F. Pietrini

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.

Functional neuroimaging in anorexia nervosa: A clinical approach

AIMS To provide a review of the available literature about the functional neuroimaging of anorexia nervosa, and to summarize the possible role of neurobiological factors in its pathogenesis. METHODS A systematic review of the literature was performed using PubMed and Medline electronic database (1950-September 2009). Eligible studies were restricted to those involving the main parameters of cerebral activity and functional neuroimaging techniques. Findings of the reviewed studies have been grouped on a diagnostic subtype basis, and their comparison has been interpreted in terms of concordance. RESULTS We found a high level of concordance among available studies with regard to the presence of frontal, parietal and cingulate functional disturbances in both anorexia nervosa restricting and binge/purging subtypes. Concordance among studies conducted regardless of the anorexia nervosa subtypes suggests an alteration in temporal and parietal functions and striatal metabolism. CONCLUSIONS The most consistent alterations in anorexia nervosa cerebral activity seem to involve the dorsolateral prefrontal cortex, the inferior parietal lobule, the anterior cingulate cortex and the caudate nucleus. They may affect different neural systems such as the frontal visual system, the attention network, the arousal and emotional processing systems, the reward processing network, and the network for the body schema.

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.

Generalized anxiety disorder: is there any specific symptom?

OBJECTIVE The main aim of the present research was to evaluate the coherence of generalized anxiety disorder (GAD) psychopathological pattern, the robustness of its diagnostic criteria, and the clinical utility of considering this disorder as a discrete condition rather than assigning it a dimensional value. METHOD The study was designed in a purely naturalistic setting and carried out using a community sample; data from the Sesto Fiorentino Study were reanalyzed. RESULTS Of the 105 subjects who satisfied the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria for the diagnosis of GAD, only 18 (17.1%) had no other comorbid DSM-IV disorder. The most frequent comorbid condition was major depressive disorder (70.4 %). Only 2 of the GAD diagnostic symptoms (excessive worry and muscle tension) showed a specific association with the diagnosis itself, whereas the others, such as feeling wound up, tense, or restless, concentration problems, and fatigue, were found to be more prevalent in major depressive disorder than in GAD. CONCLUSION Our study demonstrates that GAD, as defined by DSM-IV criteria, shows a substantial overlap with other DSM-IV diagnoses (especially with mood disorders) in the general population. Furthermore, GAD symptoms are frequent in all other disorders included in the mood/anxiety spectrum. Finally, none of the GAD symptoms, apart from muscle tension, distinguished GAD from patients without GAD.

Childhood Adversity, Cortisol Levels, and Psychosis: A Retrospective Investigation

Abstract Although it has been proposed that the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may act as a possible pathway linking early life stress to psychosis, this relationship has not yet been fully confirmed. This study aimed to investigate the relationship between childhood adversity (CA), cortisol levels, and psychosis. Eighty-five patients with psychosis and 170 control subjects were enrolled in the study. CA was evaluated using the Florence Psychiatric Interview, and Childhood Experience of Care and Abuse Questionnaire. Positive symptoms (PS) were assessed using the Positive and Negative Syndrome Scale. Cortisol levels were evaluated in saliva samples. Patients experienced more CA and showed higher cortisol levels than controls. Patients with CA showed higher morning cortisol levels and more severe PS than those without CA. Patients with higher morning cortisol levels showed severe delusions. These findings suggest that both CA and dysregulation of the HPA axis could be related to psychosis.

The effects of switching from oral to LAI antipsychotic treatment on subjective experience of schizophrenic and schizoaffective patients: Preliminary results

Abstract Objective. To present real-world preliminary evidence on the specific effects of switching from oral to long-acting injectable (LAI) antipsychotic treatment on patients subjective experience and quality of life (QoL) in a sample of clinically stable psychotic subjects. Methods. Twenty-six clinically stable adult schizophrenic and schizoaffective outpatients were recruited. All patients were under a stabilized therapy with a single oral second-generation antipsychotic and were switched to the equivalent maintenance regimen with the long-acting formulation of the same antipsychotic. Two subgroups of patients were created on the basis of the presence/absence of a complete clinical remission at enrollment. Anthropometric (body mass index), psychometric (Montgomery–Asberg Depression Rating Scale, Young Mania Rating Scale, and Positive And Negative Syndrome Scale), and patients reported outcome (Subjective Well-Being Under Neuroleptics scale short form, Drug Attitude Inventory short version, and Short Form-36 health survey) data were collected at enrollment (T0) and after 6 months from the treatment switch (T1). Results. Significant improvements in psychometric indexes, and patients’ subjective experience of treatment and attitudes toward drug (reflecting in an enrichment of patients’ health-related QoL) were found both in initial remitters and non-remitters. Conclusions. Our preliminary results suggest that the switch from oral to LAI antipsychotic treatment may help to address the subjective core of an optimal and satisfying recovery of psychotic patients. Size and duration of this study need to be expanded in order to produce more solid and generalizable results.

