Adults with depressive symptoms have lower odds of dietary supplement use.

OBJECTIVE: In this study, we aim to evaluate dietary supplement and complementary and alternative medicine (CAM) use in individuals with depressive symptoms. Furthermore, we conducted a comparative analysis of the usage of these agents among individuals with depressive symptoms, differentiating between those who were using antidepressants and those who were not. Additionally, we compared individuals with depressive symptoms who were not using antidepressants with participants who did not have depressive symptoms as well as individuals with depressive symptoms who were using antidepressants with individuals without depressive symptoms. METHOD: The National Health and Nutrition Examination Survey 2007-2018 data was collected. Depressive symptoms were assessed using patient health questionnaire-9. Dietary supplement and antidepressants use was evaluated using Dietary Supplement Use and Prescription Medications Questionnaires. RESULTS: 31,445 participants, with 2870 (8.05%) having depressive symptoms were included. Participants with depressive symptoms had significantly lower odds of dietary supplement use compared with those without depressive symptoms (aOR = 0.827, 95% CI: 0.700,0.977, p = 0.026). Participants with depressive symptoms who were using antidepressants had significantly higher odds of dietary supplement (aOR = 1.290, 95% CI: 1.038,1.604, p = 0.022) compared with participants with depressive symptoms who were not using antidepressants. Furthermore, Participants with depressive symptoms who weren't using antidepressants had significantly lower odds of dietary supplement use (aOR = 0.762, 95% CI: 0.632,0.918, p = 0.005) compared with participants without depressive symptoms. In individuals with treated depressive symptoms compared to those without depressive symptoms, CAM use was significantly lower (aOR = 0.763, 95% CI = 0.598,0.973, p = 0.030). CONCLUSION: Individuals with depressive symptoms have lower odds of dietary supplement use. Further studies are needed to replicate these findings and examine the underlying mechanisms for this association.

Digital Interventions to Understand and Mitigate Stress Response: Protocol for Process and Content Evaluation of a Cohort Study.

BACKGROUND: Staffing and resource shortages, especially during the COVID-19 pandemic, have increased stress levels among health care workers. Many health care workers have reported feeling unable to maintain the quality of care expected within their profession, which, at times, may lead to moral distress and moral injury. Currently, interventions for moral distress and moral injury are limited. OBJECTIVE: This study has the following aims: (1) to characterize and reduce stress and moral distress related to decision-making in morally complex situations using a virtual reality (VR) scenario and a didactic intervention; (2) to identify features contributing to mental health outcomes using wearable, physiological, and self-reported questionnaire data; and (3) to create a personal digital phenotype profile that characterizes stress and moral distress at the individual level. METHODS: This will be a single cohort, pre- and posttest study of 100 nursing professionals in Ontario, Canada. Participants will undergo a VR simulation that requires them to make morally complex decisions related to patient care, which will be administered before and after an educational video on techniques to mitigate distress. During the VR session, participants will complete questionnaires measuring their distress and moral distress, and physiological data (electrocardiogram, electrodermal activity, plethysmography, and respiration) will be collected to assess their stress response. In a subsequent 12-week follow-up period, participants will complete regular assessments measuring clinical outcomes, including distress, moral distress, anxiety, depression, and loneliness. A wearable device will also be used to collect continuous data for 2 weeks before, throughout, and for 12 weeks after the VR session. A pre-post comparison will be conducted to analyze the effects of the VR intervention, and machine learning will be used to create a personal digital phenotype profile for each participant using the physiological, wearable, and self-reported data. Finally, thematic analysis of post-VR debriefing sessions and exit interviews will examine reoccurring codes and overarching themes expressed across participants' experiences. RESULTS: The study was funded in 2022 and received research ethics board approval in April 2023. The study is ongoing. CONCLUSIONS: It is expected that the VR scenario will elicit stress and moral distress. Additionally, the didactic intervention is anticipated to improve understanding of and decrease feelings of stress and moral distress. Models of digital phenotypes developed and integrated with wearables could allow for the prediction of risk and the assessment of treatment responses in individuals experiencing moral distress in real-time and naturalistic contexts. This paradigm could also be used in other populations prone to moral distress and injury, such as military and public safety personnel. TRIAL REGISTRATION: ClinicalTrials.gov NCT05923398; https://clinicaltrials.gov/study/NCT05923398. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54180.

