Peripheral mitochondrial DNA as a neuroinflammatory biomarker for major depressive disorder

In the pathogenesis of major depressive disorder, chronic stress-related neuroinflammation hinders favorable prognosis and antidepressant response. Mitochondrial DNA may be an inflammatory trigger, after its release from stress-induced dysfunctional central nervous system mitochondria into peripheral circulation. This evidence supports the potential use of peripheral mitochondrial DNA as a neuroinflammatory biomarker for the diagnosis and treatment of major depressive disorder. Herein, we critically review the neuroinflammation theory in major depressive disorder, providing compelling evidence that mitochondrial DNA release acts as a critical biological substrate, and that it constitutes the neuroinflammatory disease pathway. After its release, mitochondrial DNA can be carried in the exosomes and transported to extracellular spaces in the central nervous system and peripheral circulation. Detectable exosomes render encaged mitochondrial DNA relatively stable. This mitochondrial DNA in peripheral circulation can thus be directly detected in clinical practice. These characteristics illustrate the potential for mitochondrial DNA to serve as an innovative clinical biomarker and molecular treatment target for major depressive disorder. This review also highlights the future potential value of clinical applications combining mitochondrial DNA with a panel of other biomarkers, to improve diagnostic precision in major depressive disorder.

Sleep disturbances and psychomotor retardation in the prediction of cognitive impairments in patients with major depressive disorder

BACKGROUND Symptoms of depression and comorbid anxiety are known risk factors for cognitive impairment in major depressive disorder(MDD).Understanding their relationships is crucial for developing targeted interventions to mitigate cognitive impairments in MDD patients.We expect that the severity of sleep disturbances and other depressive symptoms will be positively correlated with the degree of cognitive impairments.We also hypothesize that anxiety symptoms,especially psychic anxiety,is a key factor in predicting cognitive performance in MDD patients and may indirectly contribute to cognitive impairment by affecting sleep disturbances and other potential factors.AIM To determine which dimension of the depressive and anxiety symptoms predicts cognitive impairment during a depressive episode.METHODS A comprehensive neurocognitive test battery assessed executive function,attention,processing speed,and memory in 162 medication-free MDD patients and 142 matched healthy controls.The 24-item Hamilton Depression Rating Scale was used to assess depressive symptoms,and the 14-item Hamilton Anxiety Scale was used to assess anxiety symptoms.Linear regression analyses and mediation analyses were conducted to evaluate the impact of depressive and anxiety symptoms,as well as their interactions,on cognitive impairments.RESULTS Among the depressive symptoms,sleep disturbances were associated with poorer executive function(P=0.004),lower processing speed(P=0.047),and memory impairments(P<0.001),and psychomotor retardation(PR)was associated with lower processing speed in patients with MDD(P=0.019).Notably,PR was found to mediate the impact of sleep disturbances on the processing speed.Regarding anxiety symptoms,psychic anxiety,rather than somatic anxiety,was associated with cognitive impairments in all aspects.Sleep disturbances mediated the effect of psychic anxiety on executive function[β=-0.013,BC CI(-0.027,-0.001)]and memory[β=-0.149,BC CI(-0.237,-0.063)],while PR mediated its effect on processing speed(β=-0.023,BC CI(-0.045,-0.004)].CONCLUSION Sleep disturbances may be a key predictor of poorer executive function,lower processing speed,and memory loss,while PR is crucial for lower processing speed during a depressive episode.Psychic anxiety contributes to all aspects of cognitive impairments,mediated by sleep disturbances and PR.

Repetitive transcranial magnetic stimulation enhanced by neuronavigation in the treatment of depressive disorder and schizophrenia

This editorial assesses the advancements in neuronavigation enhanced repetitive transcranial magnetic stimulation for depressive disorder and schizophrenia treatment.Conventional repetitive transcranial magnetic stimulation faces challenges due to the intricacies of brain anatomy and patient variability.Neuronavigation offers innovative solutions by integrating neuroimaging with three-dimensional localization to pinpoint brain regions and refine therapeutic targeting.This systematic review of recent literature underscores the enhanced efficacy of neuronavigation in improving treatment outcomes for these disorders.This editorial highlights the pivotal role of neuronavigation in advancing psychiatric care.

