Hostility in medication-resistant major depression and comorbid generalized anxiety disorder is related to increased hippocampal–amygdala 5-HT(2A) receptor density

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are severe and difficult-to-treat psychiatric illnesses with high rates of comorbidity. Although both disorders are treated with serotonergic based psychotropic agents, little is known on the influence of the serotonergic neurotransmitter system on the occurrence of comorbid GAD when clinically depressed. To investigate this poorly understood clinical question, we examined the involvement of frontolimbic post-synaptic 5-HT(2A) receptors in 20 medication-resistant depressed (MRD) patients with half of them diagnosed with comorbid GAD with (123)I-5-I-R91150 SPECT. To explore whether 5-HT(2A) receptor-binding indices (BI) associated with comorbid GAD could be related to distinct psychopathological symptoms, all were assessed with the symptom Checklist-90-Revised (SCL-90-R). MRD patients with comorbid GAD displayed significantly higher 5-HT(2A) receptor BI in the hippocampal–amygdala complex, compared to MRD patients without GAD. Correlation analyses revealed that the 5-HT(2A) receptor BI in these areas were significantly related to the SCL-90-R subscale hostility (HOS), especially for those MRD patients with comorbid GAD. Comorbid MRD-GAD may be characterized with increased hippocampal–amygdala 5-HT(2A) receptor BI which could represent enhanced levels in hostility in such kinds of patients. Adapted psychotherapeutic interventions may be warranted.