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British Journal of Clinical Pharmacology Oct 2022The aim of this study was to systematically review the use of vaptans (nonpeptide vasopressin receptor antagonists) in children.
AIMS
The aim of this study was to systematically review the use of vaptans (nonpeptide vasopressin receptor antagonists) in children.
METHODS
Through a database search (Web of Science, the National Library of Medicine, Excerpta Medica), we identified case series and case reports and extracted clinical and laboratory data.
RESULTS
Twenty-six articles, published since 2008, reported on 226 patients. Among 115 children with hyponatraemic (n = 63) and oedematous disorders (n = 52), a 48 hour course of tolvaptan with an initial dose of 0.38 ± 0.27 mg/kg was administered in 106 cases, while intravenous conivaptan was reported in nine cases. An increase (P < .02) in urine output was shown in both oedematous (from 3.2 ± 2.0 to 5.3 ± 6.7 mL/kg/day) and hyponatraemic (from 3.0 ± 1.5 to 4.4 ± 2.3 mL/kg/day) patients. In these latter, sodium increased from 125 ± 6 to 133 ± 6 mmol/L (P < .0001). The increase in sodium level correlated with its basal value, but not with the administered vaptan dose. Among 111 children undergoing cardiac surgery, after tolvaptan 0.21 ± 0.01 mg/kg/day, mostly combined with conventional diuretics, an increase in diuresis by 41 ± 4% was seen within 24 hours (P < .0001). Similarly, a single add-on dose of tolvaptan 0.45 mg/kg allowed a reduced additional intravenous furosemide administration (0.26 ± 0.23 vs 0.62 ± 0.48 mg/kg, P < .005). Side effects were rarely reported, and included excessive thirst and xerostomia in seven, skin rash in one and elevated aminotransferases in one patient(s).
CONCLUSION
Vaptans appear to be safe for oedematous and hyponatraemic disorders also in children. Although they increase diuresis and natraemia, no superiority to traditional diuretics and sodium supplements has been demonstrated. Reported side effects are rare and non-serious.
Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Child; Diuretics; Heart Failure; Humans; Hyponatremia; Sodium; Tolvaptan
PubMed: 35474586
DOI: 10.1111/bcp.15367 -
Journal of Cardiovascular Pharmacology Sep 2016The vasopressin type 2 receptor antagonist tolvaptan (TLV) is available to treat congestion in patients with heart failure. However, there is paucity of evidence guiding... (Meta-Analysis)
Meta-Analysis Review
The vasopressin type 2 receptor antagonist tolvaptan (TLV) is available to treat congestion in patients with heart failure. However, there is paucity of evidence guiding its use, and lack of evidence of its long-term efficacy. Our objectives are to perform a systematic review of studies examining the effects of TLV in patients with heart failure; and a quantitative meta-analysis comparing primary and secondary outcomes between TLV and placebo. Only double-blinded randomized controlled trials, with no restriction on the language or the time of publication, were included. Our main outcome measures were all-cause mortality, change in body weight, change in urine volume, and change in serum sodium. Extracted summary estimates included mean difference and SD for change in body weight, change in urine volume and change in serum sodium levels, and hazard ratio with 95% confidence interval for all-cause mortality. We found 8 double-blinded randomized controlled trials, seven of which were included in this meta-analysis. Assessment of risk of bias was conducted by investigating random sequence generation, allocation concealment, blinding, completeness of outcome data, and potential for selective reporting. We found no evidence of significant bias. TLV showed benefits in reducing body weight, increasing urine volume, and increasing serum sodium. No reduction in mortality was detected. However, the subgroup of patients with hyponatremia might have better mortality outcome with TLV. TLV seemed to be safe, as it did not cause worsening of the renal function or hypotension. In conclusion, a meta-analysis of the published literature suggests short-term benefits of TLV. However, the impact on mortality is inconclusive.
