Boung Chul Lee

Neural correlates of affective processing in response to sad and angry facial stimuli in patients with major depressive disorder

Mood abnormalities related to major depressive disorder (MDD) seem to result from disturbances in pathways connecting the fronto-limbic and subcortical, both regions known to be involved in the processing of emotional information. Using functional magnetic resonance imaging (fMRI), we measured neural responses to viewing images of sad, angry and neutral faces in 21 patients with MDD and 15 healthy controls. When shown pictures of sad faces, patients with MDD relative controls showed decreased activations bilaterally in the dorsolateral prefrontal cortex, inferior orbitofrontal cortex (OFC), medial OFC, caudate, and hippocampus. We also found significant group differences under the angry face condition, bilaterally, in the inferior OFC and medial OFC areas. Our findings indicate that decreased activations in the fronto-limbic and subcortical regions in response to affectively negative stimuli may be associated with pathophysiology of MDD.

Alcohol and Cognition in the Elderly: A Review

Consumption of large amounts of alcohol is known to have negative effects, but consumption in smaller amounts may be protective. The effect of alcohol may be greater in the elderly than in younger adults, particularly with regard to cognition. However, the drinking pattern that will provide optimal protection against dementia and cognitive decline in the elderly has not been systematically investigated. The present paper is a critical review of research on the effect of alcohol on cognitive function and dementia in the elderly. Studies published from 1971 to 2011 related to alcohol and cognition in the elderly were reviewed using a PubMed search. Alcohol may have both a neurotoxic and neuroprotective effect. Longitudinal and brain imaging studies in the elderly show that excessive alcohol consumption may increase the risk of cognitive dysfunction and dementia, but low to moderate alcohol intake may protect against cognitive decline and dementia and provide cardiovascular benefits. Evidence suggesting that low to moderate alcohol consumption in the elderly protects against cognitive decline and dementia exists; however, because of varying methodology and a lack of standardized definitions, these findings should be interpreted with caution. It is important to conduct more, well-designed studies to identify the alcohol drinking pattern that will optimally protect the elderly against cognitive decline and dementia.

The use of AlloDerm on major burn patients: AlloDerm prevents post-burn joint contracture

In efforts to prevent and reduce joint contracture and scar formation after burn, we used the acellular human dermis (AlloDerm) as a dermal replacement in the acute stage. A total of 64 patients received AlloDerm graft selectively on joint areas during the study period from March, 2005 to July, 2007. From January to March, 2008, a total of 31 patients returned to our burn center to examine the functional results by measuring range of motion of joints. Additionally, the quality of grafted skin condition criteria of skin elasticity, scar thickness, trans-epidermal water loss, melanin and erythema level was measured in a total of 11 patients among them. By analyzing the limitation level of 55 joints excluding hand areas, we found that 24 joints (43.6%) showed no limitations, 12 joints (21.8%) showed limitations below 10%, 16 joints (29.1%) showed limitations between 10 and 19% and 3 joints (5.5%) showed limitations over 20%. The scar thickness of non-AlloDerm applied areas was 2.5+/-0.9 mm and AlloDerm applied areas was 1.8+/-0.7 mm (p = 0.396). Trans-epidermal water loss for non-AlloDerm applied areas was 20.9+/-7.7 g/h/m(2) and AlloDerm applied areas was 10.8+/-3.4 g/h/m(2) (p<0.001). Erythema value for non-AlloDerm applied areas was 436.1+/-65.8, whereas AlloDerm applied area was 394.4+/-61.2 (p<0.001). Acellular dermal matrix is a good option for treating major burns to prevent scar formation after burn and loss of joint function.

The effect of burn rehabilitation massage therapy on hypertrophic scar after burn: A randomized controlled trial

OBJECTIVE To evaluate the effect of burn rehabilitation massage therapy on hypertrophic scar after burn. METHOD One hundred and forty-six burn patients with hypertrophic scar(s) were randomly divided into an experimental group and a control group. All patients received standard rehabilitation therapy for hypertrophic scars and 76 patients (massage group) additionally received burn scar rehabilitation massage therapy. Both before and after the treatment, we determined the scores of visual analog scale (VAS) and itching scale and assessed the scar characteristics of thickness, melanin, erythema, transepidermal water loss (TEWL), sebum, and elasticity by using ultrasonography, Mexameter(®), Tewameter(®), Sebumeter(®), and Cutometer(®), respectively. RESULTS The scores of both VAS and itching scale decreased significantly in both groups, indicating a significant intragroup difference. With regard to the scar characteristics, the massage group showed a significant decrease after treatment in scar thickness, melanin, erythema, TEWL and a significant intergroup difference. In terms of scar elasticity, a significant intergroup difference was noted in immediate distension and gross skin elasticity, while the massage group significant improvement in skin distensibility, immediate distension, immediate retraction, and delayed distension. CONCLUSION Our results suggest that burn rehabilitation massage therapy is effective in improving pain, pruritus, and scar characteristics in hypertrophic scars after burn.

