A Validation Study of Mental Health Monitoring Through a Mobile Application.

OBJECTIVE: Face-to-face evaluation is the most important in psychiatric evaluation, but smart healthcare, including non-face-to-face evaluation, can be beneficial considering the situation in which face-to-face evaluation is limited or the preventive aspect of mental illness. In this paper, we aimed to check whether mental health screening tests have the same significance as paper-based tests even when collected through mobile applications. METHODS: A smart mental healthcare screening test was conducted on the 1,327 community subjects. We measured two indicators of depression (Patient Health Questionnaire 9-item scale, PHQ-9) and anxiety (Generalized Anxiety Disorder 7-item scale, GAD-7) to check mental health conditions. RESULTS: The average Cronbach's alpha value of the PHQ-9 questionnaire was good at 0.870. As a result of PHQ-9's principal component analysis, one component with an eigenvalue of 1 or more was identified, which is suitable to be described as a single factor. The average Cronbach's alpha value of the GAD-7 was 0.919. The structural validity of the GAD-7 was confirmed through principal component analysis. CONCLUSION: Our results show that PHQ-9 and GAD-7 scales performed through mobile applications can have the same meaning as paper-based tests. Surveys using a tablet PC, or smartphone application can monitor residents' mental health and accumulate data. Based on these data, smart mental health management can check the mental health of residents and treat mental illness in connection with medical services.

Conventional reversal of rocuronium-induced neuromuscular blockade by sugammadex in Korean children: pharmacokinetics, efficacy, and safety analyses.

Background: Sugammadex is known to reverse neuromuscular blockade induced by non-depolarizing agents. In children, the recommended dose for reversal of moderate neuromuscular blockade is 2 mg/kg. We investigated the pharmacokinetics and pharmacodynamics of sugammadex in Korean children. Methods: Children (2-17 years of age) undergoing brain or spine surgery were enrolled and randomly assigned to control (neostigmine) and 2, 4, or 8 mg/kg sugammadex groups. Following induction of anesthesia and monitoring of the response to train-of-four stimulation, 1 mg/kg rocuronium was intravenously administered. Upon reappearance of the second twitch to train-of-four stimulation, the study drug was administered according to group allocation. The plasma concentrations of rocuronium and sugammadex were serially measured at nine predefined time points following study drug administration. To determine efficacy, we measured the time elapsed from drug administration to recovery of T4/T1 ≥ 0.9. For pharmacokinetics, non-compartmental analysis was performed and we monitored adverse event occurrence from the time of study drug administration until 24 h post-surgery. Results: Among the 29 enrolled participants, the sugammadex (2 mg/kg) and control groups showed recovery times [median (interquartile range)] of 1.3 (1.0-1.9) and 7.7 (5.3-21.0) min, respectively (p = 0.002). There were no significant differences in recovery time among the participants in sugammadex groups. The pharmacokinetics of sugammadex were comparable to those of literature findings. Although two hypotensive events related to sugammadex were observed, no intervention was necessary. Conclusion: The findings of this pharmacokinetic analysis and efficacy study of sugammadex in Korean children indicated that sugammadex (2 mg/kg) may be safely administered for reversing moderate neuromuscular blockade. Some differences in pharmacokinetics of sugammadex were observed according to age. Clinical Trial Registration: http://clinicaltrials.gov (NCT04347486).

Reversal of rocuronium-induced intense neuromuscular blockade by sugammadex in Korean children: A pharmacokinetic and pharmacodynamic analysis.

