Effects of Selective Serotonin Reuptake Inhibitors on Interregional Relation of Serotonin Transporter Availability in Major Depression

Abstract

Selective serotonin reuptake inhibitors (SSRIs) modulate serotonergic neurotransmission by blocking reuptake of serotonin from the extracellular space. Up to now, it remains unclear how SSRIs achieve their antidepressant effect. However, task-based and resting state functional magnetic resonance imaging studies, have demonstrated connectivity changes between brain regions. Here, we use positron emission tomography (PET) to quantify SSRI’s main target, the serotonin transporter (SERT), and assess treatment-induced molecular changes in the interregional relation of SERT binding potential (BPND). Nineteen out-patients with major depressive disorder (MDD) and 19 healthy controls (HC) were included in this study. Patients underwent three PET measurements with the radioligand [11C]DASB: (1) at baseline, (2) after a first SSRI dose; and (3) following at least 3 weeks of daily intake. Controls were measured once with PET. Correlation analyses were restricted to brain regions repeatedly implicated in MDD pathophysiology. After 3 weeks of daily SSRI administration a significant increase in SERT BPND correlations of anterior cingulate cortex and insula with the amygdala, midbrain, hippocampus, pallidum and putamen (p < 0.05; false discovery rate, FDR corrected) was revealed. No significant differences were found when comparing MDD patients and HC at baseline. These findings are in line with the clinical observation that treatment response to SSRIs is often achieved only after a latency of several weeks. The elevated associations in interregional SERT associations may be more closely connected to clinical outcomes than regional SERT occupancy measures and could reflect a change in the regional interaction of serotonergic neurotransmission during antidepressant treatment.

Brain and behavioral correlates of insulin resistance in youth with depression and obesity

“…For example, modified developmental changes in intrinsic functional networks that proceed from the ACC affect key self-regulatory processes, which, when vulnerable, then increase adolescent risk for depression (Jalbrzikowski et al, 2017;Lichenstein et al, 2016). Third, the ACC and hippocampus are highly connected (de Kwaasteniet et al, 2013;James et al, 2017;Ye et al, 2016;Zeng et al, 2012) and the interdependence between these regions are implicated in understanding mesostriatal dopaminergic disturbances in approach motivation in depression (Hamilton et al, 2011). Moreover, aberrant connectivity between these regions may be mediated by oxidative stress, particularly in early stages of depressive illness (Hermens et al, 2017).…”

Cerebral serotonin transporter measurements with [11C]DASB: A review on acquisition and preprocessing across 21 PET centres

“…Twenty-nine studies used between-frame-correction to correct for motion without explicitly specifying the exact procedure (e.g. James et al 31 ). Twenty-one studies used betweenframe-correction to correct for motion, by aligning all frames to a frame with high SNR (e.g.…”

“…However, there is currently no consensus in the [ 11 C]DASB PET community about which atlas generates the best set of VOIs. Whereas a single study used the probabilistic Harvard-Oxford atlas to delineate VOIs, 31 14 published papers used PVElab, which is a data-driven anatomical probability-based labeling approach based on MRI templates from 10 healthy volunteers (e.g. Frokjaer et al 39 ).…”

Altered connectivity between striatal and extrastriatal regions in patients with schizophrenia on maintenance antipsychotics: an [18F]fallypride PET and functional MRI study

“…In addition to probing regional differences in receptor or transporter availability, recent molecular PET studies have proven useful for investigating altered neurotransmitter networks using interregional correlation analyses (Hahn et al, ; James et al, ; Tuominen, Nummenmaa, Keltikangas‐Jarvinen, Raitakari, & Hietala, ; Vanicek et al, ). Previous PET studies in healthy subjects reported patterns of inter‐correlated D 2/3 receptor availability within striatal regions, and within cortical regions, which seems generally consistent with topographical anatomic models of the nigrostriatal and mesocortical divisions of the basal ganglia and related regions (Cervenka, Varrone, Fransen, Halldin, & Farde, ; Zald et al, ).…”