Efficacy of naltrexone in the treatment of chronic refractory itching in burn patients: preliminary report of an open trial.

Pruritis (itching) constitutes a source of severe distress for burn patients. The authors administered naltrexone to burn patients suffering from itching that was refractory to treatment with antihistamine and anticonvulsant medications to examine the efficacy of this medication as a treatment for pruritis in burn patients. Nineteen burn patients admitted to the Hallym Burn Center at Hangang Sacred Heart Hospital in Seoul, Korea, with burns over 40.32% (±18.3) of their total body surface were recruited for this study. The mean number of postburn days before naltrexone treatment was 157.3 days (±114.7). The authors observed a significant decrease in itching sensations after 2 weeks of treatment with naltrexone (z = −3.32, P = .001). Scratching activity was also decreased in 44.5% (±20.5) of subjects. The authors propose that naltrexone constitutes a potential antipruritic medication for burn patients suffering from treatment-refractory itching.

Change of serum phosphate level and clinical outcome of hypophosphatemia in massive burn patient.

BACKGROUND Hypophosphatemia is relatively common phenomenon in patients with massive burn injury. Therefore, we check serum phosphate level routinely and try to supply phosphate in a timely manner. The purpose of this study was to investigate the change of the serum phosphate level of early postburn period and the impact of hypophosphatemia on the prognosis of patients. METHODS A total of 227 patients with burn injury were reviewed retrospectively. We performed analysis of serum phosphate level within 20 days from burn injury. RESULTS Patients’ mean (SD) age was 47.0 (14.1) years, and mean (SD) percentage of total body surface area burned were 47.7 (21.9). Severe hypophosphatemia (phosphate < 1.0 mg/dL) was observed in 35 patients (15.8%), and moderate hypophosphatemia (1.0 ⩽ phosphate < 2.0 mg/dL) was found in 115 patients (50.6%). Therefore, overall incidence of hypophosphatemia was 66.4%. There was no significant difference in serum phosphate level with survival, total body surface area burned, and mechanical ventilation. Age (odds ratio [OR], 3.180; 95% confidence interval [CI], 1.025–9.871; p = 0.045), total body surface area burned (OR, 20.934; 95% CI, 6.845–64.024; p = 0.000), and mechanical ventilation (OR, 5.581; 95% CI, 2.380–13.085; p = 0.002) were independently associated with mortality. However, serum phosphate level (OR, 0.828; 95% CI, 0.275–2.495; p = 0.737) does not have a statistical significance. CONCLUSION Although multiple studies have evaluated the efficacy and safety of phosphate repletion regimens, the effect on mortality and morbidity is not well reported. However, our results show that patients with massive burn injury have high incidence of hypophosphatemia, and hypophosphatemia can result in many complications. Therefore, routine check and supply of phosphate can be suggested in patients with massive burn injury. LEVEL OF EVIDENCE Prognostic study, level II.

The Effectiveness of Continuing Group Psychotherapy for Outpatients with Alcohol Dependence: 77‐Month Outcomes

BACKGROUND Group psychotherapy (PT) is one of the most common interventions used to treat alcohol dependence (AD), and it is assumed to be effective. Despite its common clinical use, long-term trials that have been conducted to examine the efficacy of group PT in the treatment of outpatients with AD are limited and often lack appropriate comparisons. On that basis, a long-term comparative trial was performed with the main objective of evaluating the effectiveness of continuing group PT for outpatients with AD. METHODS Quasi-experimental trial was conducted from January 2004 to May 2010 in 177 AD subjects who had completed an inpatient 10-week alcohol treatment program. Abstinence rates of the combined group (experimental group: outpatient individual PT plus group PT, N = 94) and the standard outpatient individual PT-only group (comparison group, N = 83) were statistically compared using Kaplan-Meier survival analysis. Predictive factors of abstinence rate for alcohol were assessed using Cox regression analysis. RESULTS Abstinence rates of the combined PT group were significantly high relative to those of the outpatient individual PT-only group. Significant predictive factors for the alcohol abstinence rate were outpatient group PT and age. Even after controlling for confounding factors, outpatient group PT was a significant predictive factor for the alcohol abstinence rate. CONCLUSIONS Our findings indicate that for AD patients who had completed an inpatient 10-week alcohol treatment, outpatient group PT appears to be an effective form of continuing care or aftercare within the context of an outpatient service delivery system.

