Function In Major Depressive Disorder Patients Research Articles

Probiotic Lactobacillus plantarum 299v supplementation in patients with major depression in a double-blind, randomized, placebo-controlled trial: A metabolomics study

BackgroundUnderstanding the multifactorial nature of major depressive disorder (MDD) is crucial for tailoring treatments. However, the complex interplay of various factors underlying the development and progression of MDD poses significant challenges. Our previous study demonstrated improvements in cognitive functions in MDD patients undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) supplemented with Lactobacillus plantarum 299v (LP299v). MethodsTo elucidate the biochemical mechanisms underlying cognitive functions improvements, we explored underlying metabolic changes. We employed multi-platform metabolomics, including LC-QTOF-MS and CE-TOF-MS profiling, alongside chiral LC-QqQ-MS analysis for amino acids. ResultsSupplementation of SSRI treatment with LP299v intensified the reduction of long-chain acylcarnitines, potentially indicating improved mitochondrial function. LP299v supplementation reduced N-acyl taurines more than four times compared to the placebo, suggesting a substantial impact on restoring biochemical balance. The LP299v-supplemented group showed increased levels of oxidized glycerophosphocholine (oxPC). Additionally, LP299v supplementation led to higher levels of sphingomyelins, L-histidine, D-valine, and p-cresol. LimitationsThis exploratory study suggests potential metabolic pathways influenced by LP299v supplementation. However, the need for further research hinders the ability to draw definitive conclusions. ConclusionsObserved metabolic changes were linked to mitochondrial dysfunction, inflammation, oxidative stress, and gut microbiota disruption. Despite the subtle nature of this alterations, our research successfully detected these differences and connected them to the metabolic disruptions associated with MDD. Our findings emphasise the intricate relationship between metabolism, gut microbiota, and mental health prompting further research into the mechanisms of action of probiotics in MDD treatment.

Stable construction and analysis of MDD modular networks based on multi-center EEG data

BackgroundThe modular structure can reflect the activity pattern of the brain, and exploring it may help us understand the pathogenesis of major depressive disorder (MDD). However, little is known about how to build a stable modular structure in MDD patients and how modules are separated and integrated. MethodWe used four independent resting state Electroencephalography (EEG) datasets. Different coupling methods, window lengths, and optimized community detection algorithms were used to find a reliable and robust modular structure, and the module differences of MDD were analyzed from the perspectives of global module attributes and local topology in multiple frequency bands. ResultsThe combination of the Phase Lag Index (PLI) and the Louvain algorithm can achieve better results and can achieve stability at smaller window lengths. Compared with Healthy Controls (HC), MDD had higher Modularity (Q) values and the number of modules in low-frequency bands. In addition, MDD showed significant structural changes in the frontal and parietal-occipital lobes, which were confirmed by further correlation analysis. ConclusionOur results provided a reliable validation of the modular structure construction method in MDD patients and contributed strong evidence for the changes in emotional cognition and visual system function in MDD patients from a new perspective. These results would afford valuable insights for further exploration of the pathogenesis of MDD.

Relationships between the gut microbiome and brain functional alterations in first-episode, drug-naïve patients with major depressive disorder

ObjectiveIncreasing evidence has shown that the microbiota-gut-brain axis (MGB) is involved in the mechanism of major depressive disorder (MDD). However, the relationship between the gut microbiome and brain function in MDD patients has not been determined. Here, we intend to identify specific changes in the gut microbiome and brain function in first-episode, drug-naïve MDD patients and then explore the associations between the two omics to elucidate how the MGB axis plays a role in MDD development. MethodsWe recruited 38 first-episode, drug-naïve MDD patients and 37 healthy controls (HC). The composition of the fecal microbiome and neural spontaneous activity alterations were examined using 16S rRNA gene amplicon sequencing analysis and regional homogeneity (ReHo). Spearman correlation analyses were conducted to assess the associations between the gut microbiome and brain function. ResultsCompared with HC, MDD patients exhibited distinct alterations in the gut microbiota and elevated ReHo in the frontal regions. In the MDD group, a positive relationship was noted between the relative abundance of Blautia and the HAMD-17 and HAMA scores, as well as between the relative abundance of Oxalobacteraceae and the HAMD-17 score. The relative abundances of Porphyromonadaceae and Parabacteroides were negatively correlated with the ReHo values of frontal regions. LimitationsOur study utilized a cross-sectional design, and the number of subjects was relatively small. ConclusionWe found that some specific gut microbiomes were associated with frontal function, and others were associated with clinical symptoms in MDD patients, which may support the role of the MGB axis underlying MDD.

