White Matter Alterations Associated with Pro-inflammatory Cytokines in Patients with Major Depressive Disorder

Objective@#Regarding the neuroinflammatory theory of major depressive disorder (MDD), little is known about the effect of pro-inflammatory cytokines on white matter (WM) changes in MDD. We aimed to investigate the relationship between pro-inflammatory cytokines and WM alterations in patients with MDD. @*Methods@#Twenty-two patients with MDD and 22 healthy controls (HC) were evaluated for brain imaging and pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, interferon-γ and tumor necrosis factor (TNF)-α. Tract-based spatial statistics and FreeSurfer were used for brain image analysis. @*Results@#The levels of TNF-αand IL-8 were significantly higher in the MDD group than in HC. Compared to HC, lower fractional anisotropy (FA), and higher median diffusivity (MD) and radial diffusivity (RD) values were found in the MDD group for several WM regions. Voxel-wise correlation analysis showed that the level of TNF-α was negatively correlated with FA, and positively correlated with MD and RD in the left body and genu of the corpus callosum, left anterior corona radiata, and left superior corona radiata. @*Conclusion@#Our findings suggest that TNF-α may play an important role in the WM alterations in depression, possibly through demyelination.

White Matter Alterations Associated with Pro-inflammatory Cytokines in Patients with Major Depressive Disorder

Objective@#Regarding the neuroinflammatory theory of major depressive disorder (MDD), little is known about the effect of pro-inflammatory cytokines on white matter (WM) changes in MDD. We aimed to investigate the relationship between pro-inflammatory cytokines and WM alterations in patients with MDD. @*Methods@#Twenty-two patients with MDD and 22 healthy controls (HC) were evaluated for brain imaging and pro-inflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8, interferon-γ and tumor necrosis factor (TNF)-α. Tract-based spatial statistics and FreeSurfer were used for brain image analysis. @*Results@#The levels of TNF-αand IL-8 were significantly higher in the MDD group than in HC. Compared to HC, lower fractional anisotropy (FA), and higher median diffusivity (MD) and radial diffusivity (RD) values were found in the MDD group for several WM regions. Voxel-wise correlation analysis showed that the level of TNF-α was negatively correlated with FA, and positively correlated with MD and RD in the left body and genu of the corpus callosum, left anterior corona radiata, and left superior corona radiata. @*Conclusion@#Our findings suggest that TNF-α may play an important role in the WM alterations in depression, possibly through demyelination.

Erratum: Effects of Uric Acid on the Alterations of White Matter Connectivity in Patients with Major Depression

The authors discovered that the p-value for group difference in sex (male/female) in Table 1 was incorrect. And the authors described unclearly whether the p-value for the sex distribution was obtained by chi-square test or Fisher's exact test.

Effects of Uric Acid on the Alterations of White Matter Connectivity in Patients with Major Depression

OBJECTIVE: Uric acid is a non-enzymatic antioxidant associated with depression. Despite its known protective role in other brain disorders, little is known about its influence on the structural characteristics of brains of patients with major depressive disorder (MDD). This study explored the association between uric acid and characteristics of white matter (WM) in patients with MDD. METHODS: A total of 32 patients with MDD and 23 healthy controls (HCs) were examined. All participants were scored based on the Beck Depression Inventory and Beck Anxiety Inventory at baseline. All patients were also rated with the Hamilton Depression Rating Scale. We collected blood samples from all participants immediately after their enrollment and before the initiation of antidepressants in case of patients. Tract-based spatial statistics were used for all imaging analyses. RESULTS: Lower fractional anisotropy (FA) and higher radial diffusivity (RD) values were found in the MDD group than in the HC group. Voxelwise correlation analysis revealed that the serum uric acid levels positively correlated with the FA and negatively with the RD in WM regions that previously showed significant group differences in the MDD group. The correlated areas were located in the left anterior corona radiata, left frontal lobe WM, and left anterior cingulate cortex WM. CONCLUSION: The present study suggests a significant association between altered WM connectivity and serum uric acid levels in patients with MDD, possibly through demyelination.

