Artificial Intelligence-Based Major Depressive Disorder (MDD) Diagnosis Using Raman Spectroscopic Features of Plasma Exosomes.

In vitro diagnosis using biomarkers for major depressive disorder (MDD) can offer considerable advantages in overcoming the lack of objective tests for depression and treating more patients. Plasma exosomes can be novel biomarkers for MDD based on their ability to pass through the blood-brain barrier and offer brain-related information. Here, we demonstrate a novel and precise MDD diagnosis using deep learning analysis and surface-enhanced Raman spectroscopy (SERS) of plasma exosomes. Our system is implemented based on 28,000 exosome SERS signals, providing sample-wise prediction results. Notably, this approach shows remarkable performance in predicting 70 test samples unused in the training step, with an area under the curve (AUC) of 0.939, a sensitivity of 91.4%, and a specificity of 88.6%. In addition, we confirm that the diagnostic scores were correlated with the degree of depression. These results show the utility of exosomes as novel biomarkers for MDD diagnosis and suggest a novel approach for prescreening techniques for psychiatric disorders.

Association of DNA Methylation of the NLRP3 Gene with Changes in Cortical Thickness in Major Depressive Disorder.

The Nod-like receptor pyrin containing 3 (NLRP3) inflammasome has been reported to be a convergent point linking the peripheral immune response induced by psychological stress and neuroinflammatory processes in the brain. We aimed to identify differences in the methylation profiles of the NLRP3 gene between major depressive disorder (MDD) patients and healthy controls (HCs). We also investigated the correlation of the methylation score of loci in NLRP3 with cortical thickness in the MDD group using magnetic resonance imaging (MRI) data. A total of 220 patients with MDD and 82 HCs were included in the study, and genome-wide DNA methylation profiling of the NLRP3 gene was performed. Among the total sample, 88 patients with MDD and 74 HCs underwent T1-weighted structural MRI and were included in the neuroimaging-methylation analysis. We identified five significant differentially methylated positions (DMPs) in NLRP3. In the MDD group, the methylation scores of cg18793688 and cg09418290 showed significant positive or negative correlations with cortical thickness in the occipital, parietal, temporal, and frontal regions, which showed significant differences in cortical thickness between the MDD and HC groups. Our findings suggest that NLRP3 DNA methylation may predispose to depression-related brain structural changes by increasing NLRP3 inflammasome-related neuroinflammatory processes in MDD.

Decreased cortical gyrification in patients with bipolar disorder.

BACKGROUND: An aberrant neural connectivity has been known to be associated with bipolar disorder (BD). Local gyrification may reflect the early neural development of cortical connectivity and has been studied as a possible endophenotype of psychiatric disorders. This study aimed to investigate differences in the local gyrification index (LGI) in each cortical region between patients with BD and healthy controls (HCs). METHODS: LGI values, as measured using FreeSurfer software, were compared between 61 patients with BD and 183 HCs. The values were also compared between patients with BD type I and type II as a sub-group analysis. Furthermore, we evaluated whether there was a correlation between LGI values and illness duration or depressive symptom severity in patients with BD. RESULTS: Patients with BD showed significant hypogyria in various cortical regions, including the left inferior frontal gyrus (pars opercularis), precentral gyrus, postcentral gyrus, superior temporal cortex, insula, right entorhinal cortex, and both transverse temporal cortices, compared to HCs after the Bonferroni correction (p < 0.05/66, 0.000758). LGI was not associated with clinical factors such as illness duration, depressive symptom severity, and lithium treatment. No significant differences in cortical gyrification according to the BD subtype were found. CONCLUSIONS: BD appears to be characterized by a significant regionally localized hypogyria, in various cortical areas. This abnormality may be a structural and developmental endophenotype marking the risk for BD, and it might help to clarify the etiology of BD.

Volumetric alterations in subregions of the amygdala in adults with major depressive disorder.

