Design and Methods of the Mood Disorder Cohort Research Consortium (MDCRC) Study

The Mood Disorder Cohort Research Consortium (MDCRC) study is designed as a naturalistic observational prospective cohort study for early-onset mood disorders (major depressive disorders, bipolar disorders type 1 and 2) in South Korea. The study subjects consist of two populations: 1) patients with mood disorders under 25 years old and 2) patients with mood disorders within 2 years of treatment under 35 years old. After successful screening, the subjects are evaluated using baseline assessments and serial follow-up assessments at 3-month intervals. Between the follow-up assessments, subjects are dictated to check their own daily mood status before bedtime using the eMood chart application or a paper mood diary. At the regular visits every 3 months, inter-visit assessments are evaluated based on daily mood charts and interviews with patients. In addition to the daily mood chart, sleep quality, inter-visit major and minor mood episodes, stressful life events, and medical usage pattern with medical expenses are also assessed. Genomic DNA from blood is obtained for genomic analyses. From the MDCRC study, the clinical course, prognosis, and related factors of early-onset mood disorders can be clarified. The MDCRC is also able to facilitate translational research for mood disorders and provide a resource for the convergence study of mood disorders.

Review of Cohort Studies for Mood Disorders

This paper aimed to review currently available cohort studies of subjects with mood disorders such as major depressive disorder (MDD) and bipolar disorder (BD). Using the PubMed and KoreaMed databases, we reviewed eight major cohort studies. Most studies recruited participants with MDD and BD separately, so direct comparison of factors associated with diagnostic changes was difficult. Regular and frequent follow-up evaluations utilizing objective mood ratings and standardized evaluation methods in a naturalistic fashion are necessary to determine detailed clinical courses of mood disorders. Further, biological samples should also be collected to incorporate clinical findings in the development of new diagnostic and therapeutic approaches. An innovative cohort study that can serve as a platform for translational research for treatment and prevention of mood disorders is critical in determining clinical, psychosocial, neurobiological and genetic factors associated with long-term courses and consequences of mood disorders in Korean patients.

The Usefulness of The Cambridge Neuropsychological Test Automated Battery (CANTAB) for Assessing Cognitive Functions in the Elderly: a Pilot Study

BACKGROUND: We selected a computerized neuropsychological test, the Cambridge Neuropsychological Test Automated Battery (CANTAB), along with other conventional neuropsychological tests. The aim of this study was to assess CANTAB's usefulness in diagnosing dementia in the elderly and to compare it with conventional neuropsychological assessment kits. METHODS: We recruited 17 dementia patients diagnosed with Alzheimer's disease or vascular dementia for the dementia group and 52 healthy persons who met our criteria for the control group. We administered four CANTAB subtests to assess their cognitive functions along with the conventional Seoul Neuropsychological Screening Battery, which includes the Rey-Osterreith Complex Figure Test (RCFT) to assess visual memory. The four CANTAB subtests chosen were big/little circle (BLC), paired associates learning (PAL), spatial recognition memory (SRM), and spatial span (SSP). RESULTS: The dementia group showed impairment on the PAL and SRM tasks. The results of the other two subtests were not different between the two groups. The mean adjusted total errors on the PAL task was higher in the dementia group (130.88) than in the control group (51.38), which was statistically significant (p<0.01). The percentage of correct response on the SRM task was lower in the dementia group (58.75%) than in the control group (67.25%), also statistically significant (p=0.03). We also compared the correlations of the CANTAB subtests with the RCFT parameters (immediate recall, delayed recall, and recognition). Again, the results showed that the PAL task correlated well with these three parameters (r=-0.59, -0.60, and -0.56, respectively). CONCLUSION: The CANTAB was useful for assessing cognition in the elderly. In particular, the PAL task, which correlated well with the RCFT parameters, can be used to assess visual memory. It showed to be a valuable tool in diagnosing dementia.

