Investigation of Liver X Receptor Gene Variants and Oxysterol Dysregulation in Autism Spectrum Disorder.

The NR1H2 gene produces the Liver X Receptor Beta (LXRB) protein, which is crucial for brain cholesterol metabolism and neuronal development. However, its involvement in autism spectrum disorder (ASD) remains largely unexplored, aside from animal studies. This study is the first to explore the potential link between autism and rs2695121/rs17373080 single nucleotide polymorphisms (SNPs) in the regulatory regions of NR1H2, known for their association with neuropsychiatric functions. Additionally, we assessed levels of oxysterols (24-Hydroxycholesterol, 25-Hydroxycholesterol, 27-Hydroxycholesterol), crucial ligands of LXR, and lipid profiles. Our cohort comprised 107 children with ASD and 103 healthy children aged 2-18 years. Clinical assessment tools included the Childhood Autism Rating Scale, Autistic Behavior Checklist, and Repetitive Behavior Scale-Revised. Genotyping for SNPs was conducted using PCR-RFLP. Lipid profiles were analyzed with Beckman Coulter kits, while oxysterol levels were determined through liquid chromatography-tandem mass spectrometry. Significantly higher total cholesterol (p = 0.003), LDL (p = 0.008), and triglyceride (p < 0.001) levels were observed in the ASD group. 27-Hydroxycholesterol levels were markedly lower in the ASD group (p ≤ 0.001). ROC analysis indicated the potential of 27-Hydroxycholesterol to discriminate ASD diagnosis. The SNP genotype and allele frequencies were similar in both groups (p > 0.05). Our findings suggest that disturbances in oxysterol metabolism, previously linked to neurodegeneration, may constitute a risk factor for ASD and contribute to its heterogeneous phenotype.

Turkish Adaptation Study of the Ask Suicide-Screening Questions in Adolescents.

Introduction: This study aimed to demonstrate the validity of the Ask Suicide-Screening Questions (ASQ) in a clinical sample consisting of adolescents admitted to child and adolescent psychiatry (CAP), and then to confirm its validation in those presenting to the pediatric emergency department (PED), which was the main target group for the study. Method: This cross-sectional study evaluated the compatibility of the ASQ with the suicide probability scale, which is a standardized measure, to identify cases with suicide risk in 248 adolescents aged 10-18 years. To demonstrate the clinical validity of the scale, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), negative likelihood ratio (NLR), Kappa, and area under the curve (AUC) performance metrics and 95% confidence interval (CI) values were calculated. Results: Positive screening rate, sensitivity, specificity, PPV and NPV for the CAP patients were calculated as 31.8%, 100% (95% CI: 100.0-100.0), 70.9% (95% CI: 63.4-78.4), 12.8% (95% CI: 3.2-22.3) and 100% (95% CI: 100.0-100.0), respectively. The PLR and AUC were calculated as 3.4% (95% CI: 2.7-4.5) and 0.855 (95% CI: 0.817-0.892), respectively. Positive screening rate, sensitivity, specificity, PPV and NPV for the PED patients were calculated as 28%, 100% (95% CI: 100.0-100.0), 75.3% (95% CI: 66.3-84.2), 21.4% (95% CI: 6.2-36.6) and 100% (95% CI: 100.0-100.0), respectively. The PLR, Kappa and AUC were 4.05% (95% CI: 2.82-5.81), 0.278 and 0.876 (95% CI: 0.832-0.921), respectively. Conclusion: This study showed the first evidence that Turkish adaptation of the ASQ is a valid screening tool for identifying those at risk of suicide among adolescents who applied to the CAP and PED.

Default mode network activity and neuropsychological profile in male children and adolescents with attention deficit hyperactivity disorder and conduct disorder.

It is known that patients with Attention Deficit and Hyperactivity disorder (ADHD) and Conduct disorder (CD) commonly shows greater symptom severity than those with ADHD alone and worse outcomes. This study researches whether Default mode network (DMN) is altered in adolescents with ADHD + CD, relative to ADHD alone and controls or not. Ten medication-naïve boys with ADHD + CD, ten medication-naïve boys with ADHD and 10-age-matched typically developing (TD) controls underwent functional magnetic resonance imaging (fMRI) scans in the resting state and neuropsychological tasks such as the Wisconsin Card Sorting Test (WCST), Stroop Test TBAG Form (STP), Auditory Verbal learning Test (AVLT), Visual Auditory Digit Span B (VADS B) were applied to all the subjects included. fMRI scans can be used only nine patients in each groups. The findings revealed group differences between cingulate cortex and primary mortor cortex; cingulate cortex and somatosensory association cortex; angular gyrus (AG) and dorsal posterior cingulate cortex, in these networks increased activity was observed in participants with ADHD + CD compared with the ADHD. We found that lower resting state (rs)-activity was observed between left AG and dorsal posterior cingulate cortex, whereas higher rs-activity connectivity were detected between right AG and somatosensory association cortex in ADHD relative to the ones with ADHD + CD. In neuropsyhcological tasks, ADHD + CD group showed poor performance in WISC-R, WCST, Stroop, AVLT tasks compared to TDs. The ADHD + CD group displayed rs-functional abnormalities in DMN. Our results suggest that abnormalities in the intrinsic activity of resting state networks may contribute to the etiology of CD and poor prognosis of ADHD + CD.