Untreated Major Depressive Disorder Patients Research Articles

Gender-related alterations of serum trace elements and neurometabolism in the anterior cingulate cortex of patients with major depressive disorder

BackgroundIt is widely known that sex differences have a significant impact on patients with major depressive disorder (MDD). This study aims to evaluate the sex-related connection between serum trace elements and changes in neurometabolism in the anterior cingulate cortex (ACC) of MDD patients. Methods109 untreated MDD patients and 59 healthy controls underwent proton magnetic resonance spectroscopy (1H-MRS) under resting conditions. We measured metabolic ratios in the ACC from both sides. Additionally, venous blood samples were taken from all participants to detect calcium (Ca), phosphorus, magnesium (Mg), copper (Cu), ceruloplasmin (CER), zinc (Zn), and iron (Fe) levels. We performed association and interaction analyses to explore the connections between the disease and gender. ResultsIn individuals with MDD, the Cu/Zn ratio increased, while the levels of Mg, CER, Zn and Fe decreased. Male MDD patients had lower Cu levels, while female patients had an increased Cu/Zn ratio. We observed significant gender differences in Cu, CER and the Cu/Zn ratio in MDD. Male patients showed a reduced N-acetyl aspartate (NAA)/phosphocreatine + creatine (PCr + Cr) ratio in the left ACC. The NAA/PCr + Cr ratio decreased in the right ACC in patients with MDD. In the left ACC of male MDD patients, the Cu/Zn ratio was inversely related to the NAA/PCr + Cr ratio, and Fe levels were negatively associated with the GPC + PC/PCr + Cr ratio. ConclusionsOur findings highlight gender-specific changes in Cu homeostasis among male MDD patients. The Cu/Zn ratio and Fe levels in male MDD patients were significantly linked to neurometabolic alterations in the ACC.

MicroRNA-124 influenced depressive symptoms via large-scale brain connectivity in major depressive disorder patients

This study aimed to investigate the neurobiological mechanisms by which microRNA 124 (miR-124) is involved in major depressive disorder (MDD). We enrolled 53 untreated MDD patients and 38 healthy control (HC) subjects who completed behavior assessments and resting-state functional MRI (rs-fMRI) scans. MiR-124 expression levels were detected in the peripheral blood of all participants. We determined that miR-124 levels could influence depressive symptoms via disrupted large-scale intrinsic intra- and internetwork connectivity, including the default mode network (DMN)-DMN, dorsal attention network (DAN)-salience network (SN), and DAN-cingulo-opercular network (CON). This study deepens our understanding of how miR-124 dysregulation contributes to depression.

Accelerated epigenetic aging and decreased natural killer cells based on DNA methylation in patients with untreated major depressive disorder

Major depressive disorder (MDD) is known to cause significant disability. Genome-wide DNA methylation (DNAm) profiles can be used to estimate biological aging and as epigenetic clocks. However, information on epigenetic clocks reported in MDD patients is inconsistent. Since antidepressants are likely confounders, we evaluated biological aging using various DNAm-based predictors in patients with MDD who had never received depression medication. A publicly available dataset consisting of whole blood samples from untreated MDD patients (n = 40) and controls (n = 40) was used. We analyzed five epigenetic clocks (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge), DNAm-based telomere length (DNAmTL), and DNAm-based age-related plasma proteins (GrimAge components), as well as DNAm-based white blood cell composition. The results indicate that patients with untreated MDD were significantly associated with epigenetic aging acceleration in HannumAge and GrimAge. Furthermore, a decrease in natural killer cells, based on DNAm, was observed in patients with untreated MDD.

Sexual health and serotonin 4 receptor brain binding in unmedicated patients with depression—a NeuroPharm study

