Alessi, N., Hottois, M.D., and Coates, J.K. (1993). The gene for ADHD? Not yet!. Journal of the American Academy of Child & Adolescent Psychiatry, 32(5), 1073-1074.

Alessi et al. comment on the report by P. Hauser et al. (1993) regarding the "discovery" of a gene for attention deficit hyperactivity disorder (ADHD). In the original article, Hauser et al. report that ADHD is associated with a rare thyroid condition. In the response, Alessi et al. argue that a direct causal relationship is not demonstrated between ADHD and the rare thyroid condition. The authors caution against jumping to conclusions about the genetic etiology of ADHD based on a study of a thyroid condition. They point out that the majority of people diagnosed with ADHD do not have this thyroid condition. The original article did not consider the possibility that the ADHD was not "simply a manifestation of the elevated thyroid state of these patients". They continue by pointing out that whereas all of patients in the thyroid study were adults, the literature suggests that ADHD occurs in very few adults. The authors then respond to the implications of the original article. They point out that the mental health community has too hastily jumped on the thyroid gene bandwagon as an explanation for ADHD. As a result, some have suggested that all ADHD children be screened for this gene - at a cost of over $379,000,000 (based on the 3% figure). Finally, the authors point out that believing that children are "hyper" solely because of a single gene is dangerous to the mental health community because it fails to take into account the environmental factors involved.

This is an good article for a number of reasons. It delineates the factors involved in what would be needed to identify an ADHD gene. It is not an empirical study, but rather a letter in response to a study. Both the summation of the study and the commentary are easy to read and understand. I learned more about the state of psychiatry and genetics in ADHD from this article than most others simply because it was written in lay terms. Since most social workers are not medically trained, simple language is crucial if information is to be shared among members of the helping professions. Finally the authors explore the social and economic costs, which is unique in the literature review of the genetic etiology of ADHD.

Biederman, J., Faraone, S.V., Mick, E., Spencer, T., Wilens, T, Kiely, K, Guite, J, Ablon, J.S., Reed, E., and Warburton, R. (1995). High risk for attention deficit hyperactivity disorder among children of parents with childhood onset of the disorder: A pilot study. American Journal of Psychiatry, 152(3), 431-435.

This article presents a study of 31 adults who have been identified through structured interviews to have had childhood-onset of ADHD. The authors cite literature that estimates that between 10%-60% of all children with ADHD maintain the disorder into adulthood. Since most professionals that work with children do not follow adults and visa versa, there is little research in this area. The authors argue that this is a crucial part of understanding the nature of the disorder.

In this study, the children of parents with childhood-onset of ADHD are considered at-risk for having ADHD. The authors found that 84% of the adults with ADHD who had children had at least one child with the disorder, and 52% had two or more children with the disorder. Of the 84 at-risk children, 48 (57%) met criteria for ADHD. This is a much higher rate than found in sibling studies (15%) and suggests a much stronger familial etiological risk factor.

I think this a very important study. Unlike many studies of ADHD, the subject size is large enough to generalize from. One criticism is that nowhere in the study do they mention the subjects' race or socio-economic status. This would be an important consideration because there has been considerable literature that points out that lower-income African-American and Mexican-American youth are more frequently labeled as having ADHD. This study is fairly easy to read and brings together a number of important points about the disorder from other sources. Finally, it hints at the importance of looking at multi-generational impacts of the disorder. Social workers can use this study in their look at the life cycle and family dynamics.

Biederman, J., Faraone, S.V., Keenan, K., Benjamin, J., et al. (1992). Further evidence for family-genetic risk factors in attention deficit hyperactivity disorder: Patterns of comorbidity in probands and relatives in psychiatrically and pediatrically referred samples. Archives of General Psychiatry, 49(9), 728-738.

In this study, the authors looked at familial and psychosocial risk factors for ADHD. They note that there has been varied success in determining a genetic basis for ADHD, and suggest that the disorder might in fact be a group of closely related conditions, rather than one "homogeneous clinical entity". For this reason they decided to subgroup children with ADHD based on the presence or absence of the following psychiatric disorders: antisocial disorders, major depressive disorders, substance dependence, and anxiety disorders. The study looked at 140 males (aged 6-17 yrs) with ADHD, 120 normal controls, and 822 1st-degree relatives.

