Social cognition in people with schizophrenia: a cluster-analytic approach.

BACKGROUND: The study aimed to subtype patients with schizophrenia on the basis of social cognition (SC), and to identify cut-offs that best discriminate among subtypes in 809 out-patients recruited in the context of the Italian Network for Research on Psychoses. METHOD: A two-step cluster analysis of The Awareness of Social Inference Test (TASIT), the Facial Emotion Identification Test and Mayer-Salovey-Caruso Emotional Intelligence Test scores was performed. Classification and regression tree analysis was used to identify the cut-offs of variables that best discriminated among clusters. RESULTS: We identified three clusters, characterized by unimpaired (42%), impaired (50.4%) and very impaired (7.5%) SC. Three theory-of-mind domains were more important for the cluster definition as compared with emotion perception and emotional intelligence. Patients more able to understand simple sarcasm (⩾14 for TASIT-SS) were very likely to belong to the unimpaired SC cluster. Compared with patients in the impaired SC cluster, those in the very impaired SC cluster performed significantly worse in lie scenes (TASIT-LI <10), but not in simple sarcasm. Moreover, functioning, neurocognition, disorganization and SC had a linear relationship across the three clusters, while positive symptoms were significantly lower in patients with unimpaired SC as compared with patients with impaired and very impaired SC. On the other hand, negative symptoms were highest in patients with impaired levels of SC. CONCLUSIONS: If replicated, the identification of such subtypes in clinical practice may help in tailoring rehabilitation efforts to the person's strengths to gain more benefit to the person.

Serotonin transporter gene polymorphism in eating disorders: Data from a new biobank and META-analysis of previous studies.

UNLABELLED: Objectives Growing interest focuses on the association between 5-HTTLPR polymorphism and eating disorders (ED), but published findings have been conflicting. Methods The Italian BIO.VE.D.A. biobank provided 976 samples (735 ED patients and 241 controls) for genotyping. We conducted a literature search of studies published up to 1 April 2015, including studies reporting on 5HTTLPR genotype and allele frequencies in obesity and/or ED. We ran a meta-analysis, including data from BIO.VE.D.A. - comparing low and high-functioning genotype and allele frequencies in ED vs. CONTROLS: Results Data from 21 studies, plus BIO.VE.D.A., were extracted providing information from 3,736 patients and 2,707 controls. Neither low- nor high-functioning genotype frequencies in ED patients, with both bi- and tri-allelic models, differed from controls. Furthermore, neither low- nor high-functioning allele frequencies in ED or in BN, in both bi- and triallelic models, differed from control groups. After sensitivity analysis, results were the same in AN vs. CONTROLS: Results remained unaltered when investigating recessive and dominant models. Conclusions 5HTTLPR does not seem to be associated with ED in general, or with AN or BN in particular. Future studies in ED should explore the role of ethnicity and psychiatric comorbidity as a possible source of bias.

Bone mineral density, osteoporosis, and fractures among people with eating disorders: a systematic review and meta-analysis.

OBJECTIVE: To provide meta-analytical evidence of bone mineral density (BMD), fractures, and osteoporosis rates in eating disorders (ED) vs. healthy controls (HCs). METHOD: Three independent authors searched major electronic databases from inception till August 2015 for cross-sectional studies reporting BMD in people with ED (anorexia nervosa, (AN); bulimia nervosa, (BN); eating disorders not otherwise specified, (EDNOS)) vs. HCs. Standardized mean differences (SMDs) ±95% and confidence intervals (CIs) were calculated for BMD, and odds ratios (ORs) for osteopenia, osteoporosis, and fractures. RESULTS: Overall, 57 studies were eligible, including 21 607 participants (ED = 6485, HCs = 15 122). Compared to HC, AN subjects had significantly lower BMD values at lumbar spine (SMD = -1.51, 95% CI = -1.75, -1.27, studies = 42), total hip (SMD = -1.56, 95%CI = -1.84, -1.28, studies = 23), intertrochanteric region (SMD = -1.80, 95%CI = -2.46, -1.14, studies = 7), trochanteric region (SMD = -1.05, 95%CI = -1.44, -0.66, studies = 7), and femoral neck (SMD = -0.98, 95%CI = -1.12, -0.77, studies = 20). Reduced BMD was moderated by ED illness duration and amenorrhea (P < 0.05). AN was associated with an increased likelihood of osteoporosis (OR = 12.59, 95%CI = 3.30-47.9, P < 0.001, studies = 4) and fractures (OR = 1.84, 95% CI = 1.17-2.89, I(2) = 56, studies = 6). No difference in BMD was found between BN and EDNOS vs. HC. CONCLUSION: People with AN have reduced BMD, increased odds of osteoporosis and risk of fractures. Proactive monitoring and interventions are required to ameliorate bone loss in AN.

