mice show alterations in eating behavior, increased body weight and adipocyte hypertrophy. BDNF also regulates the synaptic efficiency through the modulation of key neurotransmitter systems previously known to be involved in ED. These findings, together with the fact that this neurotrophin is expressed in the hypothalamus nuclei associated with weight regulation and feeding control, led us to propose BDNF as a candidate gene for ED. To investigate the possible involvement of this neurotrophin in eating behavior, we screened the BDNF gene in 95 ED patients and identified four sequence variants. Two of them, −374A/T and −256G/A, were found in two patients with anorexia nervosa (AN) and consisted of single-nucleotide mutations within the 5′ untranslated region (5′UTR). The other two polymorphisms resulted in a C to T transition located at the 5′UTR of the BDNF gene and an amino-acid substitution within the BDNF precursor protein (Val66Met). We performed a case–control study for these two Single-nucleotide polymorphisms in a sample of 143 ED patients and 112 unrelated controls and found a strong association of restricting AN (ANR) with the Met allele of the Val66Met BDNF polymorphism (2p=0.002). There was also evidence for a significant effect of this sequence variant on the minimum body mass index (MBMI) (2p=0.006). These results suggest that the BDNF Met66 variant may be a susceptibility factor to ED, mainly to ANR and low MBMI.

A brain-derived neurotrophic factor (BDNF) haplotype is associated with antidepressant treatment outcome in mood disorders.

Brain-derived neurotrophic factor (BDNF) has been studied extensively in relation to the susceptibility to mood disorders (MD), although it remains to be clarified whether BDNF is a susceptibility locus for MD phenotypes, including therapeutic response to antidepressants. We have performed a single-marker and haplotype association study of eight TagSNPs polymorphisms in the genomic region containing the BDNF gene in 342 control subjects and 374 patients with MD, and have tested the association with antidepressant treatment outcome. None of the eight single nucleotide polymorphisms (TagSNPs) was significantly associated with MD phenotype after Bonferroni correction. In the single-marker analysis, a SNP was found to be associated with the patients state of ‘remitter’ after adequate trial with a single antidepressant phenotype (odds ratio (OR)=2.95; P=0.0025). We also identified a haplotype associated with this phenotype. This study supports the implication of BDNF in antidepressant treatment outcome in MD, with specific association with 5′ upstream region of BDNF gene.

High sensitivity to punishment and low impulsivity in obsessive-compulsive patients with hoarding symptoms

Recent factor-analytic studies involving over 2000 patients have reduced the symptoms of obsessive-compulsive disorder (OCD) into a few dimensions or potentially overlapping syndromes. Hoarding consistently emerged as a separate factor in all these studies. This study investigated the relationship between OCD symptom dimensions and normal personality traits in a sample of 56 OCD patients. They were administered the Sensitivity to Punishment and Sensitivity to Reward Questionnaire and the Eysenck Personality Questionnaire, derived from Grays and Eysencks personality models, respectively. The personality scores were correlated with previously identified symptom dimensions from the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist (Y-BOCS-SC), controlling for overall illness severity. High scores on the hoarding dimension of the Y-BOCS-SC were positively correlated with scores on the Sensitivity to Punishment scale and negatively with Eysencks Psychoticism scale. While high sensitivity to punishment is a personality feature common to many OCD patients, it is more strongly pronounced in patients with hoarding symptoms. These patients also appear to be less impulsive or novelty seeking as reflected by low scores on Eysencks Psychoticism scale. High sensitivity to punishment and low novelty seeking in OCD hoarders might explain their poor compliance and response to conventional treatments, but this question needs to be explored further in a prospective treatment study.

Reliability, Validity, and Classification Accuracy of a Spanish Translation of a Measure of DSM-IV Diagnostic Criteria for Pathological Gambling

The aim of this study was to measure the reliability, validity, and classification accuracy of a Spanish translation of a measure of DSM-IV diagnostic criteria for Pathological Gambling (PG). Participants were 263 male and 23 female patients seeking treatment for PG and a matched non-psychiatric control sample of 259 men and 24 women. A Spanish translation of a 19-item measure of DSM-IV diagnostic criteria for PG (Stinchfield 2003) was administered along with other validity measures. The DSM-IV diagnostic criteria were found to be internally consistent with a coefficient alpha of .95 in the combined sample. Evidence of satisfactory convergent validity included moderate to high correlations with other measures of problem gambling. Using the standard DSM-IV cut-score of five, the ten criteria were found to yield satisfactory classification accuracy results with a high hit rate (.95), high sensitivity (.92), high specificity (.99), low false positive (.01), and low false negative rate (.08). Lowering the cut score to four resulted in modest improvements in classification accuracy and reduced the false negative rate from .08 to .05. The Spanish translation of a measure of DSM-IV diagnostic criteria for PG demonstrated satisfactory psychometric properties and a cut score of four improved diagnostic precision.

