11 results on '"O'Donovan, Michael"'
Search Results
2. Sex differences in anxiety and depression in children with ADHD:investigating genetic liability and comorbidity
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Martin, Joanna, Agha, Sharifah Shameem, Eyre, Olga, Riglin, Lucy, Langley, Kate, Hubbard, Leon, Stergiakouli , Evie, O'Donovan, Michael C, and Thapar, Anita
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sex differencesv ,polygenic risk scores ,anxiety disorders ,mental disorders ,depression ,ADHD ,ALSPAC ,behavioral disciplines and activities - Abstract
It is unknown why attention deficit hyperactivity disorder (ADHD) is more common in males, whereas anxiety and depression show a female population excess. We tested the hypothesis that anxiety and depression risk alleles manifest as ADHD in males. We also tested whether anxiety and depression in children with ADHD show a different etiology to typical anxiety and depression and whether this differs by sex. The primary clinical ADHD sample consisted of 885 (14% female) children. Psychiatric symptoms were assessed using standardized interviews. Polygenic risk scores (PRS) were derived using large genetic studies. Replication samples included independent clinical ADHD samples (N = 3,794; 25.7% female) and broadly defined population ADHD samples (N = 995; 33.4% female). We did not identify sex differences in anxiety or depression PRS in children with ADHD. In the primary sample, anxiety PRS were associated with social and generalized anxiety in males, with evidence of a sex-by-PRS interaction for social anxiety. These results did not replicate in the broadly defined ADHD sample. Depression PRS were not associated with comorbid depression symptoms. The results suggest that anxiety and depression genetic risks are not more likely to lead to ADHD in males. Also, the evidence for shared etiology between anxiety symptoms in those with ADHD and typical anxiety was weak and needs replication.
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- 2021
3. "Late-onset" ADHD symptoms in young adulthood: Is this ADHD?
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Riglin, Lucy, Wootton, Robyn E., Livingston, Lucy A., Agnew-Blais, Jessica, Arseneault, Louise, Blakey, Rachel, Agha, Sharifah Shameem, Langley, Kate, Collishaw, Stephan, O'Donovan, Michael C., Davey Smith, George, Stergiakouli, Evie, Tilling, Kate, and Thapar, Anita
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YOUNG adults ,ATTENTION-deficit hyperactivity disorder ,MONOGENIC & polygenic inheritance (Genetics) ,TASK performance ,COGNITIVE ability - Abstract
Objective: We investigated whether "late-onset" ADHD that emerges in adolescence/adulthood is similar in risk factor profile to: (1) child-onset ADHD, but emerges later because of scaffolding/compensation from childhood resources; and (2) depression, because it typically onsets in adolescence/adulthood and shows symptom and genetic overlaps with ADHD. Methods: We examined associations between late-onset ADHD and ADHD risk factors, cognitive tasks, childhood resources and depression risk factors in a population-based cohort followed-up to age 25 years (N =4224–9764). Results: Parent-rated late-onset ADHD was like child-onset persistent ADHD in associations with ADHD polygenic risk scores and cognitive task performance, although self-rated late-onset ADHD was not. Late-onset ADHD was associated with higher levels of childhood resources than child-onset ADHD and did not show strong evidence of association with depression risk factors. Conclusions: Late-onset ADHD shares characteristics with child-onset ADHD when parent-rated, but differences for self-reports require investigation. Childhood resources may delay the onset of ADHD. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Examining pathways between genetic liability for schizophrenia and patterns of tobacco and cannabis use in adolescence.
