233 research outputs found
A review of the genetic basis of problematic Internet use
Problematic Internet use (PUI) has become of increasing interest in mental health. Despite the rising number of PUI in all ages, the exact underpinning etiology is still missing. There is increasing evidence that, in particular, genetic, environmental, and personality factors are involved in the development and maintenance of PUI. However, the neurobiological mechanism of PUI has not been yet extensively investigated, and still reports conflicting results. Previous studies have focused on candidate genes, mainly of the serotonergic, dopaminergic, or acetylcholinergic pathways known partly as risk factors in other substance-use disorders. This review focuses on preexisting literature on the genetic basis of PUI, and implications for future research approaches to fill the gap of its etiology. Understanding the exact etiology and potential genetic mechanism is the basis for a better understanding of PUI and future therapy implications
The link between iron, metabolic syndrome, and Alzheimer's disease
Both Alzheimer's disease (AD), the most common form of dementia, and type-2 diabetes mellitus (T2DM), a disease associated with metabolic syndrome (MetS), affect a great number of the world population and both have increased prevalence with age. Recently, many studies demonstrated that pre-diabetes, MetS, and T2DM are risk factors in the development of AD and have many common mechanisms. The main focus of studies is the insulin resistance outcome found both in MetS as well as in brains of AD subjects. However, oxidative stress (OS)-related mechanisms, which are well known to be involved in AD, including mitochondrial dysfunction, elevated iron concentration, reactive oxygen species (ROS), and stress-related enzyme or proteins (e.g. heme oxygenase-1, transferrin, etc.), have not been elucidated in MetS or T2DM brains although OS and iron are involved in the degeneration of the pancreatic islet ÎČ cells. Therefore, this review sets to cover the current literature regarding OS and iron in MetS and T2DM and the similarities to mechanisms in AD both in human subjects as well as in animal model
In vitro study methodologies to investigate genetic aspects and effects of drugs used in attention-deficit hyperactivity disorder
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in children and adolescents, with up to 5% affected worldwide. Twin and family studies on ADHD show its high familiality with heritability estimated around 70%, but, to date, no specific polymorphism or gene was found to be specifically affected. Psychostimulants (amphetamine, methylphenidate) and non-psychostimulants (atomoxetine) are used successfully in ADHD therapy, but many of their mechanisms of action and their adverse effects are not yet fully understood. Therefore, both genetic findings and therapeutic interventions should be further investigated. One easy platform for such studies is in vitro analyses, which encompass neuronal cell culture studies, transfections of genetic constructs, binding and electrophysiology analyses. In this review, different methods will be referred in particular to ADHD findings, and new techniques will be mentioned for future studies of drug or genetic effects in vitr
Association study in siblings and case-controls of serotonin- and oxytocin-related genes with high functioning autism
BACKGROUND Autism spectrum disorder (ASD) is heritable and neurodevelopmental with unknown causes. The serotonergic and oxytocinergic systems are of interest in autism for several reasons: (i) Both systems are implicated in social behavior, and abnormal levels of serotonin and oxytocin have been found in people with ASD; (ii) treatment with selective serotonin reuptake inhibitors and oxytocin can yield improvements; and (iii) previous association studies have linked the serotonin transporter (SERT; SLC6A4), serotonin receptor 2A (HTR2A), and oxytocin receptor (OXTR) genes with ASD. We examined their association with high functioning autism (HFA) including siblings and their interaction. METHODS In this association study with HFA children (IQâ>â80), siblings, and controls, participants were genotyped for four single nucleotide polymorphisms (SNPs) in OXTR (rs2301261, rs53576, rs2254298, rs2268494) and one in HTR2A (rs6311) as well as the triallelic HTTLPR (SERT polymorphism). RESULTS We identified a nominal significant association with HFA for the HTTLPR s allele (consisting of S and LG alleles) (pâ=â.040; odds ratio (OR)â=â1.697, 95% CI 1.191-2.204)). Four polymorphisms (HTTLPR, HTR2A rs6311, OXTR rs2254298 and rs53576) in combination conferred nominal significant risk for HFA with a genetic score of â„4 (ORâ=â2.09, 95% CI 1.05-4.18, pâ=â.037). The resulting area under the receiver operating characteristic curve was 0.595 (pâ=â.033). CONCLUSIONS Our findings, combined with those of previous reports, indicate that ASD, in particular HFA, is polygenetic rather than monogenetic and involves the serotonergic and oxytocin pathways, probably in combination with other factors
Improved Generation of Induced Pluripotent Stem Cells From Hair Derived Keratinocytes â A Tool to Study Neurodevelopmental Disorders as ADHD
In the last decade, there is an increasing application of induced pluripotent stem cells (iPSCs) for disease modeling. The iPSC technology enables the study of patient-specific neuronal cell lines in vitro to evaluate dysfunction at the cellular level and identify the responsible genetic factors. This approach might be particularly valuable for filling the gap of knowledge at the cellular and molecular levels underlying the pathophysiology of various neurodevelopmental and/or psychiatric disorders, such as attention-deficit hyperactivity disorder (ADHD). However, the invasiveness of skin biopsy or blood withdrawal might represent a major impediment in such protected population. Using hair derived keratinocytes as starting somatic cells circumvents this problem as sample collections can be performed non-invasively. Here we describe an improved, convenient, standardized and effective method to culture and reprogram hair derived keratinocytes from three healthy controls and one ADHD patient into iPSCs, which in turn will be used to generate differentiated neuronal cells. All the cell types were maintained in highly defined, serum-free conditions and showed expression of the respective key marker genes, assessed by both immunocytochemistry and qRT-PCR. The described in vitro personalized neuronal model has its advantage in modeling neurodevelopmental trajectories since it can recapitulate key processes of brain development at the cellular and molecular level and is intended to be used as for example studying ADHD etiopathology
A genomeâwide association metaâanalysis of allâcause and vascular dementia
Introduction: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.
