Correction: Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

The fortieth author's name was listed incorrectly. The correct presentation is A Keski-Rahkonen.

Investigation of common, low-frequency and rare genome-wide variation in anorexia nervosa.

Anorexia nervosa (AN) is a complex neuropsychiatric disorder presenting with dangerously low body weight, and a deep and persistent fear of gaining weight. To date, only one genome-wide significant locus associated with AN has been identified. We performed an exome-chip based genome-wide association studies (GWAS) in 2158 cases from nine populations of European origin and 15 485 ancestrally matched controls. Unlike previous studies, this GWAS also probed association in low-frequency and rare variants. Sixteen independent variants were taken forward for in silico and de novo replication (11 common and 5 rare). No findings reached genome-wide significance. Two notable common variants were identified: rs10791286, an intronic variant in OPCML (P=9.89 × 10-6), and rs7700147, an intergenic variant (P=2.93 × 10-5). No low-frequency variant associations were identified at genome-wide significance, although the study was well-powered to detect low-frequency variants with large effect sizes, suggesting that there may be no AN loci in this genomic search space with large effect sizes.

Mood symptoms and suicidality across the autism spectrum.

BACKGROUND: Autism spectrum is a psychopathological dimension which encompasses a wide range of clinical presentations: from subthreshold forms and autistic traits (AT), that can be found in the general population, to full-blown autism spectrum disorder (ASD). Many studies reported high rates of comorbidity between both ASD and AT and mood disorders, as well as a high prevalence of suicidal ideation among patients with ASD/AT. The aim of this study was to investigate the presence of mood symptoms and suicidal ideation and behaviors in patients with full-blown ASD and in subjects with AT, as well in a healthy control (HC) group, with a specific focus on which of the autistic features may be predictive of suicidal ideation and behaviors. METHODS: We recruited 262 adult subjects: 34 with ASD without intellectual impairment or language disability (ASD group), 68 fulfilling only one symptom criterion for ASD according to DSM-5 but who do not meet criteria for a full-blown diagnosis of ASD (AT group), and 160 HC. All subjects were assessed with the Structured Clinical Interview for DSM-5 (SCID-5); in addition, they were asked to fill two questionnaires: The Mood Spectrum, Self-report (MOODS-SR) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). RESULTS: ASD subjects reported significantly higher AdAS Spectrum and MOODS-SR total scores, as well as higher MOODS-SR depressive component total scores, when compared with AT and HC subjects. AT subjects scored significantly higher than the HC group. No significant differences were reported between ASD and AT subjects for the suicidality score according to MOODS-SR, despite both groups scored significantly higher than the HC group. The strongest predictor of suicidality score were MOODS-SR depressive component score and AdAS Spectrum Restricted interests and rumination domain score. CONCLUSIONS: Our results highlight a correlation between autism and mood spectrum, as well as between suicidality and both ASD and AT. Subthreshold forms of ASD should be accurately investigated due to their relationship with suicidal thoughts and behaviors.

Impaired cortisol awakening response in eating disorder women with childhood trauma exposure: evidence for a dose-dependent effect of the traumatic load.

BACKGROUND: Childhood trauma is a non specific risk factor for adult eating disorders (ED), and the hypothalamic-pituitary-adrenal (HPA) axis seems to mediate such a risk. Here we explored the impact of different types of childhood trauma and of traumatic load on the cortisol awakening response (CAR) of women with anorexia nervosa (AN) or bulimia nervosa (BN). METHODS: Saliva samples were collected at awakening and after 15, 30, 60 min to measure cortisol levels by 121 women (44 AN patients, 36 BN patients and 41 healthy women). Participants filled in the Childhood Trauma Questionnaire. RESULTS: AN and BN patients with childhood maltreatment exhibited an attenuated CAR compared with non-maltreated ones. In the whole ED patient group, the CAR showed a progressive impairment with the increasing number of reported trauma types. Although significant negative correlations emerged between the type or the number of traumas and the CAR, only the number of traumas remained significantly associated with the CAR in a stepwise multiple regression analysis. CONCLUSIONS: Present findings confirm that childhood trauma is associated with an impaired CAR in adult AN and BN patients and demonstrate for the first time a negative dose-dependent effect of the traumatic load on HPA axis activity.