The association between depressive symptoms and high-sensitivity C-reactive protein: Is body mass index a moderator?

Objective: Depression and obesity are highly comorbid conditions with shared biological mechanisms. It remains unclear how depressive symptoms and body mass index (BMI) interact in relation to inflammation. This cross-sectional study investigated the independent associations of depressive symptoms and BMI with high sensitivity C-reactive protein (hs-CRP), as well as the moderating role of BMI on the depressive symptoms-hs-CRP association. Methods: Participants (n = 8827) from the 2015-2018 National Health and Nutrition Examination Surveys were aged ≥20 with a BMI ≥18.5 kg/m2, completed the Depression Screener, and had hs-CRP data. Multivariable linear regression was used to analyze hs-CRP in relation to depressive symptoms and BMI. An interaction term was included to examine whether the depressive symptoms-hs-CRP relationship differs depending on BMI. Results: There was a slight, albeit non-significant, increase in hs-CRP levels with each one-point increase in depressive symptoms (aCoef.Estm. = 0.01, 95% CI = -0.05, 0.06, p = 0.754). Participants with overweight (aCoef.Estm. = 1.07, 95% CI = 0.61, 1.53, p < 0.001) or obese (aCoef.Estm. = 3.51, 95% CI = 3.04, 3.98, p < 0.001) BMIs had higher mean hs-CRP levels than those with a healthy BMI. There were no significant interactions between depressive symptoms and overweight (aCoef.Estm. = 0.04, 95% CI = -0.04, 0.13, p = 0.278) or obese (aCoef.Estm. = 0.11, 95% CI = -0.01, 0.22, p = 0.066) BMI indicating a lack of difference in the depressive symptoms-hs-CRP association across participants in the healthy versus overweight and obese ranges. Conclusions: This study suggests that BMI might not act as a moderator in the association between depressive symptoms and hs-CRP. Results should be replicated in larger samples. Further research is warranted to understand underlying mechanisms.

A Systematic Review of Neurodevelopmental Assessments in Infancy and Early Childhood: Developing a Conceptual Framework, Repository of Measures, and Clinical Recommendations.

The first 6 years of life are when 90% of brain development occurs, setting the foundation for lifelong neurodevelopment. The field of infant and early childhood neurodevelopment has made marginal advancements since introduced in 1988. There remains a gap in knowledge around early neurodevelopmental domains and trajectories given that there are few established assessment procedures for infants and young children and controversies around reserving assessments until school age. Throughout this systematic review, we (1) identified neurodevelopmental assessment measures employed in the literature by domain and age of assessment, (2) compiled a repository of 608 domain-specific neurodevelopmental assessment measures, and (3) established a preliminary conceptual framework for cross-domain neurodevelopmental assessments across infancy and early childhood. This review adhered to PRISMA guidelines and spanned three databases (PsycINFO, MEDLINE, PubMed). Articles were reviewed for (1) infancy and early childhood (0-6 years), (2) neurodevelopmental measures, and (3) English language. This systematic review spanned 795 articles from 1978 to 2020 with international representation. Advancements in assessment methods (e.g. measures, domains, frameworks) are essential for the evaluation of early neurodevelopmental profiles to inform early interventions, thus harnessing the neuroplasticity and dynamic development notable during early childhood. We hope this work catalyzes future research and clinical guidelines around early assessments methods.

Decreased odds of depressive symptoms and suicidal ideation with higher education, depending on sex and employment status.

