The British journal of psychiatry : the journal of mental science, Jan 20, 2015
BackgroundWe previously reported an association between 5HTTLPR genotype and outcome following co... more BackgroundWe previously reported an association between 5HTTLPR genotype and outcome following cognitive-behavioural therapy (CBT) in child anxiety (Cohort 1). Children homozygous for the low-expression short-allele showed more positive outcomes. Other similar studies have produced mixed results, with most reporting no association between genotype and CBT outcome.AimsTo replicate the association between 5HTTLPR and CBT outcome in child anxiety from the Genes for Treatment study (GxT Cohort 2, n = 829).MethodLogistic and linear mixed effects models were used to examine the relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both cohorts were performed.ResultsThere was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2. Mega-analyses identified a significant association between 5HTTLPR and remission from all anxiety disorders at follow-up (odds ratio 0.45, P = 0.014), but not primary anxiety disorder outcomes.ConclusionsThe association between 5HTTLPR genotype...
Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of s... more Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner.
Five versions of the Interpersonal Needs Questionnaire (INQ), a self-report measure of perceived ... more Five versions of the Interpersonal Needs Questionnaire (INQ), a self-report measure of perceived burdensomeness and thwarted belongingness, have been used in recent studies (including 10-, 12-, 15-, 18-, and 25-items). Findings regarding the associations between perceived burdensomeness, thwarted belongingness, and suicidal ideation using different versions have been mixed, potentially due to differences in measurement scales. This study evaluated factor structure, internal consistency, and concurrent predictive validity of these five versions in three samples. Samples 1 and 2 were comprised of 449 and 218 undergraduates, respectively; Sample 3 included 114 adolescent psychiatric inpatients. All versions demonstrated acceptable internal consistency. The 10-item version and 15-item version demonstrated the best, most consistent model fit in confirmatory factor analyses. Both perceived burdensomeness and thwarted belongingness consistently predicted concurrent suicidal ideation on the 10-item INQ only. Future research should consider using the 15-item or 10-item versions.
The British journal of psychiatry : the journal of mental science, Jan 20, 2015
BackgroundWe previously reported an association between 5HTTLPR genotype and outcome following co... more BackgroundWe previously reported an association between 5HTTLPR genotype and outcome following cognitive-behavioural therapy (CBT) in child anxiety (Cohort 1). Children homozygous for the low-expression short-allele showed more positive outcomes. Other similar studies have produced mixed results, with most reporting no association between genotype and CBT outcome.AimsTo replicate the association between 5HTTLPR and CBT outcome in child anxiety from the Genes for Treatment study (GxT Cohort 2, n = 829).MethodLogistic and linear mixed effects models were used to examine the relationship between 5HTTLPR and CBT outcomes. Mega-analyses using both cohorts were performed.ResultsThere was no significant effect of 5HTTLPR on CBT outcomes in Cohort 2. Mega-analyses identified a significant association between 5HTTLPR and remission from all anxiety disorders at follow-up (odds ratio 0.45, P = 0.014), but not primary anxiety disorder outcomes.ConclusionsThe association between 5HTTLPR genotype...
Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of s... more Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT). Children with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response). Treatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response. Allele-specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype-dependent manner.
Five versions of the Interpersonal Needs Questionnaire (INQ), a self-report measure of perceived ... more Five versions of the Interpersonal Needs Questionnaire (INQ), a self-report measure of perceived burdensomeness and thwarted belongingness, have been used in recent studies (including 10-, 12-, 15-, 18-, and 25-items). Findings regarding the associations between perceived burdensomeness, thwarted belongingness, and suicidal ideation using different versions have been mixed, potentially due to differences in measurement scales. This study evaluated factor structure, internal consistency, and concurrent predictive validity of these five versions in three samples. Samples 1 and 2 were comprised of 449 and 218 undergraduates, respectively; Sample 3 included 114 adolescent psychiatric inpatients. All versions demonstrated acceptable internal consistency. The 10-item version and 15-item version demonstrated the best, most consistent model fit in confirmatory factor analyses. Both perceived burdensomeness and thwarted belongingness consistently predicted concurrent suicidal ideation on the 10-item INQ only. Future research should consider using the 15-item or 10-item versions.
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