Voxel-Based Morphometry Study of Gray Matter Abnormalities in Obsessive-Compulsive Disorder

To examine regional abnormalities in the brains of patients with obsessive-compulsive disorder (OCD), we assessed the gray matter (GM) density using voxel-based morphometry (VBM). We compared magnetic resonance images (MRIs) acquired from 71 OCD patients and 71 age- and gender-matched normal controls and examined the relationship between GM density and various clinical variables in OCD patients. We also investigated whether GM density differs among the subtypes of OCD compared to healthy controls. We detected significant reduction of GM in the inferior frontal gyrus, the medial frontal gyrus, the insula, the cingulate gyrus, and the superior temporal gyrus of OCD patients. A significant increase in GM density was observed in the postcentral gyrus, the thalamus, and the putamen. Some of these regions, including the insular and postcentral gyrus, were also associated with the severity of obsessive- compulsive symptoms. These findings indicate that the frontal-subcortical circuitry is dysfunctional in OCD, and suggest that the parietal cortex may play a role in the pathophysiology of this disease.

Characteristics of Subjects at Clinical High Risk for Schizophrenia: Natural Follow up Study in 'Seoul Youth Clinic'- Pilot Study / 신경정신의학

OBJECTIVES: The aims of this study were to identify the intake and following process for subjects at high risk of transition to schizophrenia and to examine the neurocognitive, social, and emotional functions of the subjects compared with healthy controls. METHODS: Symptomatic individuals judged at high risk for schizophrenia ('clinical high risk') within Youth Clinic were assessed and followed up. They performed a neurocognitive function test, a social function test and an affective function test. Twenty healthy controls were recruited in this study. RESULTS: Among eighty-two subjects contacted through the Youth clinic, sixteen subjects were judged as the clinical high risk group. Fourteen subjects among the clinical high risk group showed deficits in several domains of neurocognitive functions, such as visual recall memory, verbal short term memory and executive function. Social and affective functions are also impaired in the clinical high risk group compared with healthy controls. Two of 15 subjects (13%) developed a psychotic disorder within 6 months. CONCLUSION: This study illustrates the state of follow-up study for a clinical high risk group. Despite low numbers and short durations, some impairment of several functions in the clinical high risk group suggests possible predictors of psychosis.

Korean Treatment Algorithm for Obsessive-Compulsive Disorder 2007 (I) / 대한정신약물학회지

OBJECTIVE: Obsessive-compulsive disorder (OCD) is one of the more common serious mental illnesses. Effective psychological and drug treatments are available for the distressing, time-consuming, repetitive thoughts and rituals and the associated functional impairment. The decision of a treatment, however, is not easy because of the various clinical features and many treatment options. Therefore, practice guidelines and algorithms have been developed in some countries to provide the proper information to clinicians. We sought to develop the Korean Treatment Algorithm Project for OCD 2007 (KTAP-OCD 2007). METHODS: The survey questionnaire based on the Expert Consensus Guideline Series-Obsessive Compulsive disorder (1997) and was developed through modification and review by a study group for the KTAP-OCD 2007. Twenty-four (70.6%) of the 34 members of the review committee completed the survey. RESULTS: For the initial treatment of OCD, all of the selective serotonin reuptake inhibitor (SSRI)monotherapies, cognitive-behavioral therapy (CBT), and SSRI+CBT were included in the first treatment options. Fluoxetine, sertraline, paroxetine, citalopram, and fluvoxamine were included among the available SSRIs. The treatment for resistant OCD, maintenance treatment, treatment for comorbidities, and CBT for various clinical symptoms were also evaluated by the questionnaire. DISCUSSION: Most experts presented a consensus opinion as to the initial treatment of OCD, some nonconsensual opinions were expressed and gaps occurred between research data and clinical usage in some steps. And there are some differences were seen between Western countries and Korea. The KTAP-OCD 2007 is the first algorithm developed for OCD treatment in Korea, and our hope is that the KTAP-OCD will assist clinicians and researchers.

