Longitudinal trajectories of psychosocial functioning in patients with pre-existing mental disorders after one year of COVID-19 pandemic.

Aims of the present study were to prospectively assess psychosocial functioning trajectories during the COVID pandemic and the possible impact of sociodemographic variables, as well as of COVID-19 pandemic-related factors, on these trajectories, in a sample of patients with pre-existing severe mental disorders. Moreover, we aimed at identifying predictors of impairment in psychosocial functioning over a period of 9 months of COVID-19 pandemic. Patients were recruited during the 3rd wave of the COVID-19 pandemic (T0, March-April 2021) while strict containment measures were applied in Italy, and reassessed after 3 months (T1, June-July 2021), and after 6 months from T1 (T2- November-December 2021), during the 4th wave of COVID pandemic. A sample of 300 subject (out of the 527 subjects recruited at baseline) completed the T2 evaluation. Patients were assessed by: Work and Social Adjustment Scale (WSAS) for psychosocial functioning, Generalized Anxiety Disorder 7-Item (GAD-7) for anxiety symptoms, Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms and the Impact of Events Scale-Revised, for post-traumatic symptoms. Cluster analyses identified 4 trajectories of functioning: the High, Stable Functioning group (N = 77), the Improvement Functioning group (N = 62), the Progressive Impairment group (N = 83) and the Persistent Severe Impairment group (N = 78) respectively. We found that predictors of higher WSAS score at T2 were higher WSAS score at T0 (B = 0.43, p < .001), PHQ scores at baseline >10 (B = 2.89, p < .05), while not living alone was found to be a protective factor (B = -2.5, p < .05). Results of the present study provides insights into the vulnerability of individuals with psychiatric disorders during times of crisis. Study findings can contribute to a better understanding of the specific needs of this population and inform interventions and support strategies.

Pre-operative micronutrient deficiencies in patients with severe obesity candidates for bariatric surgery.

PURPOSE: In patients with obesity, micronutrient deficiencies have been reported both before and after bariatric surgery (BS). Obesity is a chronic pro-inflammatory status, and inflammation increases the risk of micronutrient malnutrition. Our objective was to assess in pre-BS patients the prevalence of micronutrient deficiencies and their correlation with blood values of C-reactive protein (CRP). METHODS: Anthropometric data, instrumental examinations, and blood variables were centrally measured in the first 200 patients undergoing a pre-BS evaluation at the "Città della Salute e della Scienza" Hospital of Torino, starting from January 2018. RESULTS: At least one micronutrient deficiency was present in 85.5% of pre-BS patients. Vitamin D deficiency was the most prevalent (74.5%), followed by folate (33.5%), iron (32%), calcium (13%), vitamin B12 (10%), and albumin (5.5%) deficiency. CRP values were high (> 5 mg/L) in 65% of the patients. These individuals showed increased rate of iron, folate, vitamin B12 deficiency, and a higher number of micronutrient deficiencies. In a multiple logistic regression model, increased CRP levels were significantly associated with deficiencies of vitamin B12 (OR = 5.84; 95% CI 1.25-27.2; p = 0.024), folate (OR = 4.02; 1.87-8.66; p < 0.001), and with the presence of ≥ 2 micronutrient deficiencies (OR = 2.31; 1.21-4.42; p = 0.01). CONCLUSIONS: Micronutrient deficiencies are common in patients with severe obesity undergoing BS, especially when inflammation is present. In the presence of increased CRP values before surgery, it might be advisable to search for possible multiple micronutrient deficiencies.

Naturalistic follow-up of subjects affected with anorexia nervosa 8 years after multimodal treatment: Personality and psychopathology changes and predictors of outcome.