Neural correlates of prenatal stress in young women.

BACKGROUND: Prenatal stress is hypothesized to have a disruptive impact on neurodevelopmental trajectories, but few human studies have been conducted on the long-term neural correlates of prenatal exposure to stress. The aim of this study was to explore the relationship between prenatal stress exposure and gray-matter volume and resting-state functional connectivity in a sample of 35 healthy women aged 14-40 years. METHOD: Voxel-based morphometry and functional connectivity analyses were performed on the whole brain and in specific regions of interest (hippocampus and amygdala). Data about prenatal/postnatal stress and obstetric complications were obtained by interviewing participants and their mothers, and reviewing obstetric records. RESULTS: Higher prenatal stress was associated with decreased gray-matter volume in the left medial temporal lobe (MTL) and both amygdalae, but not the hippocampus. Variance in gray-matter volume of these brain areas significantly correlated with depressive symptoms, after statistically adjusting for the effects of age, postnatal stress and obstetric complications. Prenatal stress showed a positive linear relationship with functional connectivity between the left MTL and the pregenual cortex. Moreover, connectivity between the left MTL and the left medial-orbitofrontal cortex partially explained variance in the depressive symptoms of offspring. CONCLUSIONS: In young women, exposure to prenatal stress showed a relationship with the morphometry and functional connectivity of brain areas involved in the pathophysiology of depressive disorders. These data provide evidence in favor of the hypothesis that early exposure to stress affects brain development and identified the MTL and amygdalae as possible targets of such exposure.

A genome-wide association study of anorexia nervosa.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.

In utero exposure to virus infections and the risk of developing anorexia nervosa.

BACKGROUND: The study aims to explore, using indirect ecological measures of exposure, the role of viral infections in the development of anorexia nervosa (AN). METHOD: The cohort of participants consisted of all female subjects born in the Veneto region in the period between 1970 and 1984, and residing in the urban and suburban area of Padua (27,682 female subjects in an area of 424 km2). The main outcome measure was the diagnosis of AN resulting from the Public Mental Health Database, the Register of Hospital Admissions, and the Register of the Eating Disorders Unit (n=402, 1.4%). The number of cases of rubella, chickenpox, influenza and measles was ascertained for each month for the 15-year period. RESULTS: Exposures during the sixth month of pregnancy to the peaks of chickenpox [odds ratio (OR) 1.6, 95% confidence interval (CI) 1.2-2.0] and rubella infections (OR 1.5, 95% CI 1.1-2.0) were significantly associated with an increased risk of developing AN, even after controlling for socio-economic status, urbanization and month of birth. We found weak evidence of a season-of-birth bias. CONCLUSIONS: In utero exposure to viral infection could be a risk factor for developing AN. We need further epidemiological and serological studies to confirm this hypothesis.

Neurocognitive functioning in bulimia nervosa: the role of neuroendocrine, personality and clinical aspects.

