Association Study of the SLC1A2 (rs4354668), SLC6A9 (rs2486001) and SLC6A5 (rs2000959) Polymorphisms in Major Depressive Disorder

Abstract Background: In recent years, a growing body of evidence highlights a causal link between glutamate and depression. The membrane excitatory amino acid transporter 2 (EAAT2), encoded by SLC1A2 is responsible for the uptake and redistribution of most of the synaptic glutamate. Glycine, an inhibitory neurotransmitter, acts as an obligatory co-agonist of N-methyl-D-aspartate (NMDA) receptors and modulates excitatory neurotransmission. The clearance of synaptic glycine is performed by glycine transporters encoded by SLC6A9 and SLC6A5. Higher synaptic glycine and glutamate levels could enhance the activation of NMDA receptors, therefore counteract the hypofunction of glutamate neurotransmission described in major depressive disorder (MDD). The aim of the study was to assess whether polymorphisms of SCL1A2, SCL6A5 and SCL6A9 play a role in the development of MDD and its clinical picture in the Polish population. Methods: The study group consisted of 161 unrelated Caucasian patients with MDD, and 462 healthy controls. Polymorphisms of SLC1A2, SLC6A5 and SLC6A9 were genotyped with PCR-RLFP and TaqMan assays. The relationship between the studied single nucleotide polymorphisms (SNPs) was assessed based on the comparison of genotype and allele distribution in the study and the control group. The research also evaluated the relationships between the studied polymorphisms and clinical variables such as age of disease onset, number of episodes, duration of depression or severity of symptoms.Results: We found a statistically significant association between SLC1A2 rs4354668 polymorphism and MDD development (the frequency of rs4354668 CC genotype and allele C was 2-fold higher in patients than in the control). Such associations were not detected for SLC6A5 and SLC6A9 polymorphisms. No statistically significant impact of the studied SNPs on clinical variables of MDD was also observed. Conclusions: The results of the current study indicate an association of rs4354668 polymorphism in SCL1A2 with depression development in Polish population. Further studies with larger samples should be performed in the future to clarify the current findings.

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Associations of Tumor Necrosis Factor–α G-308A (rs1800629) Gene Polymorphisms with Major Depressive Disorder

NeuroQuantology ◽

10.14704/nq.2021.19.7.nq21095 ◽

2021 ◽

Vol 19 (7) ◽

pp. 133-136

Author(s):

Aamal Muhsen Kadhum ◽

Bayader M. Abd Al–Kadim ◽

Thanaa Chasib Kareem ◽

Ali Ahmed Nayyef ◽

Mona N. Al-Terehi

Keyword(s):

Major Depressive Disorder ◽

Tumor Necrosis Factor ◽

Depressive Disorder ◽

Gene Polymorphisms ◽

Tumor Necrosis ◽

Control Group ◽

Major Depressive ◽

Allele Distribution ◽

Tnf Α ◽

Necrosis Factor

Pro-inflammatory cytokine polymorphisms like Tumor Necrosis Factor- (TNF), has been found associated to severe depressive disorder (MDD). The Pro-inflammatory cytokines tumor necrosis factor (TNF-α) G-308A (rs1800629) have been discovered to have an important role in the pathophysiology of depressive disorders and the mechanism of antidepressant treatment. The present study aims to study TNF-α gene polymorphisms in Major depressive disorder using allele specific PCR. The results show that family history are non- significant different between patients and control group (0.6346) and also there was non- significant different in BMI (0.3417), The genotyping data show tow alleles and three genotyping (AG, GG, AA) the statically analysis show non-significant differences between patients and controls groups (0.095, 0.800) for GG, AA and GA respectively with more frequent of GA in patients than control group, the G allele was less frequent in patient than control while A allele was more frequent in patients than control group in significant differences (0.0001). It can be concluded that TNF genotyping didn’t impact in the Major depressive disorder but the allele distribution may have potential role in MDD patients.

