G1/S Cell Cycle Checkpoint Defect in Lymphocytes from Patients with Alzheimer's Disease

OBJECTIVE: We compared the cell responsiveness of activated lymphocytes to rapamycin, which blocks the G1/S transition, between patients with Alzheimer's disease (AD) and normal controls to assess the early phase control defect in cell cycle. METHODS: Blood samples of 26 patients with AD and 28 normal controls were collected to separate peripheral lymphocytes. We measured the proportion of each cell cycle phase in activated lymphocytes using flow cytometry and evaluated the responsiveness of these lymphocytes to rapamycin. RESULTS: The patients with AD were older than the normal controls (AD 74.03+/-7.90 yr vs. control 68.28+/-6.21 yr, p=0.004). The proportion of G1 phase cells in the AD group was significantly lower than that in the control group (70.29+/-6.32% vs. 76.03+/-9.05%, p=0.01), and the proportion of S phase cells in the AD group was higher than that in control group (12.45+/-6.09% vs. 6.03+/-5.11%, p=0.001). Activated lymphocytes in patients with AD were not arrested in the G1 phase and they progressed to the late phase of the cell cycle despite rapamycin treatment, in contrast to those of normal subjects. CONCLUSION: The patients with AD probably have a control defect of early phase cell cycle in peripheral lymphocytes that may be associated with the underlying pathology of neuronal death.

A Comparison of Comorbidity and Psychological Outcomes in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

OBJECTIVE: The purpose of this study was to compare psychiatric comorbid disorders and psychological outcomes in children and adolescents with Attention-deficit/hyperactivity disorder (ADHD). METHODS: Subjects were divided into a child group (aged under 12 years) and an adolescent group (aged 12 years and above). All subjects were diagnosed with ADHD based on the DSM IV diagnostic criteria using the Kiddie-Schedule for Affective Disorders and Schizophrenia-Present and Lifetime Korean Version (K-SADS-PL-K). The K-SADS-PL-K was also used to evaluate those psychiatric disorders comorbid with ADHD. And the Korean version of the Child Behavior Checklist (K-CBCL) was used to examine the subjects' psychological outcomes. RESULTS: The rate of comorbidity in adolescent group was significantly higher than that in the child group. In particular, the adolescent group had a significantly higher ratio of comorbid conduct disorder and mood disorder than the child group. With respect to the predominantly inattentive type and Not Otherwise Specified, the school subscale scores on the K-CBCL for the children were significantly higher than those for the adolescents. CONCLUSION: These results suggest that the psychiatric comorbidity may differ between adolescents and children with ADHD. Therefore when treating adolescents with ADHD, more careful assessment and treatment targeting a range of comorbidities are needed.

Differences of Clinical Characteristics and Phenotypes between Prepubertal- and Adolescent-Onset Bipolar Disorders

The aim of this study is to describe the clinical characteristics of prepubertal- and adolescent-onset bipolar disorder (BD) and to identify any clinical differences between patients with prepubertal- and adolescent-onset BD. We analyzed the clinical records of 53 inpatients with BD. These patients were divided into prepubertal-onset and adolescent-onset groups. We also divided the subjects into narrow, intermediate, and broad phenotypes according to the definitions proposed by Leibenluft and colleagues. Of the total sample, 16 patients (30.2%) were in the prepubertal-onset group and 37 (69.8%) were in the adolescent-onset group. Patients with prepubertal-onset BD were more likely to display an insidious clinical presentation, atypical features, and comorbid psychopathology. And the majority of the subjects, especially in the prepubertal-onset group, were classified under the intermediate and broad phenotypes. These results suggest that the clinical presentation of BD with prepubertal-onset is different from that of adolescent-onset BD. It is inferred that a significant number of patients with prepubertal- and adolescent-onset BD do not meet DSM-IV criteria for mania or hypomania from the results of this study.

