Lorenzo Lelli

The Role of Life Events and HPA Axis in Anxiety Disorders: A Review

Stressful life events and dysfunctional Hypothalamic Pituitary Adrenal (HPA) axis have been implicated in the pathogenesis of psychiatric disorders, including anxiety disorders. This paper attempts to review the existing literature on childhood traumata, recent life events, HPA axis functioning and their relationship in Post-Traumatic Stress Disorder, Panic Disorder, Generalized Anxiety Disorder, Obsessive Compulsive Disorder and Social Phobia. Preclinical and clinical models will be analyzed. Stressful life events seem to have a role in the onset and in the course of these disorders and HPA axis abnormalities have been reported in almost all anxiety disorders. The hypothesis that early stressful life events may provoke alterations of the stress response and thus of the HPA axis, that can endure during adulthood, predisposing individuals to develop psychopathology, will be evaluated.

Childhood stressful events, HPA axis and anxiety disorders

Anxiety disorders are among the most common of all mental disorders and their pathogenesis is a major topic in psychiatry, both for prevention and treatment. Early stressful life events and alterations of hypothalamic pituitary adrenal (HPA) axis function seem to have a significant role in the onset of anxiety. Existing data appear to support the mediating effect of the HPA axis between childhood traumata and posttraumatic stress disorder. Findings on the HPA axis activity at baseline and after stimuli in panic disordered patients are inconclusive, even if stressful life events may have a triggering function in the development of this disorder. Data on the relationship between stress, HPA axis functioning and obsessive-compulsive disorder (OCD) are scarce and discordant, but an increased activity of the HPA axis is reported in OCD patients. Moreover, normal basal cortisol levels and hyper-responsiveness of the adrenal cortex during a psychosocial stressor are observed in social phobics. Finally, abnormal HPA axis activity has also been observed in generalized anxiety disordered patients. While several hypothesis have attempted to explain these findings over time, currently the most widely accepted theory is that early stressful life events may provoke alterations of the stress response and thus of the HPA axis, that can endure during adulthood, predisposing individuals to develop psychopathology. All theories are reviewed and the authors conclude that childhood life events and HPA abnormalities may be specifically and transnosographically related to all anxiety disorders, as well as, more broadly, to all psychiatric disorders.

Gender Identity Disorder and Eating Disorders: Similarities and Differences in Terms of Body Uneasiness

INTRODUCTION Subjects with gender identity disorder (GID) have been reported to be highly dissatisfied with their body, and it has been suggested that the body is their primary source of suffering. AIMS.: To evaluate quality and intensity of body uneasiness in GID subjects, comparing them with a sample of eating disorder patients and a control group. To detect similarities and differences between subgroups of GID subjects, on the basis of genotypic sex and transitional stage. METHODS Fifty male-to-female (MtF) GID (25 without and 25 with genital reassignment surgery performed), 50 female-to-male (FtM) GID (28 without and 22 with genital reassignment surgery performed), 88 eating disorder subjects (26 anorexia nervosa, 26 bulimia nervosa, and 36 binge eating disorder), and 107 healthy subjects were evaluated. MAIN OUTCOME MEASURES Subjects were studied by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the Symptom Checklist (SCL-90), and the Body Uneasiness Test (BUT). RESULTS GID and controls reported lower psychiatric comorbidity and lower SCL-90 General Severity Index (GSI) scores than eating disorder subjects. GID MtF without genital reassignment surgery showed the highest BUT values, whereas GID FtM without genital reassignment surgery and eating disorder subjects showed higher values compared with both GID MtF and FtM who underwent genital reassignment surgery and controls. Considering BUT subscales, a different pattern of body uneasiness was observed in GID and eating disorder subjects. GID MtF and FtM without genital reassignment surgery showed the highest BUT GSI/SCL-90 GSI ratio compared with all the eating disorder groups. CONCLUSIONS GID and eating disorders are characterized by a severe body uneasiness, which represents the core of distress in both conditions. Different dimensions of body uneasiness seem to be involved in GID subsamples, depending on reassignment stage and genotypic sex. In eating disorder subjects body uneasiness is primarily linked to general psychopathology, whereas in GID such a relationship is lacking.

Association between serotonin transporter gene polymorphism and eating disorders outcome: A 6‐year follow‐up study

