A positron emission tomography study of the serotonergic system in relation to anxiety in depression

Abstract

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-HT1A) binding in MDD and found that higher psychic and lower somatic anxiety was associated with greater 5-HT1A binding. In this work, we sought to examine the correlation between these anxiety symptom dimensions and 5-HTT. Positron emission tomography with [11C]-3-amino-4-(3-dimethylamino-methylphenylsulfanyl)-benzonitrile ([11C]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-HT1A 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-HT1A. 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.

Neuroinflammation in World Trade Center responders at midlife: A pilot study using [18F]-FEPPA PET imaging

“…Raw list-mode PET data was reconstructed offline using Siemens’ e7 Tools software and a CT-like MR-based attenuation map ( Izquierdo-Garcia et al., 2014 , Ladefoged et al., 2017 ). Motion correction and PET-to-MRI coregistration were done before time activity curves were generated as previously described ( Iscan et al., 2017 ). To obtain a quantitative measure of [ 18 F]-FEPPA uptake, two-tissue-compartmental (2 ​TC) kinetic modeling was performed to quantify the total distribution volume ( V T ) as the outcome measure, as previously validated ( Rusjan et al., 2011 ).…”

Concurrent anxiety in patients with major depression and cerebral serotonin 4 receptor binding. A NeuroPharm-1 study

“…One study found that low SERT binding in thalamus was correlated with higher anxiety symptoms in a small sample of ten unmedicated patients with MDD [11] which was later replicated (n = 10) [12]. Another group confirmed a negative correlation between somatic anxiety and SERT binding in the thalamus, midbrain and amygdala, while psychic anxiety was positively correlated with midbrain SERT binding [10].…”

“…The underlying mechanisms are not fully understood, but serotonin (5-HT) is assumed to play a key role and serotonergic-acting drugs are firstline pharmacotherapeutic options for treatment of both depression and anxiety disorders. Previous positron emission tomography (PET) studies of the serotonin system in patients with concurrent anxious depression are scarce and have mainly focused on the serotonin transporter (SERT) and the 5-HT 1A receptor [10,11]. One study found that low SERT binding in thalamus was correlated with higher anxiety symptoms in a small sample of ten unmedicated patients with MDD [11] which was later replicated (n = 10) [12].…”

Prognostic plasma exosomal microRNA biomarkers in patients with substance use disorders presenting comorbid with anxiety and depression

“…Urine-based metabolites involved in metabolic pathways were deemed as a hopeful diagnostic method for patients with depression and anxiety disorders 25 . Nevertheless, existing biomarkers in cerebrospinal fluid (CSF) [e.g., monoamine and cocaine- and amphetamine-regulated transcript (CART) peptide identify biomarkers for psychiatric diagnosis] 26 or positron emission tomography (PET) imaging [targeting serotonin transporter (5-HTT), 5-HTT and 5-HT1A, tau, neurofilament light, and neurogranin] 27 – 29 are invasive or expensive, far from comprehensive, and often lack sensitivity and specificity.…”