There are differences in clinical presentation with and without insomnia in MDD, and it is expected that there are brain biological differences that contribute to this, but functional MRI studies of MDD with insomnia vs MDD without insomnia are scarce. In particular, few studies have examined resting state functional connectivity (RSFC) seeding the habenula and septal nuclei, which play key roles in both mood and sleep.

The purpose of this study is to determine whether there are differences in habenula and septal nuclei and RSFC in the presence or absence of clinically significant insomnia in patients with MDD.

To identify the effects of insomnia in MDD group, one-way ANCOVA covariate control was used to compare differences of RSFC between MDD_w/INS and MDD_wo/INS group. The potential confounders (i.e., age, sex, education years, and total score of HDRS-17) were adjusted in this analysis. To examine the relationship between RSFC and clinical sleep questionnaires (i.e., ISI and PSQI) in the participants with MDD, Pearson’s partial correlation analysis controlling same potential confounders was performed by using Fisher-transformed correlation coefficients and scores of ISI and PSQI. For comparing the difference of RSFC between MDD and HC, the analysis was also performed with ANCOVA controlling for age, sex, education years.

The analysis in this study included 36 in the MDD_w/INS group, 21 participants in the MDD_wo/INS group, and 38 in the healthy controls (HC) group. The main finding of this study was that MDD with insomnia showed increased RSFC in Habe_L - Rolandic_Oper_R, Habe_L - Cuneus_R, Habe_R - Thal_Pul_R, and decreased RSFC in Septal - Cerebellum_Crus1_R compared to MDD without insomnia. All regions with significant results were significantly correlated with insomnia severity.

Since the RSFC of all pairs of regions that showed significant differences between the two groups in this study were significantly correlated with insomnia severity (i.e., ISI score), the association of these regions with insomnia in MDD is supported. The significance of this study is that there have been studies that have examined the RSFC in fMRI for insomnia, but there are few studies on MDD with insomnia, and since the habenula and septal nuclei play an important role in insomnia, sleep, and mood, it is meaningful to seed fMRI studies on these areas.

None Declared

Aggregation of phosphorylated tau (pTau) is a hallmark feature of Alzheimer’s disease (AD). Novel assays now allow pTau to be measured in plasma. Elevated plasma pTau predicts subsequent development of AD, cortical atrophy and AD-related pathologies in the brain. We aimed to determine whether elevated pTau is associated with cognitive functioning in older adults prior to the development of dementia.

Independently living older adults (N = 48, mean age = 70.0 years; SD = 7.7; age range 55-88 years; 35.4% male) free of dementia or clinical stroke were recruited from the community and underwent blood draw and neuropsychological assessment. Plasma was assayed using the Quanterix Simoa® pTau-181 V2 Advantage Kit to quantify pTau-181 levels and APOE genotyping was conducted on the blood cell pellet fraction obtained from plasma separation. Global cognition was assessed using the Dementia Rating Scale-2 (DRS-2) and executive function was assessed using the Stroop, D-KEFS-2 Fluency, and Trails Making Test. Diagnosis of mild cognitive impairment (MCI) was determined based on overall neuropsychological performance. Participants were diagnosed as MCI if they scored >1 SD below norm-referenced values on 2 or more tests within a domain (language, executive, memory) or on 3 tests across domains.

Multiple linear regression analysis revealed a significant negative association between plasma pTau-181 levels and DRS-2 (B = -2.57, 95% CI (-3.68, -1.47), p <.001), Stroop Color-Word score (B = -2.64, 95% CI (-4.56, - 0.71), p = .009) and Fruits and Vegetables Fluency (B = -1.67, 95% CI (-2.84, -0.49), p = .007), adjusting for age, sex, education and APOE4 status. MCI diagnosis was determined for 43 participants, of which 8 (18.6%) met criteria. Logistic regression analysis revealed that pTau-181 levels are associated with increased odds of MCI diagnosis (OR = 2.18, 95% CI (1.01, 4.68), p = .046), after accounting for age, sex, education and APOE4 status.

