Ilya Demchenko

INTRODUCTION Although anxiety symptoms frequently co-occur with major depressive disorder, few studies examined the prediction of treatment outcomes among participants with anxious depression receiving antidepressants. We investigated whether baseline anxiety, and early improvements in anxiety and depression symptoms predict eventual treatment outcomes. METHODS 111 participants with anxious depression, defined using ≥ 10 on GAD-7, received escitalopram (10-20mg) for 8 weeks. Covariate-adjusted logistic regression was conducted to examine the impact of baseline anxiety, and to assess the extent week 2 anxiety (GAD-7) and depression (QIDS-SR) percentage improvement associates with week 8 anxiety (GAD-7) and depression (MADRS) response/remission. Optimum improvement thresholds were identified using receiving-operating-curve analysis and their predictive values assessed. RESULTS Greater percentage improvement in anxiety and depression after the first 2 weeks of treatment significantly increased odds of achieving week 8 anxiety and depression response/remission (OR:1.01-1.04, p<0.05). Early anxiety (68.4%/87.2%) and depression (52.2%/83.0%) improvement thresholds around 30 and 40% provided moderate to high positive predictive value (PPV) for predicting week 8 anxiety response/remission, as well as moderate to high negative predictive value (NPV) for predicting week 8 depression response/remission (anxiety:70.8%/91.7%; depression:72.2%/90.1%). Baseline anxiety severity predicted anxiety outcomes at weeks 2 and 8. LIMITATIONS Trial lacked placebo group. CONCLUSION In anxious depression, early improvement in anxiety may be better than depression in predicting anxiety outcomes, with similar or higher PPVs. Both improvement types perform similarly in predicting depression outcomes, with the lack of improvement predictive of non-response and non-remission. Finally, baseline anxiety predicts eventual anxiety but not depression outcomes.

Schizophrenia patients make more errors and have longer reaction times (RTs) than healthy controls in most cognitive tasks. Deficits are also observed in subclinical participants having high scores on the schizotypal personality questionnaire (SPQ). They are accompanied by smaller amplitudes of the event-related brain potentials (ERPs) that index attention and semantic- and working-memory. These functions are thus thought to be impaired in individuals having various schizophrenia attributes (SzAs). Nevertheless, normal RTs were recently found in SzAs during a particular self-referential task where half of the stimuli were names of extraordinary social roles (e.g., genius). Each name (ordinary or extraordinary) was presented individually, and participants were asked to decide whether or not they would consider themselves performing the role at any moment of their lives. To further test an absence of cognitive deficits in this task, the ERPs elicited by names of social roles were also...

Greater adaptability of patients should go with easier psychosocial rehabilitation. Medications should thus also be chosen according to their impact on practice effects, as they measure adaptability. We are thus developing a pre-treatment test aimed, in fine, at assessing the impact of medications on these effects. Here, we report the practice effects observed across the two sessions of a semantic categorization task. Participants (n = 47) completed the Schizotypal Personality Questionnaire (SPQ) and performed this task twice, 1.5 hours apart. Practice was found to reduce reaction times in both low- and high-SPQ scorers. It was also found to decrease the amplitudes of the N400 event-related brain potentials elicited by semantically matching words in low SPQ scorers only, which showed the sensitivity of the task to schizotypy. Both RTs and N400 amplitudes were also found to have a good test-retest reliability across the two sessions. This task could thus be a valuable tool. On-going ...

Preliminary evidence supports the use of psychedelics for major depressive disorder (MDD). However, less attention has been given to the neural mechanisms behind their effects. We conducted a systematic review examining the neuroimaging correlates of antidepressant response following psychedelic interventions for MDD. Through MEDLINE, Embase, and APA PsycINFO, 187 records were identified and 42 articles were screened. Six published studies and one conference abstract were included. Five ongoing trials were included from ClinicalTrials.gov. Our search covered several psychedelics, though included studies were specific to psilocybin, ayahuasca, and lysergic acid diethylamide. Three psilocybin studies noted amygdala activity and functional connectivity (FC) alterations that correlated with treatment response. Two psilocybin studies reported that FC changes in the medial and ventromedial prefrontal cortices correlated with treatment response. Two trials from a single study reported glob...

