Age-specific association between body mass index and depression: The Korea National Health and Nutrition Examination Survey 2014.

BACKGROUND/OBJECTIVES: Decades of research have investigated the association between body mass index (BMI) and depression. Although it has been suggested that obesity lowers the risk of depression in elderly adults, the association of overweight and obesity with depression across age groups remains controversial. Thus, we aimed to investigate how the odds of depression vary between BMI groups in the general population. SUBJECTS/METHODS: In this study, data were collected from the sixth Korea National Health and Nutrition Examination Survey of 2014 (KNHANES VI; n=7550), and 4932 adults were included in the study sample. We investigated the adjusted association between depression, which was measured by the Patient Health Questionnaire 9 (PHQ-9), and BMI groups (underweight, normal weight, overweight, obese class I, obese classes II and III). RESULTS: In all adults, after adjusting for sex, age, income and presence of chronic illnesses, overweight had lower odds of depression than normal weight (OR, 0.811; 95% CI, 0.661-0.995), whereas underweight had higher odds of depression than normal-weight subjects (OR, 1.776; 95% CI, 1.241-2.540). Overweight elderly adults had lower odds of depression than normal-weight elderly adults (OR, 0.522, 95% CI, 0.367-0.743), and obese class I elderly adults also had lower odds of depression than normal-weight elderly adults in both men (OR, 0.482, 95% CI, 0.251-0.924) and women (OR, 0.637, 95% CI, 0.418-0.970). Furthermore, in the normal-weight-to-obese class I elderly adults group, we found that an increase of 1 kg m-2 BMI was significantly associated with a decreased prevalence of depression in both men (OR, 0.898, 95% CI, 0.808-0.997) and women (OR, 0.911, 95% CI, 0.844-0.982). CONCLUSIONS: We found that overweight and mild obesity significantly lowered the risk of depression in elderly adults. These findings suggest that mild increases in BMI beyond the normal range may be a protective factor for depression in elderly Korean adults.

SATB2-associated syndrome presenting with Rett-like phenotypes.

The SATB2-associated syndrome (SAS) was proposed recently, after the SATB2 gene was initially discovered to be associated with isolated cleft palate. This syndrome is characterized by intellectual disability with delayed speech development, facial dysmorphism, cleft or high-arched palate, and dentition problems. Here, we describe two novel SATB2 sequence variants in two unrelated patients presenting with Rett-like phenotypes. We performed trio-based whole-exome sequencing in a 17-month-old girl presenting with severe retardation and Rett-like phenotypes, which revealed a de novo missense variant in SATB2 (p.Glu396Gln). Moreover, targeted sequencing of the SATB2 gene was performed in a 2-year-old girl with severe psychomotor retardation, facial hypotonia, and cleft palate who also exhibited some features of Rett syndrome. A nonsense variant in SATB2 was identified in this patient (p.Arg459*). This study expanded the clinical and genetic spectrum of SAS. SATB2 variants should be considered in cases with psychomotor retardation alone or in any cases with Rett-like phenotypes, regardless of the typical features of SAS such as cleft palate.

Clinical applications of next-generation sequencing-based gene panel in patients with muscular dystrophy: Korean experience.

Muscular dystrophy (MD) is a genetically and clinically heterogeneous group of disorders. Here, we performed targeted sequencing of 18 limb-girdle MD (LGMD)-related genes in 35 patients who were highly suspected of having MD. We identified one or more pathogenic variants in 23 of 35 patients (65.7%), and a genetic diagnosis was performed in 20 patients (57.1%). LGMD2B was the most common LGMD type, followed by LGMD1B, LGMD2A, and LGMD2G. Among the three major LGMD types in this group, LGMD1B was correlated with the lowest creatine kinase (CK) levels and the earliest onset, whereas LGMD2B was correlated with the highest CK levels and the latest onset. Thus, next-generation sequencing-based gene panels can be a helpful tool for the diagnosis of MDs, particularly in young children and those displaying atypical symptoms.

Creatine kinase isoenzyme activity during and after an ultra-distance (200 km) run.