Association of Plasma Levels of Angiotensin-Converting Enzyme and Cytokines with Recurrent Depression : A Preliminary Study

OBJECTIVES: Angiotensin-converting enzyme (ACE) gene and plasma levels of cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), have previously been determined to be associated with depression. The purpose of this study was to investigate the association of plasma levels of ACE and cytokines with recurrent depression. METHODS: A total of 52 participants (14 male, 38 female, aged 43.9 ± 14.0 years) were enrolled after being diagnosed with depression by experienced psychiatrists using the Mini International Neuropsychiatric Interview from the outpatient clinic of the Department of Psychiatry, CHA Bundang Medical Center. The participants completed blood sampling, the Hamilton Depression Rating Scale (HAMD), the Beck Depression Inventory, the Beck Anxiety Inventory, and the Scale for Suicidal Ideation. RESULTS: ACE plasma levels are higher in patients with recurrent depression (27.4 ± 10.4 U/L) than in patients with newly diagnosed depression (19.1 ± 7.7 U/L) (p = 0.004). The levels of cytokines, such as TNF-α, IL-4, IL-6, IL-10, are not significantly different between the two groups. Additionally, the ACE plasma level is negatively correlated with a reduction in the HAMD over six weeks (r = −0.429, p = 0.046, n = 22). CONCLUSIONS: The current findings show that plasma ACE levels may be associated with recurrent depression and further suggest that the renin-angiotensin system could play a role in recurrent depression.

Induced Pluripotent Stem Cells as a Novel Tool in Psychiatric Research

Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) provides a valuable opportunity to study neurodevelopmental and neurodegenerative psychiatric diseases by offering an unlimited source for patient-specific neuronal and glial cells. The present review focuses on the recent advancements in modeling psychiatric disorders such as Phelan-McDermid syndrome, Timothy syndrome, Rett syndrome, schizophrenia, bipolar disorder, and dementia. The treatment effects identified in studies on iPSCs using known therapeutic compounds are also summarized in this review. Here we discuss validation of cellular models and explore iPSCs as a novel drug screening tool. Although there are several limitations associated with the current methods used to study mental disorders, using iPSCs as a model system provides the advantage of rewinding and reviewing the development and degeneration of human neural cells.

Impact of Mindfulness-Based Cognitive Therapy on Intolerance of Uncertainty in Patients with Panic Disorder

OBJECTIVE: Intolerance of uncertainty (IU) is a transdiagnostic construct in various anxiety and depressive disorders. However, the relationship between IU and panic symptom severity is not yet fully understood. We examined the relationship between IU, panic, and depressive symptoms during mindfulness-based cognitive therapy (MBCT) in patients with panic disorder. METHODS: We screened 83 patients with panic disorder and subsequently enrolled 69 of them in the present study. Patients participating in MBCT for panic disorder were evaluated at baseline and at 8 weeks using the Intolerance of Uncertainty Scale (IUS), Panic Disorder Severity Scale-Self Report (PDSS-SR), and Beck Depression Inventory (BDI). RESULTS: There was a significant decrease in scores on the IUS (p<0.001), PDSS (p<0.001), and BDI (p<0.001) following MBCT for panic disorder. Pre-treatment IUS scores significantly correlated with pre-treatment PDSS (p=0.003) and BDI (p=0.003) scores. We also found a significant association between the reduction in IU and PDSS after controlling for the reduction in the BDI score (p<0.001). CONCLUSION: IU may play a critical role in the diagnosis and treatment of panic disorder. MBCT is effective in lowering IU in patients with panic disorder.