Eating disorder patients show different long‐term outcomes, and trait‐related alterations of serotonergic function, which might be related with the serotonin transporter (5‐HTT) gene. We studied the relationships between 5‐HTTLPR polymorphism, eating specific and general psychopathology and the long‐term outcome of anorexia nervosa (AN) and bulimia nervosa (BN) patients. We evaluated the distribution of the functional 5‐HTTLPR polymorphism in a series of 201 Italian, Caucasian, eating disorder patients (113 with AN and 88 with BN binge/purging (BP subtype) and in 150 Caucasian unrelated controls. Prior to starting an individual cognitive behavior therapy, a clinical assessment was performed by means of the structured clinical interview for DSM‐IV axis I disorders and several self‐report questionnaires. This assessment was repeated at the end of treatment, 3 years after the end of treatment and 3 years after the first follow‐up. Diagnostic changes between AN and BN were frequent (28.3%), and the presence of depressive disorders was associated with a higher rate of diagnostic crossover during the follow‐up period. The S‐allele of the 5‐HTTLPR genotype increases the risk susceptibility for both depressive comorbidity (OR = 4.23; 95% CI, 1.45–12.37) and diagnostic crossover during the follow‐up period in AN patients (OR = 5.04; 95% CI, 1.69–14.98). Logistic regression analyses confirmed these findings, when the interaction between genotype and psychiatric comorbidity as predictors of diagnostic instability in AN patients were taken into account. No significant association was found between 5‐HTTLPR genotype and recovery. The S‐allele of the 5‐HTTLPR genotype increases the risk for depressive disorders comorbidity, and moderates the long‐term outcome of anorectic patients.

Childhood sexual abuse moderates the relationship between sexual functioning and eating disorder psychopathology in anorexia nervosa and bulimia nervosa: a 1-year follow-up study.

INTRODUCTION Sexual dysfunctions that affect all aspects of sexuality are common in patients with eating disorders. However, only few studies have provided longitudinal information on sexual functioning in patients with eating disorders. AIM To evaluate the longitudinal course of sexual functioning, and how changes in psychopathology and history of childhood abuse interact with sexual functioning in patients with anorexia nervosa (AN) and bulimia nervosa (BN). METHODS A total of 27 patients with AN and 31 with BN were assessed at baseline and at 1-year follow-up after a standard individual cognitive behavioral therapy (CBT). MAIN OUTCOME MEASURES Subjects were studied by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders IV, Female Sexual Function Index (FSFI), Eating Disorder Examination Questionnaire, Beck Depression Inventory, Spielbergs State-Trait Anxiety Inventory, Symptom Checklist-90, and Childhood Experience of Care and Abuse Questionnaire. RESULTS After treatment, both patients with AN and BN showed a significant improvement in the FSFI total score (P < 0.01 for both AN and BN) and all FSFI subscales, without significant between groups differences. Patients reporting childhood sexual abuse did not show a significant improvement in sexual functioning (β = 0.05; P = 0.58). Reduction in eating disorder severity was directly associated with FSFI improvement, but only in those subjects with no history of sexual abuse (β = 0.28; P = 0.01). CONCLUSIONS Eating disorder-specific psychopathology could be considered as a specific maintaining factor for sexual dysfunction in eating disorders subjects. Subjects reporting a history of childhood sexual abuse represent a subpopulation of patients with a profound uneasiness, involving body perception, as well as sexual functioning, which appeared not to be adequately challenged during standard CBT intervention. The results, though original, should be considered as preliminary, given the relatively small sample size.

Anorectic and Bulimic Patients Suffer from Relevant Sexual Dysfunctions

INTRODUCTION Sexual life is often impaired in anorexia nervosa (AN) and bulimia nervosa (BN), and few studies have evaluated the possible relationships between body image concerns, eating disorder psychopathology, and sexual functioning in these syndromes. AIM To evaluate sexual functioning in AN patients, BN patients, and healthy controls, and to define the predictors of sexual dysfunction in the AN and BN groups. METHODS Eighty-eight eating disorders patients (44 AN, 44 BN) referring to the Outpatient Clinic for Eating Disorders of the University of Florence, and 72 healthy females were evaluated. MAIN OUTCOME MEASURES The subjects were studied by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders IV, the Female Sexual Function Index (FSFI), the Eating Disorder Examination Questionnaire, the Emotional Eating Scale, the Beck Depression Inventory, the Spielbergs State-Trait Anxiety Inventory, the Barratt Impulsiveness Scale, and the Symptom Checklist 90. RESULTS AN restricting/type patients had lower FSFI total scores (median; quartiles: 4.8; 2.1-15.4), compared with AN binge/purging type (28.3; 20.6-30.7) and BN patients (20.1; 3.8-30.3). Multiple linear regression analysis showed that shape concern was associated with sexual dysfunction in AN restricting type patients (β=-0.61, P<0.01), whereas emotional eating (β=-0.42, P<0.01), and subjective binge eating (β=-0.55, P<0.01) were significantly associated with FSFI scores in AN binge/purging type and BN patients. CONCLUSIONS Considering the sample size, the present results must be considered as preliminary. Sexual dysfunction was found to be a relevant concern in both AN and BN patients and was associated with different pathological eating behaviors. Sexual functioning should be carefully investigated in eating disorders patients, and treatments focused on shape concern, emotional eating, and binge eating could improve the sexual life of AN and BN patients.