It is commonly assumed that creatine kinase (CK) activity in plasma is related to the state of an inflammatory response at 24-48 h, and also it has shown biphasic patterns after a marathon run. No information is available on CK isoenzymes after an ultra-marathon run. The purpose of the present study is to examine the CK isoenzymes after a 200 km ultra-marathon run and during the subsequent recovery. Blood samples were obtained during registration 1 2 h before the 200-km race and during the race at 100 km, 150 km and at the end of 200 km, as well as after a 24 h period of recovery. Thirty-two male ultra-distance runners participated in the study. Serum CPK showed a marked increase throughout the race and 24 h recovery period (p < 0.001). Serum CK during the race occurs mostly in the CK-MM isoform and only minutely in the CK-MB isoform and is unchanged in the CK-BB isoform. High-sensitivity C-reactive protein (hs-CRP), oestradiol, AST and ALT increased significantly from the pre-race value at 100 km and a further increase took place by the end of the 200 km run. The results of our study demonstrate a different release pattern of creatine kinase after an ultra-distance (200 km) run compared to the studies of marathon running and intense eccentric exercise, and changes in several biomarkers, indicative of muscle damage during the race, were much more pronounced during the latter half (100-200 km) of the race. However, the increases in plasma concentration of muscle enzymes may reflect not only structural damage, but also their rate of clearance.

Pantothenate kinase-associated neurodegeneration in Korea: recurrent R440P mutation in PANK2 and outcome of deep brain stimulation.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the mutation status of PANK2 among Korean patients with pantothenate kinase-associated neurodegeneration (PKAN) and to document the outcome of pallidal deep brain stimulation (DBS). METHODS: Direct sequencing and deletion/duplication analysis of PANK2 were conducted in 12 patients (11 unrelated) with PKAN, diagnosed on the basis of extrapyramidal dysfunction and the 'eye-of-the-tiger sign' on brain magnetic resonance imaging (MRI). Pallidal DBS was conducted in four patients, and the outcomes were measured using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). RESULTS: A PANK2 mutation was identified in both alleles in all patients. The most prevalent mutation was c.1319G>C (p.R440P) in 8/22 mutated alleles (36%). An intragenic deletion ranging from exons 2 to 4 was found in one allele (1/22, 4.5%) using deletion/duplication analysis. The outcome of pallidal DBS was favorable in two patients with atypical PKAN and moderate severity of dystonia. However, two patients with typical PKAN and relatively severe symptoms showed variable responses. CONCLUSIONS: The c.1319G>C (p.R440P) mutation appears to be a founder genotype among Korean patients with PKAN. Furthermore, this study provides additional data for the recent international effort to evaluate the efficacy of pallidal DBS in the treatment of patients with PKAN.

Brain activation by visual erotic stimuli in healthy middle aged males.

The objective of the present study was to identify brain centers, whose activity changes are related to erotic visual stimuli in healthy, heterosexual, middle aged males. Ten heterosexual, right-handed males with normal sexual function were entered into the present study (mean age 52 years, range 46-55). All potential subjects were screened over 1 h interview, and were encouraged to fill out questionnaires including the Brief Male Sexual Function Inventory. All subjects with a history of sexual arousal disorder or erectile dysfunction were excluded. We performed functional brain magnetic resonance imaging (fMRI) in male volunteers when an alternatively combined erotic and nonerotic film was played for 14 min and 9 s. The major areas of activation associated with sexual arousal to visual stimuli were occipitotemporal area, anterior cingulate gyrus, insula, orbitofrontal cortex, caudate nucleus. However, hypothalamus and thalamus were not activated. We suggest that the nonactivation of hypothalamus and thalamus in middle aged males may be responsible for the lesser physiological arousal in response to the erotic visual stimuli.

Vagus nerve stimulation therapy: a research update.

Over the past 5 years, and especially within the last year, there has been a rapid expansion of vagus nerve stimulation (VNS)-related preclinical research, as well as clinical studies in indications other than epilepsy. The research advances in understanding VNS are occurring in the midst of a blossoming of other forms of therapeutic brain stimulation, such as electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and deep brain stimulation (DBS). In general, improved understanding of the neurobiological effects of VNS therapy as a function of the different use parameters (frequency, intensity, pulse width, duration, dose) is beginning to guide clinical use and help determine which diseases, in addition to epilepsy, VNS might treat.

Effect of total sleep deprivation on the dimensional complexity of the waking EEG.

