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Papers by David Mischoulon

The Massachusetts General Hospital Guide to Depression

Susan is a 65-year-old married Caucasian woman with a long history of depression, anxiety, type 2... more Susan is a 65-year-old married Caucasian woman with a long history of depression, anxiety, type 2 diabetes, and chronic pain due to diabetic neuropathy. She is postmenopausal. She presents for treatment of her depression, which started about 10 years ago after she retired from a busy position as CEO of a small local company. Her depression worsened over the past 2 years once she began to develop complications from her diabetes, in particular a severe neuropathy that limited her ability to be physically active. One of her major complaints is trouble falling asleep and staying asleep, which she attributes to the burning pain in her legs. She also endorses hopelessness that she will ever get better, wishing she were dead, decreased attention, and decreased motivation. Her husband, Bill, notes that Susan is "sensitive to medications" often needing to stop antidepressants because of side effects before reaching a therapeutic dose. Her past medication trials have included multiple selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). She has never been on a tricyclic antidepressant and currently takes only lorazepam 0.5 mg at night for sleep. After a discussion of pharmacological and nonpharmacological treatments for comorbid depression, sleep disorder, and chronic pain, Susan is wary of starting a new medication since she has had such difficulty tolerating antidepressant medications in the past. She is interested in alternative therapies. The provider remembers reading about a study that recommended genotyping for patients over 65 years old starting nortriptyline and recommends a commercial kit offering genotyping of patients starting an antidepressant after failing multiple trials in the past. After discussing the pros and cons of genotyping with Susan, she decides to obtain the kit, which is partially covered by her insurance. While waiting for the results, Susan is referred to a holistic pain clinic where she can begin physical rehabilitation and cognitive behavioral therapy (CBT) for pain and sleep, in the hopes of becoming more active. Her genotype and recommended dosing for nortriptyline come back after a month. She is listed as a "poor metabolizer," which could explain why she has had so many side effects from antidepressants. She is started at a very low dose of nortriptyline. Two months later, Susan returns, with substantial improvement in her depression, better sleep, and less pain. She is also more active after rehabilitation. She is tolerating the nortriptyline well, with only some dry mouth as a side effect.

The Massachusetts General Hospital Guide to Depression

Journal of Clinical …, 2006

Received April 7, 2006; accepted May 24, 2006. From the Women's Mental Health Program, Depar... more Received April 7, 2006; accepted May 24, 2006. From the Women's Mental Health Program, Departments of Psychiatry, Obstetrics and Gynecology, and Nutritional Sciences, University of Arizona College of Medicine, Tucson (Dr. Freeman); the National Institute on Alcohol ...

Psychiatry research, Jan 21, 2018

Previous studies have reported dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis in pa... more Previous studies have reported dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis in patients with major depressive disorder (MDD). Outpatients diagnosed with MDD (n = 199) underwent psychological evaluation, and were followed up with a phone interview after 6 months, using the Patient Health Questionnaire (PHQ-9). At 6-month follow-up, 59 out of 199 patients with MDD were still depressed (29.5%), as shown by scores ≥ 10 on the PHQ-9. The depressed group at follow-up showed significantly higher anxiety and suicidality levels at baseline than the non-depressed group at follow-up. Among the complete blood counts, lipid profiles, and hormone levels, adrenocorticotropic hormone (ACTH) was the only parameter that was significantly increased in the still depressed group. Levels higher than 40 pg/mL of ACTH at baseline were associated with higher depression scores at follow-up. Multiple linear regression analyses revealed that ACTH and cortisol predicted depression scores at foll...

Psychiatry research, Jan 21, 2018

Regardless of categorical diagnosis, many psychiatric patients suffer from sudden attack of fear ... more Regardless of categorical diagnosis, many psychiatric patients suffer from sudden attack of fear or intense anxiety. In this study, we defined anxiety attacks to refer to these phenomena and investigated their association with depression and suicide attempts. A total of 12,532 adults randomly selected population through the one-person-per-household method completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI). A total of 5.88% reported to have experienced anxiety attacks. Among them, 46.5% reported to have experienced anxiety attacks without life-threatening situations. 'Anxiety attacks' group reported more suicidal ideation, plan, and attempts, which were even higher frequencies in 'anxiety attacks without life-threatening situations' group than 'anxiety attacks only with life-threatening situations' group and showed stronger association with lifetime suicide attempts when it had comorbid major de...