The results of this study were very similar to previous studies with regards to familial etiology of ADHD. The patterns of familial aggregation support hypotheses that (1) ADHD and mood disorders share common familial vulnerabilities, (2) ADHD plus conduct disorder may be a distinct subtype, and (3) ADHD and anxiety disorders segregate independently in families. Two important environment-related findings were that "familial risk for both CD and substance dependence fell short of attaining statistical significance after controlling for SES". The authors note that findings in New Zealand and Puerto Rico indicate that ADHD is most likely a group of conditions, rather than a single homogeneous clinical entity.

This study has a great deal to offer the field of social work. Since our work is less "medical model" than the psychiatric community, and more ecological, this study provides information on a number of disorders, their comorbidity, and environmental factors are taken into consideration. The best part about this study is that the authors consider the limitations of their methodology. They point out that parents were fully aware of their children's diagnosis and this could have some impact on the interviews. For example, the authors note that parents of children with ADHD might have been more likely to recall similar problems in their own childhood than control parents whose children do not exhibit characteristics of the disorder. The study also has a large sample size in its favor. This article adds considerable information to the exploration of the genetic influence on ADHD.

Biederman, J., Milberger, S., Faraone, S.V., Guite, J., and Warburton, R. (1994). Associations between childhood asthma and ADHD: Issues of psychiatric comorbidity and familiality. Journal of the American Academy of Child & Adolescent Psychiatry, 33(6), 842-848.

The authors studied the association between asthma and attention deficit hyperactivity disorder (ADHD). The two main reasons for studying a possible association is that 1) asthma is known to be genetically transmitted and has been implicated in school and behavior problems, and 2) and there is considerable evidence that ADHD has a genetic component, and is results in considerable school and behavioral problems. The studied looked at 140 boys (aged 6-17 yrs) with ADHD, 120 controls, and their 1st-degree relatives were studied. Information on asthma was obtained from the mother in a blind standardized manner.

The study found that the risk for asthma did not meaningfully differ between ADHD and control children. There was only one positive correlation; relatives of ADHD probands with and without asthma were at greater risk for ADHD than relatives of normal controls. The risk for asthma was significantly elevated only among relatives of children with ADHD and asthma. This suggests that both conditions are transmitted independently in families.

This study is useful for a number of reasons. First, it suggests that there is no significant association between asthma and ADHD, which opens the door for further genetic study. Second, it provides an example of a study that was not successful in disproving their null hypotheses, but were nevertheless able to draw valuable conclusions. They suggest that contrary to previous research, there is little association between atopic disorders and ADHD. They also suggest that there is less connection between asthma and school and behavior problems than previously reported. Social workers can profit from the evidence that when a client has asthma and ADHD, that the ADHD is not a secondary consequence of asthma, but rather its own disorder that requires the appropriate attention.

Biederman, J.F., Stephen V., Keenan, K., and Tsuang, M.T. (1991). Evidence of familial association between attention deficit disorder and major affective disorders. Archives of General Psychiatry, 48(7), 633-642.

The authors looked at the comorbidity between attention deficit disorder (ADD) and affective disorder (AFF) of 1st degree biologic relatives of clinically referred children and adolescents with ADD. The authors site the development of depressive disorders among individuals with ADD as rationale for doing the study. The subjects were 49 ADD probands with 169 relatives, 24 ADD and AFF probands with 86 relatives, and 26 normal controls with 88 relatives. All children were 6-17 yrs old.

The authors found that the overall risk for AFFs among the relatives of patients with ADD was significantly higher than the risk to relatives of normal control children. The risk for AFFs was the same among the relatives of ADD probands with and without comorbid AFF, and these risks were significantly higher than the risk to relatives of normal control children. ADD and AFFs did not cosegregate within families, and the association between ADD and AFFs could not be accounted for by nonrandom mating. In other words, the authors conclude that while ADD and AFFs share a common familial etiology, the fact that it manifests itself as ADD in some children but ADD + AFFs in other children suggest some environmental influence.

The emphasis on environmental influences makes this study valuable for social workers. The language used in this article would make it somewhat inaccessible to most social workers outside of those who work directly with children who have ADD or AFFs. Like most of the studies by Biederman et al, the large sample size works favorably for generalizing the findings. This article is less conclusive and appears to add less to the literature than the previously reviewed articles. This could be a function of being an older article that looked at more basic issues.

Biederman, J., Faraone, S.V., Keenan, K., Knee, D., and Tsuang, M.T. (1990). Family-genetic and psychosocial risk factors in DSM-III attention deficit disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 29(4), 526-533.