Methods: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 individuals, with 46,902 and 8702 cases of ACD and VaD, respectively. Known AD loci for ACD and VaD were replicated. Bioinformatic analyses prioritized genes that are likely functionally relevant and shared with closely related traits and risk factors.
Results: For ACD, novel loci identified were associated with energy transport (SEMA4D), neuronal excitability (ANO3), amyloid deposition in the brain (RBFOX1), and magnetic resonance imaging markers of small vessel disease (SVD; HBEGF). Novel VaD loci were associated with hypertension, diabetes, and neuron maintenance (SPRY2, FOXA2, AJAP1, and PSMA3).
Discussion: Our study identified genetic risks underlying ACD, demonstrating overlap with neurodegenerative processes, vascular risk factors, and cerebral SVD.
Highlights: We conducted the largest genome-wide association study of all-cause dementia (ACD) and vascular dementia (VaD). Known genetic variants associated with AD were replicated for ACD and VaD. Functional analyses identified novel loci for ACD and VaD. Genetic risks of ACD overlapped with neurodegeneration, vascular risk factors, and cerebral small vessel disease
Pilot study: peripheral biomarkers for diagnosing sporadic Parkinson's disease
The need for an early and differential diagnosis of Parkinson's disease (PD) is undoubtedly one of the main quests of the century. An early biomarker would enable therapy to begin sooner and would, hopefully, slow or better prevent progression of the disease. We performed transcript profiling via quantitative RT-PCR in RNA originating from peripheral blood samples. The groups were de novo (n=11) and medicated PD (n=94) subjects and healthy controls (n=34), while for negative control Alzheimer's disease (AD; n=14) subjects were recruited as an additional neurodegenerative disease. The results were retested on a second recruitment consisting 22 medicated PD subjects versus 33 controls and 12 AD. Twelve transcripts were chosen as candidate genes, according to previous postmortem brain profiling. Multiple analyses resulted in four significant genes: proteasome (prosome, macropain) subunit-alpha type-2 (PSMA2; p=0.0002, OR=1.15 95% CI 1.07-1.24), laminin, beta-2 (laminin S) (LAMB2; p=0.0078, OR=2.26 95% CI 1.24-4.14), aldehyde dehydrogenase 1 family-member A1 (ALDH1A1; p=0.016, OR=1.05 95% CI 1.01-1.1), and histone cluster-1 H3e (HIST1H3E; p=0.03, OR=0.975 95% CI 0.953-0.998) differentiating between medicated PD subjects versus controls. Using these four biomarkers for PD diagnosis, we achieved sensitivity and specificity of more than 80%. These biomarkers might be specific for PD diagnosis, since in AD subjects no significant results were observed. In the second validation, three genes (PSMA2, LAMB2 and ALDH1A1) demonstrated high reproducibility. This result supports previous studies of gene expression profiling and may facilitate the development of biomarkers for early diagnosis of P
In vitro study methodologies to investigate genetic aspects and effects of drugs used in attention-deficit hyperactivity disorder
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in children and adolescents, with up to 5 % affected worldwide. Twin and family studies on ADHD show its high familiality with heritability estimated around 70 %, but, to date, no specific polymorphism or gene was found to be specifically affected. Psychostimulants (amphetamine, methylphenidate) and non-psychostimulants (atomoxetine) are used successfully in ADHD therapy, but many of their mechanisms of action and their adverse effects are not yet fully understood. Therefore, both genetic findings and therapeutic interventions should be further investigated. One easy platform for such studies is in vitro analyses, which encompass neuronal cell culture studies, transfections of genetic constructs, binding and electrophysiology analyses. In this review, different methods will be referred in particular to ADHD findings, and new techniques will be mentioned for future studies of drug or genetic effects in vitro
- âŠ