Identifying novel types of irritability using a developmental genetic approach

Lucy Riglin; Olga Eyre; Ajay Thapar; Argyris Stringaris; Ellen Leibenluf; Daniel S Pine; Kate Tilling; George Davey Smith; Michael C O'Donovan; Anita Thapar

doi:10.1176/appi.ajp.2019.18101134

Identifying novel types of irritability using a developmental genetic approach

Lucy Riglin, Olga Eyre, Ajay Thapar, Argyris Stringaris, Ellen Leibenluf, Daniel S Pine, Kate Tilling, George Davey Smith, Michael C O'Donovan, Anita Thapar

Research output: Contribution to journal › Article (Academic Journal) › peer-review

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Abstract

ObjectiveIrritability is a common reason for referral to services, strongly associated with impairment and negative outcomes, but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. This study 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.
MethodData were analyzed in the Avon Longitudinal Study of Parents and Children, a prospective UK population-based cohort. Irritability trajectory-classes were estimated for 7924 individuals with data at multiple time-points across childhood and adolescence (4 possible time-points from approximately ages 7 to 15 years). Psychiatricdiagnoses were assessed at approximately ages 7 and 15 years. Psychiatric genetic risk wasindexed by polygenic risk scores (PRS) for attention-deficit/hyperactivity disorder (ADHD) and depression derived using large genome-wide association study results.
ResultsFive irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), latechildhood limited (5.2%) and high-persistent (2.4%). The early-onset, high-persistent trajectory was associated with male preponderance, childhood ADHD (OR=108.64 (57.45-204.41), p<0.001) and ADHD PRS (OR=1.31 (1.09-1.58), p=0.005); the adolescent-onset, increasing trajectory was associated with female preponderance, adolescent depression (OR=5.14 (2.47-10.73), p<0.001) and depression PRS (OR=1.20, (1.05-1.38), p=0.009). Both trajectory classeswere associated with adolescent depression diagnosis and ADHD PRS.
ConclusionsThe developmental context of irritability may be important in its conceptualization: early-onsetpersistent irritability maybe more 'neurodevelopmental/ADHD-like’ and later-onset irritability more ‘depression/mood-like’. This has implications for treatment as well as nosology

Original language	English
Pages (from-to)	635-642
Number of pages	8
Journal	American Journal of Psychiatry
Volume	176
Issue number	8
Early online date	1 Jul 2019
DOIs	https://doi.org/10.1176/appi.ajp.2019.18101134
Publication status	E-pub ahead of print - 1 Jul 2019

Keywords

Child Psychiatry
Diagnosis and Classification
Irritability
Longitudinal
Genetic
Polygenic Risk Scores
ALSPAC

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10.1176/appi.ajp.2019.18101134

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This is the author accepted manuscript (AAM). The final published version (version of record) is available online via American Psychiatric Association at https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2019.18101134. Please refer to any applicable terms of use of the publisher.
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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. & Davey Smith, G.
1/04/18 → 31/03/23
Project: Research
NIHR BRC BEI
Sterne, J. A. C.
1/04/17 → 31/03/22
Project: Research, Parent

Cite this

@article{f1c9303659f240719e1e98436d9c726b,

title = "Identifying novel types of irritability using a developmental genetic approach",

abstract = "ObjectiveIrritability is a common reason for referral to services, strongly associated with impairment and negative outcomes, but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. This study used a developmental approach to test the hypothesis that there are several forms of irritability, including a {\textquoteleft}neurodevelopmental/ADHD-like{\textquoteright} type with onset in childhood and a {\textquoteleft}depression/mood{\textquoteright} type with onset in adolescence. MethodData were analyzed in the Avon Longitudinal Study of Parents and Children, a prospective UK population-based cohort. Irritability trajectory-classes were estimated for 7924 individuals with data at multiple time-points across childhood and adolescence (4 possible time-points from approximately ages 7 to 15 years). Psychiatricdiagnoses were assessed at approximately ages 7 and 15 years. Psychiatric genetic risk wasindexed by polygenic risk scores (PRS) for attention-deficit/hyperactivity disorder (ADHD) and depression derived using large genome-wide association study results. ResultsFive irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), latechildhood limited (5.2%) and high-persistent (2.4%). The early-onset, high-persistent trajectory was associated with male preponderance, childhood ADHD (OR=108.64 (57.45-204.41), p<0.001) and ADHD PRS (OR=1.31 (1.09-1.58), p=0.005); the adolescent-onset, increasing trajectory was associated with female preponderance, adolescent depression (OR=5.14 (2.47-10.73), p<0.001) and depression PRS (OR=1.20, (1.05-1.38), p=0.009). Both trajectory classeswere associated with adolescent depression diagnosis and ADHD PRS. ConclusionsThe developmental context of irritability may be important in its conceptualization: early-onsetpersistent irritability maybe more 'neurodevelopmental/ADHD-like{\textquoteright} and later-onset irritability more {\textquoteleft}depression/mood-like{\textquoteright}. This has implications for treatment as well as nosology",