STUDY OBJECTIVES: Sleep deprivation can affect the waking EEG that may reflect information processing of the brain. We examined the effect of total sleep deprivation (TSD) on nonlinear dynamics of the waking EEG. DESIGN: Paired-group design. SETTING: A sleep disorders laboratory in a hospital. PARTICIPANTS: Twenty healthy male volunteers. INTERVENTIONS: Waking EEG data were recorded from subjects with eyes closed after (a) an 8-hour night's sleep and (b) TSD for 24 hours. The dimensional complexity (D2), as a nonlinear measure of complexity, of the EEG after a full night sleep were compared with those of the EEG after TSD. MEASUREMENTS AND RESULTS: The sleep-deprived states had lower D2 values at three channels (P4, O2, and C3) than normal states. CONCLUSIONS: TSD results in the decrease of complexity in the brain, which may imply sub-optimal information processing of the cerebral cortex. We suggest that the investigation of the relation between nonlinear dynamics of the waking EEG induced by TSD and cognitive performance may offer fruitful clues for understanding the role of sleep and the effects of sleep deprivation on brain function.

Reporter constructs showing proper globin gene switching in cultured erythroid cell lines.

Recent advances in the study of globin gene switching in the context of complete gene locus have contributed greatly to our understanding of developmental regulation mechanism of globin gene expression. However, it is not clear yet whether the cluster is sufficient in proper gene switching when the globin genes are replaced with conventional reporter genes. Furthermore, even though erythroid-specific and ubiquitous transcription factors involved in erythroid-specific globin gene expression have been characterized and some plausible globin gene switching models have been suggested, any specific factor directly involved in globin gene switching is not yet identified. In this study, as an effort to further understand globin switching mechanism and to identify globin switching factors, we constructed reporter vectors by juxtaposing several putative regulatory elements in human beta-globin locus to conventional reporter genes and analyzed their stage-specific expression in erythroid cell lines. At the end, we demonstrated that gammabeta-type constructs, in which both gamma-type and beta-type globin reporter genes were linked in cis below beta-globin locus control region (LCR), show proper stage-specific reporter gene expression in erythroid cell lines and also recapitulate globin switching in cell hybrids.

Isolation of developmentally regulated novel genes based on sequence identity and gene expression pattern.

Based on the surmise that a variety of genes might play important roles in embryonic development and tissue differentiation, and that some of them are likely to be expressed in undifferentiated ES cells, we attempted to identify new genes from the ES cell cDNA library. The modified method of expressed sequence tags (ESTs) and the examination of the expression patterns in adult tissues and in vitro differentiated ES cells were utilized in this study. We have isolated and identified several novel cDNA clones with interesting developmental expression pattern. Among the 83 clones randomly chosen, 23 clones (27.7%) have no homology to any sequences in public databases. The rest contain limited or complete sequence homology to the previously reported mammalian genes or ESTs, yet some clones have not been previously identified in the mouse. To examine the expression profile of clones during development and differentiation, sets of slot blots were hybridized with developmental stage specific or tissue specific probes. Out of 40 novel clones tested (21 totally unknown clones and 19 unidentified clones in mouse), most of them were up- or down-regulated as differentiation proceeded, and some clones showed differentiation-stage specific expression profiles. Surprisingly, a majority of genes were also expressed in adult tissues, and some clones even revealed tissue specific expression. These results demonstrate that not only was the strategy we employed in this study quite efficient for screening novel genes, but that the information gained by such studies would also be a useful guide for further analysis of these genes. It also suggests the feasibility of this approach to explore the genomewide network of gene expression during complicated biological processes, such as embryonic development and tissue differentiation.

Nonlinear dynamic analysis of the EEG in patients with Alzheimer's disease and vascular dementia.

To assess nonlinear EEG activity in patients with Alzheimer's disease (AD) and vascular dementia (VaD), the authors estimated the correlation dimension (D2) and the first positive Lyapunov exponent (L1) of the EEGs in both patients and age-matched healthy control subjects. EEGs were recorded in 15 electrodes from 12 AD patients, 12 VaD patients, and 14 healthy subjects. The AD patients had significantly lower D2 values than the normal control subjects, (P < H > 0.05), except at the F7 and the O1 electrodes, and the VaD patients, except at the C3 and the C4 electrodes. The VaD patients had relatively increased values of D2 and L1 compared with the AD patients, and rather higher values of D2 than the normal control subjects at the F7, F4, F8, Fp2, O1, and O2 electrodes. The L1 values of the EEGs were also lower for the AD patients than for the normal control subjects, except in the O1 and the O2 channels, and for the VaD patients at all electrodes. The L1 values were higher for the VaD patients than for the normal control subjects (F3, F4, F8, O1, and O2). In addition, the authors detected that the VaD patients had an uneven distribution of D2 values over the regions than the AD patients and the normal control subjects, although the statistics do not confirm this. By contrast, AD patients had uniformly lower D2 values in most regions, indicating that AD patients have less complex temporal characteristics of the EEG in entire regions. These nonlinear analyses of the EEG may be helpful in understanding the nonlinear EEG activity in AD and VaD.