Familial aggregation of MATRICS Consensus Cognitive Battery scores in a large sample of outpatients with schizophrenia and their unaffected relatives.

BACKGROUND: The increased use of the MATRICS Consensus Cognitive Battery (MCCB) to investigate cognitive dysfunctions in schizophrenia fostered interest in its sensitivity in the context of family studies. As various measures of the same cognitive domains may have different power to distinguish between unaffected relatives of patients and controls, the relative sensitivity of MCCB tests for relative-control differences has to be established. We compared MCCB scores of 852 outpatients with schizophrenia (SCZ) with those of 342 unaffected relatives (REL) and a normative Italian sample of 774 healthy subjects (HCS). We examined familial aggregation of cognitive impairment by investigating within-family prediction of MCCB scores based on probands' scores. METHODS: Multivariate analysis of variance was used to analyze group differences in adjusted MCCB scores. Weighted least-squares analysis was used to investigate whether probands' MCCB scores predicted REL neurocognitive performance. RESULTS: SCZ were significantly impaired on all MCCB domains. REL had intermediate scores between SCZ and HCS, showing a similar pattern of impairment, except for social cognition. Proband's scores significantly predicted REL MCCB scores on all domains except for visual learning. CONCLUSIONS: In a large sample of stable patients with schizophrenia, living in the community, and in their unaffected relatives, MCCB demonstrated sensitivity to cognitive deficits in both groups. Our findings of significant within-family prediction of MCCB scores might reflect disease-related genetic or environmental factors.

Premorbid academic and social functioning in patients with schizophrenia and its associations with negative symptoms and cognition.

OBJECTIVE: The study aimed to explore premorbid academic and social functioning in patients with schizophrenia, and its associations with the severity of negative symptoms and neurocognitive impairment. METHOD: Premorbid adjustment (PA) in patients with schizophrenia was compared to early adjustment in unaffected first-degree relatives and healthy controls. Its associations with psychopathology, cognition, and real-life functioning were investigated. The associations of PA with primary negative symptoms and their two factors were explored. RESULTS: We found an impairment of academic and social PA in patients (P ≤ 0.000001) and an impairment of academic aspects of early adjustment in relatives (P ≤ 0.01). Patients with poor PA showed greater severity of negative symptoms (limited to avolition after excluding the effect of depression/parkinsonism), working memory, social cognition, and real-life functioning (P ≤ 0.01 to ≤0.000001). Worse academic and social PA were associated with greater severity of psychopathology, cognitive impairment, and real-life functioning impairment (P ≤ 0.000001). Regression analyses showed that worse PA in the academic domain was mainly associated to the impairment of working memory, whereas worse PA in the social domain to avolition (P ≤ 0.000001). CONCLUSION: Our findings suggest that poor early adjustment may represent a marker of vulnerability to schizophrenia and highlight the need for preventive/early interventions based on psychosocial and/or cognitive programs.

Subthreshold autism spectrum disorder in patients with eating disorders.

AIM: Increasingly data suggest a possible overlap between psychopathological manifestations of eating disorders (EDs) and autism spectrum disorders (ASD). The aim of the present study was to assess the presence of subthreshold autism spectrum symptoms, by means of a recently validated instrument, in a sample of participants with EDs, particularly comparing participants with or without binge eating behaviours. METHODS: 138 participants meeting DSM-5 criteria for EDs and 160 healthy control participants (HCs), were recruited at 3 Italian University Departments of Psychiatry and assessed by the SCID-5, the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Eating Disorders Inventory, version 2 (EDI-2). ED participants included: 46 with restrictive anorexia (AN-R); 24 with binge-purging type of Anorexia Nervosa (AN-BP); 34 with Bulimia Nervosa (BN) and 34 with Binge Eating Disorder (BED). The sample was split in two groups: participants with binge eating behaviours (BEB), in which were included participants with AN-BP, BN and BED, and participants with restrictive behaviours (AN-R). RESULTS: participants with EDs showed significantly higher AdAS Spectrum total scores than HCs. Moreover, EDs participants showed significantly higher scores on all AdAS Spectrum domains with the exception of Non verbal communication and Hyper-Hypo reactivity to sensory input for AN-BP participants, and Childhood/Adolescence domain for AN-BP and BED participants. Participants with AN-R scored significantly higher than participants with BEB on the AdAS Spectrum total score, and on the Inflexibility and adherence to routine and Restricted interest/rumination AdAS Spectrum domain scores. Significant correlations emerged between the Interpersonal distrust EDI-2 sub-scale and the Non verbal communication and the Restricted interest and rumination AdAS Spectrum domains; as well as between the Social insecurity EDI-2 sub-scale and the Inflexibility and adherence to routine and Restricted interest and rumination domains in participants with EDs. CONCLUSIONS: Our data corroborate the presence of higher subthreshold autism spectrum symptoms among ED participants with respect to HCs, with particularly higher levels among restrictive participants. Relevant correlations between subthreshold autism spectrum symptoms and EDI-2 Subscale also emerged.