Topics: Antidiuretic Hormone Receptor Antagonists; Benzazepines; Body Weight; Heart Failure; Humans; Mortality; Randomized Controlled Trials as Topic; Tolvaptan
PubMed: 27159621
DOI: 10.1097/FJC.0000000000000405 -
The Cochrane Database of Systematic... Jun 2018Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Chronic (present > 48 hours) non-hypovolaemic hyponatraemia occurs frequently, can be caused by various conditions, and is associated with shorter survival and longer hospital stays. Many treatments, such as fluid restriction or vasopressin receptor antagonists can be used to improve the hyponatraemia, but whether that translates into improved patient-important outcomes is less certain.
OBJECTIVES
This review aimed to 1) look at the benefits and harms of interventions for chronic non-hypovolaemic hypotonic hyponatraemia when compared with placebo, no treatment or head-to-head; and 2) determine if benefits and harms vary in absolute or relative terms dependent on the specific compound within a drug class, on the dosage used, or the underlying disorder causing the hyponatraemia.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 1 December 2017 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. We also screened the reference lists of potentially relevant studies, contacted authors, and screened the websites of regulatory agencies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs that compared the effects of any intervention with placebo, no treatment, standard care, or any other intervention in patients with chronic non-hypovolaemic hypotonic hyponatraemia. We also included subgroups with hyponatraemia from studies with broader inclusion criteria (e.g. people with chronic heart failure or people with cirrhosis with or without hyponatraemia), provided we could obtain outcomes for participants with hyponatraemia from the report or the study authors.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data and assessed risk of bias. We expressed treatment effects as mean difference (MD) for continuous outcomes (health-related quality of life, length of hospital stay, change from baseline in serum sodium concentration, cognitive function), and risk ratio (RR) for dichotomous outcomes (death, response and rapid increase in serum sodium concentration, hypernatraemia, polyuria, hypotension, acute kidney injury, liver function abnormalities) together with 95% confidence intervals (CI).
MAIN RESULTS
We identified 35 studies, enrolling 3429 participants. Twenty-eight studies (3189 participants) compared a vasopressin receptor antagonist versus placebo, usual care, no treatment, or fluid restriction. In adults with chronic, non-hypovolaemic hypotonic hyponatraemia, vasopressin receptor antagonists have uncertain effects on death at six months (15 studies, 2330 participants: RR 1.11, 95% CI 0.92 to 1.33) due to risk of selective reporting and serious imprecision; and on health-related quality of life because results are at serious risk of performance, selective reporting and attrition bias, and suffer from indirectness related to the validity of the Short Form Health Survey (SF-12) in the setting of hyponatraemia. Vasopressin receptor antagonists may reduce hospital stay (low certainty evidence due to risk of performance bias and imprecision) (3 studies, 610 participants: MD -1.63 days, 95% CI -2.96 to -0.30), and may make little or no difference to cognitive function (low certainty evidence due to indirectness and imprecision). Vasopressin receptor antagonists probably increase the intermediate outcome of serum sodium concentration (21 studies, 2641 participants: MD 4.17 mmol/L, 95% CI 3.18 to 5.16), corresponding to two and a half as many people having a 5 to 6 mmol/L increase in sodium concentration compared with placebo at 4 to 180 days (moderate certainty evidence due to risk of attrition bias) (18 studies, 2014 participants: RR 2.49, 95% CI 1.95 to 3.18). But they probably also increase the risk of rapid serum sodium correction - most commonly defined as > 12 mmol/L/d (moderate certainty evidence due to indirectness) (14 studies, 2058 participants: RR 1.67, 95% CI 1.16 to 2.40) and commonly cause side-effects such as thirst (13 studies, 1666 participants: OR 2.77, 95% CI 1.80 to 4.27) and polyuria (6 studies, 1272 participants): RR 4.69, 95% CI 1.59 to 13.85) (high certainty evidence). The potential for liver toxicity remains uncertain due to large imprecision. Effects were generally consistent across the different agents, suggesting class effect.Data for other interventions such as fluid restriction, urea, mannitol, loop diuretics, corticosteroids, demeclocycline, lithium and phenytoin were largely absent.