BACKGROUND: Higher education is associated with reduced depressive symptoms and requires investment without guaranteed employment. It remains unclear how sex and employment status together contribute to the association between mental health and educational attainment. This study investigated the role of sex and employment status together in the associations of 1) depressive symptoms and 2) suicidal ideation with education. METHODS: Using 2005-2018 National Health and Nutrition Examination Survey data, cross-sectional analyses were conducted on individuals ≥20 years who completed the depression questionnaire and reported their employment status and highest level of education. Survey-weighted multivariable logistic regression models were used to explore how depressive symptoms and suicidal ideation are associated with educational attainment in an analysis stratified by sex and employment status. To account for multiple testing, a significance level of a < 0.01 was used. RESULTS: Participants (n = 23,669) had a weighted mean age of 43.25 (SD = 13.97) years and 47% were female. Employed females (aOR = 0.47, 95% CI 0.32, 0.69), unemployed females (aOR = 0.47, 95% CI 0.29, 0.75), and unemployed males (aOR = 0.31, 95% CI 0.17, 0.56) with college education had reduced odds of depressive symptoms compared to those with high school education. Employed females with college education also had reduced suicidal ideation odds compared to those with high school education (aOR = 0.41, 95% CI 0.22, 0.76). CONCLUSIONS: Females demonstrated significant associations between depressive symptoms and education, regardless of employment status, whereas males demonstrated an association only if unemployed. Employed females, in particular, demonstrated a significant association between suicidal ideation and education. These findings may inform future research investigating the underlying mechanisms and etiology of these sex-employment status differences in the association between mental health and education.

Does Self-Reported BMI Modify the Association Between Stroke and Depressive Symptoms?

BACKGROUND: Depressive symptoms are common in stroke survivors. While obesity has been associated with stroke and depression, its influence on the association between stroke and depressive symptoms is unknown. METHODS: Cross-sectional data from 2015 to 2016 Canadian Community Health Survey was used. History of stroke was self-reported and our outcome of interest was depressive symptoms in the prior 2 weeks, measured using the 9-item Patient Health Questionnaire. Self-reported body mass index (BMI) was modeled as cubic spline terms to allow for nonlinear associations. We used multivariable logistic regression to evaluate the association between stroke and depressive symptoms and added an interaction term to evaluate the modifying effect of BMI. RESULTS: Of the 47,521 participants, 694 (1.0%) had a stroke and 3314 (6.5%) had depressive symptoms. Those with stroke had a higher odds of depressive symptoms than those without (aOR = 3.13, 95% CI 2.48, 3.93). BMI did not modify the stroke-depressive symptoms association (P interaction = 0.242) despite the observed variation in stroke-depressive symptoms association across BMI categories,: normal BMI [18.5-25 kg/m2] (aOR† = 3.91, 95% CI 2.45, 6.11), overweight [25-30 kg/m2] (aOR† = 2.63, 95% CI 1.58, 4.20), and obese [>30 kg/m2] (aOR† = 2.76, 95% CI 1.92, 3.94). Similar results were found when depressive symptoms were modeled as a continuous measure. CONCLUSION: The association between stroke and depressive symptoms is not modified by BMI, needing additional work to understand the role of obesity on depression after stroke.

Amygdala biomarkers of treatment response in major depressive disorder: An fMRI systematic review of SSRI antidepressants.

Functional neuroimaging studies have demonstrated abnormal activity and functional connectivity (FC) of the amygdala among individuals with major depressive disorder (MDD), which may be rectified with selective serotonin reuptake inhibitor (SSRI) treatment. This systematic review aimed to identify changes in the amygdala on functional magnetic resonance imaging (fMRI) scans among individuals with MDD who received SSRIs. A search for fMRI studies examining amygdala correlates of SSRI response via fMRI was conducted through OVID (MEDLINE, PsycINFO, and Embase). The end date was April 4th, 2023. In total, 623 records were screened, and 16 studies were included in this review. While the search pertained to SSRIs broadly, the included studies were escitalopram-, citalopram-, fluoxetine-, sertraline-, and paroxetine-specific. Decreases in event-related amygdala activity were found following 6-to-12-week SSRI treatment, particularly in response to negative stimuli. Eight-week courses of SSRI pharmacotherapy were associated with increased event-related amygdala FC (i.e., with the prefrontal [PFC] and anterior cingulate cortices, insula, thalamus, caudate nucleus, and putamen) and decreased resting-state effective connectivity (i.e., amygdala-PFC). Preliminary evidence suggests that SSRIs may alter amygdala activity and FC in MDD. Additional studies are needed to corroborate findings. Future research should employ long-term follow-ups to determine whether effects persist after treatment termination.