Clinical Characteristics of Bipolar Disorder Patients with Prepubertal Onset : A Pilot Study / 신경정신의학

OBJECTIVES : This case-based, small scale study was undertaken to identify the characteristics clinical features of children who exhbiit rare prepubertal onset bipolar disorder. METHODS : We analyzed the clinical records of 13 children who had been hospitalized and diagnosed with bipolar disorder. Clinical characteristics and cognitive function of these patients was based on psychiatrists' medical records and psychologists' evaluation reports. RESULTS : Eleven (84.6%) subjects exhibited clinical features of mixed mania and had a chronic clinicalcourse. They never fulfilled the full criteria of the Diagnostic Statistical Manual of Mental disorders- Fourth Edition (DSM-IV) for manic or hypomanic episodes. Mean age at onset of typical symptoms of bipolar disorder was 9.38 (SD=1.80) and mean age at admission was 12.00 (SD=2.45). Twelve (92.3%) had psychiatric comorbidity. Attention-deficit/hyperactivity disorder was the most prevalent comorbid disease and mean age of onset of it was 6.23 (SD=2.17). CONCLUSION : Subjects with prepubertal onset bipolar disorder showed atypical clinical features. These results suggest that most prepubertal onset bipolar disorder patients fail to meet the DSM-IV criteria for typical bipolar I disorder and therefore, we need to develop alternative diagnostic criteria for pediatric bipolar disorder.

Clinical Efficacy and Safety of Memantine in Patients with Moderate to Severe Dementia / 대한정신약물학회지

OBJECTIVE: This study examined the efficacy and safety of memantine-an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist-in the treatment of moderate-to-severe dementia. METHODS: Forty-four patients with moderate-to-severe dementia received 20 mg of memantine daily for 24 weeks. The primary efficacy variable was measured by the Korean version of Severe Impairment Battery(K-SIB), and the secondary efficacy variables were measured using the Seoul-Activites of Daily Living(S-ADL) and Neuropsychiatric Inventory-Questionnaire(NPI-Q). Neuropsychological assessments were administrated at baseline, 12 weeks, and 24 weeks. Safety parameters were monitored. RESULTS: Of 44 patients recruited, 30 completed the study and 14 dropped out. Memantine-treated patients showed a therapeutic benefit in all efficacy variables ; the K-SIB, S-ADL, and NPI-Q total scores were not significantly different from baseline either at the endpoint(in the analysis of intention-to-treat, with the last observation carried forward, ITT-LOCF) or at week 24(in the analysis of observed cases, OC). The response rates, when "response" was defined as improved or unchanged in the K-SIB or the S-ADL scores, were 43.3 and 50%, respectively(in the analysis of OC). The responders showed significant improvement in the cognitive subdomain of memory function, praxis, visuospatial ability, and orienting to name. Memantine was shown to be tolerable and safe. CONCLUSIONS: Memantine treatment reduced or delayed clinical deterioration in cognition, function, and behavior in patients with moderate-to-severe dementia.

Clinical Utility of the Short Form of the Samsung Dementia Questionnaire (S-SDQ) in Mild Cognitive Impairment (MCI) / 신경정신의학

OBJECTIVES: Clinical utility of the Short Form of the Samsung Dementia Questionnaire (S-SDQ) as a screening instrument for Mild Cognitive Impairment (MCI). METHODS: Three groups (n=27, Subjective Memory Impairment (SMI); n=41 MCI; n=79, Early Alzheimer's Disease(AD)) recruited from memory clinic were administered a battery of neuropsychological tests including S-SDQ and Korean version-Mini Mental State Examination (K-MMSE). RESULTS: S-SDQ, unlike the K-MMSE, had no association with the age and education of the subjects. Scores of S-SDQ was found to correlate (r=-.496) with scores of K-MMSE. Result of Receiver Operating Characteristic (ROC) analysis revealed that S-SDQ discriminated between the SMI and the MCI groups. CONCLUSION: S-SDQ may be a solution to the problem of contamination by education and age which affect traditional cognitive screening instruments like K-MMSE, and it may be a useful tool for screening MCI.