Contemporary clinical trials, 2018

Depression is a leading cause of disease burden and disability for older adults; thus, prevention... more Depression is a leading cause of disease burden and disability for older adults; thus, prevention is a priority. Biologic and observational data support potential mental health benefits of vitamin D and omega-3 fatty acids; however, it is unclear whether these supplements can prevent late-life depression. We describe the novel methodology of a large-scale study: VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention), an ancillary to the VITAL trial. Primary Aims of VITAL-DEP are to determine effects on prevention of depression and on trajectory of mood symptoms of long-term (mean=5years) supplementation with vitamin D (vitamin D3 [cholecalciferol], 2000IU/day) and marine omega-3 fatty-acids (eicosapentaenoic acid + docosahexaenoic acid, 1g/day), in a 2×2 factorial design, among 25,874 older adults. Secondary Aims will evaluate: vitamin D's effects among African-Americans (an at-risk group for vitamin D deficiency); both agents' effects among those with high-r...

Journal of affective disorders, Feb 1, 2018

Alcohol-induced disinhibition (AID) is defined as a "loss of restraint over some form of beh... more Alcohol-induced disinhibition (AID) is defined as a "loss of restraint over some form of behavior after drinking alcohol regardless of its amount". Although many previous studies have investigated on alcohol use disorder and suicide attempt, few studies have focused on AID and suicide. A total of 9461 adults who had a history of drinking completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI) with the Suicide Module, and Barratt Impulsiveness Scale 11 (BIS-11). In this study, we defined the AID group as those who had been involved with the two antisocial behaviors, including fights, being arrested or dangerous driving, according to the K-CIDI. Among 9461 subjects, 564 were classified as the AID group (5.96%). The AID group had a significantly higher number of lifetime suicidal ideation, plan, attempt, and multiple attempts, and higher BIS-11 scores than non-AID group. The total scores of BIS-11 of the AID group r...

PloS one, 2018

Eating disorders comorbid with depression are an established risk factor for suicide. In this stu... more Eating disorders comorbid with depression are an established risk factor for suicide. In this study, we aimed to determine the effects of binge eating (BE) symptoms on suicidality and related clinical characteristics in major depressive disorder (MDD). A total of 817 community participants with MDD were included. We compared two groups (with and without lifetime BE symptoms). The MDD with BE group was subdivided into a frequent BE (FBE) subgroup (BE symptoms greater than twice weekly) and any BE (ABE) subgroup (BE symptoms greater than twice weekly). The MDD with BE group comprised 142 (17.38%) patients. The FBE and ABE subgroups comprised 75 (9.18%) and 67 (8.20%) patients, respectively. Comorbid alcohol use disorder, anxiety disorder, post-traumatic stress disorder (PTSD) and history of suicide attempt were significantly more frequent in the MDD with BE group than MDD without BE group. Sexual trauma was also reported more frequently in MDD with BE group. No significant differences...

Psychoneuroendocrinology, 2018

Reduced leukocyte telomere length (LTL) has been found to be associated with multiple common age-... more Reduced leukocyte telomere length (LTL) has been found to be associated with multiple common age-related diseases, including heart disease, diabetes, and cancer. A link has also been suggested between shortened LTL and major depressive disorder (MDD), suggesting that MDD may be a disease of accelerated aging. This prospective, longitudinal study examined the association between depression diagnosis at baseline and change in LTL over two years in a well-characterized sample of N = 117 adults with or without MDD at baseline, using rigorous entry criteria. Participants aged 18-70 were assessed with validated instruments by trained, doctoral-level clinician raters at baseline and at two-year follow-up, and blood samples were obtained at both visits. LTL was assayed under identical methods using quantitative polymerase chain reaction (qPCR). The effect of an MDD diagnosis at baseline on change in LTL over two years was examined via hierarchical mixed models, which included potential conf...

Scientific reports, Jan 17, 2017

Despite recent developments in neuroimaging, alterations of brain functional connectivity in majo... more Despite recent developments in neuroimaging, alterations of brain functional connectivity in major depressive disorder (MDD) patients with suicidal ideation are poorly understood. This study investigated specific changes of suicidal ideation in functional connectivity of MDD patients. Whole brain functional connectivity in 46 patients with MDD (23 with suicidal ideation and 23 without) and 36 age- and gender- matched healthy controls were compared using resting-state functional Magnetic Resonance Imaging (fMRI) analyzed with network-based statistics (NBS) and graph-theoretical methods. Decreased functional connectivity in a characterized sub-network was observed in patients with MDD and suicidal ideation (FDR-adjusted p < 0.05). The sub-network included the regions of the fronto-thalamic circuits in the left hemisphere. The network measures of the left superior frontal gyrus, pars orbitalis (r = -0.40, p = 0.009), left thalamus (r = -0.41, p = 0.009), and right thalamus (r = -0.5...