Serotonin Transporter and COMT Polymorphisms as Independent Predictors of Health-related Quality of Life in Patients with Panic Disorder

There is growing evidence of poor health-related quality of life (HRQOL) in patients with panic disorder (PD). However, little is known about the factors affecting HRQOL in patients with PD. The authors examined whether 5-HTTLPR tri-allelic approach and Cathechol-O-methyltransferase (COMT) Val(158)Met polymorphism can predict HRQOL in patients with PD controlling for sociodemographic factors and disorder-related symptom levels. The sample consisted of 179 patients with PD consecutively recruited from an outpatient clinic and age- and gender ratio-matched 110 healthy controls. The SF-36 was used to assess multiple domains of HRQOL. Hierarchical multiple regression analysis was performed to determine the independent effect of the 5-HTTLPR and COMT Val(158)Met on the SF-36 in panic patients. Patients with PD showed lowered HRQOL in all sub-domains of the SF-36 compared to healthy controls. The 5-HTTLPR independently and additively accounted for 2.2% of variation (6.7% of inherited variance) of perceived general health and the COMT Val(158)Met independently and additively accounted for 1.5% of variation (5.0% of inherited variance) of role limitation due to emotional problems in patient group. The present study suggests that specific genetic polymorphisms are associated with certain domains of HRQOL and provides a new insight on exploring the factors that predict HRQOL in patients with PD.

Associations between Smartphone Addiction Proneness and Psychopathology

OBJECTIVES: This study aims to investigate possible associations between proneness toward smartphone addiction and certain psychopathological variables to evaluate the psychopathological meaning of smartphone addiction. METHODS: Questionnaires were assigned to 755 adults between September and November 2012. We used the Korean Smartphone Addiction Proneness Scale (SAPS), the Beck Depression Inventory (BDI), the Beck Anxiety Inventory (BAI), the Obsessive-Compulsive Inventory-Revised (OCI-R), and the Barratt Impulsivity Scale-11 (BIS-11). Subjects were classified into two groups according to the scores of the SAPS ; the addiction proneness group and the normal-user group. RESULTS: The addiction proneness group had significantly higher scores than the normal-user group in the BDI, BAI, OCI-R, and BIS-11. The scores of the SAPS were positively correlated with the scores of the BDI, BAI, OCI-R, and BIS-11. Using logistic regression analysis, smartphone addiction proneness showed a significant association with BIS-11. CONCLUSIONS: The results of this study suggest that smartphone addiction proneness may be associated with depression, anxiety, obsessive-compulsive symptoms, and impulsivity. Furthermore, impulsivity could be a vulnerability marker for smartphone addiction proneness.

Factors Associated with Treatment Outcomes in Mindfulness-Based Cognitive Therapy for Panic Disorder

PURPOSE: Although the effectiveness of Mindfulness-Based Cognitive Therapy (MBCT) for panic disorder (PD) has been studied previously, data on the predictors of treatment outcomes in MBCT for PD are scarce. MATERIALS AND METHODS: Eighty patients with PD were screened to analyze treatment outcomes such as MBCT completion, treatment response, and remission after undergoing MBCT for PD. Sociodemographic characteristics, comorbid personality disorders, and baseline medication doses were examined. The study administered the Panic Disorder Severity Scale, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale and Anxiety Sensitivity Inventory-Revised to patients at baseline and at eight weeks. RESULTS: Sixty-five participants were enrolled in the present study. Comorbid personality disorder was significantly associated with MBCT non-completion. We found that anxiety sensitivity (AS) improvement after an eight week MBCT program was a statistically significant factor associated with treatment response. Using logistic regression analysis, AS improvement after MBCT showed significant association with PD remission after MBCT. CONCLUSION: Comorbid personality disorders of participants could be a potential predictor of MBCT non-completion. Furthermore, AS improvement after MBCT may predict treatment response and remission after MBCT for PD. However, better designed studies with a larger number of patients are needed to confirm our findings.

