Sleep features in alcohol use disorder: A systematic review and meta-analysis of polysomnographic findings in case-control studies

Background and objectives Alcohol use disorder (AUD) is often linked to sleep problems, but previous studies on sleep abnormalities in AUD have produced inconsistent results. This study aims to provide a comprehensive analysis of objectively measured sleep abnormalities in AUD and determine the impact of related and demographic factors on sleep disturbance. Methods We conducted a comprehensive search of several databases from 1968 to 2023 to identify relevant studies. A total of 12 studies, consisting of 13 datasets, were included in the analysis. We extracted information on sleep microarchitecture, as well as demographic and clinical features, from each study. The GRADE approach was used to assess the reliability and strength of the evidence. Results Patients with AUD exhibited several sleep abnormalities, including longer sleep onset latency, lower sleep efficiency, increased stage 1 sleep, decreased stage 2 sleep, reduced slow wave sleep, and elevated rapid eye movement (REM) sleep density and first REM minute. The sleep patterns in individuals with AUD were also influenced by factors such as ethnicity, age, gender, and abstinence period. Conclusions This study is the largest quantitative assessment of impaired sleep as a diagnostic marker in patients with AUD. Understanding the sleep patterns of individuals with AUD can assist clinicians in developing effective treatment plans for managing sleep-related symptoms associated with AUD. (AU)

Transdiagnostic symptom subtypes across autism spectrum disorders and attention deficit hyperactivity disorder: validated by measures of neurocognition and structural connectivity.

BACKGROUNDS: Autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD) are neurodevelopmental disorders that exhibit within-disorder heterogeneity and cross-disorder phenotypic overlap, thus suggesting that the current disease categories may not fully represent the etiologic essence of the disorders, especially for highly comorbid neurodevelopmental disorders. In this study, we explored the subtypes of a combined sample of ASD and ADHD by integrating measurements of behavior, cognition and brain imaging. METHODS: A total of 164 participants, including 65 with ASD, 47 with ADHD, and 52 controls, were recruited. Unsupervised machine learning with an agglomerative hierarchical clustering algorithm was used to identify transdiagnostic symptom clusters. Neurocognition and brain structural connectivity measurements were used to assess symptom clusters. Mediation analysis was used to explore the relationship between transdiagnostic symptoms, neurocognition and brain structural connectivity. RESULTS: We identified three symptom clusters that did not fall within the diagnostic boundaries of DSM. External measurements from neurocognition and neuroimaging domains supported distinct profiles, including fine motor function, verbal fluency, and structural connectivity in the corpus callosum between these symptom clusters, highlighting possible biomarkers for ASD and ADHD. Additionally, fine motor function was shown to mediate the relationship between the corpus callosum and perseveration symptoms. CONCLUSIONS: In this transdiagnostic study on ASD and ADHD, we identified three subtypes showing meaningful associations between symptoms, neurocognition and brain white matter structural connectivity. The fine motor function and structural connectivity of corpus callosum might be used as biomarkers for neurodevelopmental disorders with social skill symptoms. The results of this study highlighted the importance of precise phenotyping and further supported the effects of fine motor intervention on ASD and ADHD.

Metabolomics changes after rTMS intervention reveal potential peripheral biomarkers in methamphetamine dependence.

Methamphetamine is one of the most commonly used drugs around the world, leading to serious public health and psychiatric problems. Due to the lackness of objective laboratory evaluation indicators, the molecular mechanisms of methamphetamine dependence still remain unclear. Previous evidence demonstrated that repetitive transcranial magnetic stimulation (rTMS) may be useful in treating drug addiction. The aim of this study was to identify and validate plasma metabolomics biomarkers in patients with methamphetamine use disorder before and after rTMS intervention. An untargeted gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) based metabolomics approach was applied to characterize the metabolic profile of forty methamphetamine dependent subjects and thirty-eight healthy controls in peripheral blood mononuclear cells (PBMCs). Patients were randomized to receive either rTMS or sham over the DLPFC for four weeks (20 daily sessions, 900 pulses per day). Cognitive function were assessed before and after rTMS intervention. Eight PBMC metabolites responsible for distinguishing real rTMS from sham treatment were identified. These metabolites were mainly involved in energy metabolism and oxidative stress. Compared with baseline, the expression of three metabolites was reversed after rTMS intervention: alpha-tocopherol, glyceric acid and fumaric acid. Changes of the alpha-tocopherol were associated with cognitive function improvement following rTMS. These findings suggest that energy metabolism and oxidative stress system may be associated with the effect of rTMS on cognitive function in methamphetamine dependence, and warrant further investigation.