Personality characteristics in obsessive-compulsive disorder and individuals with subclinical obsessive-compulsive problems

OBJECTIVE To assess the relationship between normal personality traits and obsessive-compulsive (OC) phenomena in individuals with subclinical OC problems and patients whose problems met diagnostic criteria for obsessive-compulsive disorder (OCD). METHOD In Study 1, 25 healthy volunteers with high scores on the Padua Inventory (PI) and 28 controls with low scores on the PI were compared on the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), the Eysenck Personality Questionnaire (EPQ), and measures of depression and state anxiety. In Study 2, 56 treatment-seeking participants meeting DSM-IV criteria for OCD and 40 healthy volunteers of similar sociodemographic characteristics were compared on the same measures. RESULTS Both individuals with subclinical OC problems and OCD patients scored significantly higher than their respective control groups on sensitivity to punishment, neuroticism and psychoticism. OCD patients, but not individuals with subclinical OC problems, scored lower in extraversion than their respective controls. Neuroticism was the strongest predictor of high scores on the PI in Study 1, while psychoticism was the strongest predictor of the presence of an OCD diagnosis in Study 2. CONCLUSION Healthy participants with high scores on OC measures and OCD patients share various personality traits but can also be distinguished according to the level of extraversion, neuroticism and psychoticism.

Contribution of NTRK2 to the genetic susceptibility to anorexia nervosa, harm avoidance and minimum body mass index.

Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders (ED) with complex genetic and environmental components. Genetic studies and animal models support the participation of brain-derived neurotrophic factor (BDNF) in the vulnerability to AN and BN. We investigated the genetic contribution of the BDNF-specific receptor neurotrophic tyrosine kinase receptor type 2 (NTRK2) to the susceptibility to ED. We have screened the entire NTRK2 gene in 91 patients with ED and have identified 14 single-nucleotide polymorphisms (SNPs). A population-based association study with six SNPs from the NTRK2 locus was performed in 164 ED patients and 121 controls. Significant evidence of association for markers –69C>G and IVS13+40G>A was detected. We also observed a strong association between the C-A-insC haplotype (–69/IVS13+40/2784–2785) and binge-eating/purging AN (ANP, P=0.006; OR=2.27), and a reduced frequency of haplotype G-A-delCl in BN patients (P=0.034; OR=0.6). The analysis of ED-related phenotypes revealed a clear association between NTRK2, high scores of Harm avoidance measured by the temperament and character inventory (TCI-R; P=0.003) and minimum body mass index (minBMI; P<0.001). Our data support a contribution of NTRK2 to the genetic susceptibility of ED, mainly ANP, and ED-related phenotypic traits, such as Harm avoidance and minBMI.

Convergent and discriminant validity of the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist

Background: The factor structure of the Yale-Brown Obsessive-Compulsive Scale Symptom Checklist (Y-BOCS-SC) has been well established, but its convergent and divergent reliability have yet to be studied. Methods: Fifty-six obsessive-compulsive disorder (OCD) patients were administered the clinician-administered Y-BOCS-SC and Hamilton Rating Scale for Depression (HRSD), together with the self-administered Maudsley Obsessive Compulsive Inventory (MOCI), Padua Inventory (PI), State-Trait Anxiety Inventory (STAI), and Beck Depression Inventory (BDI). Results: Overall, the correspondence between the Y-BOCS-SC and self-administered measures of OCD symptoms was poor to moderate. Its convergent validity was adequate for its washing dimension but poor for its other dimensions. The discriminant validity of the Y-BOCS-SC was adequate, showing little overlap with overall illness severity (total Y-BOCS) and state measures (BDI, STAI, HRSD). In contrast, self-administered OCD measures were significantly correlated with overall illness severity and state measures. Conclusions: The convergent validity of the Y-BOCS-SC was generally poor and this could only be partially explained by the incomplete coverage of some OCD symptoms in the self-administered scales. Its discriminant validity was good. Both self- and clinician-administered measures should be used in OCD research, as they seem to measure relatively non-overlapping constructs. Further research on the psychometric properties of the Y-BOCS-SC is needed.

