Dr Duncan Manders (Child and Adolescent Mental Health Service, NHS Lothian, UK) opened Day 1 of the 11th Meeting of Minds and set the stage for an interactive and thought-provoking meeting, which included engaging plenary sessions on the genetics and heritability of ADHD, entrepreneurship and ADHD and psychiatric comorbidities.
Dr Manders thanked Takeda for hosting the meeting and welcomed Jon Neal (Managing Director of Takeda, UK and Ireland) to the podium to discuss the company’s ethos, its neuroscience research and development activities and its commitment to collaboration and education.
Plenary 1: ADHD in families – genetics and heritability
Moderator: Professor Tobias Banaschewski (Central Institute of Mental Health, Mannheim, Germany)
Genetic and environmental influences on ADHD; what’s new?
Professor Philip Asherson (King’s College London, UK) opened this session by reminding delegates that as evidenced by family, adoption and twin studies, ADHD can run in families.1 Professor Asherson emphasised that ADHD has a highly heritable component, and that genetic and environmental factors may contribute2 but it has been difficult to pinpoint a causal component linked to ADHD.
Professor Asherson discussed some established associations between environmental measures and ADHD and began with social environmental influences. He discussed how in a Romanian institutional orphan-rearing study, severe early deprivation for the first 0 to 42 months of life increased parent- and teacher-reported scores of inattention and overactivity in UK-adopted children compared with within-UK adoptees.3 Professor Asherson also mentioned that social adversity and hostile parenting are other social environmental influences that have been linked to symptoms of ADHD.4,5 He explained that in one study, there were significant associations found between mothers with ADHD, hostile parenting behaviour and a child’s ADHD symptoms, and that genetically influenced ADHD attributes in children can lead to more hostile parenting from mothers.5
Professor Asherson then went on to discuss the putative association of prenatal smoking and ADHD. He presented evidence from a study which showed that only genetically related children of mothers who smoked during pregnancy were more likely to develop ADHD compared with genetically unrelated mothers who had smoked during pregnancy.6 This suggests that the observed link between maternal smoking during pregnancy and ADHD may be due to an inherited effect.6
Shared genetic risk factors between ADHD and conduct problems were also emphasised, and it was highlighted that ADHD plus conduct problems is a more severe phenotype of genetic loading and clinical severity.7
Professor Asherson concluded that ADHD may be influenced by genetics and although there are many environmental measures associated with ADHD,2 he felt that a causal role is uncertain in most cases. He suggested that gene–environment interactions are likely to play a role in ADHD but to date, this has not been confirmed.
Professor Asherson: “Finding which [factors] are causal can be tricky [for ADHD]”
Discovery of first genome-wide significant risk loci for ADHD
Associate Professor Ditte Demontis (Aarhus University, Denmark) began the next session and discussed her recently published study that aimed to identify common risk variants for ADHD and characterise the polygenic architecture of the disorder.8 Using a large-scale meta-analysis of the iPSYCH cohort (including almost all cases of ADHD born in Denmark between 1981 and 2005 and diagnosed before 2013) and 11 cohorts from the Psychiatric Genomics Consortium, DNA extracted from individuals with ADHD was analysed.8 This genome-wide association study meta-analysis included 20,183 individuals with ADHD and 35,191 without ADHD.8 Meta-analysis identified 12 independent genome-wide significant loci that genetically correlated with both diagnosed ADHD and symptoms of ADHD in the general population.8 Professor Demontis then presented further analysis that indicated that genetic correlations of ADHD with other phenotypes had also been found, e.g. cognition, psychiatric disorders, weight/body mass index, smoking, reproduction and parental age at death.8 She also highlighted that several interesting loci located in or near the FOXP2 gene on chromosome 7 are implicated in neurodevelopmental processes and could be biologically relevant to ADHD.8,9
Professor Demontis: “[This study may] help clinicians pinpoint comorbidities as there is a genetic risk factor [for ADHD]”
ADHD: a family affair
Professor David Daley (University of Nottingham, UK) began his session by stating that he was going to discuss families and ADHD rather than genetics. He then presented delegates with five questions and discussed supporting evidence that represents the general consensus of the responses to these questions.
1) Does parental ADHD bias parental reports of their children’s ADHD symptoms?