Exploring the spatial working memory and visual perception in children with autism spectrum disorder and general population with high autism-like traits.

The aim of the study is to compare the spatial working memory and visual perception between children with autism spectrum disorder (ASD) and typically developing control (TDC). Furthermore, this study validated whether this impairment was a feature of autism in general population with different autism-like traits (ALTs). This study contains two parts: case-control study and community population study. The ASD group and the control group were enlisted voluntarily (ASD group, n = 52; control group, n = 32). In the population study, we recruited 2994 children. Based on the scores of Autism Spectrum Quotient (AQ), children were divided into two groups (higher ALTs n = 122, lower ALTs n = 122). The participants completed the cognition tasks focusing on spatial working memory, visual-motor integration, and Intelligence. Analysis of covariance (ANCOVA) was conducted, with potential confounders IQ, age, and gender were controlled. Pearson correlations were computed by controlling the IQ and age as covariate to better understand the relations between visual perception, spatial working memory, and autism-like traits. In the case-control study, the results of cognition tasks focusing on the spatial working memory and visual perception indicated underperformance in children with ASD. In the community population study, we found that individuals with higher ALTs performed worse than children with lower ALTs in spatial working memory. Pearson correlation analysis suggested that a correlation between SWM total errors and visual perception was identified both in the children with ASD and in community population (ASD group, r = -0.592, p<0.001; general population, r = -0.201, p = 0.003). It suggested that spatial working memory deficit was a characteristic of autism, and may be distributed across the general population. Furthermore, we speculated a correlation between spatial working memory and visual perception in children with ASD and in general population.

Risky decision-making in individuals with substance use disorder: A meta-analysis and meta-regression review.

BACKGROUND: This review aims to identify whether risky decision-making is increased in substance users, and the impact of substance type, polysubstance use status, abstinence period, and treatment status on risky decision-making. METHODS: A literature search with no date restrictions was conducted to identify case-control studies or cross-sectional studies that used behavioral tasks to measure risky decision-making in substance users. A random-effects model was performed. GRADE criteria was used to assess the quality of evidence. RESULTS: 52 studies were enrolled. The result showed that the difference in risky decision-making performance between user groups and control groups was significant (SMD = - 0.590; 95%CI = - 0.849 to - 0.330; p < 0.001; I2 = 93.4%; Pheterogeneity < 0.001). Subgroup analysis showed that users in the subgroups of alcohol (p < 0.001), tobacco (p < 0.01), cocaine (p < 0.001), opioid (p < 0.001), mixed group (p < 0.01), adult users (p < 0.001), small sample size (p < 0.001), large sample size (p < 0.01), low education (p < 0.001), high education (p < 0.001), short-abstinence period (p < 0.001), long-abstinence period (p < 0.001), without current polysubstance dependence (p < 0.001), and with treatment (p < 0.001) had increased risky decision-making when compared to the controls. On the other hand, elderly substance users with short-abstinence period showed increased risky decision-making. Moreover, current treatment status and polysubstance use may not influence the level of decision-making in substance users. CONCLUSIONS: The results show that substance use is associated with impaired risky decision-making, indicating that interventions targeting risky decision-making in substance users should be developed for relapse prevention and rehabilitation.

[Analysis of common genetic variants associated with neuro-synapse development among 60 family trios affected with sporadic autism spectrum disorders].

