Daniela Degortes

Set-shifting abilities, central coherence, and handedness in anorexia nervosa patients, their unaffected siblings and healthy controls: Exploring putative endophenotypes

Abstract Objective. There is consistent evidence that anorexia nervosa (AN) is associated with an impairment of set-shifting abilities and central coherence. No study to date investigated handedness in AN. Our aim was to study set-shifting abilities, central coherence, and handedness in subjects with lifetime AN, in a sample of unaffected sisters and in healthy controls, in order to explore their suitability as endophenotypes of AN. Methods. The Edinburgh Handedness Inventory and several neuropsychological tasks (Wisconsin Card Sorting Test, Trail Making Test, Rey-Osterrieth Complex Figure Test, Overlapping Figures Test, Object Assembly and Block Design) were administered to 153 subjects with lifetime AN, 28 unaffected sisters and 120 healthy controls. Results. AN subjects and their healthy sisters showed poorer performances on most tasks investigating set-shifting and central coherence. In addition, we did not find any differences between long-term recovered subjects, weight-restored AN patients and those in an acute phase of their illness. AN subjects were significantly more likely to be left-handed than healthy controls (OR=2.8, 95% C.I. 1.1–7.2). Conclusions. Set-shifting and central coherence seem to be promising cognitive endophenotypes that might help in the understanding of the pathogenetic processes involved in AN. Further studies on larger samples are needed to explore the generalizability and implications of our findings concerning handedness.

The Relationship Between Temperament and Impulsive Behaviors in Eating Disordered Subjects

To date, few studies have examined the personality characteristics and clinical predictors of impulsive behaviors in eating disorders (ED). The aim of this work was to study the prevalence of a wide range of impulsive behaviors in a sample of 554 ED subjects and to examine the predictors of these behaviors. Subjects were diagnosed according to DSM-IV criteria as having anorexia nervosa restricting type (ANR; n = 183), anorexia nervosa binge eating/purging type (ANBP; n = 65), bulimia nervosa purging type (BNP; n = 244), and bulimia nervosa nonpurging type (BNNP; n = 62). Nine different types of impulsive behaviors were assessed in these groups. About 55% of the whole sample reported at least one type of impulsive behavior, 35% more than one, and about 13% more than three. According to findings, impulsive and multi-impulsive subjects are characterized by the presence of purging behavior and by specific temperamental features such as high levels of novelty seeking and low persistence. The prediction of impulsive behavior is further improved by considering the presence of a history of childhood abuse, maternal psychiatric morbidity, and some specific psychological symptoms such as maturity fears, perfectionism, depression, and obsessive-compulsive symptoms. The presence of impulsive behavior appears to be associated with overall higher levels of psychiatric symptomatology and eating psychopathology, thus indicating that they are an important feature to be considered in the assessment and treatment of ED.

Typical and atypical restrictive anorexia nervosa: weight history, body image, psychiatric symptoms, and response to outpatient treatment.

OBJECTIVE Few studies have examined the characteristics of atypical restrictive anorexia nervosa (AN) with a well-powered design. The study aims to explore this issue, with particular attention paid to psychopathology and response to outpatient treatment. METHOD The sample consists of 365 participants with restrictive AN and 204 with atypical AN. Three types of atypical AN were included: subthreshold (all the criteria except weight); partial (AN without amenorrhea); and participants with AN without fear of gaining weight. RESULTS Participants with AN without fear of weight gain reported the lowest lifetime BMI and subthreshold AN the highest. Participant with partial AN reported the highest levels of psychiatric symptoms and novelty seeking. All types of atypical AN showed high rates of dropout, whereas participants with subthreshold AN showed the highest level of full remission after treatment. DISCUSSION Before considering a revision of the diagnostic criteria of AN, further studies on adequately large samples are needed.

Clinical and temperamental correlates of body image disturbance in eating disorders.