Korean Treatment Algorithm for Obsessive-Compulsive Disorder 2007(II): Initial Treatment and Treatment Resistant OCD / 대한정신약물학회지

OBJECTIVE: Treating obsessive-compulsive disorder (OCD) has always been a challenge requiring a mix of science and art. Although selective serotonin reuptake inhibitors (SSRIs) provide clinically significant relief to a large group of patients, a large number of patients do not respond to adequate trials of SSRIs. For these treatment-resistant patients, other treatment options such as augmentation, switching, combination strategies, and neurosurgical or device-based approaches have been suggested. Because several sequential treatment steps are often needed to achieve an adequate treatment benefit, we have developed a Korean treatment algorithm for OCD. METHOD: A questionnaire to survey the expert opinion of medications for OCD was completed by the review committee, which consisted of 24 experienced Korean psychiatrists. The questionnaire was composed of 47 questions, and each question included various subitems. We classified the expert opinions into three categories (1st line, 2nd line, and 3rd line). RESULTS: For initial treatment of OCD, SSRIs (fluoxetine, sertraline, paroxetine, citalopram) were recommended as 1st line therapy. If treatment by a SSRI fails, changing to another SSRI is preferred over augmentation strategy. When the response is not sufficient after changing SSRIs, augmentation strategies including atypical antipsychotics or changing to clomipramine are recommended. Among atypical antipsychotics, risperidone is the drug of choice for augmentation. Neuromodulation such as deep brain stimulation, neurosurgery, ECT, or repetitive transcranial magnetic stimulation are recommended after four or five failures of SSRIs including clomipramine. CONCLUSION: These results, which reflect recent studies and clinical experiences, suggest that the treatment strategies for OCD are changing. The development of a more comprehensive treatment algorithm for OCD, that includes cognitive-behavioral therapy, is needed.

Korean Treatment Algorithm for Obsessive-Compulsive Disorder 2007(III): A Preliminary Study for Application of Cognitive-Behavioral Therapy / 대한정신약물학회지

OBJECTIVE: The Korean College of Neuropsychopharmacology developed a Korean treatment algorithm for obsessive-compulsive disorder (OCD) to aid clinical decisions. The goal of this preliminary study was to encourage clinical practitioners to treat patients using cognitive-behavioral therapy. METHODS: We sent a questionnaire to 34 leading experts on OCD to investigate their opinions about treating patients with OCD using cognitive-behavioral therapy. RESULTS: Of the 34 experts, 12 responded to the survey. The responses indicated that most patients with obsessive-compulsive disorder should be offered cognitive-behavioral therapy, incorporating intensive and sufficient cognitive therapy with response prevention. CONCLUSION: These results may provide information about the application of cognitive-behavioral therapy to treat obsessive-compulsive disorder.

Korean Treatment Algorithm for Obsessive-Compulsive Disorder 2007(III): A Preliminary Study for Application of Cognitive-Behavioral Therapy / 대한정신약물학회지

OBJECTIVE: The Korean College of Neuropsychopharmacology developed a Korean treatment algorithm for obsessive-compulsive disorder (OCD) to aid clinical decisions. The goal of this preliminary study was to encourage clinical practitioners to treat patients using cognitive-behavioral therapy. METHODS: We sent a questionnaire to 34 leading experts on OCD to investigate their opinions about treating patients with OCD using cognitive-behavioral therapy. RESULTS: Of the 34 experts, 12 responded to the survey. The responses indicated that most patients with obsessive-compulsive disorder should be offered cognitive-behavioral therapy, incorporating intensive and sufficient cognitive therapy with response prevention. CONCLUSION: These results may provide information about the application of cognitive-behavioral therapy to treat obsessive-compulsive disorder.

