Numerous hypotheses have been put forth over the years to explain the development of bipolar disorder. Of these, circadian rhythm hypotheses have gained much importance of late. While the hypothalamus-pituitary-adrenal (HPA) axis hyperactivation hypothesis and the monoamine hypothesis somewhat explain the pathogenic mechanism of depression, they do not provide an explanation for the development of mania/hypomania. Interestingly, all patients with bipolar disorder display significant disruption of circadian rhythms and sleep/wake cycles throughout their mood cycles. Indeed, mice carrying the Clock gene mutation exhibit an overall behavioral profile that is similar to human mania, including hyperactivity, decreased sleep, lowered depression-like behavior, and lower anxiety. It was recently reported that monoamine signaling is in fact regulated by the circadian system. Thus, circadian rhythm instability, imposed on the dysregulation of HPA axis and monoamine system, may in turn increase individual susceptibility for switching from depression to mania/hypomania. In addition to addressing the pathophysiologic mechanism underlying the manic switch, circadian rhythm hypotheses can explain other bipolar disorder-related phenomena such as treatment resistant depression and mixed features.
Animals ; Bipolar Disorder* ; Chronobiology Disorders ; Circadian Rhythm* ; Depression ; Depressive Disorder, Treatment-Resistant ; Humans ; Mice

This paper reviews the bipolar spectrum concept historically and empirically. It describes how the concept derives from Kraepelin, but was lost with DSM-III, which divided the broad manic-depressive illness concept, based on recurrent mood episodes of either polarity, to the bipolar versus unipolar dichotomy, based on allowing non-recurrent mood episodes of only one polarity. This approach followed the views of Karl Leonhard and other critics of Kraepelin. Thus post DSM-III American psychiatry is not neo-Kraepelinian, as many claim, but neo-Leonhardian. The bipolar spectrum approach, as advocated by Akiskal and Koukopoulos first, harkens back to the original broad Kraepelinian view of manic-depressive illness. The evidence for and against this approach is discussed, and common misconceptions, including mistaken claims that borderline personality is similar, are revealed and critiqued.
Bipolar Disorder ; Diagnostic and Statistical Manual of Mental Disorders ; Genetic Diseases, X-Linked

During the development of the DSM-5, even the lay press questioned psychiatr's scientific validity. This review provides 21st century psychiatry residents with ways of answering these attacks by defining the concepts and history of psychiatry (a branch of medicine), medicine and science. Psychiatric language has two levels: first, describing symptoms and signs (19th century descriptive psychopathology developed in France and Germany), and second, describing disorders (psychiatric nosology was developed in the early 20th century by Kraepelin and resuscitated by the US neo-Kraepelinian revolution leading to the DSM-III). Science is a complex trial-and-error historical process that can be threatened by those who believe too much in it and disregard its limitations. The most important psychiatric advances, electroconvulsive therapy and major psychopharmacological agents, were discovered by "chance", not by scientific planning. Jaspers's General Psychopathology is a complex 100-year-old book that describes: 1) psychiatric disorders as heterogeneous and 2) psychiatry as a hybrid scientific discipline requiring a combination of understanding (a social science method) and explanation (a natural science method). In the 21st century Berrios reminds us of psychiatry's unfortunate methodological issues due to hybrid symptoms and disorders, some of which are better understood as problems in communication between interacting human beings; in those situations neuroscience methods such as brain imaging make no sense. A new language is needed in psychiatry. East Asian psychiatry residents, who are not particularly attached to the antiquated language currently used, may be particularly equipped for the task of recreating psychiatric language using 21st century knowledge.
Asia ; Asian Continental Ancestry Group ; Diagnostic and Statistical Manual of Mental Disorders ; Electroconvulsive Therapy ; Europe ; Far East ; France ; History ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Humans ; Mental Disorders ; Methods ; Natural Science Disciplines ; Neuroimaging ; Neurosciences ; Psychiatry* ; Psychopathology ; Social Sciences ; United States

OBJECTIVE: Eating disorders are a common clinical problem among young women in Asian countries. The aim of this study is to determine the medical effects of anorexia nervosa (AN) in the Korean population. METHODS: We comprehensively investigated medical complications including haemodynamic, haematologic, endocrine, and bone density abnormalities in 67 Korean women with AN, together with 194 healthy Korean women of comparable age with a cross-sectional design. RESULTS: In AN, 36.9% were anaemic, 50.8% were leukopenic, 35.5% were hypoproteinemic, 7.9% were hypokalemic, 9.5% had increased alanine aminotransferase, 6.3% were hyperbilirubinemia, 14.5% were hypercholesterolemia, 14.8% had decreased triiodothyronine. Osteopenia at any one site was identified in 43.3% and an additional 13.4% had osteoporosis. The lowest-ever body mass index was the main determinant of bone mineral density. CONCLUSION: Our data in Korean patients with AN show high frequencies of laboratory abnormalities for medical complications. This study emphasizes the importance of recognizing AN as a medical risk in young Korean women.
Alanine Transaminase ; Anorexia ; Anorexia Nervosa ; Asian Continental Ancestry Group ; Body Mass Index ; Bone Density ; Bone Diseases, Metabolic ; Feeding and Eating Disorders ; Female ; Humans ; Hyperbilirubinemia ; Hypercholesterolemia ; Osteoporosis ; Triiodothyronine

