José Luis Carrasco

Decreased platelet monoamine oxidase activity in female anorexia nervosa

Objectives: To study if platelet MAO activity, previously described as a serotonergic index, is modified in a sample of pure restrictive anorectic patients.

Microstructural white matter damage at orbitofrontal areas in borderline personality disorder.

OBJECTIVES Prefrontal cortex plays a major role in the modulation of behaviors and emotions through regulation of both information processing and impulse control. Low prefrontal function in borderline personality disorder (BPD) has been consistently reported by a number of studies using neuropsychological assessments and functional neuroimaging techniques. To further explore this findings, this study aimed to investigate microstructural damage of prefrontal white matter tracts in subjects with BPD by using the novel, voxel-based approach, tract-based spatial statistics (TBSS). METHODS A Diffusion Tensor Image (DTI) study was performed in 28 patients with DSM-IV BPD (13 males and 15 females) and in 26 healthy control subjects. Voxel wise analysis was performed using TBSS (diffusion toolbox of FSL - functional MRI Software Library) to localize regions of white matter showing significant changes of fractional anisotropy (FA). RESULTS TBSS analysis revealed a statistically significant decrease of FA in the genu and rostral areas of the corpus callosum (p<0.005), as well as in left and right prefrontal white matter fasciculi (p<0.002) in BPD participants compared with controls. White matter abnormalities were not correlated with age, neurological symptoms or comorbid ADHD. CONCLUSIONS Despite the reduced sample size, the results are in line with previous findings on reduced orbitofrontal functions in BPD with prominent affective-depressive feature and suggest that emotional and behavioral symptoms of BPD patients might be associated to damage at the connectivity tracts in these brain areas.

Brief cognitive-behavioral therapy with fibromyalgia patients in routine care

OBJECTIVE The purpose of the present study was to evaluate the effectiveness of a brief cognitive-behavioral therapy (CBT) group intervention for fibromyalgia syndrome in routine care. METHOD Thirty-four female outpatients who participated in a 5- to 6-week group CBT program were assessed for depression (Beck Depression Inventory), anxiety (State-Trait Anxiety Inventory), coping strategies (Coping Questionnaire for Chronic Pain), physical functioning (Fibromyalgia Impact Questionnaire), and somatization (Health Attitude Survey) at 3 time points (baseline, pretreatment, and posttreatment) using a pre-post, quasi-experimental design. RESULTS Twenty-three female outpatients (68% of the initial sample) for which data were available in all 3 time points were included in the analyses. No changes were found during the waiting period. During the treatment period, there were significant reductions in depression (P = .001) and anxiety (P = .006) symptoms and an increased use of distraction skills (P < .001). The analysis of rate of change showed a significant correlation between anxiety and depression (P = .004), but not between these variables and the use of distraction as a coping strategy. CONCLUSION Brief group CBT is effective in reducing emotional distress in female patients with long-standing fibromyalgia syndrome in the context of routine care. Attention-distraction skills appear to be amenable to change by means of brief CBT, but further research is needed to clarify their contribution to short-term clinical improvement.

Findings with 0.25 mg dexamethasone suppression test in eating disorders: association with childhood trauma.

INTRODUCTION While both blunted and enhanced cortisol suppression following a dexamethasone suppression test (DST) are described in eating disorders, some evidence suggests that enhanced cortisol suppression might be associated with the presence of trauma history. The objective of this study is to investigate hypothalamic-pituitary-adrenal axis response to a modified DST in eating disorders and its relationship with childhood trauma. METHODS Fifty-two patients with eating disorders were studied with a 0.25 mg DST and with measures of childhood trauma. CONCLUSION Patients with bulimia symptoms had significantly greater cortisol suppression than controls and restrictive anorexia patients (F=8.2, P<.05). Cortisol suppression was significantly correlated with intensity of childhood traumatic events (F=0.32, P<.05). Hypersensitive hypothalamic-pituitary-adrenal axis response to DST in eating disorders may be related with a history of childhood trauma and suggests some biological similarities with posttraumatic syndromes that should be further explored.

