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.

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.

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.

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.

Attribution retraining group therapy for outpatients with major depression disorder,generalized anxiety disorder,and obsessive-compulsive disorder:a pilot study

The aim of this present study is to examine the efficacy of attribution retraining group therapy （ARGT） and to compare the responses of outpatients with major depression disorder （MDD）, generalized anxiety disorder （GAD） and obsessive-compulsive disorder （OCD）. We carried out a prospective uncontrolled intervention study with a 8-weeks of ARGT on sixty three outpatients with MDD, GAD or OCD. Hamilton rating scale for depression, Hamilton rating scale for anxiety, Yale-Brown obsessive-compulsive scale, attribution style questionnaire, self-esteem scale, index of well-being, and social disability screening schedule were administered before and after treatment. Significant improvement in symptoms and psychological and social functions from pre- to posttreatment occurred for all participants. The changes favored MDD patients. Our study suggested that ARGT may improve the symptoms and psychological-social functions of MDD, GAD, and OCD patients. MDD patients showed the best response.

Characterization of event-related potentials in obsessive compulsive disorder patients: Comparison with depression and generalized anxiety disorder patients

BACKGROUND： Study results of event-refated potential in obsessive compulsive disorder （OCD） remain controversial, potentially as a result of different instruments utilized and their differing technical characteristics. OBJECTIVE： To investigate the differences in several common event-related potentials, Le. contingent negative variations, P300, and mismatch negativity （MMN）, in OCD patients, depression patients, generalized anxiety disorder （GAD） patients, and healthy controls. DESIGN, TIME AND SETTING： A case-control study was performed in the Department of Electrophysiology, Shanghai Mental Health Center from May 2002 to December 2005. PARTICIPANTS： A total of 38 OCD patients, 20 depression patients, and 18 GAD patients, who were diagnosed according to the criteria of Chinese Classification of Mental Disorders （Version 3）, formulated by the Chinese Psychiatry Association, were selected from the Outpatient Department of Shanghai Mental Health Center. Patients with two or more the above diseases were excluded. In addition, 28 healthy people, gender and age matched, were selected as controls. METHODS： Contingent negative variations, P300, and MMN were recorded by a Nicolet Spirit Instrument. All electrodes were attached at Cz according to the Intemationa11020 system, with the mastoid leads as reference and Fpz as ground. MAIN OUTCOME MEASURES： Amplitude and latency of contingent negative variations, P300, and MMN. RESULTS： The contingent negative variations, P300, and MMN were different （P 〈 0.01）. OCD patients showed an increased MI amplitude compared with controls, depression, and GAD patients （P 〈 0.01）. Target P300 amplitudes were significantly lower in OCD, depression, and GAD patients compared with controls （P 〈 0.01）. Moreover, N2 latency and latency of MMN were prolonged in OCD and depression groups compared with controls （P 〈 0.05）. CONCLUSION： Event-related potentials were different in depression, GAD, and OCD patients and healthy controls. In particular, OCD patients exhibited unique characteristics.

Review of Neuromyelitis Optica Spectrum Disorder with Pain-Depression Comorbidity

Neuromyelitis optica spectrum disorder(NMOSD)is an inflammatory disorder of the central nervous system predominantly targeting optic nerves and the spinal cord.The prevalence of the disease is much higher in Asia than in other parts of the world.Pain can be detected in more than 80%of NMOSD patients,with evoked pain mostly being caused by painful tonic muscle spasms and neuropathic pain as the most characteristic types.Depression is often comorbid with pain,and their comorbidity can severely influence quality of life.In recent years,studies have found considerable overlaps between the mechanisms of pain and depression;however,their association remains unclear.This article reviews the epidemiology,mechanism,evaluation and treatment of paindepression comorbidity in NMOSD patients.

Significance of music therapy in treating depression and anxiety disorders among people with cancer

Globally,cancer cases and mortality have recently escalated and have attracted global concern.The clinical diagnosis and manifestation of cancer can result in significant mental health issues like depression and anxiety disorders.The tendency of people with cancer to suffer from psychological disorders such as anxiety and depression is usually high.A significant number of deaths related to cancer may likely not be from the killer disease but from psychological disorders associated with the illness.The utilization of music as a remedial approach to healing mental disorders cannot be overstated.Thus,identifying the impacts of music therapy in dealing with depression and anxiety disorders among people with cancer is relevant,as the majority of methods used in treating cancer have some side effects which may trigger psychological disorders in cancer patients.Ultimately,this study explored the significance of music therapy in treating depression and anxiety disorders among people with cancer.To achieve the aim of this study,the authors employed a narrative literature review to investigate the significance of music therapy in addressing depression and anxiety disorders among people with cancer.The type of literature review employed in this study is to provide an understanding of the selected research papers.The review found that music therapy significantly reduces depression and anxiety disorders among breast cancer,lung cancer,prostate cancer,and colorectal cancer patients.It is needful for healthcare providers to incorporate music therapy interventions while treating people with cancer.This will help reduce cancer deaths resulting from psychological disorders rather than the killer disease,cancer.However,the standardized procedures and evaluation criteria for applying music-based intervention strategies in oncology medicine still need to be further established and improved.

