Joonho Choi

Cue-Exposure Therapy to Decrease Alcohol Craving in Virtual Environment

During abstinence from alcohol, craving is elicited by the cues and contexts previously associated with alcohol, which contribute to relapse. To prevent the craving and relapse experienced by alcoholics, cue-exposure therapy (CET) has been used to extinguish the association between alcohol and alcohol-related cues and contexts. This study applied CET, using a virtual reality (VR) system, to eight members of an Alcoholics Anonymous group for eight sessions. Cues and contexts most likely to elicit an urge to drink were selected through a preliminary survey in order to compose VR-CET scenarios: a glass, a bottle, food, and a bar were judged to be the most tempting for people in alcohol dependence and abstinence. Using these cues and contexts, a Japanese-style pub and a western bar were created. Each session was administered for 30 minutes by a psychiatrist and included an introduction, immersion, VR navigation, interviews about feelings, and self-report questionnaires about cravings. The eight sessions consisted of initial and closing sessions and person-, object-, and situation-focused sessions. As a result, a reduction in cue-elicited craving after VR-CET was reported. A mean score of 15.75 (SD = 10.91) on the Alcohol Urge Questionnaire in the first session decreased to 11.50 (SD = 5.76) in the final session. This study suggests that using virtual reality can enhance the effectiveness of CET.

Relation between plasma brain-derived neurotrophic factor and nerve growth factor in the male patients with alcohol dependence

Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are thought to be related to neuroprotection in cell culture and animal studies. Our aim was to verify the changes in human plasma BDNF and NGF concentrations induced by chronic alcohol use. Forty-one male patients with alcohol dependence were sampled the next morning of admission and compared with 41 healthy male subjects. Plasma BDNF and NGF were assayed using an enzyme-linked immunosorbent assay (ELISA). Mean plasma BDNF level was significantly higher in the patients with alcohol dependence (3502.21+/-1726.9 pg/mL) compared with the healthy subjects (861.75+/-478.9 pg/mL) (P=.000). Mean plasma NGF level was also significantly higher in patients with alcohol dependence (137.64+/-32.7 pg/mL) than in healthy subjects (112.61+/-90.2 pg/mL) (P=.012). Plasma BDNF and NGF levels showed significant negative correlation in alcohol dependence group (r=-0.388, P=.012). Increased plasma BDNF and NGF with negative correlation in alcohol-dependent patients may have some role in the regeneration of damage done by chronic alcohol use.

Phosphorylation of ERK and CREB in cultured hippocampal neurons after haloperidol and risperidone administration.

Abstract  The purpose of the present paper was to determine whether the brief exposure of neurons to antipsychotic drugs is associated with the activation of extracellular signal‐regulated kinases (ERK) and cyclic adenosine 3′,5′‐monophosphate (cAMP) response element (CRE) binding protein (CREB). The activation of ERK‐1/2 and CREB can be monitored by immunoblotting with antibodies that specifically recognize p‐ERK‐1/2 (phosphorylated on Thr‐202 and Tyr‐204) and p‐CREB (phosphorylated on Ser‐133). In hippocampal neuron cultures at 25 days in vitro (DIV), the levels of ERK and CREB phosphorylation significantly increased after treatment with haloperidol (50 nmol/L) and risperidone (50 nmol/L), except when risperidone was administered at the p‐CREB level. However, risperidone also increased the p‐CREB level at an insignificant rate in the same direction. At 10 DIV, none of the antipsychotic drugs significantly increased the level of ERK and CREB phosphorylation. The difference between levels of ERK and CREB phosphorylation in response to haloperidol and risperidone at 25 DIV was also observed. Risperidone significantly increased the level of ERK‐1/2 phosphorylation, but not the level of CREB phosphorylation. Haloperidol, in contrast, had a different effect. These data indicate that neuronal maturation affects the phosphorylation of ERK and CREB in response to antipsychotic drugs. Furthermore, these results demonstrate that different antipsychotic drugs could lead to different profiles of ERK and CREB phosphorylation in neurons.

