Default Mode Connectivity in Major Depressive Disorder Measured Up to 10 Days After Ketamine Administration

Abstract

Connectivity changes in the insula in subjects with MDD suggest that ketamine may normalize the interaction between the DMN and salience networks, supporting the triple network dysfunction model of MDD.

Multimodal imaging reveals a complex pattern of dysfunction in corticolimbic pathways in major depressive disorder

“…For coregistration, both T1 (T1 = 8.84 ms, TE = 3.5 ms, inversion time = 450 ms, flip angle = 13, slice thickness = 1 mm, in‐plane resolution = 1 × 1 mm 2 ) and T2 (BRAVO, TR = 7.1 s, TE = 100.6 ms, flip angle = 90, resolution = 1 mm isotropic) images were acquired. Resting‐state functional gradient‐echo planar images (EPIs) were acquired while subjects were instructed to relax with their eyes closed for the duration of the 8‐min scan (TR = 2.5 s, TE = 25 ms, flip angle = 90, slice thickness = 3.5 mm, in‐plane resolution = 3.75 × 3.75 mm 2 ); group and session differences have previously been reported (Evans, Szczepanik, et al, ). Physiological data were acquired using a pneumatic respiratory belt and pulse oximetry device.…”

“…Data were drawn from a previously conducted clinical trial that sought to elucidate the mechanism of action of the glutamatergic modulator ketamine (Nugent et al, ). While analyses of some of these data have previously been published (Evans, Lally, et al, ; Evans, Szczepanik, et al, ; Nugent et al, ), this study is the first to describe the data collected using DTI and to present all of these data together for comparative purposes. The first aim of this exploratory study was to evaluate differences between HCs and MDD subjects for markers derived from these imaging modalities, particularly in the tracts selected a priori.…”

What Is New about New Antidepressants?

“…For one thing, there is a considerable lag between the delayed onset of clinical benefit and the immediate effects of antidepressants on neurotransmitter reuptake and receptors [13]. Several studies contradict the notion of spectra of antidepressant effects attributable to actions on different neurotransmitter systems.…”

“…One way to address this issue is with an antidepressant with a nearly immediate onset of action. In a comparison of intravenous ketamine and placebo in patients with MDD and controls [13], a rapid antidepressant response to ketamine in the depressed patients was accompanied by an equally rapid improvement of connectivity between the salience network and the DMN. Examples of some of the intracellular, interneuronal, and network effects of antidepressants are summarized in Figure 1 [17, 19-31].…”

“…Ultimately, multiple discrete effects on one aspect or another of functions of and interactions between neurons, glial cells, and astrocytes are likely to result in changes in communication between networks of neurons that regulate emotion, thinking, and the stress response [17]. One such change alters depression-associated miscommunication between the default mode network (DMN), the salience network, and the central executive network [13]. The DMN, which consists of the ventromedial prefrontal cortex, the posterior cingulate cortex, the inferior parietal cortex, and the middle temporal lobe, mediates introspection and rumination.…”