AUTHORS' CONCLUSIONS
In people with chronic hyponatraemia, vasopressin receptor antagonists modestly raise serum sodium concentration at the cost of a 3% increased risk of it being rapid. To date there is very low certainty evidence for patient-important outcomes; the effects on mortality and health-related quality of life are unclear and do not rule out appreciable benefit or harm; there does not appear to be an important effect on cognitive function, but hospital stay may be slightly shorter, although available data are limited. Treatment decisions must weigh the value of an increase in serum sodium concentration against its short-term risks and unknown effects on patient-important outcomes. Evidence for other treatments is largely absent.Further studies assessing standard treatments such as fluid restriction or urea against placebo and one-another would inform practice and are warranted. Given the limited available evidence for patient-important outcomes, any study should include these outcomes in a standardised manner.
Topics: Antidiuretic Hormone Receptor Antagonists; Chronic Disease; Humans; Hyponatremia; Length of Stay; Quality of Life; Randomized Controlled Trials as Topic; Sodium
PubMed: 29953167
DOI: 10.1002/14651858.CD010965.pub2 -
Journal of Cardiac Surgery Jan 2019Arginine vasopressin (AVP) is a naturally occurring peptide with diverse effects mediated through selective V1 and V2 receptors. About 10% of patients undergoing...
BACKGROUND
Arginine vasopressin (AVP) is a naturally occurring peptide with diverse effects mediated through selective V1 and V2 receptors. About 10% of patients undergoing cardiopulmonary bypass develop postoperative vasodilatory shock requiring high-dose catecholamines. We sought to examine the role of AVP therapy in cardiac surgery.
METHODS
A search of Medline was conducted through September 2018 using key words and medical subject headings (MeSH) relating to AVP, copeptin, and cardiac surgery. A systematic review was performed on articles as they pertained to AVP for use as a vasopressor after cardiovascular surgery complicated by vasodilatory shock.
RESULTS
A relative or absolute deficiency of Arginine vasopressin is associated with vasodilatory shock after cardiopulmonary bypass. Physiologic replacement with exogenous Arginine vasopressin results in significant increases in systemic vascular resistance and mean arterial pressure with decreased requirements of catecholamines. At doses of <0.1 U/min Arginine vasopressin is safe with very few adverse effects.
CONCLUSION
Post-cardiopulmonary bypass vasodilatory shock is largely due to a relative deficiency of Arginine vasopressin. Exogenous administration of low-dose Arginine vasopressin alone or in combination with traditional catecholamines is a safe and effective way to manage this type of vasodilatory shock.
Topics: Cardiac Surgical Procedures; Humans; Shock, Surgical; Vasoconstrictor Agents; Vasodilation; Vasopressins
PubMed: 30597665
DOI: 10.1111/jocs.13968 -
Clinical Endocrinology Jun 2017International and national guidelines on the treatment of chronic nonhypovolaemic hypotonic hyponatraemia differ; therefore, we have undertaken this systematic review... (Meta-Analysis)
Meta-Analysis Review
International and national guidelines on the treatment of chronic nonhypovolaemic hypotonic hyponatraemia differ; therefore, we have undertaken this systematic review and meta-analysis to investigate the efficacy and safety of interventions for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia. Following registration of the review protocol with PROSPERO, systematic literature searches were conducted to identify randomized and quasi-randomized controlled trials assessing any degree of fluid restriction or any drug treatment with the aim of increasing serum sodium concentration in patients with chronic nonhypovolaemic hypotonic hyponatraemia. Where appropriate, outcome data were synthesized in a meta-analysis. A total of 45 716 bibliographic records were identified from the searches and 18 trials (assessing conivaptan, lixivaptan, tolvaptan and satavaptan) met the eligibility criteria. Results suggest that all four vasopressin receptor agonists ("vaptans") significantly improve serum sodium concentration. Lixivaptan, satavaptan and tolvaptan were associated with greater rates of response versus placebo. There was no evidence of a difference between each of the vaptans compared with placebo for mortality, discontinuation and rates of hypernatraemia. No RCT evidence of treatments other than the vaptans for hyponatraemia such as oral urea, salt tablets, mannitol, loop diuretics demeclocycline or lithium was identified. Vaptans demonstrated superiority over placebo for outcomes relating to serum sodium correction. Few trials documented the potential benefit of vaptans on change in health-related quality of life as a result of treatment. There was also a lack of high-quality RCT evidence on the comparative efficacy of the vaptans and other treatment strategies for the treatment of chronic nonhypovolaemic hypotonic hyponatraemia.