An estimation of the first positive Lyapunov exponent of the EEG in patients with schizophrenia.

We studied the complexity of the electroencephalogram (EEG) in schizophrenic patients by estimating the first Lyapunov exponent (L1), which might serve as an indicator of the specific brain function in schizophrenia. We recorded the EEG from 25 schizophrenic patients (12 male, 13 female; age=25.1+/-7.0 years) fulfilling DSM-IV criteria and 15 healthy controls (9 male, 6 female; age=27. 8+/-4.2 years) at 16 electrodes, different from previous studies which recorded the EEGs at limited electrodes. We employed a method with an optimal embedding dimension to calculate the L1s. For limited noisy data, this algorithm was strikingly faster and more accurate than previous ones. Our results showed that the schizophrenic patients had lower values of the L1 at the left inferior frontal and anterior temporal regions compared with normal controls. These results for L1 in non-linear analysis have some differences from those for power ratios in linear analysis. These suggest that the non-linear analysis of the EEGs such as the estimation of the L1 might be a useful tool in analyzing EEG data to explore the neurodynamics of the brains of schizophrenic patients.

Age differences in personality across the adult life span: parallels in five cultures.

Both cross-sectional and longitudinal studies in the United States have shown consistent changes between college age and middle adulthood. There appear to be declines in 3 of the 5 major factors of personality--Neuroticism, Extraversion, and Openness--and increases in Agreeableness and Conscientiousness. To examine cross-cultural generalizability of these findings, translations of the Revised NEO Personality Inventory were administered to samples in Germany, Italy, Portugal, Croatia, and South Korea (N = 7,363). Similar patterns of age differences were seen in each country, for both men and women. Common trends were also seen for the more specific traits that define the major factors. Because these nations differ substantially in culture and recent history, results suggest the hypothesis that these are universal maturational changes in adult personality.

Application of semiological seizure classification to epileptic seizures in children.

To better define seizure characteristics and to examine whether semiological seizure classification (SSC) can be appropriately applied to the seizures of infants and children, we studied 152 videotaped seizures recorded in 133 children. Seizure semiology was described on the basis of a series of behavioural, sensory, and motor phenomena according to SSC. Special emphasis was placed on whether one semiology can be representative of a patient's whole semiology sequence. If one semiology was able to represent the whole sequence, the seizure was classified according to SSC. Ninety of 152 seizures (59.2%) could be classified as a single seizure type by SSC. However, only 19 of 53 seizures (35.9%) consisting of two semiologies, three of 24 seizures (12.5%) consisting of three semiologies, and one of eight seizures (12.5%) consisting of four semiologies could be classified according to SSC. Although SSC is very efficient, it is more accurately a descriptive terminology for clinical ictal events than a classification system.

Nonlinear analysis of the EEG of schizophrenics with optimal embedding dimension.

We estimated the correlation dimensions of EEGs in patients with schizophrenia to investigate the dynamical properties underlying the EEG. We employed a new method, proposed by Kennel et al. (Kennel MB, Brown R, Abarbanel HDI. Determining embedding dimension for phase-space reconstruction using a geometrical construction. Phys Rev A 1992;45:3403-11), to calculate the correlation dimension D2. That method determined the proper minimum embedding dimension by looking at the behaviour of nearest neighbours under a change in the embedding dimension d from d to d + 1. We demonstrated that for limited noisy data, our algorithm was strikingly faster and more accurate than previous ones. We estimated the D2 of EEGs from 16 channels in patients with schizophrenia according to DSM-IV whereas previous studies, which estimated chaoticity of EEG in schizophrenia, recorded EEG only in a limited number of channels. Schizophrenic patients had a lower correlation dimension in the left inferior frontal and anterior temporal regions compared with controls. Our finding of decreased left frontal and temporal chaotic activity in schizophrenics is in line with the findings of a hypofrontality and hypotemporality reported in previous clinical studies such as EEG, blood flow, brain MRI and positron emission tomography studies in schizophrenia. This result suggests that chaos analysis may be a useful tool in analysing EEG data to explore the brain mechanism of schizophrenia.