Association Between Sleep Quality and Cognitive Symptoms in Patients with Major Depressive Disorder.

Cognitive symptoms and sleep disturbance (SD) are common non-mood-related symptoms of major depressive disorder (MDD). In clinical practice, both cognitive symptoms and SD are related to MDD progression. However, there are only a few studies investigating the connection between cognitive symptoms and SD in patients with MDD, and only preliminary evidence suggests a significant association between cognitive symptoms and SD in patients with mood disorders. This study investigates the relationship between cognitive symptoms and sleep quality in patients with major depressive disorder. Patients (n = 20) with MDD were enrolled; their mean Hamilton Depression Scale-17 score was 21.95 (±2.76). Gold standard polysomnography (PSG) was used to assess sleep quality, and the validated THINC-integrated tool (the cognitive screening tool) was used to evaluate cognitive function in MDD patients. Overall, the results showed significant correlations between the cognitive screening tool's total score and sleep latency, wake-after-sleep onset, and sleep efficiency. These findings indicate that cognitive symptoms are associated with poor sleep quality among patients with MDD.

Abnormal amplitude of low-frequency fluctuations associated with sleep efficiency in major depressive disorder

BackgroundSleep disturbance is one of the most frequent somatic symptoms in major depressive disorder (MDD), but the neural mechanisms behind it are not well understood. Sleep efficiency (SE) is a good indicator of early awakening and difficulty falling asleep in MDD patients. Our study aimed to investigate the relationship between sleep efficiency and brain function in MDD patients. MethodsWe recruited 131 MDD patients from the Fourth People's Hospital in Hefei, and 71 well-matched healthy controls who were enrolled from the community. All subjects underwent resting-state functional MRI. Brain function was measured using the fractional amplitude of low-frequency fluctuation (fALFF), sleep efficiency was objectively measured by polysomnography (PSG), and clinical scales were used to evaluate depressive symptoms and sleep status. Multivariate regression analysis was performed to assess the relationship between the amplitude of the low frequency fluctuation fraction and sleep efficiency. ResultThree brain regions with relevance to sleep efficiency in MDD patients were found: inferior occipital gyrus (Number of voxels = 25, peak MNI coordinate x/y/z = −42/-81/-6, Peak intensity = 4.3148), middle occipital gyrus (Number of voxels = 55, peak MNI coordinate x/y/z = −30/-78/18, Peak intensity = 5.111), and postcentral gyrus (Number of voxels = 26, peak MNI coordinate x/y/z = −27/-33/60, Peak intensity = 4.1263). But there was no significant relationship between fALFF and SE in the healthy controls. ConclusionThe reduced sleep efficiency in MDD may be related to their lower neural activity in the inferior occipital gyrus, middle occipital gyrus, and postcentral gyrus. The findings may provide a potential neuroimaging basis for the clinical intervention in patients with major depressive disorder with sleep disturbances.

Disrupted properties of functional brain networks in major depressive disorder during emotional face recognition: an EEG study via graph theory analysis.