BACKGROUND: Studies investigating neurocognitive impairment in subjects with eating disorders (EDs) have reported heterogeneous patterns of impairment and, in some instances, no dysfunction. The present study aimed to define the pattern of neurocognitive impairment in a large sample of bulimia nervosa (BN) patients and to demonstrate that neuroendocrine, personality and clinical characteristics influence neurocognitive performance in BN. METHOD: Attention/immediate memory, set shifting, perseveration, conditional and implicit learning were evaluated in 83 untreated female patients with BN and 77 healthy controls (HC). Cortisol and 17ß-estradiol plasma levels were assessed. Cloninger's Temperament and Character Inventory - Revised (TCI-R), the Bulimic Investigation Test Edinburgh (BITE) and the Montgomery-Asberg Depression Rating Scale (MADRS) were administered. RESULTS: No impairment of cognitive performance was found in subjects with BN compared with HC. Cortisol and 'Self-directedness' were associated with better performance on conditional learning whereas 17ß-estradiol had a negative influence on this domain; 'Reward dependence' was associated with worse performance on implicit learning; and depressive symptomatology influenced performance on the Wisconsin Card Sorting Test (WCST) negatively. CONCLUSIONS: No cognitive impairment was found in untreated patients with BN. Neuroendocrine, personality and clinical variables do influence neurocognitive functioning and might explain discrepancies in literature findings.

Pica in an eating disordered woman with multiple sclerosis: impulse dys-control, compulsive symptom or self-medication attempt?

We report about a complex case of pica in comorbidity with multiple sclerosis and binge eating disorder. Pica is classified among the feeding and eating disorders of infancy and early childhood, but there is a debate in the literature about the psychopathology and classification of this behavior. Some authors emphasize the similarities with the obsessive-compulsive spectrum disorders, whereas others propose an interpretation of pica as an addiction or as an impulsive behavior. The clinical case that we describe provides a picture of impulsive and compulsive features that are very difficult to disentangle. It is noteworthy that hypercalcemia is reported to have a protective/therapeutic effect against multiple sclerosis and seems to increase the plasmatic levels of beta-endorphins. The nature, diagnostic classification, and functions of pica are a topic worthy of future investigation.

The interaction between perinatal factors and childhood abuse in the risk of developing anorexia nervosa.

BACKGROUND: Perinatal factors seem to be implicated in the pathogenesis of anorexia nervosa (AN) and may be involved in the programming of stress response systems in humans. Our aim was to explore one of the possible pathways to explain the association between perinatal complications and a psychiatric disorder. In particular, we tested the hypothesis that neonatal immaturity may confer an enhanced vulnerability to AN after exposure to a severe stressful event, such as childhood abuse. METHOD: The sample was composed of subjects who took part in a prevalence study carried out on a representative sample of the general population and cases of AN referred to an out-patient specialist unit. All subjects (n=663) were born in the two obstetric wards of Padua Hospital between 1971 and 1979. We analysed data using both a case-control and a cohort design. RESULTS: We found that functional signs of neonatal dysmaturity, but not a low birthweight or prematurity, had a significant additive interaction with childhood abuse in determining the risk for this illness. In normal subjects, but not in subjects with AN, neonatal dysmaturity was associated with being small, short or thin for gestational age at birth. CONCLUSIONS: The synergistic effect of neonatal dysmaturity and childhood abuse in increasing the risk for AN provides evidence for the hypothesis that a prenatal programming of stress response systems can result in an impairment of the individual's resilience to severe stressful events.

Sertraline in the treatment of restricting anorexia nervosa: an open controlled trial.

Few studies to date have examined the usefulness of selective serotonin reuptake inhibitors (SSRIs) in an outpatient multidisciplinary treatment of anoxrexia nervosa. The present study consists of an open, controlled trial of sertraline in a sample of 11 restricting-type anorexics, treated in an outpatient setting, compared with a control group of patients with similar characteristics. All subjects were assessed by means of a structured interview and self-reported questionnaires at baseline and after 14 weeks of treatment. Body weight and diagnostic status were evaluated again after a 64-week follow-up. At the 14-week follow-up, the sertraline group reported a significantly greater improvement of depressive symptoms, ineffectiveness, lack of interoceptive awareness, and perfectionism when compared to the control group. Both groups reported a significant improvement in body weight. At the 64-week follow-up, only one patient of the sertraline group and five patients of the control group still had a full diagnosis of an eating disorder. Further studies are necessary to define the role of sertraline and of other SSRIs in the treatment of anorexia nervosa.

Insulin-like growth factor 1 (IGF-1), a nutritional marker in patients with eating disorders.