OBJECTIVE Although body image disturbance (BID) is considered a core symptom in anorexia nervosa (AN) and bulimia nervosa (BN), little is known about its psychopathological correlates. The present study aimed at analysing the correlation of aspects of BID with psychopathological and temperamental characteristics. METHOD A sample of 1288 patients (538 AN and 750 BN) were assessed through a structured diagnostic interview, the Eating Disorders Inventory and Tridimensional Personality Questionnaire. Cognition of body image distortion, weight checking, fear of weight gain and body dissatisfaction were assessed by specific questions during the interview. RESULTS Various aspects of BID formed similar, but not identical, dimensions in AN and BN. In both groups, anticipatory anxiety and interoceptive awareness were significantly and independently associated with body image distortion, whereas ineffectiveness was associated with weight checking. DISCUSSION Body image disturbance is a multidimensional characteristic linked to psychological features, such as anticipatory anxiety, ineffectiveness and interoceptive awareness. These findings have scientific and treatment implications, and should be considered by clinicians in adopting successful treatment strategies.

The effects of trauma among kidnap victims in Sardinia, Italy

BACKGROUND No study to date has investigated the effects of the trauma of being kidnapped for ransom. In the present study, we aimed to assess the general health status and the presence of post-traumatic stress disorder (PTSD) and major depression (MDD) in a sample of kidnap victims. We also focused attention on dissociative experiences and on the development of the Stockholm syndrome during captivity. METHODS We investigated the traumatic experiences and reported general health status of 24 kidnap victims using a semistructured interview. The Structured Clinical Interview for DSM-IV was used to assess the presence of PTSD and MDD. The Dissociative Experiences Scale was also administered. RESULTS The lifetime frequency of PTSD and MDD were 45.9% and 37.5% respectively. The Stockholm syndrome had been present in 50% of the sample during captivity. The presence of PTSD can be predicted by the number of violent experiences, whereas the number of humiliating or deprivation experiences predicts the development of the Stockholm syndrome. Subjects with both PTSD and the Stockholm syndrome reported a greater number of physical complaints at the interview. CONCLUSIONS There is no significant connection between PTSD and the Stockholm syndrome. Both are indices of the severity of the trauma of being kidnapped, but they are associated with different aspects of the traumatic experience. The presence of both syndromes appears to have a detrimental effect on physical health.

Catechol-O-methyltransferase genotype modifies executive functioning and prefrontal functional connectivity in women with anorexia nervosa

BACKGROUND Anorexia nervosa is characterized by high levels of perseveration and inflexibility, which interfere with successful treatments. Dopamine (DA) signalling seems to play a key role in modulating the prefrontal cortex, since both DA deficiency and excess nega tively influence the efficiency of cognitive functions. The present study explores the effect of a functional polymorphism (Val158Met) in the catechol-O-methyltransferase (COMT) gene on the set-shifting abilities and prefrontal functional connectivity of patients with anorexia nervosa. METHODS All participants performed the Wisconsin Card Sorting Task, and a subsample underwent resting-state functional magnetic resonance imaging. RESULTS We included 166 patients with DSM-IV lifetime anorexia nervosa and 140 healthy women in our study. Both underweight and weight-recovered patients with anorexia nervosa showed high levels of perseveration, but only in the underweight group did the Val158Met polymorphism affect cognitive performance, showing the U-shaped curve characteristic of increased DA signalling in the prefrontal cortex. Underweight patients with anorexia nervosa who are Met homozygotes had significantly higher levels of perseveration and increased prefrontal functional connectivity than underweight patients in the other genotype groups, indicating abnormal regional cortical processing. LIMITATIONS Although our data show that grey matter reduction in starving patients with anorexia nervosa did not explain our findings, the cross-sectional design of the present study did not allow us to distinguish between the effects of starvation and those of low estrogen levels. CONCLUSION Starvation affects DA release in the prefrontal cortex of patients with anorexia nervosa with different effects on executive functioning and prefrontal functional connectivity according to the COMT genotype. This observation has several therapeutic implications that need to be addressed by future studies.