The authors evaluated family-genetic and psychosocial risk factors for attention deficit disorder (ADD) among the 457 1st-degree relatives of 73 clinically referred children and adolescents with ADD, 26 psychiatric subjects, and 26 normal controls. The subjects were Caucasian, non-Hispanic, non-adopted 6-17 year old males. The psychiatric subjects referred to the same clinic for different reasons, and were included to provide a socio-demographic comparison with the ADD probands. The information was gathered through structured interviews.

The study found that relatives of children referred to the clinic with ADD had a higher risk for ADD, antisocial disorders, and mood disorders than did relatives of psychiatric and normal controls. The increased risk for ADD could not be accounted for by gender or generation of relative, the age of proband, social class, or the intactness of the family. The results confirmed and extended previous findings indicating important family-genetic risk factors in ADD.

This study adds greatly to the literature because it is the first study to address the family-genetic component of ADD while controlling for socio-economic and environmental variables. The study is fairly difficult to read because of the complicated research methodology. The discussion section includes some useful suggestions about future research (which was incorporated into some of the later studies by Biederman et al that were reviewed above). I would recommend this article to anyone who wants to get a solid basis in research on family-genetic and psychosocial risk factors in ADD.

Biederman, J., Munir, K., Knee, D., Armentano, M., Autor, S., Waternaux, C., and Tsaung, M. (1987). High rate of affective disorders in probands with attention deficit disorder and in their relatives: A controlled family study. American Journal of Psychiatry, 144(3), 330-333.

The authors conducted a controlled family study of attention deficit disorder (ADD), wherein data were collected on 1st-degree relatives of 22 children (mean age 11.1 yrs) with ADD and 20 normal children (mean age 10.4 yrs). It was hypothesized that "the rate of affective disorders would be higher in relatives of ADD probands who had a concomitant major affective disorder than in relatives of ADD probands who did not have an affective disorder". The authors note that this is the first major study to their knowledge that investigates the family relation to children with both ADD and an affective disorder.

The rate of major affective disorder was significantly higher in the ADD probands (32%) and their relatives (27%) than in the normal control subjects (0%) and their relatives (6%). It was concluded that ADD is associated with higher risk for affective disorder and that probands who have both disorders may represent a distinct subgroup.

While this article was the beginning of what has become a huge study, in and of itself it is not very pertinent. It was published 8 years ago, which means the study is even older. The same group has improved its methods, become more culturally and economically sensitive and expanded the number of subjects to facilitate generalizing results. Ironically, this article is the most difficult to read, using the most jargon and inaccessible language. In that respect it might be important to read it as an historical marker and an example of how not to write a paper.

Comings, D.E., and Comings, B.G. (1984). Tourette's syndrome and attention deficit disorder with hyperactivity: Are they genetically related?. Journal of the American Academy of Child Psychiatry, 23(2), 138-146.

The authors cite several studies which suggest a genetic etiology for ADD. They define Tourette's syndrome (TS) as a hereditary disorder which is associated with ADHD, OCD and exhibitionism. A series of 250 case studies support the hypothesis that "most cases of TS are due to a single major gene". Among the questions asked, the authors wanted to know if TS and ADD are genetically linked. Therefore, they examined prospective data on 250 consecutive, unselected patients (aged 6-71 yrs) with TS to determine the relationship of TS and ADD to hyperactivity.

Results show that ADD with hyperactivity was present in 62% of males under age 21 yrs. The examination of family histories suggested that the TS gene could be expressed as ADD with hyperactivity but without tics. It is suggested that subjects with hyperactivity who developed tics after treatment with stimulants had ADD due to a TS gene and probably would have developed tics without stimulant treatment. The authors emphasize that ADD is a disorder with many possible etiologies, despite the DSM-III criteria. They conclude by saying that the determination of a genetic interrelationship between ADD and TS will have to wait for more precise genetic markers to be developed.

While the study was important in 1984, much of the information is outdated. All of the criteria are from the DSM-III, there is no mention of gender or racial characteristics of the subjects, and they come up with nothing conclusive because the genetic technology is not sophisticated enough. This would be a great study to duplicate with today's more advanced technology. Social workers can glean from this article that when a client is referred for possible ADD, to take a complete family history for TS symptoms. This will ensure a more effective diagnosis and treatment.