Previous neuroimaging studies have revealed abnormal brain networks in patients with major depressive disorder (MDD) in emotional processing. While any cognitive task consists of a series of stages, little is yet known about the topology of functional brain networks in MDD for these stages during emotional face recognition. To address this problem, electroencephalography (EEG)-based functional brain networks of MDD patients at different stages of facial information processing were investigated in this study. First, EEG signals were collected from 16 patients with MDD and 18 age-, gender-, and education-matched normal subjects when performing an emotional face recognition task. Second, the global field power (GFP) method was employed to divide group-averaged event-related potentials into different stages. Third, using the phase transfer entropy (PTE) approach, the brain networks of MDD patients and normal individuals were constructed for each stage in negative and positive face processing, respectively. Finally, we compared the topological properties of brain networks of each stage between the two groups using graph theory approaches. The results showed that the analyzed three stages of emotional face processing corresponded to specific neurophysiological phases, namely, visual perception, face recognition, and emotional decision-making. It was also demonstrated that depressed patients showed abnormally decreased characteristic path length at the visual perception stage of negative face recognition and normalized characteristic path length in the stage of emotional decision-making during positive face processing compared to healthy subjects. Furthermore, while both the MDD and normal groups' brain networks were found to exhibit small-world network characteristics, the brain network of patients with depression tended to be randomized. Moreover, for patients with MDD, the centro-parietal region may lose its status as a hub in the process of facial expression identification. Together, our findings suggested that altered emotional function in MDD patients might be associated with disruptions in the topological organization of functional brain networks during emotional face recognition, which further deepened our understanding of the emotion processing dysfunction underlying MDD.

Psychotic symptoms and neurocognition among patients with major depressive disorder: A chained mediation model of depressive symptoms and socio-occupational functioning

BackgroundDepressive symptom and psychotic symptom have been identified as risk factors for impaired socio-occupational functioning in patients with major depressive disorder (MDD), while neurocognitive functioning is considered to be a potential protective factor against socio-occupational functioning. Nevertheless, little is known about the complex relationship among these factors in patients with MDD. The purpose of this research was to explore whether the relationship between depressive symptom severity and social-occupational functioning is mediated by neurocognitive functioning and psychotic symptom severity in MDD patients. MethodsA total of 659 eligible MDD patients included male and female, and their depressive symptoms and psychotic symptoms at baseline were assessed by the 17-item Hamilton Depression Scale (HAMD-17) and The Brief Psychiatric Rating Scale (BPRS) respectively. Cognitive domains were assessed by the MATRICS Consensus Cognitive Battery (MCCB), and subjective and objective functioning were measured by the Global Assessment of Functioning (GAF). LimitationThe analysis is cross-sectional, which limits causal inference. Result(1) The correlation between depressive symptoms and thought disturbance was positive (r = 0.125, p = 0.001), whereas the correlations with visual learning and memory (r = −0.146, p < 0.001) and socio-occupational functioning (r = −0.175, p < 0.001) were negative. (2) Depressive symptoms mainly affect the socio-occupational functioning of MDD patients via three indirect effects: the single mediating effect of psychotic symptoms and neurocognitive functioning, and the chain mediating effect of psychotic symptoms and neurocognitive functioning. ConclusionsThe results suggest that the relationship between depressive symptom severity and socio-occupational functioning in MDD patients is partially mediated by psychotic symptom severity and neurocognitive functioning.

Retinal markers of therapeutic responses in major depressive disorder: Effects of antidepressants on retinal function

BackgroundOne goal of research into major depressive disorder (MDD) is to develop markers to predict and monitor the response to psychotropic treatments. The retina is endowed with a complex neurotransmission system, composed of the main neurotransmitters involved in the pathophysiology of MDD. The retina is therefore a relevant site of investigation for the identification of reliable and robust markers. However, the effects of antidepressants on the human retina are poorly studied. Here, we seek to study the potential specific effects of various antidepressants on retinal function in MDD patients. MethodsWe assessed retinal function using flash (fERG), pattern (PERG) and multifocal (mfERG) electroretinogram in 19 MDD patients treated using antidepressants at baseline and at weeks 4, 8 and 12. ResultsWe observed reduced b-wave amplitude of photopic fERG 3.0 in patients treated with Selective Serotonin Reuptake Inhibitor (SSRI) in comparison with patients treated with Serotonin-Norepinephrine Reuptake Inhibitor (SNRI) or Tricyclic Antidepressant (TCAD). We also showed that SNRIs were associated both with a decrease in PERG P50 implicit time and an increase in fERG 3.0 b-wave amplitude. TCADs were associated with an increase in fERG flicker 3.0 a- and b-wave amplitude. ConclusionsThis is the first study in real-life conditions to show a specific effect of various antidepressants on retinal function evaluated by electroretinogram. Further investigations should be led to specify the effects of antidepressants on ERG in order to isolate reliable and reproducible markers for predicting and monitoring the response to antidepressants.