Psychiatry Investigation

ObjectiveaaTamoxifen is an estrogen receptor antagonist used to prevent recurrence of breast canc... more ObjectiveaaTamoxifen is an estrogen receptor antagonist used to prevent recurrence of breast cancer, which may provoke depression and anxiety and increase follicle-stimulating hormone (FSH) to patients. We compared anxiety and depression symptoms and FSH levels who received conventional tamoxifen alone and combination treatment of goserelin, a gonadotropin-releasing hormone (GnRH) analogue, with tamoxifen. MethodsaaSixty-four premenopausal women with hormone receptor-positive early-stage breast cancer were included and were assigned randomly to receive either tamoxifen and goserelin combination or tamoxifen alone for 12 months. The participants were evaluated blindly using the Hamilton Depression and Anxiety Rating Scale, the Beck Depression Rating Scale, and the Albany Panic and Phobia Questionnaire (APPQ). Blood FSH levels were assessed at baseline, 6 and 12 months. ResultsaaA significant time×group difference was detected in the agoraphobia trends subscale of the APPQ and in FSH levels. The combination group showed significantly less increases in agoraphobia subscale of APPQ and greater decreases in FSH level than those in the tamoxifen-alone group from baseline to 12 months of treatment. No significant differences for age, tumor grade, body mass index, or family history were found at baseline between the two groups. ConclusionaaOur results suggest that the combination treatment of tamoxifen and goserelin resulted in less agoraphobia than tamoxifen alone in premenopausal women with breast cancer, which may associated with FSH suppression of goserelin.

Psychiatry research, Nov 2, 2017

The aim of this study was to develop a screening questionnaire that could distinguish individuals... more The aim of this study was to develop a screening questionnaire that could distinguish individuals at high risk of smartphone overuse from casual users. The reliability, validity, and diagnostic ability of the Smartphone Overuse Screening Questionnaire (SOS-Q) were evaluated. Preliminary items were assessed by 50 addiction experts on-line, and 28 questions were selected. A total of 158 subjects recruited from six community centers for internet addiction participated in this study. The SOS-Q, Young's internet addiction scale, Korean scale for internet addiction, and Smartphone Scale for Smartphone Addiction (S-Scale) were used to assess the concurrent validity. Construct validity was supported by a six-factor model using an exploratory factor analysis. The internal consistency and the item-total correlations were favorable (α = 0.95, r = 0.35-0.81). The test-retest reliability was moderate (r = 0.70). The SOS-Q showed superior concurrent validity with the highest correlation betwe...

The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, Jan 12, 2017

Current evidence supports participation of neurotrophic and inflammatory factors in the pathogene... more Current evidence supports participation of neurotrophic and inflammatory factors in the pathogenesis of major depressive disorder (MDD). Some studies reported an association between the Val66Met polymorphism (rs6265) of brain-derived neurotrophic factor (BDNF) gene with MDD and peripheral BDNF levels. However, no previous studies have examined the association of this polymorphism with inflammation. The present study assessed the association of the Val66Met polymorphism with serum levels of BDNF and inflammatory markers among depressed outpatients. All participants (n = 73) met DSM-IV criteria for a unipolar depressive episode. The serum levels of BDNF and inflammatory biomarkers (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) were compared between individuals presenting with at least one Met allele (Met-carriers) and those homozygous for the Val allele. In our sample (84.9% female, mean age 52.4 ± 10.3 years), 24.7% (n = 18) were Met-carriers. After Bonferroni correction, the Met allele ...

The Journal of clinical psychiatry, 2017

A systematic review on S-adenosylmethionine (SAMe) for treatment of neuropsychiatric conditions a... more A systematic review on S-adenosylmethionine (SAMe) for treatment of neuropsychiatric conditions and comorbid medical conditions. Searches were conducted in PubMed, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Google Scholar databases between July 15, 2015, and September 28, 2016, by combining search terms for SAMe (s-adenosyl methionine or s-adenosyl-l-methionine) with terms for relevant disease states (major depressive disorder, MDD, depression, perinatal depression, human immunodeficiency virus, HIV, Parkinson's, Alzheimer's, dementia, anxiety, schizophrenia, psychotic, 22q11.2, substance abuse, fibromyalgia, osteoarthritis, hepatitis, or cirrhosis). Additional studies were identified from prior literature. Ongoing clinical trials were identified through clinical trial registries. Of the 174 records retrieved, 21 were excluded, as they were not original investigations. An additional 21 records were excluded for falling outside the scope of this review. Of the 132 studie...