BACKGROUND: Although major depressive disorder (MDD) has been associated with volumetric abnormalities in the amygdala, studies investigating the association between structural alterations of the amygdala and depression have yielded varying results. Since the amygdala comprises several subregions, it is difficult to detect subtle regional changes by measuring the total amygdala volume. This study aimed to examine the volume in each amygdala subregion in adults with and without a diagnosis of MDD. METHODS: A total of 147 participants with a current history of major depression and 144 healthy participants ranging in age from 19 to 64 years underwent 3T magnetic resonance imaging scanning. Automatic segmentation of the nine nuclei of the amygdala was performed using FreeSurfer. One-way analysis of covariance, with individual volumes as dependent variables, and age, sex, and total intracranial volume as covariates, was performed to analyze volume differences. RESULTS: Patients with MDD had significantly lower volumes of the entire amygdala and subregions, including the lateral nucleus and anterior amygdaloid area, than healthy volunteers (HCs). There were no significant associations between subregion volumes and antidepressant use, illness duration, or depression severity. LIMITATIONS: Our cross-sectional design cannot provide a causal relationship between the volume change in the amygdala subregion and the risk of MDD. CONCLUSION: Our findings suggest that specific amygdala subregions are more susceptible to volumetric alterations in patients with MDD than in HCs. These findings may advance our understanding of the neuroanatomic basis on MDD.

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.

Long working hours and depressive symptoms: moderation by gender, income, and job status.

BACKGROUND: Long working hours can be a risk factor for poor mental health; however, little is known about the potential factors moderating their relation. This study investigates the association between working hours and depressive symptoms, and explores the potential moderating effect of gender, income level, and job status on this association using a nationally representative sample of working population in South Korea. METHODS: Data of 7,082 workers aged 19 years or above were obtained from the Korea National Health and Nutrition Examination Surveys (KNHANES) conducted in 2014, 2016, and 2018 in South Korea. Working hours were categorized into 35-39, 40, 41-52, 53-68, and ≥69 hours/week. Depressive symptoms were evaluated using the Patient Health Questionnaire-9 (PHQ-9). RESULTS: Individuals working ≥69 hours/week were more likely to have moderate to severe depressive symptoms compared to those working 40 hours/week. The association between longer working hours and depressive symptoms was especially prominent in female workers, standard wage workers, and workers with low income levels. We observed significant partial mediation pathways between working hours and PHQ-9 scores through both perceived usual stress level and self-rated health in the total sample. LIMITATIONS: The cross-sectional design of the study limits causal interpretation of the findings. CONCLUSION: Working longer than the legal upper limit of 52 hours/week puts workers at a greater risk for depression. Females, low-income workers, and wage workers are more vulnerable to the negative consequences of long working hours on mental health.

Predictive inflammatory biomarkers for change in suicidal ideation in major depressive disorder and panic disorder: A 12-week follow-up study.

Previous studies have investigated the role of inflammatory markers in suicidality of patients with major depressive disorder (MDD) or panic disorder (PD). However, few studies have investigated associations between serum inflammatory cytokine levels and suicidality. We hypothesized that MDD and PD status might be significantly associated with serum inflammatory cytokines and that we could predict levels of improvement in suicide ideation intensity using serum inflammatory biomarkers in patients with MDD and PD. For this study, 41 patients with MDD, 52 patients with PD, and 59 healthy control (HC) subjects were enrolled. Psychological measurements and serum inflammatory markers such as interleukin (IL) -6, -10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and C reactive protein (CRP) were examined. A total of five visits were completed during 12 weeks. After controlling for confounding factors, log-transformed IL-6 (ln_IL-6) at baseline (MDD: 0.297 ± 0.626; PD: 0.342 ± 0.723; HC: -0.121 ± 0.858; p = 0.007, >0.0017, 0.05/30) and mean ln_IL-6 (MDD: 0.395 ± 0.550, PD: 0.249 ± 0.544, HC: -0.139 ± 0.622, p = 0.002, >0.0017, 0.05/30) levels were trends towards significantly higher in patients with MDD and PD than in HC. In MDD patients, a higher level of basal ln_TNF-α was a significant predictor of ΔSSI (changes in SSI scores between baseline and week 12) even after controlling for changes of depression symptoms and baseline SSI scores (standardized ß = 0.541, p = 0.002 < 0.0028, 0.05/18). In conclusion, we could predict ΔSSI using baseline inflammatory biomarkers for patients with MDD.

Risk of Suicide Attempt after Thyroidectomy: A Nationwide Population Study in South Korea.