OBJECTIVE: Clozapine is the treatment of choice for refractory schizophrenia. The aim of this study was to compare the pharmacokinetics of the brand name (Clozaril) formulation and a generic formulation (Clzapine) of clozapine in Korean schizophrenic patients. METHODS: A prospective, randomized, crossover study was conducted to evaluate the steady-state pharmacokinetic profiles of Clozaril and Clzapine. Schizophrenic patients were randomized to receive either the brand name or generic formulation (100 mg twice daily) for 10 days, followed by the other formulation for 10 days. Plasma samples were collected on the last day of each treatment period. RESULTS: Twenty-two of 28 patients (78.6%) completed the study. The mean C(max,ss) values for Clzapine and Clozaril were 524.62 and 551.18 ng/mL, and the mean AUC(0-12) values were 4479.90 hr.ng/mL and 4724.56 hr.ng/mL, respectively. The 90% CI values for the natural logarithmically transformed C(max,ss) and AUC(0-12) ratios (Clzapine to Clozaril) after a single oral dose (100 mg) were 0.934 (0.849-1.028) and 0.936 (0.869-1.008), respectively. Five patients (20.8%) among 24 patients who took Clzapine reported 11 adverse events and six adverse events were reported by four patients (15.4%) among 26 who took Clozaril; there were no significant differences on physical examination or in vital signs, ECG, and laboratory tests between groups. CONCLUSION: Generic clozapine (Clzapine) appears to be bioequivalent to brand name clozapine (Clozaril).
Clozapine* ; Cross-Over Studies* ; Electrocardiography ; Humans ; Pharmacokinetics ; Physical Examination ; Plasma ; Prospective Studies ; Schizophrenia ; Therapeutic Equivalency* ; Vital Signs

OBJECTIVE: To investigate the impact of regular cannabis use on long-term remission of mood symptoms in bipolar spectrum disorders. METHODS: The 24-month prospective observational study included patients (n=239) with bipolar I disorder and schizoaffective disorder, bipolar type. Participants were classified as regular cannabis users (three times or more per week) or non-users. The primary outcome measure was the achievement of remission on the evaluations during the 24 months. RESULTS: Of the 234 participants for whom data was available, 25 (10.7%) were regular cannabis users, and the group comprised significantly more males than females. In the total population, cannabis use was significantly associated with decreased likelihood of remission during the 24-month follow-up period. Subgroup analyses showed that cannabis use was significantly associated with lower remission rates on the Hamilton Depression Rating Scale in females (n=139) and patients prescribed mood stabilizers alone (n=151), whereas in males (n=95) and patients prescribed olanzapine and/or a mood stabilizer (n=83), cannabis use was significantly associated with lower remission rates on the Young Mania Rating Scale. Remission rates were lowest in the concurrent cannabis and tobacco smoking group (n=22) followed by the tobacco smoking only group (n=97), and the non-smoker group (n=116). The post-hoc analysis revealed that all remission rates were significantly lower in the concurrent cannabis and the tobacco smoking group compared to the non-smoker group. CONCLUSION: Cannabis use negatively affects the long-term clinical outcome in patients with bipolar spectrum disorders. A comprehensive assessment and integrated management of cannabis use are required to achieve better treatment outcomes for bipolar spectrum disorders.
Bipolar Disorder ; Cannabis* ; Depression ; Female ; Follow-Up Studies ; Humans ; Male ; Observational Study ; Outcome Assessment (Health Care) ; Prospective Studies ; Psychotic Disorders* ; Smoking