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Preventive Effect of Liothyronine on Electroconvulsive Therapy-Induced Memory Deficit in Patients with Major Depressive Disorder: A Double-Blind Controlled Clinical Trial

BioMed Research International ◽

10.1155/2015/503918 ◽

2015 ◽

Vol 2015 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Arash Mohagheghi ◽

Asghar Arfaie ◽

Shahrokh Amiri ◽

Masoud Nouri ◽

Salman Abdi ◽

...

Keyword(s):

Clinical Trial ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Electroconvulsive Therapy ◽

Visual Memory ◽

Memory Deficit ◽

Control Group ◽

Major Depressive ◽

Double Blind ◽

The Impact

Introduction and Objective. Despite the effectiveness of electroconvulsive therapy (ECT) in treating major depressive disorder (MDD), its cognitive side effects make it less popular. This study investigated the impact of liothyronine on ECT-induced memory deficit in patients with MDD.Methodology. This is a double-blind clinical trial, in which 60 patients with MDD who were referred for ECT were selected. The diagnosis was based on the criteria of DSM-IV-TR. Patients were divided randomly into two groups to receive either liothyronine (50 mcg every morning) or placebo. After the assessment with Wechsler Memory Scale-Revised (WMS-R) before first session of ECT, posttests were repeated again, two months after the completion of ECT.Findings. By controlling the pretest scores, the mean scores of the experimental group were higher than the control group in delayed recall, verbal memory, visual memory, general memory, and attention/concentration scales (P<0.05).Conclusion. Liothyronine may prevent ECT-induced memory impairment in patients with MDD. This study has been registered in IRCT underIRCT201401122660N2.

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Optical Coherence Tomography and Pattern Electroretinography Changes in Egyptian Patients with Major Depressive Disorder

QJM ◽

10.1093/qjmed/hcab109.023 ◽

2021 ◽

Vol 114 (Supplement_1) ◽

Author(s):

Mostafa S ElShaarawi ◽

Ayman A Gaafar ◽

Hisham S. Saad Eldin ◽

Randa H Ali

Keyword(s):

Optical Coherence Tomography ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Control Group ◽

Ophthalmological Examination ◽

Optical Coherence ◽

Fiber Layer ◽

Major Depressive ◽

Cross Sectional ◽

Pattern Electroretinography

Abstract Background Major depressive disorder (MDD) is a common psychiatric disorder that affects nearly 11.1-14.6 % of the population in their lifetime. Pathophysiology and brain imaging findings show that degenerative and inflammatory processes may play a role. Meta-analysis of voxel-based morphometry studies in MDD demonstrated significant gray matter loss. From anatomical and embryological perspectives, the retina can be considered a unique extension of the brain and is able to reflect axonal histopathology. Being unmyelinated, it can provide insight into the pathophysiological processes of diseases with a neurodegenerative element. Aim to compare retinal optical coherence tomography (OCT) parameters in a group of MDD patients with a healthy control group and to correlate OCT parameters with pattern electroretinography (PERG) parameters. Method a controlled cross sectional study was conducted on 30 MDD patients and 28 age and sex matched controls. Both groups had a full ophthalmological examination, OCT imaging and 7 patients and 11 controls have PERG recorded. Results Thinning of the superior retinal nerve fiber layer, thinning of most of the ganglion cell inner plexiform (GCIP) layer, thinning of most of the macular thickness and thinning of macular volume in both eyes were detected. There was a statistically significant positive correlation between the left GCIP layer and the amplitude of the N95 wave. Also a statistically significant negative correlation existed between MDD duration in years with the left eye's average volume of the outer ring of the macula. Conclusion Significant retinal changes were detected by OCT in MDD patients supporting the theory of neurodegeneration as a pathophysiology of MDD.

