Utrecht/Kenniscongres2016/14.1./ D. Brinksma/Determinanten lange termijnbeloop ADHD symptomen
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Determinanten lange termijnbeloop ADHD symptomen
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Utrecht/Kenniscongres2016/14.1./ D. Brinksma/Determinanten lange termijnbeloop ADHD symptomen
- 1. DETERMINANTEN LANGE TERMIJNBELOOP ADHD SYMPTOMEN ONTWIKKELINGSEFFECTEN EN GENETISCHE EFFECTEN Djûke M. Brinksma Pieter J. Hoekstra Annelies de Bildt Jan K. Buitelaar Barbara van den Hoofdakker Catharina A. Hartman Andrea Dietrich
- 2. ADHD • Prevalentie: 6% kinderen en 3% volwassenen • Genen, omgevingsfactoren spelen een rol in de etiologie én ontwikkeling van ADHD symptomen • Wat ‘kost’ ADHD? Persoon Maatschappij Gezin School
- 3. Onze studie • Determinanten lange termijnbeloop van ADHD symptomen over de adolescentie • TRacking Adolescents’ Individual Lives Survey [TRAILS]
- 5. Perinatale factoren Wat? Waarom ? Hoe? Zijn kandidaat genen, een set van pre- en perinatale factoren en diens interacties gerelateerd aan veranderende levels van ADHD symptomen van de vroege en late adolescentie? Perinatale factoren gerelateerd aan etiologie van ADHD, maar is dit ook zo tijdens het lange termijnbeloop van ADHD symptomen? Vragenlijsten en genetische data van 1,667 adolescenten
- 6. Perinatale Factoren: Resultaten Low activity MAOA High activity MAOA
- 7. Perinatale Factoren: Conclusies • Interacties tussen genetische factoren en perinatale factoren hebben invloed op veranderlijke niveau’s van ADHD symptomen • Invloed G×E op ADHD symptomen neemt af met leeftijd en lijkt te verdwijnen als adolescenten volwassen worden ONTWIKKELINGS -EFFETEN GENEN ZIJN BELANGRIJK OMGEVING IS BELANGRIJK
- 9. Stress Factoren Wat? Waarom ? Hoe? Birectionele associaties tussen ADHD symptomen en stressoren die variëren in afhankelijkheid bekeken tussen verschillende genotype van de 5-HTTLPR over de adolescentie Verhelderen beeld ADHD – stress relatie wat betreft richting, specifieke stressoren en verschillen in 5-HTTLPR Vragenlijsten en genetische data van 1,495 adolescenten
- 10. Stress Factoren: Resultaten 12 jaar 14 jaar 16 jaar PERSOONS GERELATEERDE STRESSOREN GEEN verschillen 5-HTTLPR WEL verschillen 5-HTTLPR
- 11. Stress Factoren: Resultaten OMGEVINGS GERELATEERDE STRESSOREN 12 jaar 14 jaar 16 jaar
- 12. • Adolescenten met een genetische kwetsbaarheid (homozygoot voor de S-allele 5-HTTLPR) én hoge ADHD symptomen lopen het risico om meer persoons gerelateerde stressoren te ervaren in de late adolescentie • Extra aandacht en preventie voor sociaal-emotionele problemen voor deze kwetsbare groep, met name naarmate ze ouder worden Stress Factoren: Conclusies ONTWIKKELINGS -EFFETEN GENEN ZIJN BELANGRIJK OMGEVING IS BELANGRIJK
- 14. Opvoedingsfactoren Wat? Waarom ? Hoe? Vragenlijsten en genetische data van 1,730 adolescenten Zijn kandidaat genen, opvoedingsfactoren en diens interacties gerelateerd aan lange termijnbeloop van ADHD symptomen? Kan het lange termijn beloop van ADHD symptomen worden voorspeld door genen, opvoedingsfactoren en diens interacties?
- 16. • Verschillende trajecten van ADHD symptomen te onderscheiden van vroege tot late adolescentie • De ervaring van afwijzing onderscheidend voor trajecten van ADHD symptomen • Genen of gen-omgevingsinteractie zijn zijn niet onderscheidend Opvoedingsfactoren: Conclusies ONTWIKKELINGS -EFFETEN OMGEVING IS BELANGRIJK
- 17. En nu ???
- 18. En nu ???