BACKGROUND: Eating disorders (EDs) are serious mental illnesses of growing clinical and social impact. Despite their severity, there is still no satisfactory evidence-based treatment. Follow-up investigations are the most reliable studies to enlighten long-term outcome predictors and modifiers. METHODS: In total, 59 subjects affected with anorexia nervosa were assessed 8 years after their admission into an outpatient multimodal treatment program for eating disorders. The follow-up changes in diagnostic criteria were compared with Chi-square test. Improved and not-improved subjects were compared. Clinical, personality and psychopathology features between T0 and T1 were compared with t-test for repeated measures. Correlation between T0 features and changes at T1 in personality and psychopathology features were assessed. RESULTS: The rate of complete remission was 42%, an overall rate of 67.8% improved, a rate of 18.6% worsened. Concerning personality, a significant decrease of harm avoidance and increase in self-directedness were evidenced. Interoceptive awareness, drive for thinness, bulimia were significantly reduced at follow-up. Many T0 personality facets were related to personality and psychopathology improvement at follow-up. CONCLUSION: Multimodal treatment encompassing psychiatric, nutritional and psychological approaches is at the moment the most reliable approach for the treatment of moderate to severe anorexia nervosa with a discrete rate of improvement. Some personality and psychopathology characteristics may represent specific factors which favor resistance and impair improvement. Future approaches should consider the personalization of therapeutic approach according to these features.

Identifying neuroanatomical signatures of anorexia nervosa: a multivariate machine learning approach.

BACKGROUND: There are currently no neuroanatomical biomarkers of anorexia nervosa (AN) available to make clinical inferences at an individual subject level. We present results of a multivariate machine learning (ML) approach utilizing structural neuroanatomical scan data to differentiate AN patients from matched healthy controls at an individual subject level. METHOD: Structural neuroimaging scans were acquired from 15 female patients with AN (age = 20, s.d. = 4 years) and 15 demographically matched female controls (age = 22, s.d. = 3 years). Neuroanatomical volumes were extracted using the FreeSurfer software and input into the Least Absolute Shrinkage and Selection Operator (LASSO) multivariate ML algorithm. LASSO was 'trained' to identify 'novel' individual subjects as either AN patients or healthy controls. Furthermore, the model estimated the probability that an individual subject belonged to the AN group based on an individual scan. RESULTS: The model correctly predicted 25 out of 30 subjects, translating into 83.3% accuracy (sensitivity 86.7%, specificity 80.0%) (p < 0.001; χ 2 test). Six neuroanatomical regions (cerebellum white matter, choroid plexus, putamen, accumbens, the diencephalon and the third ventricle) were found to be relevant in distinguishing individual AN patients from healthy controls. The predicted probabilities showed a linear relationship with drive for thinness clinical scores (r = 0.52, p < 0.005) and with body mass index (BMI) (r = -0.45, p = 0.01). CONCLUSIONS: The model achieved a good predictive accuracy and drive for thinness showed a strong neuroanatomical signature. These results indicate that neuroimaging scans coupled with ML techniques have the potential to provide information at an individual subject level that might be relevant to clinical outcomes.

Intrinsic connectivity networks within cerebellum and beyond in eating disorders.

Cerebellum seems to have a role both in feeding behavior and emotion regulation; therefore, it is a region that warrants further neuroimaging studies in eating disorders, severe conditions that determine a significant impairment in the physical and psychological domain. The aim of this study was to examine the cerebellum intrinsic connectivity during functional magnetic resonance imaging resting state in anorexia nervosa (AN), bulimia nervosa (BN), and healthy controls (CN). Resting state brain activity was decomposed into intrinsic connectivity networks (ICNs) using group spatial independent component analysis on the resting blood oxygenation level dependent time courses of 12 AN, 12 BN, and 10 CN. We extracted the cerebellar ICN and compared it between groups. Intrinsic connectivity within the cerebellar network showed some common alterations in eating disordered compared to healthy subjects (e.g., a greater connectivity with insulae, vermis, and paravermis and a lesser connectivity with parietal lobe); AN and BN patients were characterized by some peculiar alterations in connectivity patterns (e.g., greater connectivity with the insulae in AN compared to BN, greater connectivity with anterior cingulate cortex in BN compared to AN). Our data are consistent with the presence of different alterations in the cerebellar network in AN and BN patients that could be related to psychopathologic dimensions of eating disorders.

Does it exist a personality core of mental illness? A systematic review on core psychobiological personality traits in mental disorders.

