Jong Woo Paik

Demonstration of decreased gray matter concentration in the midbrain encompassing the dorsal raphe nucleus and the limbic subcortical regions in major depressive disorder: An optimized voxel-based morphometry study

BACKGROUNDnPrevious neuroimaging studies in patients with major depressive disorder (MDD) have reported changes in several brain areas, such as the medial and dorsolateral orbital cortex, amygdala, hippocampus, and basal ganglia. However, the results of these studies are inconsistent, and relatively few studies have been conducted using voxel-based morphometry (VBM) to detect gray matter concentration (GMC) abnormalities in patients with MDD.nnnMETHODSnWe examined 47 MDD patients and 51 healthy controls to investigate structural abnormalities using a 1.5 T magnetic resonance imaging system, which was normalized to a customized T1 template and segmented with optimized VBM. Analysis of covariance with age and gender as covariates was adopted for the VBM statistics; the level of statistical significance was set at P<0.05 for the corrected false discovery rate.nnnRESULTSnDecreased GMC was found in MDD patients in the bilateral amygdalae, hippocampi, fusiform gyri, lingual gyri, insular gyri, middle-superior temporal gyri, thalami, cingulate gyri, the central lobule of the cerebellum, and the midbrain encompassing the dorsal raphe nuclei (DRN).nnnLIMITATIONSnHalf of our study subjects were taking antidepressants. This may have been a potential confounding factor if any of the medications affected cortical volume.nnnCONCLUSIONSnThe results suggest that the GMC of several regions associated with emotion regulation was lower in MDD patients. In particular, we found decreased GMC in the DRN. These findings may provide a better understanding of the anatomical properties of the neural mechanisms underlying the etiology of MDD.

Symptom severity and attitudes toward medication: Impacts on adherence in outpatients with schizophrenia

OBJECTIVEnThe primary aim of this study was to compare electronic monitoring with other measures of adherence to antipsychotic medication in outpatients with schizophrenia. The secondary aim of the study was to analyze the relationships between adherence and other clinical parameters.nnnMETHODnFifty-one patients diagnosed with schizophrenia were monitored over an eight-week period. Medication adherence was assessed using the Medication Event Monitoring System (MEMS), which is a bottle cap with a microprocessor that records the occurrence and times of bottle opening, patient self-reports, a clinician rating scale, and pill counts. Agreements among adherence measures and the relationships between adherence and other clinical factors were assessed.nnnRESULTSnThe rate of non-adherence according to the MEMS was 41.2%, considerably higher than those of pill counting (7.8%), clinician rating scale (7.8%), or self-reporting (25.5%). Excitement, impulse control, and preoccupation symptoms on the Positive and Negative Syndrome Scale (PANSS) were higher in the non-adherent patients than in the adherent patients. The full Drug Attitude Inventory (DAI) score was higher in adherent versus non-adherent patients and the significant other subscale of the Multidimensional Scale of Perceived Social Support score was lower in the adherent patients. The Clinical Global Impression-Severity score was negatively correlated with adherence as measured by the MEMS (r=-0.426, p<0.05) and DAI scores were positively correlated with adherence according to the MEMS and the clinician rating scale (r=0.498, p<0.01 and r=0.387, p<0.05). Multivariate analysis showed that PANSS and DAI scores significantly contributed to MEMS adherence.nnnCONCLUSIONnAdherence as measured by the MEMS showed a discrepancy with other measures of adherence in patients with schizophrenia. The severity of disease and attitudes toward medication were related to adherence. Further studies are needed to evaluate the impacts of medication adherence in schizophrenia.

