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Biochemical Markers in Ophthalmology
Published in Ching-Yu Cheng, Tien Yin Wong, Ophthalmic Epidemiology, 2022
Abdus Samad Ansari, Pirro G. Hysi
In parallel, this applies to the genetic risk alleles contributing to endophenotype variation. There is therefore a good rationale to study genetic contribution to endophenotypes in the context of discrete clinical diseases, such as POAG. Variants associated with endophenotypes contribute to the development of diseases, but they also present advantages in terms of statistical power. Subjects enrolled from general populations, unselected for any particular disease characteristic, but assessed purely with respect to the value of the endophenotype they express, are much easier to ascertain and enrol in genetic studies, as part of multi-purpose population-wide cohorts and biobanks. Endophenotype GWAS throughout the years have greatly contributed to our understanding of POAG pathophysiology and selection of powerful genomic markers of the disease. Several endophenotypes are known to be correlated to POAG risk [44], of which two, IOP and vertical cup-to-disc ratio (VCDR), will be described in most detail below.
Choice Impulsivity
Published in Hanna Pickard, Serge H. Ahmed, The Routledge Handbook of Philosophy and Science of Addiction, 2019
Annabelle M. Belcher, Carl W. Lejuez, F. Gerard Moeller, Nora D. Volkow, Sergi Ferré
It has been argued that molecular genetics will continue to be mostly unsuccessful in the search for genes associated with neuropsychiatric disorders for two reasons: (1) any observable direct genetic effects are subject to strong environmental influences; and (2) the causal link between the gene and the disease is likely to be too long and complex to be directly observable (Gottesman and Gould 2003). The introduction of the ‘endophenotype’ concept has provided an invaluable approach for the identification of genes that predispose or indemnify individuals from mental and psychiatric disorders. The endophenotype concept is understood as simpler clues to genetic underpinnings than the disease syndrome itself, and involves the genetic analysis of any of a variety of biological markers (cognitive, neurophysiological, anatomical, biochemical, etc.) of the disease. The concept promotes the view that psychiatric diagnoses can be decomposed or deconstructed into more tractable intermediate phenotypes by virtue of their assumed proximity to the genetic antecedents of the disease (Gottesman and Gould 2003; Bearden and Freimer 2006).
Eating Disorders in Males
Published in Jonna Fries, Veronica Sullivan, Eating Disorders in Special Populations, 2017
Helen B. Murray, Adelaide S. Robb
Genetic vulnerability for disordered eating exists through pathways such as temperament, personality traits, or related psychopathology (Bulik 2005) interacting with environmental factors. Risk and maintenance factors are then mediated by endophenotype contributions, linking risk from genes and environment with observed symptoms (phenotypes; Gottesman and Gould 2003). Endophenotype research on cognitive processes (i.e., set-shifting, central coherence, impulsivity) and eating disorders is growing, mostly with female samples (Lopez et al. 2009). Males may have some differences that future research should identify, for example, a negative association between set-shifting and focus on muscularity (Griffiths et al. 2013). Similar to females, comorbid pathologies such as obsessive–compulsive disorder, personality disorders, or substance abuse (Fichter and Krenn 2003) may also affect the onset and maintenance of eating disorder behavior.