Sugammadex, a selective antagonist of steroidal non-depolarizing neuromuscular blocking agents, has been used in children in limited circumstances. However, neither pharmacokinetics (PKs) nor recovery profile of sugammadex for intense neuromuscular blockade reversal in children have been reported. This prospective study aimed to obtain a PK model of sugammadex and evaluate its efficacy and safety for intense neuromuscular blockade reversal in children. Forty children (age, 2-17 years) who underwent surgery that required early neuromuscular blockade reversal were enrolled. After neuromuscular blockade with 1 mg∙kg-1 of rocuronium, sugammadex (2, 4, and 8 mg∙kg-1 ) or a conventional dose of neostigmine (0.03 mg∙kg-1 ) was administered randomly after confirmation of zero post-tetanic count. The plasma concentrations of rocuronium and sugammadex were measured 2 min after rocuronium injection; immediately before, 2, 5, 15, 60, 120, 240, and 480 min after the study drug injection. Response to train-of-four stimulation was continuously recorded. Noncompartmental analysis and population PK modeling were performed. For pharmacodynamics, the recovery profile was measured. Three-compartment PK model was established for sugammadex. The median (interquartile range [IQR]) time from injection of 8 mg∙kg-1 of sugammadex to recovery of T4 /T1 greater than or equal to 0.9 at train-of-four stimulation was 1.1 (IQR: 0.88-1.8) min. No adverse events related to sugammadex were observed. We present a PK analysis of sugammadex for rocuronium-induced intense neuromuscular blockade reversal in children with its recovery profile. The time to recover T4 /T1 greater than or equal to 0.9 at train-of-four stimulation with 8 mg∙kg-1 of sugammadex was less than 3 min and comparable to that in adults.

Long-read transcriptome sequencing provides insight into lignan biosynthesis during fruit development in Schisandra chinensis.

BACKGROUND: Schisandra chinensis, an ancient member of the most basal angiosperm lineage which is known as the ANITA, is a fruit-bearing vine with the pharmacological effects of a multidrug system, such as antioxidant, anti-inflammatory, cardioprotective, neuroprotective, anti-osteoporosis effects. Its major bioactive compound is represented by lignans such as schisandrin. Molecular characterization of lignan biosynthesis in S. chinensis is of great importance for improving the production of this class of active compound. However, the biosynthetic mechanism of schisandrin remains largely unknown. RESULTS: To understand the potential key catalytic steps and their regulation of schisandrin biosynthesis, we generated genome-wide transcriptome data from three different tissues of S. chinensis cultivar Cheongsoon, including leaf, root, and fruit, via long- and short-read sequencing technologies. A total of 132,856 assembled transcripts were generated with an average length of 1.9 kb and high assembly completeness. Overall, our data presented effective, accurate gene annotation in the prediction of functional pathways. In particular, the annotation revealed the abundance of transcripts related to phenylpropanoid biosynthesis. Remarkably, transcriptome profiling during fruit development of S. chinensis cultivar Cheongsoon revealed that the phenylpropanoid biosynthetic pathway, specific to coniferyl alcohol biosynthesis, showed a tendency to be upregulated at the postfruit development stage. Further the analysis also revealed that the pathway forms a transcriptional network with fruit ripening-related genes, especially the ABA signaling-related pathway. Finally, candidate unigenes homologous to isoeugenol synthase 1 (IGS1) and dirigent-like protein (DIR), which are subsequently activated by phenylpropanoid biosynthesis and thus catalyze key upstream steps in schisandrin biosynthesis, were identified. Their expression was increased at the postfruit development stage, suggesting that they may be involved in the regulation of schisandrin biosynthesis in S. chinensis. CONCLUSIONS: Our results provide new insights into the production and accumulation of schisandrin in S. chinensis berries and will be utilized as a valuable transcriptomic resource for improving the schisandrin content.

The Role of Decreased Cortical Thickness and Volume of Medial Temporal Lobe Structures in Predicting Incident Psychosis in Patients With Alzheimer's Disease: A Prospective Longitudinal MRI Study.

