Relationships of Antidepressant Medication With Its Various Factors Including Nitrogen Dioxides Seasonality: Machine Learning Analysis Using National Health Insurance Data

Objective@#This study employs machine learning and population-based data to examine major factors of antidepressant medication including nitrogen dioxides (NO2) seasonality. @*Methods@#Retrospective cohort data came from Korea National Health Insurance Service claims data for 43,251 participants with the age of 15–79 years, residence in the same districts of Seoul and no history of antidepressant medication during 2002–2012. The dependent variable was antidepressant-free months during 2013–2015 and the 103 independent variables for 2012 or 2015 were considered, e.g., particulate matter less than 2.5 micrometer in diameter (PM2.5), PM10, NO2, ozone (O3), sulphur dioxide (SO2) and carbon monoxide (CO) in each of 12 months in 2015. @*Results@#It was found that the Cox hazard ratios of NO2 were statistically significant and registered values larger than 10 for every three months: March, June–July, October, and December. Based on random forest variable importance and Cox hazard ratios in brackets, indeed, the top 20 factors of antidepressant medication included age (0.0041 [1.69–2.25]), migraine and sleep disorder (0.0029 [1.82]), liver disease (0.0017 [1.33–1.34]), exercise (0.0014), thyroid disease (0.0013), cardiovascular disease (0.0013 [1.20]), asthma (0.0008 [1.19–1.20]), September NO2 (0.0008 [0.01]), alcohol consumption (0.0008 [1.31–1.32]), gender - woman (0.0007 [1.80–1.81]), July NO2 (0.0007 [14.93]), July PM10 (0.0007), the proportion of the married (0.0005), January PM2.5 (0.0004), September PM2.5 (0.0004), chronic obstructive pulmonary disease (0.0004), economic satisfaction (0.0004), January PM10 (0.0003), residents in welfare facilities per 1,000 (0.0003 [0.97]), and October NO2 (0.0003). @*Conclusion@#Antidepressant medication has strong associations with neighborhood conditions including NO2 seasonality and welfare support.

Childhood Sexual Abuse and Cortical Thinning in Adults With Major Depressive Disorder

Objective@#A growing body of evidence reports on the effect of different types of childhood abuse on the structural and functional architecture of the brain. In the present study, we aimed to investigate the differences in cortical thickness according to specific types of childhood abuse between patients with major depressive disorder (MDD) and healthy controls (HCs). @*Methods@#A total of 61 patients with MDD and 98 HCs were included in this study. All participants underwent T1-weighted magnetic resonance imaging, and the occurrence of childhood abuse was assessed using the Childhood Trauma Questionnaire. We investigated the association between whole-brain cortical thickness and exposure to any type of childhood abuse and specific type of childhood abuse in the total sample using the FreeSurfer software. @*Results@#No significant difference was reported in the cortical thickness between the MDD and HC groups nor between the “any abuse” and “no abuse” groups. Compared to no exposure to childhood sexual abuse (CSA), exposure to CSA was significantly associated with cortical thinning in the left rostral middle frontal gyrus (p=0.00020), left (p=0.00240), right fusiform gyri (p=0.00599), and right supramarginal gyrus (p=0.00679). @*Conclusion@#Exposure to CSA may lead to cortical thinning of the dorsolateral prefrontal cortex, which is deeply involved in emotion regulation, to a greater extent than other types of childhood abuse.

Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice

Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.

The Indirect Effect of Prefrontal Gray Matter Volume on Suicide Attempts among Individuals with Major Depressive Disorder

Trait impulsivity is a known risk factor for suicidality, and the prefrontal cortex plays a key role in impulsivity and its regulation. However, the relationship between trait impulsivity, neural basis, and suicidality has been inconsistent. Therefore, this study aimed to explore the relationship between impulsivity and its structural correlates (prefrontal gray matter volume), suicidal ideation, and actual suicide attempts. A total of 87 individuals with major depressive disorder participated in study, and the gray matter volume of the prefrontal regions was extracted from T1 images based on region of interest masks. The variables for the mediation models were selected based on correlation analysis and tested for their ability to predict suicide attempts, with impulsivity and suicidal ideation as the mediation variables and gray matter volume as the independent variable. A significant correlation was observed between suicidal ideation and the left dorsolateral prefrontal cortex and right dorsomedial prefrontal cortex. The dual-mediation model revealed a significant indirect relationship between gray matter volume in both regions and suicide attempts mediated by motor impulsivity and suicidal ideation. The counterintuitive positive relationship between gray matter volume and suicidality was also discussed.