European archives of psychiatry and clinical neuroscience, 2017

An impaired ability to suppress currently irrelevant mental-sets is a key cognitive deficit in de... more An impaired ability to suppress currently irrelevant mental-sets is a key cognitive deficit in depression. Mindfulness-based cognitive therapy (MBCT) was specifically designed to help depressed individuals avoid getting caught in such irrelevant mental-sets. In the current study, a group assigned to MBCT plus treatment-as-usual (n = 22) exhibited significantly lower depression scores and greater improvements in irrelevant mental-set suppression compared to a wait-list plus treatment-as-usual (n = 18) group. Improvements in mental-set-suppression were associated with improvements in depression scores. Results provide the first evidence that MBCT can improve suppression of irrelevant mental-sets and that such improvements are associated with depressive alleviation.

The Journal of clinical psychiatry, Feb 28, 2017

Chronic pain is a disabling illness, often comorbid with depression. We performed a randomized co... more Chronic pain is a disabling illness, often comorbid with depression. We performed a randomized controlled pilot study on mindfulness-based cognitive therapy (MBCT) targeting depression in a chronic pain population. Participants with chronic pain lasting ≥ 3 months; DSM-IV major depressive disorder (MDD), dysthymic disorder, or depressive disorder not otherwise specified; and a 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C₁₆) score ≥ 6 were randomly assigned to MBCT (n = 26) or waitlist (n = 14). We adapted the original MBCT intervention for depression relapse prevention by modifying the psychoeducation and cognitive-behavioral therapy elements to an actively depressed chronic pain population. We analyzed an intent-to-treat (ITT) and a per-protocol sample; the per-protocol sample included participants in the MBCT group who completed at least 4 of 8 sessions. Changes in scores on the QIDS-C₁₆ and 17-item Hamilton Depression Rating Sale (HDRS₁₇) were the ...

PloS one, 2017

Internet addiction (IA) is defined as a psychological dependence on the internet, regardless of t... more Internet addiction (IA) is defined as a psychological dependence on the internet, regardless of the type of activities once logged on, and previous studies have focused on adolescents and young adults. The aim of this study was to investigate the association between suicide attempts and sleep among community-dwelling adults with IA. The Young's Internet Addiction Test (IAT), the Korean version of the Composite International Diagnostic Interview (K-CIDI) and a suicide questionnaire were used in this cross-sectional multistage, cluster sampling population-based study. A total of 3212 adults aged 18-64 years were interviewed face-to-face, and they had been randomly selected through a one-person-per-household method. Of the 3212 adults, 204 were assessed as having IA (6.35%). Adults with IA were younger, and more frequently male, unmarried, and unemployed, and had poorer sleep quality than adults without IA (32.8% vs. 19.8%), whereas there was no significant difference in the absolu...

Journal of affective disorders, Jan 15, 2017

Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy ... more Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy as augmentation for depressive breakthrough on pro-dopaminergic antidepressant regimens. 12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stimulants, dopamine agonists, bupropion [≥300mg/day], aripiprazole [≤2.5mg/day], or sertraline [≥150mg/day]) were randomized to naltrexone 1mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks. All subjects completed the trial. Hamilton Depression Rating Scale (HAM-D-17) scores (primary outcome measure) decreased from 21.2±2.0 to 11.7±7.7 for LDN, from 23.7±2.3 to 17.8±5.9 for placebo (Cohen's d=0.62; p=0.3 between treatment groups). HAM-D-28 scores decreased from 26.2±4.0 to 12.0±9.8 for LDN, from 26.3±2.6 to 19.8±6.6 for placebo (d=1.15; p=0.097). Montgomery-Asberg Depression Rating Scale (MADRS-10 item) scores decreased from 30.4±4.9 to 12.2±8.4 for LDN,...

