Fernando Fernández-Aranda

Association of BDNF with restricting anorexia nervosa and minimum body mass index: a family-based association study of eight European populations

Eating disorders (ED), such as anorexia nervosa (AN) and bulimia nervosa (BN), are complex psychiatric disorders where different genetic and environmental factors are involved. Several lines of evidence support that brain-derived neurotrophic factor (BDNF) plays an essential role in eating behaviour and that alterations on this neurotrophic system participates in the susceptibility to both AN and BN. Accordingly, intraventricular administration of BDNF in rats determines food starvation and body weight loss, while BDNF or its specific receptor NTRK2 knockout mice develop obesity and hyperphagia. Case–control studies also suggest a BDNF contribution in the aetiology of ED: we have previously reported a strong association between the Met66 variant within the BDNF gene, restricting AN (ANR) and minimum body mass index (minBMI) in a Spanish sample, and a positive association between the Val66Met and −270C/T BDNF SNPs and ED in six different European populations. To replicate these results, avoiding population stratification effects, we recruited 453 ED trios from eight European centres and performed a family-based association study. Both haplotype relative risk (HRR) and haplotype-based haplotype relative risk (HHRR) methods showed a positive association between the Met66 allele and ANR. Consistently, we also observed an effect of the Met66 variant on low minBMI and a preferential transmission of the −270C/Met66 haplotype to the affected ANR offspring. These results support the involvement of BDNF in eating behaviour and further suggest its participation in the genetic susceptibility to ED, mainly ANR and low minBMI.

Video games as a complementary therapy tool in mental disorders: PlayMancer, a European multicentre study

Background Previous review studies have suggested that computer games can serve as an alternative or additional form of treatment in several areas (schizophrenia, asthma or motor rehabilitation). Although several naturalistic studies have been conducted showing the usefulness of serious video games in the treatment of some abnormal behaviours, there is a lack of serious games specially designed for treating mental disorders. Aim The purpose of our project was to develop and evaluate a serious video game designed to remediate attitudinal, behavioural and emotional processes of patients with impulse-related disorders. Method and results The video game was created and developed within the European research project PlayMancer. It aims to prove potential capacity to change underlying attitudinal, behavioural and emotional processes of patients with impulse-related disorders. New interaction modes were provided by newly developed components, such as emotion recognition from speech, face and physiological reactions, while specific impulsive reactions were elicited. The video game uses biofeedback for helping patients to learn relaxation skills, acquire better self-control strategies and develop new emotional regulation strategies. In this article, we present a description of the video game used, rationale, user requirements, usability and preliminary data, in several mental disorders.

Executive functions profile in extreme eating/weight conditions: from anorexia nervosa to obesity

Background Extreme weight conditions (EWC) groups along a continuum may share some biological risk factors and intermediate neurocognitive phenotypes. A core cognitive trait in EWC appears to be executive dysfunction, with a focus on decision making, response inhibition and cognitive flexibility. Differences between individuals in these areas are likely to contribute to the differences in vulnerability to EWC. The aim of the study was to investigate whether there is a common pattern of executive dysfunction in EWC while comparing anorexia nervosa patients (AN), obese subjects (OB) and healthy eating/weight controls (HC). Methods Thirty five AN patients, fifty two OB and one hundred thirty seven HC were compared using the Wisconsin Card Sorting Test (WCST); Stroop Color and Word Test (SCWT); and Iowa Gambling Task (IGT). All participants were female, aged between 18 and 60 years. Results There was a significant difference in IGT score (F(1.79); p<.001), with AN and OB groups showing the poorest performance compared to HC. On the WCST, AN and OB made significantly more errors than controls (F(25.73); p<.001), and had significantly fewer correct responses (F(2.71); p<.001). Post hoc analysis revealed that the two clinical groups were not significantly different from each other. Finally, OB showed a significant reduced performance in the inhibition response measured with the Stroop test (F(5.11); p<.001) compared with both AN and HC. Conclusions These findings suggest that EWC subjects (namely AN and OB) have similar dysfunctional executive profile that may play a role in the development and maintenance of such disorders.

Impulse control disorders in women with eating disorders.

