scholarly journals Structural brain characteristics in treatment-resistant depression: review of magnetic resonance imaging studies

BJPsych Open ◽  
2019 ◽  
Vol 5 (5) ◽  
Author(s):  
Margit Philomène C. Klok ◽  
Philip. F. van Eijndhoven ◽  
Miklos Argyelan ◽  
Aart H. Schene ◽  
Indira Tendolkar
Keyword(s):  
White Matter ◽  
Anterior Cingulate ◽  
Cochrane Library ◽  
Precentral Gyrus ◽  
Healthy Controls ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Brain Changes ◽  
Resistant Depression ◽  
Structural Brain

Background Major depressive disorder (MDD) has been related to structural brain characteristics that are correlated with the severity of disease. However, the correlation of these structural changes is less well clarified in treatment-resistant depression (TRD). Aims To summarise the existing literature on structural brain characteristics in TRD to create an overview of known abnormalities of the brain in patients with MDD, to form hypotheses about the absence or existence of a common pathophysiology of MDD and TRD. Method A systematic search of PubMed and the Cochrane Library for studies published between 1998 and August of 2016 investigating structural brain changes in patients with TRD compared with healthy controls or patients with MDD. Results Fourteen articles are included in this review. Lower grey matter volume (GMV) in the anterior cingulate cortex, right cerebellum, caudate nucleus, superior/medial frontal gyrus and hippocampus does not seem to differentiate TRD from milder forms of MDD. However, lower GMV in the putamen, inferior frontal gyrus, precentral gyrus, angular- and post-central gyri together with specific mainly parietal white matter tract changes seem to be more specific structural characteristics of TRD. Conclusions The currently available data on structural brain changes in patients with TRD compared with milder forms of MDD and healthy controls cannot sufficiently distinguish between a ‘shared continuum hypothesis’ and a ‘different entity hypothesis’. Our review clearly suggests that although there is some overlap in affected brain regions between milder forms of MDD and TRD, TRD also comes with specific alterations in mainly the putamen and parietal white matter tracts. Declaration of interest None.

scholarly journals Prolonged ketamine infusion modulates limbic connectivity and induces sustained remission of treatment-resistant depression

2021 ◽  
Author(s):  
Joshua S. Siegel ◽  
Ben J. A. Palanca ◽  
Beau M. Ances ◽  
Evan D. Kharasch ◽  
Julie A. Schweiger ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Limbic System ◽  
Anterior Cingulate ◽  
Sustained Remission ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Open Label ◽  
Subgenual Anterior Cingulate Cortex ◽  
Post Infusion ◽  
Resistant Depression

AbstractKetamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unknown. In this open-label, proof-of-principle study, adults with treatment-resistant depression (N = 23) underwent a 96-h infusion of intravenous ketamine (0.15 mg/kg/h titrated toward 0.6 mg/kg/h). Clonidine was co-administered to reduce psychotomimetic effects. We measured clinical response for 8 weeks post-infusion. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in patients pre- and 2 weeks post-infusion and in matched non-depressed controls (N = 27). We hypothesized that responders to therapy would demonstrate response-dependent connectivity changes while all subjects would show treatment-dependent connectivity changes. Most participants completed infusion (21/23; mean final dose 0.54 mg/kg/h, SD 0.13). The infusion was well tolerated with minimal cognitive and psychotomimetic side effects. Depressive symptoms were markedly reduced (MADRS 29 ± 4 at baseline to 9 ± 8 one day post-infusion), which was sustained at 2 weeks (13 ± 8) and 8 weeks (15 ± 8). Imaging demonstrated a response-dependent decrease in hyperconnectivity of the subgenual anterior cingulate cortex to the default mode network, and a treatment-dependent decrease in hyperconnectivity within the limbic system (hippocampus, amygdala, medial thalamus, nucleus accumbens). In exploratory analyses, connectivity was increased between the limbic system and frontal areas, and smaller right hippocampus volume at baseline predicted larger MADRS change. A single prolonged infusion of ketamine provides a tolerated, rapid, and sustained response in treatment-resistant depression and normalizes depression-related hyperconnectivity in the limbic system and frontal lobe.ClinicalTrials.gov: Treatment Resistant Depression (Pilot), NCT01179009.