The Massachusetts General Hospital Guide to Depression

Susan is a 65-year-old married Caucasian woman with a long history of depression, anxiety, type 2... more Susan is a 65-year-old married Caucasian woman with a long history of depression, anxiety, type 2 diabetes, and chronic pain due to diabetic neuropathy. She is postmenopausal. She presents for treatment of her depression, which started about 10 years ago after she retired from a busy position as CEO of a small local company. Her depression worsened over the past 2 years once she began to develop complications from her diabetes, in particular a severe neuropathy that limited her ability to be physically active. One of her major complaints is trouble falling asleep and staying asleep, which she attributes to the burning pain in her legs. She also endorses hopelessness that she will ever get better, wishing she were dead, decreased attention, and decreased motivation. Her husband, Bill, notes that Susan is "sensitive to medications" often needing to stop antidepressants because of side effects before reaching a therapeutic dose. Her past medication trials have included multiple selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). She has never been on a tricyclic antidepressant and currently takes only lorazepam 0.5 mg at night for sleep. After a discussion of pharmacological and nonpharmacological treatments for comorbid depression, sleep disorder, and chronic pain, Susan is wary of starting a new medication since she has had such difficulty tolerating antidepressant medications in the past. She is interested in alternative therapies. The provider remembers reading about a study that recommended genotyping for patients over 65 years old starting nortriptyline and recommends a commercial kit offering genotyping of patients starting an antidepressant after failing multiple trials in the past. After discussing the pros and cons of genotyping with Susan, she decides to obtain the kit, which is partially covered by her insurance. While waiting for the results, Susan is referred to a holistic pain clinic where she can begin physical rehabilitation and cognitive behavioral therapy (CBT) for pain and sleep, in the hopes of becoming more active. Her genotype and recommended dosing for nortriptyline come back after a month. She is listed as a "poor metabolizer," which could explain why she has had so many side effects from antidepressants. She is started at a very low dose of nortriptyline. Two months later, Susan returns, with substantial improvement in her depression, better sleep, and less pain. She is also more active after rehabilitation. She is tolerating the nortriptyline well, with only some dry mouth as a side effect.

The Massachusetts General Hospital Guide to Depression

Journal of Clinical …, 2006

Received April 7, 2006; accepted May 24, 2006. From the Women's Mental Health Program, Depar... more Received April 7, 2006; accepted May 24, 2006. From the Women's Mental Health Program, Departments of Psychiatry, Obstetrics and Gynecology, and Nutritional Sciences, University of Arizona College of Medicine, Tucson (Dr. Freeman); the National Institute on Alcohol ...

Psychiatry research, Jan 21, 2018

Previous studies have reported dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis in pa... more Previous studies have reported dysfunction in the hypothalamic-pituitary-adrenal (HPA) axis in patients with major depressive disorder (MDD). Outpatients diagnosed with MDD (n = 199) underwent psychological evaluation, and were followed up with a phone interview after 6 months, using the Patient Health Questionnaire (PHQ-9). At 6-month follow-up, 59 out of 199 patients with MDD were still depressed (29.5%), as shown by scores ≥ 10 on the PHQ-9. The depressed group at follow-up showed significantly higher anxiety and suicidality levels at baseline than the non-depressed group at follow-up. Among the complete blood counts, lipid profiles, and hormone levels, adrenocorticotropic hormone (ACTH) was the only parameter that was significantly increased in the still depressed group. Levels higher than 40 pg/mL of ACTH at baseline were associated with higher depression scores at follow-up. Multiple linear regression analyses revealed that ACTH and cortisol predicted depression scores at foll...

Psychiatry research, Jan 21, 2018

Regardless of categorical diagnosis, many psychiatric patients suffer from sudden attack of fear ... more Regardless of categorical diagnosis, many psychiatric patients suffer from sudden attack of fear or intense anxiety. In this study, we defined anxiety attacks to refer to these phenomena and investigated their association with depression and suicide attempts. A total of 12,532 adults randomly selected population through the one-person-per-household method completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI). A total of 5.88% reported to have experienced anxiety attacks. Among them, 46.5% reported to have experienced anxiety attacks without life-threatening situations. 'Anxiety attacks' group reported more suicidal ideation, plan, and attempts, which were even higher frequencies in 'anxiety attacks without life-threatening situations' group than 'anxiety attacks only with life-threatening situations' group and showed stronger association with lifetime suicide attempts when it had comorbid major de...

