Suicidal behaviors (SBs), which range from suicidal ideation to suicide attempts and completed suicide, represent a fatal dimension of mental ill-health. The involvement of genetic risk factors in SB is supported by family, twin, and adoption studies. The aim of this paper is to review recent genetic association studies in SBs including (i) case–control studies, (ii) family-based association studies, and (iii) genome-wide association studies (GWAS). Various studies on genetic associations have tended to suggest that a number of genes [e.g., tryptophan hydroxylase, serotonin receptors and transporters, or brain-derived neurotrophic factors (BDNFs)] are linked to SBs, but these findings are not consistently supported by the results obtained. Although the candidate–gene approach is useful, it is hampered by the present state of knowledge concerning the pathophysiology of diseases. Interpretations of GWAS results are mostly hindered by a lack of annotation describing the functions of most variation throughout the genome. Association studies have addressed a wide range of single-nucleotide polymorphisms in numerous genes. We have included 104 such studies, of which 10 are family-based association studies and 11 are GWAS. Numerous meta-analyses of case–control studies have shown significant associations of SB with variants in the serotonin transporter gene (5-HTT or SLC6A4) and the tryptophan hydroxylase 1 gene (TPH1), but others report contradictory results. The gene encoding BDNF and its receptor (NTRK2) are also promising candidates. Only two of the GWAS showed any significant associations. Several pathways are mentioned in an attempt to understand the lack of reproducibility and the disappointing results. Consequently, we review and discuss here the following aspects: (i) sample characteristics and confounding factors; (ii) statistical limits; (iii) gene–gene interactions; (iv) gene, environment, and by time interactions; and (v) technological and theoretical limits.
This is the accepted version of the paper.This version of the publication may differ from the final published version.Permanent repository link: https://openaccess.city.ac.uk/id/eprint/23359/ Link to published version: http://dx. Abstract:To address inconsistencies in the literature on memory in Autism Spectrum Disorder (ASD), we report the first ever meta-analysis of short-term (STM) and episodic longterm (LTM) memory in ASD, evaluating the effects of type of material, type of retrieval and the role of inter-item relations. Analysis of 64 studies comparing individuals with ASD and typical development (TD) showed greater difficulties in ASD compared to TD individuals in STM (Hedges' g=-0.53 [95%CI -0.90; -0.16], p=.005, I²=96%) compared to LTM (g=-0.30 [95%CI -0.42; -0.17], p<.00001, I²=24%), a small difficulty in verbal LTM (g=-0.21, p=.01), contrasting with a medium difficulty for visual LTM (g= -0.41, p=.0002) in ASD compared to TD individuals. We also found a general diminution in free recall compared to cued recall and recognition (LTM, free recall: g=-0.38, p<.00001, cued recall: g=-0.08, p=.58, recognition: g=-0.15, p=.16; STM, free recall: g=-0.59, p=.004, recognition: g=-0.33, p=.07).We discuss these results in terms of their relation to semantic memory. The limited diminution in verbal LTM and preserved overall recognition and cued recall (supported retrieval) may result from a greater overlap of these tasks with semantic long-term representations which are overall preserved in ASD. By contrast, difficulties in STM or free recall may result from less overlap with the semantic system or may involve additional cognitive operations and executive demands. These findings highlight the need to support STM functioning in ASD and acknowledge the potential benefit of using verbal materials at encoding and broader forms of memory support at retrieval to enhance performance. ABSTRACTTo address inconsistencies in the literature on memory in Autism Spectrum Disorder (ASD), we report the first ever meta-analysis of short-term (STM) and episodic long-term (LTM) memory in ASD, evaluating the effects of type of material, type of retrieval and the role of inter-item relations.Analysis of 64 studies comparing individuals with ASD and typical development (TD) showed greater difficulties in ASD compared to TD individuals in STM (Hedges' g=-0.53 [95%CI -0.90; -0.16], p=.005, I²=96%) compared to LTM (g=-0.30 [95%CI -0.42; -0.17], p<.00001, I²=24%), a small difficulty in verbal LTM (g=-0.21, p=.01), contrasting with a medium difficulty for visual LTM (g= -0.41, p=.0002) in ASD compared to TD individuals. We also found a general diminution in free recall compared to cued recall and recognition (LTM, free recall: g=-0.38, p<.00001, cued recall: g=-0.08, p=.58, recognition: g=-0.15, p=.16; STM, free recall: g=-0.59, p=.004, recognition: g=-0.33, p=.07).We discuss these results in terms of their relation to semantic memory. The limited diminution in verbal LTM and preserved overall recognition and cued recall (supported retrieval)...
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