Adult Autism Subthreshold Spectrum (AdAS Spectrum): Validation of a questionnaire investigating subthreshold autism spectrum.

AIM: Increasing literature has shown the usefulness of a dimensional approach to autism. The present study aimed to determine the psychometric properties of the Adult Autism Subthreshold Spectrum (AdAS Spectrum), a new questionnaire specifically tailored to assess subthreshold forms of autism spectrum disorder (ASD) in adulthood. METHODS: 102 adults endorsing at least one DSM-5 symptom criterion for ASD (ASDc), 143 adults diagnosed with a feeding and eating disorder (FED), and 160 subjects with no mental disorders (CTL), were recruited from 7 Italian University Departments of Psychiatry and administered the following: SCID-5, Autism-Spectrum Quotient (AQ), Ritvo Autism and Asperger Diagnostic Scale 14-item version (RAADS-14), and AdAS Spectrum. RESULTS: The AdAS Spectrum demonstrated excellent internal consistency for the total score (Kuder-Richardson's coefficient=.964) as well as for five out of seven domains (all coefficients>.80) and sound test-retest reliability (ICC=.976). The total and domain AdAS Spectrum scores showed a moderate to strong (>.50) positive correlation with one another and with the AQ and RAADS-14 total scores. ASDc subjects reported significantly higher AdAS Spectrum total scores than both FED (p<.001) and CTL (p<.001), and significantly higher scores on the Childhood/adolescence, Verbal communication, Empathy, Inflexibility and adherence to routine, and Restricted interests and rumination domains (all p<.001) than FED, while on all domains compared to CTL. CTL displayed significantly lower total and domain scores than FED (all p<.001). A significant effect of gender emerged for the Hyper- and hyporeactivity to sensory input domain, with women showing higher scores than men (p=.003). A Diagnosis* Gender interaction was also found for the Verbal communication (p=.019) and Empathy (p=.023) domains. When splitting the ASDc in subjects with one symptom criterion (ASD1) and those with a ASD, and the FED in subjects with no ASD symptom criteria (FED0) and those with one ASD symptom criterion (FED1), a gradient of severity in AdAS Spectrum scores from CTL subjects to ASD patients, across FED0, ASD1, FED1 was shown. CONCLUSIONS: The AdAS Spectrum showed excellent internal consistency and test-retest reliability and strong convergent validity with alternative dimensional measures of ASD. The questionnaire performed differently among the three diagnostic groups and enlightened some significant effects of gender in the expression of autistic traits.

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.

Responses of peripheral endocannabinoids and endocannabinoid-related compounds to hedonic eating in obesity.

PURPOSE: Hedonic eating occurs independently from homeostatic needs prompting the ingestion of pleasurable foods that are typically rich in fat, sugar and/or salt content. In normal weight healthy subjects, we found that before hedonic eating, plasma levels of 2-arachidonoylglycerol (2-AG) were higher than before nonhedonic eating, and although they progressively decreased after food ingestion in both eating conditions, they were significantly higher in hedonic eating. Plasma levels of anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), instead, progressively decreased in both eating conditions without significant differences. In this study, we investigated the responses of AEA, 2-AG, OEA and PEA to hedonic eating in obese individuals. METHODS: Peripheral levels of AEA, 2-AG, OEA and PEA were measured in 14 obese patients after eating favourite (hedonic eating) and non-favourite (nonhedonic eating) foods in conditions of no homeostatic needs. RESULTS: Plasma levels of 2-AG increased after eating the favourite food, whereas they decreased after eating the non-favourite food, with the production of the endocannabinoid being significantly enhanced in hedonic eating. Plasma levels of AEA decreased progressively in nonhedonic eating, whereas they showed a decrease after the exposure to the favourite food followed by a return to baseline values after eating it. No significant differences emerged in plasma OEA and PEA responses to favourite and non-favourite food. CONCLUSION: Present findings compared with those obtained in our previously studied normal weight healthy subjects suggest deranged responses of endocannabinoids to food-related reward in obesity.

