altanserin and Borderline-Personality-Disorder

Impulsivity and aggressiveness are personality traits associated with a vulnerability to suicidal behavior. Behavioral expression of these traits differs by gender and has been related to central serotonergic function. We assessed the relationships between serotonin-2A receptor function, gender, and personality traits in borderline personality disorder (BPD), a disorder characterized by impulsive-aggression and recurrent suicidal behavior. Participants, who included 33 BPD patients and 27 healthy controls (HC), were assessed for Axis I and II disorders with the Structured Clinical Interview for DSM-IV and the International Personality Disorders Examination, and with the Diagnostic Interview for Borderline Patients-Revised for BPD. Depressed mood, impulsivity, aggression, and temperament were assessed with standardized measures. Positron emission tomography with [(18)F]altanserin as ligand and arterial blood sampling was used to determine the binding potentials (BPND) of serotonin-2A receptors in 11 regions of interest. Data were analyzed using Logan graphical analysis, controlling for age and non-specific binding. Among BPD subjects, aggression, Cluster B co-morbidity, antisocial PD, and childhood abuse were each related to altanserin binding. BPND values predicted impulsivity and aggression in BPD females (but not BPD males), and in HC males (but not HC females.) Altanserin binding was greater in BPD females than males in every contrast, but it did not discriminate suicide attempters from non-attempters. Region-specific differences in serotonin-2A receptor binding related to diagnosis and gender predicted clinical expression of aggression and impulsivity. Vulnerability to suicidal behavior in BPD may be related to serotonin-2A binding through expression of personality risk factors.

Topics: Adult; Aggression; Borderline Personality Disorder; Contrast Media; Depression; Female; Fluorodeoxyglucose F18; Humans; Impulsive Behavior; Ketanserin; Male; Personality; Positron-Emission Tomography; Radiopharmaceuticals; Receptor, Serotonin, 5-HT2A; Serotonin Antagonists; Sex Factors; Suicidal Ideation; Suicide, Attempted; Temperament

Postmortem studies in suicide victims demonstrate an increase in the number of post-synaptic 5-HT(2A) receptor binding sites in ventral lateral and orbital frontal cortex. Diminished metabolic responses to serotonergic activation are noted in these areas in impulsive subjects with borderline personality disorder (BPD), a group at high risk for suicidal behaviors. We examined 5HT(2A) receptor binding potential (BP) in impulsive subjects with BPD, with positron emission tomography neuroimaging with [(18)F] altanserin.. Fourteen female subjects with BPD were assessed for Axis I comorbidity, depressed mood, impulsivity, aggression, suicidality, childhood abuse, and compared with 11 healthy female control subjects. The 5HT(2A) receptor binding was evaluated in prefrontal cortex, anterior cingulate, hippocampus, temporal lobe, occipital cortex, and thalamus. Data were analyzed with Logan graphical analysis and a four-compartment (4C) model.. Hippocampal 5HT(2A) receptor binding was significantly increased in BPD subjects compared with control subjects in both Logan and 4C analyses, covarying for age. Hippocampal BP values were related to comorbid major depressive episode, with highest values found in non-depressed BPD subjects and lowest in healthy control subjects. The BP values were not related to depressed mood, impulsivity, aggression, suicidality, or childhood abuse.. 5HT(2A) receptor binding is increased in the hippocampus of BPD subjects independent of depressed mood, impulsivity, aggression, suicidality, or childhood abuse. Dysregulation of serotonergic function in hippocampus might contribute to affective and behavioral symptoms in BPD.

Topics: Adult; Aggression; Borderline Personality Disorder; Brain; Child; Child Abuse; Depression; Female; Fluorodeoxyglucose F18; Frontal Lobe; Hippocampus; Humans; Impulsive Behavior; Ketanserin; Positron-Emission Tomography; Receptor, Serotonin, 5-HT2A; Risk Factors; Suicide