AIM: Research investigating the relationship between mental disorders and personality traits leads to interesting results. Individuals affected by several mental disorders have been worldwide assessed according to the psychobiological model of personality. This review aims to explore which temperament and character traits are recurrent in mental disorders and to highlight what traits may be shared determinants or consequences of the expression of a mental disorder. METHODS: Systematic search of Medline database between 1998 and 2011 has been conducted to select the studies exploring the Temperament and Character Inventory (TCI) dimensions in the most relevant axis I psychiatric disorders. Of the 110 studies that were retrieved, 88 met the inclusion/exclusion criteria and were analyzed. RESULTS: High HA (HA) and low self-directedness are recurrent and can be considered as a "personality core" regardless of the diagnosis. They may be risk factors and relapse-related, they can indicate incomplete remission or chronic course of mental disorders, and consistently influence patients' functioning. Furthermore, they can be modified by medications or psychotherapy and represent outcome predictors of treatments. CONCLUSION: This "core" may represent a personality diathesis to psychopathology. Relational environment can influence the development of both temperament and character, thus prevention of mental disorders should promote a positive development of these traits. Although further research is needed, psychotherapeutic interventions should be performed also considering that mental disorders could benefit from HA desensitization and SD reinforcement. Finally, these traits may be used to provide diagnostic, prognostic, quality of life and efficacy inferences on psychiatric treatments.

The borderline personality organization in a dimensional perspective: the TCI and SWAP-200 in comparison.

AIM: The categorical assessment of personality disorders, in particular of the borderline personality disorder is being debated by most authors. This study focuses on the structural organization of personality, namely on Kernberg's borderline personality organization (BPO). It aims to explore the dimensional personality assessment and to test the convergence on this construct of two dimensional instruments: the Temperament and Character Inventory (TCI) and the Shedler-Westen Assessment Procedure (SWAP-200). METHODS: BPO was assessed with the Temperament and Character Inventory (TCI) and the Shedler-Westen Assessment Procedure (SWAP-200). Thirty-four BPO subjects were recruited in the study. TCI profiles of BPO subjects were compared with 34 non-BPO matched controls. TCI and SWAP-200 profiles were correlated with each other and with clinical data. RESULTS: BPO subjects showed higher harm avoidance and lower self-directedness (TCI). The SWAP-200 evidenced a schizotypal configuration (categorical classification) and histrionic and schizoid traits (Q-sort classification). CONCLUSION: The instruments displayed limited correlation. Instead they both extensively correlated with clinical history of BPO subjects. Implications for BPO assessment and its relationship with mental disorders are discussed. The knowledge of the BPO dimensional characteristics will improve clinical management and therapeutic strategies for BPO patients. Moreover the comparison of two dimensional instruments on the construct of BPO may shed a light on their strengths and weaknesses.

Amenorrhea in eating disorders: poor stability of symptom after a one-year treatment.

OBJECTIVE: To examine whether patients with Eating Disorders (ED) who restore menses differ from those who remain amenorrheic after treatment and to provide longitudinal data about this debated criterion of Anorexia Nervosa (AN). METHODS: 184 outpatients were recruited: 50 patients with AN Restrictive type, 75 amenorrheic Eating Disorder Not Otherwise Specified (EDNOS) patients, 24 patients who recovered from AN with persistent amenorrhea, and 35 amenorrheic patients without ED. All participants were clinically assessed by psychiatrists and gynaecologists at the beginning of treatment and at the one-year follow-up. They also completed several psychometric tests: Eating Disorder Inventory-2, Temperament and Character Inventory, and Beck Depression Inventory. RESULTS: After treatment, a large portion of the sample resumed menses but very few recovered completely from the ED. No psychopathological variables could clearly predict the recovery of menses in the different groups. However, Body Mass Index and some biological variables were associated with restoration of menses in ED patients. CONCLUSION: Resumption of menses was not associated with a less severe eating symptomatology at the beginning of treatment nor with unequivocal psychopathological changes after treatment. It is important that clinicians consider not only the presence or absence of regular menses but also that they improve both ED screening and assessment in amenorrheic patients. Amenorrhea does not seem to represent a specific predictor of severity of illness or to show prognostic value.