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THE PATTERN OF IRRATIONAL BELIEFS ASSOCIATED WITH MAJOR DEPRESSIVE DISORDER

Social Behavior and Personality An International Journal ◽

10.2224/sbp.1992.20.3.199 ◽

1992 ◽

Vol 20 (3) ◽

pp. 199-212 ◽

Cited By ~ 6

Author(s):

Lyne Prud'homme ◽

Pierre Barron

Keyword(s):

Major Depressive Disorder ◽

Discriminant Analysis ◽

Depressive Disorder ◽

Symptom Severity ◽

Irrational Beliefs ◽

Irrational Belief ◽

Normal Control Group ◽

Control Group ◽

Major Depressive ◽

Normal Controls

In light of Rational-Emotive Theory, this study was undertaken to determine the pattern of irrational beliefs underlying Major Depressive Disorder (MDD). A total of 126 subjects (50 males, 76 females) volunteered to participate. Patients clinically diagnosed with MDD (unipolar type) and a control group of non-depressed patients were solicited from the inpatient and outpatient facilities of several Ottawa and Montreal hospitals; the normal control group comprised students and civil servants. The subjects completed questionnaires to measure irrational belief endorsement (IBT, RBI) and symptom severity (STAI, BDI) and to verify the depression diganosis (IDD). Multivariate statistics were used to determine the pattern of beliefs which best discriminates between the MDD group, the psychiatric control group, and the normal controls. Discriminant analysis of the IBT revealed a pattern of four irrational beliefs generally known as demand for approval, frustration reactivity, anxious overconcern, and helplessness over past. The implications of such findings for RET theory are discussed.

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The effects of intramuscular administration of scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled trial

Therapeutic Advances in Psychopharmacology ◽

10.1177/2045125320938556 ◽

2020 ◽

Vol 10 ◽

pp. 204512532093855

Author(s):

Jingjing Zhou ◽

Jian Yang ◽

Xuequan Zhu ◽

Tarek Zghoul ◽

Lei Feng ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Dose Group ◽

Response Rate ◽

Secondary Outcome ◽

Control Group ◽

Placebo Control ◽

High Dose ◽

Major Depressive ◽

Double Blind

Introduction: Major depressive disorder (MDD) is a common affective disorder. Currently established pharmacotherapies lack rapid clinical response, thereby limiting their ability to bring instant relief to patients. A series of clinical trials has demonstrated the antidepressant effects of scopolamine, yet few have studied the effects of add-on scopolamine to currently available antidepressants. It is not known whether conventional antidepressant treatment with a 3-day scopolamine injection could speed up oral antidepressant efficacy. The main focus of this study is to detect the capacity of the rapid-onset efficacy of such a treatment option. Methods and analysis: This study consisted of a single-centre, double-blind, three-arm randomized trial with a 4-week follow-up period. Sixty-six participants meeting entry criteria were randomly allocated to three treatment groups: a high-dose group, a low-dose group and a placebo control group. Psychiatric rating scales were administered at baseline and seven viewing points following the administration of intramuscular injections. The primary outcome measure was length of time from randomization (baseline) to early improvement. Results: Both primary and secondary outcome measures consistently showed no differences among the three groups. The cumulative response rate and the remission rate were 72.7% (48/66) and 47.0% (31/66). Intramuscular scopolamine treatment was relatively well tolerated. Two subjects with high-dose injections dropped out because of a drug-related side effect. Conclusion: Contrary to our prediction, we found that, compared to placebo (0.9% saline i.m.), scopolamine was not associated with a significantly faster antidepressant response rate. Trial registration: ClinicalTrials.gov, NCT03131050. Registered on 18 April 2017.

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Employment and earnings trajectories before and after sickness absence due to major depressive disorder: a nationwide case–control study

Occupational and Environmental Medicine ◽

10.1136/oemed-2020-106660 ◽

2020 ◽

pp. oemed-2020-106660

Author(s):

