ADHD, CD, and ODD: Systematic review of genetic and environmental risk factors

May combine two claims.

Low activity of the MAOA gene, significantly associated with ADHD in 65% of studies, increases children's sensitivity to adverse environments and amplifies the risk of conduct disorders.

“low activity of the monoamine oxidase A (MAOA) gene, which was found to be signi fi cantly associated with ADHD in 65% of the studies, seems to increase the children ' s sensitivity to adverse environments, amplifying the risk of conduct disorders”

• cites Ouellet-Morin et al., 2016 sourcePartly supported

  The Discussion and the section on interactions between violence and MAOA report that MAOA variants moderated antisocial outcomes, including conduct disorder symptoms, in young males exposed to higher levels of violence. The paper also describes earlier findings concerning a low-activity MAOA allele and childhood maltreatment. It does not report that low MAOA activity was associated with ADHD in 65% of studies, and its own results concern low-frequency alleles rather than establishing their activity level. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

All genetic influences between CD and ODD may be shared, while environmental effects seem specific for each disorder.

“all genetic in fl uences may be shared, while environmental e ff ects seem to be speci fi c for each disorder”

• cites Knopik et al., 2014 sourceSupported

May combine two claims.

Genetic effects represent 50-62% of the variance of behavioral problems, except for CD-like problems in females, which are 26%.

“genetic e ff ects represent 50 -62% of the variance of behavioral problems, with the exception of problems similar to CD in female (26%)”

• cites Kerekes et al., 2014 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

SLC6A4 genotypes may moderate environmental effects on conduct disorders in children and teenagers with ADHD.

“Previous research also suggests that SLC6A4 genotypes may moderate the environmental e ff ects on conduct disorders in children and teenagers with ADHD”

• cites Sonuga-Barke et al., 2009 sourcePartly supported

  The Conduct problems section reports that serotonin-transporter (5HTT/SLC6A4) genotype significantly moderated the association between positive maternal expressed emotion and conduct-problem scores. However, the study measured conduct problems rather than effects on diagnosed conduct disorder, and its sample was limited to boys with ADHD aged 5–17 (Participants; Measures). (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Early expression of ODD may be more influenced by genetic factors, whereas later expression in childhood or adolescence may be more influenced by environmental causes.

“the early expression of ODD may be more in fl uenced by genetic factors, whereas later expression of ODD in childhood or adolescence may be more in fl uenced by environmental causes”

• cites Harvey, Breaux, & Lugo-Candelas, 2016 sourceSupported

May combine two claims. The quote only partly states this claim.

Specific alleles of DRD4 and SNAP25 were significantly associated with ADHD in more than 70% of studies, whereas DRD5 and SLC6A3 were slightly above 60%, and SLC6A4 and HTR1B were less consistent.

“speci fi c alleles of the DRD4 and SNAP25 genes were found to be signi fi cantly associated with ADHD in more than 70% of the studies, whereas the percentage of signi fi cant associations for DRD5 and SLC6A3 is slightly above 60%”

• cites Zhang et al., 2011 sourcePartly supported

  The Introduction says DRD4 and SLC6A3 have been implicated in ADHD, while also describing study results as inconsistent. The paper’s core-data section explains how it classifies significant associations, but our copy gives no study percentages for DRD4, SNAP25, DRD5, or SLC6A3, and does not establish the claimed comparison. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Differential susceptibility theory postulates that children differ in their susceptibility to environmental experiences or qualities, with some more susceptible to both negative and positive conditions.

“the di ff erential susceptibility theory, postulates that children di ff er in their susceptibility to experiences or qualities of the environment”

• cites Belsky, 1997, 2005Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Ellis & Boyce, 2011 sourceSupported

Probably not a substantial claim: may not pass S3 (load-bearing).

Individuals carrying specific variants in plasticity genes are more susceptible to environmental factors, regardless of whether those factors are risk-promoting or development-enhancing.

