Neuropathology and Synaptic Alterations in Neurodevelopmental Disorders

2013 ◽  
pp. 980-994
Author(s):  
Mara Dierssen ◽  
Salvador Martínez
Keyword(s):  
Cognitive Processing ◽  
Neurodevelopmental Disorders ◽  
Genetic Risk ◽  
Disease Onset ◽  
Brain Maturation ◽  
Brain Circuits ◽  
Symptom Domains ◽  
Genetic Risks ◽  
Physiological Abnormalities ◽  
Chronic Course

Neurodevelopmental disorders include a myriad of conditions, in which symptomatic presentation and disease onset is identifiable in early postnatal years, prior to full brain maturation. Both genetic and environmental insults can lead to neurodevelopmental disorders, which result from anatomical and physiological abnormalities during the development and maturation of brain circuits. Mental disorders become symptomatic in childhood or adolescence and are affected by early environmental conditions that may interact with genetic risk factors. Neurodevelopmental disorders share a number of similarities in terms of common genetic risks, co-occurrence of neurodevelopmental symptom domains, cognitive processing deficits, early onset and chronic course. Schizophrenia, autism and intellectual disabilities, for example, are spectrums of diseases with broad sets of causes that have overlapping phenotypes and genetics, which is suggestive of common deficits.

Brain Circuits

2016 ◽  
Author(s):  
Juan Zhou ◽  
William W. Seeley
Keyword(s):  
Risk Factors ◽  
Neurodegenerative Disease ◽  
Frontotemporal Dementia ◽  
Genetic Risk ◽  
Disease Onset ◽  
Selective Vulnerability ◽  
The Past ◽  
Brain Circuits ◽  
Common Causes ◽  
Key Concepts

Each neurodegenerative disease is defined by selectively vulnerable neurons, regions, networks, and functions, as well as genetic risk factors. In the past decade, new network-sensitive neuroimaging methods have made it possible to test the notion of network-based degeneration in living humans. This chapter focuses on two common causes of dementia, Alzheimer’s disease (AD) and frontotemporal dementia (FTD), but uses these diseases to illustrate class-wide neurodegeneration principles whenever possible. It first introduces two key concepts of neurodegenerative disease selective vulnerability: onset and progression. In parallel, it addresses two distinct but related observations about neurodegenerative disease: clinico-anatomical convergence and phenotypic heterogeneity. It then examines disease onset and models of progression in more detail, based on available neuroimaging evidence. Finally, it touches on the most important frontiers in the field of network-based neurodegeneration.

Assessment of The Influence of Non-Genetic Risk Factors on The Disease Onset and Progression of Androgenetic Alopecia in Egyptian Males

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Naziha Hafez Khafagy ◽  
Marwa Yassin Soltan ◽  
Ahmed Adel Ali Ali
Keyword(s):  
Risk Factors ◽  
Hair Loss ◽  
Genetic Risk ◽  
Disease Onset ◽  
Genetic Risk Factors ◽  
Androgenetic Alopecia ◽  
Major Type ◽  
Young Males ◽  
Potential Risk Factors ◽  
The Impact

Abstract Background Androgenetic alopecia (AGA) is a patterned hair loss with multifactorial background including genetic, hormonal as well as environmental and lifestyle-related risk factors. The impact of non-genetic risk factors on the onset and disease progression of androgenetic alopecia in Egyptian males. Objective To explore the potential role of non-genetic risk factors on the disease development and progression of androgenetic alopecia in Egyptian males. Patients and Methods The study included 2000 subjects with and without AGA, during the period from February 2019 to September 2019. The study protocol was approved by faculty of medicine, Ain Sham University, Research ethics committee (FWA 000017585). An informed written consent for participation in this study was obtained from patients and controls before enrollment. One thousand male patients with AGA were recruited in the study. The diagnosis was made via clinical diagnosis, dermatological findings, trichoscopic assessment. Results Our study showed that after skin examination 416 patients had acne and 344 patients had seborrhea, with statistically significant association to AGA cases. Conclusion From our study, it can be concluded that AGA became a major type of hair loss complaint among Egyptian males especially young males. Many potential risk factors were found to be associated with the disease as smoking, stress, obesity, family history, exercise, HTN and unbalanced diet. Avoidance of such risk factors may help improve the disease.

scholarly journals Heredity Indexes for Estimating Heritability Using Known and Unknown Family Data Based on the Model of Polygenic Inheritance

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Hui Liu
Keyword(s):  
Correlation Coefficient ◽  
Genetic Risk ◽  
Binary Data ◽  
Disease Onset ◽  
Simulated Data ◽  
Family Data ◽  
Lookup Table ◽  
Continuous Data ◽  
Pedigree Data ◽  
Polygenic Inheritance