Growing up with a congenital heart disease: neuro-cognitive, psychopathological and quality of life outcomes.

About 1% of newborn presents some form of congenital heart disease (CHD). Eighty-five percent of these children, thanks to medical and surgical improvement, reaches adulthood. This open up new challenges in patients management, such as the evaluation and optimization of psychosocial functioning and quality of life of CHD subjects. The present review collects research literature regarding neurocognitive and psychopathological adjustment, and personality and quality of life of these patients, analyzing variables that may influence their development. Literature data lean towards a multifactorial process implied into an insufficient outcome of neurocognitive development in many patients. Psychopathological development seems "problematic" with the expression of behavioural disorders both externalising and internalising. But current researches don't consent univocal and definitive conclusions. The need for interventions to improve existential outcome for CHD subjects emerges: research on genetic factors and early recognition of at risk subjects must go with the necessity for research aiming to determine protective and risk factors related to personality, environment and relational aspects entailed in the development of CHD subjects. Finally, some evidences noticed in CHD subjects psychopathological and quality of life outcomes which are even better than normal ones. These results depend on the elaboration of their disease that CHD subjects have carried on. Factors regarding mainly personality development are essential in determining these outcomes.

Self-esteem and personality in subjects with and without body dysmorphic disorder traits undergoing cosmetic rhinoplasty: preliminary data.

BACKGROUND: Many individuals with body dysmorphic disorder (BDD) seek non-psychiatric treatment. BDD occurs in about 5% of patients who seek cosmetic surgery, and rhinoplasty is the most frequently sought treatment. A correlation exists between individuals' self-esteem and demand for cosmetic surgery. OBJECTIVE: To investigate whether those subjects with BDD traits requesting cosmetic rhinoplasty differ from those without BDD traits in self-esteem, personality and quality of life. METHODS: This study included 54 patients applying to the 1st ENT Division of Turin University. Assessment of the patients before cosmetic rhinoplasty includes: nasal obstruction symptom evaluation, health-related quality of life, Rosenberg self-esteem scale, body dysmorphic disorder questionnaire (BDDQ) and temperament and character inventory (TCI). Based on their responses to BDDQ questions 1, 3 and 4, patients were subdivided into subgroups and then compared. RESULTS: No difference emerged in the objective data. Lower self-esteem, higher harm avoidance (HA) and lower self-directedness (SD) are found in subjects who are worried about how they look, in those with interference in their social life due to this worry and in those who spend more than 3h per day thinking about the way they look. Novelty seeking (NS) is significantly higher in subjects who think about their looks for up to 3h than in those who spend less than 1h. CONCLUSION: Different subgroups of patients are identified. The first group includes pessimistic, shy, insecure subjects; people with fragile and immature personality and poor self-esteem; individuals concerned about the way they look and those who spend more time thinking about it. The second group includes more confident subjects with stronger personality and greater self-esteem. A third, less differentiated group, includes more impulsive (high NS) subjects who spend an intermediate amount of time thinking about the way they look. Patients should be carefully screened and assessed before cosmetic surgery interventions to avoid frustration to both, clinicians and patients.

Day hospital programmes for eating disorders: a review of the similarities, differences and goals.

Day hospital (DH) treatments for eating disorders (EDs) provide intensive daily care and allow patients to maintain and test their social relations and coping skills at home and outside. Although widespread, their description is lacking. This review compares the different types of DH described in the literature and presents our DH experience in Turin, Italy. We searched Psychinfo and Pubmed with the following keywords: anorexia nervosa, bulimia nervosa, EDs, DH, day treatment and partial hospitalisation. We found and reviewed the DH programmes of eleven specialised centres, which have some shared features but also many differences, suggesting that DH treatments are still largely experimental. Briefly, the shared elements are: biopsychosocial model as reference frame; cognitive-behavioural model or techniques; behavioural contract; patients' selection; body image therapy; involvement of family; weight normalisation/weight gain and modification/normalisation of eating behaviour as objectives. Nonetheless, shared opinions concerning inclusion criteria are lacking; the duration of DH treatment is surprisingly different among centres (from 3 to 39 weeks); the approach to eating and compensation behaviours ranges from control to autonomy; followup and psychometric assessment can be either performed or not; psychological and behavioural objectives can be different. This review suggests the existence of two different DH models: the first has a shorter duration and is mainly symptom-focused; the second is more individual-focused, has a longer duration and is focused on patients' relational skills, psychodynamic understanding of symptoms and more gradual changes in body weight. Further investigation is required to make DH treatment programmes measurable and comparable.