Is dialdehyde starch a valuable cross-linking agent for collagen/elastin based materials?

Collagen and elastin are the main structural proteins in mammal bodies. They provide mechanical support, strength, and elasticity to various organs and tissues, e.g. skin, tendons, arteries, and bones. They are readily available, biodegradable, biocompatible and they stimulate cell growth. The physicochemical properties of collagen and elastin-based materials can be modified by cross-linking. Glutaraldehyde is one of the most efficient cross-linking agents. However, the unreacted molecules can be released from the material and cause cytotoxic reactions. Thus, the aim of our work was to investigate the influence of a safer, macromolecular cross-linking agent--dialdehyde starch (DAS). The properties of hydrogels based on collagen/elastin mixtures (95/5, 90/10) containing 5 and 10% of DAS and neutralized via dialysis against deionized water were tested. The homogenous, transparent, stiff hydrogels were obtained. The DAS addition causes the formation of intermolecular cross-linking bonds but does not affect the secondary structure of the proteins. As a result, the thermal stability, mechanical strength, and, surprisingly, swelling ability increased. At the same time, the surface properties test and in vitro study show that the materials are attractive for 3T3 cells. Moreover, the materials containing 10% of DAS are more resistant to enzymatic degradation.

Is avolition in schizophrenia associated with a deficit of dorsal caudate activity? A functional magnetic resonance imaging study during reward anticipation and feedback.

BACKGROUND: The neurobiological underpinnings of avolition in schizophrenia remain unclear. Most brain imaging research has focused on reward prediction deficit and on ventral striatum dysfunction, but findings are not consistent. In the light of accumulating evidence that both ventral striatum and dorsal caudate play a key role in motivation, we investigated ventral striatum and dorsal caudate activation during processing of reward or loss in patients with schizophrenia. METHOD: We used functional magnetic resonance imaging to study brain activation during a Monetary Incentive Delay task in patients with schizophrenia, treated with second-generation antipsychotics only, and in healthy controls (HC). We also assessed the relationships of ventral striatum and dorsal caudate activation with measures of hedonic experience and motivation. RESULTS: The whole patient group had lower motivation but comparable hedonic experience and striatal activation than HC. Patients with high avolition scores showed lower dorsal caudate activation than both HC and patients with low avolition scores. A lower dorsal caudate activation was also observed in patients with deficit schizophrenia compared to HC and patients with non-deficit schizophrenia. Dorsal caudate activity during reward anticipation was significantly associated with avolition, but not with anhedonia in the patient group. CONCLUSIONS: These findings suggest that avolition in schizophrenia is linked to dorsal caudate hypoactivation.

Cortisol awakening response in patients with anorexia nervosa or bulimia nervosa: relationships to sensitivity to reward and sensitivity to punishment.

BACKGROUND: Sensitivity to punishment (SP) and sensitivity to reward (SR) are personality characteristics that may have relevance for the pathophysiology of eating disorders (EDs). Moreover, personality characteristics are known to modulate the activity of the hypothalamus-pituitary-adrenal (HPA) axis, which is the main component of the endogenous stress response system. As stress has been implicated in the aetiology and the maintenance of EDs, we aimed to study the HPA axis activity in relation to SP and SR, as conceptualized by Gray's reinforcement sensitivity theory (RST), in patients with anorexia nervosa (AN) or bulimia nervosa (BN). METHOD: Twenty-five women with AN, 23 women with BN and 19 healthy women volunteered for the study. HPA axis activity was assessed by measurement of the salivary cortisol awakening response (CAR). The subjects' SP and SR were measured by the behavioural inhibition system (BIS)/behavioural approach system (BAS) scales. RESULTS: The CAR was significantly enhanced in AN patients, but not in BN patients, compared to healthy women. The CAR correlated significantly with BAS measures, negatively in healthy controls and positively in binge-purging AN patients and BN women. SP, measured by the BIS scale, was higher in patients than in controls. CONCLUSIONS: These findings confirm the occurrence of an enhanced activity of the HPA axis in symptomatic AN, but not in symptomatic BN, and show for the first time that the CAR is associated with SR, as conceptualized by the RST, negatively in healthy subjects but positively in binge-purging ED patients.