OBJECTIVE: To investigate the association between thyroidectomy and suicide attempt. METHODS: A nationwide population-based electronic medical records database of South Korea between January 1, 2009 and June 30, 2016 was used to investigate incidence rate ratios (IRRs) of suicide attempts and probable suicide attempts before and after thyroidectomy using a self-controlled case series design. RESULTS: In 2,986 patients who attempted suicide or probable suicide, the IRRs of suicidal behaviors during risk periods one year before and after thyroidectomy were investigated. Generally, after thyroidectomy, there was no increase in IRR compared to the non-risk period. When data were analyzed according to thyroidectomy type, after partial thyroidectomy, IRR increased up to 1.43 (95% CI: 1.03-1.98, p=0.032) in the days 91-181 period. In the subgroup with major depressive disorder (MDD), the IRR increased up to 1.74 (95% CI: 1.21-2.51, p=0.003) before thyroidectomy, and increased up to 1.67 (95% CI: 1.16-2.41, p=0.006) after thyroidectomy. CONCLUSION: Although the general risk of suicide attempt was not increased after thyroidectomy, patients with MDD showed increased risk of suicide attempt before and after thyroidectomy. These results suggest that suicidality should be evaluated when depressive symptoms are present in patients who have undergone thyroidectomy.

Social participation and depressive symptoms in community-dwelling older adults: Emotional social support as a mediator.

Previous studies have documented the protective effects of social participation on depression in older adults. In this study, we investigated the association between social participation and depressive symptoms and the associated gender difference in older adults. In addition, we explored the mediating role of emotional social support in the association between social participation and depressive symptoms. We collected data from 4751 community-dwelling adults aged 60 and above from the Korean Retirement and Income Study (KReIS) conducted in 2017 and 2018. The relationship between social participation (participation in different types of activities, frequency of participation, and the number of activities participated) and the risk for depressive symptoms was examined. Older adults who participated in social activity, volunteer work, and donation had decreased risk of depressive symptoms. More frequent and more diverse participation in activities further reduced the risk. Overall, women benefited more from social participation than men. Importantly, emotional social support significantly mediated the relationship between social participation and depressive symptoms. Social participation was associated lower odds for depression in older adults, particularly in older women. Our findings provided one of very few pieces of evidence that documents the mediating role of emotional social support in the relationship between social participation and depression among the elderly.

Shape and Volumetric Differences in the Corpus Callosum between Patients with Major Depressive Disorder and Healthy Controls.

OBJECTIVE: This study aimed to investigate the morphometric differences in the corpus callosum between patients with major depressive disorder (MDD) and healthy controls and analyze their relationship to gray matter changes. METHODS: Twenty female MDD patients and 21 healthy controls (HCs) were included in the study. To identify the difference in the regional gray matter concentration (GMC), VBM was performed with T1 magnetic resonance imaging. The shape analysis of the corpus callosum was processed. Diffusion tensor imaging (DTI) fiber-tracking was performed to identify the regional tract pathways in the damaged corpus callosal areas. RESULTS: In the shape analysis, regional shape contractions in the rostrum and splenium were found in the MDD patients. VBM analysis showed a significantly lower white matter concentration in the genu and splenium, and a significantly lower GMC in the frontal, limbic, insular, and temporal regions of the MDD patients compared to the HCs. In DTI fiber-tracking, the fibers crossing the damaged areas of the genu, rostrum, and splenium were anatomically connected to the areas of lower GMC in MDD patients. CONCLUSION: These findings support that major depressive disorder may be due to disturbances in multiple neuronal circuits, especially those associated with the corpus callosum.

Heart Rate Variability for the Prediction of Treatment Response in Major Depressive Disorder.

Major depressive disorder (MDD) is one of the disabling diseases in the world-wide, and known to increase cardiac morbidity and mortality. Therefore, previous studies related heart rate variability (HRV) have been conducted to evaluate and diagnose MDD, and to predict treatment outcomes in patient with MDD. We reviewed extensively on the previous peer-reviewed publications associated with this issue, using Pub-Med. In this review article, we introduce the basic concept of HRV and HRV measures, and present several important findings associated with diagnosis and treatment prediction in MDD with using HRV parameters. Furthermore, we discuss the possible underlying mechanism of this phenomenon, and suggest several considerations for the future research.

Changes in cortical thickness and volume of cerebellar subregions in patients with bipolar disorders.