Personality and psychopathology correlates of dropout in an outpatient psychiatric service.

AIM: The dropout from care in public psychiatric units is a frequent event and strategies to reduce its incidence are still debated. This study aims to determine which personality and psychopathology dimensions influence the dropout in a psychiatric unit. METHODS: All new patients referred to a public psychiatric outpatient service were tested with self-administered inventories assessing personality traits (TCI), parental bonding (PBI), and psychopathology (SCL-90; BDI; STAXI). Completers were divided into nondropout, late dropout, and early dropout groups which were compared with each other with respect to diagnosis, referral, demographic data and the inventories. Logistic regression was performed between dropout and non dropout subjects with respect to the significantly differing variables. RESULTS: No clinical or demographic characteristic predict dropout. Numerous SCL-90 psychopathology scales, state anger and some TCI personality facets distinguish dropout from in care subjects. Psychoticism and sentimentalism have been evidenced independent predictors of dropout. CONCLUSION: In the present study dropout from the psychiatric unit is more related to personal characteristics than to sociodemographic variables or diagnosis. Dropout is related to personality and psychopathology characteristics which may reduce subject's relational skills and impair therapeutic alliance. These traits may also influence subjects' perception of the service quality and of the assessment procedure. The acknowledgement of such traits as possible determinants of dropout may orient service organization and personnel education to prevent this phenomenon in health care services. Strategies for preventing dropout are discussed.

Clinical, psychological and personality features related to age of onset of anorexia nervosa.

BACKGROUND: To investigate the relationship between age of onset and clinical and personality features of patients with anorexia nervosa (AN). SAMPLING AND METHOD: We assessed 250 outpatients with AN with the Temperament and Character Inventory, the Eating Disorder Inventory 2, the Beck Depression Inventory and the Body Shape Questionnaire. The patients were subdivided into 3 groups: early (n=73), intermediate (n=96) and late onset (n=81), based on age of onset of symptoms. RESULTS: The early-onset group shows higher body dissatisfaction, maturity fear, impulsivity and asceticism than the other 2 groups. This group shows a greater character fragility, as described in particular by a lower self-directedness, than the other 2 groups. CONCLUSIONS: Even several years after the onset of the disorder, early-onset subjects affected by AN seem characterized by a more disturbed personality, with a higher body dissatisfaction than late-onset subjects affected by AN and a pursuit of thinness based on an ascetic drive.

Eating disorders and the Internet: cure and curse.

OBJECTIVE: The role of culture and the mass-media in relation to eating disorders (EDs) is widely acknowledged, and the Internet has become an important part of this over the last few years. The aim of this report is to suggest the general features and potential clinical implications of "pro-Ana" websites and those concerning the treatment of EDs. METHOD: We conducted a Google search using the key words "anorexia nervosa (AN) and treatment", "AN and psychotherapy", "AN and pharmacotherapy", and then "pro-anorexia", "pro-ana sites", "thinspiration" and "anorexicnation". RESULTS: The first group of queries gave respectively 546,000, 212,000 and 39,100 results; the second 257,000, 18,600, 14,200 and 577. Forty-seven of 100 randomly selected pro-ana websites were thoroughly visited. CONCLUSIONS: Internet websites may increase the accessibility of treatments but also strengthen some of the core psychopathological and symptomatological issues of AN, such as asceticism, competition, purging behaviours and obsession for control. Greater attention should be paid to the health policy of countries in which pro-ana websites flourish, and the clinical implications of the websites themselves.

Baseline personality characteristics of responders to 6-month psychotherapy in eating disorders: preliminary data.