Cortical Thickness and Surface Area Abnormalities in Bipolar I and II Disorders

Objective@#Although bipolar II disorder (BD II) is not simply a mitigated form of bipolar I disorder (BD I), their neurobiological differences have not been elucidated. The present study aimed to explore cortical thickness (CT) and surface area (SA) in patients with BD I and BD II and healthy controls (HCs) to investigate the shared and unique neurobiological mechanisms of BD subtypes. @*Methods@#We enrolled 30 and 44 patients with BD I and BD II, respectively, and 100 HCs. We evaluated CT and SA using FreeSurfer and estimated differences in CT and SA among the three groups (BD I vs. BD II vs. HC). We adjusted for age, sex, educational level, and intracranial volume as confounding factors. @*Results@#We found widespread cortical thinning in the bilateral frontal, temporal, and occipital regions; cingulate gyrus; and insula in patients with BD. Alterations in SA, including increased SA of the pars triangularis and decreased SA of the insula, were noted in patients with BD. Overall, we found BD II patients demonstrated decreased SA in the right long insula compared to BD I patients. @*Conclusion@#Our results suggest that decreased SA in the right long insula is crucial for differentiating BD subtypes.

Association of Prefrontal Cortex Thinning with High Impulsivity in Healthy Adults

Objective@#Studies have been conducted to identify brain structural alterations related to high impulsivity in psychiatric populations. However, research on healthy subjects is relatively less extensive. Therefore, we aimed to investigate the correlation between the cortical thickness of whole brain regions and the impulsivity level in a healthy population. @*Methods@#We included 100 healthy participants aged 19–65 years. Their T1-weighted magnetic resonance images and the 23-item Barratt Impulsiveness Scale (BIS) score were obtained. The patients were divided into high and low impulsivity groups according to the 75th percentile score of the BIS in the sample. The thickness of each cortical region was calculated using the FreeSurfer, and the difference in cortical thickness of the whole brain between the high and low impulsivity groups was analyzed using one-way analysis of covariance including age, sex, education level, and total intracranial cavity volume as covariates. @*Results@#The high impulsivity group showed significant cortical thinning in the left pars opercularis. The cortical thickness of the left pars opercularis significantly correlated negatively with the total, attention, and motor scores of the BIS scale. @*Conclusion@#Our findings suggest that prefrontal cortex thinning may play an important role in the development of high impulsivity in healthy adults.

How Inflammation Affects the Brain in Depression:A Review of Functional and Structural MRI Studies

This narrative review discusses how peripheral and central inflammation processes affect brain function and structure in depression, and reports on recent peripheral inflammatory marker-based functional and structural magnetic resonance imaging (MRI) studies from the perspective of neural-circuit dysfunction in depression. Chronic stress stimulates the activity of microglial cells, which increases the production of pro-inflammatory cytokines in the brain. In addition, microglial activation promotes a shift from the synthesis of serotonin to the synthesis of neurotoxic metabolites of the kynurenine pathway, which induces glutamatemediated excitotoxicity in neurons. Furthermore, the region specificity of microglial activation is hypothesized to contribute to the vulnerability of specific brain regions in the depressionrelated neural circuits to inflammation-mediated brain injury. MRI studies are increasingly investigating how the blood levels of inflammatory markers such as C-reactive protein, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α are associated with functional and structural neuroimaging markers in depression. Functional MRI studies have found that peripheral inflammatory markers are associated with aberrant activation patterns and altered functional connectivity in neural circuits involved in emotion regulation, reward processing, and cognitive control in depression. Structural MRI studies have suggested that peripheral inflammatory markers are related to reduced cortical gray matter and subcortical volumes, cortical thinning, and decreased integrity of white matter tracts within depression-related neural circuits. These neuroimaging findings may improve our understanding of the relationships between neuroinflammatory processes at the molecular level and macroscale in vivo neuralcircuit dysfunction in depression.