- 21. D.M. Brinksma MSc (Res.) • d.brinksma@accare.nl • www.linkedin.com/in/DMBrinksma Contact
Editor's Notes
- Aandachtstekortstoornis met hyperactiviteit (ADHD) is een multifactoriële en klinisch heterogene aandoening die wordt geassocieerd met een enorme financiële last, stress op gezinnen en negatieve academische en beroepsonderwijs uitkomsten ADHD is een klinisch heterogene aandoening waaraan meerdere factoren ten grondslag liggen. Twin and adoption studies show that ADHD has a strong genetic component, with heritability estimated at 76%
- Genen, omgevingsfactoren en diens gen-omgevingsinteracties (G×E’s) spelen een rol bij het ontstaan en de ontwikkeling van ADHD-symptomen. Echter, de invloed van deze factoren op het lange termijnbeloop van ADHD-symptomen is nog onvoldoende onderzocht. Het doel van ons onderzoek (onderdeel TRacking Adolescents’ Individual Lives Survey [TRAILS]) was om te kijken hoe verschillende leefdomeinen (o.a., stress, opvoeding, perinatale factoren), genen en G×E’s een rol spelen bij de ontwikkeling van ADHD-symptomen gedurende de adolescentie (10-18 jaar). Enkele resultaten: Jongeren met ADHD symptomen lopen het risico om meer stressvolle gebeurtenissen mee te maken maar dit effect is afhenkelijk van leeftijd en of zij een bepaald gen (S-allel HTTLPR) De invloed van interacties tussen genen en perinatale factoren hebben met name invloed op het beloop van ADHD symptomen tijdens de vroege adolescentie maar dit effect neemt af naarmate jongeren ouder worden.
- Therefore, we were interested in relationship between ADHD symptoms and stress. A growing literature implicates an association between life stressors (e.g. family and peer conflicts) and ADHD. On the other hand, it is often implied that life stressors may enhance ADHD symptoms. Surprisingly, few have examined the impact of ADHD symptoms on subsequent exposure to life stressors. For example, a prospective cohort study found that 5-year-olds with ADHD symptoms and problem behaviors were at elevated risk of becoming more socially isolated at age 12. Furhtermore, it has been reported that 5-year-olds with ADHD symptoms were at elevated risk of social isolation at age 12 years, but not the other way around (Matthews et al., 2015). However, it is very important this associations within the genetic conext of the 5-HTTLPR. A few recent studies have shown moderation of the relation between life stressors and ADHD by the serotonin transporter polymorphism. S-allele carriers were more reactive to life stress. Notably, in a large two-wave study of adolescents with (subthreshold) ADHD, only S-allele carriers showed a prospective positive association between life stressors and severity of ADHD symptoms, but not L-allele. This is in line with previous studies investigating this specific G×E on internalizing disorders. Specifically , the 5-HTTLPR S-allele has been shown to modify an individual’s response to stress and has been linked to increased stress sensitivity and reactivity compared to L-allele homozygotes, due to increased amygdala activation in response to emotional stimuli. The potentially differentiating role of the 5-HTTLPR genotype in the influence of ADHD symptoms on the exposure to life stressors is less straightforward. However, it is conceivable that S-allele carriers evoke more interpersonal conflict as part of their personal characteristics and behaviors. In these individuals also higher stress sensitivity may play a role, resulting in increased exposure to life stressors. Moreover, the role of genetic and environmental risk factors for ADHD has been suggested to vary across development. it is necessary to distinguish between person-related (‘dependent’) and environment-related (‘independent’) life stressors, The genetic and environmental origins of these stressors have been found to vary over adolescent development, which may suggest different developmental risk pathways of stress exposure in relation to psychopathology over time. Person-related life stressors are thought to be mainly ‘dependent’ on a person’s behavior and personality traits and are more genetically influenced than environment-related stressors, with genetic factors increasing in magnitude during the transition to adolescence. Environment-related life stressors are thought to occur in a person’s environment largely ‘independent’ of the person’s direct involvement and personal traits and are less genetically influenced than dependent stressors; shared environmental influences appear to play a greater role in exposure to life stressors in childhood, with decreasing influences during adolescence. This is in line with adolescents’ social-emotional development towards personality building and growing into independence. This sensitive period of life is typically characterized by increasing peer influences and social relations, self-awareness, sensitivity to environmental social cues (particularly social acceptance), inter-personal conflicts, and mental health problems, resulting from personal experiences, maturation, and neurobiological changes, which may make the developing adolescent more susceptible to person-related life stressors. In sum, we assume that with increasing adolescent age, person-related stressors are of greater importance in the relation between life stressors and ADHD symptoms than environment-related life stressors, while the role of the latter likely prevails during early adolescence, a period characterized by the child’s greater dependency on the family system and a possibly greater susceptibility to independent environment-related stressors than in later adolescence.