Perinatal complications in unaffected sisters of anorexia nervosa patients: testing a covariation model between genetic and environmental factors

Although perinatal complications are hypothesized to be risk factors for the development of anorexia nervosa (AN), no study to date explored this issue using a discordant sibling design. This type of design allows to explore whether the risk for obstetric complications is itself a consequence of the genetic vulnerability for AN (covariation model) or whether obstetric complications increase the risk of AN independently of (additive model), or in interaction with (interaction model), the disorder’s genetic liability. The presence of perinatal complications was assessed through review of the obstetric records of 60 AN subjects, 60 unaffected sisters, and 70 healthy subjects. Unaffected sisters and healthy controls were compared in relation to perinatal characteristics and complications. There was no evidence for an elevated rate of complications in unaffected siblings of AN patients. Mothers with a positive psychiatric history tended to have more perinatal complications. Perinatal complications seem to be independent risk factors that may interact with, but are not caused by, familial risk factors for AN. In terms of prevention, a particular attention should be paid to mothers with a lifetime history of psychiatric disorders.

Functional connectivity correlates of response inhibition impairment in anorexia nervosa

Anorexia nervosa (AN) is a disorder characterized by high levels of cognitive control and behavioral perseveration. The present study aims at exploring inhibitory control abilities and their functional connectivity correlates in patients with AN. Inhibitory control - an executive function that allows the realization of adaptive behavior according to environmental contingencies - has been assessed by means of the Stop-Signal paradigm. The study involved 155 patients with lifetime AN and 102 healthy women. A subsample underwent resting-state functional magnetic resonance imaging and was genotyped for COMT and 5-HTTLPR polymorphisms. AN patients showed an impaired response inhibition and a disruption of the functional connectivity of the ventral attention circuit, a neural network implicated in behavioral response when a stimulus occurs unexpected. The 5-HTTLPR genotype appears to significantly interact with the functional connectivity of ventral attention network in explaining task performance in both patients and controls, suggesting a role of the serotoninergic system in mechanisms of response selection. The disruption of the ventral attention network in patients with AN suggests lower efficiency of bottom-up signal filtering, which might be involved in difficulties to adapt behavioral responses to environmental needs. Our findings deserve further research to confirm their scientific and therapeutic implications.

Neural signatures of the interaction between the 5-HTTLPR genotype and stressful life events in healthy women

A change in neural connectivity of brain structures implicated in the memory of negative life events has been hypothesized to explain the enhancement of memory encoding during the processing of negative stimuli in depressed patients. Here, we investigated the effects of the interaction between negative life events and the 5-HTTLPR genotype - a polymorphism of the serotonin transporter gene - on the functional and structural connectivity of the hippocampal area in 34 healthy women. All participants were genotyped for the presence of the 5-HTTLPR short variant and for the A/G single-nucleotide polymorphism; they underwent clinical assessment including structured diagnostic interviews to exclude the presence of psychiatric disorders and to assess the presence of stressful life events. Resting state functional magnetic resonance imaging and diffusion tensor imaging scans were performed. We found significant interactions between stressful events and the 5-HTTLPR genotype in both the functional connectivity of the parahippocampus with the posterior cingulate cortex and the structural connectivity between the hippocampus and both the amygdala and the putamen. In addition, we found several genotype-related differences in the relationship between functional/structural connectivity of the hippocampal area and the ability to update expectations or stress-related phenotypes, such as anxiety symptoms. If confirmed by future studies, these mechanisms may clarify the role of the 5HTTLPR genotype as a risk factor for depression, in interaction with negative events.

Effects of obstetric complications on volume and functional connectivity of striatum in anorexia nervosa patients

OBJECTIVE To investigate the volume and functional connectivity of dorsal and ventral striatal nuclei in anorexia nervosa (AN) and their relationship with early exposure to obstetric complications. METHOD Fifty-one patients with lifetime AN (35 acute, 16 recovered) and 34 healthy controls underwent high-resolution and resting-state functional magnetic resonance imaging. RESULTS The AN group showed reduced functional connectivity of the putamen compared with healthy women, and this reduction was more evident in patients with lifetime binge eating/purging. Both acute and recovered AN groups showed a larger left accumbens area compared with that of healthy women. The functional connectivity of bilateral nucleus accumbens and putamen showed significant negative correlations with number of obstetric complications in the AN group. DISCUSSION This study supports the hypothesis that AN is associated with structural and functional alterations of striatal networks, and reveals the possible role of obstetric complications in the pathogenesis of striatal dysfunction.