Fractal Analysis of EEG in Hypnosis and its Relationship with Hypnotizability

Fractal analysis was applied to study the trends of EEG signals in the hypnotic condition. The subjects were 19 psychiatric outpatients. Hypnotizability was measured with the Hypnotic Induction Profile (HIP). Fifty-four sets of EEG data were analyzed by detrended fluctuation analysis (DFA), a well-established fractal analysis technique. The scaling exponents, which are the results of fractal analysis, are reduced toward white noise during the hypnotic condition, which differentiates the hypnotic condition from the waking condition. Further, the decrease in the scaling exponents during hypnosis was solely associated with the eye-roll sign within specific cortical areas (F3, C4, and O1/2) closely related to eye movements and attention. In conclusion, the present study has found that the application of the fractal analysis technique can demonstrate the electrophysiological correlations with hypnotic influence on cerebral activity.

Changes in the Regional Cerebral Perfusion After Eye Movement Desensitization and Reprocessing: A SPECT Study of Two Cases

Eye movement desensitization and reprocessing (EMDR) has emerged as a promising new treatment for trauma and other anxiety-based disorders. However, the neurobiological mechanism of EMDR has not been well understood. This study reports changes in the resting regional cerebral blood flow after successful EMDR treatment in two patients with posttraumatic stress disorder (PTSD). Brain 99mTc-ECD-SPECT (Technetium 99m–ethyl cysteinate dimmer–single photon emission computerized tomography) was performed before and after EMDR, and, in addition, a pre- and posttreatment comparison was made with 10 non-PTSD participants as a control group. After EMDR, cerebral perfusion increased in bilateral dorsolateral prefrontal cortex and decreased in the temporal association cortex. The differences between participants and normal controls also decreased. Changes appeared mainly in the limbic area and the prefrontal cortex. These results are in line with current understanding of neurobiology of PTSD. EMDR treatment appears to reverse the functional imbalance between the limbic area and the prefrontal cortex.

Is the Psychotic Depression Assessment Scale a useful diagnostic tool?: The CRESCEND study

BACKGROUND The Psychotic Depression Assessment Scale (PDAS) has been validated as a method of assessing the severity and treatment outcomes of psychotic depression (PD). We aimed to compare the results of the PDAS in PD and non-psychotic depression (non-PD) patients and validate the PDAS as a diagnostic tool for PD. METHODS We included 53 patients with PD and 441 with non-PD who participated in the Clinical Research Center for Depression study in South Korea. In addition to the PDAS, psychometric tools including the HAMD17, HAMA, BPRS, CGI-S, SOFAS, SSI-Beck, WHOQOL-BREF, AUDIT, and FTND were used to assess, respectively, depression, anxiety, overall symptoms, global severity, social functioning, suicidal ideation, quality of life, alcohol use, and nicotine use. RESULTS After adjusting for age and total HAMD17 score, PD patients had higher scores for depressive mood, hallucinations, unusual thought content, suspiciousness, blunted affect, and emotional withdrawal on the PDAS and higher total scores on the SSI-Beck than non-PD patients. Binary logistic regression identified hallucinatory behavior and emotional withdrawal as predictors of PD. Receiver operating characteristic analysis showed that emotional withdrawal could be used to differentiate psychotic from non-psychotic depression. LIMITATIONS The inter-rater reliability for psychometric assessments was not evaluated. CONCLUSIONS In addition to assessing the severity and treatment outcomes of PD, PDAS can help in the diagnosis of PD.

Is the BPRS-5 subscale of the psychotic depression assessment scale a reliable screening tool for psychotic depression?: Results from the CRESCEND Study

BACKGROUND The detection of psychotic depression (PD) among patients with depressive disorders is important for both treatment and monitoring. Therefore, in continuation of our previous work, this study aimed to test the ability of the five-item Brief Psychiatric Rating Scale (BPRS-5) of the Psychotic Depression Assessment Scale (PDAS) in separating patients with psychotic depression from those with non-psychotic depression (non-PD) and to compare this discriminative validity to that of other item sets. METHODS A receiver operating characteristics curve was used to identify the optimal cut-off score of the BPRS-5 subscale for sensitive and specific distinction between PD and non-PD in a sample of 494 patients with depressive disorders (53 with PD and 441 with non-PD). RESULTS Using an optimal cut-off score of 1, the sensitivity and the specificity of the BPRS-5 subscale in detecting PD were 71.2% and 87.2%, respectively. The BPRS-5 outperformed other item sets of the PDAS and the positive symptom subscale of the BPRS in identifying patients with PD. LIMITATIONS The inter-rater reliability of the PDAS and the BPRS-5 subscale was not evaluated in this study. CONCLUSIONS The BPRS-5 subscale can be regarded as a more sensitive screening method for PD compared to other item sets from the PDAS and the BPRS. Hence, from a screening perspective, a positive score on any of the five symptoms of the BPRS-5 subscale (hallucinatory behavior, unusual thought content, suspiciousness, blunted affect, and emotional withdrawal) is indicative of PD, and should lead to more thorough diagnostic assessment.