The Genetic Effect of Copy Number Variations on the Risk of Alcoholism in a Korean Population

BACKGROUND Alcoholism, a chronic behavioral disorder characterized by excessive alcohol consumption, has been a leading cause of morbidity and premature death. This condition is believed to be influenced by genetic factors. As copy number variation (CNV) has been recently discovered in human genome, genomic diversity of human genome is more frequent than previously thought. Many studies have reported evidences that CNV is associated with the development of complex diseases. In this study, we hypothesized that CNV can predict the risk of alcoholism. METHODS Using the Illumina HumanHap660W-Quad BeadChip (∼660 k markers), genome-wide genotyping was performed to obtain signal and allelic intensities from 116 alcoholic cases and 1,022 healthy controls (total n = 1,138) in a Korean population. To identify alcoholism-associated CNV regions, we performed a genome-wide association analysis, using multivariate logistic regression model controlling for age and gender. RESULTS We identified a total of 255,732 individual CNVs and 3,261 CNV regions (1,067 common CNV regions, frequency > 1%) in this study. Results from multivariate logistic regression showed that the chr20:61195302-61195978 regions were significantly associated with the risk of alcoholism after multiple corrections (p = 5.02E-05, p(corr) = 0.04). Most of the identified variations in this study overlapped with the previously reported CNVs in the Database of Genomic Variants (95.3%). The identified CNVs, which encompassed 3,226 functional genes, were significantly enriched in the cellular part, in the membrane-bound organelle, in the cell part, in developmental processes, in cell communication, in neurological system process, in sensory perception of smell and chemical stimulus, and in olfactory receptor activity. CONCLUSIONS This is the first genome-wide association study to investigate the relationship between common CNV and alcoholism. Our results suggest that the newly identified CNV regions may contribute to the development of alcoholism.

Effort-Based Reinforcement Processing and Functional Connectivity Underlying Amotivation in Medicated Patients with Depression and Schizophrenia

Amotivation is a common phenotype of major depressive disorder and schizophrenia, which are clinically distinct disorders. Effective treatment targets and strategies can be discovered by examining the dopaminergic reward network function underlying amotivation between these disorders. We conducted an fMRI study in healthy human participants and medicated patients with depression and schizophrenia using an effort-based reinforcement task. We examined regional activations related to reward type (positive and negative reinforcement), effort level, and their composite value, as well as resting-state functional connectivities within the meso–striatal–prefrontal pathway. We found that integrated reward and effort values of low effort-positive reinforcement and high effort-negative reinforcement were behaviorally anticipated and represented in the putamen and medial orbitofrontal cortex activities. Patients with schizophrenia and depression did not show anticipation-related and work-related reaction time reductions, respectively. Greater amotivation severity correlated with smaller work-related putamen activity changes according to reward type in schizophrenia and effort level in depression. Patients with schizophrenia showed feedback-related putamen hyperactivity of low effort compared with healthy controls and depressed patients. The strength of medial orbitofrontal-striatal functional connectivity predicted work-related reaction time reduction of high effort negative reinforcement in healthy controls and amotivation severity in both patients with schizophrenia and those with depression. Patients with depression showed deficient medial orbitofrontal-striatal functional connectivity compared with healthy controls and patients with schizophrenia. These results indicate that amotivation in depression and schizophrenia involves different pathophysiology in the prefrontal-striatal circuitry. SIGNIFICANCE STATEMENT Amotivation is present in both depression and schizophrenia. However, treatment involves the use of drugs that enhance serotonin activity in depression and inhibit serotonin and dopamine activity in schizophrenia. Understanding how motivation processed in the mesocorticolimbic and nigostriatal pathways is affected in depression and schizophrenia is important in discovering treatment targets and strategies for amotivation. To our knowledge, this is the first study to compare patients with depression and schizophrenia in a common functional construct. By using an effort-based reinforcement task and examining resting-state functional connectivity in the dopaminergic network, we propose that difference in striato–orbitofrontal dysfunction in effort-based reinforcement between depression and schizophrenia may be related to differences in the extent of functional dysconnectivity in the dopaminergic pathway.

Aripiprazole augmentation for treatment of patients with chronic or recurrent major depressive disorder: A 12-week prospective open-label multicentre study

Patients with chronic or recurrent major depressive disorder (MDD) have faced a dearth of treatment options. The present study evaluated the effectiveness and tolerability of aripiprazole augmentation for the treatment of chronic or recurrent MDD. This was the first 12-week prospective, multicentre, open-label study of the effectiveness and tolerability of flexibly dosed aripiprazole as an augmentation to ongoing antidepressant treatment in patients with chronic or recurrent MDD. The primary outcome measure for effectiveness was changes between baseline and endpoint (week 12) in total scores on the Montgomery–Asberg Depression Rating Scale. Adverse events (AEs) occurring throughout the trial are also reported. The Montgomery–Asberg Depression Rating Scale total scores decreased significantly between the baseline and the endpoint (magnitude of difference=−11.6, P<0.0001). At the endpoint, the response rate was 55.2% and the remission rate was 41.3%. Adjunctive aripiprazole treatment administered from week 1 through the endpoint was associated with remission and significant treatment responses. More than half (55.8%) of those taking adjunctive aripiprazole completed the study and relatively few patients discontinued participation because of AEs. None of the patients discontinued participation in the study because of an inadequate therapeutic response. Common AEs included headache, akathisia, insomnia and constipation. The mean dose of aripiprazole at the endpoint was 6.6 mg/day. Adjunctive aripiprazole may be effective and tolerable for patients with chronic or recurrent MDD. Adequately powered and controlled clinical trials should be conducted to confirm our open-label study findings.