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.

Disruption of visuospatial and somatosensory functional connectivity in anorexia nervosa.

BACKGROUND: Although body image disturbance is considered one of the core characteristics of anorexia nervosa (AN), the exact nature of this complex feature is poorly understood. Task-related functional magnetic resonance imaging studies can only partially explore the multimodal complexity of body consciousness, which is a complex cognition underpinned by aspects of visual perception, proprioception, and touch. The aim of the present study was to explore the functional connectivity of networks involved in visuospatial and somatosensory processing in AN. METHODS: Twenty-nine subjects with AN, 16 women who had recovered from it, and 26 healthy women underwent a resting-state functional magnetic resonance imaging scan and neuropsychological assessment of their visuospatial abilities using the Rey-Osterrieth Complex Figure Test. RESULTS: Both AN groups showed areas of decreased connectivity in the ventral visual network, a network involved in the "what?" pathway of visual perception. Even more interestingly, the AN group, but not the recovered AN group, displayed increased coactivation in the left parietal cortex, encompassing the somatosensory cortex, in an area implicated in long-term multimodal spatial memory and representation, even in the absence of visual information. A neuropsychological assessment of visuospatial abilities revealed that aspects of detail processing and global integration (central coherence) showed correlations with connectivity of this brain area in the AN group. CONCLUSIONS: Our findings show that AN is associated with double disruption of brain connectivity, which shows a specific association with visuospatial difficulties and may explain the failure of the integration process between visual and somatosensory perceptual information that might sustain body image disturbance.

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.

[Tattoos and piercings in adolescents: family conflicts and temperament]. / Tatuaggi e piercing negli adolescenti: correlati familiari e temperamentali.

INTRODUCTION: The phenomenon of body art, such as tattoos and piercings, has ancient roots, rediscovered in Western society during the '70s. The aim of this research is to investigate the prevalence and the characteristics of tattoos and piercings among Italian adolescents of high school in Padua, with particular attention to family context and temperament. METHODS: Some questionnaires about the presence or the wish of tattoos/piercings, smoke and alcohol use, familiar conflicts, and some temperamental features, such as novelty seeking, harm avoidance and reward dependence, have been administered to a sample of 829 students. RESULTS: Tattoo and piercing's prevalence among adolescents was respectively 4% and 24%; 2.5% of the sample had both. Respectively 62% and 35% of the subjects expressed the desire of having a tattoo or piercing. A significant association has been found between tattoo/piercing's presence and smoke and alcohol use (p < 0.001). Subjects with tattoos and piercings, are more likely to have familiar conflicts and minor perceived support and they have higher scores on the novelty seeking scale. Those who wish a tattoo/piercing showed higher reward dependence. CONCLUSIONS: This study confirms that tattoos/piercings are common among young people and it stresses the relevance of familiar and temperamental features, and the association between tattoos/piercings and some maladaptive behaviors, like smoke and alcohol use.

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

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.

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.

Time trends in age at onset of anorexia nervosa and bulimia nervosa.

OBJECTIVE: This study aims to explore the time trends in age at onset of anorexia nervosa and bulimia nervosa. METHOD: The sample was composed of 1,666 anorexia nervosa subjects and 793 bulimia nervosa subjects (according to DSM-IV criteria) without previous anorexia nervosa consecutively referred to our outpatient unit in the period between 1985 and 2008. Time trends in illness onset were analyzed according to the year of birth of subjects. RESULTS: In both anorexia nervosa and bulimia nervosa, age at onset showed a significant decrease according to year of birth. A regression model showed a significant independent effect of socioeconomic status, age at menarche, and number of siblings in predicting age at onset lower than 16 years. CONCLUSION: Age at onset of anorexia nervosa and bulimia nervosa is decreasing in younger generations. The implications of our findings in terms of long-term outcome remain to be understood. Biologic and sociocultural factors explaining this phenomenon need to be explored in future studies.