5HT2A Receptor Binding is Increased in Borderline Personality Disorder

Background Postmortem studies in suicide victims demonstrate an increase in the number of post-synaptic 5-HT2A 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 5HT2A receptor binding potential (BP) in impulsive subjects with BPD, with positron emission tomography neuroimaging with [18F] altanserin. Methods 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 5HT2A 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. Results Hippocampal 5HT2A 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. Conclusions 5HT2A 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.