- Therefore, we were interested in relationship between ADHD symptoms and stress. A growing literature implicates an association between life stressors (e.g. family and peer conflicts) and ADHD. On the other hand, it is often implied that life stressors may enhance ADHD symptoms. Surprisingly, few have examined the impact of ADHD symptoms on subsequent exposure to life stressors. For example, a prospective cohort study found that 5-year-olds with ADHD symptoms and problem behaviors were at elevated risk of becoming more socially isolated at age 12. Furhtermore, it has been reported that 5-year-olds with ADHD symptoms were at elevated risk of social isolation at age 12 years, but not the other way around (Matthews et al., 2015). However, it is very important this associations within the genetic conext of the 5-HTTLPR. A few recent studies have shown moderation of the relation between life stressors and ADHD by the serotonin transporter polymorphism. S-allele carriers were more reactive to life stress. Notably, in a large two-wave study of adolescents with (subthreshold) ADHD, only S-allele carriers showed a prospective positive association between life stressors and severity of ADHD symptoms, but not L-allele. This is in line with previous studies investigating this specific G×E on internalizing disorders. Specifically , the 5-HTTLPR S-allele has been shown to modify an individual’s response to stress and has been linked to increased stress sensitivity and reactivity compared to L-allele homozygotes, due to increased amygdala activation in response to emotional stimuli. The potentially differentiating role of the 5-HTTLPR genotype in the influence of ADHD symptoms on the exposure to life stressors is less straightforward. However, it is conceivable that S-allele carriers evoke more interpersonal conflict as part of their personal characteristics and behaviors. In these individuals also higher stress sensitivity may play a role, resulting in increased exposure to life stressors. Moreover, the role of genetic and environmental risk factors for ADHD has been suggested to vary across development. it is necessary to distinguish between person-related (‘dependent’) and environment-related (‘independent’) life stressors, The genetic and environmental origins of these stressors have been found to vary over adolescent development, which may suggest different developmental risk pathways of stress exposure in relation to psychopathology over time. Person-related life stressors are thought to be mainly ‘dependent’ on a person’s behavior and personality traits and are more genetically influenced than environment-related stressors, with genetic factors increasing in magnitude during the transition to adolescence. Environment-related life stressors are thought to occur in a person’s environment largely ‘independent’ of the person’s direct involvement and personal traits and are less genetically influenced than dependent stressors; shared environmental influences appear to play a greater role in exposure to life stressors in childhood, with decreasing influences during adolescence. This is in line with adolescents’ social-emotional development towards personality building and growing into independence. This sensitive period of life is typically characterized by increasing peer influences and social relations, self-awareness, sensitivity to environmental social cues (particularly social acceptance), inter-personal conflicts, and mental health problems, resulting from personal experiences, maturation, and neurobiological changes, which may make the developing adolescent more susceptible to person-related life stressors. In sum, we assume that with increasing adolescent age, person-related stressors are of greater importance in the relation between life stressors and ADHD symptoms than environment-related life stressors, while the role of the latter likely prevails during early adolescence, a period characterized by the child’s greater dependency on the family system and a possibly greater susceptibility to independent environment-related stressors than in later adolescence.
