scholarly journals Impulsivity and Venturesomeness in an Adult ADHD Sample: Relation to Personality, Comorbidity, and Polygenic Risk

2020 ◽  
Vol 11 ◽  
Author(s):  
Oliver Grimm ◽  
Heike Weber ◽  
Sarah Kittel-Schneider ◽  
Thorsten M. Kranz ◽  
Christian P. Jacob ◽  
...  
Keyword(s):  
Adult Adhd ◽  
Principal Component ◽  
Basic Feature ◽  
Self Report ◽  
Polygenic Risk Score ◽  
Comorbid Disorders ◽  
Psychiatric Comorbidities ◽  
Polygenic Risk ◽  
Different Genetic Background ◽  
Inattentive Type

While impulsivity is a basic feature of attention-deficit/hyperactivity disorder (ADHD), no study explored the effect of different components of the Impulsiveness (Imp) and Venturesomeness (Vent) scale (IV7) on psychiatric comorbidities and an ADHD polygenic risk score (PRS). We used the IV7 self-report scale in an adult ADHD sample of 903 patients, 70% suffering from additional comorbid disorders, and in a subsample of 435 genotyped patients. Venturesomeness, unlike immediate Impulsivity, is not specific to ADHD. We consequently analyzed the influence of Imp and Vent also in the context of a PRS on psychiatric comorbidities of ADHD. Vent shows a distinctly different distribution of comorbidities, e.g., less anxiety and depression. PRS showed no effect on different ADHD comorbidities, but correlated with childhood hyperactivity. In a complementary analysis using principal component analysis with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD criteria, revised NEO Personality Inventory, Imp, Vent, and PRS, we identified three ADHD subtypes. These are an impulsive–neurotic type, an adventurous–hyperactive type with a stronger genetic component, and an anxious–inattentive type. Our study thus suggests the importance of adventurousness and the differential consideration of impulsivity in ADHD. The genetic risk is distributed differently between these subtypes, which underlines the importance of clinically motivated subtyping. Impulsivity subtyping might give insights into the organization of comorbid disorders in ADHD and different genetic background.

scholarly journals Polygenic risk prediction based on singular value decomposition with applications to alcohol use disorder

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
James J. Yang ◽  
Xi Luo ◽  
Elisa M. Trucco ◽  
Anne Buu
Keyword(s):  
Alcohol Use ◽  
Alcohol Use Disorder ◽  
Large Scale ◽  
Methodological Issue ◽  
Secondary Data ◽  
Principal Component ◽  
Polygenic Risk Score ◽  
Adult Health ◽  
Polygenic Risk ◽  
Target Data

Abstract Background/aim The polygenic risk score (PRS) shows promise as a potentially effective approach to summarize genetic risk for complex diseases such as alcohol use disorder that is influenced by a combination of multiple variants, each of which has a very small effect. Yet, conventional PRS methods tend to over-adjust confounding factors in the discovery sample and thus have low power to predict the phenotype in the target sample. This study aims to address this important methodological issue. Methods This study proposed a new method to construct PRS by (1) approximating the polygenic model using a few principal components selected based on eigen-correlation in the discovery data; and (2) conducting principal component projection on the target data. Secondary data analysis was conducted on two large scale databases: the Study of Addiction: Genetics and Environment (SAGE; discovery data) and the National Longitudinal Study of Adolescent to Adult Health (Add Health; target data) to compare performance of the conventional and proposed methods. Result and conclusion The results show that the proposed method has higher prediction power and can handle participants from different ancestry backgrounds. We also provide practical recommendations for setting the linkage disequilibrium (LD) and p value thresholds.

scholarly journals Novel polygenic risk score links depression-related cortical transcriptomic changes to brain morphology and symptom severity

2021 ◽  
Author(s):  
Amy E Miles ◽  
Fernanda C Dos Santos ◽  
Enda M Byrne ◽  
Miguel E Renteria ◽  
Andrew M McIntosh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Risk Score ◽  
Symptom Severity ◽  
Self Report ◽  
Brain Morphology ◽  
Polygenic Risk Score ◽  
Depression Diagnosis ◽  
Polygenic Risk ◽  
Depression Risk ◽  
Common Genetic Variants