Decreased platelet monoamine oxidase activity in female bulimia nervosa

UNLABELLED The involvement of brain serotonin systems in the pathophysiology of eating disorders has been repeatedly demonstrated in recent studies. Platelet MAO activity is an index of brain serotonin activity and lowered platelet MAO levels have been found in association with impulsive behaviors. In addition, some preliminary reports indicate that platelet MAO could be lowered in eating disorder patients. METHODS 47 patients with DSM-IV eating disorders were studied, including 30 with bulimia nervosa and 17 with anorexia nervosa binge eating-purging type. Platelet MAO activity was measured by isotopic methods using C-14 benzylamine and compared with a control group of 30 healthy subjects. Impulsive personality features were studied with specific rating scales. RESULTS Platelet MAO activity was significantly lower (4.4+/-2.4 nmol/h/10(8) platelets) in the bulimic patients than in the control group (6.9+/-2.5) (p<0.001). No significant differences were found between pure bulimics and binge eating-purging anorectics. Platelet MAO was inversely and significantly correlated with scores on impulsivity scales and with borderline personality disorder characteristics. CONCLUSIONS Platelet MAO activity is lowered in patients with bulimia, which may reflect dysfunction in impulse control mechanisms. Since platelet MAO has a predominant genetic component, there is need for studies on the association of low platelet MAO and higher risk for developing eating disorders.

Enhanced cortisol suppression in eating disorders with impulsive personality features

Evidence of both blunted and enhanced cortisol suppression with the dexamethasone test (DST) is available in eating disorders (ED), suggesting that different subtypes of ED might be characterized by distinct neurobiological stress response dysfunctions. Other evidence indicates that ED patients with impulsive clinical features might have enhanced cortisol suppression similar to patients with impulsive personality disorders. A group of 52 patients with restrictive anorexia, binge eating-purging anorexia and bulimia nervosa were studied with a very low dose (0.25 mg) dexamethasone test and measures of phenomenology, personality and impulsivity. Patients with bulimic symptoms had significantly higher rates of cortisol suppression than controls and than restrictive anorectic patients. Percent cortisol suppression showed a strong and significant correlation with the patients score on the Barratt Impulsiveness Scale. A hypersensitive cortisol response to dexamethasone, which might reflect hypothalamic-pituitary-adrenal axis dysfunctions might be specifically associated with impulsive subtypes of eating disorders.

Safety of olanzapine versus conventional antipsychotics in the treatment of patients with acute schizophrenia. A naturalistic study.

BACKGROUND Conventional antipsychotics although effective in treating acute psychotic and behavioural symptoms are subject to certain limitations due to the high incidence of side effects associated, mainly extrapyramidal symptoms (EPS), and insufficient response shown in some cases. EPS are a major factor in neuroleptic non compliance and high relapse rates among patients. This study was designed to assess the safety and effectiveness of olanzapine compared to typical antipsychotics drugs in the treatment of schizophrenic inpatients at acute psychiatric in-patient units. METHOD Data from 904 patients schizophrenic patients (F20 of ICD10, WHO) were collected in this prospective, comparative, non-randomized, open and observational study. Patients were followed during their entire hospital stay. Safety was assessed through the collection of spontaneous adverse events and a specific extrapyramidal symptoms questionnaire (EPS). Clinical status was measured through the Brief Psychiatric Rating Scale (BPRS), Clinical Global Impression of Severity (CGI-S), Patient Global Impression of Improvement (PGI) and the Nursing Observational Scale for In-patient Evaluation (NOSIE). RESULTS A total of 483 patients received olanzapine (olanzapine group, OG), and 421 received typical antipsychotics (control group, CG). Treatment emergent EPS, or worsening of previous EPS were statistically significantly higher in the CG (P=0.001). Responder rate was statistically greater in the OG (P<0.001). Mean change in BPRS-total, BPRS-negative, BPRS-agitation subscales and PGI was significantly higher in the OG (P<0.001). Mean decrease in CGI, BPRS positive and BPRS depression sub-scales was also significantly lower (P< or =0.05). Mean change in the NOSIE scale was similar between both groups. CONCLUSION Olanzapine has been shown to be better tolerated in comparison with conventional antipsychotics in a large unselected sample of acutely psychotic schizophrenic in-patients. Its effectiveness may be greater than that of conventional antipsychotics.