Cortical Thickness and Surface Area Abnormalities in Bipolar I and II Disorders

Objective@#Although bipolar II disorder (BD II) is not simply a mitigated form of bipolar I disorder (BD I), their neurobiological differences have not been elucidated. The present study aimed to explore cortical thickness (CT) and surface area (SA) in patients with BD I and BD II and healthy controls (HCs) to investigate the shared and unique neurobiological mechanisms of BD subtypes. @*Methods@#We enrolled 30 and 44 patients with BD I and BD II, respectively, and 100 HCs. We evaluated CT and SA using FreeSurfer and estimated differences in CT and SA among the three groups (BD I vs. BD II vs. HC). We adjusted for age, sex, educational level, and intracranial volume as confounding factors. @*Results@#We found widespread cortical thinning in the bilateral frontal, temporal, and occipital regions; cingulate gyrus; and insula in patients with BD. Alterations in SA, including increased SA of the pars triangularis and decreased SA of the insula, were noted in patients with BD. Overall, we found BD II patients demonstrated decreased SA in the right long insula compared to BD I patients. @*Conclusion@#Our results suggest that decreased SA in the right long insula is crucial for differentiating BD subtypes.

Association of Prefrontal Cortex Thinning with High Impulsivity in Healthy Adults

Objective@#Studies have been conducted to identify brain structural alterations related to high impulsivity in psychiatric populations. However, research on healthy subjects is relatively less extensive. Therefore, we aimed to investigate the correlation between the cortical thickness of whole brain regions and the impulsivity level in a healthy population. @*Methods@#We included 100 healthy participants aged 19–65 years. Their T1-weighted magnetic resonance images and the 23-item Barratt Impulsiveness Scale (BIS) score were obtained. The patients were divided into high and low impulsivity groups according to the 75th percentile score of the BIS in the sample. The thickness of each cortical region was calculated using the FreeSurfer, and the difference in cortical thickness of the whole brain between the high and low impulsivity groups was analyzed using one-way analysis of covariance including age, sex, education level, and total intracranial cavity volume as covariates. @*Results@#The high impulsivity group showed significant cortical thinning in the left pars opercularis. The cortical thickness of the left pars opercularis significantly correlated negatively with the total, attention, and motor scores of the BIS scale. @*Conclusion@#Our findings suggest that prefrontal cortex thinning may play an important role in the development of high impulsivity in healthy adults.

Alterations in the Occipital Cortex of Drug-Naïve Adults With Major Depressive Disorder: A Surface-Based Analysis of Surface Area and Cortical Thickness

Objective@#Advances in surface-based morphometric methods have allowed researchers to separate cortical volume into cortical thickness (CTh) and surface area (SA). Although CTh alterations in major depressive disorder (MDD) have been observed in numerous studies, few studies have described significant SA alterations. Our study aimed to measure patients’ SAs and to compare it with their CTh to examine whether SA exhibits alteration patterns that differ from those of CTh in drug-naïve patients with MDD. @*Methods@#A total of 71 drug-naïve MDD patients and 111 healthy controls underwent structural magnetic resonance imaging, and SA and CTh were analyzed between the groups. @*Results@#We found a smaller SA in the left superior occipital gyrus (L-SOG) in drug-naïve patients with MDD. In the CTh analysis, the bilateral fusiform gyrus, left middle occipital gyrus, left temporal superior gyrus, and right posterior cingulate showed thinner cortices in patients with MDD, while the CTh of the bilateral SOG, right straight gyrus, right posterior cingulate, and left lingual gyrus were increased. @*Conclusion@#Compared with the bilateral occipito-temporal changes in CTh, SA alterations in patients with MDD were confined to the L-SOG. These findings may improve our understanding of the neurobiological mechanisms of SA alteration in relation to MDD.