Sexual dysfunction is prominent in Major Depressive Disorder (MDD) and affects women with depression more than men. Patients with MDD relative to healthy controls have lower brain levels of the serotonin 4 receptor (5-HT4R), which is expressed with high density in the striatum, i.e. a key hub of the reward system. Reduced sexual desire is putatively related to disturbed reward processing and may index anhedonia in MDD. Here, we aim to illuminate plausible underlying neurobiology of sexual dysfunction in unmedicated patients with MDD. We map associations between 5-HT4R binding, as imaged with [11C]SB207145 PET, in the striatum, and self-reported sexual function. We also evaluate if pre-treatment sexual desire score predicts 8-week treatment outcome in women. From the NeuroPharm study, we include 85 untreated MDD patients (71% women) who underwent eight weeks of antidepressant drug treatment. In the mixed sex group, we find no difference in 5-HT4R binding between patients with sexual dysfunction vs normal sexual function. However, in women we find lower 5-HT4R binding in the sexual dysfunctional group compared to women with normal sexual function (β = −0.36, 95%CI[−0.62:−0.09], p = 0.009) as well as a positive association between sexual desire and 5-HT4R binding (β = 0.07, 95%CI [0.02:0.13], p = 0.012). Sexual desire at baseline do not predict treatment outcome (ROC curve AUC = 52%[36%:67%]) in women. Taken together, we find evidence for a positive association between sexual desire and striatal 5-HT4R availability in women with depression. Interestingly, this raises the question if direct 5-HT4R agonism can target reduced sexual desire or anhedonia in MDD.

Prevalence of suicide attempts and correlates among first-episode and untreated major depressive disorder patients with comorbid dyslipidemia of different ages of onset in a Chinese Han population: a large cross-sectional study

BackgroundPatients with dyslipidemia are at increased risk for suicide, especially those with major depressive disorder (MDD). Few studies have investigated the independent effects of suicide attempts on comorbid dyslipidemia in patients with MDD. Moreover, there are no comparisons of differences in factors associated with suicide attempts among patients with MDD with dyslipidemia at different ages of onset. The aim of this study was to investigate the prevalence of suicide attempts and associated variables in first episode and untreated patients with MDD with comorbid dyslipidemia at different ages of onset.MethodsWe recruited 1718 patients with first-episode untreated MDD in this study. Demographical and clinical data were collected, and lipid profiles, thyroid function, and blood glucose levels were measured. The Hamilton Depression Scale 17 (HAMD-17), Hamilton Anxiety Scale (HAMA), Clinical Global Impression Severity Scale (CGI), and Positive and Negative Syndrome Scale (PANSS) positive subscale were assessed for depression, anxiety and illness severity, as well as psychotic symptoms, respectively.ResultsThe percentage of patients with MDD with comorbid dyslipidemia was 61% (1048/1718). Among patients with MDD with comorbid dyslipidemia, the incidence of suicide attempts was 22.2% (170/765) for early adulthood onset and 26.5% (75/283) for mid-adulthood onset. Independent factors associated with suicide attempts in early adulthood onset patients with MDD with dyslipidemia were as follows: HAMA score (B = 0.328, P < 0.0001, OR = 1.388), Suspicion /persecution (B = -0.554, P = 0.006, OR = 0.575), CGI (B = 0.878, P < 0.0001, OR = 2.406), systolic blood pressure (B = 0.048, P = 0.004, OR = 1.049), hallucinatory behavior (B = 0.334, P = 0.025, OR = 1.397), and TPOAb (B = 0.003, p < 0.0001, OR = 1.003). Independent factors associated with suicide attempts in mid-adulthood onset patients with MDD with comorbid dyslipidemia were as follows: HAMA score (B = 0.182, P < 0.0001, OR = 1.200), CGI (B = 1.022, P < 0.0001, OR = 2.778), and TPOAb (B = 0.002, P = 0.009, OR = 1.002).ConclusionOur findings suggest an elevated risk of suicide attempts in patients with MDD with comorbid dyslipidemia. The incidence of suicide attempts was similar in the early- and mid-adulthood onset subgroups among patients with MDD with dyslipidemia, but the factors associated with suicide attempts were different in these two subgroups.

Multiple Pre-Treatment miRNAs Levels in Untreated Major Depressive Disorder Patients Predict Early Response to Antidepressants and Interact with Key Pathways.

Major depressive disorder (MDD) is a life-impairing disorder, and early successful treatment is important for a favorable prognosis. However, early response to antidepressants differs widely among individuals, and is difficult to predict pre-treatment. As miRNAs have been reported to play important roles in depression, identification of miRNAs associated with antidepressant treatment responses and their interacting genes and pathways will be beneficial in understanding the predictors and molecular mechanisms of depression treatment. This randomized control trial examined miRNAs correlated with the early therapeutic effect of selective serotonin reuptake inhibitors (SSRIs; paroxetine or sertraline) and mirtazapine monotherapy. Before medication, we comprehensively analyzed the miRNA expression of 92 depressed participants and identified genes and pathways interacting with miRNAs. A total of 228 miRNAs were significantly correlated with depressive symptoms improvements after 2 weeks of SSRIs treatment, with miR-483.5p showing the most robust correlation. These miRNAs are involved in 21 pathways, including TGF-β, glutamatergic synapse, long-term depression, and the mitogen-activated protein kinase (MAPK) signaling pathways. Using these miRNAs enabled us to predict SSRI response at week 2 with a 57% difference. This study shows that pre-treatment levels of miRNAs could be used to predict early responses to antidepressant administration, a knowledge of genes, and an identification of genes and pathways associated with the antidepressant response.