Professor Daley proposed that given the nature of ADHD, parental symptoms of ADHD, such as inattention and impulsivity, may bias parental reporting of their children’s ADHD. He pointed out that this could be problematic as clinicians are reliant on parental reporting of ADHD for both diagnosis and treatment monitoring. Professor Daley stated that there was a lack of rigorous data examining this important issue, and that only one really high-quality study had been carried out, published in 2003,10 that compared rates of reported ADHD among three groups of children with ADHD: no parental ADHD (n = 231), maternal ADHD (n = 63) and paternal ADHD (n = 57).10 Results showed that with the exception of one symptom (shifts activities), the rates of reporting between groups were not different.10 He indicated that these results were consistent, regardless of child gender or referral status, and that they do not support the notion that parental ADHD affects reports of childhood ADHD.10
2) Is parental ADHD associated with more severe clinical presentation?
Professor Daley presented data from a study that explored the relationship between maternal ADHD and the clinical presentation of their child’s ADHD (n = 117) compared with those without ADHD (n = 149).11 This study showed that maternal ADHD symptoms are associated with an increase in the symptom severity of ADHD (p = 0.01) as well as reduced quality of life (p = 0.003) for children.11
3) How does parental ADHD impact on parenting?
A study that explored maternal parenting of 192 pre-school children with and without ADHD was next presented by Professor Daley.12 This study demonstrated that child ADHD symptoms were associated with negative maternal comments, and maternal ADHD symptoms were linked to a negative emotional relationship (e.g. criticism and low warmth).12 However, maternal ADHD symptoms were associated with more positive parenting behaviours towards children with ADHD (similarity-fit hypothesis).12 Professor Daley suggested that in his opinion, it may be easier for a mother with ADHD to be more empathetic in her parenting towards her child with ADHD. Interestingly, this effect is the opposite for paternal ADHD with high levels of ADHD in fathers exacerbating the effects of their child’s ADHD (similarity-misfit hypothesis).13
4) How might parental ADHD impact on pharmacological treatment?
Professor Daley stated that he felt that parental ADHD (e.g. forgetfulness, lack of response, lack of belief) may influence the use of pharmacological treatment and response in children with ADHD; however, very little is known about this. He highlighted that most studies on adherence to pharmacological treatment and treatment discontinuation use pharmacy databases and these do not contain information on parental ADHD status. Professor Daley did say that the Multimodal Treatment Study of Children with ADHD (MTA) study did explore the impact of parental depression on pharmacological treatment management but that parental ADHD was not studied.14
5) How might parental ADHD impact behavioural treatment?
Engagement in and maintenance of behavioural interventions may be difficult for parents with ADHD. Professor Daley pointed out that studies have shown that the effects of behavioural parent training are reduced in children of mothers with high levels of ADHD.15 In addition, it has been shown that parents who are at risk for ADHD may have difficulty maintaining treatment effects for themselves and their child.16
Professor Daley concluded his presentation with the following take-home messages:
- Parental ratings of child ADHD symptoms can be relied upon, even if the parent has ADHD
- High levels of parental ADHD symptoms could be a marker for more severe clinical presentation of a child’s ADHD, and this could be considered in a treatment plan
- Parental ADHD may have an impact on a child’s ADHD; therefore, clinicians should use the empathy that may arise from maternal ADHD to help keep the family together and reflect on how treatment regimens and engagement in behavioural interventions can be made easier for parents with ADHD
Professor David Daley: “Clinically, we are so heavily reliant on parental reporting for child diagnosis [of ADHD]”
Entrepreneurship and ADHD: how ADHD can be productively harnessed
Professor Johan Wiklund (Syracuse University, NY, USA) concluded the first plenary session by discussing how ADHD can be productively harnessed through entrepreneurship. Professor Wiklund described how entrepreneurs could design jobs to fit their unique needs and strengths. He stated that in his opinion, instead of viewing individuals with ADHD as having problems adapting their energy levels to what a situation requires, those with ADHD might instead have problems adapting the situation to what their energy level requires. Professor Wiklund presented his own model for the uncertainty of entrepreneurship where a trial-and-error approach is better than an analytical approach, and therefore, more suited to individuals with ADHD. He also opined that symptoms of ADHD could be linked to entrepreneurship as follows: reward-seeking and disinhibition links to innovation and creativity; activation level and lack of premeditation links to action despite uncertainty; and sensation-seeking links to risk-taking.17
Professor Wiklund then provided a few examples of where ADHD has been associated with entrepreneurship: hyperactivity and impulsivity have a positive influence on self-employment (and inattention has no negative influence); ADHD symptoms and diagnosis may increase aspirations of entrepreneurship; ADHD symptoms may enhance the chances of an individual starting a business; and individuals with a diagnosis of ADHD believe entrepreneurship ‘fits’ them.18-21 Professor Wiklund concluded that there are many negative implications of ADHD but the positive aspects are less well studied; however, by changing the context and not the individual with ADHD then certain contexts are well suited for this disorder.