OBJECTIVE: Comprehensive neuropsychological tests are important in the diagnosis and follow-up of patients with MCI; however, most were developed without consideration of illiteracy. We developed the Literacy Independent Cognitive Assessment (LICA) as a comprehensive neuropsychological assessment battery applicable to older adults who are either literate or illiterate. This study aimed to assess the reliability and validity of the LICA for diagnosis of MCI. METHODS: Normal controls (n=634) and patients with MCI (n=128) were recruited from 13 centers were included in this study. Participants were divided into illiterate or literate groups, based on their performance on a brief reading and writing test. The LICA, Korean Mini-Mental State Examination (K-MMSE), and Seoul Neuropsychological Screening Battery (SNSB) were administered. RESULTS: Total LICA scores distinguished MCI patients from controls (p<0.001). They were closely and positively correlated to the K-MMSE scores (r=0.632, p<0.001) but negatively correlated to clinical dementia rating (CDR) (r=-0.358, p<0.001) and CDR sum of boxes (r=-0.339, p<0.001). Area under the receiver operating characteristic curve for patients with MCI by total LICA score was 0.827 (0.783-0.870), superior to that presented by the K-MMSE. For the classification of MCI subtypes, inter-method reliability of LICA with the SNSB was good (kappa 0.773; 0.679-0.867, p<0.001). CONCLUSION: The results of this study show that the LICA may be reliably used to distinguish MCI patients from cognitively intact adults, to identify MCI subtypes and monitor progression toward dementia, regardless of illiteracy.
Adult* ; Classification ; Dementia ; Diagnosis ; Literacy ; Follow-Up Studies ; Humans ; Mass Screening ; Mild Cognitive Impairment* ; Neuropsychological Tests ; Reproducibility of Results ; ROC Curve ; Sensitivity and Specificity ; Seoul ; Writing

OBJECTIVE: Many studies have reported that Taekwondo training could improve body perception, control and brain activity, as assessed with an electroencephalogram. This study aimed to assess body intelligence and brain connectivity in children with Taekwondo training as compared to children without Taekwondo training. METHODS: Fifteen children with Taekwondo training (TKD) and 13 age- and sex-matched children who had no previous experience of Taekwondo training (controls) were recruited. Body intelligence, clinical characteristics and brain connectivity in all children were assessed with the Body Intelligence Scale (BIS), self-report, and resting state functional magnetic resonance imaging. RESULTS: The mean BIS score in the TKD group was higher than that in the control group. The TKD group showed increased low-frequency fluctuations in the right frontal precentral gyrus and the right parietal precuneus, compared to the control group. The TKD group showed positive cerebellum vermis (lobe VII) seed to the right frontal, left frontal, and left parietal lobe. The control group showed positive cerebellum seed to the left frontal, parietal, and occipital cortex. Relative to the control group, the TKD group showed increased functional connectivity from cerebellum seed to the right inferior frontal gyrus. CONCLUSION: To the best of our knowledge, this is the first study to assess the effect of Taekwondo training on brain connectivity in children. Taekwondo training improved body intelligence and brain connectivity from the cerebellum to the parietal and frontal cortex.
Brain* ; Cerebellum ; Child ; Electroencephalography ; Humans ; Intelligence* ; Magnetic Resonance Imaging ; Parietal Lobe ; Rabeprazole

OBJECTIVE: The goal of this study was to examine the association between IQ and suicide in psychiatric patients. METHODS: We conducted a nested case-control study using data obtained from psychiatric patients affiliated with a general hospital in Seoul, Korea. In a one-to-two ratio the psychiatric patients who died of suicide (Suicide Group; n=35) were matched to those who didn't (Non-suicide Group; n=70) by age, gender, psychiatric diagnosis and approximate time of first treatment. IQ was measured using the Korean version of the Wechsler Adult Intelligence Scale-Revised. RESULTS: There were no significant differences in any type of IQ between suicide patients and non-suicide patients. Logistic regression showed no evidence of an association between IQ and suicide. CONCLUSION: These results do not support the existence of an association between IQ and suicide.
Adult ; Case-Control Studies* ; Hospitals, General ; Humans ; Intelligence ; Korea ; Logistic Models ; Mental Disorders ; Retrospective Studies* ; Seoul ; Suicide*

OBJECTIVE: Patients visiting the emergency department (ED) after a suicide attempt are generally assessed for suicide risk by psychiatric residents. Psychiatric residents' competence in evaluating the risk posed by the patients who attempted suicide is critical to preventing suicide. METHODS: We investigated factors considered important by psychiatric residents when evaluating suicide risk. This study included 140 patients admitted to the ED after attempting suicide. Psychiatric residents rated patients' severity of current and future suicide risk as low/moderate/high using the Brief Emergency Room Suicide Risk Assessment (BESRA). The association between each BESRA variable and level of suicide risk was analyzed. RESULTS: Many factors were commonly considered important in evaluating the severity of current and future suicide risk. However, the following factors were only associated with future suicide risk: female gender, having no religion, family psychiatric history, history of axis I disorders, having a will, harboring no regrets, and social isolation. CONCLUSION: Psychiatric residents use diverse factors when assessing suicide risk. Psychiatric residents might put more emphasis on non-modifiable demographic and clinical factors, concrete evidence showing suicide determination, and social isolation to assess the risk of future suicide.
Axis, Cervical Vertebra ; Emergency Service, Hospital ; Female ; Humans ; Mental Competency ; Risk Assessment* ; Risk Factors* ; Social Isolation ; Suicide* ; Suicide, Attempted