EFFECT OF SEROTONIN RECEPTOR 2A GENE POLYMORPHISM ON MIRTAZAPINE RESPONSE IN MAJOR DEPRESSION

The 5-HTR2A gene is a candidate gene for influencing the clinical response to treatment with antidepressants. The purpose of this study was to determine the relationship between the -1438A/G polymorphism of the 5-HTR2A gene and the response to mirtazapine in a Korean population with major depressive disorder. Mirtazapine was administered for eight weeks to the 101 patients who completed the study, during which we evaluated the clinical outcome using repeated-measures ANCOVA. A main effect of genotype or an effect of genotype-time interactions on the decrease in HAMD score during the eight-week follow-up was not found, which suggests that the 5-HTR2A -1438A/G polymorphism does not affect the clinical outcome to mirtazapine administration. However, significant effects of genotype and allele carriers on the decrease in the sleep score over the eight weeks were found (genotype: F = 4.093, p = 0.017; allele: F = 4.371, p = 0.037), whereas no effect of genotype-time interactions on the decrease in the HAMD score over the eight-week follow-up was found. These observations suggest that the -1438A/G polymorphism affects the sleep improvement but not the sleep pattern over time. A t-test-based evaluation of the effect of the 5-HTR2A -1438A/G polymorphism on the sleep improvement at each time period revealed significant differences in the sleep scores after two weeks of mirtazapine administration. The sleep scores were lower for carriers of the A+ allele than of the A — allele after two weeks of mirtazapine administration (p = 0.041), which means that the -1438GG genotype is associated with less improvement in sleep, and suggests that the effect of mirtazapine on improving the sleep quality differs with the 5-HTR2A -1438A/G polymorphism within two weeks of mirtazapine treatment. In conclusion, although the -1438A/G polymorphism affects the sleep improvement resulting from the administration of mirtazapine to Korean patients with major depressive disorder, our results do not support the hypothesis that this polymorphism of the 5-HTR2A gene is involved in the therapeutic response to mirtazapine.

Association of the adrenergic alpha 2a receptor − 1291C/G polymorphism with weight change and treatment response to mirtazapine in patients with major depressive disorder

BACKGROUNDnAdrenergic alpha2a receptors (ADRA2A) are expressed in the central nervous system and peripheral tissues. The primary mechanism of action of mirtazapine is the antagonism of central presynaptic alpha2 receptors. Mirtazapine is reportedly associated with weight gain. Our objective was to determine whether the ADRA2A -1291C/G polymorphism is associated with weight gain and treatment response to mirtazapine in patients with major depressive disorder (MDD).nnnMETHODSnThe ADRA2A -1291C/G polymorphism was analyzed in 314 MDD patients and 162 control subjects. All patients were evaluated using the 21-item Hamilton Depression Rating Scale at the beginning of the study and at 1, 2, 4, and 8 weeks of mirtazapine treatment.nnnRESULTSnNo relationship was observed between the ADRA2A -1291C/G polymorphism and MDD. No significant difference was found between responder and non-responder groups when comparing the ADRA2A genotype distribution with treatment response to mirtazapine. Repeated measures ANOVA with the last observation carry-forward test indicated that after adjusting for baseline body weight, age, and gender, the subjects with the C/C genotype exhibited a greater mean body weight gain than the subjects with the C/G or G/G genotype after 8 weeks of mirtazapine treatment (p=0.052).nnnCONCLUSIONSnThe ADRA2A -1291C/G polymorphism does not appear to be a predictor of treatment response to mirtazapine. This polymorphism was weakly associated with weight change after 8 weeks of mirtazapine treatment. Further investigation is required to determine whether other polymorphisms of this gene influence treatment response and weight change in patients receiving mirtazapine.

Alexithymia and low cooperativeness are associated with suicide attempts in male military personnel with adjustment disorder: A case–control study

Subpopulations of patients with adjustment disorder are at increased risk for suicide. The current study investigated whether personality traits, including alexithymia, temperament, and character, are associated with an increased risk of suicide in individuals with adjustment disorder. Age- and sex-matched patients meeting the diagnostic and statistical manual of mental disorders (DSM-IV) criteria for adjustment disorder with (n=92) and without (n=92) a history of suicide attempts were recruited for the present study. Ninety-two healthy individuals who did not meet diagnostic criteria for Axis I or II diagnoses were used as controls. The Toronto alexithymia scale-20 (TAS-20) and the temperament and character inventory (TCI) were used to assess personality traits. Significantly higher total and subscale scores on the TAS-20, including on the difficulty-identifying-feelings (DIF) and difficulty-describing-feelings (DDF) subscales, and lower scores on the TCI cooperativeness subscale were noted in adjustment-disorder patients with previous suicide attempts. In the multivariate regression analysis, high DDF and DIF and low cooperativeness increased the risk of suicide attempts in adjustment-disorder patients. A subsequent path analysis revealed that high DDF had a direct effect on suicide attempts, whereas high DIF had an indirect effect on suicide attempts via low cooperativeness.

The neural substrates of affective face recognition in patients with Hwa-Byung and healthy individuals in Korea.

