One‐week escitalopram intake alters the excitation–inhibition balance in the healthy female brain

Abstract

Neural health relies on cortical excitation-inhibition balance (EIB). Previous research suggests a link between increased cortical excitation and neuroplasticity induced by selective serotonin reuptake inhibitors (SSRIs). Whether there are modulations of EIB following SSRI-administration in the healthy human brain, however, remains unclear.Thus, in a randomized double-blind study, we administered a clinically relevant dose of 20 mg escitalopram for 7 days (time when steady state is achieved) in 59 healthy women (28 escitalopram, 31 placebo) on oral contraceptives. We acquired restingstate electroencephalography data at baseline, after a single dose, and at steady state. We assessed 1/f slope of the power spectrum as a marker of EIB, compared individual trajectories of 1/f slope changes contrasting single dose and 1-week drug intake, and tested the relationship of escitalopram plasma levels and cortical excitatory and inhibitory balance shifts. Escitalopram-intake was associated with decreased 1/f slope, indicating an EIB shift in favor of excitation. Furthermore, 1/f slope at baseline and after a single dose of escitalopram was associated with 1/f slope at steady state. Higher plasma escitalopram levels at a single dose were associated with better maintenance of these EIB changes throughout the drug administration week. These findings demonstrate the potential for 1/f slope to predict individual cortical responsivity to SSRIs and widen the lens through which we map the human brain by testing an interventional psychopharmacological design in a clearly defined endocrinological state.

Increased aperiodic neural activity during sleep in major depressive disorder

“…In addition, we found that the medicated state showed flatter slopes compared to the own unmedicated state. In line with our findings, a recent study in healthy females has reported that one week of intake of the SSRI escitalopram induces a flattening of aperiodic slopes during rest in favor of excitation (31). Assuming that flatter aperiodic slopes reflect noisier neural background and, therefore, less efficient sleep, our record confirms the previous studies stating that some antidepressants (for example, such SNRI as venlafaxine) may disrupt sleep due to their activating effects (32).…”

Sleep alterations as a function of 88 health indicators

“…SSRI antidepressants are known for their inhibition of the reuptake of serotonin from the synaptic cleft, thus potentiating the effect of the transmitter on pre- and postsynaptic receptors. Our findings on the overall acceleration of sleep EEG frequencies in patients treated with SSRIs confirm the overall excitatory profile of these drugs [38] and cohere with former studies performed on a low number of healthy volunteers [39–41]. We found that these effects were specific to SSRI treatment, with different patterns emerging for other antidepressants.…”

Aperiodic and Hurst EEG exponents across early human brain development: a systematic review

“…For example, Smit, Linkenkaer-Hansen and de Geus (2013) identify EOR PLE maxima in the central midline (0.20-0.40) whilst Muthukumaraswamy and Liley (2018) use IRASA to account for knees in the spectra by modelling multiple slopes, identifying global AE of 1.36 (β 1 :0.1-2.5Hz, frontal maxima) and 1.48 (β 2 :20-100Hz, central maxima) respectively. AE studies cluster between 1.30-1.60, similar to the range described by Merkin et al ., (2023), irrespective of whether FOOOF (Donoghue et al ., 2020; Pathania et al ., 2021, 2022; Zsido et al ., 2022; Cross et al ., 2022), IRASA (Muthukumaraswamy and Liley, 2018) or other methods (Barry and De Blasio, 2021) are utilised, and with similar patterns for ECR and EOR, though ECR AE remains higher. Two exceptions to this are noted (Ke et al ., 2022; Immink et al ., 2021), with one of these (Immink et al ., 2021) identifying ECR AE estimates falling within the tentative infant AE range (>2.00).…”