MRNA Expression of SMPD1 Encoding Acid Sphingomyelinase Decreases upon Antidepressant Treatment.

Major depressive disorder (MDD) is a severe psychiatric condition with key symptoms of low mood and lack of motivation, joy, and pleasure. Recently, the acid sphingomyelinase (ASM)/ceramide system has been implicated in the pathogenesis of MDD. ASM is a lysosomal glycoprotein that catalyzes the hydrolysis of sphingomyelin, an abundant component of membranes, into the bioactive sphingolipid ceramide, which impacts signaling pathways. ASM activity is inhibited by several common antidepressant drugs. Human and murine studies have confirmed that increased ASM activity and ceramide levels are correlated with MDD. To define a molecular marker for treatment monitoring, we investigated the mRNA expression of SMPD1, which encodes ASM, in primary cell culture models, a mouse study, and a human study with untreated MDD patients before and after antidepressive treatment. Our cell culture study showed that a common antidepressant inhibited ASM activity at the enzymatic level and also at the transcriptional level. In a genetically modified mouse line with depressive-like behavior, Smpd1 mRNA expression in dorsal hippocampal tissue was significantly decreased after treatment with a common antidepressant. The large human study showed that SMPD1 mRNA expression in untreated MDD patients decreased significantly after antidepressive treatment. This translational study shows that SMPD1 mRNA expression could serve as a molecular marker for treatment and adherence monitoring of MDD.

Guanine-Based Purines as an Innovative Target to Treat Major Depressive Disorder.

Guanine-Based Purines as an Innovative Target to Treat Major Depressive Disorder.

The Association of Major Depressive Disorder with Activation of NLRP3 Inflammasome, Lipid Peroxidation, and Total Antioxidant Capacity.

Increasing number of studies indicates that chronic inflammation and oxidative stress play an essential role in pathophysiology and some symptoms of major depressive disorder (MDD). In the present study, the inflammasome activity and oxidative stress status in untreated and antidepressant-treated MDD patients were compared to the healthy group. Blood samples were taken from 20 MDD patients receiving treatment, 20 first-episode MDD patients not receiving treatment, and 20 healthy controls. The expression level of NLRP3 and caspase-1 was measured by real-time PCR and the serum TAC and MDA were examined in the patients and the control groups. The results showed that the mRNA level of NLRP3 and caspase-1 genes was significantly elevated in MDD groups compared with that in the healthy volunteers (P < 0.005). The expression level of NLRP3 and caspase-1 has slightly decreased in the treated group compared with that in the untreated one, but it was not a meaningful decrease. Moreover, the serum MDA was significantly higher and TAC statistically was lower in untreated MDD patients compared with those in the healthy control group (P = 0.001, P = 0.001). It can be concluded that NLRP3 inflammasome is upregulated in MDD patients. Statistically significant reduction in the level of TAC along with increased lipid peroxidation was detectable in MDD patient's plasma. In contrast, there was no significant difference between the treated and non-treated groups in terms of oxidative stress (P = 0.6, P = 0.1). Our results suggested that inflammasome signaling pathway is a therapeutic potential for MDD.

Is it importance to take co-occurrence of obesity and cigarette smoking into account in brain imaging studies in major depressive disorder?

Objective: To date, a small number of studies have investigated cortical thickness, cortical surface area, and subcortical volume abnormalities in first-episode, untreated patients with Major Depressive Disorder (MDD). The findings of previous studies are not entirely consistent. Previous studies did not match first-episode, untreated patients with MDD to controls regarding body mass index (BMI) and smoking, which could contribute to the inconsistency of results. The aim of the current study was to examine whether morphological abnormalities are present in first-episode and untreated MDD patients in comparison with well-matched controls, particularly concerning BMI and smoking status. Method: Twenty first-episode, untreated patients with MDD were enrolled in the study along with 20 healthy controls (HC) matched for age, education, sex, BMI and smoking status. Thickness and area of the cortex and subcortical volumes were measured using surface-based morphometry implemented with Freesurfer (v5.3.0). Results: There were no significant differences in cortical thickness, surface area, and subcortical volumes between the first-episode, untreated patients with MDD and HC groups. Conclusion: This study provides evidence that cortical thickness, cortical surface area, and subcortical volumes might be normal in first-episode untreated patients with MDD in comparison with well-matched controls, particularly for BMI and smoking status.