Cognition, Emotion and Social Function: Are Vulnerability Markers for Developing Schizophrenia? / 신경정신의학

OBJECTIVES: Vulnerability marker in biological relatives of schizophrenia may be very useful in identifying the propensity for the development of schizophrenia. This study suggests that the relatives at risk for genetically developing schizophrenia have impairments in several domains of cognition, social function and affective function as a vulnerability marker. METHODS: A neurocognitve function test, a social function test and an affective function test were administered to fifteen healthy relatives from families with two or more patients with schizophrenia (geneticallly high risk subjects). Fifteen healthy controls matched for age and gender were recruited in this study. RESULTS: Compared to the control subject, the genetic high risk subjects performed significantly more poorly in the selective attention and recall memory of neurocognitive function. The high risk subjects also had lower scores in independence-performance and independence-competence of the social function test and emotion control of the affective function test. CONCLUSION: Selective attention, recall memory, independence-performance, independence-competence and emotion control ability may be a valuable marker for genetic study of schizophrenia.

The Contemplation of Neuropathological Abnormalities of the Corpus Callosum in Schizophrenia: A Diffusion Tensor Imaging Study / 신경정신의학

OBJECTIVES: Diffusion tensor imaging (DTI) is a new technique that can be used to visualize and measure the diffusion of water in brain tissue. It is particularly useful for evaluating white matter abnormalities. In this paper, we investigated the neuropathology of the corpus callosum in patients with schizophrenia through the new methods, diffusion tensor imaging. METHODS: Diffuse tensor imaging was performed in 19 schizophrenic patients and 26 healthy controls. One complementary measure, fractional anisotropy (FA), which is considered to be sensitive indices of axonal integrity, was obtained from regions of interest in the five areas of the corpus callosum. Neuropsychological measurement also underwent for measurement of frontal lobe function in two groups. RESULTS: There were no significant differences of FA in the DTI measures for either the schizophrenic patients compared with controls. FA was significantly decreased in women compared with men. Neuropsychological measurements such as Wisconsin card sorting test were correlated with FA of patients with schizophrenia. CONCLUSION: FA measures revealed no differences between schizophrenia and controls. The findings suggest that the structural integrity of white matter in patient with schizophrenia was not disrupted. The results are discussed in relation to previous studies reporting positive and negative findings. It is concluded that further studies using DTI in larger samples, improved and standardized methods of data acquisition and analysis are needed.

Correlates of N-acetylaspartate and Cognitive Dysfunctions in Drug-naive Patients with Obsessive-compulsive Disorder: A Proton MRSI Study / 신경정신의학

OBJECTIVES: Reductions of N-acetylaspartate (NAA), a putative marker of neuronal viability, within the subcortical structures in patients with obsessive-compulsive disorder (OCD) are well documented. However, there has been no report of the NAA level in cortical structures. The authors used proton magnetic resonance spectroscopic imaging (1H-MRSI) to assess potential reductions of NAA in the frontal white matter, prefrontal gray matter, parietal gray and white matter, and the cingulate in drugnaive patients with OCD and explored the relationship between the brain metabolites and the degree to the dysfunction on the neuropsychological performances. METHODS : Thirteen drug-naive patients who met DSM-IV criteria for OCD and 13 healthy age-, sex-, handness- matched control subjects were studied. Subjects underwent MRI and 1H-MRSI and the peaks of NAA, creatine+phosphocreatine (Cr), and choline-containing compounds (Cho) were measured. Differences between patients and control subjects were tested for each metabolite ratio, and the relations between metabolite ratios and clinical symptoms, neuropsychological performances were examined. RESULTS : Upon comparison with normal controls, NAA/Cr ratio was significantly reduced in patients for the prefrontal gray matter, frontal white matter and anterior cingulate. There was no difference in Cho/Cr or NAA/Cho in any region. Also, a significant positive correlation was found between prefrontal NAA/Cr ratio and the delayed recall score of the Rey-Osterrieth Complex Figure Test in patients with OCD. CONCLUSION : The reduced NAA/Cr ratio in the prefrontal gray matter and frontal white matter suggests that OCD patients have lower neuronal viability than normal comparisons and it may be related to impaired organizational strategies in patients with OCD. These results support a role for the frontal-subcortical circuitry in a neurobiologic model of OCD.