The relationship between executive functions and chronotype in healthy siblings of children with autism spectrum disorder
Published in Chronobiology International, 2023
Murat Yaşar, Fatih Hilmi Çetin, Serhat Türkoğlu, Halit Necmi Uçar
The executive function (EF) theory is one of the main cognitive theories of ASD. The etiology, including the genetic mechanisms that mediate this type of dysfunction, remains unclear (Seng et al. 2021). In a meta-analysis, it was stated that participants with ASD performed worse in EF compared to the control group (Demetriou et al. 2018). Examining executive functions in unaffected relatives may provide a more complete understanding of the mechanisms underlying inadequate EF in individuals with ASD (McLean et al. 2014). As an interconnection between phenotypes and genes, the endophenotype is defined as the traits associated with the condition, found in both unaffected and affected family members. Unaffected siblings of individuals with ASD, who share half of the genetic components with probands and therefore may have the broad autism phenotype (BAP), are considered ideal candidates for such research (Seng et al. 2021). Some studies have found that unaffected siblings do not have significant EF deficits compared to healthy controls (McLean et al. 2014; Wong et al. 2006). Other studies have shown impairments in executive functions such as working memory, attentional orientation, planning, and inhibition in unaffected siblings of children and adolescents with ASD compared to controls (Hughes et al. 1999; Warren et al. 2012). In a meta-analysis, it was determined that the group diagnosed with ASD showed widespread impairment in EF, especially flexibility and planning, compared to the control group (Xie et al. 2020).
Innovative screening models for the discovery of new schizophrenia drug therapies: an integrated approach
Published in Expert Opinion on Drug Discovery, 2021
Marinos G. Sotiropoulos, Eleni Poulogiannopoulou, Foteini Delis, Christina Dalla, Katerina Antoniou, Nikolaos Kokras
Setting aside possible shortcomings of current clinical trial methodology, as was briefly mentioned previously, a key question was elegantly phrased by Holly Moore: ‘Based on translational research findings, how many false positive signals can the industry sustain in order to find a new treatment mechanism, and how can we limit those failures?’ [33]. Clinical trials could routinely incorporate measurements of available endophenotypes: this will provide valuable feedback to translational neuroscience about the validity of modeling but will also provide a guide about the proof-of-concept data of the compound studied. The tested compound may modify the endophenotype, but not the phenotype routinely measured with clinical scales used in current trials. However, as mentioned elsewhere [24], this bi-directional flow of information is not happening. Moreover, the existing unidirectional flow of information from translational to clinical research is based on unrealistic expectations from animal modeling. Closer collaboration between the industry and academia – which mostly develops models of the disease – will facilitate a better understanding of the strengths and the limitations of animal models of schizophrenia from the part of the industry. This is of paramount importance, given the significant downsizing of the industry in-house CNS research and development, and will also aid academia in improving animal models of schizophrenia by learning from the failed clinical trials [113] (Figure 1).
Test of Everyday Attention for Children (TEA-Ch): Greek Normative Data and Discriminative Validity for Children with Combined Type of Attention Deficit-Hyperactivity Disorder
Published in Developmental Neuropsychology, 2019
Amaryllis-Chryssi Malegiannaki, Eleni Aretouli, Panayiota Metallidou, Lambros Messinis, Dimitrios Zafeiriou, Mary H. Kosmidis
The second goal of the study was to investigate which TEA-Ch subtest/(s) could differentiate the ADHD sample from that of their typically developing peers, and how accurately. ADHD was selected as a clinical comparison group due to the prominent attentional deficits presented in the affected children. Neuropsychological deficits are considered part of its endophenotype (Gau & Shang, 2010; Sonuga-Barke & Coghill, 2014). Despite the existence of inter-individual heterogeneity in the cognitive manifestation of ADHD (Sonuga-Barke & Haplerin, 2010), neuropsychological studies have reported the presence of well-described impairments in specific attentional abilities (sustained attention, Kaufmann et al., 2010; Palumbo & Diehl, 2007; executive attention functions (i.e., divided or shifting attention), (Seidman, 2006; Sjöwall, Bohlin, Rydell, & Thorell, 2017). In contrast to the core deficit hypothesis for ADHD (Barkley, 1997), which posits that a selective impairment in impulsivity control is the etiological basis of nearly any other secondary cognitive deficit observed in ADHD, the results of the present study are in line with more current hypotheses (Lambek et al., 2010; Sonuga-Barke, Bitsakou, & Thompson, 2010), suggesting the existence of distinct multiple deficits (multiple substrates hypothesis). The present findings suggest the presence of deficits in nearly all attentional functions captured by the TEA-Ch among children with ADHD-C.