Psychological trauma,posttraumatic stress disorder and traumarelated depression:A mini-review

There are various types of traumatic stimuli,such as catastrophic events like wars,natural calamities like earthquakes,and personal trauma from physical and psychological neglect or abuse and sexual abuse.Traumatic events can be divided into type I and type II trauma,and their impacts on individuals depend not only on the severity and duration of the traumas but also on individuals’self-evaluation of the traumatic events.Individual stress reactions to trauma include posttraumatic stress disorder(PTSD),complex PTSD and trauma-related depression.Trauma-related depression is a reactive depression with unclear pathology,and depression occurring due to trauma in the childhood has gained increasing attention,because it has persisted for a long time and does not respond to conventional antidepressants but shows good or partial response to psychotherapy,which is similar to the pattern observed for PTSD.Because trauma-related depression is associated with high risk of suicide and is chronic with a propensity to relapse,it is necessary to explore its pathogenesis and therapeutic strategy.

Effects of music therapy in depression and anxiety disorder

Mental disorders are considerate "the evil of the century" by renowned researchers, because a large part of the population in many countries is a diagnosticated, and currently afect youth and children. Among the numerous therapeutic interventions, the music therapy is a non-invasive approach. However, there are very few people who are professionally engaged in research and studies on the subject. Therefore, this article is a literature to talk about the benefits of music therapy sessions for people with stress, depression and anxiety disorders.

Increased P wave duration in patients with depression or anxiety disorder

BACKGROUND： Activation of the sympathetic nervous system plays an important role in regulating cardiovascular actions. P wave parameters can provide general information on central cardiovascular autonomic regulatory responses, which are altered in patients with anxiety disorders and depression. In particular, there are no reports addressing changes in P wave duration and dispersion. OBJECTIVE： To compare the differences in P wave duration and P wave dispersion between patients with anxiety disorders and depression, because patients with anxiety disorders and depression develop abnormal electrocardiograms. DESIGN, TIME AND SETTING： A non-randomized concurrent controlled study was performed. Patients with depression and general anxiety disorders were admitted at the psychiatry outpatient clinics of the Medical Faculty of Duezce University of Turkey between May 2005 and October 2006. PARTICIPANTS： A total of 71 consecutive patients with depression and anxiety disorders, as well as 50 physically and mentally healthy age- and gender-matched controls were selected. METHODS： Electrocardiogram records were obtained at the time of admission to the outpatient clinics. MAIN OUTCOME MEASURES： P wave duration and P wave dispersion were measured. RESULTS： Both the maximum （Prnax） and minimum （Pmin） P wave duration were greater in patients with psychiatric disorders than in healthy controls. Pmax was significantly greater in patients with depression or anxiety disorders （Bonferroni test, P 〈 0.017）. The P wave dispersion was similar between patients and controls （P 〉 0.017）. P waves were similar between panic patients and other anxiety patients. Beck depression results were positively correlated with Prawn and Prnax （r= 0.374, 0.302, P = 0.013, 0.049, respectively）, and not associated with P wave dispersion （P 〉 0.05）. CONCLUSION： Psychiatric disorders are associated with increases in Prnax, but not with P wave dispersion. The P wave changes were associated with the degree of depression.

THE COMPARATIVE STUDY OF EVENT RELATED POTENTIALSIN PATIENTS WITH OBSESSIVE COMPULSIVE DISORDER,DEPRESSION AND ANXIETY

Objective:To investigate the variations of contingent negative varisations(CNV),P300 and mismatch negativity (MMN) in patients with obsessive compulsive disorder(OCD),depressiopn and anxiety.MEthods:Event-related potentials CNV,P300 and MMN were recorded in 31 patients with OCD by Nicolet SPirit Instrument,and were compared with that of 20 depression controls(DC) and 17 anxiety controls(AC)and 28 normal controls(NC),Results:A significant difference of CNV among 4 sulbject groups was found in both post-imperative negative variation(PINV) and amplitudes(M1)(P<0.01)(emergence of PINV were 45%),60%,35%,and 4% in OCD,DC,AC and NC groups respectively),Compared with NC group,DC and AC groups showed decreased M1 amplitude(P<0.01).A significant difference of P300 among 4 groups was found in both latencies(Cz/N2) and P3 and nontarget-P2 amplitudes(P<0.05-0.01),The delayed MMN latencies of OCD and DC were similar to that of P300 changes,Conclusions:CNV,P300 and MMN are useful tools for assessing the brain malfunction of OCD,DC and AC,and its clinical application are suggested.The characteristics ERPs of those patients might be useful indexes in distinguishing OCD from DC and AC patients.

Rate of social anxiety disorder, its comorbidity with depression and paroxetine effects in outpatients in Japan

The prevalence of persons with social anxiety disorder (SAD) in Japan remains unknown. This study examined 293 patients with age between 20 and 60 at first visit on the outpatient clinic of psychiatry by the section of social phobia of M.I.N.I. and DSM-IV. After that, 10 patients with both SAD out of 16 patients (trial recruited) completed 12 weeks of treatment with paroxetine. Among 63 patients with 4 points and 40 patients with 3 points on the M.I.N.I., 21 patients (33%) and 16 patients (40%) were diagnosed as SAD on DSM-IV criteria, respectively. Together, 37 patients (12.6%) were diagnosed as SAD out of the 293 outpatients. Among 37 patients with SAD, 23 patients (62%) had comorbid depression. As for 10 patients after treatment with paroxetine, 8 patients improved from the point of recovery of depression (HAM-D scores below 10), whereas only 4 patients improved from the point of recovery of social phobia (L-SAS scores below 30). Three points as well as 4 points on the M.I.N.I. is meaningful for the diagnosis of SAD. For a while, paroxetine exerted less beneficial effects on SAD rather than on depression.