Reflectance confocal microscopy as a non-invasive diagnostic tool for Hailey-Hailey disease.

BACKGROUND/PURPOSE: Reflectance confocal microscopy (RCM) is a non-invasive method for high-resolution, in vivo imaging of the epidermis and upper dermis. The purpose of the study was to evaluate the potential usefulness of RCM as a non-invasive diagnostic tool for Hailey-Hailey disease (familial benign chronic pemphigus). METHODS: Four patients with Hailey-Hailey disease were examined by RCM. Subsequently, punch biopsies were taken to compare RCM images with corresponding histopathologic findings. RESULTS: On RCM images, the most sticking feature was acantholysis at the level of the granular and spinous layer, resembling a 'dilapidated brick wall'. We suggest the term 'dilapidated brick wall RCM sign' to describe this feature and to distinguish from the corresponding histopathology finding. Other RCM features included: epidermal disarray, intraepidermal clefts, inflammatory cells in the epidermis and in the superficial dermis. These RCM abnormalities correlated with analogous histopathology findings. CONCLUSION: Reflectance confocal microscopy is a promising non-invasive diagnostic tool for Hailey-Hailey disease. The method may also be considered useful for choosing the best site for biopsy, which may aid pathology evaluation and spare time needed to establish the diagnosis.

SorLA regulates the activity of lipoprotein lipase by intracellular trafficking.

Many different tissues and cell types exhibit regulated secretion of lipoprotein lipase (LPL). However, the sorting of LPL in the trans Golgi network has not, hitherto, been understood in detail. Here, we characterize the role of SorLA (officially known as SorLA-1 or sortilin-related receptor) in the intracellular trafficking of LPL. We found that LPL bound to SorLA under neutral and acidic conditions, and in cells this binding mainly occurred in vesicular structures. SorLA expression changed the subcellular distribution of LPL so it became more concentrated in endosomes. From the endosomes, LPL was further routed to the lysosomes, which resulted in a degradation of newly synthesized LPL. Consequently, an 80% reduction of LPL activity was observed in cells that expressed SorLA. By analogy, SorLA regulated the vesicle-like localization of LPL in primary neuronal cells. Thus, LPL binds to SorLA in the biosynthetic pathway and is subsequently transported to endosomes. As a result of this SorLA mediated-transport, newly synthesized LPL can be routed into specialized vesicles and eventually sent to degradation, and its activity thereby regulated.

Patient characteristics and symptoms associated with perceived coercion during hospital treatment.

OBJECTIVE: Large numbers of psychiatric patients either are involuntarily admitted to hospital treatment or feel coerced despite a legally voluntary admission. For ethical and clinical reasons, their perceived coercion should be reduced as far as possible. There is however limited evidence on patient characteristics associated with perceived coercion during hospital treatment. This study aimed to identify i) sociodemographic and clinical characteristics associated with perceived coercion at admission and ii) changes in symptoms and global functioning associated with changes in perceived coercion over time. METHOD: Three thousand and ninety three in-patients who were involuntarily admitted or felt coerced to hospital treatment despite a legally voluntary admission were recruited in the European evaluation of coercion in psychiatry and harmonization of best clinical practice - EUNOMIA project in 11 European countries. Perceived coercion, global functioning and symptoms were assessed after admission and at a 3-month follow-up. RESULTS: Involuntary admission, female gender, poorer global functioning and more positive symptoms were associated with higher levels of perceived coercion at admission. Perceived coercion significantly decreased over time, and the improvements in global functioning and positive symptoms were associated with reduction in perceived coercion. CONCLUSION: Female patients perceive more coercion in psychiatric hospital treatment. Effective treatment for positive symptoms and improving patients' global functioning may lead to a reduction in perceived coercion.

