High frequency of mitochondrial DNA rearrangements in the peripheral blood of adults with intellectual disability.

Background: Mitochondrial DNA (mtDNA) rearrangements are recognised factors in mitochondrial disorders and ageing, but their involvement in neurodevelopmental disorders, particularly intellectual disability (ID) and autism spectrum disorder (ASD), remains poorly understood. Previous studies have reported mitochondrial dysfunction in individuals with both ID and ASD. The aim of this study was to investigate the prevalence of large-scale mtDNA rearrangements in ID and ID with comorbid ASD (ID-ASD).

High number of mitochondrial DNA alterations in postmortem brain tissue of patients with schizophrenia compared to healthy controls.

Previous studies have shown mitochondrial dysfunction in schizophrenia (SZ) patients, which may be caused by mitochondrial DNA (mtDNA) alterations. However, there are few studies in SZ that have analyzed mtDNA in brain samples by next-generation sequencing (NGS). To address this gap, we used mtDNA-targeted NGS and qPCR to characterize mtDNA alterations in brain samples from patients with SZ (n = 40) and healthy controls (HC) (n = 40).

Coexpression network analysis of the adult brain sheds light on the pathogenic mechanism of DDR1 in schizophrenia and bipolar disorder.

DDR1 has been linked to schizophrenia (SCZ) and bipolar disorder (BD) in association studies. DDR1 encodes 58 distinct transcripts, which can be translated into five isoforms (DDR1a-e) and are expressed in the brain. However, the transcripts expressed in each brain cell type, their functions and their involvement in SCZ and BD remain unknown.

CAAStools: a toolbox to identify and test Convergent Amino Acid Substitutions.

Motivation: Coincidence of Convergent Amino Acid Substitutions (CAAS) with phenotypic convergences allow pinpointing genes and even individual mutations that are likely to be associated with trait variation within their phylogenetic context. Such findings can provide useful insights into the genetic architecture of complex phenotypes.

Results: Here we introduce CAAStools, a set of bioinformatics tools to identify and validate CAAS in orthologous protein alignments for predefined groups of species representing the phenotypic values targeted by the user.

Human genetic adaptation related to cellular zinc homeostasis.

SLC30A9 encodes a ubiquitously zinc transporter (ZnT9) and has been consistently suggested as a candidate for positive selection in humans. However, no direct adaptive molecular phenotype has been demonstrated. Our results provide evidence for directional selection operating in two major complementary haplotypes in Africa and East Asia.

High blood levels of brain-derived neurotrophic factor (BDNF) mRNA in early psychosis are associated with inflammatory markers.

The brain-derived neurotrophic factor (BDNF) single nucleotide polymorphism (SNP) rs6265C > T, Val66Met, affects BDNF secretion and has been related to inflammatory processes. Both the rs6265 and BDNF protein levels have been widely investigated in neuropsychiatric disorders with conflicting results. In the present study we examined BDNF mRNA expression in blood considering the SNP rs6265 and its relationship with inflammatory markers in the early stages of psychosis.

Gradual Increase in Inflammation-Linked Glycoproteins and a Proatherogenic Lipoprotein Profile in the Early Stages of Psychosis as Characterized by H NMR Blood Analysis.

Minimally invasive prognostic markers of inflammation and dyslipidemia in individuals with a risk of psychosis, also called "at-risk mental state" (ARMS), or in the first episode of psychosis (FEP) are of utmost clinical importance to prevent cardiovascular disorders. We analyzed the plasma concentration of inflammation-linked glycoproteins (Glycs) and lipoprotein subclasses by proton nuclear magnetic resonance (H NMR) in a single acquisition. Study participants were healthy controls (HCs, N = 67) and patients with ARMS ( = 58), FEP ( = 110), or early psychosis diagnosis with ≥2 episodes (critical period (CP), = 53).

Metabolic Overlap between Alzheimer's Disease and Metabolic Syndrome Identifies the Gene as a New Modulator of Diabetic Dyslipidemia.

Background: Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) share metabolic alterations such as abnormal insulin and lipid metabolism and have some common genetic factors such as genotype. Taking this into account, we hypothesized that we could identify common genetic factors involved in the development of diabetes and cardiovascular diseases.

Methodology: We first genotyped 48 single nucleotide polymorphisms (SNPs) previously associated with AD in a cohort composed of 330 patients with cognitive impairment (CI) to assess their association with plasma lipids.

Shared genetic architecture between attention-deficit/hyperactivity disorder and lifespan.

There is evidence linking ADHD to a reduced life expectancy. The mortality rate in individuals with ADHD is twice that of the general population and it is associated with several factors, such as unhealthy lifestyle behaviors, social adversity, and mental health problems that may in turn increase mortality rates. Since ADHD and lifespan are heritable, we used data from genome-wide association studies (GWAS) of ADHD and parental lifespan, as proxy of individual lifespan, to estimate their genetic correlation, identify genetic loci jointly associated with both phenotypes and assess causality.

Polygenic risk scores enhance prediction of body mass index increase in individuals with a first episode of psychosis.