Fluoxetine Up-Regulates Bcl-xL Expression in Rat C6 Glioma Cells.

Objective To analyze both differentially expressed genes and the Bcl-xL protein expression after acute and chronic treatment with fluoxetine in rat C6 glioma cells. Methods C6 glioma cells were cultured for 24 h or 72 h after treatment with 10 µM fluoxetine, and gene expression patterns were observed using microarray and qRT-PCR. Then, cells were cultured for 6 h, 24 h, 72 h or 96 h after treatment with 10 µM fluoxetine, and the expression of Bcl-xL protein was measured using western blot. Results As determined by microarray, treatment with fluoxetine for 24 h up-regulated 33 genes (including Bcl-xL and NCAM140) and down-regulated 7 genes (including cyclin G-associated kinase). Treatment with fluoxetine for 72 h up-regulated 53 genes (including Gsα and Bcl-xL) and down-regulated 77 genes (including Gαi2 and annexin V). Based on the qRT-PCR results, there was an increase in Gsα mRNA and a decrease in Gαi2 mRNA at 72 h in fluoxetine-treated cells as compared to control, a result that was consistent with microarray. We also observed an increase in Bcl-xL mRNA (both at 24 h and at 72 h) in fluoxetine-treated cells as compared to control, demonstrating a tendency to increase gradually. Bcl-xL protein expression increased as the duration of fluoxetine treatment increased. Conclusion These results suggest that chronic treatment with fluoxetine not only initiates the cAMP pathway through inducing Gsα expression but also induces Bcl-xL expression, thus inhibiting apoptosis.

Knowledge and Attitude of 851 Nursing Personnel toward Depression in General Hospitals of Korea

Our study aimed to examine the knowledge and attitude of nursing personnel toward depression in general hospitals of Korea. A total of 851 nursing personnel enrolled at four university-affiliated general hospitals completed self-report questionnaires. Chi-square tests were used to compare the knowledge and attitude of registered or assistant nurses toward depression. In addition, binary logistic regression analysis was used to adjust for the following confounders: age-group and workplace. Registered and assistant nurses differed in their knowledge and attitude toward depression. The proportion of rational and/or correct responses were higher in registered nurses than assistant nurses for the following: constellation of depressive symptoms defined by DSM-IV (adjusted odds ratio [aOR], 3.876; P<0.001); suicide risk in depression recovery (aOR, 3.223; P=0.001) and psychological stress as a cause of depression (aOR, 4.370; P<0.001); the relationship between chronic physical disease and depression (aOR, 8.984; P<0.001); and other items. Our results suggest that in terms of the biological model of depression, the understanding of registered nurses is greater than that of assistant nurses. Moreover, specific psychiatric education programs for nursing personnel need to be developed in Korea. Our findings can contribute to the development of a general hospital-based model for early detection of depression in patients with chronic medical diseases. Graphical Abstract

Increased Transforming Growth Factor-beta1 in Alcohol Dependence

Ethanol and its metabolite acetaldehyde increase transforming growth factor beta1 (TGF-β1) expression in animal studies. TGF-β1 is related with the hepatic stellate cell (the key element of hepatic fibrogenesis) and the radial glia (the key element of neuronal migration). Blood samples were collected from 41 patients with alcohol dependence, TGF-β1 levels measured by ELISA were compared with 41 normal subjects. Plasma TGF-β1 levels in the patients with alcohol dependence (1,653.11±532.45 pg/mL) were significantly higher than those of healthy subjects (669.87±366.53 pg/mL) (P=0.000). Patients with or without liver pathology showed no difference in TGF-β1 (P=0.36). Increased TGF-β1 may mediate deleterious effect of alcohol such as hepatic fibrosis and suppressed neuronal developments in alcohol dependence patients.