BACKGROUND: Numerous studies have suggested that structural changes in the cerebellum are implicated in the pathophysiology of bipolar disorder (BD). We aimed to investigate differences in the volume and cortical thickness of the cerebellar subregions between patients with BD and healthy controls (HCs). METHODS: Ninety patients with BD and one hundred sixty-six HCs participated in this study and underwent T1-weighted structural magnetic resonance imaging. We analyzed the volume and cortical thickness of each cerebellar hemisphere divided into 12 subregions using T1-weighted images of participants. One-way analysis of covariance was used to evaluate differences between the groups, with age, sex, medication, and total intracranial cavity volume used as covariates. RESULTS: The BD group had significantly increased cortical thickness of the cerebellum in all cerebellar subregions compared to the HC group. The cortical thicknesses of the whole cerebellum and each hemisphere were also significantly thicker in the BD group than in the HC group. The volume of the left lobule IX was significantly lower in patients with BD than in HCs, whereas no significant differences in the volumes were observed in the other subregions. LIMITATIONS: Our cross-sectional design cannot provide a causal relationship between the increased cortical thickness of the cerebellum and the risk of BD. CONCLUSIONS: We observed widespread and significant cortical thickening in all the cerebellar subregions. Our results provide evidence for the involvement of the cerebellum in BD. Further studies are required to integrate neurobiological evidence and structural brain imaging to elucidate the pathophysiology of BD.

Shape Deformation in the Brainstem of Medication-Naïve Female Patients with Major Depressive Disorder.

OBJECTIVE: Although neuroimaging studies have shown volumetric reductions, such as the anterior cingulate, prefrontal cortices, and hippocampus in patients with major depressive disorder (MDD), few studies have investigated the volume of or shape alterations in the subcortical regions and the brainstem. We hypothesized that medication-naïve female adult patients with MDD might present with shape and volume alterations in the subcortical regions, including the brainstem, compared to healthy controls (HCs). METHODS: A total of 20 medication-naïve female patients with MDD and 21 age-matched female HCs, underwent 3D T1-weighted structural magnetic resonance scanning. We analyzed the volumes of each subcortical region and each brainstem region, including the midbrain, pons, and medulla oblongata. We also performed surface-based vertex analyses on the subcortical areas and brainstem. RESULTS: Female patients with MDD showed non-significant volumetric differences in the subcortical regions, whole brainstem, and each brainstem region compared to the HCs. However, in the surface-based vertex analyses, significant shape contractions were observed in both cerebellar peduncles located on the lateral wall of the posterior brainstem [threshold-free cluster enhancement, corrected for family-wise error (FWE) at p<0.05] in patients with MDD. CONCLUSION: We revealed shape alterations in the posterior brainstem in female patients with MDD.

Comparison of shape alterations of the thalamus and caudate nucleus between drug-naïve major depressive disorder patients and healthy controls.

BACKGROUND: Although structural alterations have been reported in patients with major depressive disorder (MDD), very few studies have compared the shape alterations of the subcortical regions between drug-naïve MDD patients and healthy controls (HCs). Therefore, we investigated and compared the subcortical shape alterations and volumetric changes between drug-naïve MDD patients and HCs in this study. METHODS: This study included 45 drug-naïve MDD patients and 83 HCs, who underwent three-dimensional (3-D) T1-weighted structural magnetic resonance imaging. Surface-based vertex analysis (SVA) was performed with automated segmentation of the bilateral caudate nuclei, putamina, nuclei accumbens, thalami, pallidum, hippocampi, amygdalae, and brainstem. SVA revealed regional contractions of the thalamus (bilateral medial and lateral nuclei) and right caudate nucleus (medial wall and anterosuperior areas) in the drug-naïve MDD patients when compared to HCs RESULTS: In volume analysis, the drug-naïve MDD patients showed a significant decrease in the volume of bilateral thalami compared with HCs (after Bonferroni correction p < 0.003). We identified morphometric contractions in bilateral thalami and right caudate nucleus in the drug-naïve MDD patients (p < 0.05). CONCLUSIONS: The present study implied that with cortical shape changes, the subcortical brain alterations could contribute to emotional dysregulation in the drug-naïve MDD patients.

Comorbid Anxiety and Depression: Clinical and Conceptual Consideration and Transdiagnostic Treatment.