Abnormal functional connectivity of the amygdala in first-episode and untreated adult major depressive disorder patients with different ages of onset.

Major depressive disorder (MDD) is a common mental disorder with high morbidity. As a part of the limbic system, the amygdala is important in the processing of emotional information. Structural and functional connectivity (FC) abnormalities in the amygdala have been observed in MDD patients. The present study was carried out to identify the features of amygdala FC in adult MDD patients with different ages of onset. Sixty-nine first-episode and untreated MDD patients and 81 healthy controls (CTLs) were included in this study and underwent 3D structural imaging and resting-state functional MRI scanning. The patients and CTLs were divided into two groups according to age of onset: young adult (<30 years old) and old adult (≥30 years old). Voxel-based morphometry methods were used to investigate volume differences in MDD patients with different ages of onset at the whole-brain level. Then, the resting-state FC of bilateral amygdala seeds to the whole brain of MDD patients and matched CTLs in these two different onset age groups were analysed. We found that the volume of the bilateral amygdala increased to a greater extent in young adult patients compared with old adult patients. We also observed a trend toward different amygdala FC by onset age in MDD patients. In young adult patients, the left amygdala showed more abnormal resting-state FC with other regions compared with matched controls. However, in old adult patients, compared with matched controls, the right amygdala showed more abnormal changes in the resting-state FC with other regions. MDD patients with different ages of onset showed different changes in the structure and FC of the amygdala. These results might help us to understand the high heterogeneity of MDD.

Emotional Experience and the Mood-Congruent Working Memory Effect in First-Onset and Untreated Depressive Disorder Patients

Using an improved Sternberg working memory paradigm and affective pictures of different valences, this study investigates the emotional experience capability of 22 first-onset and untreated major depressive disorder patients (MDD) compared with the matching 22 healthy control participants (HC) and whether there is a moodcongruent working memory effect. We employed a general linear model analysis of variance (ANOVA) with two-factor repeated measures analysis on the emotional experience capability (pupil diameter changes) and the working memory performance (accuracy). The results show that the pupil diameter changes of positive emotions are significantly greater in MDD than those in HC (p<0.001), and the pupil diameter changes of negative emotions are not significantly different between two groups (p=0.055), which suggest that MDD have a significantly decrease in the ability to experience pleasure (anhedonia). In addition, the results only present that the working memory performances of negative emotions are significantly greater in MDD than those of positive emotions (p<0.05), which indicates that there is a mood-congruent memory effect. Moreover, in MDD, a positive correlation is found between the pupil diameter changes and working memory performances of positive emotions, however there is no correlation between those of negative emotions. Taken together, these results suggest that MDD have a moodcongruent memory effect and anhedonia, and the mood-congruent memory effect may be due to the decreased memory performances of positive emotions (a decrease in the ability to experience pleasure), but not those of negative emotions increased. This study not only illustrates that the core symptoms of depressive patients may be a mood-congruent memory effect and anhedonia but also enriches the connotation of anhedonia as an endophenotype indicator.

Blood BDNF level is gender specific in severe depression.

Though the role of brain derived neurotrophic factor (BDNF) as a marker for major depressive disorder (MDD) and antidepressant efficacy has been widely studied, the role of BDNF in distinct groups of patients remains unclear. We evaluated the diagnostic value of BDNF as a marker of disease severity measured by HAM-D scores and antidepressants efficacy among MDD patients. Fifty-one patients who met DSM-IV criteria for MDD and were prescribed antidepressants and 38 controls participated in this study. BDNF in serum was measured at baseline, 1st, 2nd and 8th treatment weeks. Depression severity was evaluated using the Hamilton Rating Scale for Depression (HAM-D). BDNF polymorphism rs6265 (val66met) was genotyped. We found a positive correlation between blood BDNF levels and severity of depression only among untreated women with severe MDD (HAM-D>24). Serum BDNF levels were lower in untreated MDD patients compared to control group. Antidepressants increased serum BDNF levels and reduced between-group differences after two weeks of treatment. No correlations were observed between BDNF polymorphism, depression severity, duration of illness, age and BDNF serum levels. Further supporting the role of BDNF in the pathology and treatment of MDD, we suggest that it should not be used as a universal biomarker for diagnosis of MDD in the general population. However, it has diagnostic value for the assessment of disease progression and treatment efficacy in individual patients.