Professor Wiklund: “Individuals with ADHD are by definition human outliers”
Plenary 2: ADHD and comorbidities
Moderator: Professor Luis Rohde (Federal University of Rio Grande do Sul, Porto Alegre, Brazil)
ADHD and autism spectrum disorder
Professor Jan Buitelaar (Radboud University Medical Centre, The Netherlands) began the second plenary session by describing the clinical overlap between ADHD and autism spectrum disorder (ASD) and how this may have clinical implications as well as an effect on services and pharmacological treatments. He then reminded the audience that the core symptoms of ADHD are hyperactivity, impulsivity and inattention as defined by the Diagnostic and Statistical Manual of Mental Disorders – 5th Edition (DSM-5TM); and that social-communication deficits, fixated interests, repetitive behaviours and abnormal sensory processing are the core symptoms of ASD.22 Professor Buitelaar then highlighted that although ADHD and ASD are developmental disorders with early onset and a strong persistence over time, the age of onset is earlier for ASD (starting before age 3 years vs 12 years for ADHD).22 Professor Buitelaar pointed out that 20‒50% of children with ADHD also meet the criteria for ASD and that inattention is the link between these two disorders.23
Professor Buitelaar presented his own general schema for methods to assess and diagnose ADHD and ASD that included: gathering and interpreting information on comorbid psychopathologies in the light of what is known about an individual’s history related to ASD; use of multiple methods and informants where possible; and a recognition that older people with ASD may present differently from young children due to differences in developmental level and experience. He also thought that many girls and women with ASD may not be diagnosed as they can, in his opinion, become very good at masking their disorder.
Professor Buitelaar then emphasised that for him, the aims and objectives for treatment of individuals with ADHD and ASD is ‘more care than cure’. He felt that clinicians should aim to reduce symptoms of ADHD and/or ASD, reduce comorbid symptoms, reduce the risk of further complications, educate the individual and their environment about the disorder, adapt the environment to the individual’s needs, enhance the individual’s/parents’/teacher’s coping skills and change maladaptive views.
He then presented evidence that ADHD comorbidity in ASD requires clinical attention. For example, individuals with ADHD and ASD have more general psychopathology regarding both internalising and externalising symptoms.24 Those with ADHD and ASD have more impairments in social interaction, and symptoms of ADHD in children with ASD are associated with more severe oppositional, aggressive and ASD symptoms.25,26 Professor Buitelaar also mentioned that in his experience, ADHD symptoms might interfere with an individual’s ability to benefit from educational and behaviour modification interventions.