Coping with Neuropsychiatric Side Effects of Pegylated Interferon Alpha Therapy in Hepatitis C Virus Positive (HCV+) Patients: an Observational Study.

Background HCV is the most frequent cause of chronic hepatitis and a risk factor for liver cirrhosis and hepatocellular carcinoma. Despite recent advances in HCV therapy, Pegylated Interferon Alpha (PegIFNα) remains the treatment backbone, even if it can cause serious neuropsychiatric symptoms (from irritability to psychosis) that could reduce treatment compliance to the point of failure. Aims To describe the neuropsychiatric symptoms during PegIFNα treatment in a group of HCV patients without any psychiatric morbidity at enrolment, and drop-out rate. Methods Eleven HCV+ outpatients, scheduled for PegIFNα treatment, were assessed at enrolment (T0), and after one (T1) and two months (T2) to investigate psychiatric symptoms by means of SCID-I, HAM-D, HAM-A, PHQ-9, MDRS and MRS. A pharmacological therapy, based on clinical evidence, were provided at their onset. Results Comparing T0, T1 and T2 mean scores, we found a increasing trend in all psychometric scales, statistically significant for HAM-D and HAM-A. An item-by-item analysis showed a significative increase in the mean scores of HAM-D somatic items (#11 to 14), and HAM-A Anxious mood(#1), Tension(#2) and somatic items (#8 to 10, 12, 13). Drop-up occurred in two outpatients (18%), both after T1 assessment, due to HCV relapse (one patient), and serious somatic side effects (one patient). Conclusions Patients at early stages of PegIFNα treatment may develop a psychiatric comorbidity, particularly tension, anxiety and somatic symptoms, even without a psychiatric hystory. This confirmes a need for psychiatric assessment in patients scheduled for antiviral therapy, to identify early symptoms and reduce drop-out rates.

EPA-1128 – Long-acting second-generation antipsychotics: Improving subjective experience of pharmacological treatment and quality of life

Introduction Long-acting injectable (LAI) antipsychotics have been used as an alternative to oral antipsychotic formulations. Aims to evaluate the impact of switching to a LAI second-generation antipsychotic (SGA) in terms of changes in patients psychopathology, subjective experience of drug and quality of life. Methods 18 adult outpatients diagnosed with Schizoaffective disorder (by means of the SCID-I/P) and attending the Psychiatric Unit of the University of Florence were recruited. All patients were under a stabilized therapy with a single oral SGA (either olanzapine or paliperidone) and were switched to its corresponding LAI formulation (olanzapine pamoate or paliperidone palmitate). Patients were assessed by means of the following questionnaires: MADRS, YMRS, PANSS, DAI-10, SWN and SF-36 at enrolment (T0) and after 6 months (T1). Results A significant reduction was found between T0 and T1 (p Conclusions Treatment with LAI SGAs seems to be a valid alternative in patients with Schizoaffective disorder. Our preliminary data suggest an improvement in patients subjective experience of pharmacological therapy and health-related quality of life, together with a similar efficacy on psychopathology.

1029 – Relationship between aberrant salience processing and psychotic symptoms in a clinical trans-diagnostic sample: preliminary data

Introduction Aberrant salience consists of the unusual or incorrect assignment of salience, significance or value to different innocuous stimuli. It has been hypothesized that subjects with an aberrant salience could be proneness to develop psychosis. Despite the importance of this concept in psychosis, only few instruments assess aberrant salience. Objectives and aims To evaluate aberrant salience processing in a clinical trans-diagnostic sample and its relationship with psychotic symptoms. Methods Thirty-six outpatient subjects attending the Psychiatric Unit of the University of Florence were recruited: 9 with Major Depression Disease (MDD), 8 with Schizophrenia (SC), 19 with Bipolar Disorder (BD). Patients were assessed by means of a clinical interview (SCID-I/P) and several questionnaires, including the Aberrant Salience Inventory (ASI). Results The three groups showed significant differences in the lifetime presence of psychotic symptoms, with higher frequency in BD and SC patients (p 14) reported more frequently past and lifetime psychotic symptoms (p Conclusion Aberrant salience is significantly associated to lifetime psychotic symptoms. Thus it represents a relevant psychopathologic dimension that requires a careful investigation in patients with an history of psychotic events. The ASI could represent an useful instrument to evaluate the proneness of clinical and pre-clinical samples to develop psychotic symptoms.