“Individuals carrying speci fi c variants in these genes are more susceptible to environmental factors, regardless of their risk-promoting or development-enhancing nature”

• cites Belsky et al., 2009 sourcePartly supported

  The Abstract and Conclusion describe certain gene variants as potentially making individuals more responsive to both adverse and supportive environments. The source presents this as a suggested interpretation of the evidence, however, whereas the claim states it as an established fact. (LLM, conf=0.83)

  Experimental — accuracy not yet measured
• cites Ellis & Boyce, 2011 sourceSupported

May combine two claims.

ADHD has a genetic basis that implicates several neuropsychological factors causing attentional changes, impulsivity, and motor agitation in the child.

“The ADHD has a genetic basis, which implicates several neuropsychological factors that cause attentional changes, impulsivity, and motor agitation in the child”

• cites Cardo & Servera-Barceló, 2005Not checked — no full text of the source
• cites Jin, Du, Zhong, & David, 2014 sourcePartly supported

  The Introduction describes reduced attention span and overactivity, and the Discussion mentions inattention and impulsivity. The Discussion only suggests that ADHD may be related to neurobiological abnormalities; it does not establish the claimed causal chain from a genetic basis through neuropsychological factors to those symptoms. In the Results, ADHD family history was not significantly associated with prevalence. Page numbers were not available in our copy. (LLM, conf=0.87)

  Experimental — accuracy not yet measured

May combine two claims.

Shared environmental correlation between CD and ODD is 0.28, and nonshared environmental correlation is 0.03.

“Shared environmental correlations obtained a result of 0.28, and nonshared environmental correlations yielded a result of 0.03”

• cites Knopik et al., 2014 sourceSupported

May combine two claims.

The genetic correlation between CD and ODD is 0.52 (95% CI 0.18-1.00), meaning genetic influences in CD represent 27% of the genetic variation in ODD.

“the genetic correlation between the disorders is 0.52 (IC 95% = 0.18 -1.00), which means that genetic in fl uences in CD represent 27% of the genetic variation in ODD”

• cites Knopik et al., 2014 sourceSupported

May combine two claims.

In boys, 37% of variance is attributed to common genetic influences for both ADHD and ODD and 21% to common problems between ADHD and CD; in girls, the corresponding numbers are 13% and 7%.

“with 37% of the variance attributed to common genetic in fl uences for both ADHD and ODD and 21% to the common problems between ADHD and CD, in boys. For girls, the corresponding numbers are 13% and 7%, respectively”

• cites Kerekes et al., 2014 sourceSupported

May combine two claims.

Common environmental effects had some influence on ODD behavior, while dominant genetic effects had an influence on ADHD behavior.

“Common environmental e ff ects had some in fl uence on ODD behavior, while dominant genetic e ff ects had an in fl uence on ADHD behavior”

• cites Zeeuw et al., 2015 sourceSupported

May combine two claims.

In a sample of 476 children with ODD and 159 children with CD, the prevalence of both disorders was higher in males than females (3.5% vs 2.1% for ODD, and 1.3% vs 0.6% for CD).

“in a sample of 476 children with ODD and 159 children with CD, the prevalence of both disorders was higher in male than in boys than in girs (3.5% compared to 2.1% for ODD, and 1.3% compared to 0.6% for CD, respectively)”

• cites Kerekes et al., 2014 sourcePartly supported

  The Results (‘Prevalence, age at onset, and overlap’) give the stated counts and boy–girl percentages. However, the 476 and 159 children scored above cut-offs for ODD-like and CD-like problems; the paper does not identify them as children diagnosed with ODD or CD. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

In ADHD samples, heritability for CD was 0.33 and for ODD was 0.64.