Contemporary clinical trials, 2018

Depression is a leading cause of disease burden and disability for older adults; thus, prevention... more Depression is a leading cause of disease burden and disability for older adults; thus, prevention is a priority. Biologic and observational data support potential mental health benefits of vitamin D and omega-3 fatty acids; however, it is unclear whether these supplements can prevent late-life depression. We describe the novel methodology of a large-scale study: VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention), an ancillary to the VITAL trial. Primary Aims of VITAL-DEP are to determine effects on prevention of depression and on trajectory of mood symptoms of long-term (mean=5years) supplementation with vitamin D (vitamin D3 [cholecalciferol], 2000IU/day) and marine omega-3 fatty-acids (eicosapentaenoic acid + docosahexaenoic acid, 1g/day), in a 2×2 factorial design, among 25,874 older adults. Secondary Aims will evaluate: vitamin D's effects among African-Americans (an at-risk group for vitamin D deficiency); both agents' effects among those with high-r...

Journal of affective disorders, Feb 1, 2018

Alcohol-induced disinhibition (AID) is defined as a "loss of restraint over some form of beh... more Alcohol-induced disinhibition (AID) is defined as a "loss of restraint over some form of behavior after drinking alcohol regardless of its amount". Although many previous studies have investigated on alcohol use disorder and suicide attempt, few studies have focused on AID and suicide. A total of 9461 adults who had a history of drinking completed a face-to-face interview using the Korean version of Composite International Diagnostic Interview (K-CIDI) with the Suicide Module, and Barratt Impulsiveness Scale 11 (BIS-11). In this study, we defined the AID group as those who had been involved with the two antisocial behaviors, including fights, being arrested or dangerous driving, according to the K-CIDI. Among 9461 subjects, 564 were classified as the AID group (5.96%). The AID group had a significantly higher number of lifetime suicidal ideation, plan, attempt, and multiple attempts, and higher BIS-11 scores than non-AID group. The total scores of BIS-11 of the AID group r...

PloS one, 2018

Eating disorders comorbid with depression are an established risk factor for suicide. In this stu... more Eating disorders comorbid with depression are an established risk factor for suicide. In this study, we aimed to determine the effects of binge eating (BE) symptoms on suicidality and related clinical characteristics in major depressive disorder (MDD). A total of 817 community participants with MDD were included. We compared two groups (with and without lifetime BE symptoms). The MDD with BE group was subdivided into a frequent BE (FBE) subgroup (BE symptoms greater than twice weekly) and any BE (ABE) subgroup (BE symptoms greater than twice weekly). The MDD with BE group comprised 142 (17.38%) patients. The FBE and ABE subgroups comprised 75 (9.18%) and 67 (8.20%) patients, respectively. Comorbid alcohol use disorder, anxiety disorder, post-traumatic stress disorder (PTSD) and history of suicide attempt were significantly more frequent in the MDD with BE group than MDD without BE group. Sexual trauma was also reported more frequently in MDD with BE group. No significant differences...

Psychoneuroendocrinology, 2018

Reduced leukocyte telomere length (LTL) has been found to be associated with multiple common age-... more Reduced leukocyte telomere length (LTL) has been found to be associated with multiple common age-related diseases, including heart disease, diabetes, and cancer. A link has also been suggested between shortened LTL and major depressive disorder (MDD), suggesting that MDD may be a disease of accelerated aging. This prospective, longitudinal study examined the association between depression diagnosis at baseline and change in LTL over two years in a well-characterized sample of N = 117 adults with or without MDD at baseline, using rigorous entry criteria. Participants aged 18-70 were assessed with validated instruments by trained, doctoral-level clinician raters at baseline and at two-year follow-up, and blood samples were obtained at both visits. LTL was assayed under identical methods using quantitative polymerase chain reaction (qPCR). The effect of an MDD diagnosis at baseline on change in LTL over two years was examined via hierarchical mixed models, which included potential conf...

Scientific reports, Jan 17, 2017

Despite recent developments in neuroimaging, alterations of brain functional connectivity in majo... more Despite recent developments in neuroimaging, alterations of brain functional connectivity in major depressive disorder (MDD) patients with suicidal ideation are poorly understood. This study investigated specific changes of suicidal ideation in functional connectivity of MDD patients. Whole brain functional connectivity in 46 patients with MDD (23 with suicidal ideation and 23 without) and 36 age- and gender- matched healthy controls were compared using resting-state functional Magnetic Resonance Imaging (fMRI) analyzed with network-based statistics (NBS) and graph-theoretical methods. Decreased functional connectivity in a characterized sub-network was observed in patients with MDD and suicidal ideation (FDR-adjusted p < 0.05). The sub-network included the regions of the fronto-thalamic circuits in the left hemisphere. The network measures of the left superior frontal gyrus, pars orbitalis (r = -0.40, p = 0.009), left thalamus (r = -0.41, p = 0.009), and right thalamus (r = -0.5...

