Marina Díaz-Marsá

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.

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.

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.

The perception of emotion-free faces in schizophrenia: a magneto-encephalography study.

OBJECTIVE To analyze how patients suffering from schizophrenia perceive faces of unknown individuals that show no actual emotions in order to investigate the attribution of meanings to a relatively non-significant but complex sensory experience. DESIGN Analysis of baseline and poststimulation magneto-encephalographic recordings. The stimuli consisted of four pictures with neutral emotional expression of male and female faces of Spanish individuals unknown to research subjects. PARTICIPANTS Twelve right-handed patients suffering from schizophrenia (DSM IV-TR criteria), age 18-65, with active delusional activity (SAPS score in delusions above 39) and 15 right-handed sex- and age-matched control subjects. RESULTS Compared to controls patients have a significant higher activity of both hemispheres (0-700 ms) being the activity in the right hemisphere (RH) higher than in the left hemisphere (LH). Patients also have a higher activity on the middle fusiform gyrus (BA 37) in the LH (200-300 ms), on the superior temporal areas (BA 22, 41 and 42) in both hemispheres (100-700 ms) and on the temporal pole (BA 38) in the RH (300-400 ms) and a lower activity in the LH of the latter. CONCLUSIONS The areas that are more activated in our study are those involved in the process of thinking, in attributing meanings to perceptions and in activities such as theory of mind, which are essential for social interaction. The anterior temporal areas less activated indicate a reduced semantic memory for faces that could explain the social withdrawal of schizophrenia. These alterations are suggestive of a dysfunction of left hemisphere neuronal networks.

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.

Inflammatory activation and cholinergic anti-inflammatory system in eating disorders

Dysfunctional serotoninergic regulation and hypothalamic-pituitary-adrenal (HPA) axis overreactivity have been consistently reported in research studies with eating disorders (ED). In addition, the links between stress response, serotonin function, HPA axis and inflammatory mechanisms in ED have also been suggested in a number of studies. In our study, inflammatory parameters in white blood cells were investigated in 26 female patients with ED and 25 healthy control subjects matched for sex, age and ethnicity. Patients were free of medication for at least two weeks at the time of the study. Results showed a significant increase in plasma levels of the proinflammatory cytokine IL1β and the protein expression of cyclooxygenase 2 (COX2) in peripheral mononuclear blood cells (PMBCs) in ED patients compared with controls. As well as a significant increase of the oxidative-nitrosative marker TBARS (Thiobarbituric Acid Reactive Substances) in plasma. These findings were associated with increased expression of the alpha7 subunit of the nicotinic receptor (α7nAChR) in PMBC in ED patients independent of plasma cotinine levels. These results suggest that a pro-inflammatory and oxidant phenotype might be present in ED patients. Further research on cellular inflammatory and anti-inflammatory pathways might be oriented to investigate differences between ED subtypes and to search for new potential targets for pharmacological treatment.