“In ADHD samples, hereditability for CD was 0.33 and for ODD was 0.64”

• cites Knopik et al., 2014 sourcePartly supported

  The Results (Genetic analyses) report heritability estimates of 0.33 for CD and 0.64 for ODD once ADHD is controlled for. The paper does not describe these as estimates from an ADHD sample; its Current Study section describes a sample of female twins. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Symptoms originating from ADHD disrupt family functioning and consequently contribute to the development of ODD symptoms.

“the symptoms originating from ADHD disrupt family functioning and, consequently, contribute to the development of ODD symptoms”

• cites Harvey et al., 2016 sourcePartly supported

  The ‘Theoretical Models of Comorbidity Between ADHD and ODD’ section describes the proposed pathway: ADHD symptoms may disrupt family functioning and thereby place children at risk for ODD. But it presents this as a theory, not an established causal finding. The ‘Developmental Precursors Model’ discussion says the causal mechanisms still need to be identified. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Children with ADHD and ODD also exhibit poor motor control, but their inhibition remains intact, suggesting inhibition is more related to ADHD than to ODD.

“Although children with ADHD and ODD also exhibit poor motor control, their inhibition remains intact, which suggests that this function is more related to ADHD than to ODD”

• cites Luman et al., 2009 sourceSupported

May combine two claims.

There is covariance between verbal ability and CD of approximately 16%, but it is associated with influences shared with ADHD.

“there is a covariance with CD (approximately 16%), but it is associated with in fl uences shared with ADHD”

• cites Smith et al., 2011 sourcePartly supported

  The Discussion says that covariance between verbal ability and CD is significant and that most of it is associated with influences also shared with ADHD. But its approximately 16% figure refers to the variance of CD attributable to influences common to all three traits, not to the magnitude of the covariance between verbal ability and CD. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

May combine two claims.

Common environmental factors have greater influence on ODD behavior, whereas genetic effects have influence on ADHD behavior.

“the common environmental factors have greater in fl uence on ODD behavior, whereas genetic e ff ects have in fl uence on ADHD behavior”

• cites Zeeuw, van Beijsterveldt, Lubke, Glasner, & Boomsma, 2015 sourcePartly supported

  The Discussion reports some common environmental influence on ODD behavior and dominant genetic influence on ADHD behavior. But it also says heritability is substantial for both; the Results describe common environmental effects on ODD as negligible at most ages in boys and present to some extent in girls. The source therefore does not support an unqualified claim that common environmental factors have greater influence on ODD behavior. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

Children with only ADHD exhibit inhibition problems, which along with poor motor response may explain part of the behavioral symptoms of impulse control.

“Children with only ADHD exhibit inhibition problems, which along with poor motor response may explain part of the behavioral symptoms of impulse control”

• cites Luman et al., 2009 sourceSupported

May combine two claims.

Environmental influences are specific to each disorder and seem more pronounced in typical behavior of ODD than of ADHD, where genetic influences seem greater.

“certain studies (e.g., Knopik et al., 2014) argue that they are speci fi c to each disorder, and seem to be more pronounced in typical behavior of ODD than of ADHD, where genetic in fl uences seem to be greater”

• cites Knopik et al., 2014 sourcePartly supported

  The Results (Genetic analyses; page unavailable) suggest that shared environmental effects are specific to ODD and CD. The paper does not establish that environmental influences are more pronounced in ODD than in ADHD, or that genetic influences are greater in ADHD; its ADHD-adjusted estimates compare ODD with CD. (LLM, conf=0.88)

  Experimental — accuracy not yet measured
• cites Zeeuw et al., 2015 sourceSupported

May combine two claims.

There is a strong relationship between CD and ODD, which seem to share genetic influences, specifically a unique genetic influence that increases the tendency for externalization in both disorders and most likely in ADHD, although each disorder may also have its own genetic characteristics.

