Introduction
affective and anxiety-related disorders, heterogeneous syndrome, depressive disorder, MDD, depression, neuropsychiatric disorders
DYSFUNCTION
Drugs targeting the serotonin system, specifically the serotonin transporter, have long been the primary pharmacological treatment for affective and anxiety-related disorders [Despite years of research, the question of how inhibition of the serotonin transporter leads to symptom relief in neuropsychiatric conditions, remains unresolved. Major depressive disorder (MDD) is a vastly heterogeneous syndrome [One hypothesis for the mechanism of action in neuropsychiatric disorders is that strengthened serotonergic neurotransmission induces neuroplasticity and, in turn, improves cognitive and emotion processing [PET studies on several neuropsychiatric disorders linked to synaptic dysfunction, including depression, have found lower cerebral SV2A density in patients compared to healthy individuals [Given the limited knowledge of SSRIs’ neurobiological effects in humans, such as their capacity to induce neuroplasticity, we here aim to investigate if SSRI administration over several weeks can alter synaptic density in the healthy human brain, specifically in the hippocampus and the neocortex. The hippocampus is often the target of research on neuroplasticity as it is a key region in learning and memory, and patients with severe depression have been found to have lower SV2A in the hippocampus and several neocortical regions [Here, we used a double-blind, semi-randomized, placebo-controlled design to test the hypothesis that healthy participants receiving daily SSRI administration would have higher SV2A binding in the hippocampus and the neocortex than those receiving a placebo. We further hypothesized that SV2A binding would be positively associated with the duration of escitalopram intervention.