Serotonergic Modulation of Intrinsic Functional Connectivity

Abstract

Serotonin functions as an essential neuromodulator that serves a multitude of roles, most prominently balancing mood. Serotonergic challenge has been observed to reduce intrinsic functional connectivity in brain regions implicated in mood regulation. However, the full scope of serotonergic action on functional connectivity in the human brain has not been explored. Here, we show evidence that a single dose of a serotonin reuptake inhibitor dramatically alters functional connectivity throughout the whole brain in healthy subjects (n = 22). Our network-centrality analysis reveals a widespread decrease in connectivity in most cortical and subcortical areas. In the cerebellum and thalamus, however, we find localized increases. These rapid and brain-encompassing connectivity changes linked to acute serotonin transporter blockade suggest a key role for the serotonin transporter in the modulation of the functional macroscale connectome.

Time related effects on functional brain connectivity after serotonergic and cholinergic neuromodulation

“…In our study, both agents altered resting state functional connectivity within our time frame of measurements. The results of our study replicate the finding that SSRIs can have an immediate and widespread diminishing impact on interactions of the healthy neural system [Klaassens et al, 2015; Murphy et al, 2009; Schaefer et al, 2014]. In conjunction with other SSRIs, citalopram had clear neuroendocrine effects [Seifritz et al, 1996], but did not induce cognitive or subjective changes as measured with the NeuroCart ® battery.…”

“…In congruence with both task‐related [Bruhl and Herwig, 2009; Murphy et al, 2009] and resting‐state fMRI paradigms with SSRIs [Klaassens et al, 2015; Schaefer et al, 2014], citalopram rapidly lowered connectivity in several cortical and subcortical regions. This is consistent with the numerous afferent and efferent serotonergic fibers originating from the brain stem's raphe nuclei [Baumgarten and Grozdanovic, 1995].…”

“…Several studies point to normalization of DMN connectivity in depression after SSRI administration [McCabe and Mishor, 2011; McCabe et al, 2011; Van de Ven et al, 2013; Van Wingen et al, 2014]. Yet, there is also proof of more extensive effects of SSRIs on brain connectivity [Klaassens et al, 2015; Schaefer et al, 2014]. In AD patients, cholinergic stimulation induces alterations in connectivity for DMN regions [Goveas et al, 2011; Li et al, 2012; Solé‐Padullés et al, 2013], as well as networks involved in attention, control, and salience processing [Wang et al, 2014].…”

Low environmental levels of neuro-active pharmaceuticals alter phototactic behaviour and reproduction in Daphnia magna

“…Negative phototactic behaviour of adult females decreased from 1 ng/L to 1 g/L of fluoxetine, from 0.01 to 1 g/L of carbamazepine and from 0.1 to 1 g/L of diazepam Despite that D. magna juveniles had lower negative phototactic behaviour, they responded similarly to the tested chemicals than adults. There is reported evidence showing that antidepressant action of fluoxetine in humans occurs after long exposures of about a month (Pérez et al, 2001), but recent studies indicated that effects of antidepressants can be detected within hours when more sensitive responses are measured (Schaefer et al, 2014). This is not the case for carbamazepine or diazepam that act shortly after being ingested (Besser, 1967;Post, 1988).…”

Large-Scale Persistent Network Reconfiguration Induced by Ketamine in Anesthetized Monkeys: Relevance to Mood Disorders

“…Moreover, we argue the potential effect of anesthetic agents was removed by contrasting the saline and ketamine treatments in the same group subjects and the thresholds for network construction were applied uniformly to each subject in both conditions. However, overinterpretation of the present findings from healthy subjects should be kept in mind (49,(64)(65)(66) until monkey models of mood disorders, such as depression and anxiety, have been developed (30) and used under the same experimental protocol. It was reported previously that schizophrenia-like symptoms can be induced by acute ketamine administration (67), although after a delay period (, 5 hours), the psychotomimetic effects do not last long in monkeys (32).…”