Orbitofrontal dysfunction related to depressive symptomatology in subjects with borderline personality disorder

OBJECTIVE In order to explore the relationships of fronto-limbic dysfunction with the clinical features of borderline personality disorder (BPD), the authors investigated brain electrophysiological activity in BPD patients following stimulation with emotionally arousing images. METHODS Seventeen non-medicated patients with borderline personality disorder were studied with magneto-encephalography. Regional cortical activities were obtained by minimum norm estimate (MNE) of steady-state visual evoked fields (ssVEFs). Linear regression models were conducted to explore clinical correlates of brain activity. RESULTS Although no interaction group × picture category × brain region was found, a significant interaction group × brain region appeared for orbito-frontal cortex (OFC). BPD patients showed significantly reduced magnetocortical activity in left OFC across all picture categories (F = 26.4; p<.05; F = 31.4). Left OFC activity was inversely correlated with depression score in the BDI (r: -0.48, p < 0.05), with score in the Cornell Dysthymia rating scale (r: -0.52, p < 0.05) and with the number of criteria met for depressive personality disorder (r: -0.44, p < 0.05). Left orbitofrontal activity was also inversely correlated with the global score in the GAF (r-0.63, p < 0.01). No correlations were found between OFC activity and impulsivity or global severity of BPD symptoms. CONCLUSIONS Abnormal functioning at orbitofrontal areas in BPD could be related to the presence of affective symptomatology and is associated with greater functional deterioration of patients.

Low platelet monoamine oxidase activity in sensation-seeking bullfighters

In this study, we attempt to demonstrate an association between low platelet monoamine oxidase (MAO) activity, as assessed by isotopic methods, and the stable behavioral pattern of sensation- and risk-seeking of professional bullfighters. Sixteen professional bullfighters were studied and compared with a control group of 46 healthy control subjects who did not engage in risky jobs or activities. The group of bullfighters had significantly reduced platelet MAO activity compared with the control group (P<0.05). Bullfighters were shown to be significantly more extroverted and sensation-seeking than controls on various temperament scales. A predisposition to engage in risky activities (eg, bullfighting) and sensation-seeking could be partly conditioned by the presence of biological components of personality manifested by a significantly decreased platelet MAO activity.

Activation of the cholinergic anti-inflammatory system in peripheral blood mononuclear cells from patients with Borderline Personality Disorder

A case-control study including patients (n = 20) with Borderline Personality Disorder (BPD) and healthy controls (n = 33) was carried out. To avoid interferences of other clinical conditions on biological findings, patients were free of current major depressive episodes or substance dependence disorders, and had no life history of schizophrenia, bipolar or neuropsychiatric disorders. Patients were free of medication for at least two weeks at the time of the study. Studies carried out in peripheral mononuclear blood cells and plasma evidence a systemic inflammatory condition in unstable-impulsive BPD patients. Specifically, a significant increase in some intracellular components of two main pro-inflammatory pathways such as iNOS and COX-2, as well as an increase in the plasma levels of the inflammatory cytokine IL1β. Interestingly, patients have an increase in the protein expression of the anti-inflammatory subtype of nicotinic receptor α7nAChR. This finding may reflect a possible mechanism trying to maintain intracellular inflammation pathways under control. All together, these results describe an imbalanced, pro-inflammatory and oxidant phenotype in BPD patients independent of plasma cotinine levels. Although more scientific evidence is needed, the determination of multiple components of pro- and anti-inflammatory cellular pathways have interesting potential as biological markers for BPD and other generalized impulsive syndromes, specially data obtained with α7nAChR and its lack of correlation with plasma levels of nicotine metabolites. Their pharmacological modulation with receptor modulators can be a promising therapeutic target to take into account in mental health conditions associated with inflammatory or oxido/nitrosative consequences. Also, identifying at-risk individuals would be of importance for early detection and intervention in adolescent subjects before they present severe behavioural problems.