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Jones, Hannah J., Hammerton, Gemma, McCloud, Tayla, Hines, Lindsey A., Wright, Caroline, Gage, Suzanne H., Holmans, Peter, Jones, Peter B, Davey Smith, George, Linden, David E. J., O'Donovan, Michael C., Owen, Michael J., Walters, James T., Munafò, Marcus R., Heron, Jon, and Zammit, Stanley
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SCHIZOPHRENIA risk factors ,GENETICS of schizophrenia ,CANNABIS (Genus) ,GENETICS ,CONFIDENCE intervals ,SINGLE nucleotide polymorphisms ,COGNITION ,RISK assessment ,CELLULAR signal transduction ,DISEASE susceptibility ,DESCRIPTIVE statistics ,ODDS ratio ,EMOTIONS ,TOBACCO - Abstract
Background: It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies. Methods: Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes. Results: The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses. Conclusions: Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Associations between schizophrenia genetic risk, anxiety disorders and manic/hypomanic episode in a longitudinal population cohort study
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Richards, Alexander, Horwood, John, Boden, Joseph, Kennedy, Martin, Sellers, Ruth, Riglin, Lucy, Mistry, Sumit, Jones, Hannah, Smith, Daniel J., Zammit, Stanley, Owen, Michael, O'Donovan, Michael C., Harold, Gordon T., Boden, Joseph [0000-0003-1502-1608], Riglin, Lucy [0000-0002-5124-5230], Jones, Hannah [0000-0002-5883-9605], Smith, Daniel J [0000-0002-2267-1951], Zammit, Stanley [0000-0002-2647-9211], and Apollo - University of Cambridge Repository
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Adult ,Male ,Depressive Disorder, Major ,Multifactorial Inheritance ,Bipolar Disorder ,Adolescent ,Comorbidity ,ALSPAC ,anxiety ,CHDS ,Anxiety Disorders ,behavioral disciplines and activities ,United Kingdom ,Alcoholism ,Young Adult ,Risk Factors ,mental disorders ,polygenic risk score ,Schizophrenia ,Journal Article ,Humans ,Female ,Longitudinal Studies ,New Zealand - Abstract
Background: \ud Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.\ud \ud Aims: \ud We examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia.\ud \ud Method: \ud Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and – using linear regression – total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children).\ud \ud Results: \ud Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode.\ud \ud Conclusions: \ud The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.\ud \ud Declarations of interest: \ud None.
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- 2019
6. ADHD and depression: investigating a causal explanation.
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Riglin, Lucy, Leppert, Beate, Dardani, Christina, Thapar, Ajay K., Rice, Frances, O'Donovan, Michael C., Davey Smith, George, Stergiakouli, Evie, Tilling, Kate, and Thapar, Anita
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MENTAL depression risk factors ,GENETICS ,CONFIDENCE intervals ,ATTENTION-deficit hyperactivity disorder ,RISK assessment ,DISEASE relapse ,COMPARATIVE studies ,ATTRIBUTION (Social psychology) ,GENOMES ,ODDS ratio ,CAUSALITY (Physics) ,LONGITUDINAL method ,DISEASE complications ,CHILDREN ,ADULTS - Abstract
Background: Attention-deficit hyperactivity disorder (ADHD) is associated with later depression and there is considerable genetic overlap between them. This study investigated if ADHD and ADHD genetic liability are causally related to depression using two different methods. Methods: First, a longitudinal population cohort design was used to assess the association between childhood ADHD (age 7 years) and recurrent depression in young-adulthood (age 18–25 years) in N = 8310 individuals in the Avon Longitudinal Study of Parents and Children (ALSPAC). Second, two-sample Mendelian randomization (MR) analyses examined relationships between genetic liability for ADHD and depression utilising published Genome-Wide Association Study (GWAS) data. Results: Childhood ADHD was associated with an increased risk of recurrent depression in young-adulthood (OR 1.35, 95% CI 1.05–1.73). MR analyses suggested a causal effect of ADHD genetic liability on major depression (OR 1.21, 95% CI 1.12–1.31). MR findings using a broader definition of depression differed, showing a weak influence on depression (OR 1.07, 95% CI 1.02–1.13). Conclusions: Our findings suggest that ADHD increases the risk of depression later in life and are consistent with a causal effect of ADHD genetic liability on subsequent major depression. However, findings were different for more broadly defined depression. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Identifying Novel Types of Irritability Using a Developmental Genetic Approach.
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Riglin, Lucy, Eyre, Olga, Thapar, Ajay K., Stringaris, Argyris, Leibenluft, Ellen, Pine, Daniel S., Tilling, Kate, Davey Smith, George, O'Donovan, Michael C., and Thapar, Anita
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IRRITABILITY (Psychology) ,MENTAL health services ,ATTENTION-deficit hyperactivity disorder ,PARENT-child relationships ,PSYCHIATRIC diagnosis ,THERAPEUTICS - Abstract
Objective: Irritability, which is strongly associated with impairment and negative outcomes, is a common reason for referral to mental health services but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. The authors used a developmental approach to test the hypothesis that there are several forms of irritability, including a "neurodevelopmental/ADHD-like" type, with onset in childhood, and a "depression/mood" type, with onset in adolescence.Methods: Data were analyzed from the Avon Longitudinal Study of Parents and Children, a prospective U.K. population-based cohort. Irritability trajectory classes were estimated for 7,924 individuals with data at multiple time points across childhood and adolescence (four possible time points from approximately ages 7 to 15). Psychiatric diagnoses were assessed at approximately ages 7 and 15. Psychiatric genetic risk was indexed by polygenic risk scores (PRSs) for attention deficit hyperactivity disorder (ADHD) and depression, derived using large genome-wide association study results.Results: Five irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), late-childhood limited (5.2%), and high-persistent (2.4%). The early-onset high-persistent trajectory was associated with male preponderance, childhood ADHD (odds ratio=108.64, 95% CI=57.45-204.41), and ADHD PRS (odds ratio=1.31, 95% CI=1.09-1.58). The adolescent-onset increasing trajectory was associated with female preponderance, adolescent depression (odds ratio=5.14, 95% CI=2.47-10.73), and depression PRS (odds ratio=1.20, 95% CI=1.05-1.38). Both the early-onset high-persistent and adolescent-onset increasing trajectory classes were associated with adolescent depression diagnosis and ADHD PRS.Conclusions: The developmental context of irritability may be important in its conceptualization: early-onset persistent irritability may be more neurodevelopmental/ADHD-like and later-onset irritability more depression/mood-like. These findings have implications for treatment as well as nosology. [ABSTRACT FROM AUTHOR]- Published
- 2019
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8. Developmental Contributions of Schizophrenia Risk Alleles and Childhood Peer Victimization to Early-Onset Mental Health Trajectories.