We compared symptom patterns, severity of illness, and comorbidity in individuals with eating disorders with and without impulse control disorders (ICD), and documented the temporal pattern of illness onset. Lifetime ICD were present in 16.6% of 709 women with a history of eating disorders. The most common syndromes were compulsive buying disorder and kleptomania. ICD occurred more in individuals with binge eating subtypes, and were associated with significantly greater use of laxatives, diuretics, appetite suppressants and fasting, and with greater body image disturbance, higher harm avoidance, neuroticism, cognitive impulsivity, and lower self-directedness. In addition, individuals with ICD were more likely to have obsessive-compulsive disorder, any anxiety disorder, specific phobia, depression, cluster B personality disorder, avoidant personality disorder, and to use psychoactive substances. Among those with ICD, 62% reported the ICD predated the eating disorder and 45% reported the onset of both disorders within the same 3-year window. The presence of a lifetime ICD appears to be limited to eating disorders marked by binge eating and to be associated with worse eating-related psychopathology, more pathological personality traits, and more frequent comorbid Axis I and II conditions. Untreated ICD may complicate recovery from eating disorders.

Lifetime obesity in patients with eating disorders: increasing prevalence, clinical and personality correlates

Objectives : The aims of our study were to examine the lifetime prevalence of obesity rate in eating disorders (ED) subtypes and to examine whether there have been temporal changes among the last 10 years and to explore clinical differences between ED with and without lifetime obesity. Methods : Participants were 1383 ED female patients (DSM-IV criteria) consecutively admitted, between 2001 and 2010, to Bellvitge University Hospital. They were assessed by means of the Eating Disorders Inventory-2, the Symptom Checklist-90—Revised, the Bulimic Investigatory Test Edinburgh and the Temperament and Character Inventory—Revised. Results : The prevalence of lifetime obesity in ED cases was 28.8% (ranging from 5% in anorexia nervosa to 87% in binge-eating disorders). Over the last 10 years, there has been a threefold increase in lifetime obesity in ED patients (p < .001). People with an ED and obesity had higher levels of childhood and family obesity (p < .001), a later age of onset and longer ED duration; and had higher levels of eating, general and personality symptomatology. Conclusions : Over the last 10 years, the prevalence of obesity associated with disorders characterized by the presence of binge episodes, namely bulimic disorders, is increasing, and this is linked with greater clinical severity and a poorer prognosis. Copyright

Systematic review and meta-analysis of prevalence studies in transsexualism.

BACKGROUND Over the last 50 years, several studies have provided estimates of the prevalence of transsexualism. The variation in reported prevalence is considerable and may be explained by factors such as the methodology and diagnostic classification used and the year and country in which the studies took place. Taking these into consideration, this study aimed to critically and systematically review the available literature measuring the prevalence of transsexualism as well as performing a meta-analysis using the available data. METHODS Databases were systematically searched and 1473 possible studies were identified. After initial scrutiny of the article titles and removal of those not relevant, 250 studies were selected for further appraisal. Of these, 211 were excluded after reading the abstracts and a further 18 after reading the full article. This resulted in 21 studies on which to perform a systematic review, with only 12 having sufficient data for meta-analysis. The primary data of the epidemiological studies were extracted as raw numbers. An aggregate effect size, weighted by sample size, was computed to provide an overall effect size across the studies. Risk ratios and 95% confidence intervals (CIs) were calculated. The relative weighted contribution of each study was also assessed. RESULTS The overall meta-analytical prevalence for transsexualism was 4.6 in 100,000 individuals; 6.8 for trans women and 2.6 for trans men. Time analysis found an increase in reported prevalence over the last 50 years. CONCLUSIONS The overall prevalence of transsexualism reported in the literature is increasing. However, it is still very low and is mainly based on individuals attending clinical services and so does not provide an overall picture of prevalence in the general population. However, this study should be considered as a starting point and the field would benefit from more rigorous epidemiological studies acknowledging current changes in the classification system and including different locations worldwide.

Identification of new putative susceptibility genes for several psychiatric disorders by association analysis of regulatory and non-synonymous SNPs of 306 genes involved in neurotransmission and neurodevelopment†‡

A fundamental difficulty in human genetics research is the identification of the spectrum of genetic variants that contribute to the susceptibility to common/complex disorders. We tested here the hypothesis that functional genetic variants may confer susceptibility to several related common disorders. We analyzed five main psychiatric diagnostic categories (substance‐abuse, anxiety, eating, psychotic, and mood disorders) and two different control groups, representing a total of 3,214 samples, for 748 promoter and non‐synonymous single nucleotide polymorphisms (SNPs) at 306 genes involved in neurotransmission and/or neurodevelopment. We identified strong associations to individual disorders, such as growth hormone releasing hormone (GHRH) with anxiety disorders, prolactin regulatory element (PREB) with eating disorders, ionotropic kainate glutamate receptor 5 (GRIK5) with bipolar disorder and several SNPs associated to several disorders, that may represent individual and related disease susceptibility factors. Remarkably, a functional SNP, rs945032, located in the promoter region of the bradykinin receptor B2 gene (BDKRB2) was associated to three disorders (panic disorder, substance abuse, and bipolar disorder), and two additional BDKRB2 SNPs to obsessive‐compulsive disorder and major depression, providing evidence for common variants of susceptibility to several related psychiatric disorders. The association of BDKRB2 (odd ratios between 1.65 and 3.06) to several psychiatric disorders supports the view that a common genetic variant could confer susceptibility to clinically related phenotypes, and defines a new functional hint in the pathophysiology of psychiatric diseases.