Genetic susceptibility to obsessive-compulsive hoarding: the contribution of neurotrophic tyrosine kinase receptor type 3 gene1

Recent work suggests that neurotrophic factors may contribute to the genetic susceptibility to obsessive–compulsive disorder (OCD). Among other clinical dimensions, the presence of hoarding obsessions and compulsions has been shown to be correlated with a number of clinical and neuroimaging findings, as well as with a different pattern of genetic inheritance. We used a linkage disequilibrium (LD)‐mapping approach to investigate whether neurotrophic tyrosine kinase receptor type 3 (NTRK3), the high‐affinity receptor of neurotrophin 3 (NT‐3), plays a role in increasing susceptibility to hoarding in OCD. We performed an association study of 52 tag single nucleotide polymorphisms (tagSNPs) covering the whole NTRK3 gene in a sample comprising 120 OCD patients and 342 controls. Single nucleotide polymorphism association and haplotype analysis were performed. Thirty‐six of our patients (30%) exhibited significant hoarding obsessions and compulsions. A significant association of two SNPs in the 3′ downstream region of NTRK3 gene and obsessive–compulsive hoarding was identified: rs1017412 [odds ratio (OR) = 2.16; P = 0.001] and rs7176429 (OR = 2.78; P = 0.0001), although only the latter remained significant after Bonferroni correction. Although the haplotype analysis did not show significant results, a more extended block of LD in the OCD hoarders with respect to the control group was observed, suggesting a lower haplotype diversity in these individuals. Our findings suggest that NTRK3 may contribute to the genetic susceptibility to hoarding in OCD and may constitute an interesting gene to focus on in studies of the genetic basis of obsessive–compulsive hoarding.

Marital status and eating disorders: An analysis of its relevance

OBJECTIVES This study attempts to understand the clinical impact of marital status on the psychopathology and symptomatology of anorexia (AN) and bulimia nervosa (BN) patients. METHOD Eating disorder (ED) patients (n=332, 198 BN and 134 AN) consecutively admitted to our unit participated in the study. All subjects met DSM-IV criteria for those pathologies and were female. Our sample was divided retrospectively into three subgroups based on their marital status. For the assessment, commonly applied questionnaires in the field of ED were used [Eating Attitudes Test (EAT-40), Eating Disorder Inventory (EDI), Bulimic Investigatory Test Edinburgh (BITE), Body Shape Questionnaire (BSQ), Beck Depression Inventory (BDI) and Social Avoidance and Distress Scale (SAD)]. RESULTS 2 x 3 (Diagnostic x Marital status) ANOVA and ANCOVA (with age as covariance) designs were applied in the current study. Our results suggested that ED patients who lived with a partner were significantly different with respect to the other ED patients in the following variables: higher age (P<.0001), higher motivation for change (P<.004), perfectionism (P<.03) and purging behavior (P<.04). DISCUSSION The main finding in this study is that ED patients who live with a partner are those who presented greater eating symptomatology and psychopathology but even higher motivation for change. Interpersonal functionality has to be considered in the development and maintenance of ED.

Individual versus group cognitive–behavioral treatment for obsessive–compulsive disorder: a controlled pilot study

Abstract This study sought to examine the effectiveness of group and individual cognitive–behavioral treatment (CBT) and to compare the results with those of a wait-list control group among a sample of patients with obsessive–compulsive disorder (OCD). Fifty-seven individuals diagnosed with OCD were evaluated pre- and posttreatment with the Yale-Brown Obsessive Compulsive Scale and the Hamilton Rating Scales for Anxiety and Depression. Both group and individual CBT obtained statistically significant reductions in anxiety and depressive symptoms. Patients in individual treatment achieved a statistically significant reduction in OCD symptoms compared with those in group treatment, but their dropout rate was twice as high. Patients with symmetry and order rituals presented less improvement in anxiety symptoms than those with other rituals. Associated general symptoms were lower in patients receiving either mode of CBT compared with wait-list participants. The authors found that individual treatment is more effective in reducing obsessive–compulsive symptoms than group treatment.