Deutsch, C.K., Matthysse, S., Swanson, J.M., and Farkas, L.G. (1990). Genetic latent structure analysis of dysmorphology in attention deficit disorder. Journal of the American Academy of Child & Adolescent Psychiatry, 29(2), 189-194.

The authors look at dysmorphology, which is the presence of minor physical abnormalities (such as wide-set eyes, abnormally shaped ears, or single palmar creases) as a possible genetic clue to ADD. They observed an overrepresentation of dysmorphology in the form of minor physical anomalies in 48 probands (aged 6-14 yrs) with attention deficit disorder (ADD) and in 82 of their 1st-degree relatives compared with 85 non-ADD subjects. Further, ADD probands without dysmorphology had non-ADD relatives who were dysmorphic; this familial pattern suggests that a single underlying factor may influence transmission of both traits. The authors fit a genetic latent structure model these data to describe the factor's mode of transmission. The concluded that "in this analysis, an autosomal dominant model emerged".

This article is effectively useless to social workers, like myself, who have no training in genetics. The article used highly technical language which made it completely inaccessible. Even after defining a few terms, the concepts were far too advanced to be comprehended. Furthermore, there is little insight that would be applicable to individual clients.

Faraone, S.V., Biederman, J., Lehman, B.K., Keenan, K., Norman, D., Seidman, L.J., Kolodny, R., Kraus, H., Perrin, J. and Chen W.J. (1993). Evidence for the independent familial transmission of attention deficit hyperactivity disorder and learning disabilities: Results from a family genetic study. American Journal of Psychiatry, 150(6), 891-895.

The authors begin by stating that the etiologies of ADHD and LDs are both known to have familial and, possibly, genetic components, and cite a twin study that concluded that they were genetically independent. They explored the relationship between ADHD and learning disabilities LDs by assessing LDs in 140 children with ADHD, 120 normal comparison children, and probands' 822 1st-degree relatives.

The study found that the risk for LDs was highest among relatives of probands with both ADHD and LDs. Interestingly, the authors found that the spouses of individuals with an ADHD child were more likely to have higher rates of LDs than spouses of individuals without ADHD. They called this nonrandom mating. Thus, the 2 disorders are transmitted independently in families, and their cooccurrence may be due to nonrandom mating. They conclude that ADHD is likely to be etiologically independent from LDs.

This is a useful article because of the information it presents about ADHD and LDs even though the language is somewhat inaccessible. One disadvantage is that like many of the studies it cannot be generalized beyond Caucasian males. The study does well in describing the methodology and could be replicated with a different population. It is a fairly recent article and will no doubt spawn a number of like articles in the future.

Faraone, S.V., Biederman, J., Keenan, K., Tsuang, M.T. (1991). A family-genetic study of girls with DSM-III attention deficit disorder. American Journal of Psychiatry, 148(1), 112-117. Abstract

Despite the fact that the prevalence of ADHD is 2-9 times greater in boys than girls, there are compelling reasons why it is important to study ADD in girls. The authors note that girls with ADHD are less likely than boys to receive stimulant treatment, even though there is evidence that it works equally well with both populations. They also cite literature that show girls with ADD as having higher rates of cognitive impairment, depression, low self esteem and lower rates of sever behavioral disturbances than boys with ADD. The authors call this "underidentification and undertreatment" of girls with ADHD and suggest that this might have considerable implications for mental health and education.

They evaluated family-genetic risk factors in girls with attention deficit disorder (ADD) and compared these results to findings in a previous study by J. Biederman et al. (1990) of boys with ADD. Twenty-one girls with ADD and 20 normal comparison girls (all aged 6-17 years) were assessed. They also looked at 69 first-degree relatives of ADD subjects and 71 first-degree relatives of normal subjects. Consistent with the findings of Biederman et al. on boys, the authors found that relatives of ADD girls had higher risks for ADD, antisocial disorders, major depression, and anxiety disorders.

Social workers will find this article fairly accessible and full of important information. It is one of the few studies of girls, not boys, although they are all Caucasian. The article is well organized and clearly delineates the methodology. The discussion section looks at the ecological factors of social class and family intactness and notes they made no difference on the results.

Gillis, J.J., Gilger, J.W., Pennington, B.F., DeFries, J.C. (1992). Attention deficit disorder in reading-disabled twins: Evidence for a genetic etiology. Journal of Abnormal Child Psychology, 20(3), 303-315.