OBJECTIVE: To investigate the effect of decreased cortical thickness or volume of medial temporal lobe structures on the risk of incident psychosis in patients with AD. DESIGN, SETTING, AND PARTICIPANTS: This hospital-based prospective longitudinal study enrolled 109 patients with AD. All patients with AD were evaluated at 3-month intervals to investigate the effect of decreased cortical thickness or volume of medial temporal lobe structures on the risk of incident psychosis in patients with AD. OUTCOME MEASURE: The main outcome measure was time-to-progression from AD to incident psychosis. The thickness or volume of medial temporal lobe structures (i.e., the hippocampus, entorhinal cortex, and parahippocampus) were measured using magnetic resonance imaging and the Freesurfer automated segmentation pipeline at baseline. RESULTS: Multivariate Cox proportional hazards regression analysis revealed that a decreased cortical thickness or volume of medial temporal region was associated with a higher risk of incident psychosis in patients with AD. The hazard ratios for decreased cortical thickness of the left entorhinal cortex and decreased cortical volume of the right hippocampus were 4.291 (95% confidence interval [CI], 1.196-15.384) and 2.680 [(CI, 1.003-1.196]), respectively. CONCLUSION: Our study revealed that decreased cortical thickness or volume of medial temporal sub-regions is a risk factor for incident psychosis in patients with AD. A careful assessment of the thickness or volume of the medial temporal lobe structures in AD may improve early detection and intervention of psychosis in AD.

The Relationship of Plasma Transthyretin Level with Global or Regional Amyloid Beta Burden in Subjects with Amnestic Mild Cognitive Impairment: Cross-Sectional Amyloid PET Study.

Background: To investigate the relationships of plasma transthyretin levels with amyloid beta deposition and medial temporal atrophy in amnestic mild cognitive impairment. Methods: This is a cross-sectional study of association of subjects with amnestic mild cognitive impairment. Plasma transthyretin levels, brain magnetic resonance imaging, and 18F-florbetaben positron emission tomography were simultaneously measured in subjects with amnestic mild cognitive impairment. Results: Plasma transthyretin levels were positively associated with amyloid beta deposition in global (r = 0.394, P = .009), frontal cortex (r = 0.316, P = .039), parietal cortex (r = 0.346, P = .023), temporal cortex (r = 0.372, P = .014), occipital cortex (r = 0.310, P = .043), right posterior cingulate (r = 0.350, P = .021), left precuneus (r = 0.314, P = .040), and right precuneus (r = 0.398, P = .008). No association between plasma transthyretin level and medial temporal sub-regional atrophies was found. Conclusions: Our findings of positive association of plasma transthyretin levels with global and regional amyloid beta burden suggest upregulation of transthyretin level as a reactive response to amyloid beta deposition during the early stages of the Alzheimer's disease process.

Anticancer Effect of Heparin-Taurocholate Conjugate on Orthotopically Induced Exocrine and Endocrine Pancreatic Cancer.

Pancreatic cancers are classified based on where they occur, and are grouped into those derived from exocrine and those derived from neuroendocrine tumors, thereby experiencing different anticancer effects under medication. Therefore, it is necessary to develop anticancer drugs that can inhibit both types. To this end, we developed a heparin-taurocholate conjugate, i.e., LHT, to suppress tumor growth via its antiangiogenic activity. Here, we conducted a study to determine the anticancer efficacy of LHT on pancreatic ductal adenocarcinoma (PDAC) and pancreatic neuroendocrine tumor (PNET), in an orthotopic animal model. LHT reduced not only proliferation of cancer cells, but also attenuated the production of VEGF through ERK dephosphorylation. LHT effectively reduced the migration, invasion and tube formation of endothelial cells via dephosphorylation of VEGFR, ERK1/2, and FAK protein. Especially, these effects of LHT were much stronger on PNET (RINm cells) than PDAC (PANC1 and MIA PaCa-2 cells). Eventually, LHT reduced ~50% of the tumor weights and tumor volumes of all three cancer cells in the orthotopic model, via antiproliferation of cancer cells and antiangiogenesis of endothelial cells. Interestingly, LHT had a more dominant effect in the PNET-induced tumor model than in PDAC in vivo. Collectively, these findings demonstrated that LHT could be a potential antipancreatic cancer medication, regardless of pancreatic cancer types.

Reduced Thickness of the Anterior Cingulate Cortex as a Predictor of Amnestic-Mild Cognitive Impairment Conversion to Alzheimer's Disease with Psychosis.