How Inflammation Affects the Brain in Depression:A Review of Functional and Structural MRI Studies

This narrative review discusses how peripheral and central inflammation processes affect brain function and structure in depression, and reports on recent peripheral inflammatory marker-based functional and structural magnetic resonance imaging (MRI) studies from the perspective of neural-circuit dysfunction in depression. Chronic stress stimulates the activity of microglial cells, which increases the production of pro-inflammatory cytokines in the brain. In addition, microglial activation promotes a shift from the synthesis of serotonin to the synthesis of neurotoxic metabolites of the kynurenine pathway, which induces glutamatemediated excitotoxicity in neurons. Furthermore, the region specificity of microglial activation is hypothesized to contribute to the vulnerability of specific brain regions in the depressionrelated neural circuits to inflammation-mediated brain injury. MRI studies are increasingly investigating how the blood levels of inflammatory markers such as C-reactive protein, interleukin (IL)-1β, IL-6, and tumor necrosis factor-α are associated with functional and structural neuroimaging markers in depression. Functional MRI studies have found that peripheral inflammatory markers are associated with aberrant activation patterns and altered functional connectivity in neural circuits involved in emotion regulation, reward processing, and cognitive control in depression. Structural MRI studies have suggested that peripheral inflammatory markers are related to reduced cortical gray matter and subcortical volumes, cortical thinning, and decreased integrity of white matter tracts within depression-related neural circuits. These neuroimaging findings may improve our understanding of the relationships between neuroinflammatory processes at the molecular level and macroscale in vivo neuralcircuit dysfunction in depression.

Network Analysis of the Symptoms of Depressive Disorders Over the Course of Therapy: Changes in Centrality Measures

Objective@#Network analysis can be used in terms of a novel psychopathological approach for depressive syndrome. We aimed to estimate the successive network structures of depressive symptoms in patients with depressive disorder using data from the Clinical Research Center for Depression study. @*Methods@#We enrolled 1,152 South Korean adult patients with depressive disorders who were beginning treatment for first-onset or recurrent depressive episodes. We examined the network structure of the severities of the items on the Hamilton Depression Rating Scale (HAMD) at baseline and at weeks 2, 12, 25, and 52. The node strength centrality of all the HAMD items at baseline and at week 2, 12, 25, and 52 in terms of network analysis. @*Results@#In the severity networks, the anxiety (psychic) item was the most centrally situated in the initial period (baseline and week 2), while loss of weight was the most centrally situated item in the later period (weeks 25 and 52). In addition, the number of strong edges (i.e., edges representing strong correlations) increased in the late period compared to the initial period. @*Conclusion@#Our findings support a period-specific and symptom-focused therapeutic approach that can provide complementary information to the unidimensional total HAMD score.

Morphologic Alterations in Amygdala Subregions of Adult Patients with Bipolar Disorder

OBJECTIVES: Previous studies have revealed inconsistent results on amygdala volume in adult bipolar disorder (BD) patients compared to healthy controls (HC). Since the amygdala encompasses multiple subregions, the subtle volume changes in each amygdala nucleus might have not been fully reflected in the measure of the total amygdala volume, causing discrepant results. Thus, we aimed to investigate volume changes in each amygdala subregion and their association with subtypes of BD, lithium use and clinical status of BD. METHODS: Fifty-five BD patients and 55 HC underwent T1-weighted structural magnetic resonance imaging. We analyzed volumes of the whole amygdala and each amygdala subregion, including the anterior amygdaloid area, cortico-amygdaloid transition area, basal, lateral, accessory basal, central, cortical, medial and paralaminar nuclei using the atlas in the FreeSurfer. The volume difference was analyzed using a one-way analysis of covariance with individual volumes as dependent variables, and age, sex, and total intracranial volume as covariates. RESULTS: The volumes of whole right amygdala and subregions including basal nucleus, accessory basal nucleus, anterior amygdaloid area, and cortico-amygdaloid transition area in the right amygdala of BD patients were significantly smaller for the HC group. No significant volume difference between bipolar I disorder and bipolar II disorder was found after the Bonferroni correction. The trend of larger volume in medial nucleus with lithium treatment was not significant after the Bonferroni correction. No significant correlation between illness duration and amygdala volume, and insignificant negative correlation were found between right central nucleus volume and depression severity. CONCLUSIONS: Significant volume decrements of the whole amygdala, basal nucleus, accessory basal nucleus, anterior amygdaloid area, and cortico-amygdaloid transition area were found in the right hemisphere in adult BD patients, compared to HC group. We postulate that such volume changes are associated with altered functional activity and connectivity of amygdala nuclei in BD.