BACKGROUND AND AIMS: Though low levels of insulin-like growth factor-1 (IGF-1) have been repeatedly reported in patients with eating disorders, the nutritional significance of IGF-1 has not been evaluated. The study aimed to assess the utility of IGF-1 for screening malnutrition and for monitoring nutrition intervention in patients with eating disorders. METHODS: IGF-1 and nutritional status were evaluated in 82 patients, 59 with anorexia nervosa (AN), and 23 with bulimia nervosa (BN). Nutritional assessment included the evaluation of body mass index (BMI), body fat (FAT) and muscle mass (MM), assessed by skinfold anthropometry, serum albumin, transthyretin and retinol-binding protein, energy and protein intake. IGF-1 and nutritional parameters were reevaluated in the early phase of refeeding (2-4 weeks) in 20 AN patients who entered a refeeding program. RESULTS: Mean IGF-1 z-score was -1.74+/-0.74 in AN, and -0.74+/-0.91 in BN. Serum proteins were reduced in only a minority of patients. IGF-1 correlated with BMI (r=0.64), FAT (r=0.57), MAMC (mid-arm muscle circumference) (r=0.58) and MM (r=0.66) (P<0.001), while it did not correlate with serum proteins. In the early phase of nutritional repletion serum proteins and anthropometric parameters did not vary significantly, while a prompt and marked increase (73.9%) of IGF-1 was observed. CONCLUSIONS: IGF-1 represents a biochemical marker of malnutrition and a sensitive index of nutritional repletion in patients with eating disorders.

Efficacy and tolerability of moclobemide in bulimia nervosa: a placebo-controlled trial.

A 6-week double-blind placebo-controlled trial was carried out to examine the efficacy and tolerability of moclobemide, a monoamine oxidase type A selective and reversible inhibitor, in the treatment of bulimia nervosa. Patients were admitted to the study even if they were unable to adhere to a tyramine-free diet. Fifty-two normal-weight women (age range 18-40 years) suffering from bulimia nervosa (DSM-IV criteria) completed the trial. Particular emphasis was placed on evaluating the incidence of hypertension and other side-effects in chronically treated patients. At the usual antidepressant dose of 600 mg, moclobemide was not significantly superior to placebo in the reducing the weekly number of binge eating episodes or in improving several measures of eating attitudes and behaviour (BITE, EDI, TFEQ) in normal-weight bulimia nervosa. The dropout rate was relatively low (29%), and the side-effects were limited and equally distributed between the two treatment groups. No patient experienced a hypertensive crisis during the study and no serious side-effect was detected. The study indicates that moclobemide 600 mg pro die is not efficacious in bulimia nervosa, but it can be safely administered, even to young subjects, at a very high risk of consuming large amounts of tyramine-rich foods without dietary restrictions.

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.

Self-injurious behavior in anorexia nervosa.

Recent reports have postulated the existence of two different types of self-injurious behavior: impulsive and compulsive. The aim of the present study is to analyze the dimensionality of self-injurious behavior and to study the link between self-injurious behavior and clinical features in anorexia nervosa. The study involved 236 consecutive patients with anorexia nervosa, diagnosed by DSM-IV criteria. Subjects were evaluated by means of a semistructured interview and self-reported questionnaires, such as the Eating Disorders Inventory and Hopkins Symptom Checklist. A principal component analysis was used to study the dimensionality of different types of self-injurious behavior, including purging. Our findings confirm the distinction between impulsive and compulsive self-injurious behavior. The dimensions appear to be represented as a continuum in both the anorexia nervosa diagnostic subgroups. A third distinct dimension emerged that included self-induced vomiting and laxative/diuretics abuse. Childhood sexual abuse and anxiety significantly predict the presence of impulsive self-injury, whereas obsessionality and age predict compulsive self-injury. The coexistence of a positive score on both dimensions of self-injurious behavior was the strongest predictor of treatment dropout. The present study highlights the importance of self-injurious behavior; it should be given due consideration in future outcome studies on anorexia nervosa

Tryptophan levels, excessive exercise, and nutritional status in anorexia nervosa.