Major depressive disorder is associated with mitochondrial ND6 T14502C mutation in two Han Chinese families

BACKGROUND Globally,the World Health Organization ranks major depressive disorder(MDD)as the leading cause of disability.However,MDD molecular etiology is still poorly understood.AIM To explore the possible association between mitochondrial ND6 T14502C mutation and MDD.METHODS Clinical data were collected from two pedigrees,and detailed mitochondrial genomes were obtained for the two proband members.The assessment of the resulting variants included an evaluation of their evolutionary conservation,allelic frequencies,as well as their structural and functional consequences.Detailed mitochondrial whole genome analysis,phylogenetic,and haplotype analysis were performed on the probands.RESULTS Herein,we reported the clinical,genetic,and molecular profiling of two Chinese families afflicted with MDD.These Chinese families exhibited not only a range of onset and severity ages in their depression but also extremely low penetrances to MDD.Sequence analyses of mitochondrial genomes from these pedigrees have resulted in the identification of a homoplasmic T14502C(I58V)mutation.The polymorphism is located at a highly conserved isoleucine at position 58 of ND6 and distinct mitochondrial DNA(mtDNA)polymorphisms originating from haplogroups M10 and H2.CONCLUSION Identifying the T14502C mutation in two individuals with no genetic relation who exhibit symptoms of depression provides compelling evidence that this mutation may be implicated in MDD development.Nonetheless,the two Chinese pedigrees that carried the T14502C mutation did not exhibit any functionally significant mutations in their mtDNA.Therefore,the phenotypic expression of the T14502C mutation related to MDD may be influenced by the nuclear modifier gene(s)or environmental factors.

Vulnerable brain regions in adolescent major depressive disorder:A resting-state functional magnetic resonance imaging activation likelihood estimation meta-analysis

BACKGROUND Adolescent major depressive disorder(MDD)is a significant mental health concern that often leads to recurrent depression in adulthood.Resting-state functional magnetic resonance imaging(rs-fMRI)offers unique insights into the neural mechanisms underlying this condition.However,despite previous research,the specific vulnerable brain regions affected in adolescent MDD patients have not been fully elucidated.AIM To identify consistent vulnerable brain regions in adolescent MDD patients using rs-fMRI and activation likelihood estimation(ALE)meta-analysis.METHODS We performed a comprehensive literature search through July 12,2023,for studies investigating brain functional changes in adolescent MDD patients.We utilized regional homogeneity(ReHo),amplitude of low-frequency fluctuations(ALFF)and fractional ALFF(fALFF)analyses.We compared the regions of aberrant spontaneous neural activity in adolescents with MDD vs healthy controls(HCs)using ALE.RESULTS Ten studies(369 adolescent MDD patients and 313 HCs)were included.Combining the ReHo and ALFF/fALFF data,the results revealed that the activity in the right cuneus and left precuneus was lower in the adolescent MDD patients than in the HCs(voxel size:648 mm3,P<0.05),and no brain region exhibited increased activity.Based on the ALFF data,we found decreased activity in the right cuneus and left precuneus in adolescent MDD patients(voxel size:736 mm3,P<0.05),with no regions exhibiting increased activity.CONCLUSION Through ALE meta-analysis,we consistently identified the right cuneus and left precuneus as vulnerable brain regions in adolescent MDD patients,increasing our understanding of the neuropathology of affected adolescents.

Multimodal abnormalities of brain structures in adolescents and young adults with major depressive disorder:An activation likelihood estimation meta-analysis

BACKGROUND Major depressive disorder(MDD)in adolescents and young adults contributes significantly to global morbidity,with inconsistent findings on brain structural changes from structural magnetic resonance imaging studies.Activation likeli-hood estimation(ALE)offers a method to synthesize these diverse findings and identify consistent brain anomalies.METHODS We performed a comprehensive literature search in PubMed,Web of Science,Embase,and Chinese National Knowledge Infrastructure databases for neuroi-maging studies on MDD among adolescents and young adults published up to November 19,2023.Two independent researchers performed the study selection,quality assessment,and data extraction.The ALE technique was employed to synthesize findings on localized brain function anomalies in MDD patients,which was supplemented by sensitivity analyses.RESULTS Twenty-two studies comprising fourteen diffusion tensor imaging(DTI)studies and eight voxel-based morphome-try(VBM)studies,and involving 451 MDD patients and 465 healthy controls(HCs)for DTI and 664 MDD patients and 946 HCs for VBM,were included.DTI-based ALE demonstrated significant reductions in fractional anisotropy(FA)values in the right caudate head,right insula,and right lentiform nucleus putamen in adolescents and young adults with MDD compared to HCs,with no regions exhibiting increased FA values.VBM-based ALE did not demonstrate significant alterations in gray matter volume.Sensitivity analyses highlighted consistent findings in the right caudate head(11 of 14 analyses),right insula(10 of 14 analyses),and right lentiform nucleus putamen(11 of 14 analyses).CONCLUSION Structural alterations in the right caudate head,right insula,and right lentiform nucleus putamen in young MDD patients may contribute to its recurrent nature,offering insights for targeted therapies.