- Therefore, we were interested in relationship between ADHD symptoms and stress. A growing literature implicates an association between life stressors (e.g. family and peer conflicts) and ADHD. On the other hand, it is often implied that life stressors may enhance ADHD symptoms. Surprisingly, few have examined the impact of ADHD symptoms on subsequent exposure to life stressors. For example, a prospective cohort study found that 5-year-olds with ADHD symptoms and problem behaviors were at elevated risk of becoming more socially isolated at age 12. Furhtermore, it has been reported that 5-year-olds with ADHD symptoms were at elevated risk of social isolation at age 12 years, but not the other way around (Matthews et al., 2015). However, it is very important this associations within the genetic conext of the 5-HTTLPR. A few recent studies have shown moderation of the relation between life stressors and ADHD by the serotonin transporter polymorphism. S-allele carriers were more reactive to life stress. Notably, in a large two-wave study of adolescents with (subthreshold) ADHD, only S-allele carriers showed a prospective positive association between life stressors and severity of ADHD symptoms, but not L-allele. This is in line with previous studies investigating this specific G×E on internalizing disorders. Specifically , the 5-HTTLPR S-allele has been shown to modify an individual’s response to stress and has been linked to increased stress sensitivity and reactivity compared to L-allele homozygotes, due to increased amygdala activation in response to emotional stimuli. The potentially differentiating role of the 5-HTTLPR genotype in the influence of ADHD symptoms on the exposure to life stressors is less straightforward. However, it is conceivable that S-allele carriers evoke more interpersonal conflict as part of their personal characteristics and behaviors. In these individuals also higher stress sensitivity may play a role, resulting in increased exposure to life stressors. Moreover, the role of genetic and environmental risk factors for ADHD has been suggested to vary across development. it is necessary to distinguish between person-related (‘dependent’) and environment-related (‘independent’) life stressors, The genetic and environmental origins of these stressors have been found to vary over adolescent development, which may suggest different developmental risk pathways of stress exposure in relation to psychopathology over time. Person-related life stressors are thought to be mainly ‘dependent’ on a person’s behavior and personality traits and are more genetically influenced than environment-related stressors, with genetic factors increasing in magnitude during the transition to adolescence. Environment-related life stressors are thought to occur in a person’s environment largely ‘independent’ of the person’s direct involvement and personal traits and are less genetically influenced than dependent stressors; shared environmental influences appear to play a greater role in exposure to life stressors in childhood, with decreasing influences during adolescence. This is in line with adolescents’ social-emotional development towards personality building and growing into independence. This sensitive period of life is typically characterized by increasing peer influences and social relations, self-awareness, sensitivity to environmental social cues (particularly social acceptance), inter-personal conflicts, and mental health problems, resulting from personal experiences, maturation, and neurobiological changes, which may make the developing adolescent more susceptible to person-related life stressors. In sum, we assume that with increasing adolescent age, person-related stressors are of greater importance in the relation between life stressors and ADHD symptoms than environment-related life stressors, while the role of the latter likely prevails during early adolescence, a period characterized by the child’s greater dependency on the family system and a possibly greater susceptibility to independent environment-related stressors than in later adolescence.
- De verschillende werelden moeten worden afgebeeld: links de wetenschap (screen shot data base, veel tijd) en rechts de klinische praktijk (patient met ADHD, snel willen helpen) Op deze manier willen wij nuance geven in het beel dat bestaat. Op deze manier proberen we de wereld om ons heen beter te begrijpen. Het is belangrijk om de contet te beschrijven. Veel aspecten in het leven staan niet los van elkaar en het is goed als we, inderdaad beetje bij beetje, dingen in een breder perspectief gaan zien. Context helpt bij het voeren van een discussie op basis van feiten en kennis. Persoonlijke medicatie gebaseerd op basis van DNA (met plaatje?)g Meten is soms meer dan weten, het kan een kader scheppen Hulpvraag snel willen helpen
- De verschillende werelden moeten worden afgebeeld: links de wetenschap (screen shot data base, veel tijd) en rechts de klinische praktijk (patient met ADHD, snel willen helpen) Op deze manier willen wij nuance geven in het beel dat bestaat. Op deze manier proberen we de wereld om ons heen beter te begrijpen. Het is belangrijk om de contet te beschrijven. Veel aspecten in het leven staan niet los van elkaar en het is goed als we, inderdaad beetje bij beetje, dingen in een breder perspectief gaan zien. Context helpt bij het voeren van een discussie op basis van feiten en kennis. Persoonlijke medicatie gebaseerd op basis van DNA (met plaatje?)g Meten is soms meer dan weten, het kan een kader scheppen Hulpvraag snel willen helpen
- Net als bij de voorkant van de doos weten we hoe het totaal plaatje er uit ziet, maar het lastige maar ook de uitdaging van een puzzel is om het plaatje compleet te krijgen.