Cortisol Modulation by Ayahuasca in Patients With Treatment Resistant Depression and Healthy Controls

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.

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S127. Heart Rate Variability in Patients With Treatment-Resistant Depression and Healthy Controls After Treatment With Ketamine

Biological Psychiatry ◽

10.1016/j.biopsych.2019.03.878 ◽

2019 ◽

Vol 85 (10) ◽

pp. S345-S346

Author(s):

Grace Cavanaugh ◽

Dede Greenstein ◽

Cristan Farmer ◽

Carlos Zarate ◽

Jennifer Evans

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Healthy Controls ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Resistant Depression

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

BJPsych Open ◽

10.1192/bjo.2019.58 ◽

2019 ◽

Vol 5 (5) ◽

Cited By ~ 3

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.

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Genetic and clinical characteristics of treatment-resistant depression using primary care records in two UK cohorts

Molecular Psychiatry ◽

10.1038/s41380-021-01062-9 ◽

2021 ◽

Author(s):

Chiara Fabbri ◽

Saskia P. Hagenaars ◽

Catherine John ◽

Alexander T. Williams ◽

Nick Shrine ◽

...

Keyword(s):

Primary Care ◽

Clinical Characteristics ◽

Antidepressant Drugs ◽

Demographic Characteristics ◽

Polygenic Risk Score ◽

Healthy Controls ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Genetic Characteristics ◽

Resistant Depression

AbstractTreatment-resistant depression (TRD) is a major contributor to the disability caused by major depressive disorder (MDD). Primary care electronic health records provide an easily accessible approach to investigate TRD clinical and genetic characteristics. MDD defined from primary care records in UK Biobank (UKB) and EXCEED studies was compared with other measures of depression and tested for association with MDD polygenic risk score (PRS). Using prescribing records, TRD was defined from at least two switches between antidepressant drugs, each prescribed for at least 6 weeks. Clinical-demographic characteristics, SNP-based heritability (h2SNP) and genetic overlap with psychiatric and non-psychiatric traits were compared in TRD and non-TRD MDD cases. In 230,096 and 8926 UKB and EXCEED participants with primary care data, respectively, the prevalence of MDD was 8.7% and 14.2%, of which 13.2% and 13.5% was TRD, respectively. In both cohorts, MDD defined from primary care records was strongly associated with MDD PRS, and in UKB it showed overlap of 71–88% with other MDD definitions. In UKB, TRD vs healthy controls and non-TRD vs healthy controls h2SNP was comparable (0.25 [SE = 0.04] and 0.19 [SE = 0.02], respectively). TRD vs non-TRD was positively associated with the PRS of attention deficit hyperactivity disorder, with lower socio-economic status, obesity, higher neuroticism and other unfavourable clinical characteristics. This study demonstrated that MDD and TRD can be reliably defined using primary care records and provides the first large scale population assessment of the genetic, clinical and demographic characteristics of TRD.

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Can we change depressive beliefs? Modulation of belief updating by ketamine in treatment resistant depression

10.31234/osf.io/zx5vr ◽

2021 ◽

Author(s):

HUGO BOTTEMANNE ◽

Orphée Morlaàs ◽

Anne Claret ◽

Philippe Fossati

Keyword(s):

Clinical Improvement ◽

Depression Scale ◽

Healthy Controls ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Belief Updating ◽

Estimation Errors ◽

The Future ◽

Before And After ◽

Resistant Depression

Treatment resistant depression (TRD) is a tremendous health problem that has encouraged novel treatment strategies involving sub-anesthetic ketamine infusions. While ketamine induces rapid and sustained clinical improvement, its cognitive effects are less well known. Here we tested if ketamine alters the negative expectancies about the future that are insensitive to disconfirming information, and play a key role for the maintenance of depression. Twenty-six TRD patients performed a belief-updating task before and after ketamine treatment, and were compared to a group of thirty healthy controls. The task involved estimating likelihoods of experiencing adverse life events before and after receiving information about the actual occurrence of events in the general public. A computational reinforcement-learning (RL) model tested how much belief updating was explained by learning from positive (better than thought) and negative (worser than thought) estimation errors. Global clinical improvement was assessed by the Montgomery Asberg Depression scale (MADRS). Following a single ketamine infusion patients updated their beliefs about the future more after favorable, and less after unfavorable information, controlled for sequential testing effects by comparison to healthy controls. The emergence of optimism biases in belief updating was underpinned by asymmetric learning from positive rather than negative estimation errors, and formally mediated precocious clinical responsiveness at one week of treatment observed in 19% of the patients. These findings provide novel insight into the cognitive mechanisms of ketamine action in TRD, and through it open the window toward promising perspectives for augmented psychotherapy in mood disorder.