Topics: Antidiuretic Hormone Receptor Antagonists; Benzamides; Benzazepines; Humans; Hyponatremia; Morpholines; Osmotic Pressure; Pyrroles; Randomized Controlled Trials as Topic; Receptors, Vasopressin; Spiro Compounds; Tolvaptan
PubMed: 28214374
DOI: 10.1111/cen.13315 -
International Urology and Nephrology Nov 2016Lithium is an essential treatment in bipolar disorder and treatment-resistant depression; however, its use has been limited by concerns regarding its renal adverse... (Review)
Review
PURPOSE
Lithium is an essential treatment in bipolar disorder and treatment-resistant depression; however, its use has been limited by concerns regarding its renal adverse effects. An improved understanding of potential molecular mechanisms can help develop prevention and treatment strategies for lithium-associated renal disease.
METHODS
We conducted a systematic literature search using MEDLINE, Embase, and PsychINFO including English-language original research articles published prior to November 2015 that specifically investigated lithium's effects on nephrogenic diabetes insipidus (NDI) and chronic kidney disease (CKD), using molecular markers.
RESULTS
From a total of 3510 records, 71 pre-clinical studies and two relevant clinical studies were identified. Molecular alterations were reported in calcium signaling, inositol monophosphate, extracellular-regulated, prostaglandin, sodium/solute transport, G-protein-coupled receptors, nitric oxide, vasopressin/aquaporin, and inflammation-related pathways in lithium-associated renal disease. The majority of studies found that these mechanisms were implicated in NDI, while few studies had examined CKD.
DISCUSSION
Future studies will have to focus on (1) validating the present findings in human subjects and (2) examining CKD, which is the most clinically relevant lithium-associated renal effect. This will improve our understanding of lithium's biological effects, as well as inform a personalized medicine approach, which could lead to safer lithium prescribing and less renal adverse events.
Topics: Animals; Aquaporins; Calcium; Diabetes Insipidus, Nephrogenic; Humans; Lithium; Prostaglandins; Receptors, G-Protein-Coupled; Renal Insufficiency, Chronic; Signal Transduction; Sodium; Symporters; Vasopressins
PubMed: 27357223
DOI: 10.1007/s11255-016-1352-6 -
Canadian Journal of Kidney Health and... 2021Acute kidney injury (AKI) is a potentially fatal complication of Coronavirus Disease-2019 (COVID-19). Binding of the Severe Acute Respiratory Syndrome Coronavirus 2...
BACKGROUND
Acute kidney injury (AKI) is a potentially fatal complication of Coronavirus Disease-2019 (COVID-19). Binding of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, to its viral receptor, angiotensin converting enzyme 2 (ACE2), results in viral entry and may cause AKI.
OBJECTIVES
We performed a systematic review and meta-analysis of the frequencies of AKI and renal replacement therapy (RRT) in critically ill COVID-19 patients and compared those frequencies with patients who were infected by respiratory viruses that bind or downregulate ACE2 (ACE2-associated viruses) and viruses that do not bind nor downregulate ACE2 (non-ACE2-associated viruses).
DESIGN
Systematic review and meta-analysis.
SETTING
Observational studies on COVID-19 and other respiratory viral infections reporting AKI and RRT were included. The exclusion criteria were non-English articles, non-peer-reviewed articles, review articles, studies that included patients under the age of 18, studies including fewer than 10 patients, and studies not reporting AKI and RRT rates.
PATIENTS
Adult COVID-19, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and influenza patients.
MEASUREMENTS
We extracted the following data from the included studies: author, year, study location, age, sex, race, diabetes mellitus, hypertension, chronic kidney disease, shock, vasopressor use, mortality, intensive care unit (ICU) admission, ICU mortality, AKI, and RRT.