Professor Buitelaar: “ASD is a very important comorbidity for ADHD, [clinicians] should probe for ASD”
ADHD and substance use disorder
Dr Cleo Crunelle (University Hospital Brussels, Belgium) began her presentation by highlighting that earlier-onset, severe, chronic and poly-substance use disorder (SUD) is all associated with ADHD.27 She stated that comorbidity of ADHD and SUD may influence further treatment and response to treatment.27 Dr Crunelle then presented a variety of evidence showing that depending on the substance abused, pharmacological treatments for ADHD may not be effective in reducing the effects of ADHD and SUD. However, treatment with methylphenidate for individuals with ADHD and amfetamine abuse can be effective for ADHD and SUD.28 Additionally, extended-release mixed amfetamine salts along with cognitive behavioural therapy has been effective in reducing ADHD and SUD symptoms in individuals abusing cocaine.29
Dr Crunelle felt that it was important that all adults with ADHD are also screened for SUD and that a history of substance use could be gathered using a personal interview, screening assessments (e.g. Alcohol Use Disorders Identification Test and Drug Abuse Screening Test) and using toxicological confirmation (e.g. blood, hair and urine samples).27 The preliminary diagnosis should then be confirmed via follow ups as the presentation of ADHD can change over time in those with SUD. Dr Crunelle opined that it was important that the SUD is treated in those with ADHD, and that the effect of pharmacotherapy is enhanced when combined with psychotherapy.27 She highlighted that the risk of misuse and diversion could be greater in individuals with ADHD and SUD, especially for adolescents and young adults; therefore, clinicians may consider long-acting pharmacotherapies.27 Dr Crunelle also stated that the risk of adverse events in individuals with ADHD and SUD is comparable with those without SUD and pharmacotherapy may not precipitate the onset of SUD.27 She recommended that individuals with ADHD and SUD are closely monitored and they should be informed about the importance of safeguarding medication.27 Dr Crunelle concluded her presentation by advising that a combined treatment approach should be used for individuals with ADHD and SUD and treatment with stimulants should not necessarily be avoided.27
Dr Crunelle: “Focus on alcohol- and drug-free periods in an individual’s life [during history taking for SUD]”
ADHD and occupational outcomes: the role of psychiatric comorbidity
Andreas Jangmo, a PhD student from the Karolinska Institutet, Stockholm, Sweden, concluded the second plenary session. He first discussed the effect of ADHD on occupational outcomes; mentioning that ADHD is associated with unemployment and workplace impairment and that education can have a large mediating effect, as can psychiatric comorbidity.30-32 Mr Jangmo then opined that there are few large-scale studies investigating the role of psychiatric comorbidity in ADHD and occupational outcomes, and that the longitudinal relationship has also not been studied. He then presented unpublished data from his own research that aimed to address the following: 1) association between ADHD and occupational outcomes; 2) the role of education and psychiatric comorbidity in this relationship; and 3) how these relationships evolve over time.
Mr Jangmo: “Data suggests that ADHD is associated with occupational impairment”
- Faraone SV, Biederman J, Monuteaux MC. Toward guidelines for pedigree selection in genetic studies of attention deficit hyperactivity disorder. Genet Epidemiol 2000; 18: 1-16.
- Banerjee TD, Middleton F, Faraone SV. Environmental risk factors for attention-deficit hyperactivity disorder. Acta Paediatr 2007; 96: 1269-1274.
- Kreppner JM, O’Connor TG, Rutter M. Can inattention/overactivity be an institutional deprivation syndrome? J Abnorm Child Psychol 2001; 29: 513-528.
- Froehlich TE, Anixt JS, Loe IM, et al. Update on environmental risk factors for attention-deficit/hyperactivity disorder. Curr Psychiatry Rep 2011; 13: 333-344.
- Harold GT, Leve LD, Barrett D, et al. Biological and rearing mother influences on child ADHD symptoms: revisiting the developmental interface between nature and nurture. J Child Psychol Psychiatry 2013; 54: 1038-1046.
- Thapar A, Rice F, Hay D, et al. Prenatal smoking might not cause attention-deficit/hyperactivity disorder: evidence from a novel design. Biol Psychiatry 2009; 66: 722-727.
- Thapar A, Harrington R, McGuffin P. Examining the comorbidity of ADHD-related behaviours and conduct problems using a twin study design. Br J Psychiatry 2001; 179: 224-229.
- Demontis D, Walters RK, Martin J, et al. Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder. Nat Genet 2019; 51: 63-75.
- Schreiweis C, Bornschein U, Burguiere E, et al. Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance. Proc Natl Acad Sci U S A 2014; 111: 14253-14258.
- Faraone SV, Monuteaux MC, Biederman J, et al. Does parental ADHD bias maternal reports of ADHD symptoms in children? J Consult Clin Psychol 2003; 71: 168-175.
- Efron D, Furley K, Gulenc A, et al. Maternal ADHD symptoms, child ADHD symptoms and broader child outcomes. Arch Dis Child 2018; 103: 841-846.