OBJECTIVE: The Karolinska Psychodynamic Profile (KAPP) was used for the assessment of the six-month outcome of Brief Adlerian Psychodynamic Psychotherapy (B-APP). METHOD: Fifty-seven eating disordered women (28 with anorexia nervosa, 29 with bulimia nervosa), were included in the study. The sample was evaluated at baseline (time 0) and after six months (T6) with a clinical assessment and with Temperament and Character Inventory (TCI), Eating Disorder Inventory (EDI-2), State-Trait Anger Expression Inventory (STAXI), and KAPP. RESULTS: Based on symptomatologic improvement, two sub-groups were obtained: responders (66.6%) and non-responders (33.3%). Significantly higher baseline scores emerged in the responders group on Ineffectiveness and Impulsivity (EDI-2) and on Harm Avoidance (TCI). Several KAPP items and areas improved in both groups at T6. CONCLUSION: Multimodal treatment centered on B-APP lead to both a global clinical improvement and an improvement in several psychological and psychopathological features as assessed by EDI-2, STAXI and KAPP. The results suggest interesting clinical implications, though outcome predictors are quite weak.

Psychological treatment of eating disorders. A review of the literature.

The aim of this study is to review the existing literature (PubMed database) on the psychological treatments for eating disorders (EDs), subdivided in individual, group and family therapies. Moreover new approaches and directions in this field are addressed. An extensive literature review is performed to identify the psychological treatment trials in anorexia nervosa (AN) and bulimia nervosa (BN) published over the past 2 decades. Eighty-two studies focused on psychotherapeutic treatment of EDs are reviewed. Only a minor part of these studies are randomised and controlled. While there is evidence of the efficacy of cognitive behavioral therapy (CBT), this is still missing for other psychotherapeutic approaches. However, there is general agreement about the importance of psychotherapy in multimodal treatments. There is still a need for a shared concept of outcome in EDs, since the efficacy of psychological treatment is greatly influenced by the definition of outcome adopted (concerning symptoms, psychosocial functioning, personality).

Temperament and character in eating disorders: ten years of studies.

In recent years a number of studies of personality have been performed in subjects with Eating Disorders (EDs) to investigate the clinical differences between controls and ED patients and among EDs subtypes, and its role in the development and course of symptoms. The Tridimensional Personality Questionnaire (TPQ) and the Temperament and Character Inventory (TCI) have been widely used at this purpose, allowing the description of specific temperament and character profiles for EDs. High Harm Avoidance (HA) and low Self-Directedness (SD) are shared by all EDs. Slight differences on some facets have been found among ED subgroups. Nevertheless, HA is influenced by mood and both high HA and low SD are personality traits shared by many mental disorders, whose specificity is rather low. Restrictor anorectics are characterized by high Persistence (P) and a relatively higher SD, and bulimics by higher Novelty Seeking (NS) and the lowest SD, while binge/purging and purging anorectics share some traits with anorexia and some with bulimia. Though current data justify the discrimination among anorexia subtypes, they are not in contrast with the thesis of a continuum in ED personality traits. Since some personality traits display a prognostic value with regard to therapy and clinical outcome, further studies are needed on treatments and prognostic factors in EDs. Moreover, studies attempting to define the neurobiological and genetic correlates of temperament should be supported by clinical pharmacological trials.

The adrenal sensitivity to ACTH stimulation is preserved in anorexia nervosa.