The role of nesfatin-1 in impaired appetite in patients with major depressive disorder

AimThe aim of the present study was to explore whether plasma nesfatin-1 levels are associated with impaired appetite in major depressive disorder (MDD). MethodsPatients were recruited from outpatients who consecutively sought treatment in the psychiatric outpatient clinic of the University Hospital since March 2012. All patients were diagnosed with major depressive disorder according to DSM-IV. The appetite of patients was assessed by specific questionnaire. We categorized patients into two groups according to their appetite. Study group consisted of 30 patients with increased appetite (MDD-IA), 28 patients with decreased appetite (MDD-DA) and 28 healthy controls. Plasma nesfatin-1 levels and body mass index (BMI) were measured. ResultsThere was no statistically significant difference in nesfatin-1 between groups. The mean serum nesfatin-1 level did not show any correlation with age, BMI, HAM-D scores and fasting blood glucose in patients groups. ConclusionOur findings suggest that fasting plasma nesfatin-1 levels are unchanged in untreated MDD patients and there is no evidence for nesfatin-1 playing a role in impaired appetite in patients with MDD.

Increase in nitric oxide levels and mitochondrial membrane potential in platelets of untreated patients with major depression

Alterations in platelet activity have been associated with the onset of major depressive disorder (MDD) and with ischemic cardiovascular events through mechanisms that remain unknown. The present study evaluated nitric oxide (NO) levels, mitochondrial membrane potential (PMMP), and P-selectin expression in platelets from 30 untreated MDD patients and 30 matched controls by flow cytometry. In addition, tryptophan and serotonin concentrations were measured in the whole blood by high performance liquid chromatography. Patients were assessed with the Mini International Neuropsychiatric Interview and the Hamilton Depression Rating Scale. The patients had not had antidepressant treatment or any other pharmacological interventions for at least 1 year. MDD patients significantly differed from controls in levels of major fluorescent platelets for NO, PMMP, and P-selectin compared with those observed in control subjects. Serotonin concentrations in MDD patients did not differ from those in controls These results demonstrate that untreated MDD patients show increased platelet activation, suggesting an alteration in the platelet function.

Val66Met polymorphism and serum brain-derived neurotrophic factor concentration in depressed patients.

Zhang X, Wang X, Sha W, Zhou H, Zhang Y. Val66Met polymorphism and serum brain-derived neurotrophic factor concentration in depressed patients.Objective: Accumulating evidence has suggested a pathophysiological role for brain-derived neurotrophic factor (BDNF) in major depressive disorder (MDD). The present study evaluated serum levels of BDNF and explored whether Val66Met BDNF gene polymorphism is correlated with changes in circulating BDNF levels in patients with MDD and control subjects.Methods: Subjects were 76 patients with MDD and 50 controls. Diagnosis of MDD was determined by the use of a structured clinical interview according to Diagnostic and Statistical Manual of Mental Disorder-IV (DSM-IV) criteria. The concentrations of BDNF were measured by using the enzyme-linked immunosorbent assay. The Val66Met BDNF gene polymorphism was examined by the polymerase chain reaction technique.Results: Serum BDNF was significantly lower in MDD patients than in normal control subjects (p &lt; 0.001). There were no significant differences either in allele or genotype in the Val66Met polymorphism between the MDD and control groups. Moreover, genotype did not significantly correlate with the BDNF serum levels in the MDD or control groups.Conclusions: Our study suggests that there is a decrease in serum BDNF levels in untreated MDD patients. However, serum BDNF levels were not associated with the Val66Met polymorphism.

Specific Serotonin Reuptake Inhibition in Major Depressive Disorder Adversely Affects Novel Markers of Cardiac Risk

