Depression in the Primary Care Setting

Park, Lawrence T.; Zarate, Carlos A.

doi:10.1056/nejmcp1712493

Cited by 267 publications

(212 citation statements)

References 49 publications

Supporting

Mentioning

156

Contrasting

Unclassified

Order By: Relevance

“…It is considered to be the third leading cause of disability worldwide ( 2 ). There is increasing interest in developing a more effective MDD treatment in order to improve the poor response experienced in approximately a third of the patients ( 3 ). Many neurobiological systems have been implicated in the etiopathogenesis and pathophysiology of MDD ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder

et al. 2021

View full text Add to dashboard Cite

Background: Major Depressive Disorder (MDD) is associated with both proinflammatory and adaptive immune response abnormalities. Regulatory T lymphocytes (Tregs), a subtype of CD4+ T cells, are relevant for maintaining immune-inflammatory system homeostasis and control of inflammation such as the kind potentially induced by the interactions between the intestinal microbiome and gut mucosa. We investigated the Treg population and its distribution along their stages of differentiation/activation, as well as its function in MDD patients without concomitant diseases. We also studied the potential association between Treg alterations, intestinal barrier damage, and bacterial translocation.Methods: 30 MDD patients and 20 healthy controls were studied. The levels of circulating CD25FoxP3+ Tregs and their distribution on the naïve (TN), effector (TE), central (TCM), and effector memory(TEM) differentiation/activation stages were analyzed using polychromatic flow cytometry. Chemokine receptors (CCR) 2, 5, and 6, and the intracytoplasmic IL-10 expression by the Tregs were also analyzed. The serum IL-10 was measured using Luminex. The serum levels of zonulin and the intestinal fatty acid-binding protein (I-FABP), both markers of gut barrier function, and the LPS-binding protein (LBP), a marker of bacterial translocation, were measured using an enzyme-linked immunosorbent assay.Results: MDD patients had increased number of circulating Tregs cells with enhanced number of Tregs at the TN, TE, TCM, and TEM stages. The percentage of Tregs cells at TN stage was significantly higher in MDD patients. The percentage of Tregs that expressed CCR2 and CCR6 was increased as well as those expressing IL-10. MDD patients had significantly increased levels of circulating I-FABP and LBP. MDD patients with high LBP levels had a significant reduction in the number of circulating Tregs compared to normal-LBP MDD patients.Conclusions: MDD patients showed an expansion of circulating Tregs and their CD25highFoxP3+ and CD25lowFoxP3+ subsets throughout the different stages of CD4+ T lymphocyte differentiation/activation. Tregs also showed an increased frequency of cells expressing CCR6 and CCR2. IL-10 Treg production was also enhanced in MDD patients that concurrently had increased serum IL-10 levels. However, this Treg expansion was blunted in MDD patients with gut barrier damage and increased bacterial translocation.

show abstract

Section: Introductionmentioning

confidence: 99%

Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder

et al. 2021

View full text Add to dashboard Cite

show abstract

“…As reliability and practical use are vital aspects of animal models for translational research, OBX presents advantages over the UCMS 9 . Considering the interest in novel and fast-acting antidepressant agents, the purposes of this study were: (1) to investigate if systemic GUO induces fast-onset antidepressant effects in the OBX model of depression in mice, and (2) verify the involvement of the mechanistic target of rapamycin (RAP), the mammalian target of rapamycin (mTOR) pathway, a key target in the fast onset effect of ketamine (Ket) 12 . Figure 1 shows the effects of GUO and Ket in the Splash test (SPT).…”

mentioning

confidence: 99%

Guanosine fast onset antidepressant-like effects in the olfactory bulbectomy mice model