The association between overweight/obesity and poor cognitive function is mediated by inflammation in patients with major depressive disorder

BackgroundCognitive dysfunction is a common and core feature of major depressive disorder (MDD). Evidences exerted a potentially harmful role of obesity and higher peripheral levels of inflammation in cognitive function, but few studies have explored whether markers of peripheral inflammation might mediate the association between overweight/obesity and deficits in cognitive function. Our study aimed to examine the cognitive function in MDD patients and clarify the effects of overweight/obesity and inflammatory cytokines on cognitive dysfunction in this population. MethodWe used a cross-sectional design in this study. A total of 265 patients with MDD were enrolled and divided into underweight, normal weight and overweight/obese groups. The MATRICS Consensus Cognitive Battery (MCCB) was administered to measure the cognition. Plasma levels of nineteen cytokines were measured using high sensitivity multiplex bead-based assays. ResultsWe found overweight/obese MDD patients associated with higher plasma levels of tumor necrosis factor (TNF)-α, interleukin (IL)-8, and macrophage inflammatory protein (MIP)-1β and worse performance in speed of processing and working memory. The mediation analysis found higher levels of IL-8 (direct: β = −0.591 (95 % Confidence Interval (CI): −1.0 to −0.2), P = 0.002; indirect: β = 0.060 (95 % CI.: 0.0–0.2), P = 0.032) and TNF-α (direct: β = −0.589 (95 % CI.: −1.0 to −0.2), P = 0.002; indirect: β = 0.059 (95 % CI.: 0.1–0.2), P = 0.037) were associated with more deficits in speed of processing, and partially mediated the relationship between body mass index and speed of processing. ConclusionOur results suggest that elevated inflammation might be one biological mechanism underlying the link between higher body mass and deficits in processing speed in patients with MDD.

Association between inflammation and neural plasticity biomarkers in olfactory neuroepithelium – derived cells and cognitive performance in patients with major depressive disorder

IntroductionInflammation and neural plasticity play a significant role in major depressive disorder (MDD) pathogenesis and cognitive dysfunction. The olfactory neuroepithelium (ON), closely related to the central nervous system (CNS), allows a non-invasive, low-cost study of neuropsychiatric disorders. However, few studies have used ON cells to ascertain them as biomarkers for MDD.ObjectivesDetermine the relationship between inflammatory/neural plasticity markers and cognitive functioning in MDD patients and healthy controls.MethodsSample: 9 MDD patients and 7 healthy controls. Exclusion criteria: other Axis I mental disorders (patients) or any mental disorder (controls) and any inflammatory, autoimmune, or CNS diseases. Assessment: sociodemographic, clinical, and cognitive variables (CANTAB) were recorded. mRNA was isolated from ON cells and MAPK14, IL6, TNF-α, Mecp2, BDNF, GSK3, GRIA2, and FosB gene expression levels were quantified using quantitative polymerase chain reaction.ResultsMDD patients showed decreased levels of BDNF (p=0.022), GSK3 (p=0.027), and working memory (p=0.024) compared with healthy controls. In healthy controls, planning was positively correlated with NRF2, BDNF, and MAPK14 gene expression. In MDD patients no correlation between cognitive parameters and inflammation/neural plasticity biomarkers was found.ConclusionsThese results reveal that: (1) Plasticity biomarkers such as BDNF and GSK3 could be useful diagnostic tools for MDD (2) MDD is associated with working memory deficits; (3) no association could be determined between planning and NRF2, BDNF, and MAPK14 gene expression in MDD and (4) the ON is a promising model in the study of neuropsychiatric disorders.DisclosureNo significant relationships.