OBJECTIVE: It has been hypothesized that reduced dietary availability of tryptophan may be the cause of impaired serotonin activity in underweight anorexics. The study reported here evaluated the relationship between tryptophan availability in the blood and nutritional status in anorexia nervosa. METHODS: The total amount of tryptophan and the ratio between tryptophan and other large neutral amino acids (TRP/LNAA) were assessed in a sample of 16 starving anorexic patients. Body weight and composition and energy intake were evaluated in all patients. All subjects also completed self-reported questionnaires such as the Hopkins Symptom Checklist and Eating Disorders Inventory (EDI). RESULTS: The TRP/LNAA ratio seems to be higher in patients with a more severe catabolic status. It is, in fact, significantly inversely correlated with body mass index, body fat, muscle mass, daily energy intake, and daily tryptophan intake. The TRP/LNAA ratio also correlates with growth hormone and the EDI drive for thinness. Patients who exercise excessively had significantly higher TRP/LNAA ratios. CONCLUSIONS: In starving anorexic patients, the TRP/LNAA ratio does not seem to be determined by the content of tryptophan in the diet, but it correlates with measures of catabolism. The relationship of the TRP/LNAA ratio to excessive exercise and starvation indicates the importance of further investigations exploring the role of tryptophan availability in maintaining anorexia nervosa.

[Construction and validation of a new screnning questionnaires for eating disorders: the inventory for the screening of eating disorders/(ISED)]. / Costruzione e validazione di un nuovo strumento di screening per i disturbi dell'alimentazione: the Inventory for the Screening of Eating Disorders (ISED).

OBJECTIVE: The study aims to construct and validate a new screening questionnaire for the identification of cases at risk for eating disorders. SETTING AND SAMPLE: We assessed 218 female adolescent students recruited in a vocational school in Mestre (VE) and 88 patients consecutively referred to the Eating Disorders Unit of the University of Padova. PROCEDURE AND MAIN OUTCOME MEASURES: All subjects completed the new questionnaire, the Inventory for the Screening of Eating Disorders (ISED), and the Eating Attitudes Test (EAT). Sixty-two percent of female students and all the patients underwent a structured diagnostic interview (SCID for DSM-IV) for the diagnosis of eating disorders. The reliability, validity and screening ability of the questionnaire have been assessed. RESULTS: The reliability of the ISED, measured by Cronbach's alpha, is good (alpha = 0.87), as is the convergent validity (correlations with EAT). In order to improve the screening ability, the questionnaire has been further divided in two subscales: one for the identification of cases at risk for anorexia nervosa (ISED-AN) and the other for cases at risk for bulimia nervosa (ISED-BN). The screening ability of the two subscales is greater than that of EAT, although the difference is not statistically significant. The ISED cutoff points have greater positive predictive values than those of EAT in the screening of both anorexia nervosa and bulimia nervosa. CONCLUSIONS: The ISED appears to be a valid and reliable questionnaire among female adolescents. Its use might improve the identification of cases at risk for eating disorders and in particular those at risk for anorexia nervosa. Other studies are needed to confirm the validity and performance of the questionnaire among samples of different ages and socio-economic status.

Binge eating and eating attitudes among Nazi concentration camp survivors.

BACKGROUND: Prisoners in Nazi concentration camps lived through extreme situations that included starvation. We test our hypothesis that there is a greater lifetime presence of binge eating among survivors from concentration camps than in a control group. METHODS: The subjects were 51 political prisoners who survived Nazi concentration camps and 47 ex-partisans of similar age and sex. A clinical interview investigated the lifetime occurrence of binge eating. The Eating Attitudes Test was also administered. RESULTS: The mean reported loss of weight among survivors was 27-3 kg. Thirty-three per cent of them and 4% of the ex-partisans reported going on eating binges at some time in their lives (P < 0.0007). There was no significant difference in the Eating Attitudes Test scores of survivors and ex-partisans, but, among survivors, the Bulimia subscale significantly discriminated subjects who reported current binge eating. CONCLUSIONS: Our study confirms that subjects who have survived a period of extreme food deprivation are more likely to develop binge eating behaviour.