BACKGROUND: A long-term follow-up study in patients with amnestic mild cognitive impairment (aMCI) is needed to elucidate the association between regional brain volume and psychopathological mechanisms of Alzheimer's disease with psychosis (AD + P). OBJECTIVE: The purpose of this study was to investigate the effect of the thickness of the angular cingulate cortex (ACC) on the risk of AD + P conversion in patients with aMCI. METHODS: This was a hospital-based prospective longitudinal study including 174 patients with aMCI. The main outcome measure was time-to-progression from aMCI to AD + P. Subregions of the ACC (rostral ACC, rACC; caudal ACC, cACC) and hippocampus (HC) were measured as regions of interest with magnetic resonance imaging and the Freesurfer analysis at baseline. Survival analysis with time to incident AD + P as an event variable was calculated with Cox proportional hazards models using the subregions of the ACC and HC as a continuous variable. RESULTS: Cox proportional hazard analyses showed that the risk of AD + P was associated with sub-regional ACC thickness but not HC volume: reduced cortical thickness of the left cACC (HR [95%CI], 0.224 [0.087-0.575], p = 0.002), right cACC (HR [95%CI], 0.318 [0.132-0.768], p = 0.011). This association of the cACC with the risk of AD also remained significant when adjusted for HC volume. CONCLUSION: We found that reduced cortical thickness of the cACC is a predictor of aMCI conversion to AD + P, independent of HC, suggesting that the ACC plays a vital role in the underlying pathogenesis of AD + P.

Psychometric Properties of Behavioral Checklist for Coping with Stress in Patients with Mood Disorders.

OBJECTIVE: Even though the importance of stress-coping, there is no reliable and valid scale to measure the stress-coping behavior yet. The purpose of this study is to explore the psychometric properties of Behavioral Checklist for Coping with Stress (BCCS). METHODS: A total of 458 subjects including healthy subjects and patients with bipolar or depressive disorders were analyzed. The reliability and validity of BCCS were examined by Chronbach's alpha and exploratory factor analysis using Principal Component Analysis. In order to evaluate criterion-related validity, the Pearson's correlation analyses between factors of BCCS and relevant scales were performed. RESULTS: BCCS showed good Chronobach's alpha (0.695-0.833) and had acceptable validity. Factor 1 and factor 4 of BCCS were negatively correlated with depression, anxiety and positivity correlated with task and problem-solving, avoidance, tension-releasing copings in common. Factor 2 and 3 were positively correlated with impulsivity, emotionality, avoidance, behavioral and verbal aggression and tension-releasing copings in common. Different from factor 2, factor 3 was positively correlated with depression, anxiety and anger-suppression. CONCLUSION: The results of this study suggest that this BCCS might be a reliable and valid scale for measuring stress-coping behaviors. This scale could facilitate research to investigate clinical implications related to behavioral stress-coping.

Association of Temporolimbic Volumes with Treatment Response to Antipsychotic Medication for Delusion in Patients with Alzheimer's Disease.

Objective: This study investigated the association between gray matter volume and the treatment response to antipsychotic medication in patients with Alzheimer's disease (AD). Methods: We included 26 AD patients with delusions from the Memory Impairment Center of the Pusan National University Hospital in South Korea. All participants underwent baseline brain magnetic resonance imaging and took risperidone as an antipsychotic medication for 6 weeks. Gray matter volumes were measured using voxel-based morphometry at baseline. Treatment response with respect to delusional symptoms was defined as the change in delusion item scores in the Korean version of the Neuropsychiatry Inventory (K-NPI), from baseline to 6 weeks later. A voxel-based multiple linear regression model integrated with statistical parametric mapping was used to investigate the association between gray matter volume and treatment response after controlling for covariates. Results: The treatment response was significantly positively correlated with gray matter volume in the temporal lobe (both the fusiform gyri and the left superior and inferior temporal gyri) and the limbic system (the left parahippocampal gyrus and left amygdala) after controlling for age, sex, education level, total intracranial volume, risperidone dosage, baseline Korean version of the Mini-Mental Status Examination scores, and baseline K-NPI scores for the delusion and non-delusion domains (P < .001, uncorrected, KE > 100 voxels). Conclusion: Our findings suggest that specific gray matter volumes, including those of the temporal region and the limbic system, may affect treatment response to antipsychotic medication in terms of delusional symptoms in patients with AD.