Hyperactivity of hypothalamus-pituitary-adrenal (HPA) axis in anorexia nervosa (AN) has been demonstrated and is likely to reflect a central nervous system (CNS)-mediated effect of starvation. Alterations in the adrenal response to ACTH in AN have also been reported by some authors. In order to define the adrenal sensitivity to ACTH in this condition, we studied cortisol (F), aldosterone (A) and DHEA responses to the sequential administration of low and supramaximal ACTH 1-24 doses (0.06 microg/m2 ACTH 1-24 iv at 0 min and 250 microg ACTH 1-24 iv at +60 min, respectively) in 10 young women with AN [ANW, age 21.2 +/- 0.9 yr, body mass index (BMI) 15.7 +/- 0.6 kg/m2]. The results in this group were compared with those recorded in 10 healthy normal women (HW, 23.4 +/- 1.1 yr, 21.9 +/- 0.9 kg/m2). In ANW urinary F levels were similar to those in HW. Basal serum F, A and DHEA levels in ANW were not significantly different from those in HW. In HW the lowest ACTH dose induced a significant (p<0.05) increase of F, A and DHEA. The maximal ACTH dose induced F, A and DHEA increases greater (p<0.05) than those induced by the lowest ACTH dose. In ANW both ACTH doses induced significant (p<0.05) F and DHEA increases which were not significantly different from those in HW, though a trend toward a lower cortisol response after ACTH 0.06 microg/m2 in ANW was present. Like in HW, in ANW the maximal ACTH dose induced F and DHEA increases greater (p<0.01) than those induced by the lowest dose. Unlike HW, in ANW A levels did not increase after the lowest ACTH dose while they increased after the maximal one overlapping the response in HW. In conclusion, the cortisol and DHEA responses to a very low and a supra-maximal ACTH dose in patients with AN were similar to those in healthy subjects, indicating that the sensitivity to ACTH of the fasciculata and reticularis adrenal zones is preserved in this condition. On the other hand, a reduced sensitivity to ACTH of the glomerularis adrenal zone in patients with AN is suggested by the lack of aldosterone response to the lowest corticotropin dose.

The endocrine response to acute ghrelin administration is blunted in patients with anorexia nervosa, a ghrelin hypersecretory state.

OBJECTIVE: Ghrelin, a gastric-derived natural ligand of the GH secretagogue (GHS)-receptor (GHS-R), strongly stimulates GH secretion but also possesses other neuroendocrine actions, stimulates food intake and modulates the endocrine pancreas and energy homeostasis. Ghrelin secretion is negatively modulated by food intake. Similarly, glucose and also insulin probably exert an inhibitory effect on ghrelin secretion. Fasting ghrelin levels are reduced in obesity, elevated in anorexia nervosa and restored by weight recovery. The chronic elevation of circulating ghrelin levels in anorexia suggested the hypothesis of an alteration of the sensitivity to the orexigenic action of ghrelin in this condition. The aim of this study was to define the endocrine actions of ghrelin in patients with anorexia nervosa. DESIGN: We enrolled nine women with anorexia nervosa of restricter type [AN; age (mean +/- SEM) 24.2 +/- 1.8 years; body mass index (BMI) 14.7 +/- 0.4 kg/m2] and seven normal young women in their early follicular phase as control group (NW; age 30.6 +/- 3.1 years; BMI 20.3 +/- 0.5 kg/m2). MEASUREMENTS: In all the subjects we studied the GH, PRL, ACTH, cortisol, insulin and glucose responses to acute ghrelin administration (1.0 microg/kg as i.v. bolus). The GH response to GHRH (1.0 microg/kg as i.v. bolus) and basal ghrelin and IGF-I levels were also evaluated in all the subjects. RESULTS: Basal morning ghrelin and GH levels in AN (643.6 +/- 21.3 ng/l and 10.4 +/- 0.5 microg/l, respectively) were higher (P < 0.05) than in NW (233.5 +/- 14.2 ng/l and 0.7 +/- 0.7 microg/l, respectively). However, IGF-I levels in AN (145.3 +/- 10.9 microg/l) were lower (P < 0.05) than in NW (325.4 +/- 12.6 microg/l). The GH response to GHRH in AN was higher (P < 0.05) than that in NW, but in AN the GH response to ghrelin was lower (P < 0.05) than that in NW. In AN and NW ghrelin also induced similar increases (P < 0.05) in PRL, ACTH and cortisol levels. Ghrelin administration was followed by significant increase in glucose levels in NW (P < 0.05) but not in AN. CONCLUSIONS: This study demonstrates that anorexia nervosa, a clinical condition of ghrelin hypersecretion, shows a specific reduction in the GH response to ghrelin, despite the hyper-responsiveness to GHRH administration. The impaired GH response to ghrelin in anorexia nervosa agrees with previous evidence of blunted GH response to synthetic GH secretagogues and could reflect desensitization of the GHS receptor induced by the chronic elevation of ghrelin levels in this pathological state.