Christian Hakulinen ◽

Petri Böckerman ◽

Laura Pulkki-Råback ◽

Marianna Virtanen ◽

Marko Elovainio

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Sickness Absence ◽

Lower Probability ◽

Control Group ◽

Major Depressive ◽

Earnings Losses ◽

Before And After ◽

History Of ◽

And Gender

ObjectivesTo examine employment and earnings trajectories before and after the first sickness absence period due to major depressive disorder (MDD).MethodsAll individuals (n=158 813) in Finland who had a first sickness absence period (lasting longer than 9 days) due to MDD between 2005 and 2015 were matched with one randomly selected individual of the same age and gender with no history of MDD. Employment status and earnings were measured using register-based data annually from 2005 to 2015. Generalised estimating equations were used to examine the trajectories of employment and earnings before and after MDD diagnosis in men and women separately.ResultsSickness absence due to MDD was associated with increased probability of non-employment during and after the year of the first sickness absence period. In men, but not in women, the probability of being employed was lower 5 years before the sickness absence period due to MDD. When compared with the individuals in the control group, men had around 34% and women 15% lower earnings 1 year, and 40% and 23%, respectively, 5 years, after the first sickness absence period due to MDD. More severe MDD and longer duration of sickness absence period were associated with lower probability of being employed.ConclusionsSickness absence due to MDD was associated with considerable reduction in employment and earnings losses. For men and individuals with more severe MDD, this reduction was before the first sickness period. This supports a reciprocal association between employment and earnings with MDD.

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Deficient testosterone levels in men above 45 years with major depressive disorder - an age-matched case control study

South African Journal of Psychiatry ◽

10.4102/sajpsychiatry.v13i3.21 ◽

2007 ◽

Vol 13 (3) ◽

pp. 5

Author(s):

A M Dikobe ◽

C W Van Staden ◽

S Reif ◽

M Bornman

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Treatment Options ◽

Serum Testosterone ◽

Control Group ◽

Major Depressive ◽

Age Related ◽

Appropriate Treatment ◽

Matched Case

Background. Symptoms of partial androgen deficiency in ageing men (PADAM) overlap considerably with those of major depressive disorder. The relationship between these conditions is complicated by the usual age-related decline in serum testosterone concentrations.Objectives. To test the hypothesis that depressed men above 45 years of age have lower serum testosterone concentrations than age-matched controls.Method. Serum testosterone fractions of 20 men above the age of 45 years suffering from a major depressive disorder were compared with those of 20 healthy men. An age-matched controlled design was used to account for the usual age-related decline in serum testosterone concentrations.Results. Testosterone concentrations of men suffering from a major depressive disorder were statistically significantly lower than those of an age-matched control group without depression. Conclusion. The role of testosterone deficiency in depressed men needs to be examined further in order for appropriate treatment options to be developed.

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Escitalopram in Treatment of Sleep Disturbances in Major Depressive Disorder

European Psychiatry ◽

10.1016/s0924-9338(09)70865-x ◽

2009 ◽

Vol 24 (S1) ◽

pp. 1-1

Author(s):

N. Zivkovic ◽

G. Djokic ◽

D. Pavicevic ◽

V. Ilic

Keyword(s):

Major Depressive Disorder ◽

Adverse Effects ◽

Depressive Disorder ◽

Sleep Disturbances ◽

Rating Scale ◽

Statistical Significance ◽

Control Group ◽

Major Depressive ◽

High Statistical Significance ◽

Experimental Group

Major depressive disorder (MDD) is common and severe affective disorder with sleep disturbances and non-bizarre delusions which are organized in permanent and unshakeable delusional system. Neurobiological basis of MDD is still completely unknown, but significant role has serotoninergic and noradrenergic neuronal systems. Escitalopram is highly potent and highly selective serotonin re-uptake inhibitor.Purpose of this study was to estimate efficacy of the escitalopram in treatment of sleep disturbances in MDD.Methods:This prospective clinical study included 95 patients diagnosed by ICD-10 criteria for MDD, who are randomly divided into control (30 patients) and experimental group (65 patients). Patients were observed for 6 months in hospital and outpatients conditions, according to specially designed protocol, which included Hamilton Depression Rating Scale (HAMD) and Leeds Sleeping Evaluation Questionnaire (LSEQ). Control group was treated with maprotiline (75-150 mg/24h) and experimental group with escitalopram (10-20 mg/24h).Results:Escitalopram therapy influenced on HAMD score with high statistical significance vs. maprotiline, p=0.000. Escitalopram therapy improves LSEQ score after 6 months in comparison to maprotiline therapy with high statistical significance p=0.000. Percentage of adverse effects is significantly lower in escitalopram (10.76%) than in maprotiline (26.67%) group.Conclusion:Escitalopram has significantly better efficacy and lower adverse effects rate in treatment of depressive symptoms and sleep disturbances in MDD patients comparing to maprotiline.