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Functional Dysconnectivity of Frontal Cortex to Striatum Predicts Ketamine Infusion Response in Treatment-Resistant Depression

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa056 ◽

2020 ◽

Vol 23 (12) ◽

pp. 791-798

Author(s):

Mu-Hong Chen ◽

Wan-Chen Chang ◽

Wei-Chen Lin ◽

Pei-Chi Tu ◽

Cheng-Ta Li ◽

...

Keyword(s):

Functional Connectivity ◽

Frontal Cortex ◽

Depression Symptoms ◽

Healthy Controls ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Ketamine Infusion ◽

Resistant Depression ◽

The Right ◽

Superior Frontal Cortex

Abstract Background Frontostriatal disconnectivity plays a crucial role in the pathophysiology of major depressive disorder. However, whether the baseline functional connectivity of the frontostriatal network could predict the treatment outcome of low-dose ketamine infusion remains unknown. Methods In total, 48 patients with treatment-resistant depression were randomly divided into 3 treatment groups (a single-dose 40-minute i.v. infusion) as follows: 0.5 mg/kg ketamine, 0.2 mg/kg ketamine, and saline placebo infusion. Patients were subsequently followed-up for 2 weeks. Resting-state functional magnetic resonance imaging was performed for each patient before infusion administration. In addition, the baseline frontostriatal functional connectivity of patients with treatment-resistant depression was also compared with that of healthy controls. Results Compared with the healthy controls, patients with treatment-resistant depression had a decreased functional connectivity in the frontostriatal circuits, especially between the right superior frontal cortex and executive region of the striatum and between the right paracingulate cortex and rostral-motor region of the striatum. The baseline hypoconnectivity of the bilateral superior frontal cortex to the executive region of the striatum was associated with a greater reduction of depression symptoms after a single 0.2-mg/kg ketamine infusion. Conclusion Reduced connectivity of the superior frontal cortex to the striatum predicted the response to ketamine infusion among patients with treatment-resistant depression.

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Abnormal expression profile of plasma-derived exosomal microRNAs in patients with treatment-resistant depression

Human Genomics ◽

10.1186/s40246-021-00354-z ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

Lian-Di Li ◽

Muhammad Naveed ◽

Zi-Wei Du ◽

Huachen Ding ◽

Kai Gu ◽

...

Keyword(s):

Target Genes ◽

Treatment Effectiveness ◽

Enrichment Analysis ◽

Small Sample ◽

Pathway Enrichment Analysis ◽

Healthy Controls ◽

Treatment Resistant Depression ◽

Treatment Resistant ◽

Novel Biomarkers ◽

Resistant Depression

AbstractWhether microRNAs (miRNAs) from plasma exosomes might be dysregulated in patients with depression, especially treatment-resistant depression (TRD), remains unclear, based on study of which novel biomarkers and therapeutic targets could be discovered. To this end, a small sample study was performed by isolation of plasma exosomes from patients with TRD diagnosed by Hamilton scale. In this study, 4 peripheral plasma samples from patients with TRD and 4 healthy controls were collected for extraction of plasma exosomes. Exosomal miRNAs were analyzed by miRNA sequencing, followed by image collection, expression difference analysis, target gene GO enrichment analysis, and KEGG pathway enrichment analysis. Compared with the healthy controls, 2 miRNAs in the plasma exosomes of patients with TRD showed significant differences in expression, among which has-miR-335-5p were significantly upregulated and has-miR-1292-3p were significantly downregulated. Go and KEGG analysis showed that dysregulated miRNAs affect postsynaptic density and axonogenesis as well as the signaling pathway of axon formation and cell growths. The identification of these miRNAs and their target genes may provide novel biomarkers for improving diagnosis accuracy and treatment effectiveness of TRD.

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