“There is a strong relationship between CD and ODD (Rowe et al., 2002), which seem to share genetic in fl uences (Knopik et al., 2014), speci fi cally an unique genetic in fl uence that increases the tendency for externalization in both disorders (Dick et al., 2005) and, most likely, in ADHD, although each disorder may also have its own genetic characteristics”

• cites Rowe et al., 2002 sourceNot checked — no full text of the source
• cites Knopik et al., 2014 sourcePartly supported

  Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

  Experimental — accuracy not yet measured
• cites Dick et al., 2005 sourceNot checked — no full text of the source

May combine two claims.

Heritability of ODD and ADHD behavior is lower among twins who do not share a classroom, suggesting some behavioral differences are attributable to differences in classroom environments.

“hereditability of ODD and ADHD behavior is lower among twins who do not share a classroom, which suggests that some of the behavioral di ff erences are attributable to the di ff erences in classroom environments”

• cites Zeeuw et al., 2015 sourceSupported

May combine two claims.

Overall, the causes for the onset and maintenance of ADHD, ODD, and CD are more associated with genetic factors than environmental factors, although the importance of environmental factors is recognized.

“Overall, the results suggest that (a) the causes for the onset and maintenance of these disorders are more associated with genetic factors than environmental factors, although the importance of the latter is recognized”

May combine two claims.

Most studies fall within population genetics, and there are few molecular genetics data that allow knowing the specific genes involved in each of these conditions.

“The most of the studies fall within the scope of population genetics and, therefore, there are few molecular genetics data that allow us to know the speci fi c genes involved in each of these conditions”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Children with ADHD presented social maladjustment at school and an inability to interact with other children.

“Children with ADHD presented social maladjustment at school, have an inability to interact with other children;”

May combine two claims.

Both ODD and CD are strongly associated with ADHD.

“Both ODD and CD are strongly associated with ADHD.”

May combine two claims.

ADHD, CD, and ODD seem influenced at a genetic level, increasing the tendency for externalization, as well as at an environmental level, as the manifestation of symptoms varies according to context and education.

“these disorders seem to be in fl uenced at a genetic level, increasing the tendency for externalization in both disorders, as well as at an environmental level, as the manifestation of the symptoms of the disorders vary according to the context in which the children are inserted and the way they are educated”

May combine two claims.

High rates of maternal depression, family problems, parental alcohol or drug problems, and crime are specific environmental factors influencing both CD and ODD.

“High rates of maternal depression, family problems, parental alcohol or drug problems, and crime, are speci fi c environmental factors in fl uencing both CD and ODD.”

May combine two claims.

There is a genetic covariation between CD and ODD of 0.52, with specific shared environmental effects contributing to the individual differences of each disorder.

“There is a genetic covariation between CD and ODD of 0.52, with speci fi c shared environmental e ff ects that contribute to the individual di ff erences of each disorder.”

• cites Burt et al.Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

Although CD and ODD share genetic responsibility, each disorder may possess a unique genetic influence.

“although there is a shared genetic responsibility, each disorder may possess a unique genetic in fl uence”

• cites Dick et al., 2005 sourceNot checked — no full text of the source

May combine two claims.

CD and ODD are related in their behavioral manifestations, and children with CD often exhibit some ODD behavior, suggesting a shared developmental relationship.

“CD and ODD are related in their behavioral manifestations. Children with a diagnosis of CD often exhibit some ODD behavior, thus suggesting they may share a developmental relationship”

• cites Rowe, Maughan, Pickles, Costello, & Angold, 2002 sourceNot checked — no full text of the source

May combine two claims.

The etiology of ADHD is complex, with both genetic and environmental factors implicated in the disorder.

“The etiology of ADHD is complex, with both genetic and environmental factors implicated in the disorder”

• cites Biederman & Faraone, 2005 sourceNot checked — no full text of the source

May combine two claims.

The correlation between genetic factors of CD and ODD is .58, but there is no overlap of these factors.

“reported a higher correlation between the genetic factors of CD and ODD (.58), but not an overlap of these factors”

• cites Dick, Viken, Kaprio, Pulkkinen, & Rose, 2005 sourceNot checked — no full text of the source

May combine two claims.