Resting-state functional magnetic resonance imaging and support vector machines for the diagnosis of major depressive disorder in adolescents

BACKGROUND Research has found that the amygdala plays a significant role in underlying pathology of major depressive disorder(MDD).However,few studies have explored machine learning-assisted diagnostic biomarkers based on amygdala functional connectivity(FC).AIM To investigate the analysis of neuroimaging biomarkers as a streamlined approach for the diagnosis of MDD in adolescents.METHODS Forty-four adolescents diagnosed with MDD and 43 healthy controls were enrolled in the study.Using resting-state functional magnetic resonance imaging,the FC was compared between the adolescents with MDD and the healthy controls,with the bilateral amygdala serving as the seed point,followed by statistical analysis of the results.The support vector machine(SVM)method was then applied to classify functional connections in various brain regions and to evaluate the neurophysiological characteristics associated with MDD.RESULTS Compared to the controls and using the bilateral amygdala as the region of interest,patients with MDD showed significantly lower FC values in the left inferior temporal gyrus,bilateral calcarine,right lingual gyrus,and left superior occipital gyrus.However,there was an increase in the FC value in Vermis-10.The SVM analysis revealed that the reduction in the FC value in the right lingual gyrus could effectively differentiate patients with MDD from healthy controls,achieving a diagnostic accuracy of 83.91%,sensitivity of 79.55%,specificity of 88.37%,and an area under the curve of 67.65%.CONCLUSION The results showed that an abnormal FC value in the right lingual gyrus was effective as a neuroimaging biomarker to distinguish patients with MDD from healthy controls.

Association between 5-HTR1A gene C-1019G polymorphism and antidepressant response in patients with major depressive disorder:A meta-analysis

BACKGROUND Major depressive disorder(MDD)is a substantial global health concern,and its treatment is complicated by the variability in individual response to antide-pressants.AIM To consolidate research and clarify the impact of genetic variation on MDD treatment outcomes.METHODS Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines,a systematic search across PubMed,EMBASE,Web of Science,and the Cochrane Library was conducted without date restrictions,utilizing key terms related to MDD,serotonin 1A receptor polymorphism(5-HTR1A),C-1019G polymorphism,and antidepressant response.Studies meeting inclusion criteria were thoroughly screened,and quality assessed using the Newcastle-Ottawa Scale.Statistical analyses,includingχ2 and I²values,were used to evaluate heterogeneity and fixed-effect or random-effect models were applied accordingly.RESULTS The initial search yielded 1216 articles,with 11 studies meeting criteria for inclusion.Analysis of various genetic models showed no significant association between the 5-HTR1A C-1019G polymorphism and antidepressant efficacy.The heterogeneity was low to moderate,and no publication bias was detected through funnel plot symmetry and Egger's and Begg's tests.CONCLUSION This meta-analysis does not support a significant association between the 5-HTR1A C-1019G polymorphism and the efficacy of antidepressant treatment in MDD.The findings call for further research with larger cohorts to substantiate these results and enhance the understanding of antidepressant pharmacogenetics.

Self-experience of buried seeds at auricular points in depressive patients with sleep disorder: a qualitative research

Objective To explore the self-experience of burying seeds at auricular points in depressive patients with sleep disorder,so as to seek possible approaches to improve the quality of care.Methods Eleven patients involved in a three-week randomized controlled clinical trial were purposefully interviewed by the experienced,qualified counselor.The process of thematic analysis was applied in this study,the self-experience was discussed and recorded,transcribed,and analyzed accordingly.Results Four themes related to self-experience were extracted,these included the deficiency in relevant support,passive acceptance,distrust,expectation and further advice.Conclusion There was an urgent demand of humane care and emotional support,which might improve compliance of the treatment to some extent in terms of health education.Additionally,medical practitioners should provide the patient with comprehensive support,professional health education,as well as standardize training program for TCM operator and control the operation’s quality.