Anger-Related Characteristics According to Chronotypes in Bipolar or Depressive Disorders.

OBJECTIVE: Though anger was highly associated with eveningness in general population, there is no study on the relationship between chronotype and anger-related characteristics in bipolar or depressive disorders. This study aimed to investigate the difference of anger-related characteristics according to chronotypes in bipolar or depressive disorders. METHODS: Patients with bipolar or depressive disorders (n=238) were included in this study. Their chronotypes and anger-related characteristics were assessed with a self-evaluation of the Composite Scale of Morningness (CSM), the State Trait Anger Expression Inventory (STAXI) and the Anger Coping Scale (ACS). RESULTS: The eveningness group in patients with mood disorders showed the highest scores of anger-trait (p<0.001), anger-expression (p=0.002) and anger-in (p<0.001) in STAXI subscales, verbal aggression (p=0.010) in ACS subscales among three groups, but the morningess group showed the lowest scores of these subscales among three groups. However, there were no significant differences in all subscales of the STAXI and ACS according to diagnostic subtypes in the Friedman test. CONCLUSION: The results of this study suggested that eveningness in patients with mood disorders might be related to anger proneness and maladaptive anger coping. To manage anger emotion in the patients with mood disorders, therapeutic interventions to modulate eveningness might be helpful.

Various Psychiatric Manifestation in DiGeorge Syndrome (22q11.2 Deletion Syndrome): A Case Report.

This case report aimed to describe various psychiatric manifestation and treatment course in a patient with DiGeorge syndrome. Psychiatric symptoms and treatment course in a female patient with DiGeorge syndrome were described. This patient showed psychotic symptoms, mood symptoms, and intellectual disability. As well as various psychiatric symptoms, treatment response and sensitivity of side effect by antipsychotics were different from typical characteristics in psychiatric disorders. This case suggests that the genetic defect in DiGeorge syndrome might have a great association with psychiatric problems and response of antipsychotics.

Similarities and Differences of Strategies between Bipolar and Depressive Disorders on Stress Coping.

OBJECTIVE: As coping strategies can influence the illness course of mood disorder, they could be potential targets for psychological intervention. The current study investigated the similarities and differences in stress coping styles between bipolar disorder (BD) and depressive disorder (DD). METHODS: Subjects with BD (n=135) and DD (n=100) who met the DSM-IV diagnostic criteria were included in this analysis. Coping strategies were assessed using the coping inventory for stressful situations and depressive symptoms were assessed by Beck depression inventory. RESULTS: The BD group showed significantly more avoidant and task-oriented coping than the DD group (t=2.714, p=0.007; t=2.193, p=0.039). After excluding the effect of the depressive symptoms themselves (by comparing two groups in non-depressive state), the BD group still showed significantly more avoidant and task-oriented coping than the DD group (t=2.040, p=0.045; t=2.556, p=0.013), but when the symptoms of depression get greater, the difference between BD and DD coping strategies were reduced. CONCLUSION: Subjects with BD tend to use more task and avoidant coping than DD subjects. But when the symptoms of depression get greater, the difference in coping strategies between BD and DD were reduced.

Investigation of Maternal Effects, Maternal-Fetal Interactions, and Parent-of-Origin Effects (Imprinting) for Candidate Genes Positioned on Chromosome 18q21, in Probands with Schizophrenia and their First-Degree Relatives.

OBJECTIVE: A popular design for the investigation of such effects, including effects of parent-of-origin (imprinting), maternal genotype, and maternal-fetal genotype interactions, is to collect deoxyribonucleic acid (DNA) from affected offspring and their mothers and to compare with an appropriate control sample. We investigate the effects of estimation of maternal, imprinting and interaction effects using multimodal modeling using parents and their offspring with schizophrenia in Korean population. METHODS: We have recruited 27 probands (with schizophrenia) with their parents and siblings whenever possible. We analyzed 20 SNPs of 7 neuronal genes in chromosome 18. We used EMIM analysis program for the estimation of maternal, imprinting and interaction effects using multimodal modeling. RESULTS: Of analyzed 20 single nucleotide polymorphisms (SNPs), significant SNP (rs 2276186) was suggested in EMIM analysis for child genetics effects (p=0.0225438044) and child genetic effects allowing for maternal genetic effects (p=0.0209453210) with very stringent multiple comparison Bonferroni correction. CONCLUSION: Our results are the pilot study for epigenetic study in mental disorder and help to understanding and use of EMIM statistical genetics analysis program with many limitations including small pedigree numbers.