Background: Antidepressant use for major depressive disorder (MDD) is frequently associated with sexual dysfunction. Aims: Cross-sectional and longitudinal relationships between antidepressant treatment outcomes and sexual functioning (SF) were evaluated separately for males and females receiving escitalopram. We further assessed the association between pre- and posttreatment SF. Methods: In all, 208 of the 211 CAN-BIND-1 trial participants (77 males and 131 females) with MDD and detectable drug blood levels were eligible for the analyses. All received escitalopram (10–20 mg) for 8 weeks. At baseline and Week 8, participants completed the Montgomery–Åsberg Depression Rating Scale (MADRS) and the SexFx scale, which measures sexual satisfaction and SF frequency. Mixed-model repeated measures assessed baseline to Week 8 SF changes among participants with different response/remission statuses. Multiple linear regression analyses examined SF differences between treatment outcomes at Week...

Supplemental material, sj-docx-2-css-10.1177_24705470211055176 for Stellate Ganglion Block for Psychiatric Disorders: A Systematic Review of the Clinical Research Landscape by Jaimie Kerzner, Helen Liu, Ilya Demchenko, David Sussman, Duminda N. Wijeysundera, Sidney H. Kennedy, Karim S. Ladha and Venkat Bhat in Chronic Stress

Supplemental material, sj-docx-1-css-10.1177_24705470211055176 for Stellate Ganglion Block for Psychiatric Disorders: A Systematic Review of the Clinical Research Landscape by Jaimie Kerzner, Helen Liu, Ilya Demchenko, David Sussman, Duminda N. Wijeysundera, Sidney H. Kennedy, Karim S. Ladha and Venkat Bhat in Chronic Stress

Supplemental material, sj-docx-3-css-10.1177_24705470211055176 for Stellate Ganglion Block for Psychiatric Disorders: A Systematic Review of the Clinical Research Landscape by Jaimie Kerzner, Helen Liu, Ilya Demchenko, David Sussman, Duminda N. Wijeysundera, Sidney H. Kennedy, Karim S. Ladha and Venkat Bhat in Chronic Stress

Conventional monoamine-based pharmacotherapy, considered the first-line treatment for major depressive disorder (MDD), has several challenges, including high rates of non-response. To address these challenges, preclinical and clinical studies have sought to characterize antidepressant response through monoamine-independent mechanisms. One striking example is glutamate, the brain's foremost excitatory neurotransmitter: since the 1990s, studies have consistently reported altered levels of glutamate in MDD, as well as antidepressant effects following molecular targeting of glutamatergic receptors. Therapeutically, this has led to advances in the discovery, testing, and clinical application of a wide array of glutamatergic agents, particularly ketamine. Notably, ketamine has been demonstrated to rapidly improve mood symptoms, unlike monoamine-based interventions, and the neurobiological basis behind this rapid antidepressant response is under active investigation. Advances in brain ...

Stellate ganglion block (SGB) is a procedure involving the injection of a local anesthetic surrounding the stellate ganglion to inhibit sympathetic outflow. The objective of this review was to summarize existing evidence on the use of SGB in adults with psychiatric disorders. A systematic search identified 17 published studies and 4 registered clinical trials. Eighty-eight percent of published studies, including 2 randomized controlled trials (RCTs), used SGB for posttraumatic stress disorder (PTSD), although its use for schizophrenia spectrum disorders was also explored. Administration of 1 to 2 SGBs using right-sided laterality with 0.5% ropivacaine was most common. Preliminary evidence from clinical trials and case studies supports the feasibility of SGB for treating psychiatric disorders involving dysregulation of the sympathetic nervous system, although effectiveness evidence from RCTs is mixed. One RCT concluded that improvement in PTSD symptoms was significant, while the othe...

Neuroimaging studies have demonstrated aberrant structure and function of the "cognitive-affective cerebellum" in major depressive disorder (MDD), although the specific role of the cerebello-cerebral circuitry in this population remains largely uninvestigated. The objective of this study was to delineate the role of cerebellar functional networks in depression. A total of 308 unmedicated participants completed resting-state functional magnetic resonance imaging scans, of which 247 (148 MDD; 99 healthy controls, HC) were suitable for this study. Seed-based resting-state functional connectivity (RsFc) analysis was performed using three cerebellar regions of interest (ROIs): ROI1 corresponded to default mode network (DMN)/inattentive processing; ROI2 corresponded to attentional networks, including frontoparietal, dorsal attention, and ventral attention; ROI3 corresponded to motor processing. These ROIs were delineated based on prior functional gradient analyses of the cerebel...