ABSTRACTOur group developed a transcriptome-based polygenic risk score (T-PRS) that uses common genetic variants to capture ‘depression-like’ shifts in cortical gene expression. Here, we mapped T-PRS onto diagnosis and symptom severity in major depressive disorder (MDD) cases and controls from the Psychiatric Genomics Consortium (PGC). To evaluate potential mechanisms, we further mapped T-PRS onto discrete measures of brain morphology and broad depression risk in healthy young adults. Genetic, self-report, and/or neuroimaging data were available in 29,340 PGC participants (59% women; 12,923 MDD cases, 16,417 controls) and 482 participants in the Duke Neurogenetics Study (DNS: 53% women; aged 19.8±1.2 years). T-PRS was computed from SNP data using PrediXcan to impute cortical expression levels of MDD-related genes from a previous post-mortem transcriptome meta-analysis. Sex-specific regressions were used to test effects of T-PRS on depression diagnosis, symptom severity, and Freesurfer-derived subcortical volume, cortical thickness, surface area, and local gyrification index in the PGC and DNS samples, respectively. T-PRS did not predict depression diagnosis (OR=1.007, 95%CI=[0.997-1.018]); however, it correlated with symptom severity in men (rho=0.175, p=7.957×10−4) in one large PGC cohort (N=762, 48% men). In DNS, T-PRS was associated with smaller amygdala volume in women (β=-0.186, t=-3.478, p=.001) and less prefrontal gyrification (max≤-2.970, p≤.006) in both sexes. In men, prefrontal gyrification mediated an indirect effect of T-PRS on broad depression risk (b=.005, p=.029), indexed using self-reported family history of depression. Depression-like shifts in cortical gene expression predict symptom severity in men and may contribute to disease vulnerability through their effect on cortical gyrification.

scholarly journals Minimal phenotyping yields GWAS hits of reduced specificity for major depression

2018 ◽  
Author(s):  
Na Cai ◽  
Joana A. Revez ◽  
Mark J Adams ◽  
Till F. M. Andlauer ◽  
Gerome Breen ◽  
...  
Keyword(s):  
Association Studies ◽  
Self Report ◽  
Risk Scores ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Polygenic Risk ◽  
Case Identification ◽  
Disease Case ◽  
Psychiatric Conditions ◽  
Cardinal Symptoms

AbstractMinimal phenotyping refers to the reliance on the use of a small number of self-report items for disease case identification. This strategy has been applied to genome-wide association studies (GWAS) of major depressive disorder (MDD). Here we report that the genotype derived heritability (h2SNP) of depression defined by minimal phenotyping (14%, SE = 0.8%) is lower than strictly defined MDD (26%, SE = 2.2%). This cannot be explained by differences in prevalence between definitions or including cases of lower liability to MDD in minimal phenotyping definitions of depression, but can be explained by misdiagnosis of those without depression or with related conditions as cases of depression. Depression defined by minimal phenotyping is as genetically correlated with strictly defined MDD (rG = 0.81, SE = 0.03) as it is with the personality trait neuroticism (rG = 0.84, SE = 0.05), a trait not defined by the cardinal symptoms of depression. While they both show similar shared genetic liability with neuroticism, a greater proportion of the genome contributes to the minimal phenotyping definitions of depression (80.2%, SE = 0.6%) than to strictly defined MDD (65.8%, SE = 0.6%). We find that GWAS loci identified in minimal phenotyping definitions of depression are not specific to MDD: they also predispose to other psychiatric conditions. Finally, while highly predictive polygenic risk scores can be generated from minimal phenotyping definitions of MDD, the predictive power can be explained entirely by the sample size used to generate the polygenic risk score, rather than specificity for MDD. Our results reveal that genetic analysis of minimal phenotyping definitions of depression identifies non-specific genetic factors shared between MDD and other psychiatric conditions. Reliance on results from minimal phenotyping for MDD may thus bias views of the genetic architecture of MDD and may impede our ability to identify pathways specific to MDD.

scholarly journals Evidence that polygenic risk for psychotic disorder is expressed in the domain of neurodevelopment, emotion regulation and attribution of salience

2017 ◽  
Vol 47 (14) ◽  
pp. 2421-2437 ◽  
Author(s):  
J. van Os ◽  
Y. van der Steen ◽  
Md. A. Islam ◽  
S. Gülöksüz ◽  
B. P. Rutten ◽  
...  
Keyword(s):  
Emotion Regulation ◽  
Psychotic Disorder ◽  
Repeated Measures ◽  
Threshold Model ◽  
Structured Interview ◽  
Self Report ◽  
Polygenic Risk Score ◽  
Genetic Associations ◽  
Polygenic Risk ◽  
The One