ADHD, ODD, and CD are polygenic and some genes may have pleiotropic influences in different traits of these disorders.

“The ADHD, ODD, and CD are polygenic and some genes may have pleiotropic in fl uences in di ff erent traits of these disorders”

May combine two claims.

Some genes may represent a general risk factor increasing the risk of all externalization disorders, while others contribute to specific symptoms of individual disorders.

“Some genes may represent a potential general risk factor (e.g., temperament, personality, behavioral disinhibition), which increase the risk of all externalization disorders, while others may contribute to speci fi c symptoms of individual disorders”

• cites Dick et al., 2005 sourceNot checked — no full text of the source

May combine two claims.

ADHD has an estimated comorbidity rate of 16-20% with CD, and this comorbidity is more common in boys than in girls.

“ADHD has an estimated comorbidity rate of 16 -20% with CD, although evidence indicates that this comorbidity is more common in boys than in girls”

• cites Biederman et al., 2002 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The index of agreement in the study selection process was almost perfect, with Cohen's Kappa = 0.936, p < 0.001.

“The index of agreement in the study selection process was evaluated by Cohen ' s Kappa and revealed almost perfect agreement, K =0.936, p &lt; 0.001”

• cites Landis & Koch, 1977 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

In children with ADHD, oppositional behavior is the most frequent additional difficulty and the most responsible for the child's difficulty in regulating emotions.

“it is common to fi nd, in children with ADHD, other challenges and di ffi culties, with oppositional behavior being the most frequent and most responsible for the child ' s di ffi culty in regulating emotions”

• cites Barkley et al., 2008Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim. May combine two claims.

Study selection for eligibility and data extraction were conducted by two independent reviewers to reduce the likelihood of missing studies and to minimize classification errors.

“the selection of the studies for eligibility and data extraction was conducted by two independent reviewers, in order to reduce the likelihood of missing any study and to minimize classi fi cation errors”

• cites Higgins & Green, 2011Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

ADHD has high comorbidity with several disorders, but none greater than with ODD, with comorbidity rates estimated at approximately 60%.

“The ADHD has high rates of comorbidity with several disorders, but none greater than with ODD, with comorbidity rates estimated to be approximately 60%”

• cites APA, 2013Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Maughan, Rowe, Messer, Goodman, & Meltzer, 2004 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Irrespective of the disorders exhibited by children, the mean age for their appearance is around 4-5 years.

“Irrespective of the disorders exhibited by children, the mean age for their appearance is around 4 -5 years”

• cites Rowe et al., 2002 sourceNot checked — no full text of the source

May combine two claims.

Children with only ADHD exhibit social maladjustment in school, experience rejection by peers, and manifest bullying.

“children with only ADHD exhibit social maladjustment in school, experience rejection by peers and manifest bullying”

• cites Tseng et al., 2011 sourceNot checked — no full text of the source

May combine two claims.

Severe discipline is specifically associated with CD in boys, but associated with both disorders in girls.

“severe discipline was speci fi cally associated with CD in boys, but associated with both disorders in girls”

• cites Rowe et al., 2002 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

The covariance between ADHD, CD, and ODD seems to come from a single common environmental factor.

“the covariance between ADHD, CD, and ODD seems to come from a single common environmental factor”

• cites Burt, Krueger, McGue, & Iacono, 2001 sourceNot checked — no full text of the source

May combine two claims.

Environmental factors influencing children with CD and ODD are related to maternal depression, family disturbances (social disadvantage and atypical family structures), high crime rates, and parental drug and alcohol problems, which were higher in families of children with CD and ODD.

“environmental factors which in fl uenced children with CD and ODD disorders were related to: (1) maternal depression; (2) familiar disturbs, represented in terms of social disadvantage and atypical family structures; (3) high crime rates and (4) parental drug and alcohol problems, which were higher in the families of the children who exhibited CD and ODD”

• cites Rowe et al., 2002 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

In one study, 96 boys and 70 girls presented ODD criteria, and 132 boys and 47 girls presented CD criteria.