The Effects of 5-HTR1A Polymorphism on Cingulum Connectivity in Patients with Panic Disorder

OBJECTIVE: Serotonin-1A receptors (5-HTR1A) is suggested to be involved in the etiology of several psychiatric disorders including panic disorder (PD). A few imaging studies have suggested the alterations of the cingulum bundle in PD. The objective of this study is to examine the structural changes of cingulum related to the 5-HTR1A polymorphism rs6295 in the patients with PD. METHODS: Thirty-two right-handed patients with PD [11 men, 21 women; 40.34+/-13.17 (mean+/-SD) age] who met the diagnostic criteria in Structured Clinical Interview for DSM-IV were examined by means of MRI at 3 Tesla. We divided the patients with PD into CC genotype group and non CC genotype group (GG/CG genotype group) of the 5-HTR1A rs6295 polymorphism to compare the cingulum white matter connectivity. RESULTS: Tract-based spatial statistics showed significantly increased fractional anisotropy (FA) values in cingulate gyrus process of left cingulum in 5-HTR1A CC genotype compared to GG/CG genotype in PD. Significant positive correlations were shown between the Albany Panic and Phobia Questionnaire (APPQ) interoceptive fear subscale scores, the Anxiety Sensitivity Inventory-Revised fear of publicly observable anxiety reaction subscale scores and FA values of cingulate gyrus process of left cingulum in 5-HTR1A rs6295 GG/CG genotype group. In CC genotype group, APPQ total, APPQ agoraphobia subscale and APPQ social phobia subscale scores also showed significant positive correlations with FA values of hippocampal process of right cingulum. CONCLUSION: This preliminary study suggests that 5-HTR1A polymorphism may be associated with the cingulum white matter connectivity in PD.

The Tolerability of Mirtazapine Augmentation in Schizophrenic Patients Treated with Risperidone: A Preliminary Randomized Placebo-controlled Trial

OBJECTIVE: Some patients with schizophrenia may need mirtazapine augmentation to improve negative and cognitive symptoms. However there have been a few studies about the tolerability of mirtazapine augmentation to antipsychotics such as akathisia, extrapyramydal symptoms, weight gain, and body mass index (BMI). METHODS: This study was an eight-week double-blind, randomized controlled trial (RCT) of mirtazapine augmentation to risperidone. Twenty-one stabilized participants diagnosed with schizophrenia and undergoing treatment with risperidone were randomized to adjunctive treatment with mirtazapine (15 mg/day for the first two weeks, 30 mg/day for the next six weeks) or placebo. Eleven patients were assigned to the mirtazapine group, and nine patients were given placebo. RESULTS: There was no significant difference between the mirtazapine and placebo groups with respect to Barnes Akathisia rating Scale (BAS) and Sympsom-Angus Scale (SAS). However, the mirtazapine group exhibited a statistically significant increase in weight and BMI (p<0.05). CONCLUSION: These results suggest that mirtazapine augmentation can be tolerable in schizophrenic patients treated with risperidone; however, we should pay attention to the weight gain with mirtazapine. Our results should be replicated in a large-scale lengthy trial.

What is Depression? From the Viewpoint of Modern Psychiatry / 신경정신의학

Depression is heterogeneous in terms of its clinical aspect, diagnosis, cause, neurobiology, drug response and course. Because of the heterogeneity of major depressive disorder (MDD), DSM-IV classified MDD into various subtypes, such as melancholic, atypical, severe with psychotic feature, severe without psychotic feature, with postpartum onset, with catatonic feature, early-onset, late-onset, chronic, single or recurrent. In spite of the efforts of many clinicians trying to classify and explain the nature of MDD, depression is still qualified as a syndrome rather than a disease. When we see patients with MDD in clinical setting, we still use several subtypes of classical classification in order to comprehend the patient better. Psychiatrist should treat the patients with MDD according to their specific features and integrate the various information from them. For these reasons, depression is regarded as a complicated disease to identify and treat. Therefore, mental health professionals, especially psychiatrists should be trained on these diverse characteristics of MDD and it is recommended that the treatment of depression should be referred to a psychiatrist.