Selective serotonin reuptake inhibitors (SSRIs) are frequently combined to the antipsychotic medication of schizophrenia patients, to treat their depressed, cognitive or negative symptoms. No convincing neurochemical theory exists for this combination. The role of serotonin in those psychophysiological parameters of attention that are already found to be disturbed in schizophrenia, e.g. processing negativity (PN), mismatch negativity (MMN) and P300 amplitude, is poorly understood. In the present study the effects of increased serotonergic activity on these psychophysiological parameters is investigated. In a balanced, double-blind, placebo-controlled, cross-over experiment 18 healthy male volunteers received an oral dose of either placebo or of 10 mg escitalopram (a highly specific SSRI) on two separate test days, after which they were tested in an auditory selective attention paradigm and a MMN paradigm. Escitalopram significantly increased PN and MMN compared to placebo, without affecting the P300 amplitude. Furthermore, administration of escitalopram resulted in a small, yet significant, reduction of task performance in the selective attention paradigm compared to placebo, while it did not affect reaction time. Contrary to what was expected, escitalopram enhanced PN and MMN, without affecting the P300 amplitude. The results are discussed in the light of dosage issues and subtypes of serotonergic receptors.

Information processing deficits are commonly found in psychiatric illnesses, while at the biochemical level serotonin seems to play a role in nearly all psychiatric disorders. Processing negativity (PN), mismatch negativity (MMN) and P300 amplitude are electrophysiological measures of information processing. The present study was designed to replicate and further extent the results of our initial study on the effects of a low dose of escitalopram (10 mg) on MMN, PN and P300 amplitude. In a randomised, double-blind, cross-over experiment, 20 healthy male volunteers received either a single, orally administered dose of 15 mg escitalopram (a highly selective serotonin reuptake inhibitor (SSRI)) or placebo, after which their PN, MMN and P300 amplitude were assessed. Similar to our initial study with 10 mg escitalopram, 15 mg escitalopram significantly increased MMN, while it did not affect P300 amplitude. In contrast to our initial study, however, the currently higher dose of escitalopram did not increase PN. Results support the view that a broad range of increased serotonergic activity enhances MMN, while the relationship between serotonin and PN seems more complex. The current study does not support a serotonergic involvement in P300 amplitude.

In the current study, escitalopram did not affect P50 suppression in healthy male volunteers, which indicates that sensory gating is not affected by a nonspecific increase in serotonergic activity. Furthermore, a generator with a fronto-central location in the brain (possibly the anterior cingulate) was found to be the primary source of the P50 evoked potential.

Sensorimotor gating is critical to normal brain functioning, and disruptions are associated with certain mental illnesses, such as schizophrenia. Prepulse inhibition of the acoustic startle reflex (ASR) (PPI) is an operational measure of sensorimotor gating, of which evidence for a serotonergic modulation is currently inconsistent. In a double-blind placebo-controlled crossover design, 18 healthy male volunteers received either placebo or a dose of 10 mg of escitalopram (SSRI), after which they were tested in both PPI and habituation of the startle reflex paradigms. No significant differences between the two treatments were observed on PPI, although escitalopram was found to significantly delay habituation of the ASR. In the current study, escitalopram was found to delay habituation, but it did not affect PPI in healthy male volunteers. As escitalopram is a highly specific SSRI, the results suggest that an increased serotonergic activity disrupts habituation, but not PPI in healthy volunteers.