BACKGROUND Recently, a small literature has emerged suggesting that repetitive transcranial magnetic stimulation (rTMS) may offer benefit for MDD even in BPD patients, perhaps by enhancing cognitive control, and/or disrupting excessive 'non-reward' activity in right orbitofrontal regions. This study aimed primarily to assess the therapeutic effects of dorsomedial prefrontal cortex (DMPFC)-rTMS against MDD symptoms in BPD patients, and secondarily to assess whether the therapeutic effects ensued via mechanisms of reduced impulsivity and core BPD pathology on clinical scales (BIS-11, ZAN-BPD) or of reduced alpha- and theta-band activity on EEG recordings of right orbitofrontal cortex.. METHODS In a crossover-design trial, 20 BPD patients with MDD underwent 2 × 30 session/15 day blocks of either active-then-sham or sham-then-active bilateral 20 Hz DMPFC-rTMS. RESULTS Sixteen out of 20 patients completed treatment. A significant (p=0.00764) crossover effect was detected, with overall reductions in HamD17 score from 23.1±SD3.1 to 10.75±SD5.8. Nine out of 16 (56.3%) treatment completers achieved response (>50% improvement) and 6/16 (37.5%) achieved remission (HamD≤7), maintained at 1 month followup. BIS-11 scores remained unchanged, and ZAN-BPD scores improved similarly in both groups with no significant crossover effect. Change in low-band power over right orbitofrontal regions correlated with clinical improvement. LIMITATIONS This was a crossover study with a small sample size. A randomized controlled trial with larger sample size will be needed to establish the efficacy more definitively. CONCLUSIONS The results suggest efficacy for DMPFC-rTMS in treating MDD in BPD, and provide a foundation for a larger future trial.

We write to comment on “Maternal mood symptoms in pregnancy and postpartum depression: association with exclusive breastfeeding in a population-based birth cohort” [1]. This study evaluated the associations between maternal mood symptoms during pregnancy and exclusive breastfeeding at 3 months postpartum, and between exclusive breastfeeding at 3 months and maternal depression at 12 months postpartum in a large birth cohort (n = 4,231) in Pelotas, Brazil. Our first concern is with the assessment of mood symptoms by a single question: “During pregnancy, did you have depression or nervous problems?” Single-question assessments can lead to underreporting [2]. Moreover, “depression” and “nervous problems” were left undefined. This approach may have misrepresented the true prevalence of women experiencing such symptoms. When using singleitem measures to assess mood, it is recommended to show convergent validity with a reliable scale [3], but it appears that this step was not taken. The Edinburgh Postpartum Depression Scale (EPDS) [4] was used to identify cases. The typical cut-off score on the EPDS to indicate the possibility of postpartum depression is 13, contrary to the cut-off score of 10 used. Furthermore, because some EPDS items assess anxiety and not depression (e.g., “I have been anxious or worried for no good reason”) or events that can normally occur when caring for an infant (e.g., “Things have been getting on top of me”), verifying its factor structure in this sample would have been important. Farías-Antúnez et al. cite a validation study of a Portuguese version of the EPDS involving mothers from the Pelotas birth cohort study [5]. That study showed that the specificity of the EPDS when using a cut-off score of 10 was low (65%). Additionally, a recent systematic review assessing the reliability and validity of the EPDS in lowand middleincome countries concluded that most non-English language versions of the EPDS do not meet the criteria necessary to formally validate the instrument [6], which calls into question its validity and cultural appropriateness for Brazil. This could have compromised participants’ interpretations of the This correspondence refers to an article previously published in Social Psychiatry and Psychiatric Epidemiology. The original article can be found here: https ://link.sprin ger.com/artic le/10.1007/s0012 7-019-01827 -2.