METHODS
We systematically searched PubMed and EMBASE for articles reporting AKI or RRT. AKI was defined by authors of included studies. Critical illness was defined by ICU admission. We performed a random effects meta-analysis to calculate pooled estimates for the AKI and RRT rate within each virus group using a random intercept logistic regression model.
RESULTS
Of 23 655 hospitalized, critically ill COVID-19 patients, AKI frequencies were not significantly different between COVID-19 patients (51%, 95% confidence interval [CI]: 44%-57%) and critically ill patients infected with ACE2-associated (56%, 95% CI: 37%-74%, = .610) or non-ACE2-associated viruses (63%, 95% CI: 43%-79%, = .255). Pooled RRT rates were also not significantly different between critically ill, hospitalized patients with COVID-19 (20%, 95% CI: 16%-24%) and ACE2-associated viruses (18%, 95% CI: 8%-33%, = .747). RRT rates for both COVID-19 and ACE2-associated viruses were significantly different ( < .001 for both) from non-ACE2-associated viruses (49%, 95% CI: 44%-54%). After adjusting for shock or vasopressor use, AKI and RRT rates were not significantly different between groups.
LIMITATIONS
Limitations of this study include the heterogeneity of definitions of AKI that were used across different virus studies. We could not match severity of infection or do propensity matching across studies. Most of the included studies were conducted in retrospective fashion. Last, we did not include non-English publications.
CONCLUSIONS
Our findings suggest that viral ACE2 association does not significantly alter the rates of AKI and RRT among critically ill patients admitted to the ICU. However, the rate of RRT is lower in patients with COVID-19 or ACE2-associated viruses when compared with patients infected with non-ACE2-binding viruses, which might partly be due to the lower frequencies of shock and use of vasopressors in these two virus groups. Prospective studies are necessary to demonstrate whether modulation of the ACE2 axis with Renin-Angiotensin System inhibitors impacts the rates of AKI and whether they are beneficial or harmful in COVID-19 patients.
PubMed: 34733538
DOI: 10.1177/20543581211052185 -
Nephrology (Carlton, Vic.) Apr 2014Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disorder that leads to kidney failure. Our aim was to undertake a meta-analysis of randomized... (Meta-Analysis)
Meta-Analysis Review
AIM
Autosomal dominant polycystic kidney disease (ADPKD) is a monogenetic disorder that leads to kidney failure. Our aim was to undertake a meta-analysis of randomized trials of interventions that have been hypothesized to reduce the progression of total kidney volume (TKV) and renal function in ADPKD.
METHODS
Relevant trials were identified, and outcomes were: change in TKV, total cyst volume (TCV), renal function and adverse events. Meta-analysis used random effects, with results expressed as mean difference and risk ratio both with 95% confidence intervals (CI).
RESULTS
Eleven trials (2262 patients) were included. Compared with placebo, Target of Rapamycin complex 1 (TORC1) inhibitors (5 trials, n = 619), showed no significant change in TKV (P = 0.21), TCV (P = 0.06) or eGFR (P = 0.22). Somatostatin analogues (3 trials, n = 157) reduced TKV by 9% (95% CI -10.33 to -7.58%) but did not alter eGFR. The vasopressin receptor antagonist (n = 1455) attenuated TKV increase to 3%/year (95% CI -3.48 to -2.52) and slowed kidney function decline over a 3-year period. A single trial (n = 41) of eicosapentaenoic acid did not alter the progression of either TKV (P = 0.9) or renal dysfunction (P = 0.78). Adverse events were significant for interventions in all trials compared with placebo.
CONCLUSION
These data suggest that somatostatin analogues and vasopressin receptor antagonists attenuate TKV increase. The neutral effects of TORC1 inhibitors on TKV could be true, or due to heterogeneity in study population, drug efficacy and follow-up duration. In the future, further well-designed and powered trials of longer duration using new biomarkers or therapeutic agents with better tolerance are required.
Topics: Disease Progression; Humans; Kidney; Molecular Targeted Therapy; Polycystic Kidney, Autosomal Dominant; Randomized Controlled Trials as Topic; Renal Insufficiency; Time Factors; Treatment Outcome; Urological Agents
PubMed: 24460701
DOI: 10.1111/nep.12211 -
Frontiers in Neuroscience 2018Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are...