Examining Patterns of Polypharmacy in Bipolar Disorder: Findings from the REAP-BD, Korea

Based on Korean data from the Research on Asian Psychotropic Prescription Pattern for Bipolar Disorder, this study tried to present prescription patterns in biopolar disorder (BD) and its associated clinical features. Based on the information obtained from the study with structured questions, the tendency of prescription pattern was studied and analyzed. Polypharmacy was predominant, including simple polypharmacy in 51.1% and complex polypharmacy in 34.2% of patients. Subjects associated with simple or complex polypharmacy were significantly younger, had higher inpatient settings, a larger portion of onset with manic episode, a shorter duration of untreated illness, a shorter duration of current episode, were more overweight, used less antidepressants and used more anxiolytics. These findings can suggest higher polypharmacy rate in more severe BD and highlight the necessity of monitoring the weight of subjects with polypharmacy.

Erratum: Morphologic Alterations in Amygdala Subregions of Adult Patients with Bipolar Disorder

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Changes in the Volume and Cortical Thickness of the Specific Regions of Cerebellum of Patients with Major Depressive Disorder

OBJECTIVES: A growing body of evidence has suggested that morphologic changes in cerebellum may be implicated with pathophysiology of major depressive disorder (MDD). The aim of this study is to investigate a difference in the volume and cortical thickness of the specific region of cerebellum between patients with MDD and healthy controls (HC). METHODS: A total of 127 patients with MDD and 105 HC participated in this study and underwent T1-weighted structural magnetic resonance imaging. We analyzed volume and cortical thickness of each twelve cerebellum regions divided by left and right and the volume and cortical thickness of the whole cerebellum from T1-weigted image of participants. One-way analysis of covariance was used to investigate the volume and cortical thickness difference of total and specific regions between two groups adjusting for age, gender, medication, and total intracranial cavity volume. RESULTS: We found that the patients with MDD had significantly greater volume in the left cerebellum lobule III region [false discovery rate (FDR)-corrected p = 0.034] compared to HC. Also, our findings indicate that cortical thickness of left lobule VIIB (FDR-corrected p = 0.032) and lobule VIIIB (FDR-corrected p = 0.032) are significantly thinner in the patients with MDD compared with the HC. No significant volume and cortical thickness differences were observed in other sub-regions of the cerebellum. The volumes and cortical thickness of whole cerebellum between patients with MDD and HC did not differ significantly. CONCLUSIONS: We observed the region-specific volume and cortical thickness difference in cerebellum between the patients with MDD and HC. The results of our study implicate that the information about structural alterations in cerebellum with further replicative studies might provide a stepping stone toward a specific marker to diagnose MDD.

Current Clinical Applications of Diffusion-Tensor Imaging in Neurological Disorders

Diffusion-tensor imaging (DTI) is a noninvasive medical imaging tool used to investigate the structure of white matter. The signal contrast in DTI is generated by differences in the Brownian motion of the water molecules in brain tissue. Postprocessed DTI scalars can be used to evaluate changes in the brain tissue caused by disease, disease progression, and treatment responses, which has led to an enormous amount of interest in DTI in clinical research. This review article provides insights into DTI scalars and the biological background of DTI as a relatively new neuroimaging modality. Further, it summarizes the clinical role of DTI in various disease processes such as amyotrophic lateral sclerosis, multiple sclerosis, Parkinson's disease, Alzheimer's dementia, epilepsy, ischemic stroke, stroke with motor or language impairment, traumatic brain injury, spinal cord injury, and depression. Valuable DTI postprocessing tools for clinical research are also introduced.

Alterations of Cortical Folding Patterns in Patients with Bipolar I Disorder: Analysis of Local Gyrification Index