OBJECTIVE: To explore susceptibility genes for autism spectrum disorders (ASD). METHODS: Whole-exome sequencing was carried out for 60 family trios affected with sporadic ASD. Genetic variants discovered in over 10% of the patients were selected for genotype-phenotype correlation and pathway enrichment analysis using Phenolyzer software and metascape database. Combining gene-phenotypic scores, pathway-related genes associated with neural and neurite triggering were screened for the candidates. RESULTS: A total of 170 common variants were found to be associated with the ASD phenotype. Among these, there was only one high-confidence gene [SHANK2(0.8146)] and four medium-confidence genes [ERBB2(0.1322), LAMC3(0.1117), PPFIA4(0.1059), DISC1(0.1002)]. Twenty-pathways and four biological processes were found to be statistically significant by pathway enrichment analysis, which included neuron projection morphogenesis (GO: 0048812), regulation of neuroblast proliferation (GO: 1902692), modulation of excitatory postsynaptic potential (GO: 0098815), and dendrite morphogenesis (GO: 0048813). Twenty-one genes were found to be closely associated with neurological and neurite triggering, among which only SHANK2, ERBB2, and DISC1 had above-medium confidence correlation scores with the ASD phenotypes. CONCLUSION: Abnormal neuron projection morphogenesis (GO: 0048812) may be closely related to the occurrence of ASD. SHANK2, ERBB2, and DISC1 are susceptibility genes for ASD.

Identification of De Novo JAK2 and MAPK7 Mutations Related to Autism Spectrum Disorder Using Whole-Exome Sequencing in a Chinese Child and Adolescent Trio-Based Sample.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with high phenotypic and genetic heterogeneity. Whole-exome sequencing studies have shown that de novo single-nucleotide variations (SNVs) play an important role in sporadic ASD. The present study aimed to search for de novo SNVs using whole-exome sequencing in 59 unrelated Chinese ASD sporadic trios, and found 24 genes (including five reported ASD candidate genes CACNA1D, ACHE, YY1, TTN, and FBXO11) with de novo harmful SNVs. Five genes (CACNA1D, JAK2, ACHE, MAPK7, and PRKAG2) classified as "medium-confidence" genes were found to be related to ASD using the Phenolyzer gene analysis tool, which predicts the correlation between the candidate genes and the ASD phenotype. De novo SNVs in JAK2, MAPK7, and PRKAG2 were first found in ASD. Both JAK2 and MAPK7 were involved in the regulation of the MAPK signaling pathway. Gene co-expression and inter-gene interaction networks were constructed and gene expression data in different brain regions were further extracted, revealing that JAK2 and MAPK7 genes were associated with certain previously reported ASD genes and played an important role in early brain development. The findings of this study suggest that the aforementioned five reported ASD genes and JAK2 and MAPK7 may be related to ASD susceptibility. Further investigations of expression studies in cellular and animal models are needed to explore the mechanism underlying the involvement of JAK2 and MAPK7 in ASD.

Parents' impaired emotion recognition abilities are related to children's autistic symptoms in autism spectrum disorder.

OBJECTIVE: We aimed to explore whether parents of children with autism spectrum disorder (ASD) had impaired emotion recognition abilities and whether this deficit was related to their children's autistic symptoms. METHODS: The autistic symptoms of 31 ASD children were assessed using the Autism Diagnostic Interview-Revised (ADI-R). Fifty parents of ASD children and 34 parents of typically developing (TD) children completed an emotion recognition task (ERT). RESULTS: The numbers of correct ERT responses were lower for parents of ASD children than for parents of TD children with respect to recognizing sadness, disgust, fear, and all emotions (P=0.01, 0.04, 0.02, and 0.00, respectively). Controlled for parental age, gender, and the intelligence quotients of both the parents and children, a negative correlation was found between the total number of correct ERT responses for parents of ASD children and these children's "restricted, repetitive, and stereotyped patterns of behavior" scores on the ADI-R (r=-0.32; P=0.03). CONCLUSION: Parents of ASD children showed impaired emotion recognition abilities compared with parents of TD children. This parental deficit in emotion recognition ability was related to the autistic symptoms of ASD children.

Increased Left Inferior Temporal Gyrus Was Found in Both Low Function Autism and High Function Autism.

Previous neuroimaging studies of autism spectrum disorder (ASD) have focused on subjects with IQ > 70 or ASD without considering IQ levels. It remains unclear whether differences in brain anatomy in this population are associated with variations in clinical phenotype. In this study, 19 children with low functioning autism (LFA) and 19 children with high functioning autism (HFA) were compared with 27 healthy controls (HC). We found increased gray matter volume (GMV) in the left inferior temporal gyrus in subjects with both HFA and LFA and increased GMV of left middle temporal gyrus BA21 was found only in the LFA group. A significant negative correlation was found between the left inferior temporal gyrus (LITG) and the score of repetitive behavior in the HFA group.