Gut Microbiome Composition Linked to Inflammatory Factors and Cognitive Functions in First-Episode, Drug-Naive Major Depressive Disorder Patients.

ObjectiveThe microbiota–gut–brain axis, especially the inflammatory pathway, may play a critical role in the pathogenesis of cognitive impairment in major depressive disorder (MDD). However, studies on the microbiota-inflammatory-cognitive function axis in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and explore the correlation between gut microbiota and inflammatory factors, cognitive function in MDD patients.MethodStudy participants included 66 first-episode, drug naïve MDD patients as well as 43 healthy subjects (HCs). The composition of fecal microbiota was evaluated using16S rRNA sequencing and bioinformatics analysis. The cytokines such as hs-CRP, IL-1β, IL-6, IL-10, and TNF-α in peripheral blood were detected via enzyme linked immunosorbent assay (ELISA); assessment of cognitive functions was performed using the Color Trail Test (CTT), The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and the Stroop Color-Word Test (SCWT).ResultsWe found that compared with HCs, MDD patients had cognitive impairments and showed different α-diversity and β-diversity of gut microbiota composition. LDA effect size (LEfSe) analysis found MDD have higher Deinococcaceae and lower Bacteroidaceae, Turicibacteraceae, Clostridiaceae and Barnesiellaceae at family level. Deinococcus and Odoribacter was higher in the MDD group, however, Bacteroides, Alistipes, Turicibacter, Clostridium, Roseburia, and Enterobacter were lower at genus level. Furthermore, In MDD patients, the Bacteroidaceae and Bacteroides were both positively correlated with hsCRP, CCT1, CCT2. Alistipes was positively correlated with IL-6, Word time, Color time, Word-Color time, Color-Word time and negatively correlated with Delayed Memory, Total score and Standardized score. Turicibacteraceae and Turicibacter were both negatively correlated with IL-1β and IL-6.ConclusionThe present findings confirm that the gut microbiota in MDD patients have altered gut microbes that are closely associated with inflammatory factors and cognitive function in MDD patients.

The Correlation Between Thyroid Function, Frontal Gray Matter, and Executive Function in Patients With Major Depressive Disorder.

The present study was aimed to investigate the relationships between serum thyroid hormones (THs), frontal gray matter volume, and executive function in selected patients with major depressive disorder (MDD). One hundred and four MDD patients and seventy-five healthy controls (HCs) were subjected to thyroid-stimulating hormone (TSH), free Triiodothyronine (fT3), free Thyroxine (fT4), and executive function tests and underwent structural magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) analysis was performed to compare group differences in the gray matter for the frontal lobe. Furthermore, mediation analysis was used to investigate whether gray matter volumes of the frontal gyrus mediated the relationship between serum THs and executive function in MDD patients. MDD patients exhibited significant gray matter volume reduction in several brain regions, including the left rectus, right middle frontal cortex, and left middle frontal cortex. Serum TSH levels are positively associated with altered regional gray matter volume patterns within MFG and executive function. Importantly, gray matter in the right MFG was a significant mediator between serum TSH levels and executive function. These findings expand our understanding of how thyroid function affects brain structure changes and executive function in MDD patients.

AGEADJUSTED NORMATIVE DATA AND DISCRIMINATIVE VALIDITY OF COGNITIVE TESTS IN THE UKRAINIAN ADULT PATIENTS WITH MAJOR DEPRESSIVE DISORDER

AGEADJUSTED NORMATIVE DATA AND DISCRIMINATIVE VALIDITY OF COGNITIVE TESTS IN THE UKRAINIAN ADULT PATIENTS WITH MAJOR DEPRESSIVE DISORDER

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

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.