The P300 Source Localization in the Patients with Obsessive-Compulsive Disorder using the LORETA Imaging and SPM

OBJECTIVES: We investigated the characteristics of P300 generators in obsessive-compulsive disorder(OCD) patients by using voxel-based statistical parametric mapping of current density images. METHODS: P300 generators, produced by a rare target tone of 1500Hz under a frequent non-target tone of 1,000Hz, were measured in 15 right-handed OCD patients and 15 controls. Low Resolution Electromagnetic Tomography(LORETA), using a realistic head model of the boundary element method based on individual MRI, was applied to the 128-channel EEG. Statistical parametric mapping(SPM) was applied for the statistical analysis. RESULTS: We found that both groups had the mean current density of P300 in the parietal, temporal and prefrontal lobe. There was a trend for decreased current density in the prefrontal area in OCD patients. The statistical comparison showed current density increase in the supraparietal area, a statistically significant longer P300 latency and a trend for reduced P300 amplitude in OCD patients. CONCLUSION: It suggests that P300 source of both groups exists in multiple brain regions at the same time. And both groups had no statistically significant differences in the current density of P300 except for increased current density in the supraparietal area in OCD patients. But, considering the statistically significant longer P300 latency, a trend for reduced P300 amplitude and relative mean current density reduction in the prefrontal area in OCD patients, this study suggests that the frontal lobe may have a reduced normal inhibitory process in OCD patients.

A 2-Year Naturalistic Study on Trends in Pharmacotherapy and Change of Clinical Symptoms in the Patients with Obsessive-Compulsive Disorder / 대한정신약물학회지

OBJECTIVE: The purpose of this study was to examine the pharmacological treatment patterns and clinical responses in inpatients and/or outpatients with obsessive compulsive disorder (OCD) at a university hospital. METHODS: A total of 71 OCD patients were included and followed during the first 4 months, first year and second year from 1998. The patterns of medication use and clinical responses according to the Yale-Brown obsessive-compulsive scale (Y-BOCS) were analyzed descriptively in this period. RESULTS: During the first 4 months, 26.7% of the patients underwent monotherapy in which most of the drugs were serotonin reuptake inhibitors (SRIs). Therapy with two or more drugs was administered in 66.6% of the patients and combination drugs with SRIs were atypical antipsychotics and clonazepam. The clinical response rate using Y-BOCS was 24.0% compared with baseline score. During the first year, the frequency of the monotherapy decreased to 6.5%, while that of therapy with two or more drugs increased to 80.6% (two and three drug frequencies were 35.3%, and 32.3%, respectively). The clinical response rate was 26.4% during this period. During the second year, the frequency of the monotherapy was 25% and that of multidrug therapy was 70.8% (two and three drug frequencies were 20.8%, and 45.8%, respectively). The clinical response rate was 39.3% compared with baseline score. CONCLUSIONS: In this study, the frequency of the combination therapy was relatively high compared with SRI monotherapy during the first 4 months and it increased further during the first year. The combination therapy was maintained without change of SRI dosage during the second year. Most of the drugs used in the combination therapy were atypical antipsychotics and clonazepam.

The Effect of Straight Leg Raising on F-wave Parameters in Healthy Subjects and Patients with Lumbosacral Radiculopathy

OBJECTIVE: To determine if stretching the sciatic nerve in control and patients with lumbosacral radiculopathy significantly alters F-wave parameters. METHOD: We studied F-waves in the deep peroneal & posterior tibial nerves of 20 patients with unilateral lumbosacral radiculopathies and 22 controls. F-waves were recorded bilaterally in the neutral position and supine in 30o & 60o straight leg raising (SLR). F-wave parameters included minimal latency (F min), maximal latency (F max), mean latency (F mean), latency difference between F min and F max (chronodispersion), mean duration (F dur) and side to side difference in F min, F max, F mean and F dur. RESULTS: In controls, the F-wave latency was found to be longer in supine with SLR than in neutral position. In patients with lumbosacral radiculopathy, significant differences of F max, F mean and F dur between sides during 30o SLR were noted in the deep peroneal nerves, but all parameters in the posterior tibial nerves during SLR were not changed. CONCLUSION: In this study, we observed significant changes in F-wave latency in control during straight leg raising, but no significant changes in patients with lumbosacral radiculopathy. For the clinical application to lumbosacral radiculopathy, further study is needed.