OBJECTIVES: Local gyrification reflects the early neural development of cortical connectivity, and is regarded as a potential neural endophenotype in psychiatric disorders. Several studies have suggested altered local gyrification in patients with bipolar I disorder (BD-I). The purpose of the present study was to investigate the alterations in the cortical gyrification of whole brain cortices in patients with BD-I. METHODS: Twenty-two patients with BD-I and age and sex-matched 22 healthy controls (HC) were included in this study. All participants underwent T1-weighted structural magnetic resonance imaging (MRI). The local gyrification index (LGI) of 66 cortical regions were analyzed using the FreeSurfer (Athinoula A. Martinos Center for Biomedical Imaging). One-way analysis of covariance (ANCOVA) was used to analyze the difference of LGI values between two groups adjusting for age and sex as covariates. RESULTS: The patients with BD-I showed significant hypogyria in the left pars opercularis (uncorrected-p = 0.049), the left rostral anterior cingulate gyrus (uncorrected-p = 0.012), the left caudal anterior cingulate gyrus (uncorrected-p = 0.033). However, these findings were not significant after applying the multiple comparison correction. Severity or duration of illness were not significantly correlated with LGI in the patients with BD-I. CONCLUSIONS: Our results of lower LGI in the anterior cingulate cortex and the ventrolateral prefrontal cortex in the BD-I group implicate that altered cortical gyrification in neural circuits involved in emotion-processing may contribute to pathophysiology of BD-I.

Association between the Alu Insertion/Deletion Polymorphism in the Tissue-Type Plasminogen Activator Gene and Mirtazapine Response in Koreans with Major Depression

OBJECTIVES: To determine the relationship between the Alu insertion/deletion (I/D) polymorphism in the tissue-type plasminogen activator (tPA) gene and the clinical outcome of mirtazapine treatment in Korean major depressive disorder (MDD) patients. METHODS: We enrolled 422 patients in this study. Symptoms were evaluated using the 21-item Hamilton Depression Rating (HAMD-21) Scale. After 1, 2, 4, and 8 weeks of mirtazapine treatment, the association between the Alu I/D polymorphism in the tPA gene and remission/response outcomes were evaluated. RESULTS: The proportion of I/I homozygotes in responders was higher than that in non-responders, whereas the proportion of D/D homozygotes in responders was lower than that in non-responders at 8 weeks of treatment (p = 0.032, OR = 1.57). The percentage decline of HAMD-21 scores in I allele carriers was larger than that of D/D homozygotes at 2 and 8 weeks of treatment (p = 0.035 and 0.007, respectively). I allele carriers were associated with remission at 8 weeks of treatment (p = 0.047, OR = 2.2). CONCLUSIONS: These results show that treatment response and remission to mirtazapine were associated with the Alu I/D polymorphism of the tPA gene. This suggests the Alu I/D polymorphism may be a potential genetic marker for the prediction of therapeutic response to mirtazapine treatment in patients with MDD.

Associations between Vasomotor Symptoms and Depression, Stress and Quality of Life in Midlife Women / 정신신체의학

OBJECTIVES: The aim of this study was to evaluate the associations between vasomotor symptoms and factors such as sociodemographics, health behaviors, medical condition, depression, stress, anxiety, attitude toward menopause, and quality of life. METHODS: We conducted a cross-sectional study in peri- and post-menopausal women enrolled by the Korean Association of Health Promotion. Subjects submitted self-report questionnaires about vasomotor symptoms and other clinical symptoms. Associations between vasomotor symptoms and clinical variables were analyzed using stepwise multiple regression analyses. RESULTS: 1951 women completed self-report questionnaires and 1022 women were enrolled in the study. The prevalence of vasomotor symptoms in peri- and post-menopausal women was 63.9%. Variables showing significant differences between subjects with vasomotor symptoms and subjects without them were score of Beck Depression Inventory, Brief Encounter Psychosocial Instrument-Korean Version, proportions of clinically significant depression(Beck Depression Inventory≥16), Menopausal rating scale, attitude towards menopause, the 4 subscales of World Health Organization Quality of Life-BREF(Physical health, psychological, social relationships, environment), and a History of Premenstrual syndrome/Premenstrual dysphoric disorder. Stepwise multiple regression analyses indicated that Beck Depression Inventory, Brief Encounter Psychosocial Instrument-Korean Version, Menopausal Rating Scale, and the Psychological subscale of World Health Organization Quality of Life -BREF show associations with vasomotor symptoms. CONCLUSIONS: Menopausal vasomotor symptoms are associated with various psychological factors, especially with depression. Midlife women suffering vasomotor symptoms should therefore be screened for depression. Future prospective studies where clinical subjects are diagnosed using structured interviews, focusing on the causal relationship between depression and vasomotor symptoms are necessary.