Temporal associations of BMI and glucose parameters with depressive symptoms among US adults.

As the prevalence of obesity, diabetes, and depression increases, it is important to examine how their associations are changing overtime. We investigated the temporal trends in the association between depressive symptoms, body mass index (BMI) and glucose profile parameters using data from 2005 to 2018 National Health and Nutrition Examination Survey. Depressive symptoms were assessed using the Patient Health Questionnaire. A total of 32,653 participants were included. Risk of depressive symptoms increased with higher BMI (aOR = 1.586, 95 % CI [1.364, 1.843]), insulin (aOR = 1.327, 95 % CI [1.159, 1.519]), HbA1c (aOR = 1.330, 95 % CI [1.116, 1.585]), or fasting glucose (aOR = 1.565, 95 % CI [1.247, 1.964]) levels compared to those with low levels. Sex differences were found, as overweight males had lower odds of depressive symptoms compared to healthy males, while overweight and obese females had higher odds compared to healthy females. High BMI and glucose parameters were consistently associated with higher depressive symptoms prevalence over time. Temporal variations were observed in the depressive symptoms-BMI and depressive symptoms-HbA1c associations, particularly at the 2007-2008 cycle. This study provides analytic insights into population level trends concerning physical and mental health problems.

Sustained Mood Improvement with Laughing Gas Exposure (SMILE): Study protocol for a randomized placebo-controlled pilot trial of nitrous oxide for treatment-resistant depression.

BACKGROUND: Nitrous oxide has shown potentially as an efficacious intervention for treatment-resistant depression, yet there remains insufficient evidence pertaining to repeated administration of nitrous oxide over time and active placebo-controlled studies with optimal blinding. Thus, we aim to examine the feasibility and preliminary efficacy of a six-week follow up study examining the effects of a 4 week course of weekly administered nitrous oxide as compared to the active placebo, midazolam. METHODS: In this randomized, active placebo-controlled, pilot trial, 40 participants with treatment-resistant depression will receive either inhaled nitrous oxide (1 hour at 50% concentration) plus intravenous saline (100mL) or inhaled oxygen (1 hour at 50% concentration) plus intravenous midazolam (0.02 mg/kg in 100mL, up to 2mg) once per week, for 4 consecutive weeks. Participants will be followed up for 6 weeks starting from the first treatment visit. Primary feasibility outcomes include recruitment rate, withdrawal rate, adherence, missing data, and adverse events. The primary exploratory clinical outcome is change in Montgomery-Åsberg Depression Rating Scale (MADRS) score at day 42 of the study. Other exploratory clinical outcomes include remission (defined as MADRS score <10), response (defined as ≥ 50% reduction in MADRS score), and adverse side effects. DISCUSSION: This pilot study will provide valuable information regarding the feasibility and preliminary efficacy of repeated nitrous oxide administration over time for treatment-resistant depression. If feasible, this study will inform the design of a future definitive trial of nitrous oxide as an efficacious and fast-acting treatment for treatment-resistant depression. TRIAL REGISTRATION: ClinicalTrials.gov NCT04957368. Registered on July 12, 2021.

The course of insomnia symptoms during the acute treatment of major depressive disorder: A CAN-BIND-1 report.