Abnormal Neural Basis of Emotional Conflict Control in Treatment-Resistant Depression

2016 ◽  
Vol 48 (2) ◽  
pp. 103-110 ◽  
Author(s):  
Song Xue ◽  
Shanshan Wang ◽  
Xia Kong ◽  
Jiang Qiu
Keyword(s):  
Stroop Task ◽  
Event Related Potentials ◽  
Frontal Region ◽  
Healthy Controls ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Neural Basis ◽  
Emotional Conflict ◽  
Related Potentials ◽  
Resistant Depression

Emotional conflict has received increased attention as a research topic. The objective of this study is to confirm that the processing of emotional conflict is impaired in treatment-resistant depression (TRD). We compared the event-related potentials of 17 patients with TRD and 17 healthy controls during the face-word Stroop task, which is an effective way of assessing the effects of emotional conflict directly. Compared with healthy controls, the accuracy scores of the TRD patients were lower in both “congruent stimuli” and “incongruent stimuli” conditions, and their response times were longer. The TRD patients also had larger N2 amplitudes over the frontal region, regardless of stimulus condition, which might reflect that TRD patients pay more attention to emotional information. A larger P3 amplitude over the frontal region for “incongruent stimuli minus congruent stimuli” was also found among patients with TRD, which indicates interference effects in the Stroop task. The results of this study provide novel behavioral and neurophysiological evidence of anomalies in cognitive inhibition among patients with TRD using the word-face task. These findings not only improve our understanding of deficient inhibition in TRD, but also pave the way for a cognitive neuropsychiatric model of depression.

scholarly journals Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD)

2019 ◽  
Author(s):  
Eleanor J. Cole ◽  
Katy H. Stimpson ◽  
Brandon S. Bentzley ◽  
Merve Gulser ◽  
Kirsten Cherian ◽  
...  
Keyword(s):  
Side Effects ◽  
Rating Scale ◽  
Neuropsychological Testing ◽  
Anterior Cingulate ◽  
High Dose ◽  
Delayed Response ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resting Motor Threshold ◽  
Resistant Depression

AbstractBackgroundCurrent treatments for depression are limited by suboptimal efficacy, delayed response, and frequent side effects. Intermittent theta-burst stimulation (iTBS) is a non-invasive brain stimulation treatment that is FDA-approved for treatment-resistant depression (TRD). Recent methodological advancements suggest iTBS could be improved through 1) treating with multiple sessions per day at optimally-spaced intervals, 2) applying a higher overall pulse-dose of stimulation and 3) precision targeting of the left dorsolateral prefrontal cortex (L-DLPFC) to subgenual anterior cingulate cortex (sgACC) circuit. We examined the feasibility, tolerability, and preliminary efficacy of an accelerated, high-dose, resting-state functional connectivity MRI (fcMRI)-guided iTBS protocol for TRD termed ‘Stanford Accelerated Intelligent Neuromodulation Therapy (SAINT)’.MethodsTwenty-one participants with TRD received open-label SAINT. FcMRI was used to individually target the region of L-DLPFC most anticorrelated with sgACC. Fifty iTBS sessions (1800 pulses per session, 50-minute inter-session interval) were delivered as 10 daily sessions over 5 consecutive days at 90% resting motor threshold (adjusted for cortical depth). Neuropsychological testing was conducted before and after SAINT.ResultsNineteen of 21 participants (90.48%) met criteria for remission (≤10 on the Montgomery-Åsberg Depression Rating Scale) immediately after SAINT. Neuropsychological testing demonstrated no negative cognitive side-effects. There were no seizures or other severe adverse events.DiscussionOur accelerated, high-dose, iTBS protocol with fcMRI-guided targeting (SAINT) was well tolerated and safe. Efficacy was strikingly high, especially for this treatment-resistant population. Double-blinded sham-controlled trials are required to confirm the high remission rate found in this initial study.Trial registrationClinicalTrials.gov NCT03240692

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