Research progress on the effects of positive stress reduction on positive awareness and psychosocial functioning in patients with depressive disorders

To review the current research status of positive thought stress reduction therapy(PTSRT),psychosocial functioning of patients with depressive disorders,the shortcomings and outlook of the influence of PTSRT on positive thought awareness,and psychosocial functioning of patients with depressive disorders.This review has the objective to provide clinical healthcare personnel with essential information about the use of PTSRT to improve the level of positive thought and psychosocial functioning of patients with depressive disorders.

Research progress on BDNF in Sjogren's syndrome with depressive disorder

Brain-derived neurotrophic factor(BDNF)is a widely studied neurotrophic factor,which plays an important role in the growth,development,dif-ferentiation,injury,repair,survival and apoptosis of nerve cells.More and more studies have found that there is a high prevalence of depressive disorders in patients with autoimmune diseases.Sjogren's syndrome is a chronic autoimmune exocrine disease characterized by lympho-cytic infiltration and exocrine gland destruction.Depres-sive disorders are common in patients with Sjogren's syndrome.The quality of life of patients with Sjogren's syndrome with depression was generally lower than that of patients with Sjogren's syndrome without depres-sion.In this article,we reviewed the research progress of BDNF and depression in Sjogren's syndrome at home and abroad.

Research progress on brain-derived neurotrophic factor and non-suicidal self-injury addictive behavior associated with depressive disorders in adolescents

In recent years,non-suicidal self-injury(NSSI)behavior has emerged in a large number of adoles-cent depression.NSSI associated with adolescent depres-sion may be an addictive behavior,which has many sim-ilar neurobiological mechanisms to substance addiction.Brain-derived neurotrophic factor(BDNF)and precursor of BDNF(proBDNF)play an important role in addiction behavior,and they may be related to endogenous opioid receptors.The location and distribution of opioidμre-ceptors in the brain are related to reward,motivation and emotion regulated by behavioral addiction.The purpose of this paper is to review the general situation,mechanism and relationship between the characteristics of NSSI be-havior addiction and brain-derived nutritional factors in adolescents with depression.

Targeting TrkB–PSD-95 coupling to mitigate neurological disorders

Tropomyosin receptor kinase B(TrkB)signaling plays a pivotal role in dendritic growth and dendritic spine formation to promote learning and memory.The activity-dependent release of brain-derived neurotrophic factor at synapses binds to pre-or postsynaptic TrkB resulting in the strengthening of synapses,reflected by long-term potentiation.Postsynaptically,the association of postsynaptic density protein-95 with TrkB enhances phospholipase Cγ-Ca^(2+)/calmodulin-dependent protein kinaseⅡand phosphatidylinositol 3-kinase-mechanistic target of rapamycin signaling required for long-term potentiation.In this review,we discuss TrkB-postsynaptic density protein-95 coupling as a promising strategy to magnify brain-derived neurotrophic factor signaling towards the development of novel therapeutics for specific neurological disorders.A reduction of TrkB signaling has been observed in neurodegenerative disorders,such as Alzheimer's disease and Huntington's disease,and enhancement of postsynaptic density protein-95 association with TrkB signaling could mitigate the observed deficiency of neuronal connectivity in schizophrenia and depression.Treatment with brain-derived neurotrophic factor is problematic,due to poor pharmacokinetics,low brain penetration,and side effects resulting from activation of the p75 neurotrophin receptor or the truncated TrkB.T1 isoform.Although TrkB agonists and antibodies that activate TrkB are being intensively investigated,they cannot distinguish the multiple human TrkB splicing isoforms or cell type-specific functions.Targeting TrkB–postsynaptic density protein-95 coupling provides an alternative approach to specifically boost TrkB signaling at localized synaptic sites versus global stimulation that risks many adverse side effects.

Brain Research on Mental Disorders: A Criticism

Objective: To expose the problems and inherent limitations of neuroscience-based brain research on mental disorders. Method: Discussion of the theory underlying brain research on mental disorders, followed by a systematic evaluation of typical studies. Results: The fundamental problem is that brain researchers fail to differentiate between biological mental disorders in which brain processes cause the disorder (notably schizophrenia, bipolar disorder, and melancholic depression) and learned mental disorders in which brain processes mediate but do not cause the disorder (which is the case with reactive depression, reactive anxiety, OCD, and PTSD). Researchers have been unsuccessful in identifying mechanisms in the brain that cause biological mental disorders, and will never be able to locate the innumerable specific neural connections that mediate learned mental disorders. Moreover, the author’s review of typical studies in this field shows that they have serious problems with theory, measurement, and data analysis, and that their findings cannot be trusted. Conclusions: Neuroscience-based brain research on mental disorders, unlike other neurological research, has been an expensive failure and it is not worth continuing.