Despite considerable efforts to study the relationship between insomnia and depression, there is minimal research investigating whether insomnia symptoms change over time during a course of antidepressant pharmacotherapy. This study investigated the course of insomnia symptoms during the acute treatment of major depressive disorder (MDD) using a secondary analysis of data from MDD patients (N = 180) who were treated with open-label escitalopram (10-20 mg/day) for 8-weeks. Montgomery-Asberg Depression Rating Scale without sleep item (modified-MADRS) assessed depression and Self-reported Quick Inventory Depressive Scale (QIDS-SR) measured subjective sleep-onset, mid-nocturnal, and early-morning insomnia throughout 8-weeks of treatment. Pittsburgh Sleep Quality Index (PSQI) was used to assess subjective sleep quality, duration, onset latency, and efficiency throughout 8-weeks of treatment. Remission of depression was defined as modified-MADRS ≤10 at week-8. Mixed model repeated measures (MMRMs) were conducted with remission status as an independent variable and each sleep variable as a dependent variable. MMRMs demonstrated that remitters had significantly lower QIDS-SR sleep-onset and mid-nocturnal insomnia scores as well as a significantly lower PSQI sleep quality score than non-remitters throughout 8-weeks of treatment. Monitoring subjective sleep-onset and mid-nocturnal insomnia during the course of treatment with serotonergic antidepressants may be useful for predicting acute remission of depression.

Impact of COVID-19 on electroconvulsive therapy practice across Canadian provinces during the first wave of the pandemic.

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). RESULTS: Clinical operations of ECT programs were disrupted across all four regions - however, centres in Atlantic Canada were able to best preserve outpatient and maintenance care, while centres in Western Canada were able to best preserve inpatient and acute care. Similarly, Atlantic and Western Canada demonstrated the best decision-making practices of involving the ECT team and clinical ethicists in the development of pandemic-related guidelines. Across all four regions, ECT practice was affected by the redeployment of professionals, the shortage of personal protective equipment, and the need to enforce social distancing. Attempts to introduce modifications to the ECT delivery room and minimize bag-valve-mask ventilation were consistently reported. All four regions developed a new patient prioritization framework, and Western Canada, notably, aimed to provide ECT to only the most severe cases. CONCLUSIONS: The results suggest that ECT provision was disproportionately affected across different parts of Canada. Possible factors that could explain these interregional differences include population, distribution of urban vs. rural areas, pre-pandemic barriers in access to ECT, number of cases, ability to control the spread of infection, and the general reduction in physicians' activities across different areas of health care. Studying these factors in the future will inform how medical centres should respond to public health emergencies and pandemic-related circumstances in the context of procedural treatments.

Local Injection for Treating Mood Disorders (LIFT-MOOD): A Pilot Feasibility RCT of Stellate Ganglion Block for Treatment-Resistant Depression.

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 adverse events. As a secondary, exploratory objective, we explored the efficacy of SGB in improving symptoms of depression by calculating the change in scores from baseline to follow-up on day 42 for each treatment group. Results: The recruitment rate was reasonable and sufficient, retention and adherence were high, missing data were low, and adverse events were mild and temporary. Both treatment groups demonstrated decreases in Montgomery-Åsberg Depression Rating Scale scores, compared to baseline, by the end of the study. Conclusion: This study supports the feasibility of a confirmatory trial of SGB in participants with TRD. Conclusions regarding efficacy cannot be made based on this preliminary study due to the small number of participants who completed active treatment. Larger-scale randomized controlled trials with long-term follow-ups and alternate sham procedures are needed to assess the efficacy and duration of symptom improvement with the use of SGB in TRD.

Efficacy of ketamine for comorbid depression and acute or chronic pain: A systematic review.