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The Use of Art Therapy in Complex Treatment on the Quality of Remission in Patients with Melancholy in Major Depressive Disorder

European Psychiatry ◽

10.1016/j.eurpsy.2017.01.1473 ◽

2017 ◽

Vol 41 (S1) ◽

pp. s777-s777 ◽

Cited By ~ 1

Author(s):

H. Kozhyna ◽

V. Korostiy ◽

S. Hmain ◽

V. Mykhaylov

Keyword(s):

Quality Of Life ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Art Therapy ◽

Depressive Disorders ◽

Combined Treatment ◽

Control Group ◽

Complex Treatment ◽

Major Depressive

IntroductionAccording to studies done in recent years regarding the treatment of patients with melancholy in major depressive disorder, a shift of interest from studies evaluating the effectiveness of therapy to the study of remission is seen. Despite significant progress in the development of pharmacotherapy of depressive disorders, difficulty in achieving rapid reduction in depressive symptoms and stable remission in patients with melancholic depression necessitated the search for new approaches to the treatment of this pathology.AimsEvaluating the effectiveness of art therapy in treatment in patients with melancholy in major depressive disorder on the quality of remission.MethodsThe study involved 135 patients – 60 male and 75 female patients aged from 18 to 30 years old. The main group of patients apart the combined treatment also participated in group art therapy with the use of drawing techniques, while the control group – statutory standard therapy.ResultsThe results of the use of art therapy in complex treatment in patients with major depressive disorder is detected primarily in reducing of the level of anxiety at the early stages of treatment (60% of patients have noticed decreasing of melancholic state), as well as improving the quality of life in remission period.ConclusionThese results support the use of art therapy in treatment in patients with melancholy in major depressive disorder during period of active treatment, and after achieving clinical remission contributes to achieving and maintaining high-quality and stable remission with full restoration of quality of life and social functioning.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Neurocognitive profiles in elderly patients with frontotemporal degeneration or major depressive disorder

Journal of the International Neuropsychological Society ◽

10.1017/s1355617704105067 ◽

2004 ◽

Vol 10 (5) ◽

pp. 753-771 ◽

Cited By ~ 32

Author(s):

VIRGINIA ELDERKIN-THOMPSON ◽

KYLE B. BOONE ◽

SUN HWANG ◽

ANAND KUMAR

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Early Stage ◽

Effect Sizes ◽

Control Group ◽

Neurocognitive Deficits ◽

Major Depressive ◽

Depressed Patients ◽

Community Volunteers ◽

Neurocognitive Profiles

Major depressive disorder (MDD) and frontotemporal dementia (FTD) are both disorders in elderly populations that involve the prefrontal cortex and appear to have similar neurocognitive deficits. This review examined whether there are testable deficits in cognition that are consistent across individuals within the same neuropathological condition that could be used to facilitate early diagnoses. Medline and PsychInfo databases were searched for cognitive studies of depressed and FTD patients that used a matched control group and reported findings with means and standard deviations (N= 312). Effect sizes for FTD patients with mild and moderately advanced disease were compared to effect sizes within subgroups of depressed patients, such as inpatients, outpatients and community volunteers. Moderately advanced FTD patients were more impaired than depressed patients over all domains, particularly in language ability, although depressed inpatients appeared similar to FTD patients in some domains. Effect sizes for FTD patients who were in the mild, or early, stage of the disease (MMSE= 28) were similar to those of depressed outpatients but slightly worse than those of community volunteers in all domains except semantic memory and executive ability. In the latter two domains, even mild FTD patients had notably large deficits. All FTD patients showed more severe deficits in some domains relative to other domains. In contrast, depressed patients tended to vary by clinical presentation or disease severity, but the magnitude of impairment for each subgroup remained relatively consistent across domains and they did not have the severe focal deficits in one or two domains demonstrated by FTD patients. (JINS, 2004,10, 753–771.)

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