Investigating the relationship between autistic traits and symptoms and Catatonia Spectrum.

BACKGROUND: In recent years, numerous studies have highlighted the overlap between autism spectrum disorder (ASD) and catatonia, both from a clinical and pathophysiological perspective. This study aimed to investigate the relationship between the autism spectrum (autistic traits and ASD signs, symptoms, and behavioral manifestation) and Catatonia Spectrum (CS). METHODS: A total sample of 376 subjects was distributed in four diagnostic groups. Subjects were assessed with the Structured Clinical Interview for DSM-5, Research Version, the Adult Autism Subthreshold Spectrum (AdAS Spectrum), and CS. In the statistical analyses, the total sample was also divided into three groups according to the degree of autism severity, based on the AdAS Spectrum total score. RESULTS: A statistically significant positive correlation was found between AdAS Spectrum and CS total score within the total sample, the gender subgroups, and the diagnostic categories. The AdAS Spectrum domains found to be significantly and strongly correlated with the total CS score were hyper-hypo reactivity to sensory input, verbal communication, nonverbal communication, restricted interests and rumination, and inflexibility and adherence to routine. The three groups of different autistic severity were found to be distributed across all diagnostic groups and the CS score increased significantly from the group without autistic traits to the group with ASD. CONCLUSIONS: Our study reports a strong correlation between autism spectrum and CS.

Cloning and molecular characterization of Dashurin encoded by C20orf116, a PCI-domain containing protein.

BACKGROUND: Characterization of gene products originating from undefined open reading frames and delineation of biological functions has become the task after the human genome has been decoded. METHODS: We cloned the human C20orf 116 and defined its transcript in liver, kidney and various brain regions by Northern analysis. Antibodies against recombinant protein used for immunofluorescence and immunoblots confirmed its expression in these tissues. With the focus on kidney, its tubular expression and presence in glomerula were shown. RESULTS: A 28 aa long signal peptide predicted by in silico analysis is reflected by visualization of size variants of approximately 3kDa difference suggesting a signal peptidase cleavage of the proform. Cell compartment separation confirmed the presence of Dashurin in peroxisomes/mitochondria, microsomes, cytosol and nucleus. This is in line with green fluorescent protein (GFP)-Dashurin fusion protein shuttling between cytosol and nucleus. Luciferase reporter studies revealed a 2-3 fold increase of promoter activities upon over-expression. Bioinformatic analysis identified a PCI-domain at the C-terminus providing protein-protein interaction capabilities. CONCLUSION: Our present findings suggest the involvement of Dashurin in gene transcription or mRNA translation. GENERAL SIGNIFICANCE: Dashurin shares the PCI-domain with three multisubunit protein complexes (26S proteasome, COP9 signalosome and eIF3 translation initiation factor).

Asymmetry of salivary cortisol and α-amylase responses to psychosocial stress in anorexia nervosa but not in bulimia nervosa.

BACKGROUND: The stress response involves the activation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). As a role for stress in determining of the onset and the natural course of eating disorders (EDs) has been proposed, the study of the psychobiology of the stress response in patients with anorexia nervosa (AN) and bulimia nervosa (BN) should be helpful in understanding the pathophysiology of these disorders. The two neurobiological components of the stress response can be easily explored in humans by the measurement of salivary cortisol and α-amylase response to a stressor. Therefore, we assessed salivary cortisol and α-amylase responses to the Trier Social Stress Test (TSST) in symptomatic patients with AN and BN compared to healthy controls. METHOD: Seven AN women, eight BN women and eight age-matched healthy females underwent the TSST between 1530 and 1700 h. Salivary cortisol and α-amylase levels were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Compared to healthy women, AN patients showed a normal cortisol response to the TSST, although this occurred at significantly increased hormone levels, and an almost complete absence of response of α-amylase. BN women, however, exhibited enhanced pre-stress levels of salivary α-amylase but a normal response of the enzyme and cortisol to the TSST. CONCLUSIONS: These findings demonstrate, for the first time, the occurrence of an asymmetry between the HPA axis and SNS components of the stress response in the acute phase of AN but not in BN. The pathophysiological significance of this asymmetry remains to be determined.

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.