Mechanism of action of the trastuzumab biosimilar CT-P6.

Objectives: Therapeutic monoclonal antibody biosimilars are expected to help reduce the sizeable economic burden of targeted treatments. Trastuzumab (Herceptin®), a recombinant humanized monoclonal antibody that binds to the extracellular domain of HER2, is approved for use in HER2-overexpressing breast cancer (in both the adjuvant and metastatic settings) and HER2-positive gastric cancer. CT-P6 (Herzuma®) is a biosimilar of trastuzumab, designed to bind with high affinity and specificity to the same HER2 epitope as the reference product. We investigated whether CT-P6 exerts its effects through the same mechanism of action as trastuzumab. Methods: The mechanism of action of CT-P6 and trastuzumab, both as monotherapy and in combination with paclitaxel or pertuzumab, was compared in HER2-overexpressing breast cancer and gastric cancer cell models. Results: We confirmed that CT-P6 functions in a manner similar to trastuzumab by binding to the HER2 receptor, which is central to the effects of trastuzumab in all indications. Conclusions: Collectively, the results of this study show that the mechanisms of action of CT-P6 and trastuzumab are similar in HER2-positive breast cancer and gastric cancer models and, therefore, CT-P6 can be expected to perform similarly in the clinical setting.

Right hippocampus atrophy is independently associated with Alzheimer's disease with psychosis.

AIM: The purpose of this study was to determine whether regionally distributed medial temporal cortex thickness (or hippocampal volume) and frontal lobe volume are independently associated with the onset of Alzheimer's disease (AD) with psychosis. METHODS: We identified 26 AD patients with psychosis (AD+P) and 48 AD patients without psychosis (AD-P) from the Memory Impairment Clinic at Pusan National University Hospital in South Korea. They were matched for age, gender, duration of AD, and Clinical Dementia Rating sum of box score. All participants met the National Institute of Neurological and Communication Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for probable AD. Psychosis was diagnosed according to Jeste and Finkel's proposed diagnostic criteria for psychosis of AD. All participants underwent 3-T magnetic resonance imaging, and 3-D magnetization-prepared rapid gradient echo sequence was acquired for each. The FreeSurfer version 5.1 software package was used to analyze cortical thickness and volume on 3-D T1 -weighted images. anova was used to investigate the differences in cortical thickness and the volume of the total frontal cortex, total temporal cortex, and subregions of the medial temporal cortex between groups after age, gender, years of education, Clinical Dementia Rating sum of box score, duration of AD, and total intracranial volume were controlled for. Furthermore, we added the total frontal volume as an additional variable to investigate whether the association between the medial temporal cortex and AD+P is independent of the frontal cortex. RESULTS: We found that both left and right hippocampal volume were smaller in AD+P than in AD-P. In particular, there was a significant difference in right hippocampal volume between the AD+P and AD-P groups after total frontal volume was added as an additional variable. CONCLUSION: We found that more severe hippocampal atrophy is associated with AD+P than with AD-P. In addition, atrophy of the right hippocampus remained significant among AD+P after adjustment for frontal volume. These findings suggest that right hippocampal atrophy is independently associated with AD+P.

Heritability and familiality of psychopathologic dimensions in Korean families with schizophrenia.