There exists a growing body of evidence linking depression with cardiovascular events, although the mechanisms responsible remain unknown. We investigated the role of the autonomic nervous system and inflammation in the link between coronary heart disease and major depressive disorder (MDD), and examined the cardiac risk modification following pharmacological treatment of depression. We measured cardiac baroreflex function, heart rate variability, pulse pressure and high sensitivity C-reactive protein (hsCRP), all of which have an impact on cardiac risk, pre- and post-treatment in 25 patients with MDD, with no history of coronary heart disease, and in 15 healthy subjects. Treatment consisted of selective serotonin reuptake inhibitors for approximately 12 weeks. No significant differences were observed between untreated MDD patients and healthy subjects in blood pressure, heart rate, baroreflex sensitivity or heart rate variability. Pulse pressure and hsCRP, however, were significantly elevated in patients with MDD prior to treatment (p=0.023 and p=0.025, respectively). Moreover, while pharmacotherapy was effective in alleviating depression, surprisingly, each of cardiac baroreflex function, heart rate variability, pulse pressure and hsCRP was modified (p<0.05) in a manner likely to increase cardiac risk. In conclusion, this study demonstrated higher pulse pressure and hsCRP plasma levels in patients with MDD, which might contribute to increased cardiac risk. Following treatment vagal activity was reduced, as indicated by reductions in baroreflex sensitivity and heart rate variability, accompanied by increases in pulse pressure and plasma hsCRP levels. Mechanisms potentially responsible for generating cardiac risk in patients treated with selective serotonin reuptake inhibitors may need to be therapeutically targeted to reduce the incidence of coronary heart disease in this population.

Decreased plasma BDNF level in depressive patients

Background Recent reports have suggested a pathophysiological role for brain-derived neurotrophic factor (BDNF) in major depressive disorder (MDD). We evaluated plasma levels of BDNF in patients with MDD. Methods Plasma BDNF levels were measured in 77 MDD patients and 95 normal controls. The severity of psychiatric symptoms was measured with the Hamilton Depression Rating Scale and the Brief Psychiatric Rating Scale. Results Plasma BDNF levels were significantly lower in MDD patients than in normal control subjects ( p < 0.001). Plasma BDNF levels were significantly lower in MDD patients with recurrent episodes than in MDD patients with the first episode or normal controls ( p < 0.001). Plasma BDNF levels were significantly lower in non-psychotic MDD patients than in psychotic MDD patients or normal controls ( p < 0.001). Plasma BDNF in suicidal MDD patients were significantly lower than those in non-suicidal MDD patients ( p < 0.001). Limitations We measured only plasma levels of BDNF. However, the cellular sources of BDNF in human plasma are not yet clearly defined. Conclusions Our study suggests that there is a decrease in plasma BDNF levels in untreated MDD patients. However, relapsed or recurrent episodes, suicidal behavior, and psychotic features could also affect the plasma levels of BDNF. Further studies are required to understand the source and role of the circulating BDNF in depression.

Expression of cAMP Response Element-Binding Protein in Major Depression before and after Antidepressant Treatment

Antidepressants usually take weeks to exert significant therapeutic effects. This lag phase is suggested to be due to neural plasticity, which may be mediated by the coupling of receptors to their respective intracellular signal transduction pathways. Phosphorylated cAMP response element-binding protein (CREB), a downstream target of the cAMP signaling pathway, has been reported to be a molecular state marker for the response to antidepressant treatment in patients with major depressive disorder (MDD). In order to explore the role of CREB expression in MDD, we used quantitative reverse transcriptase-polymerase chain reaction to quantify CREB messenger RNA of the peripheral lymphocytes obtained from 21 MDD patients, before and after antidepressant treatment, and 21 normal controls. The results revealed no significant difference of CREB expression between untreated MDD patients and normal controls. However, after 8 weeks of antidepressant treatment, CREB expression was significantly decreased in MDD patients (p = 0.025). The CREB change is not associated with the types of antidepressants and therapeutic response.

Elevated platelet vesicular monoamine transporter density in untreated patients diagnosed with major depression

The intraneuronal uptake of monoamines into brain synaptic vesicles is mediated by the vesicular monoamine transporter (VMAT2). This transporter plays a major role in monoamine storage and quantal release. Recently we demonstrated a high degree of similarity between the pharmacodynamic characteristics of platelet and brain VMAT2. In the present study we measured the VMAT2 density, using [ 3H]dihydrotetrabenazine ([ 3H]TBZOH) as a ligand, in platelets of untreated patients diagnosed with major depressive disorder (MDD) ( n=10; three with recurrent depression and seven with first episode depression) compared to sex- and age-matched healthy control subjects ( n=23). A significant elevation in the VMAT2 density ( B max) was observed in the platelets of untreated MDD patients (+24%) compared to healthy control subjects. No significant change was found in the affinity constant ( K d). The increased platelet VMAT2 density may reflect depression-related enhancement of the capacity to accumulate monoamines in the vesicles in the presence of lower monoamine turnover.