Brain structural network alterations related to serum cortisol levels in drug-na\xefve, first-episode major depressive disorder patients: a source-based morphometric study

Higher cortisol levels due to a hyperactive hypothalamic–pituitary–adrenal axis have been reported in patients with major depressive disorder (MDD). Increased cortisol levels change both the brain morphology and function in MDD patients. The multivariate source-based morphometry (SBM) technique has been applied to investigate neuroanatomical changes in some neuropsychiatric diseases, but not MDD. We aimed to examine the alterations in gray matter (GM) networks and their relationship with serum cortisol levels in first-episode, drug-naïve MDD patients using SBM. Forty-two patients with MDD and 39 controls were recruited via interviews. Morning serum cortisol levels were measured, and high-resolution T1-weighted imaging followed by SBM analysis was performed in all participants. The patients had significantly higher serum cortisol levels than the controls. We found two GM sources, which were significantly different between patients with MDD and controls (prefrontal network, p < .01; insula-temporal network, p < .01). Serum cortisol levels showed a statistically significant negative correlation with the loading coefficients of the prefrontal network (r = − 0.354, p = 0.02). In conclusion, increased serum cortisol levels were associated with reductions in the prefrontal network in the early stage of MDD, and SBM may be a useful approach for analyzing structural MRI data.

Efficacy of Buspirone Augmentation of Escitalopram in Patients with Major Depressive Disorder with and without Atypical Features: A Randomized, 8 Week, Multicenter, Open-Label Clinical Trial.

Objective This study investigated the treatment response and cognitive enhancement effects of buspirone augmentation of escitalopram in patients with major depressive disorder (MDD), according to atypical feature subtypes of MDD. Methods An 8 week, randomized, parallel-controlled, open-label study was conducted. The Columbia Atypical Depression Diagnostic Scale was administered to evaluate atypical features. Patients were assigned randomly to the buspirone augmentation or non-buspirone groups. Symptom severity and cognitive function were evaluated using the 17-item Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Beck Depression Inventory, Beck Anxiety Inventory, digit span test, word fluency test, and Trail Making Tests A and B. Results A total of 89 patients were recruited. There were no significant differences in the measures between the groups; however, among the MDD patients without atypical features, the digit span and word fluency tests were improved by treatment. In the MDD patients without atypical features, the buspirone augmentation group showed a significant improvement on the digit span test compared to the non-buspirone group. Conclusion Buspirone augmentation did not demonstrate significant benefits in MDD patients; however, buspirone augmentation showed greater efficacy for the improvement of cognitive function in MDD patients without atypical features. Our study suggests that atypical features are an important factor for cognitive enhancement in buspirone augmentation treatment in patients with MDD.

Antidepressant Drugs and Physical Activity: A Possible Synergism in the Treatment of Major Depression?

Major depressive disorder (MDD) is a severe mental illness that affects 5–20% of the general population. Current antidepressant drugs exert only a partial clinical efficacy because approximately 30% of depressed patients failed to respond to these drugs and antidepressants produce remission only in 30% of patients. This can be explained by the fact that the complex pathophysiology of depression has not been completely elucidated, and treatments have been mainly developed following the “monoaminergic hypothesis” of depression without considering the key role of other factors involved in the pathogenesis of MDD, such as the role of chronic stress and neuroinflammation. Chronic stress acts as a risk factor for the development of MDD through the impairment of neurotrophins signaling such as brain-derived neurotrophic factor (BDNF) and transforming-growth-factor-β1 (TGF-β1). Stress-induced depressive pathology contributes to altered BDNF level and function in MDD patients and, thereby, an impairment of neuroplasticity at the regional and circuit level. Recent studies demonstrate that aerobic exercise strongly increases BDNF production and it may contribute as a non-pharmacological strategy to improve the treatment of cognitive and affective symptoms in MDD. Here we will provide a general overview on the possible synergism between physical activity and antidepressants in MDD. Physical activity can synergize with antidepressant treatment by rescuing neurotrophins signaling in MDD patients, promoting neuronal health and recovery of function in MDD-related circuits, finally enhancing pharmacotherapeutic response. This synergism might be particularly relevant in elderly patients with late-life depression, a clinical subgroup with an increased risk to develop dementia.