BackgroundThe liability-threshold model of psychosis risk predicts stronger phenotypic manifestation of the polygenic risk score (PRS) in the healthy relatives of patients, as compared with healthy comparison subjects.MethodsFirst-degree relatives of patients with psychotic disorder (871 siblings and 812 parents) and healthy comparison subjects (n= 523) were interviewed three times in 6 years. Repeated measures of two psychosis phenotypes, the Community Assessment of Psychic Experiences (CAPE; self-report – subscales of positive, negative and depressive symptoms) and the Structured Interview for Schizotypy – Revised (SIS-R; clinical interview – subscales of positive and negative schizotypy), were examined for association with PRS. Interview-based lifetime rate of depressive and manic episodes were also examined, as was association with repeated measures of intelligence quotient (IQ).ResultsIn the relatives, PRS was associated with CAPE/SIS-R total score (respectively,B= 0.12, 95% CI 0.02–0.22 andB= 0.11, 95% CI 0.02–0.20), the SIS-R positive subscale (B= 0.16, 95% CI 0.04–0.28), the CAPE depression subscale (B= 0.21, 95% CI 0.07–0.34), any lifetime affective episode (OR 3.1, 95% CI 1.04–9.3), but not with IQ (B= −1.8, 95% CI −8.0 to 4.4). In the controls, similar associations were apparent between PRS on the one hand and SIS-R total score, SIS-R positive, SIS-R negative, any lifetime affective episode and, in contrast, lower IQ (B= −8.5, 95% CI −15.5 to −1.6).ConclusionsIn non-ill people, polygenic risk for psychotic disorder is expressed pleiotropically in the domain of neurodevelopment, emotion regulation and attribution of salience. In subjects at elevated genetic risk, emerging expression of neurodevelopmental alterations may create floor effects, obscuring genetic associations.

Adult ADHD Self-Report Scale--Italian Version

2019 ◽  
Author(s):  
Antonella Somma ◽  
Serena Borroni ◽  
Andrea Fossati
Keyword(s):  
Adult Adhd ◽  
Self Report ◽  
Italian Version

1645-P: Polygenic Risk Score for Prediction of Complications in Men and Women with Type 2 Diabetes

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1645-P
Author(s):  
JOHANNE TREMBLAY ◽  
REDHA ATTAOUA ◽  
MOUNSIF HALOUI ◽  
RAMZAN TAHIR ◽  
CAROLE LONG ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Men And Women ◽  
Polygenic Risk ◽  
Prediction Of Complications

304-OR: Polygenic Risk Score Predicts Type 2 Diabetes Susceptibility in a Diverse Consumer Genetic Database

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 304-OR
Author(s):  
MICHAEL L. MULTHAUP ◽  
RYOSUKE KITA ◽  
NICHOLAS ERIKSSON ◽  
STELLA ASLIBEKYAN ◽  
JANIE SHELTON ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Score ◽  
Polygenic Risk Score ◽  
Diabetes Susceptibility ◽  
Genetic Database ◽  
Polygenic Risk

Samuel, D.B. & Ranseen, J.R. (2006, October). Stimulant medication’s effects on adult ADHD symptoms and NEO PI-R personality traits

2018 ◽  
Author(s):  
Douglas Samuel ◽  
John D. Ranseen
Keyword(s):  
Personality Traits ◽  
Neuropsychological Tests ◽  
Adult Adhd ◽  
Self Report ◽  
Emotional States ◽  
Limited Information ◽  
Stimulant Treatment ◽  
Hyperactivity Disorder ◽  
Dsm Iv ◽  
Adhd Symptomatology

Previous studies have indicated a consistent profile of basic personality traits correlated with adult Attention Deficit Hyperactivity Disorder (ADHD) (e.g., Ranseen, Campbell, & Baer, 1998; Nigg et al., 2002). In particular, research has found that low scores of the Conscientiousness trait and high scores on Neuroticism have been correlated with ADHD symptomatology. However, to date there is limited information concerning the range of effect resulting from medication treatment for adult ADHD. During an 18 month period, 60 adults were diagnosed with ADHD based on strict, DSM-IV criteria at an outpatient clinic. This evaluation included a battery of neuropsychological tests and a measure of general personality (i.e., the NEO PI-R). Eleven of these participants returned to complete the battery a second time. The pre-post comparisons revealed significant changes following sustained stimulant treatment on both the neuropsychological and self-report measures. These individuals also displayed significant changes on two domains of the NEO PI-R. They showed a significant decrease on the domain of Neuroticism, indicating that now see themselves as less prone to experience negative emotional states such as anxiety and depression. Additionally, they also reported a significant increase on their scores on the domain of conscientiousness. This increase suggests that they see themselves as more organized and dependable.

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