Almeida

Pocharski

Rodrigues

et al. 2020

Sci Rep

View full text Add to dashboard Cite

The treatment of major depressive disorder (MDD) is still a challenge. In the search for novel antidepressants, glutamatergic neuromodulators have been investigated as possible fast-acting antidepressants. Innovative studies suggest that the purine cycle and/or the purinergic signaling can be dysregulated in MDD, and the endogenous nucleoside guanosine has gained attention due to its extracellular effects. This study aimed to verify if guanosine produces fast-onset effects in the wellvalidated, reliable and sensitive olfactory bulbectomy (OBX) model of depression. The involvement of the mTOR pathway, a key target for the fast-onset effect of ketamine, was also investigated. Results show that a single i.p. injection of guanosine, or ketamine, completely reversed the OBX-induced anhedonic-like behavior 24 or 48 h post treatment, as well as the short-term recognition memory impairment 48 h post treatment. The antidepressant-like effects of guanosine and ketamine were completely abolished by rapamycin. This study shows, for the first time, that guanosine, in a way similar to ketamine, is able to elicit a fast antidepressant response in the OBX model in mice. The results support the notion that guanosine represents a new road for therapeutic improvement in MDD. Major depressive disorder (MDD), a severe psychiatric condition, is characterized by high prevalence 1 and disability for affected individuals 2,3 , leading to elevated economic burden 1,4 and a substantial percentage (circa 30%) of patients unresponsive to treatment 4,5. Though this picture vindicates the search for superior medication 6 , unfortunately most research results has been limited to more drugs with the same mechanism of action, or at best certain incremental innovation 7,8. A major flaw in treating depression is the time lag between the onset of the treatment and the remission of the symptoms 4. Especially relevant for treating patients is skepticism, this delay obstructs adhesion, prolongs suffering and disability, and increase suicide risk 4,9. Ketamine has emerged as a fast-acting antidepressant agent that is effective to elicit rapid effect even for severe depressed patients refractory to antidepressant treatment 10. However, ketamine seems to be an unsecure drug especially under repeated administration. This limitation of ketamine's use has lead to renewed efforts for pursuing novel fast-acting antidepressant agents, especially glutamatergic neuromodulators, including guanosine (GUO) 9,11-13. Several lines of evidence suggest that the purine cycle and/or the purinergic signaling could be dysregulated in MDD patients 14-17. As purinergic signaling modulate cell proliferation, differentiation, neuron-glia crosstalk, and inflammation 17-19 , disturbances in purine homeostasis contribute to the pathophysiological process underlying MDD 15,18. GUO is an endogenous nucleoside with neuroprotective effects shown in different animal models of brain disorders 17,20,21. In conditions under which brain homeostasis is disrupted GUO seems to play an importa...

show abstract

“…With increasing trends of deliberate self-harm, there is a need of a holistic approach to manage depression and other common mental health problems in primary care for preventing people from taking extreme steps. [910]…”

Section: Discussionmentioning

confidence: 99%

Profile of acute poisoning cases and their outcome in a teaching hospital of north India

Mathew

Jamshed

Aggarwal

et al. 2019

J Family Med Prim Care

View full text Add to dashboard Cite

Objectives:Aim of this study was to characterize acute poisoning and snakebite cases and their outcome in the Emergency Department (ED).Methods:This was a prospective study done in the ED of a tertiary healthcare center. Study included 184 patients of acute poisoning and 16 cases of snakebite. Data regarding demographics, type, time, and mode of poisoning, lag time in reaching the hospital, initiation of treatment, first aid, in-hospital treatment, and comorbid illness were obtained. Data regarding requirement of antidote, duration of hospitalization, and outcome were also obtained.Results:Out of 200 cases, 181 (90.5%) were adults and 19 (9.5%) were of pediatric age group. Poisoning was common among males (57%) than females (43%). Majority (40%) were from the age group of 21–30 years. Out of 200, 115 (57.5%) poisonings were suicidal, 68 (34%) were accidental, and 17 (8.5%) were homicidal. Acute poisonings included corrosive 54 (27%), drug overdose 26 (13%), organophosphorus compounds 20 (10%), rodenticides 20 (10%), and symptomatic snakebite 16 (8%). Seventy-two (36%) were admitted with a median hospital stay of 6 days with 5 (2.5%) deaths. Logistic regression analysis revealed poorer outcome for 15–30 years age [OR 12.6 (1.6–97.5), P = 0.015], males [OR 2.5 (1.4–4.4) P = 0.04], patients coming from >30 km [OR 4.3 (1.5–12.1), P = 0.006].Conclusion:Our study demonstrated an increased incidence of corrosive ingestion. With increasing rates of suicidal ingestions, there is a need for holistic approach to manage mental health issues at primary care level.

show abstract

Depression in the Primary Care Setting

Cited by 267 publications

References 49 publications

Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder

Blunted Expansion of Regulatory T Lymphocytes Is Associated With Increased Bacterial Translocation in Patients With Major Depressive Disorder

Guanosine fast onset antidepressant-like effects in the olfactory bulbectomy mice model

Profile of acute poisoning cases and their outcome in a teaching hospital of north India

Contact Info

Product

Resources

About