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Auteur N. MELHEM |
Documents disponibles écrits par cet auteur (2)
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Childhood maltreatment, neuropsychological function and suicidal behavior / J. ZELAZNY in Journal of Child Psychology and Psychiatry, 60-10 (October 2019)
[article]
Titre : Childhood maltreatment, neuropsychological function and suicidal behavior Type de document : Texte imprimé et/ou numérique Auteurs : J. ZELAZNY, Auteur ; N. MELHEM, Auteur ; G. PORTA, Auteur ; C. BIERNESSER, Auteur ; J. G. KEILP, Auteur ; J. J. MANN, Auteur ; M. A. OQUENDO, Auteur ; B. STANLEY, Auteur ; David A. BRENT, Auteur Article en page(s) : p.1085-1093 Langues : Anglais (eng) Mots-clés : Maltreatment depression executive function suicidal behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Suicide is the second leading cause of death in young people. Childhood maltreatment, neuropsychological dysfunction and psychopathology have each been shown to increase risk for suicidal behavior. However, few studies have examined their interactions and the effects of those interactions on suicidal behavior. METHODS: Across two sites, a total of 382 offspring of depressed parents underwent neuropsychological assessments. This high-risk sample included nearly equal numbers of males and females. Average age at the time of neuropsychological assessment was 18.5 years. The most prevalent lifetime psychiatric disorders were mood (43%), anxiety (37%) and alcohol and substance use disorders (21%). Childhood maltreatment was reported by 44% of offspring. Participants underwent extensive neuropsychological testing assessing the following domains: attention, memory, executive function, working memory, language fluency, and impulse control. Logistic regression was used to examine the association of reported childhood maltreatment, neuropsychological functioning, psychopathology and their interactions with suicidal behavior. Bonferroni correction was used to adjust for multiple comparisons. RESULTS: Maltreatment was associated with increased risk of suicidal behavior with odds ratios ranging between 2.40 and 4.43. Moderation analyses found that adaptive neuropsychological functioning was not protective against childhood maltreatment's effect on suicidal risk. While lifetime history of mood disorder was strongly associated with suicidal behavior, higher scores in working memory (OR = 0.21; 95% CI = 0.09, 0.45; p < .001) and executive function (OR = 0.15; 95% CI = 0.05, 0.43; p < .001) were protective against suicidal behavior even in the presence of a lifetime history of mood disorder. CONCLUSIONS: Further research is needed to determine how neuropsychological capacity protects depressed patients against the risk of suicidal behavior. En ligne : http://dx.doi.org/10.1111/jcpp.13096 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=406
in Journal of Child Psychology and Psychiatry > 60-10 (October 2019) . - p.1085-1093[article] Childhood maltreatment, neuropsychological function and suicidal behavior [Texte imprimé et/ou numérique] / J. ZELAZNY, Auteur ; N. MELHEM, Auteur ; G. PORTA, Auteur ; C. BIERNESSER, Auteur ; J. G. KEILP, Auteur ; J. J. MANN, Auteur ; M. A. OQUENDO, Auteur ; B. STANLEY, Auteur ; David A. BRENT, Auteur . - p.1085-1093.
Langues : Anglais (eng)
in Journal of Child Psychology and Psychiatry > 60-10 (October 2019) . - p.1085-1093
Mots-clés : Maltreatment depression executive function suicidal behavior Index. décimale : PER Périodiques Résumé : BACKGROUND: Suicide is the second leading cause of death in young people. Childhood maltreatment, neuropsychological dysfunction and psychopathology have each been shown to increase risk for suicidal behavior. However, few studies have examined their interactions and the effects of those interactions on suicidal behavior. METHODS: Across two sites, a total of 382 offspring of depressed parents underwent neuropsychological assessments. This high-risk sample included nearly equal numbers of males and females. Average age at the time of neuropsychological assessment was 18.5 years. The most prevalent lifetime psychiatric disorders were mood (43%), anxiety (37%) and alcohol and substance use disorders (21%). Childhood maltreatment was reported by 44% of offspring. Participants underwent extensive neuropsychological testing assessing the following domains: attention, memory, executive function, working memory, language fluency, and impulse control. Logistic regression was used to examine the association of reported childhood maltreatment, neuropsychological functioning, psychopathology and their interactions with suicidal behavior. Bonferroni correction was used to adjust for multiple comparisons. RESULTS: Maltreatment was associated with increased risk of suicidal behavior with odds ratios ranging between 2.40 and 4.43. Moderation analyses found that adaptive neuropsychological functioning was not protective against childhood maltreatment's effect on suicidal risk. While lifetime history of mood disorder was strongly associated with suicidal behavior, higher scores in working memory (OR = 0.21; 95% CI = 0.09, 0.45; p < .001) and executive function (OR = 0.15; 95% CI = 0.05, 0.43; p < .001) were protective against suicidal behavior even in the presence of a lifetime history of mood disorder. CONCLUSIONS: Further research is needed to determine how neuropsychological capacity protects depressed patients against the risk of suicidal behavior. En ligne : http://dx.doi.org/10.1111/jcpp.13096 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=406 How rare and common risk variation jointly affect liability for autism spectrum disorder / L. KLEI in Molecular Autism, 12 (2021)
[article]