Hwa-Byung (HB) is a Korean culture-bound psychiatric syndrome caused by the suppression of anger. HB patients have various psychological and somatic symptoms, such as chest discomfort, a sensation of heat, and the sensation of having an epigastric mass. In this study, we measured brain activity in HB patients and healthy individuals in response to affective facial stimuli. Using functional magnetic resonance imaging (fMRI), the current study measured neural responses to neutral, sad, and angry facial stimuli in 12 healthy individuals and 12 patients with HB. In response to all types of facial stimuli, HB patients showed increased activations in the lingual gyrus and fusiform gyrus compared with healthy persons, but they showed relatively lower activation in the thalamus. We also found that patients with HB showed lower activity in response to the neutral condition in the right ACC than healthy controls. The current study indicates that the suppression of affect results in aberrant function of the brain regions of the visual pathway, and functional impairment in the ACC may contribute to the pathophysiology of HB.

Temperament and character of young male conscripts with adjustment disorder: a case-control study.

Abstract Personality is an important clinical factor for successful adjustment in stressful situations. The aim of this study was to examine possible differences in temperament and character dimensions between patients with adjustment disorder with depressed mood and healthy controls. Among the young male conscripts, 86 subjects with adjustment disorder with depressed mood and 86 healthy controls were included. The mean scores in the 7 dimensions and 25 subscales of the Temperament and Character Inventory were compared between the patients with adjustment disorder with depressed mood and the control group by an independent t-test. The patients with adjustment disorder with depressed mood had significantly higher scores on harm-avoidance and lower scores on self-directedness, cooperativeness, and self-transcendence than did the controls. There were no differences in novelty seeking, reward dependence, and persistence in temperament between the two groups. The results of this study suggest that the personality traits of the subjects with adjustment disorder with depressed mood would make them vulnerable to stressful situations and less skilled in coping with conscription.

A Meta-Analysis Comparing Open-Label versus Placebo-Controlled Clinical Trials for Aripiprazole Augmentation in the Treatment of Major Depressive Disorder: Lessons and Promises

Objective The present study is to provide whether open-label studies (OLS) may properly foresee the efficacy of randomized, placebo-controlled trials (RCTs) using OLSs and RCTs data for aripiprazole in the treatment of MDD, with the use of meta-analysis approach. Methods A search of the studies used the key terms depression and aripiprazole from the databases of PubMed/PsychInfo from Jan 2005 through July 2013. The data were selected and verified for publication in English-based peer-reviewed journals based on rigorous inclusion criteria. Extracted data were delivered into and run by the Comprehensive Meta Analysis program v2. Results The pooled SMDs for the primary efficacy measure was statistically significant, pointing out the significant reduction of depressive symptoms after aripiprazole augmentation (AA) to current antidepressant treatment in OLSs (pooled SMD=-2.114, z=-9.625, p<0.001); similar results were also found in RCTs (pooled SMD=-2.202, z=-6.862, p<0.001). The meta-regression analysis revealed no influence of the study design for treatment outcome. Conclusion There was no difference in the treatment effects of aripiprazole as an augmentation therapy in both OLSs and RCTs, indicating that open-label design may be a potentially useful predictor for treatment outcomes of controlled-clinical trials. The proper conduction of OLSs may provide informative, useful and preliminary clinical data and factors to be involved in controlled-clinical trials, by which we may have better understanding on the role of AA (e.g., dosing issues, proper duration of treatment, specific population for AA) implicated in the treatment of MDD in clinical practice.

Evidence-Based, Pharmacological Treatment Guideline for Depression in Korea, Revised Edition

This paper aims to introduce, summarize, and emphasize the importance of the Evidence-Based, Pharmacological Treatment Guideline for Depression in Korea, Revised Edition. The guideline broadly covers most aspects of the pharmacological treatment of patients in Korea diagnosed with moderate to severe major depression according to the DSM-IV TR. The guideline establishment process involved determining and answering a number of key questions, searching and selecting publications, evaluating recommendations, preparing guideline drafts, undergoing external expert reviews, and obtaining approval. A guideline adaptation process was conducted for the revised edition. The guideline strongly recommends pharmacological treatment considered appropriate to the current clinical situation in Korea, and should be considered helpful when selecting the appropriate pharmacological treatment of patients diagnosed with major depressive disorder. Therefore, the wide distribution of this guideline is recommended.

Delays in depression treatment among Korean population

Delays in mental health service utilization for patients with depression have been observed globally. To elucidate some aspects of delays, age‐related associations with a series of variables representing different stages of mental health service use were studied concurrently.