Elevated plasma pTau-181 is associated with worse cognition, particularly executive function, and predicts MCI diagnosis in older adults. Higher plasma pTau-181 was associated with increased odds of MCI diagnosis. Detection of pTau-181 in plasma allows a novel, non-invasive method to detect burden of one form of AD pathology. These findings lend support to the use of plasma pTau-181 as a valuable marker in detecting even early cognitive changes prior to the development of AD. Additional longitudinal studies are warranted to explore the prognostic value of plasma pTau-181 over time.

The locus coeruleus (LC) innervates the cerebrovasculature and plays a crucial role in optimal regulation of cerebral blood flow. However, no human studies to date have examined links between these systems with widely available neuroimaging methods. We quantified associations between LC structural integrity and regional cortical perfusion and probed whether varying levels of plasma Alzheimer’s disease (AD) biomarkers (Aß42/40 ratio and ptau181) moderated these relationships.

64 dementia-free community-dwelling older adults (ages 55-87) recruited across two studies underwent structural and functional neuroimaging on the same MRI scanner. 3D-pCASL MRI measured regional cerebral blood flow in limbic and frontal cortical regions, while T1-FSE MRI quantified rostral LC-MRI contrast, a well-established proxy measure of LC structural integrity. A subset of participants underwent fasting blood draw to measure plasma AD biomarker concentrations (Aß42/40 ratio and ptau181). Multiple linear regression models examined associations between perfusion and LC integrity, with rostral LC-MRI contrast as predictor, regional CBF as outcome, and age and study as covariates. Moderation analyses included additional terms for plasma AD biomarker concentration and plasma x LC interaction.

Greater rostral LC-MRI contrast was linked to lower regional perfusion in limbic regions, such as the amygdala (ß = -0.25, p = 0.049) and entorhinal cortex (ß = -0.20, p = 0.042), but was linked to higher regional perfusion in frontal cortical regions, such as the lateral (ß = 0.28, p = 0.003) and medial (ß = 0.24, p = 0.05) orbitofrontal (OFC) cortices. Plasma amyloid levels moderated the relationship between rostral LC and amygdala CBF (Aß42/40 ratio x rostral LC interaction term ß = -0.31, p = 0.021), such that as plasma Aß42/40 ratio decreased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and amygdala perfusion decreased. Plasma ptau181levels moderated the relationship between rostral LC and entorhinal CBF (ptau181 x rostral LC interaction term ß = 0.64, p = 0.001), such that as ptau181 increased (i.e., greater pathology), the strength of the negative relationship between rostral LC integrity and entorhinal perfusion decreased. For frontal cortical regions, ptau181 levels moderated the relationship between rostral LC and lateral OFC perfusion (ptau181 x rostral LC interaction term ß = -0.54, p = .004), as well as between rostral LC and medial OFC perfusion (ptau181 x rostral LC interaction term ß = -0.53, p = .005), such that as ptau181 increased (i.e., greater pathology), the strength of the positive relationship between rostral LC integrity and frontal perfusion decreased.

LC integrity is linked to regional cortical perfusion in non-demented older adults, and these relationships are moderated by plasma AD biomarker concentrations. Variable directionality of the associations between the LC and frontal versus limbic perfusion, as well as the differential moderating effects of plasma AD biomarkers, may signify a compensatory mechanism and a shifting pattern of hyperemia in the presence of aggregating AD pathology. Linking LC integrity and cerebrovascular regulation may represent an important understudied pathway of dementia risk and may help to bridge competing theories of dementia progression in preclinical AD studies.

Blood pressure variability (BPV), independent of traditionally targeted average blood pressure levels, is an emerging vascular risk factor for stroke, cerebrovascular disease, and dementia, possibly through links with vascular-endothelial injury. Recent evidence suggests visit-to-visit (e.g., over months, years) BPV is associated with cerebrovascular disease severity, but less is known about relationships with short-term (e.g., < 24 hours) fluctuations in blood pressure. Additionally, it is unclear how BPV may be related to angiogenic growth factors that play a role in cerebral arterial health.

We investigated relationships between short-term BPV, white matter hyperintensities on MRI, and levels of plasma vascular endothelial growth factor (VEGF) in a sample of community-dwelling older adults (n = 57, ages 55-88) without history of dementia or stroke. Blood pressure was collected continuously during a 5-minute resting period. BPV was calculated as variability independent of mean, a commonly used index of BPV uncorrelated with average blood pressure levels. Participants underwent T2-FLAIR MRI to determine severity of white matter lesion burden. Severity of lesions was classified as Fazekas scores (0-3). Participants also underwent venipuncture to determine levels of plasma VEGF. Ordinal logistic regression examined the association between BPV and Fazekas scores. Multiple linear regression explored relationships between BPV and VEGF. Models controlled for age, sex, and average blood pressure.