Cognitive Disorders, Depression and Anxiety in Temporal Lobe Epilepsy: An Overview

Partial epilepsies, originating in a specific brain region, affect about 60% of adults with epilepsy. Temporal lobe epilepsy (TLE) is the most prevalent subtype within this category, often necessitating surgical intervention due to its refractoriness to antiepileptic drugs (AEDs). Hippocampal sclerosis, a common underlying pathology, often exacerbates the severity by introducing cognitive and emotional challenges. This review delves deeper into the cognitive profile of TLE, along with the risk factors for cognitive disorders, depression, and anxiety in this population.

Reconsidering the role of depression and common psychiatric disorders as partners in the type 2 diabetes epidemic

Common psychiatric disorders(CPDs)and depression contribute significantly to the global epidemic of type 2 diabetes(T2D).We postulated a possible pathophysiological mechanism that through Bridge-Symptoms present in depression and CPDs,promotes the establishment of emotional eating,activation of the reward system,onset of overweight and obesity and,ultimately the increased risk of developing T2D.The plausibility of the proposed pathophysiological mechanism is supported by the mechanism of action of drugs such as naltrexonebupropion currently approved for the treatment of both obesity/overweight with T2D and as separate active pharmaceutical ingredients in drug addiction,but also from initial evidence that is emerging regarding glucagon-like peptide 1 receptor agonists that appear to be effective in the treatment of drug addiction.We hope that our hypothesis may be useful in interpreting the higher prevalence of CPDs and depression in patients with T2D compared with the general population and may help refine the integrated psychiatric-diabetic therapy approach to improve the treatment and or remission of T2D.

Saffron (Crocus sativus L.) and major depressive disorder:a meta-analysis of randomized clinical trials

Due to safety concerns and side effects of many antidepressant medications, herbal psychopharmacology research has increased, and herbal remedies are becoming increasingly popular as alternatives to prescribed medications for the treatment of major depressive disorder （MDD）. Of these, accumulating trials reveal positive effects of the spice saffron （Crocus sativus L.） for the treatment of depression. A comprehensive and statistical review of the clinical trials examining the effects of saffron for treatment of MDD is warranted. OBJECTIVE： The purpose of this study was to conduct a meta-analysis of published randomized controlled trials examining the effects of saffron supplementation on symptoms of depression among participants with MDD. SEARCH STRATEGY： We conducted electronic and non-electronic searches to identify all relevant randomized, double-blind controlled trials. Reference lists of all retrieved articles were searched for relevant studies. INCLUSION CRITERIA： The criteria for study selection included the following： （1） adults （aged 18 and older） with symptoms of depression, （2） randomized controlled trial, （3） effects of saffron supplementation on depressive symptoms examined, and （4） study had either a placebo control or antidepressant comparison group. DATA EXTRACTION AND ANALYSIS： Using random effects modeling procedures, we calculated weighted mean effect sizes separately for the saffron supplementation vs placebo control groups, and for the saffron supplementation vs antidepressant groups. The methodological quality of all studies was assessed using the Jadad score. The computer software Comprehensive Meta- analysis 2 was used to analyze the data. RESULTS： Based on our pre-specified criteria, five randomized controlled trials （n = 2 placebo controlled trials, n = 3 antidepressant controlled trials） were included in our review. A large effect size was found for saffron supplementation vs placebo control in treating depressive symptoms （M ES = 1.62, P 〈 0.001）, revealing that saffron supplementation significantly reduced depression symptoms compared to the placebo control. A null effect size was evidenced between saffron supplementation and the antidepressant groups （M ES = -0.15） indicating that both treatments were similarly effective in reducing depression symptoms. The mean Jadad score was 5 indicating high quality of trials. CONCLUSION： Findings from clinical trials conducted to date indicate that saffron supplementation can improve symptoms of depression in adults with MDD. Larger clinical trials, conducted by research teams outside of Iran, with long-term follow-ups are needed before firm conclusions can be made regarding saffron＇s efficacy and safety for treating depressive symptoms.