Background: Individuals with a first episode of psychosis (FEP) show rapid weight gain during the first months of treatment, which is associated with a reduction in general physical health. Although genetics is assumed to be a significant contributor to weight gain, its exact role is unknown.

Methods: We assembled a population-based FEP cohort of 381 individuals that was split into a Training ( = 224) set and a Validation ( = 157) set to calculate the polygenic risk score (PRS) in a two-step process.

DDR1 and Its Ligand, Collagen IV, Are Involved in In Vitro Oligodendrocyte Maturation.

Discoidin domain receptor 1 (DDR1) is a tyrosine kinase receptor expressed in epithelial cells from different tissues in which collagen binding activates pleiotropic functions. In the brain, DDR1 is mainly expressed in oligodendrocytes (OLs), the function of which is unclear. Whether collagen can activate DDR1 in OLs has not been studied.

Cross-sectional and longitudinal assessment of the association between DDR1 variants and processing speed in patients with early psychosis and healthy controls.

Recent evidence indicates that DDR1 participates in myelination and that variants of DDR1 are associated with decreased cognitive processing speed (PS) in schizophrenia (SZ). Here, we explored whether DDR1 variants were associated with PS in subjects diagnosed with an early psychosis (EP), a condition often preceding SZ. Data from two Spanish independent samples (from Reus and Santander) including patients with EP (n = 75 and n = 312, respectively) and healthy controls (HCs; n = 57 and n = 160) were analyzed.

Risk factors for metabolic syndrome in individuals with recent-onset psychosis at disease onset and after 1-year follow-up.

Metabolic syndrome (MetS) is a cluster of parameters encompassing the most dangerous heart attack risk factors, associated with increased morbidity and mortality. It is highly prevalent in recent-onset psychosis (ROP) patients. In this pilot study, we evaluated MetS parameters (fasting glucose, high-density lipoprotein (HDL) cholesterol (HDL-c), fasting triglycerides, waist circumference, and systolic and diastolic blood pressure), clinical symptoms, pharmacological treatment, lifestyle, and inflammatory markers in 69 patients with ROP and 61 healthy controls (HCs).

Maximal Sensitivity to Child Maltreatment at the Ages of 6 and 11 Years is Associated with the Risk of Bipolar Disorder.

Adverse childhood experiences, including child maltreatment (CM), are relevant environmental risk factors for bipolar disorder (BD). However, little is known about the interaction of the type, duration and frequency of abuse with the timing of abuse in BD. The aim of this study was to investigate the different patterns of childhood trauma (frequency, type and chronology) between BD patients and healthy controls (HCs) and to identify BD-sensitive periods of exposure to CM that could influence functioning outcomes.

Comprehensive summary of mitochondrial DNA alterations in the postmortem human brain: A systematic review.

Background: Mitochondrial DNA (mtDNA) encodes 37 genes necessary for synthesizing 13 essential subunits of the oxidative phosphorylation system. mtDNA alterations are known to cause mitochondrial disease (MitD), a clinically heterogeneous group of disorders that often present with neuropsychiatric symptoms. Understanding the nature and frequency of mtDNA alterations in health and disease could be a cornerstone in disentangling the relationship between biochemical findings and clinical symptoms of brain disorders.

Polygenic contribution to the relationship of loneliness and social isolation with schizophrenia.

Previous research suggests an association of loneliness and social isolation (LNL-ISO) with schizophrenia. Here, we demonstrate a LNL-ISO polygenic score contribution to schizophrenia risk in an independent case-control sample (N = 3,488). We then subset schizophrenia predisposing variation based on its effect on LNL-ISO.

A polygenic approach to the association between smoking and schizophrenia.

Smoking prevalence in schizophrenia is considerably larger than in general population, playing an important role in early mortality. We compared the polygenic contribution to smoking in schizophrenic patients and controls to assess if genetic factors may explain the different prevalence. Polygenic risk scores (PRSs) for smoking initiation and four genetically correlated traits were calculated in 1108 schizophrenic patients (64.

[Parental perceptions of increased child-to-parent violence of Spanish adolescents during covid-19 lockdown.].

Objective: Internationally, there was a warning of the risk of increased domestic violence during lockdown due to the COVID-19 pandemic, including child-to-parent violence. The objective of our study was to assess the prevalence of different violent behaviors from children to parents during pre-lockdown, lockdown and immediately after, between March 14 and June 20, 2020, and to assess differences in behaviors between pre-lockdown and lockdown and between pre-lockdown and post-lockdown.

Methods: The researchers developed a survey with closed questions about different violent behaviors of the children (poor responses, insults and physical aggression).

Coexpression of the discoidin domain receptor 1 gene with oligodendrocyte-related and schizophrenia risk genes in the developing and adult human brain.

Background: Discoidin domain receptor tyrosine kinase 1 (DDR1) is present in multiple types of epithelial cells and is highly expressed in the nervous system. Previous studies have revealed that DDR1 is involved in schizophrenia (SCZ). Although the expression of DDR1 in oligodendrocytes has been described, its role in brain myelination is not well understood.