Psychiatry Investigation

ObjectiveaaTamoxifen is an estrogen receptor antagonist used to prevent recurrence of breast canc... more ObjectiveaaTamoxifen is an estrogen receptor antagonist used to prevent recurrence of breast cancer, which may provoke depression and anxiety and increase follicle-stimulating hormone (FSH) to patients. We compared anxiety and depression symptoms and FSH levels who received conventional tamoxifen alone and combination treatment of goserelin, a gonadotropin-releasing hormone (GnRH) analogue, with tamoxifen. MethodsaaSixty-four premenopausal women with hormone receptor-positive early-stage breast cancer were included and were assigned randomly to receive either tamoxifen and goserelin combination or tamoxifen alone for 12 months. The participants were evaluated blindly using the Hamilton Depression and Anxiety Rating Scale, the Beck Depression Rating Scale, and the Albany Panic and Phobia Questionnaire (APPQ). Blood FSH levels were assessed at baseline, 6 and 12 months. ResultsaaA significant time×group difference was detected in the agoraphobia trends subscale of the APPQ and in FSH levels. The combination group showed significantly less increases in agoraphobia subscale of APPQ and greater decreases in FSH level than those in the tamoxifen-alone group from baseline to 12 months of treatment. No significant differences for age, tumor grade, body mass index, or family history were found at baseline between the two groups. ConclusionaaOur results suggest that the combination treatment of tamoxifen and goserelin resulted in less agoraphobia than tamoxifen alone in premenopausal women with breast cancer, which may associated with FSH suppression of goserelin.

Psychiatry research, Nov 2, 2017

The aim of this study was to develop a screening questionnaire that could distinguish individuals... more The aim of this study was to develop a screening questionnaire that could distinguish individuals at high risk of smartphone overuse from casual users. The reliability, validity, and diagnostic ability of the Smartphone Overuse Screening Questionnaire (SOS-Q) were evaluated. Preliminary items were assessed by 50 addiction experts on-line, and 28 questions were selected. A total of 158 subjects recruited from six community centers for internet addiction participated in this study. The SOS-Q, Young's internet addiction scale, Korean scale for internet addiction, and Smartphone Scale for Smartphone Addiction (S-Scale) were used to assess the concurrent validity. Construct validity was supported by a six-factor model using an exploratory factor analysis. The internal consistency and the item-total correlations were favorable (α = 0.95, r = 0.35-0.81). The test-retest reliability was moderate (r = 0.70). The SOS-Q showed superior concurrent validity with the highest correlation betwe...

The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, Jan 12, 2017

Current evidence supports participation of neurotrophic and inflammatory factors in the pathogene... more Current evidence supports participation of neurotrophic and inflammatory factors in the pathogenesis of major depressive disorder (MDD). Some studies reported an association between the Val66Met polymorphism (rs6265) of brain-derived neurotrophic factor (BDNF) gene with MDD and peripheral BDNF levels. However, no previous studies have examined the association of this polymorphism with inflammation. The present study assessed the association of the Val66Met polymorphism with serum levels of BDNF and inflammatory markers among depressed outpatients. All participants (n = 73) met DSM-IV criteria for a unipolar depressive episode. The serum levels of BDNF and inflammatory biomarkers (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) were compared between individuals presenting with at least one Met allele (Met-carriers) and those homozygous for the Val allele. In our sample (84.9% female, mean age 52.4 ± 10.3 years), 24.7% (n = 18) were Met-carriers. After Bonferroni correction, the Met allele ...

The Journal of clinical psychiatry, 2017

A systematic review on S-adenosylmethionine (SAMe) for treatment of neuropsychiatric conditions a... more A systematic review on S-adenosylmethionine (SAMe) for treatment of neuropsychiatric conditions and comorbid medical conditions. Searches were conducted in PubMed, EMBASE, PsycINFO, Cochrane Library, CINAHL, and Google Scholar databases between July 15, 2015, and September 28, 2016, by combining search terms for SAMe (s-adenosyl methionine or s-adenosyl-l-methionine) with terms for relevant disease states (major depressive disorder, MDD, depression, perinatal depression, human immunodeficiency virus, HIV, Parkinson's, Alzheimer's, dementia, anxiety, schizophrenia, psychotic, 22q11.2, substance abuse, fibromyalgia, osteoarthritis, hepatitis, or cirrhosis). Additional studies were identified from prior literature. Ongoing clinical trials were identified through clinical trial registries. Of the 174 records retrieved, 21 were excluded, as they were not original investigations. An additional 21 records were excluded for falling outside the scope of this review. Of the 132 studie...