Although anxiety and depression have been considered as two distinct entities according to the diagnostic criteria, anxious depression (comorbid anxiety and depression) is relatively a common syndrome. According to the DSM-5 criteria, it uses "with anxious distress specifier" to define anxious depression in its MDD section. Anxious depression is known to have different neurobiological profiles compared to non-anxious depression. Several studies have revealed significant differences between anxious depression and non-anxious depression regarding the hypothalamic-pituitary-adrenal (HPA) axis function, structural and functional brain imaging findings, inflammation markers, etc. Patients with anxious depression were significantly more likely to be found in primary care setting and more likely to be associated with female gender, non-single, unemployed, less educated, and more severe depression. Previous reports also showed that patients with anxious depression had more frequent episodes of major depression and a higher risk of suicidal ideation and previous suicide attempts than those with non-anxious depression. Although anxious depression is known to be associated with poor treatment outcomes in several studies, recent researches have sought to find better treatment strategy to improve patients with anxious depression.

Predictive factors of diagnostic conversion from major depressive disorder to bipolar disorder in young adults ages 19-34: A nationwide population study in South Korea.

BACKGROUND: Predicting patients who convert to bipolar disorder is important for deciding appropriate treatment for young adults with major depressive disorder (MDD). We focused on the predictive factors of bipolar conversion in a large population of young adults. METHODS: A nationwide, population-based electronic medical records database from the Health Insurance Review & Assessment service of South was used to investigate adjusted hazard ratio (HR) of each potential predictor of the bipolar converter group compared to the non-converter group using Cox regression analysis including age of onset, medication use, clinical features, comorbid disorders, admission, self-harm, and negative life events in childhood. RESULTS: Among 291,721 subjects who were initially diagnosed with MDD in young adults, 12,376 subjects experienced diagnostic conversion to bipolar disorder. The cumulative incidence was 6.46% during the average 3.26 years of follow-up. Among the predictive factors during diagnosis of MDD, antipsychotic use (HR 3.12, 95%CI, 2.99-3.26, p < 0.0001) and mood stabilizers (HR 2.45, 95%CI, 2.35-2.55, p < 0.0001) showed the strongest association with diagnostic conversion to bipolar disorder. In addition, female sex, younger age of onset, mood stabilizer use, recurrent depression, psychotic symptoms, and admission to a psychiatric ward during diagnosis of MDD were also associated with diagnostic conversion to bipolar disorder. CONCLUSION: In young adults with MDD, antipsychotic and mood stabilizer use during diagnosis of MDD were the strongest predictive factors with diagnostic conversion to bipolar disorder during follow-up. If young adults with MDD need antipsychotics or mood stabilizer, patients should be carefully evaluated for possibility of bipolar disorder.

Risks of suicide attempts after prescription of zolpidem in people with depression: a nationwide population study in South Korea.

OBJECTIVES: To investigate the association between zolpidem prescription and suicide attempts in people with depression. METHODS: A nationwide, population-based electronic medical records database from the Health Insurance Review & Assessment Service of South was used to investigate the incidence rate ratios (IRRs) of suicide attempts and probable suicide attempts in people with depression before and after zolpidem prescription using self-controlled case series design. RESULTS: In a total of 445 people who attempted suicide and 23 141 people who attempted probable suicide attempt, the IRRs of suicidal behavior during the risk periods before and after zolpidem prescription increased compared with those at the baseline. The IRRs gradually increased and peaked immediately before the prescription of zolpidem. The IRR was 70.06 (95% CI: 25.58-191.90) on day 2 before zolpidem prescription and 63.35 (95% CI: 22.99-174.59) on day 1 after zolpidem prescription in the suicide attempt group. The IRR was 24.07 (95% CI: 20.50-28.26) on the day before zolpidem prescription and 14.96 (95% CI: 12.21-18.34) on the day after zolpidem prescription in the probable suicide attempt group. The ratios declined eventually after zolpidem was prescribed. CONCLUSIONS: Although zolpidem prescription was associated with an increased risk of suicide attempts in people with depression, the risk increased and peaked immediately before zolpidem prescription. The risk declined gradually thereafter. This result indicates that the risk of suicide attempts increases at the time of zolpidem prescription. However, zolpidem prescription does not contribute to additional increase in the risk of suicide attempts.

Paranoid Ideation Without Psychosis Is Associated With Depression, Anxiety, and Suicide Attempts in General Population.