Objective Neuroimaging studies have demonstrated aberrant structure and function of the “cognitive-affective cerebellum” in Major Depressive Disorder (MDD), although the specific role of the cerebello-cerebral circuitry in this population remains largely uninvestigated. The objective of this study was to delineate the role of cerebellar functional networks in depression. Methods A total of 308 unmedicated participants completed resting-state functional magnetic resonance imaging scans, of which 247 (148 MDD; 99 Healthy Controls, HC) were suitable for this study. Seed-based resting-state functional connectivity (RsFc) analysis was performed using three cerebellar regions of interest (ROIs): ROI1 corresponded to default mode network (DMN) / inattentive processing; ROI2 corresponded to attentional networks including frontoparietal, dorsal attention, and ventral attention; ROI3 corresponded to motor processing. These ROIs were delineated based on prior functional gradient analyses of th...

1. Bartoli F, Crocamo C, Carrà G. Cannabis use disorder and suicide attempts in bipolar disorder: a meta-analysis. Neurosci Biobehav Rev. 2019;103(1):14-20. 2. Carrà G, Bartoli F, Crocamo C. Trends of major depressive episode among people with cannabis use: findings from the national survey on drug use and health 2006-2015. Subst Abus. 2019;40(2):178-184. 3. Silote GP, Sartim A, Sales A, et al. Emerging evidence for the antidepressant effect of cannabidiol and the underlying molecular mechanisms. J Chem Neuroanat. 2019;98(5):104-116. 4. Pinto JV, Saraf G, Frysch C, et al. Cannabidiol as a treatment for mood disorders: a systematic review. Can J Psychiatry. 2020; 65(1):213-227. 5. Black N, Stockings E, Campbell G, et al. Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: a systematic review and meta-analysis. Lancet Psychiatry. 2019;6(4):995-1010.

Background Electroconvulsive therapy (ECT) is a procedural treatment that is potentially life-saving for some patients with severe psychiatric illness. At the start of the global coronavirus disease 2019 (COVID-19) pandemic, ECT practice was remarkably disrupted, putting vulnerable individuals at increased risk of symptom exacerbation and death by suicide. This study aimed to capture the self-reported experiences of psychiatrists based at healthcare facilities across Canadian provinces who were delivering ECT treatments during the first phase of the COVID-19 pandemic (i.e., from mid-March 2020 to mid-May 2020). Methods A multidisciplinary team of experts developed a survey focusing on five domains: ECT unit operations, decision-making, hospital resources, ECT procedure, and mitigating patient impact. Responses were collected from psychiatrists providing ECT at 67 ECT centres in Canada, grouped by four geographical regions (Ontario, Quebec, Atlantic Canada, and Western Canada). Resul...

Background Major Depressive Disorder (MDD) is associated with interoceptive deficits expressed throughout the body, particularly the facial musculature. According to the facial feedback hypothesis, afferent feedback from the facial muscles suffices to alter the emotional experience. Thus, manipulating the facial muscles could provide a new “mind-body” intervention for MDD. This article provides a conceptual overview of functional electrical stimulation (FES), a novel neuromodulation-based treatment modality that can be potentially used in the treatment of disorders of disrupted brain connectivity, such as MDD. Methods A focused literature search was performed for clinical studies of FES as a modulatory treatment for mood symptoms. The literature is reviewed in a narrative format, integrating theories of emotion, facial expression, and MDD. Results A rich body of literature on FES supports the notion that peripheral muscle manipulation in patients with stroke or spinal cord injury ma...

Background With nearly one-third of patients with major depressive disorder being resistant to available antidepressants, there is a need to develop new treatments for this population. Stellate ganglion block (SGB) is a procedure used to block sympathetic input to the central autonomic system; it has been administered to treat several conditions, including pain. Recently, indications for SGB have extended and the potential benefits for psychiatric disorders are under investigation. Methods The Local Injection For Treating Mood Disorders (LIFT-MOOD) study investigated the feasibility of a trial of 2 right-sided injections of bupivacaine 0.5% (7 mL) at the stellate ganglion in participants with treatment-resistant depression (TRD) using a randomized, placebo-controlled, pilot trial. Ten participants were randomized in a 1:1 allocation to receive active treatment or placebo (saline). Primary feasibility outcomes included recruitment rate, withdrawal, adherence, missing data, and advers...