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Riglin, Lucy, Hammerton, Gemma, Heron, Jon, Collishaw, Stephan, Arseneault, Louise, Thapar, Ajay K., Maughan, Barbara, O'Donovan, Michael C., and Thapar, Anita
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DIAGNOSIS of schizophrenia ,AGE factors in disease ,COMPARATIVE studies ,GENETICS ,LONGITUDINAL method ,RESEARCH methodology ,MEDICAL cooperation ,MENTAL health ,PSYCHOLOGICAL tests ,PSYCHOLOGY ,PATHOLOGICAL psychology ,RESEARCH ,RISK assessment ,SCHIZOPHRENIA ,PSYCHOLOGY of crime victims ,EVALUATION research ,CONFOUNDING variables - Abstract
Objective: Twin studies suggest that genetic factors contribute to continuity in mental health problems and that environmental factors are the major contributor to developmental change. The authors investigated the influence of psychiatric risk alleles on early-onset mental health trajectories and whether the trajectories were subsequently modified by exposure to childhood victimization.Methods: The sample was a prospective U.K. population-based cohort, the Avon Longitudinal Study of Parents and Children. The developmental trajectories of emotional problems were estimated in childhood (approximately ages 4-8 years) and adolescence (approximately ages 12-17 years). Psychiatric risk alleles were indexed by polygenic risk scores (PRS) for schizophrenia using genome-wide association study results from the Psychiatric Genomics Consortium. Chronic peer victimization in late childhood (ages 8.5 and 10.5 years) was assessed as an index of environmental exposure. Individuals with sufficient data on emotional problems, the PRS, and victimization were included in the main analyses (N=3,988).Results: Higher schizophrenia PRSs were associated with a trajectory of early-onset increasing emotional problems (odds ratio=1.18, 95% CI=1.02-1.36) compared with a trajectory of low-stable emotional problems. Subsequent exposure to victimization increased the likelihood of transitioning from a trajectory of low-stable emotional problems during childhood (before exposure) to an increasing trajectory in adolescence (after exposure) (odds ratio=2.59, 95% CI=1.48-4.53).Conclusions: While the early development of emotional problems was associated with genetic risk (schizophrenia risk alleles), the subsequent course of emotional problems for those who might otherwise have remained on a more favorable trajectory was altered by exposure to peer victimization, which is a potentially modifiable environmental exposure. [ABSTRACT FROM AUTHOR]- Published
- 2019
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9. Neurocognitive abilities in the general population and composite genetic risk scores for attention-deficit hyperactivity disorder.