Elevated BPV was related to greater white matter lesion burden (i.e., Fazekas score) (systolic: OR = 1.17 [95% CI 1.01, 1.37]; p = .04; diastolic: OR = 2.47 [95% CI 1.09, 5.90]; p = .03) and increased levels of plasma VEGF (systolic: ß = .39 [95% CI .11, .67]; adjusted R2 = .16; p = .007; diastolic: ß = .48 [95% CI .18, .78]; adjusted R2 = .18; p = .003).

Findings suggest short-term BPV may be related to cerebrovascular disease burden and angiogenic growth factors relevant to cerebral arterial health, independent of average blood pressure. Understanding the role of BPV in cerebrovascular disease and vascular-endothelial health may help elucidate the increased risk for stroke and dementia associated with elevated BPV.

In South Korea, all men at the age of 18 or older are required to serve at military for a certain period as an obligation. These recruits should be able to withstand psychological stress and pressures of rapid adaptation of the unique and new environment in military.

The current study attempted to identify distinct subgroups of patients referred for military service suitability and further to investigate whether there is a difference in clinical features such as treatment responsiveness and prognosis among those subgroups.

Subjects were male patients aged 18 to 28 years who visited the department of psychiatry at the University Hospital for evaluating mental health problems related to military service. We conducted a latent profile analysis (LPA) using 10 clinical scales of MMPI-2 as an indicator variable to investigate the subgroups of subjects. The clinical state of subjects was assessed with CGI-S and GAF scale for three time point (0, 3, and 6 month).

The results showed that the best fitting model corresponded to a three-class model: each class was named ‘Class 1: mild maladjustment’, ‘Class 2: neurotic depression and anxiety’, and ‘Class 3: highly vulnerable and hypervigilant’ respectively. Subsequent analysis was also carried out to identify changes in clinical symptoms and functional level across treatment time of each subgroup identified in LPA. We demonstrated that the three subgroups displayed differential characteristics in treatment responsiveness and clinical course evaluated by CGI-S and GAF over a treatment period of 6 months. Three subgroups indicated significant differences in the number of medications prescribed as well. Class 3 had more antidepressants and anxiolytics on use than Class 1 and 2. Antipsychotic agents and a combination of three antidepressants were prescribed more frequently in Class 3 than in Class 1 and 2.

While Class 1 and 2 significantly improved over 6 months, Class 3 showed little or no improvement in our clinical parameters even with more medications. This study has a clinical significance that it has classified qualitatively different subgroups within the sample by conducting LPA with clinical profiles of MMPI-2 and provides a basis for comprehensively understanding their differentiated clinical features. This study suggests clinical implications for treatment plan and intervention of each subgroup classified based on MMPI-2 clinical profiles of military recruits who might show maladjustment to serve.

None Declared

Three-dimensional chromatin interactions regulate gene expressions. The significance of de novo mutations (DNMs) in chromatin interactions remains poorly understood for autism spectrum disorder (ASD).

To investigate the genomic architecture of ASD in terms of non-coding de novo mutations and 3-dimensional chromatin interactions

We generated 813 whole-genome sequences from 242 Korean simplex families to detect DNMs, and identified target genes which were putatively affected by non-coding DNMs in chromatin interactions.

Non-coding DNMs in chromatin interactions were significantly involved in transcriptional dysregulations related to ASD risk. Correspondingly, target genes showed spatiotemporal expressions relevant to ASD in developing brains and enrichment in biological pathways implicated in ASD, such as histone modification. Regarding clinical features of ASD, non-coding DNMs in chromatin interactions particularly contributed to low intelligence quotient levels in ASD probands. We further validated our findings using two replication cohorts, Simons Simplex Collection (SSC) and MSSNG, and showed the consistent enrichment of non-coding DNM-disrupted chromatin interactions in ASD probands. Generating human induced pluripotent stem cells in two ASD families, we were able to demonstrate that non-coding DNMs in chromatin interactions alter the expression of target genes at the stage of early neural development.