Psychopathological and Clinical Features of Remitted Anorexia Nervosa Patients: A Six-year Follow-up Study

OBJECTIVE Remission from anorexia nervosa (AN) is a controversial issue, as remitted individuals have been found to show residual anorectic attitudes and concerns about weight and shape. The aims of this study were to evaluate the psychopathological features of remitted AN subjects 6 years after the end of a cognitive behavioural therapy and the predictors of reduction in psychopathology. METHODS The sample was composed of 134 AN subjects, evaluated at baseline, at the end of treatment, 3 and 6 years after the end of treatment, by means of the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and several self-reported questionnaires. RESULTS Remitted patients at 6 years of follow-up still showed higher eating and shape concerns, compared with healthy controls. Duration of illness, obsessive-compulsive and depressive symptoms were moderators of change in psychopathology across time. DISCUSSION Psychopathological features represent an enduring trait for AN patients. General psychopathology showed different effects on symptoms reduction across time.

Sexuality in eating disorders patients: etiological factors, sexual dysfunction and identity issues. A systematic review.

Abstract The scientific community appears to be less interested in sexuality of eating disorders (EDs) as compared to other psychiatric or medical comorbidities. However, a clear association between sexual problems and ED psychopathology was reported from different perspectives. The overarching goal of this systematic review was to evaluate the general approach of the scientific literature toward the topic of sexuality and EDs. In particular, four different categories of research have been individuated, encompassing the role of puberty, and sexual abuse in the pathogenesis of the disorders, sexual dysfunctions, and the association between sexual orientation and EDs psychopathology. Timing of puberty with its hormonal consequences and the changes in the way persons perceive their own body represent a crucial period of life for the onset of the disorder. Sexual abuse, and especially childhood sexual abuse are well-recognized risk factors for the development of ED, determining a worse long-term outcome. Recent research overcome the approach that considers sexual activity of EDs patients, in terms of hypersexuality and dangerous sexual behaviors, considering the sexuality of EDs persons in terms of sexual desire, satisfaction, orgasm and pain. Results from this line of research are promising, and describe a clear relationship between sexual dysfunction and the core psychopathological features of EDs, such as body image disturbances. Finally, the analysis of the literature showed an association between sexual orientation and gender dysphoria with EDs psychopathology and pathological eating behaviors, confirming the validity of research developing new models of maintaining factors of EDs related to the topic of self-identity.

Neuroendocrinology and brain imaging of reward in eating disorders: A possible key to the treatment of anorexia nervosa and bulimia nervosa

ABSTRACT Anorexia nervosa and bulimia nervosa are severe eating disorders whose etiopathogenesis is still unknown. Clinical features suggest that eating disorders may develop as reward‐dependent syndromes, since eating less food is perceived as rewarding in anorexia nervosa while consumption of large amounts of food during binge episodes in bulimia nervosa aims at reducing the patients negative emotional states. Therefore, brain reward mechanisms have been a major focus of research in the attempt to contribute to the comprehension of the pathophysiology of these disorders. Structural brain imaging data provided the evidence that brain reward circuits may be altered in patients with anorexia or bulimia nervosa. Similarly, functional brain imaging studies exploring the activation of brain reward circuits by food stimuli as well as by stimuli recognized to be potentially rewarding for eating disordered patients, such as body image cues or stimuli related to food deprivation and physical hyperactivity, showed several dysfunctions in ED patients. Moreover, very recently, it has been demonstrated that some of the biochemical homeostatic modulators of eating behavior are also implicated in the regulation of food‐related and non‐food‐related reward, representing a possible link between the aberrant behaviors of ED subjects and their hypothesized deranged reward processes. In particular, changes in leptin and ghrelin occur in patients with anorexia or bulimia nervosa and have been suggested to represent not only homeostatic adaptations to an altered energy balance but to contribute also to the acquisition and/or maintenance of persistent starvation, binge eating and physical hyperactivity, which are potentially rewarding for ED patients. On the basis of such findings new pathogenetic models of EDs have been proposed, and these models may provide new theoretical basis for the development of innovative treatment strategies, either psychological and pharmacological, with the aim to improve the outcomes of so severe disabling disorders. HIGHLIGHTSEating disorders (EDs) have been proposed to develop as reward‐dependent syndromes.Brain imaging studies demonstrated structural and functional alterations of brain reward circuits in ED patients.Neuroendocrine modulators of eating behavior are implicated also in reward regulation.Changes in leptin and ghrelin occurring in the acute phase of an ED may sustain aberrant rewarding behaviors.This conceptualization may provide new theoretical basis for the development of innovative treatments of EDs.

Associations between Liver Enzymes, Psychopathological and Clinical Features in Eating Disorders

Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are frequently reported in patients with anorexia nervosa (AN) and in subjects who are overweight or with hyperlipidemia, which can be found to be associated with binge eating disorder (BED) and bulimia nervosa (BN). Liver functioning and psychopathological features have been evaluated in 43 patients with AN, 33 with BN, and 32 with BED. Body mass index was found to be inversely associated with AST and ALT in AN, and directly associated with AST and ALT in BED. A positive association between ALT and AST and body shape concern in AN was observed. Liver enzymes could be considered as an index of severity in AN and BED patients.