AIM: Categorical syndromes such as schizophrenia could be a combination of many continuous mental structure phenotypes including several personality development/degeneration dimensions. This study investigated the heritability and familiality of symptom check list (SCL) psychopathologic dimensions in Korean schizophrenia linkage disequilibrium families. METHOD: We recruited 204 probands (with schizophrenia) with their parents and siblings whenever possible. We used the SCL questionnaire to measure psychopathologic dimensions. The heritability of symptomatic dimensions in 543 family members was estimated using Sequential Oligogenic Linkage Analysis Routines (SOLAR). Psychopathologic dimensions in the 543 family members were compared with those in 307 healthy unrelated controls to measure familiality on using analysis of variance (ANOVA) analysis. RESULTS: Five of the nine SCL variables were significantly heritable and were included in the subsequent analyses. The three groups (control, unaffected first-degree relative, schizophrenia patient) were found to be significantly different with regard to the expected order of average group scores for all heritable dimensions. CONCLUSION: Aberrations in several symptomatic dimensions could contribute to the complexity of schizophrenia syndrome as a result of genetic-environment coaction or interaction in spite of some limitations (recruited family, phenotyping).

A whole exome sequencing study of a Korean proband with idiopathic basal ganglia calcification and its daughter.

Idiopathic basal ganglia calcification (IBGC) is characterized by brain calcification and a wide variety of neurological and psychiatric symptoms. In families displaying an autosomal dominant inheritance pattern, three causative genes have been identified: SLC20A2, PDGFRB, and very recently, PDGFB. While in clinical practice sporadic presentation of IBGC is frequent, well-documented reports of true sporadic occurrences are rare. We report a case of a 61-year-old woman who presented with depressive and dystonic symptoms revealing IBGC. Her 41-year-old daughter was healthy. In the proband, we identified 4 mutations in PDGFB, and 1 exonic mutation in SLC20A2, all of which were absent in the daughter. These mutations may result in a loss-of-function of PDGF-B or SLC20A2, which has been shown to cause IBGC in humans and disrupts the blood-brain barrier in mice resulting in brain calcification. Herein, we present the occurrence of a sporadic patient of IBGC and its causative mutations.

Protein Kinase C Activity and Delayed Recovery of Sleep-Wake Cycle in Mouse Model of Bipolar Disorder.

OBJECTIVE: Previous studies reported the delayed recovery group after circadian rhythm disruption in mice showed higher quinpiroleinduced locomotor activity. This study aimed to compare not only Protein Kinase C (PKC) activities in frontal, striatal, hippocampus and cerebellum, but also relative PKC activity ratios among brain regions according to recovery of circadian rhythm. METHODS: The circadian rhythm disruption protocol was applied to eight-week-old twenty male Institute Cancer Research mice. The circadian rhythm recovery patterns were collected through motor activities measured by Mlog system. Depressive and manic proneness were examined by forced swim test and quinpirole-induced open field test respectively. Enzyme-linked immunosorbent assay was employed to measure PKC activities. RESULTS: The delayed recovery group presented greater locomotor activities than the early recovery group (p=0.033). The delayed recovery group had significantly lower frontal PKC activity than the other (p=0.041). The former showed lower frontal/cerebellar PKC activity ratio (p=0.047) but higher striatal/frontal (p=0.038) and hippocampal/frontal (p=0.007) PKC activities ratios than the latter. CONCLUSION: These findings support potential mechanism of delayed recovery after circadian disruption in bipolar animal model could be an alteration of relative PKC activities among mood regulation related brain regions. It is required to investigate the PKC downstream signaling related to the delayed recovery pattern.

Can Residual Symptoms During Inter-Episode Period after Partial Remission in Bipolar I Disorder Have Cyclic Patterns with Specific Frequencies?

This case report aimed to describe cyclic patterns of residual mood symptoms in partially remitted bipolar I patient. In a 24-year-old woman with bipolar I disorder, residual mood symptoms measured by self-rated daily mood chart for 18 months were analyzed using wavelet analysis. A 146-day periodicity was prominent for the first 100 days after discharge. Between 100-200 days, 146-day periodicity was progressively diminished and 21- and 8-day periodicity was prominent. Between 200-516 days, 21-day periodicity was diminished and 85-day periodicity became prominent. This case suggest that bipolar patients might have cyclic residual symptoms with specific frequencies.