Pain and depression frequently co-occur. Due to its antidepressant and analgesic properties, ketamine has been used for the management of treatment-resistant depression and pain. This systematic review examined the literature on the efficacy of sub-anesthetic doses of ketamine in individuals experiencing comorbid depression and chronic pain (CDCP), as well as comorbid depression and acute pain (CDAP). A secondary objective was to provide an assessment of dosage, route, and adverse effects of ketamine treatment for CDCP and CDAP. A literature search was conducted on MEDLINE, PsycINFO, and Embase databases, coupled with a manual screening of the bibliography sections of included articles. In addition, registered ongoing and planned trials were searched on Clinicaltrials.gov. The end date of the search was April 9th, 2022. Included studies assessed changes in depression and pain in patients receiving at least one sub-anesthetic dose of ketamine. Assessment of quality was conducted using the GRADE checklist. Of the 7 CDCP clinical trials, 3 reported a reduction in depression and pain, 3 reported a reduction in depression or pain only, and 1 reported no improvement in either comorbidity. Among the 7 CDAP clinical trials, 4 studies found improvements in depression and pain while the remaining 3 reported improvements in only one parameter. Ten of the 12 case studies and 2 of the 3 observational studies assessing CDCP and CDAP found improvements in pain and depression scores post-treatment with effects of variable duration. The planned methodologies of the registered clinical trials are in line with those of the published research. Preliminary evidence supports the efficacy of ketamine in treating CDCP and CDAP. However, the current review identified a small number of heterogeneous studies with mixed results, preventing comprehensive conclusions. More longitudinal placebo-controlled studies are needed to identify the effects of ketamine for patients with CDCP and CDAP.

Neuroimaging Correlates of Treatment Response with Psychedelics in Major Depressive Disorder: A Systematic Review.

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 subjective outcomesTrials.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 global decreases in brain network modularity which correlated with antidepressant response. One ayahuasca study reported increased activity in the limbic regions following treatment. Preliminary evidence suggests that the default mode and limbic networks may be a target for future research on the neural mechanisms of psychedelics. More data is required to corroborate these initial findings as the evidence summarized in this review is based on four datasets.

Contrasting the amygdala activity and functional connectivity profile between antidepressant-free participants with major depressive disorder and healthy controls: A systematic review of comparative fMRI studies.

Functional neuroimaging research suggests that the amygdala is implicated in the pathophysiology of major depressive disorder (MDD). This systematic review aimed to identify consistently reported amygdala activity and functional connectivity (FC) abnormalities in antidepressant-free participants with MDD as compared to healthy controls at baseline (i.e., before treatment initiation or experimental manipulation). A search for relevant published studies and registered clinical trials was conducted through OVID (MEDLINE, PsycINFO, and Embase) and ClinicalTrials.gov with an end date of March 7th, 2022. Fifty published studies and two registered clinical trials were included in this review. Participants with MDD frequently exhibited amygdala hyperactivity in response to negative stimuli, abnormal event-related amygdala-anterior cingulate cortex (ACC) FC, and abnormal resting-state amygdala FC with the insula and the prefrontal, temporal, and parietal cortices. Decreased resting-state FC was consistently found between the amygdala and the orbitofrontal cortex, striatum, cerebellum, and middle/inferior frontal gyri. Due to the limited number of studies examining resting-state amygdala activity and FC with specific subregions of interest, including those within the ACC, further investigation is warranted.

Intrinsic Connectivity Networks of Glutamate-Mediated Antidepressant Response: A Neuroimaging Review.

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 imaging techniques, including functional magnetic resonance imaging, magnetic resonance spectroscopy, and positron emission tomography, enable the identification of the brain network-based characteristics distinguishing rapid glutamatergic modulation from the effect of slow-acting conventional monoamine-based pharmacology. Here, we review brain imaging studies that examine brain connectivity features associated with rapid antidepressant response in MDD patients treated with glutamatergic pharmacotherapies in contrast with patients treated with slow-acting monoamine-based treatments. Trends in recent brain imaging literature suggest that the activity of brain regions is organized into coherent functionally distinct networks, termed intrinsic connectivity networks (ICNs). We provide an overview of major ICNs implicated in depression and explore how treatment response following glutamatergic modulation alters functional connectivity of limbic, cognitive, and executive nodes within ICNs, with well-characterized anti-anhedonic effects and the enhancement of "top-down" executive control. Alterations within and between the core ICNs could potentially exert downstream effects on the nodes within other brain networks of relevance to MDD that are structurally and functionally interconnected through glutamatergic synapses. Understanding similarities and differences in brain ICNs features underlying treatment response will positively impact the trajectory and outcomes for adults suffering from MDD and will facilitate the development of biomarkers to enable glutamate-based precision therapeutics.