Short tandem repeat expansions in cortical layer-specific genes implicate in phenotypic severity and adaptability of autism spectrum disorder.

AIM: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes. METHODS: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci. RESULTS: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers. CONCLUSION: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population.

Detection and differentiation of ataxic and hypokinetic dysarthria in cerebellar ataxia and parkinsonian disorders via wave splitting and integrating neural networks.

Dysarthria may present during the natural course of many degenerative neurological conditions. Hypokinetic and ataxic dysarthria are common in movement disorders and represent the underlying neuropathology. We developed an artificial intelligence (AI) model to distinguish ataxic dysarthria and hypokinetic dysarthria from normal speech and differentiate ataxic and hypokinetic speech in parkinsonian diseases and cerebellar ataxia. We screened 804 perceptual speech analyses performed in the Samsung Medical Center Neurology Department between January 2017 and December 2020. The data of patients diagnosed with parkinsonian disorders or cerebellar ataxia were included. Two speech tasks (numbering from 1 to 50 and reading nine sentences) were analyzed. We adopted convolutional neural networks and developed a patch-wise wave splitting and integrating AI system for audio classification (PWSI-AI-AC) to differentiate between ataxic and hypokinetic speech. Of the 395 speech recordings for the reading task, 76, 112, and 207 were from normal, ataxic dysarthria, and hypokinetic dysarthria subjects, respectively. Of the 409 recordings of the numbering task, 82, 111, and 216 were from normal, ataxic dysarthria, and hypokinetic dysarthria subjects, respectively. The reading and numbering task recordings were classified with 5-fold cross-validation using PWSI-AI-AC as follows: hypokinetic dysarthria vs. others (area under the curve: 0.92 ± 0.01 and 0.92 ± 0.02), ataxia vs. others (0.93 ± 0.04 and 0.89 ± 0.02), hypokinetic dysarthria vs. ataxia (0.96 ± 0.02 and 0.95 ± 0.01), hypokinetic dysarthria vs. none (0.86 ± 0.03 and 0.87 ± 0.05), and ataxia vs. none (0.87 ± 0.07 and 0.87 ± 0.09), respectively. PWSI-AI-AC showed reliable performance in differentiating ataxic and hypokinetic dysarthria and effectively augmented data to classify the types even with limited training samples. The proposed fully automatic AI system outperforms neurology residents. Our model can provide effective guidelines for screening related diseases and differential diagnosis of neurodegenerative diseases.

Heat shock protein family D member 1 in boar spermatozoa is strongly related to the litter size of inseminated sows.

BACKGROUND: Sperm quality evaluation is the logical first step in increasing field fertility. Spermatozoa contain cytoplasmic organelles and biomolecules known as sperm-intrinsic factors, which play key roles in sperm maturation, sperm-oocyte fusion, and embryo development. In particular, sperm membrane proteins [e.g., arginine vasopressin receptor 2, beta-actin, prohibitin, and heat shock protein family D member 1 (HSPD1)] and RNA could be used as functional indicators of male fertility. We sought to clarify the effects of differential mRNA expression of selected genes on several fertilisation parameters, including sperm motility, motion kinematics, capacitation, and litter size, in a porcine model. RESULTS: Our results demonstrated that HSPD1 expression was significantly correlated with male fertility, as measured by the litter size of inseminated sows. The expression of HSPD1 mRNA was linked to sperm motility and other motion kinematic characteristics. Furthermore, HSPD1 had a 66.7% overall accuracy in detecting male fertility, and the high-litter size group which was selected with the HSPD1 marker had a 1.34 greater litter size than the low-litter size group. CONCLUSIONS: Our findings indicate that HSPD1 might be a helpful biomarker for superior boar selection for artificial insemination, which could boost field fertility.

The comparison of temperament and character between patients with internet gaming disorder and those with alcohol dependence.

BACKGROUND: The differences in prevalence, natural history, and disease progression between Internet gaming disorder (IGD) and substance use disorder contribute to the controversy over IGD as a diagnosis under substance-related and addictive disorders. AIMS: The purpose of the current study was to assess the temperament and character of subjects with IGD in comparison with those with alcohol dependence (AD). METHODS: Temperament and character were assessed using Cloningernt temperament and character inventory (TCI). The severity of IGD or AD, depressed mood, anxiety, attention and impulsiveness were assessed using each of the six scales. RESULTS: Among patients with AD, after controlling for other variables, the severity of AD was positively correlated with harm avoidance (HA) score and depressed mood. Among patients with IGD, after controlling for other variables, the severity of IGD was positively correlated with novelty seeking (NS) score, impulsiveness and attention. CONCLUSIONS: There were significant differences in temperament and character between the IGD and AD groups as measured using the TCI. These results suggest that IGD and AD need to be categorized separately in a diagnostic classification system and benefit from different treatment approaches.

Comparative study of the effects of bupropion and escitalopram on Internet gaming disorder.