Taken together, our findings indicate that non-coding DNMs in ASD probands lead to early neurodevelopmental disruption implicated in ASD risk via chromatin interactions.

None Declared

Lamina-specific alterations of inhibitory circuitries have been considered the crucial pathogenesis of perceptual, cognitive and behavioral symptoms presented in schizophrenia and mood disorders. Especially, with emerging evidences indicating the close lamina-specific relationship between synaptic defects and γ-Aminobutyric acid (GABA)-related gene dysfunctions, it has been suggested the mRNA dysregulations of Tyrosine kinase B (TrkB) and Glutamate decarboxylase 67 (GAD67) could particularly be implicated in middle and deep layers of neocortex of patients with major psychiatric disorders.

Giving inquiries of whether defects of these mRNA levels in Orbitofrontal cortex (OFC) would be involved as lamina-specific patterns in individuals with schizophrenia and mood disorders.

We examined mRNA levels of BDNF, TrkB and GAD67 in each OFC layer I through VI. We analyzed data from postmortem brain tissue of the Stanley Neuropathology Consortium Integrative Database (SNCID). SNCID consists of 15 subjects in each of four groups (schizophrenia, bipolar disorder, major depression without psychotic features, and unaffected controls). All groups were matched for age, sex, race, brain pH and post-mortem interval.

We found TrkB mRNA levels to be significantly reduced in layer VI in both groups with schizophrenia (25.8%) and bipolar disorder (35.7%) compared with controls. GAD67 mRNA levels were also significantly reduced in layer III and IV in patients with schizophrenia (23.4% and 22.7%, respectively) and bipolar disorder (31.2% and 24.9%, respectively) compared with controls. Individuals with major depression showed only trends toward decreased mRNA levels of GAD67 in layer III and IV and of TrkB in layer VI compared with controls. TrkB mRNA levels in layer VI were significantly correlated with GAD67 mRNA levels in layer III (ρ=0.581, p=0.037) and IV (ρ=0.857, p<0.001) in subjects with bipolar disorder, but not in those with schizophrenia. When analyzed with partial correlation controlling the effects of pH and PMI, significance of correlation remained only between GAD67 mRNA in layer IV and TrkB mRNA in layer VI in individuals with bipolar disorder (ρ=0.768, p=0.006).

The resulting lamina-specific decreases in inhibitory tone across layers of OFC may contribute to the unrestrained irritability and violent behaviors in common shared by both patients with schizophrenia and bipolar disorder. Nonetheless, our findings indicate the obvious correlations between lamina-specifically altered TrkB and GAD67 mRNA levels in OFC might be a candidate for endophenotype of bipolar disorder.

None Declared

To analyse the treatment results of bilobed flap reconstruction performed for skin defects after parotid carcinoma surgery.

Ten patients who underwent bilobed flap reconstruction for skin defects after parotid carcinoma surgery in our hospital, from 2014 to 2020, were retrospectively enrolled.

All patients underwent bilobed flap reconstruction for skin defects after parotid carcinoma surgery. The size of the skin defect was 2.7 × 2.2 cm in the smallest dimension and 9.0 × 6.3 cm in the largest dimension. All bilobed flaps except one healed without any problems. One patient developed partial flap necrosis in the retroauricular region, and was treated with skin grafts after removal of the necrotic tissue under local anaesthesia. All bilobed flaps, including the cases in which skin grafts were performed, survived after post-operative radiotherapy or chemotherapy.

A bilobed flap is a good reconstruction option for skin defects after parotid carcinoma surgery in some cases.

The use of three-dimensional printing has been rapidly expanding over the last several decades. Virtual surgical three-dimensional simulation and planning has been shown to increase efficiency and accuracy in various clinical scenarios.

To report the feasibility of three-dimensional printing in paediatric laryngotracheal stenosis and discuss potential applications of three-dimensional printed models in airway surgery.

Retrospective case series in a tertiary care aerodigestive centre.

Three-dimensional printing was undertaken in two cases of paediatric laryngotracheal stenosis. One patient with grade 4 subglottic stenosis with posterior glottic involvement underwent an extended partial cricotracheal reconstruction. Another patient with grade 4 tracheal stenosis underwent tracheal resection and end-to-end anastomosis. Models of both tracheas were printed using PolyJet technology from a Stratasys Connex2 printer.