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Martin, Joanna, Hamshere, Marian L., Stergiakouli, Evangelia, O'Donovan, Michael C., and Thapar, Anita
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ATTENTION-deficit hyperactivity disorder ,COGNITION ,STATISTICAL correlation ,GENETIC polymorphisms ,LONGITUDINAL method ,NEUROPSYCHOLOGICAL tests ,MEMORY ,REGRESSION analysis ,T-test (Statistics) ,SECONDARY analysis ,STRUCTURAL equation modeling ,RELATIVE medical risk ,DATA analysis software ,GENOTYPES ,GENETICS - Abstract
Background The genetic architecture of ADHD is complex, with rare and common variants involved. Common genetic variants (as indexed by a composite risk score) associated with clinical ADHD significantly predict ADHD and autistic-like behavioural traits in children from the general population, suggesting that ADHD lies at the extreme of normal trait variation. ADHD and other neurodevelopmental disorders share neurocognitive difficulties in several domains (e.g. impaired cognitive ability and executive functions). We hypothesised that ADHD composite genetic risk scores derived from clinical ADHD cases would also contribute to variation in neurocognitive abilities in the general population. Methods Children ( N = 6,832) from a UK population cohort, the Avon Longitudinal Study of Parents and Children ( ALSPAC), underwent neurocognitive testing. Parent-reported measures of their children's ADHD and autistic-like traits were used to construct a behavioural latent variable of 'neurodevelopmental traits'. Composite genetic risk scores for ADHD were calculated for ALSPAC children based on findings from an independent ADHD case-control genome-wide association study. Structural equation modelling was used to assess associations between ADHD composite genetic risk scores and IQ, working memory, inhibitory control and facial emotion recognition, as well as the latent 'neurodevelopmental trait' measure. Results The results confirmed that neurocognitive and neurodevelopmental traits are correlated in children in the general population. Composite genetic risk scores for ADHD were independently associated with lower IQ ( β = −.05, p < .001) and working memory performance ( β = −.034, p = .013), even after accounting for the relationship with latent neurodevelopmental behavioural trait scores. No associations were found between composite genetic risk scores and inhibitory control or emotion recognition ( p > .05). Conclusions These findings suggest that common genetic variants relevant to clinically diagnosed ADHD have pleiotropic effects on neurocognitive traits as well as behavioural dimensions in the general population. This further suggests that the well-recognised association between cognition and neurodevelopmental behavioural traits is underpinned at a biological level. [ABSTRACT FROM AUTHOR]
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- 2015
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10. A Population-Based Study of Genetic Variation and Psychotic Experiences in Adolescents.
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Zammit, Stanley, Hamshere, Marian, Dwyer, Sarah, Georgiva, Lyudmila, Timpson, Nic, Moskvina, Valentina, Richards, Alexander, Evans, David M, Lewis, Glyn, Jones, Peter, Owen, Michael J., and O’Donovan, Michael C.
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PSYCHOSES ,PSYCHOSES risk factors ,CONFIDENCE intervals ,HUMAN genome ,PROBABILITY theory ,RESEARCH funding ,SCHIZOPHRENIA ,LOGISTIC regression analysis ,SECONDARY analysis ,DEMOGRAPHIC characteristics ,DATA analysis software ,ODDS ratio ,ADOLESCENCE ,GENETICS - Abstract
Psychotic experiences are not uncommon in general population samples, but no studies have examined to what extent confirmed risk variants for schizophrenia are associated with such experiences. A total of 3483 children in a birth cohort study participated in semistructured interviews for psychotic experiences at ages 12 and 18. We examined whether (1) a composite measure of risk for schizophrenia conferred by common alleles (polygenic score) was associated with psychotic experiences, (2) variants with genome-wide evidence for association with schizophrenia were associated with psychotic experiences, and (3) we could identify genetic variants for psychotic experiences using a genome-wide association (GWA) approach. We found no evidence that a schizophrenia polygenic score, or variants showing genome-wide evidence of association with schizophrenia, were associated with adolescent psychotic experiences within the general population. In fact, individuals who had a higher number of risk alleles for genome-wide hits for schizophrenia showed a decreased risk of psychotic experiences. In the GWA study, no variants showed GWA for psychotic experiences, and there was no evidence that the strongest hits (P < 5 × 10−5) were enriched for variants associated with schizophrenia in large consortia. Although polygenic scores are weak tools for prediction of schizophrenia, they show strong evidence of association with this disorder. Our findings, however, lend little support to the hypothesis that psychotic experiences in population-based samples of adolescents share a comparable genetic architecture to schizophrenia, or that utilizing a broader and more common phenotype of psychotic experiences will be an efficient approach to increase understanding of the genetic etiology of schizophrenia. [ABSTRACT FROM PUBLISHER]
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- 2014
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11. Associations between schizophrenia genetic risk, anxiety disorders and manic/hypomanic episode in a longitudinal population cohort study
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Richards, Alexander, Horwood, John, Boden, Joseph, Kennedy, Martin, Sellers, Ruth, Riglin, Lucy, Mistry, Sumit, Jones, Hannah, Smith, Daniel J, Zammit, Stanley, Owen, Michael, O'Donovan, Michael C, and Harold, Gordon T
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Adult ,Male ,Depressive Disorder, Major ,Multifactorial Inheritance ,Bipolar Disorder ,Adolescent ,Comorbidity ,ALSPAC ,CHDS ,anxiety ,behavioral disciplines and activities ,Anxiety Disorders ,United Kingdom ,3. Good health ,Alcoholism ,Young Adult ,Risk Factors ,mental disorders ,polygenic risk score ,Schizophrenia ,Humans ,Female ,Longitudinal Studies ,New Zealand - Abstract
BACKGROUND: Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.AimsWe examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia. METHOD: Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and - using linear regression - total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children). RESULTS: Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode. CONCLUSIONS: The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.Declarations of interestNone.
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