Metabolomic and structural brain connectomic evidence validating traditional Chinese medicine diagnostic classification of major depressive disorder

OBJECTIVE Major depressive disorder(MDD) is a highly heterogeneous mental illness.Further classification may help characterize its heterogeneity.The purpose of this study was to examine metabolomic and brain connectomic associations with traditional Chinese medicine(TCM) diagnostic classification of MDD.METHODS Fifty unmedicated depressed patients were classified into Liver Qi Stagnation(LQS,n=30) and Heart and Spleen Deficiency(HSD,n=20) subtypes according to TCM diagnosis.Healthy volunteers(n=28) were included as controls.Gas chromatography-mass spectrometry(GC-MS) and diffusion tensor imaging were used to detect serum and urinary metabolomic profiles and whole-brain white matter connectivity,respectively.RESULTS In metabolomic analysis,28 metabolites were identified for good separations between TCM subtypes and healthy controls in serum and urine samples.While both TCM subtypes had similar profiles in proteinogenic branched-chain amino acids and energy metabolism-related metabolites that were differentiated from healthy controls,the LQS subtype additionally differed from healthy controls in multiple amino acid metabolites that are involved in the biosynthesis of monoamine and amino acid neurotransmitters.Several metabolites are differentially associated with the two subtypes.In connectomic analysis,The LQS subtype showed significant differences in multiple network metrics of the angular gyrus,middle occipital gyrus,calcarine sulcus,and Heschl′ s gyrus when compared to the other two groups.The HSD subtype had markedly greater regional connectivity of the insula,parahippocampal gyrus,and posterior cingulate gyrus than the other two groups,and microstructural abnormalities of the frontal medial orbital gyrus and middle temporal pole.The insular betweenness centrality was strongly inversely correlated with the severity of depression and dichotomized the two subtypes at the optimal cutoff value with acceptable sensitivity and specificity.CONCLUSION The LQS subtype may represent an MDD subpopulation mainly characterized by abnormalities in the biosynthesis of monoamine and amino acid neurotransmitters,closer associations with stress-related pathophysiology,and aberrant connectivity of the audiovisual perception-related temporal-occipital network,whereas the HSD subtype is more closely associated with hyperconnectivity and microstructural abnormalities of the limbicparalimbic network.Certain metabolomic and connectomic variables are potential biomarkers for TCM diagnostic subtypes which is perhaps an alternative classification for depressive disorders.

Abnormal activation of the occipital lobes during emotion picture processing in major depressive disorder patients

A large number of studies have demonstrated that depression patients have cognitive dysfunction. With recently developed brain functional imaging, studies have focused on changes in brain function to investigate cognitive changes. However, there is still controversy regarding abnormalities in brain functions or correlation between cognitive impairment and brain function changes. Thus, it is important to design an emotion-related task for research into brain function changes. We selected positive, neutral, and negative pictures from the International Affective Picture System. Patients with major depressive disorder were asked to judge emotion pictures. In addition, functional MRI was performed to synchronously record behavior data and imaging data. Results showed that the total correct rate for recognizing pictures was lower in patients compared with normal controls. Moreover, the consistency for recognizing pictures for depressed patients was worse than normal controls, and they frequently recognized positive pictures as negative pictures. The consistency for recognizing pictures was negatively correlated with the Hamilton Depression Rating Scale. Functional MRI suggested that the activation of some areas in the frontal lobe, temporal lobe, parietal lobe, limbic lobe, and cerebellum was enhanced, but that the activation of some areas in the frontal lobe, parietal lobe and occipital lobe was weakened while the patients were watching positive and neutral pictures compared with normal controls. The activation of some areas in the frontal lobe temporal lobe, parietal lobe, and limbic lobe was enhanced, but the activation of some areas in the occipital lobe were weakened while the patients were watching the negative pictures compared with normal controls. These findings indicate that patients with major depressive disorder have negative cognitive disorder and extensive brain dysfunction. Thus, reduced activation of the occipital lobe may be an initiating factor for cognitive disorder in depressed patients.

The norepinephrine transporter gene is associated with the retardation symptoms of major depressive disorder in the Han Chinese population

The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder. Consequently, the norepinephrine transporter gene is an attractive candidate in major depressive disorder research. In the present study, we evaluated the depression symptoms of subjects with major depressive disorder, who were all from the North of China and of Hart Chinese origin, using the Hamilton Depression Scale. We examined the relationship between two single nucleotide polymorphisms in the norepinephrine transporter, rs2242446 and rs5569, and the retardation symptoms of major depressive disorder using quantitative trait testing with the UNPHASED program, rs5569 was associated with depressed mood, and the GG genotype may be a risk factor for this; rs2242446 was associated with work and interest, and the TT genotype may be a risk factor for loss of interest. Our findings suggest that rs2242446 and rs5569 in the norepinephrine transporter gene are associated with the retardation symptoms of depression in the Hart Chinese population.