“96 boys and 70 girls presented ODD criteria, and 132 boys and 47 girls presented CD criteria”

• cites Rowe et al., 2002 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Excessively invasive and overprotective parenting is associated with CD only in girls and has no association with diagnostic status in boys.

“Excessively invasive and overprotective parenting was associated with CD only in girls, and had no association with diagnostic status in boys”

• cites Rowe et al., 2002 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

In males, the prevalence of ADHD is higher, at a ratio of approximately 2:1 compared to females.

“In male, the prevalence of ADHD is higher, at a ratio of approximately 2:1 when compared to female”

• cites Martin et al., 2006 sourceNot checked — no full text of the source

May combine two claims.

Children with only ODD are impaired in the family domain and have negative family relationships, especially with siblings, due to defiant behavior, suggesting ODD is associated with family dysfunction.

“Children with only ODD are impaired in the family domain, and have negative family relationships, especially with their siblings, due to their de fi ant behavior, as opposed to children with ADHD, suggesting that ODD is associated with family dysfunction”

• cites Tseng et al., 2011 sourceNot checked — no full text of the source

Classified as probably not a substantial claim. May combine two claims.

ADHD, CD, and ODD have mostly a genetic covariation, even if they can also be influenced by the environment.

“these three disorders have mostly a genetic covariation, even if they can also be in fl uenced by the environment”

• cites Burt et al., 2001 sourceNot checked — no full text of the source

May combine two claims.

At younger ages, comorbidity between ADHD and ODD or CD is noticeable and seems to share a behavioral dimension originating in a common genetic mechanism.

“at younger ages, the comorbidity between ADHD and ODD or CD is noticeable, and it seems to share a behavioral dimension, originating in a common genetic mechanism”

• cites Silberg et al., 1996 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

An estimated covariance of 1.0 between each pair of ADHD, CD, and ODD indicates that the same shared environmental factor influences the development of each disorder.

“An estimated covariance of 1.0 between each pair of disorders indicates that the same-shared environmental factor in fl uences the development of each disorder”

• cites Burt et al., 2001 sourceNot checked — no full text of the source

May combine two claims.

CD is strongly associated with the impulsive form of ADHD (ADHD-HI), but exhibits a weaker relationship with the inattentive form (ADHD-I), with shared genetic heritability of 37% and 35%, respectively.

“CD is strongly associated with the impulsive form of the attention de fi cit hyperactivity disorder (ADHD-HI), but exhibits a weaker relationship with the inattentive form (ADHD-I), with shared genetic hereditability being 37% and 35%, respectively”

• cites Martin et al., 2006 sourceNot checked — no full text of the source

May combine two claims.

Children with ADHD display social maladjustment in several areas, which predisposes them to ODD behavior towards relatives or conduct disorders towards peers.

“children with ADHD display social maladjustment in several areas (e.g., school, peers, siblings, parents), which predisposes them to ODD behavior towards their relatives or conduct disorders towards their peers”

• cites Tseng et al., 2011 sourceNot checked — no full text of the source

May combine two claims.

Environmental factors that influence CD and ODD are parental alcohol and drug problems, previous history of parental crime, maternal depression, and family disorders.

“Environmental factors that in fl uence CD and ODD are parental alcohol and drug problems, previous history of parental crime, maternal depression, and family disorders”

• cites Rowe et al., 2002 sourceNot checked — no full text of the source

May combine two claims.

In ODD, the most affected domain is the family environment, but defiant behavior may explain why ODD is more strongly associated with family dysfunction.

“literature suggests that in ODD the most a ff ected domain is the family environment, but in this fi nding one must take into account the de fi ant behavior, which is typical of this disorder and may explain the fact that ODD is more strongly associated with family dysfunction”

• cites Tseng et al., 2011 sourceNot checked — no full text of the source