Working Posture and Muscle Tension according to Screen Position during VDT Operation

OBJECTIVE: To evaluate working condition in way of measuring working posture and muscle tension using the desktop personal computer and notebook personal computer having different screen height. METHOD: Seventeen healthy men performed wordprocessing task in three workstation: desktop PC on the conventional computer table (DPC (on)); desktop PC under the 'inside' type computer table (DPC (under)); notebook PC on the table (NPC). The viewing distance and angle, head and neck angle, thoracic bending and trunk inclination were measured. Muscle tension of right posterior neck muscle, upper trapezius, sternocleidomastoid (SCM), and upper back muscle was also measured by integrated electromyogram (IEMG). RESULTS: 1) The viewing distance was the longest in DPC (under). 2) The lower the screen height, the more downward viewing angle and more flexed position in upper neck. 3) The posterior neck muscle tension was the lowest in DPC (on). 4) Stooped position was most frequently seen in NPC and the highest tension of posterior neck muscle and upper back muscle was shown in NPC. 5) In relation between postural analysis and muscle tension, muscle tension decreased with increasing backward reclining position, and the neck and thorax became more erect with increasing in viewing distance. CONCLUSION: These results suggest that the stooped posture was worst and most frequently seen in NPC. If neck flexion is avoided, DPC (under) position could lessen the visual and musculoskeletal problem. More Ergonomical study would be needed about working posture using computer.

Status of Using Lower Extremity Orthoses in Patients with Chronic Stroke and Traumatic Brain Injury

OBJECTIVE: Lower extremity orthoses are important in the rehabilitation of the patients with stroke and traumatic brain injury. But it is unknown how much they are used in the social activity after the discharge from the hospital. This study was carried out to investigate the status of using orthosis in social activity and complaints about orthosis. METHOD: The questionnaires were given to 42 cases with stroke and 17 cases with traumatic brain injury. RESULTS: The user of lower extremity orthosis in social activity were 55.9%, and the causes of disuse were patient's poor condition, improved gait pattern, inappropriate design and defect of orthosis, and patient's refusal. The degree of satisfaction with orthosis for comfort, external appearance and weight were 79.3%, 86.2%, and 72.4%, respectively. CONCLUSION: Physiatrists should give more attention in orthosis at follow-up of patients with stroke and traumatic brain injury and make efforts to improve function and external appearance of orthosis.

Upper Extremity Peripheral Nerve Entrapments among Wheelchair Users

Pain, numbness, and weakness in the upper extremity are the common problems among wheelchair users. The prevalence of nerve injury of the upper extremity in the wheelchair users has been reported variously by many authors in other nations. To determine the prevalence, location, and risk factors of upper extremity peripheral nerve entrapment among wheelchair users, we performed clinical and electrodiagnostic assessments on both upper extremities of wheelchair users (n=49) and able-bodied controls (n=49). The prevalence of nerve entrapment of the upper extremity among the wheelchair users was 15.6% according to clinical criteria, and 46.9% according to electrodiagnostic criteria. Electrodiagnostically, median nerve entrapment was identified in 28.6% of tested cases, and ulnar nerve entrapment was identified in 22.4% of tested cases among wheelchair users. The carpal tunnel was the most common site of nerve entrapment. The duration of wheelchair use was found to be correlated negatively with median wrist to palm and wrist to digit sensory conduction velocity, whereas age correlated positively with distal median and ulnar motor latency.