Titre : How rare and common risk variation jointly affect liability for autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : L. KLEI, Auteur ; L. L. MCCLAIN, Auteur ; B. MAHJANI, Auteur ; K. PANAYIDOU, Auteur ; S. DE RUBEIS, Auteur ; A. S. GRAHNAT, Auteur ; G. KARLSSON, Auteur ; Y. LU, Auteur ; N. MELHEM, Auteur ; X. XU, Auteur ; A. REICHENBERG, Auteur ; S. SANDIN, Auteur ; C. M. HULTMAN, Auteur ; Joseph D. BUXBAUM, Auteur ; K. ROEDER, Auteur ; B. DEVLIN, Auteur Article en page(s) : 66 p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder De novo mutation Genomic-Best Linear Unbiased Prediction (G-BLUP) Liability Polygenic risk score Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic studies have implicated rare and common variations in liability for autism spectrum disorder (ASD). Of the discovered risk variants, those rare in the population invariably have large impact on liability, while common variants have small effects. Yet, collectively, common risk variants account for the majority of population-level variability. How these rare and common risk variants jointly affect liability for individuals requires further study. METHODS: To explore how common and rare variants jointly affect liability, we assessed two cohorts of ASD families characterized for rare and common genetic variations (Simons Simplex Collection and Population-Based Autism Genetics and Environment Study). We analyzed data from 3011 affected subjects, as well as two cohorts of unaffected individuals characterized for common genetic variation: 3011 subjects matched for ancestry to ASD subjects and 11,950 subjects for estimating allele frequencies. We used genetic scores, which assessed the relative burden of common genetic variation affecting risk of ASD (henceforth "burden"), and determined how this burden was distributed among three subpopulations: ASD subjects who carry a potentially damaging variant implicated in risk of ASD ("PDV carriers"); ASD subjects who do not ("non-carriers"); and unaffected subjects who are assumed to be non-carriers. RESULTS: Burden harbored by ASD subjects is stochastically greater than that harbored by control subjects. For PDV carriers, their average burden is intermediate between non-carrier ASD and control subjects. Both carrier and non-carrier ASD subjects have greater burden, on average, than control subjects. The effects of common and rare variants likely combine additively to determine individual-level liability. LIMITATIONS: Only 305 ASD subjects were known PDV carriers. This relatively small subpopulation limits this study to characterizing general patterns of burden, as opposed to effects of specific PDVs or genes. Also, a small fraction of subjects that are categorized as non-carriers could be PDV carriers. CONCLUSIONS: Liability arising from common and rare risk variations likely combines additively to determine risk of any individual diagnosed with ASD. On average, ASD subjects carry a substantial burden of common risk variation, even if they also carry a rare PDV affecting risk. En ligne : http://dx.doi.org/10.1186/s13229-021-00466-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 66 p.[article] How rare and common risk variation jointly affect liability for autism spectrum disorder [Texte imprimé et/ou numérique] / L. KLEI, Auteur ; L. L. MCCLAIN, Auteur ; B. MAHJANI, Auteur ; K. PANAYIDOU, Auteur ; S. DE RUBEIS, Auteur ; A. S. GRAHNAT, Auteur ; G. KARLSSON, Auteur ; Y. LU, Auteur ; N. MELHEM, Auteur ; X. XU, Auteur ; A. REICHENBERG, Auteur ; S. SANDIN, Auteur ; C. M. HULTMAN, Auteur ; Joseph D. BUXBAUM, Auteur ; K. ROEDER, Auteur ; B. DEVLIN, Auteur . - 66 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 66 p.
Mots-clés : Autism spectrum disorder De novo mutation Genomic-Best Linear Unbiased Prediction (G-BLUP) Liability Polygenic risk score Index. décimale : PER Périodiques Résumé : BACKGROUND: Genetic studies have implicated rare and common variations in liability for autism spectrum disorder (ASD). Of the discovered risk variants, those rare in the population invariably have large impact on liability, while common variants have small effects. Yet, collectively, common risk variants account for the majority of population-level variability. How these rare and common risk variants jointly affect liability for individuals requires further study. METHODS: To explore how common and rare variants jointly affect liability, we assessed two cohorts of ASD families characterized for rare and common genetic variations (Simons Simplex Collection and Population-Based Autism Genetics and Environment Study). We analyzed data from 3011 affected subjects, as well as two cohorts of unaffected individuals characterized for common genetic variation: 3011 subjects matched for ancestry to ASD subjects and 11,950 subjects for estimating allele frequencies. We used genetic scores, which assessed the relative burden of common genetic variation affecting risk of ASD (henceforth "burden"), and determined how this burden was distributed among three subpopulations: ASD subjects who carry a potentially damaging variant implicated in risk of ASD ("PDV carriers"); ASD subjects who do not ("non-carriers"); and unaffected subjects who are assumed to be non-carriers. RESULTS: Burden harbored by ASD subjects is stochastically greater than that harbored by control subjects. For PDV carriers, their average burden is intermediate between non-carrier ASD and control subjects. Both carrier and non-carrier ASD subjects have greater burden, on average, than control subjects. The effects of common and rare variants likely combine additively to determine individual-level liability. LIMITATIONS: Only 305 ASD subjects were known PDV carriers. This relatively small subpopulation limits this study to characterizing general patterns of burden, as opposed to effects of specific PDVs or genes. Also, a small fraction of subjects that are categorized as non-carriers could be PDV carriers. CONCLUSIONS: Liability arising from common and rare risk variations likely combines additively to determine risk of any individual diagnosed with ASD. On average, ASD subjects carry a substantial burden of common risk variation, even if they also carry a rare PDV affecting risk. En ligne : http://dx.doi.org/10.1186/s13229-021-00466-2 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459