Clozapine is the antipsychotic of choice for treatment-resistant schizophrenia and has minimal risk for extrapyramidal symptoms. Therapeutic benefits, however, are accompanied by a myriad of cardiometabolic side-effects. The specific reasons for clozapine's high propensity to cause adverse cardiometabolic events remain unknown, but it is believed that autonomic dysfunction may play a role in many of these. This systematic review summarizes the literature on autonomic dysfunction and related cardiovascular side effects associated with clozapine treatment. A search of the EMBASE, MEDLINE, and EBM Cochrane databases was conducted using the search terms antipsychotic agents, antipsychotic drug, antipsychotic, schizophrenia, schizophren, psychos, psychotic, mental ill, mental disorder, neuroleptic, cardiovascular, cardiovascular diseases, clozapine, clozaril, autonomic, sympathetic, catecholamine, norepinephrine, noradrenaline, epinephrine, adrenaline. The search yielded 37 studies that were reviewed, of which only 16 studies have used interventions to manage cardiovascular side effects. Side effects reported in the studies include myocarditis, orthostatic hypotension and tachycardia. These were attributed to sympathetic hyperactivity, decreased vagal contribution, blockade of cholinergic and adrenergic receptors, reduced heart rate variability and elevated catecholamines with clozapine use. Autonomic neuropathy was identified by monitoring blood pressure and heart rate changes in response to stimuli and by spectral analysis of heart rate variability. Metoprolol, lorazepam, atenolol, propranolol, amlodipine, vasopressin and norepinephrine infusion were used to treat tachycardia and fluctuations in blood pressure, yet results were limited to case reports. The results indicate there is a lack of clinical studies investigating autonomic dysfunction and a limited use of interventions to manage cardiovascular side effects associated with clozapine. As there is often no alternative treatment for refractory schizophrenia, the current review highlights the need for better designed studies, use of autonomic tests for prevention of cardiovascular disease and development of novel interventions for clozapine-induced side effects.
PubMed: 29670504
DOI: 10.3389/fnins.2018.00203 -
Acta Neuropsychiatrica Jan 2020Gene-environment (GxE) interactions may comprise an important part of the aetiology of depression, and childhood maltreatment (CM), a significant stressor, has...
OBJECTIVE
Gene-environment (GxE) interactions may comprise an important part of the aetiology of depression, and childhood maltreatment (CM), a significant stressor, has consistently been linked to depression. Hence, in this systematic review, we aimed to investigate the interaction between hypothalamus-pituitary-adrenal axis (HPA-axis) genes and CM in depression.
METHODS
We conducted a literature search using the Pubmed, Embase, and PsychINFO databases in adherence with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. We included studies investigating GxE interactions between HPA-axis genes [Angiotensin Converting Enzyme (ACE), Arginine Vasopressin (AVP), Corticotrophin Releasing Hormone (CRH), Corticotrophin Releasing Hormone Receptor 1 (CRHR1), Corticotrophin Releasing Hormone Receptor 2 (CRHR2), FK506 binding protein (FKBP5), Nuclear Receptor subfamily 3 group C member 1 (NR3C1), Nuclear Receptor subfamily 3 group C member 2 (NR3C2)] and CM in depression.
RESULTS
The literature search identified 159 potentially relevant studies. Following screening, 138 of these were excluded. Thus, 21 studies, investigating a total of 51 single nucleotide polymorphisms, were included in the final study. The most prevalent genes in the current study were CRHR1 and FKBP5. Significant GxE interactions were reported in seven of eight studies for CRHR1:rs110402 and CM, and in five of eight studies for FKBP5:rs1360780 and CM. In summary, our results suggest possible GxE interactions between CRHR1, FKBP5, NR3C1, and NR3C2 and CM, respectively. For the remaining genes, no relevant literature emerged.
CONCLUSIONS
We find that genetic variation in four HPA-axis genes may influence the effects of CM in depression.
PubMed: 31902387
DOI: 10.1017/neu.2020.1