European archives of psychiatry and clinical neuroscience, 2017

An impaired ability to suppress currently irrelevant mental-sets is a key cognitive deficit in de... more An impaired ability to suppress currently irrelevant mental-sets is a key cognitive deficit in depression. Mindfulness-based cognitive therapy (MBCT) was specifically designed to help depressed individuals avoid getting caught in such irrelevant mental-sets. In the current study, a group assigned to MBCT plus treatment-as-usual (n = 22) exhibited significantly lower depression scores and greater improvements in irrelevant mental-set suppression compared to a wait-list plus treatment-as-usual (n = 18) group. Improvements in mental-set-suppression were associated with improvements in depression scores. Results provide the first evidence that MBCT can improve suppression of irrelevant mental-sets and that such improvements are associated with depressive alleviation.

The Journal of clinical psychiatry, Feb 28, 2017

Chronic pain is a disabling illness, often comorbid with depression. We performed a randomized co... more Chronic pain is a disabling illness, often comorbid with depression. We performed a randomized controlled pilot study on mindfulness-based cognitive therapy (MBCT) targeting depression in a chronic pain population. Participants with chronic pain lasting ≥ 3 months; DSM-IV major depressive disorder (MDD), dysthymic disorder, or depressive disorder not otherwise specified; and a 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C₁₆) score ≥ 6 were randomly assigned to MBCT (n = 26) or waitlist (n = 14). We adapted the original MBCT intervention for depression relapse prevention by modifying the psychoeducation and cognitive-behavioral therapy elements to an actively depressed chronic pain population. We analyzed an intent-to-treat (ITT) and a per-protocol sample; the per-protocol sample included participants in the MBCT group who completed at least 4 of 8 sessions. Changes in scores on the QIDS-C₁₆ and 17-item Hamilton Depression Rating Sale (HDRS₁₇) were the ...

PloS one, 2017

Internet addiction (IA) is defined as a psychological dependence on the internet, regardless of t... more Internet addiction (IA) is defined as a psychological dependence on the internet, regardless of the type of activities once logged on, and previous studies have focused on adolescents and young adults. The aim of this study was to investigate the association between suicide attempts and sleep among community-dwelling adults with IA. The Young's Internet Addiction Test (IAT), the Korean version of the Composite International Diagnostic Interview (K-CIDI) and a suicide questionnaire were used in this cross-sectional multistage, cluster sampling population-based study. A total of 3212 adults aged 18-64 years were interviewed face-to-face, and they had been randomly selected through a one-person-per-household method. Of the 3212 adults, 204 were assessed as having IA (6.35%). Adults with IA were younger, and more frequently male, unmarried, and unemployed, and had poorer sleep quality than adults without IA (32.8% vs. 19.8%), whereas there was no significant difference in the absolu...

Journal of affective disorders, Jan 15, 2017

Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy ... more Given the proposed dopaminergic mechanism of low-dose naltrexone (LDN), we examined its efficacy as augmentation for depressive breakthrough on pro-dopaminergic antidepressant regimens. 12 adults (67% female, mean age = 45±12) with recurrent DSM-IV major depressive disorder (MDD) on dopaminergic antidepressant regimens (stimulants, dopamine agonists, bupropion [≥300mg/day], aripiprazole [≤2.5mg/day], or sertraline [≥150mg/day]) were randomized to naltrexone 1mg b.i.d. (n=6) or placebo (n=6) augmentation for 3 weeks. All subjects completed the trial. Hamilton Depression Rating Scale (HAM-D-17) scores (primary outcome measure) decreased from 21.2±2.0 to 11.7±7.7 for LDN, from 23.7±2.3 to 17.8±5.9 for placebo (Cohen's d=0.62; p=0.3 between treatment groups). HAM-D-28 scores decreased from 26.2±4.0 to 12.0±9.8 for LDN, from 26.3±2.6 to 19.8±6.6 for placebo (d=1.15; p=0.097). Montgomery-Asberg Depression Rating Scale (MADRS-10 item) scores decreased from 30.4±4.9 to 12.2±8.4 for LDN,...