Objective. To establish a model for estimating genetic risk using known and unknown family data. Methods. Four simulated datasets were generated for four paternal and maternal chromosomes. The simulated data for children were generated from the parental data according to the Mendelian law. The correlation coefficient between the children’s and paternal data was calculated, and 2R was defined as the heredity index for continuous data (HIC). The simulated continuous data were transformed into binary data according to the gene accumulation threshold (incidence); the incidences of children in the parental no-disease group and the disease onset group were obtained; the correlation coefficient (R) was calculated as expected R (Re). The ratio of observed R (Ro) and Re was defined as the Heredity index for binary data (HIB). Results. Different actual pedigree data (lunula and holding a hammer in the right or left hand) were successfully used to verify the accuracy of the model. The genetic risk was estimated according to the incidence in a population using a lookup table. Conclusion. Our findings indicate the reliability of the model based on the fact that the multigene effect constitutes the normal distribution. Thus, this model can be used for comprehensive analysis of the influence of genetic and nongenetic factors on the genetic phenotype and to estimate genetic risk using known and unknown family data.

scholarly journals Investigating gender-specific effects of familial risk for attention-deficit hyperactivity disorder and other neurodevelopmental disorders in the Swedish population

BJPsych Open ◽  
2020 ◽  
Vol 6 (4) ◽  
Author(s):  
Joanna Martin ◽  
Laura Ghirardi ◽  
Qi Chen ◽  
Catharina A. Hartman ◽  
Mina A. Rosenqvist ◽  
...  
Keyword(s):  
Gender Differences ◽  
Attention Deficit Hyperactivity Disorder ◽  
Eating Disorders ◽  
Attention Deficit ◽  
Neurodevelopmental Disorders ◽  
Familial Risk ◽  
Female Patients ◽  
Hyperactivity Disorder ◽  
Genetic Risks ◽  
Gender Specific

Background Many psychiatric disorders show gender differences in prevalence. Recent studies suggest that female patients diagnosed with anxiety and depression carry more genetic risks related to attention-deficit hyperactivity disorder (ADHD) compared with affected males. Aims In this register-based study, we aimed to test whether female patients who received clinical diagnoses of anxiety, depressive, bipolar and eating disorders are at higher familial risk for ADHD and other neurodevelopmental disorders, compared with diagnosed male patients. Method We analysed data from a record-linkage of several Swedish national registers, including 151 025 sibling pairs from 103 941 unique index individuals diagnosed with anxiety, depressive, bipolar or eating disorders, as well as data from 646 948 cousin pairs. We compared the likelihood of having a relative diagnosed with ADHD/neurodevelopmental disorders in index males and females. Results Female patients with anxiety disorders were more likely than affected males to have a brother with ADHD (odd ratio (OR) = 1.13, 95% CI 1.05–1.22). Results for broader neurodevelopmental disorders were similar and were driven by ADHD diagnoses. Follow-up analyses revealed similar point estimates for several categories of anxiety disorders, with the strongest effect observed for agoraphobia (OR = 1.64, 95% CI 1.12–2.39). No significant associations were found in individuals with depressive, bipolar or eating disorders, or in cousins. Conclusions These results provide modest support for the possibility that familial/genetic risks for ADHD may show gender-specific phenotypic expression. Alternatively, there could be gender-specific biases in diagnoses of anxiety and ADHD. These factors could play a small role in the observed gender differences in prevalence of ADHD and anxiety.

scholarly journals The Impact of Genetic Information Disclosure Related to Body Mass Index on Diet Quality: A Randomized Controlled Trial

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 848-848
Author(s):  
Ga Young Lee ◽  
Sung Nim Han
Keyword(s):  
Dietary Intake ◽  
Diet Quality ◽  
Genetic Risk ◽  
Genetic Information ◽  
Intervention Group ◽  
Test Results ◽  
Genetic Risks ◽  
The Impact ◽  
Time Point ◽  
Female Subjects