Impact of GRIK4 gene polymorphisms on cognitive dysfunction in patients with major depression

An increasing body of research has focused on the functions of the glutamate receptor ionotropic kainate 4 (GRIK4) gene in treatment for depression, memory, as well as neurodegenerative diseases. It is widely recognized that major depressive disorder (MDD) patients often display cognitive dysfunctions, which do not strictly correlate with the severity of depressive symptoms, and in some individuals persist after clinical remission. However, little is known regarding the particular role of GRIK4 in cognitive functions of patients suffering from a MDD. The current study therefore sought to examine the impact of GRIK4 polymorphism on cognitive functions in MDD patients. A total of 217 MDD patients participated in this study. Their depressive severity was determined with the 17-item Hamilton Depression Rating Scale, and cognitive functions were evaluated using the Stroop Neuropsychological Screening Test, tests of visual reproduction and immediate logical memory, and the verbal fluency test (VFT). All patients were genotyped to determine GRIK4 polymorphisms. Results of VFT revealed statistical differences among all single-nucleotide polymorphism (SNP) genotypes. In the Stroop-color-word test, only rs6589847 was discovered to be statistically different. No significant difference was found in the Stroop-color task scores, the visual reproduction test, or the immediate logical memory test. GRIK4 polymorphism exerted a significant effect on long-term memory retrieval and selective attention, but did not affect immediate memory.

Altered Brain Function in Drug-Naïve Major Depressive Disorder Patients With Early-Life Maltreatment: A Resting-State fMRI Study.

Childhood Maltreatment (CM) is an important risk factor for major depressive disorder (MDD). Previous studies using emotional task-state functional magnetic resonance (task-state fMRI) found that altered brain function in prefrontal-limbic regions was the key neuropathological mechanism in adult MDD patients with experience of early-life maltreatment. However, to the best of our knowledge, there is no published study investigating brain function in MDD patients with CM experience using resting-state fMRI (rs-fMRI). In present study, we aimed to detect altered resting-state brain activity in MDD patients with CM experience, and identify significantly activated brain regions, which may provide new insights into the neural mechanism underlying the relationship between MDD and CM experience. The results showed MDD patients with CM experience were associated with increased amplitude of low-frequency fluctuation (ALFF) and altered function connection (FC) in the prefrontal cortex, when compared to MDD patients without CM. Of note, left frontal middle gyrus (LFEG) was found as a specific brain region which differentiates MDD patients with CM from patients without CM. These results suggest that rs-fMRI is a useful method in studying the correlation between MDD and CM experience and altered function of LFEG in resting-state may explain the correlation between MDD and CM experience.

Major Depressive Disorder and Magnetic Resonance Imaging: A Mini-Review of Recent Progress.

Major depressive disorder (MDD) has been a prominent topic in recent years due to its unknown etiology and pathology, high prevalence rate, and the high cost of treatment. Due to its high resolution for soft tissue, magnetic resonance imaging (MRI) has become an essential noninvasive tool for the evaluation of the brain substrates underlying mental disorders. MRI enables characterization of brain morphology and function in MDD patients. Compared to healthy controls, MDD patients have structural changes in certain brain regions such as the prefrontal cortex, cingulate cortex, precuneus, thalamus, and hippocampus. Abnormal brain functions as indicated by various MRI measurements including region homogeneity, the amplitude of low-frequency fluctuation, functional connectivity, and mean kurtosis may also contribute to the pathogenesis of MDD. This mini-review summarizes recent MRI findings on the neural manifestations of MDD. We discuss the potential of MRI biomarkers that may prove clinically useful for early diagnosis and evaluation of treatment outcomes for depression.