Association of Irisin with Fat Mass, Resting Energy Expenditure, and Daily Activity in Conditions of Extreme Body Mass Index

FNDC5/irisin has been recently postulated as beneficial in the treatment of obesity and diabetes because it is induced in muscle by exercise, increasing energy expenditure. However, recent reports have shown that WAT also secretes irisin and that circulating irisin is elevated in obese subjects. The aim of this study was to evaluate irisin levels in conditions of extreme BMI and its correlation with basal metabolism and daily activity. The study involved 145 female patients, including 96 with extreme BMIs (30 anorexic (AN) and 66 obese (OB)) and 49 healthy normal weight (NW). The plasma irisin levels were significantly elevated in the OB patients compared with the AN and NW patients. Irisin also correlated positively with body weight, BMI, and fat mass. The OB patients exhibited the highest REE and higher daily physical activity compared with the AN patients but lower activity compared with the NW patients. The irisin levels were inversely correlated with daily physical activity and directly correlated with REE. Fat mass contributed to most of the variability of the irisin plasma levels independently of the other studied parameters. Conclusion. Irisin levels are influenced by energy expenditure independently of daily physical activity but fat mass is the main contributing factor.

Internet-based cognitive-behavioral therapy for bulimia nervosa: a controlled study.

The object of this study was to examine the effectiveness of an Internet-based therapy (IBT) for bulimia nervosa (BN) as compared to a waiting list (WL). Sixty-two female BN patients, diagnosed according to DSM-IV criteria, were assigned to either the IBT or a WL. The control participants (WL) were matched to the IBT group in terms of age, duration of the disorder, number of previous treatments, and severity of the disorder. Assessment measures included the EDI, SCL-90-R, BITE, the TCI-R, and other clinical and psychopathological indices, which were administrated before and after the treatment. Considering the IBT, while the mean scores were lower at the end of the treatment for some EDI scales (bulimic, interpersonal distrust, maturity fears, and total score) and the BITE symptomatology subscale, the mean BMI was higher at posttherapy. Predictors of good IBT outcome were higher scores on the EDI perfectionism scale and EAT and a higher minimum BMI. Drop-out (after IBT 35.5% of cases) was related to higher SCL-anxiety scores, a lower hyperactivity, a lower minimum BMI, and lower TCI-reward dependence scores. At the end of the treatment, bingeing and vomiting abstinence rates differed significantly between the two groups. Results suggest that an online self-help approach appears to be a valid treatment option for BN when compared to a WL control group, especially for people who present a lower severity of their eating disorder (ED) symptomatology and some specific personality traits.

Altered brain-derived neurotrophic factor blood levels and gene variability are associated with anorexia and bulimia

Murine models and association studies in eating disorder (ED) patients have shown a role for the brain‐derived neurotrophic factor (BDNF) in eating behavior. Some studies have shown association of BDNF −270C/T single‐nucleotide polymorphism (SNP) with bulimia nervosa (BN), while BDNF Val66Met variant has been shown to be associated with both BN and anorexia nervosa (AN). To further test the role of this neurotrophin in humans, we screened 36 SNPs in the BDNF gene and tested for their association with ED and plasma BDNF levels as a quantitative trait. We performed a family‐based association study in 106 ED nuclear families and analyzed BDNF blood levels in 110 ED patients and in 50 sib pairs discordant for ED. The rs7124442T/rs11030102C/rs11030119G haplotype was found associated with high BDNF levels (mean BDNF TCG haplotype carriers = 43.6 ng/ml vs. mean others 23.0 ng/ml, P = 0.016) and BN (Z = 2.64; P recessive = 0.008), and the rs7934165A/270T haplotype was associated with AN (Z =−2.64; P additive = 0.008). The comparison of BDNF levels in 50 ED discordant sib pairs showed elevated plasma BDNF levels for the ED group (mean controls = 41.0 vs. mean ED = 52.7; P = 0.004). Our data strongly suggest that altered BDNF levels modulated by BDNF gene variability are associated with the susceptibility to ED, providing physiological evidence that BDNF plays a role in the development of AN and BN, and strongly arguing for its involvement in eating behavior and body weight regulation.