Spatio-temporal pattern of EEG in young brain respiration-training children.

We have evaluated the effect of 'Brain Respiration' training on brain activity using Karhunen-Loeve (KL) decomposition as a method for spatio-temporal analysis of the electroencephalogram (EEG). BR training is a form of breath-work to optimize the function of the brain by concentrating Qi energy in the brain. Recently, BR-training has been reported to improve emotional maturity (i.e., EQ), short-term memory and intuition (Yoo et al., 1998). EEG data were taken during BR-training from 12 young BR-trainees (average age: 9.4 years) who had trained for 4 to 14 months, and during relaxation from age matched non-trained children. Spatio-temporal analysis showed a significant difference of EEG dynamics in right prefrontal, right inferior frontal, posterior temporal, parietal and occipital areas between BR-trainees and the control group. Amplitude of eigenvector components of BR-trainees in the areas of frontal, temporal and occipital cortex was larger than that of non-trained children (values were smaller in parietal cortex), with remarkably high amplitude alpha coherence all over the scalp. These results suggest that BR-training possibly activates brain function through changes in the activity of the frontal association area where higher mental integration and creative activities are mediated.

The effect of repetitive transcranial magnetic stimulation on fear extinction in rats.

Facilitating fear extinction is clinically important to improve the efficacy of current exposure therapies for the treatment of anxiety disorders, such as post-traumatic stress disorder (PTSD). The aim of this study was to determine if repeated transcranial magnetic stimulation (rTMS) facilitates fear extinction in rats, especially when paired with exposure to a conditioned stimulus (CS). Thirty-five rats were conditioned to a tone CS by pairing the tone with an electric foot shock as an aversive unconditioned stimulus (US). We assessed the effects of 10 Hz rTMS before fear extinction (experiment 1) and rTMS paired with CS during extinction (experiment 2) on the following day. Fear responses of the rats were estimated using the level of freezing upon tone stimulus and were compared between the rTMS and corresponding sham groups. The rats treated with rTMS before fear extinction showed no difference in freezing time when compared with the sham group. However, the rats treated with rTMS paired with CS during extinction showed significantly less freezing behavior than the sham group, and this enhancement of fear extinction remained after 24 h without further stimulation. This finding suggests that high-frequency rTMS paired with trauma-reminding stimuli enhances fear extinction and that rTMS in conjunction with exposure therapy is potentially useful for facilitating extinction memory in the treatment of PTSD.

Specific hippocampal choline decrease in an animal model of depression.

A decreased level of the hippocampal choline signal was found in patients with depression in previous proton magnetic resonance spectroscopy ((1)H-MRS) studies. The objective of this study is to compare choline levels before and after the forced swimming test (FST), an animal model of depression typically used for assessing antidepressant activity. (1)H-MRS spectra were obtained from both the left and right hippocampus. After the FST, rats showed a significant decrease of the choline/creatine (Cho/Cr, p = 0.037) and choline/N-acetylaspartate (Cho/NAA, p = 0.048) ratios in the left hippocampus, but not in the right hippocampus. This finding was analogous to results from patients with depression. It suggests that decreased Cho/Cr and Cho/NAA ratios in the left hippocampal regions might be considered to be biomarkers in rats with depression.

Transcription factor CP2 is crucial in hemoglobin synthesis during erythroid terminal differentiation in vitro.

The transcription factor CP2 was initially identified to bind to the promoter region of the murine alpha-globin gene and known to stimulate the expression of alpha-globin by increasing CP2 transcripts 3- to 5-fold during induced differentiation of mouse erythroleukemic (MEL) cells in vitro. Here, we report that this increment of CP2 expression is crucial in erythroid-specific globin gene expression and hemoglobin synthesis. When antisense CP2 was overexpressed in MEL cells, production of endogenous CP2 protein was reduced 70-80%, and significant loss of its promoter binding activity was observed. During HMBA-induced terminal differentiation of antisense CP2 expressing MEL cells, the transcription of endogenous alpha-globin gene was suppressed as expected. Moreover, both beta-globin gene expression and hemoglobin synthesis were also severely impaired, without affecting the expression of key heme enzyme genes or HMBA-induced proliferation and viability.