- Psychogiou L, Daley DM, Thompson MJ, et al. Do maternal attention-deficit/hyperactivity disorder symptoms exacerbate or ameliorate the negative effect of child attention-deficit/hyperactivity disorder symptoms on parenting? Dev Psychopathol 2008; 20: 121-137.
- Psychogiou L, Daley D, Thompson M, et al. Testing the interactive effect of parent and child ADHD on parenting in mothers and fathers: A further test of the similarity‐fit hypothesis. Br J Dev Psychol 2007; 25: 327-498.
- Owens EB, Hinshaw SP, Kraemer HC, et al. Which treatment for whom for ADHD? Moderators of treatment response in the MTA. J Consult Clin Psychol 2003; 71: 540-552.
- Chronis-Tuscano A, O’Brien KA, Johnston C, et al. The relation between maternal ADHD symptoms & improvement in child behavior following brief behavioral parent training is mediated by change in negative parenting. J Abnorm Child Psychol 2011; 39: 1047-1057.
- Dawson AE, Wymbs BT, Marshall SA, et al. The role of parental ADHD in sustaining the effects of a family-school intervention for ADHD. J Clin Child Adolesc Psychol 2016; 45: 305-319.
- Wiklund J, Yu W, Tucker R, et al. ADHD, impulsivity and entrepreneurship. J Bus Ventur 2017; 32: 627-656.
- Verheul I, Rietdijk W, Block J, et al. The association between attention-deficit/hyperactivity (ADHD) symptoms and self-employment. Eur J Epidemiol 2016; 31: 793-801.
- Lerner DA, Verheul I, Thurik R. Entrepreneurship and attention deficit/hyperactivity disorder: a large-scale study involving the clinical condition of ADHD. Small Bus Econ 2019; 53: 381-392.
- Thurik R, Khedhaouria A, Torrès O, et al. ADHD symptoms and entrepreneurial orientation of small firm owners. Appl Psychol 2016; 65: 568-586.
- Verheul I, Block J, Burmeister-Lamp K, et al. ADHD-like behavior and entrepreneurial intentions. Small Bus Econ 2015; 45: 85-101.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. 2013.
- Rommelse NN, Franke B, Geurts HM, et al. Shared heritability of attention-deficit/hyperactivity disorder and autism spectrum disorder. Eur Child Adolesc Psychiatry 2010; 19: 281-295.
- Holtmann M, Bolte S, Poustka F. Attention deficit hyperactivity disorder symptoms in pervasive developmental disorders: association with autistic behavior domains and coexisting psychopathology. Psychopathology 2007; 40: 172-177.
- Sprenger L, Buhler E, Poustka L, et al. Impact of ADHD symptoms on autism spectrum disorder symptom severity. Res Dev Disabil 2013; 34: 3545-3552.
- Gadow KD, DeVincent CJ, Pomeroy J. ADHD symptom subtypes in children with pervasive developmental disorder. J Autism Dev Disord 2006; 36: 271-283.
- Crunelle CL, van den Brink W, Moggi F, et al. International Consensus Statement on screening, diagnosis and treatment of substance use disorder patients with comorbid attention deficit/hyperactivity disorder. Eur Addict Res 2018; 24: 43-51.
- Konstenius M, Jayaram-Lindstrom N, Guterstam J, et al. Methylphenidate for attention deficit hyperactivity disorder and drug relapse in criminal offenders with substance dependence: a 24-week randomized placebo-controlled trial. Addiction 2014; 109: 440-449.
- Levin FR, Mariani JJ, Specker S, et al. Extended-release mixed amphetamine salts vs placebo for comorbid adult attention-deficit/hyperactivity disorder and cocaine use disorder: a randomized clinical trial. JAMA Psychiatry 2015; 72: 593-602.
- Kupper T, Haavik J, Drexler H, et al. The negative impact of attention-deficit/hyperactivity disorder on occupational health in adults and adolescents. Int Arch Occup Environ Health 2012.
- Rietveld CA, Patel PC. ADHD and later-life labor market outcomes in the United States. Eur J Health Econ 2019; 20: 949-967.
- Fredriksen M, Dahl AA, Martinsen EW, et al. Childhood and persistent ADHD symptoms associated with educational failure and long-term occupational disability in adult ADHD. Atten Defic Hyperact Disord 2014; 6: 87-99.