It is feasible to demonstrate stenosis in three-dimensional printed models, allowing for patient-specific pre-operative surgical simulation. The models serve as an educational tool for patients’ understanding of the surgery, and for teaching residents and fellows.

The aims of this study were to investigate the effects of either hearing, vision or dual sensory impairment on depressive symptoms and to identify subgroups that are vulnerable and significantly affected.

Data from the 2006–2014 Korean Longitudinal Study of Aging (KLoSA) were used and a total of 5832 individuals were included in this study. Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression (CES-D10) scale. Sensory impairment was assessed according to the levels of self-reported hearing or vision, which were categorised as either good (excellent, very good or good) or poor (fair or poor). The changes in hearing or vision from records of previous survey were investigated. Changes from good to poor, which indicates new onset, were defined as hearing impairment or vision impairment. Interactions of changes in hearing and vision were considered in the analysis. Dual sensory impairment was indicated when hearing impairment and vision impairment both developed at the same time. Demographic, socioeconomic and health-related factors were considered as potential confounders and were adjusted for in the generalised estimating equation model.

Individuals with hearing impairment demonstrated significantly more severe depressive symptoms [β = 0.434, standard errors (s.e.) = 0.097, p < 0.001] than those who had good hearing. Those with vision impairment also showed significantly elevated depressive symptoms (β = 0.253, s.e. = 0.058, p < 0.001) than those with good vision. When the interactions between hearing and vision were considered, participants with dual sensory impairment showed significantly more severe depressive symptoms (β = 0.768, s.e. = 0.197, p < 0.001) than those with good hearing and vision. The effect of a single and dual sensory impairment on depressive symptoms was significant in both sexes and across age groups, except for vision impairment in male participants.

Hearing, vision and dual sensory impairment are significantly associated with depressive symptoms. Our results suggest that treatment or rehabilitation of either hearing or vision impairment would help prevent depression.

Clinical research studies of behavioral variant frontotemporal dementia (bvFTD) often use Alzheimer disease (AD) as a comparison group for control of dementia variables, using tests of cognitive function to match the groups. These two dementia syndromes, however, are very different in clinical manifestations, and the comparable severity of these dementias may not be reflected by commonly used cognitive scales such as the Mini-Mental State Examination (MMSE).

We evaluated different measures of dementia severity and symptoms among 20 people with bvFTD compared to 24 with early-onset AD.

Despite similar ages, disease-duration, education, and cognitive performance on two tests of cognitive function, the MMSE and the Montreal Cognitive Assessment (MoCA), the bvFTD participants, compared to the AD participants, were significantly more impaired on other measures of disease severity, including function (Functional Assessment Questionnaire (FAQ)), neuropsychiatric symptoms (Neuropsychiatric Inventory (NPI)), and global dementia stage (Clinical Dementia Rating Scales (CDRs)). However, when we adjusted for the frontotemporal lobar degeneration-CDR (FTLD-CDR) in the analyses, the two dementia groups were comparable across all measures despite significant differences on the cognitive scales.

We found tests of cognitive functions (MMSE and MoCA) to be insufficient measures for ensuring comparability between bvFTD and AD groups. In clinical studies, the FTLD-CDR, which includes additional language and behavior items, may be a better overall way to match bvFTD and AD groups on dementia severity.

To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas.

Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53.

Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours.

The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.

This study aimed to evaluate the efficacy of post-operative voice therapy after phonomicrosurgery for vocal polyp removal.

The study retrospectively enrolled 55 consecutive patients who had undergone voice therapy after phonomicrosurgery for vocal polyp removal occurring between June 2010 and June 2011. A historical group of 63 similar patients not receiving voice therapy was used as an external control. We compared voice analysis parameters and Voice Handicap Index scores for the two groups.

Most objective and subjective voice outcome parameters were significantly improved after surgical treatment. Although the study and control groups showed no significant difference regarding objective parameters (using acoustic and aerodynamic analysis) or the subjective parameters assessed using the grade-roughness-breathiness-asthenia-strain scale, the study group had significantly better final Voice Handicap Index scores.

Following surgery for vocal polyps, post-operative voice therapy can improve patients' vocal discomfort, emotional responses and everyday self-perception.