AIM: We compared the efficacy of bupropion and escitalopram treatments in Internet gaming disorder (IGD) patients. METHODS: We recruited 119 adolescents and adults with IGD. We treated these participants for 6 weeks in three groups as follows: 44 participants were treated with bupropion SR (bupropion group), 42 participants were treated with escitalopram (escitalopram group), and 33 patients without any medication were observed in the community (observation group). At baseline and at the 6-week follow-up visit, all subjects were evaluated using the Clinical Global Impression-Severity Scale, the Young Internet Addiction Scale, the Beck Depression Inventory, the ADHD Rating Scale, and the Behavioral Inhibition and Activation Scales. RESULTS: Both the escitalopram group and the bupropion group showed improvement on all clinical symptom scales after 6 weeks of treatment compared to the observation group. Additionally, the bupropion group showed greater improvement on scores for the Clinical Global Impression-Severity Scale, the Young Internet Addiction Scale, the ADHD Rating Scale, and the Behavioral Inhibition Scale than the escitalopram group. CONCLUSION: Both bupropion and escitalopram were effective in treating and managing IGD symptoms. Moreover, bupropion appeared to be more effective than escitalopram in improving attention and impulsivity in IGD patients. In addition, attention and impulsivity seem to be important for the management of IGD.

Virtual Reality Therapy for the Treatment of Alcohol Dependence: A Preliminary Investigation With Positron Emission Tomography/Computerized Tomography.

OBJECTIVE: Virtual reality therapy (VRT) uses multimodal stimulation that includes visual, auditory, olfactory, and gustatory stimuli. The aim of this study was to assess the effectiveness of VRT in treating subjects with alcohol dependence (AD) by evaluating changes in brain metabolism. METHOD: The VRT protocol consisted of three steps: relaxation, presentation of a high-risk situation, and presentation of an aversive situation. Twelve alcohol-dependent subjects underwent 10 sessions of VRT. The alcohol-dependent subjects were assessed with 18F-fluorodeoxyglucose positron emission tomography images before and after VRT, whereas the control group underwent imaging according to the same protocol only at baseline. RESULTS: Compared with the healthy control group, AD subjects showed higher metabolism in the right lentiform nucleus and right temporal lobe (BA20) at baseline (P(FDR < .05) = .026). In addition, the metabolism in the left anterior cingulate was lower in subjects with AD (P(uncorr) = .001). After VRT, alcohol-dependent subjects showed decreased brain metabolism in the right lentiform nucleus (P(FDR < .05) = .026) and right temporal lobe (BA38, P(FDR < .05) = .032) relative to that at baseline. CONCLUSIONS: Our results suggest a neurobiological imbalance, notably, a high sensitivity to stimuli, in the limbic system in subjects with AD. Furthermore, we determined that metabolism decreased in the basal ganglia after VRT, which may explain the limbic-regulated responses of reward and regulation. Therefore, we tentatively recommend VRT to treat AD through its regulating effect on limbic circuits.

Association between harmful alcohol use and periodontal status according to gender and smoking.

BACKGROUND: the aim of this study is to assess the association of harmful alcohol use based on the alcohol use disorders identification test (AUDIT) score with periodontal status according to gender and smoking in a representative sample of Korean adults. METHODS: This study analyzed 5,291 participants older than 19 years whose data of harmful alcohol use and periodontal status were available. Harmful alcohol use was defined by the WHO guidelines for the administration of AUDIT. The periodontal status was assessed by the Community Periodontal Index (CPI). Multivariate logistic regression analysis was performed with adjustment for socio-demographic variables, oral and general health behavior, oral health status and systemic conditions. All analyses considered a complex sampling design, and multivariate analysis was also performed in the subgroups. RESULTS: Multivariate logistic regression analysis revealed a marginal association between harmful alcohol use and higher CPI in the total sample. The adjusted odds ratio (OR) of harmful alcohol use was 1.16 (0.97 to 1.38) for higher CPI. Higher CPI was significantly associated with harmful alcohol use in men (OR: 1.28; 95% CI: 1.03-1.60) and non-smokers (OR: 1.29; 95% CI: 1.06-1.57). CONCLUSION: Periodontal status is significantly associated with harmful alcohol use in men and non-smokers in a representative sample of Korean adults.

Correlation between gray matter volume in the temporal lobe and depressive symptoms in patients with Alzheimer's disease.

Recent studies have suggested that depression might be an aggravating factor in Alzheimer's disease (AD). The aim of the study was to compare depressive symptoms and gray matter volume between AD patients with comorbid depression and patients with dementia only. Forty-nine patients with AD, 57 with mild cognitive impairment (MCI), and 50 healthy control subjects were assessed using the Consortium to Establish a Registry for Alzheimer's disease (CERAD) and the Geriatric Depression Scale (GDS). All magnetic resonance imaging (MRI)s were analyzed using voxel-based morphometry (VBM). Seventeen AD patients with depression versus 32 patients with dementia only showed decreased immediate recall for a word list (8.7±1.1 vs. 10.1±1.5, z=3.6, p<0.01) and constructional praxis scores (3.7±0.9 vs. 5.3±2.1, z=2.5, p=0.01). Compared to 32 patients with dementia, seventeen AD patients with depression showed decreased gray matter volume in the left inferior temporal gyrus (-56, -19, -31; KE=578, t=3.80, Puncorr<0.001). The MCI group showed decreased gray matter volume in the right hippocampal gyrus compared to healthy control group. Our results suggest that depressive symptoms may be associated with the volume changes of frontal and temporal lobe in patients with AD.

A Case of Very-late-onset Schizophrenia-like Psychosis.

This paper presents the case of a 67-year-old woman who visited the Psychiatry Department complaining of persecutory ideas and auditory hallucinations after a buccal cancer operation. On neuropsychological testing, she demonstrated paranoid psychosis and bizarre thoughts. Hospital admission was recommended for supportive care and treatment with antipsychotics. She was initially treated with olanzapine, but this medication had little effect and was replaced with amisulpride, which reduced the residual symptoms. The aim of this report was to discuss the diagnostic process and treatment of very late-onset schizophrenia-like psychosis.