This study aimed to characterize the association between paranoid ideation without psychosis (PIP) and suicide attempts in a general population. A total of 12,532 adults were randomly selected as the study sample through one-person-per-household method. Subjects completed a face-to-face interview. Among 12,532 subjects, 471 (3.76%) met criteria for the PIP group. The PIP group was younger with more divorced/widowed/separated and lower income than the non-PIP group. The PIP group showed more than fivefold higher lifetime suicide attempt (LSA) rates and ninefold multiple attempt rates than the non-PIP group. Among PIP symptoms, "spouse was being unfaithful" showed the strongest association with LSA (adjusted odds ratio [AOR], 4.49; 95% confidence interval, 2.95-6.85). Major depressive disorder (MDD) in combination with PIP was associated with a higher risk of LSA (AOR, 15.39; 95% confidence interval, 9.63-24.59) compared with subjects without MDD or PIP. In conclusion, PIP, especially "doubting spouse," was significantly associated with LSA. PIP in combination with comorbid MDD showed higher risk of LSA than subjects without PIP or MDD.

Detection of major depressive disorder from linear and nonlinear heart rate variability features during mental task protocol.

BACKGROUND: Major depressive disorder (MDD) is one of the leading causes of disability; however, current MDD diagnosis methods lack an objective assessment of depressive symptoms. Here, a machine learning approach to separate MDD patients from healthy controls was developed based on linear and nonlinear heart rate variability (HRV), which reflects the autonomic cardiovascular regulation. METHODS: HRV data were collected from 37 MDD patients and 41 healthy controls during five 5-min experimental phases: the baseline, a mental stress task, stress recovery, a relaxation task, and relaxation task recovery. The experimental protocol was designed to assess the autonomic responses to stress and recovery. Twenty HRV indices were extracted from each phase, and a total of 100 features were used for classification using a support vector machine (SVM). SVM-recursive feature elimination (RFE) and statistical filter were employed to perform feature selection. RESULTS: We achieved 74.4% accuracy, 73% sensitivity, and 75.6% specificity with two optimal features selected by SVM-RFE, which were extracted from the stress task recovery and mental stress phases. Classification performance worsened when individual phases were used separately as input data, compared to when all phases were included. The SVM-RFE using nonlinear and Poincaré plot HRV features performed better than that using the linear indices and matched the best performance achieved by using all features. CONCLUSIONS: We demonstrated the machine learning-based diagnosis of MDD using HRV analysis. Monitoring the changes in linear and nonlinear HRV features for various autonomic nervous system states can facilitate the more objective identification of MDD patients.

Increased Morbidity of Major Depressive Disorder After Thyroidectomy: A Nationwide Population-Based Study in South Korea.

Background: The number of thyroidectomies in South Korea has been increasing rapidly due to extensive checkups for thyroid cancer. However, few studies have examined the association between thyroidectomy and major depressive disorder (MDD). We investigated the association between thyroidectomy and the risk of MDD. Methods: A population-based electronic medical records database from South Korea was used to identify 187,176 individuals who underwent partial or total thyroidectomy between 2009 and 2016. A self-controlled case series design and Cox regression analyses were used to identify risk factors for MDD. Results: Among the 187,176 individuals who underwent thyroidectomy, 16,744 (8.9%) were diagnosed with MDD during the observation period. Of those, 3837 (22.9%) underwent partial thyroidectomy and 12,907 (77.1%) underwent total thyroidectomy. An elevated MDD risk was found during the one-year period before thyroidectomy, with incidence rate ratios (IRRs) of 1.29 ([95% confidence interval [CI] 1.18-1.41], p < 0.0001) for subjects with partial thyroidectomy and 1.27 ([95% CI 1.21-1.33], p < 0.0001) for subjects with total thyroidectomy. After total thyroidectomy, the IRR increased for 31-60 days (IRR 1.81; [95% CI 1.59-2.06], p < 0.0001) and remained elevated for up to 540 days, whereas after partial thyroidectomy, the IRR increased for 31-60 days (IRR 1.68; [95% CI 1.32-2.13], p < 0.0001) but returned to baseline levels after 270 days. Total thyroidectomy was associated with a prolonged risk of MDD compared with partial thyroidectomy in patients with cancer, which was different from the results in patients without cancer. Conclusion: The incidence of MDD increased in the period immediately after thyroidectomy and remained high for one to two years. This study highlights the importance of relatively long-term regular psychiatric assessments in patients who undergo partial or total thyroidectomy.