[Reliability and Validity of the Abridged Chinese Version of Autism Spectrum Quotient-Child form in China].

OBJECTIVE: To determine the reliability and validity of the abridged Chinese version of the autism spectrum quotient (AQ) -child form. METHODS: A total of 86 children with autism spectrum disorder (ASD) were recruited from the West China Hospital from July 2014 to December 2016, along with 6 896 children recruited from three schools in Chengdu. The participants completed the AQ scale under instructions from a trained interviewer. Then 170 school children were selected and repeated the AQ scale within one month. RESULTS: All subscale scores were correlated with the scale score, but with weak inter-subscale correlations. The total AQ score of the control group was continuously distributed in the population, which was similar to the normal distribution. The skewness was -0.127 and the kurtosis was -0.124, indicating that the total AQ score was negatively skewed and slightly flat in the population.There were differences in AQ scores between different genders in community children (P<0.01), with male group (42.09±9.92) higher than female group (40.07±9.94).There was no gender difference in the ASD individuals. There was a correlation between age and AQ score (R=0.06).The autistic children had a higher AQ score (54.49±14.16) than the school children (41.12±9.98)(P<0.01). Similar results were found in the subscale scores, except for"attention to detail". The AQ scale had a Cronbach α coefficient of 0.71: ranging from 0.21 to 0.69 for the subscales. The test-retest reliability was good for the scale and the subscales (all P>0.05) . The sensitivity and specificity of AQ for screening ASD was both 0. 71. CONCLUSION: The abridged Chinese version of the AQ-child scale has good psychometrics properties and may be a valid and reliable instrument for ASD screening with a cut-off score of 48.

Associations of endocrine stress-related gene polymorphisms with risk of autism spectrum disorders: Evidence from an integrated meta-analysis.

Autism spectrum disorders (ASD) are related to serotonin transporter (5-HTT) and catechol-O-methyl transferase (COMT) as two most monoaminergic polymorphic variations. However, multiple studies assessing rs4680 and 5-HTTLPR variants in ASD have reported inconsistent results. Therefore, we conducted an integrated meta-analysis to combine case-control and transmission/disequilibrium test (TDT) studies to determine whether COMT and 5-HTT are associated with ASD. We searched multiple electronic databases (PubMed, EmBase and Web of Science) to identify studies assessing the rs4680 and 5-HTTLPR variants in ASD from Jan 1997 to Dec 2016. Then allelic data from case-control and TDT studies were analyzed by the Catmap package in the R software. A total of 5 studies were eligible for the meta-analysis of rs4680, including 3 case-control, 1 TDT and 1 TDT & case-control studies. Meanwhile, 22 studies of 5-HTTLPR were available, including 16 TDT, 4 case-control and 2 TDT & case-control studies. The current meta-analysis included 814 ASD cases, 741 controls and 311 families related to rs4680; 749 ASD cases, 1,118 controls and 1,861 families relevant to 5-HTTLPR were also evaluated. For rs4680, the pooled OR was 1.18 (95% CI = 0.87-1.59, P = 0.29, Pheterogeneity < 0.00001). There was no significant association of rs4680 with risk of ASD between the two subgroups. For 5-HTTLPR, the pooled OR was 1.05 (95% CI = 0.92-1.20, P = 0.4652, Pheterogeneity < 0.00001). Meanwhile, we found no significant risk in individual case-control or TDT studies. The above findings indicated that neither COMT rs4680 nor 5-HTT 5-HTTLPR polymorphism significantly affects ASD risk. Autism Res 2017, 10: 1722-1736. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Our results showed no evidence of significant association of either COMT rs4680 or 5-HTT 5-HTTLPR variants with ASD, showing that these two genes may not be major susceptible genetic factors in ASD occurrence, and may have a reciprocal action with each other in combination with environmental factors. These findings further provide evidence that a single gene variant may not dictate autism occurrence, but possibly contributes to a specific phenotype or subtype of ASD.