A Positron Emission Tomography Study of the Serotonergic System in Relation to Anxiety in Depression

Symptoms of anxiety are highly comorbid with major depressive disorder (MDD) and are known to alter the course of the disease. To help elucidate the biological underpinnings of these prevalent disorders, we previously examined the relationship between components of anxiety (somatic, psychic and motoric) and serotonin 1A receptor (5-HT) binding in MDD and found that higher psychic and lower somatic anxiety was associated with greater 5-HT binding. In this work, we sought to examine the correlation between these anxiety symptom dimensions and 5-HTT binding. Positron emission tomography with [C]-3-amino-4-(3-dimethylamino-methylphenylsulfanyl)-benzonitrile ([C]DASB) and a metabolite-corrected arterial input function were used to estimate regional 5-HTT binding in 55 subjects with MDD and anxiety symptoms. Somatic anxiety was negatively correlated with 5-HTT binding in the thalamus (β=-.33, p=.025), amygdala (β=-.31, p=.007) and midbrain (β=-.72, p<.001). Psychic anxiety was positively correlated with 5-HTT binding in midbrain only (β=.46, p=.0025). To relate to our previous study, correlation between 5-HT and 5-HTT binding was examined, and none was found. We also examined how much of the variance in anxiety symptom dimensions could be explained by both 5-HTT and 5-HT binding. The developed model was able to explain 68% (p<.001), 38% (p=.012) and 32% (p=.038) of the total variance in somatic, psychic, and motoric anxiety, respectively. Results indicate the tight coupling between the serotonergic system and anxiety components, which may be confounded when using aggregate anxiety measures. Uncovering serotonin's role in anxiety and depression in this way may give way to a new generation of therapeutics and treatment strategies.