Abstract Objectives DTC genetic test results are provided directly to consumers without involvement of medical institution, which allows individual access to genetic information. Although studies have been conducted to determine the effects of genetic background recognition on behavioral changes, the effectiveness of DTC test on dietary change remains unclear. In this study, we examined the impact of disclosing DTC results on dietary intake using the Healthy Eating Index (HEI) as an indicator of diet quality. Methods A total of 100 disease-free healthy adults (50 male and 50 female) aged 25–35 y were stratified by sex, BMI (body mass index, kg/m2) and genetic risk, then randomly assigned into two groups. The intervention group (n = 65) was informed of the DTC test results on body fat mass (FTO, MC4R, BDNF), while the control group (n = 35, CON) was not. Based on the genetic risks reported, the intervention group was classified into Intervention-Non Risk (low risk, INR) or Intervention-Risk (borderline and high risk, IR) groups. Anthropometric and dietary intake data were collected at baseline, 1, 2, 3, and 6 mo-time point. Diet quality was evaluated by the HEI 2015, which is consisted of 13 dietary components that reflects the key recommendations by the 2015–2020 Dietary Guidelines for Americans. Results Participants with genetic risks (IR) regarding the MC4R gene showed a significant decrease in body weight (kg) and BMI compared to the INR at 1 and 2 mo. In addition, WHR ratio (%) was decreased significantly in the IR compared to the INR at 3 mo. Regarding diet quality, the HEI of the IR was higher than that of the INR at 3 mo in female subjects (57.2 ± 5.36 vs. 51.3 ± 4.8). Among female subjects, dietary fat intake tended to increase in the INR compared to the CON (5.91 ± 14.46 vs. -1.93 ± 8.88). Saturated fatty acids intake increased significantly in the INR compared to IR at 3 mo time point. Conclusions In conclusion, following the recognition of DTC results, female subjects with genetic risk for high BMI showed a decrease in body weight and WHR ratio compared to those with low genetic risk. The decrease in weight and WHR ratio might be attributed to healthier dietary intake in the risk group. Funding Sources Supported by Seoul National University Research Grant in 2018 (350–20,180,049).

scholarly journals Transcriptomic and Cellular Decoding of Regional Brain Vulnerability to Neurodevelopmental Disorders

2019 ◽  
Author(s):  
Jakob Seidlitz ◽  
Ajay Nadig ◽  
Siyuan Liu ◽  
Richard A.I. Bethlehem ◽  
Petra E. Vértes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Spatial Patterns ◽  
Neurodevelopmental Disorders ◽  
Copy Number Variations ◽  
Brain Anatomy ◽  
Specific Cell ◽  
Expression Data ◽  
Regional Brain ◽  
Genetic Risks ◽  
Neuroimaging Data

AbstractNeurodevelopmental disorders are highly heritable and associated with spatially-selective disruptions of brain anatomy. The logic that translates genetic risks into spatially patterned brain vulnerabilities remains unclear but is a fundamental question in disease pathogenesis. Here, we approach this question by integrating (i) in vivo neuroimaging data from patient subgroups with known causal genomic copy number variations (CNVs), and (ii) bulk and single-cell gene expression data from healthy cortex. First, for each of six different CNV disorders, we show that spatial patterns of cortical anatomy change in youth are correlated with spatial patterns of expression for CNV region genes in bulk cortical tissue from typically-developing adults. Next, by transforming normative bulk-tissue cortical expression data into cell-type expression maps, we further link each disorder’s anatomical change map to specific cell classes and specific CNV-region genes that these cells express. Finally, we establish convergent validity of this “transcriptional vulnerability model” by inter-relating patient neuroimaging data with measures of altered gene expression in both brain and blood-derived patient tissue. Our work clarifies general biological principles that govern the mapping of genetic risks onto regional brain disruption in neurodevelopmental disorders. We present new methods that can harness these principles to screen for potential cellular and molecular determinants of disease from readily available patient neuroimaging data.

scholarly journals Life Writing in the Era of Genetics: Contemporary Genetic Risk Narratives in Great Britain and America

2021 ◽  
Vol 11 (3) ◽  
pp. 45
Author(s):  
Tingting Zhou
Keyword(s):  
Great Britain ◽  
Genetic Risk ◽  
Risk Group ◽  
High Risk Group ◽  
The Body ◽  
Personal Meaning ◽  
Complex Situation ◽  
Genetic Risks ◽  
Disease Related Genes ◽  
Genetic Science

The development of genetic science brings forth a third group besides the healthy and the ill: the high-risk group who carries certain disease-related genes. In the era of genetics, people try to assess risks with statistical numbers and eliminate risks by Western medical measures. In this context, personal genetic risk narratives (usually in the form of memoirs) emerged in Great Britain and America in the 1990s. The thesis has a close reading of three British and American genetic risk memoirs and wants to find the characteristics and values of the new genre. The memoirs are featured by their vivid description of the narrator’s difficult and complex situation in face of genetic risks. In an era when the body is dominated by statistical numbers, these narratives make personal meaning of impersonal statistics. Genetic risk narratives express a strong belief in genetic technology and Western medical myth. However, the narrative divergence and self-contradiction in the memoirs exposes the limitation of genetic determinism and thus deconstructs the Western medical myth.

T70EARLY MANIFESTATIONS OF GENETIC RISK FOR NEURODEVELOPMENTAL DISORDERS

2019 ◽  
Vol 29 ◽  
pp. S252-S253
Author(s):  
Ragna Askeland ◽  
Laurie Hannigan ◽  
Helga Ask ◽  
Martin Tesli ◽  
Elizabeth Corfield ◽  
...  
Keyword(s):  
Neurodevelopmental Disorders ◽  
Genetic Risk
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