keywords = "Child Psychiatry, Diagnosis and Classification, Irritability, Longitudinal, Genetic, Polygenic Risk Scores, ALSPAC",

author = "Lucy Riglin and Olga Eyre and Ajay Thapar and Argyris Stringaris and Ellen Leibenluf and Pine, {Daniel S} and Kate Tilling and {Davey Smith}, George and O'Donovan, {Michael C} and Anita Thapar",

year = "2019",

month = jul,

day = "1",

doi = "10.1176/appi.ajp.2019.18101134",

language = "English",

volume = "176",

pages = "635--642",

journal = "American Journal of Psychiatry",

issn = "0002-953X",

publisher = "American Psychiatric Association Publishing",

number = "8",

}

TY - JOUR

T1 - Identifying novel types of irritability using a developmental genetic approach

AU - Riglin, Lucy

AU - Eyre, Olga

AU - Thapar, Ajay

AU - Stringaris, Argyris

AU - Leibenluf, Ellen

AU - Pine, Daniel S

AU - Tilling, Kate

AU - Davey Smith, George

AU - O'Donovan, Michael C

AU - Thapar, Anita

PY - 2019/7/1

Y1 - 2019/7/1

N2 - ObjectiveIrritability is a common reason for referral to services, strongly associated with impairment and negative outcomes, but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. This study 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. MethodData were analyzed in the Avon Longitudinal Study of Parents and Children, a prospective UK population-based cohort. Irritability trajectory-classes were estimated for 7924 individuals with data at multiple time-points across childhood and adolescence (4 possible time-points from approximately ages 7 to 15 years). Psychiatricdiagnoses were assessed at approximately ages 7 and 15 years. Psychiatric genetic risk wasindexed by polygenic risk scores (PRS) for attention-deficit/hyperactivity disorder (ADHD) and depression derived using large genome-wide association study results. ResultsFive irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), latechildhood limited (5.2%) and high-persistent (2.4%). The early-onset, high-persistent trajectory was associated with male preponderance, childhood ADHD (OR=108.64 (57.45-204.41), p<0.001) and ADHD PRS (OR=1.31 (1.09-1.58), p=0.005); the adolescent-onset, increasing trajectory was associated with female preponderance, adolescent depression (OR=5.14 (2.47-10.73), p<0.001) and depression PRS (OR=1.20, (1.05-1.38), p=0.009). Both trajectory classeswere associated with adolescent depression diagnosis and ADHD PRS. ConclusionsThe developmental context of irritability may be important in its conceptualization: early-onsetpersistent irritability maybe more 'neurodevelopmental/ADHD-like’ and later-onset irritability more ‘depression/mood-like’. This has implications for treatment as well as nosology

AB - ObjectiveIrritability is a common reason for referral to services, strongly associated with impairment and negative outcomes, but is a nosological and treatment challenge. A major issue is how irritability should be conceptualized. This study 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. MethodData were analyzed in the Avon Longitudinal Study of Parents and Children, a prospective UK population-based cohort. Irritability trajectory-classes were estimated for 7924 individuals with data at multiple time-points across childhood and adolescence (4 possible time-points from approximately ages 7 to 15 years). Psychiatricdiagnoses were assessed at approximately ages 7 and 15 years. Psychiatric genetic risk wasindexed by polygenic risk scores (PRS) for attention-deficit/hyperactivity disorder (ADHD) and depression derived using large genome-wide association study results. ResultsFive irritability trajectory classes were identified: low (81.2%), decreasing (5.6%), increasing (5.5%), latechildhood limited (5.2%) and high-persistent (2.4%). The early-onset, high-persistent trajectory was associated with male preponderance, childhood ADHD (OR=108.64 (57.45-204.41), p<0.001) and ADHD PRS (OR=1.31 (1.09-1.58), p=0.005); the adolescent-onset, increasing trajectory was associated with female preponderance, adolescent depression (OR=5.14 (2.47-10.73), p<0.001) and depression PRS (OR=1.20, (1.05-1.38), p=0.009). Both trajectory classeswere associated with adolescent depression diagnosis and ADHD PRS. ConclusionsThe developmental context of irritability may be important in its conceptualization: early-onsetpersistent irritability maybe more 'neurodevelopmental/ADHD-like’ and later-onset irritability more ‘depression/mood-like’. This has implications for treatment as well as nosology

KW - Child Psychiatry

KW - Diagnosis and Classification

KW - Irritability

KW - Longitudinal

KW - Genetic

KW - Polygenic Risk Scores

KW - ALSPAC

U2 - 10.1176/appi.ajp.2019.18101134

DO - 10.1176/appi.ajp.2019.18101134

M3 - Article (Academic Journal)

C2 - 31256611

SN - 0002-953X

VL - 176

SP - 635

EP - 642

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

IS - 8

ER -

Identifying novel types of irritability using a developmental genetic approach

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Keywords

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IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

NIHR BRC BEI

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