The authors examined the genetic etiology of attention deficit hyperactivity disorder (ADHD) in 37 identical and 37 fraternal twin pairs (aged 8-20 years) in which at least one member had a reading disability. Their analysis supported the concept of ADHD as highly heritable and adjusting the scores for either IQ or reading performance differences did not substantially change the results.

This article works well within the literature of genetic factors involved in ADHD. The link with reading disabilities is important because both contribute greatly to problems at school. As social workers, this article is useful because it identifies the Diagnostic Interview for Children and Adolescents (DICA) as a useful instrument for diagnosing ADHD. It would be important to make sure that it had been updated from the DSM-III-R criteria to any changes in the DSM-IV.

Heffron, W.A., Martin, C.A., Welsh, R.J. (1984). Attention deficit disorder in three pairs of monozygotic twins: A case report. Journal of the American Academy of Child Psychiatry, 23(3), 299-301.

The authors present case reports of 3 pairs of monozygotic twins (7- and 8-year-old Black males and 6.5-year-old White males), all concordant for attention deficit disorder (ADD). The literature on the genetic implications of ADD is reviewed, including twin, family, and adoption studies. The authors conclude that the presence of ADD in the twins adds support to the idea of a genetic ideology of ADD. They also point out that the twins were at significant risk for premature birth, abuse, and neglect. These environmental factors are suggested to have a possible impact, although these variables were not controlled for.

This article is very useful as an historical document. The strength of the study is that it looks at both blacks and whites and considers the above mentioned environmental factors as possible contributors. This article could encourage social workers to pursue the ecological issues that come up as important. The weakness of the article is that the research is over 12 years old, the sample size (2 pairs of twins) is too small to generalize from, and cannot be applied to girls. Because of these limitations, I would not recommend this article other than a short, historical perspective on the evolution of the research literature.

McGhee, R., Williams, S., and Silva, P. (1987). A comparison of girls and boys with teacher-identified problems of attention. Journal of the American Academy of Child & Adolescent Psychiatry, 26(5) 711-717.

The authors begin their article by noting the prevalence of literature on ADD in boys, even though there is evidence that the associated characteristics and etiology of ADD my be the same in both boys and girls. The authors contend that this focus on boys represents a bias in the literature. They suggest that "it may be more meaningful to identify children with hyperactivity/ADD by reference to the same-sex distribution of scores". Therefore, they looked at the inattentive scales provided by teachers for both sexes. It was found that relative to their attentive peers, the inattentive boys and girls showed the same pattern of deficits on measures of IQ, verbal comprehension, reading, spelling, speech articulation, and tapping speed.

This is a useful article because it provides a comparison between boys and girls in the same study. The usefulness is limited by the age of the study, and the population, which was over 1,000 New Zealand youth with mainly European backgrounds. While this in and of itself is not a limiting factor (and in fact has been used in previously reviewed articles as support that ADHD is not a culturally-limited disorder), social workers would be advised to make note of the population and the age of the study. Social workers who work in schools will be able to utilize the information on teacher reporting.

Pauls, D.L., Leckman, J.F., Cohen, D.J. (1993). Familial relationship between Gilles de la Tourette's syndrome, attention deficit disorder, learning disabilities, speech disorders, and stuttering. Journal of the American Academy of Child & Adolescent Psychiatry, 32(5), 1044-1050.

The authors present a study that tested the findings of a study that has been reviewed earlier in this paper (Comings and Comings, 1990). The authors examined the familial relationship between Gilles de la Tourette's syndrome (GTS) and attention deficit disorder (ADD), learning problems, speech disorders, and stuttering. Data were obtained from 338 first-degree relatives of 85 GTS probands (aged 7-62 years) and 113 controls. Relatives were assessed using structured interviews, and family history information was collected from all family members. Best-estimate diagnoses were assigned for GTS, ADD, learning problems, speech disorders, and stuttering.

The authors' findings did not support the earlier study. There was no evidence that ADD, learning problems, speech disorders, or stuttering represent genetically variant expressions of GTS. Interestingly, relatives with GTS were at increased risk for ADD regardless of the ADD diagnosis of the GTS proband.

This study is useful because of there was a large number of subjects and they were both male and female. The authors took great care to ensure that females were proportionately represented. Social workers can use this information as support for the need to identify and treat all possible client disorders individually, and not as just symptomatic of GTS. That the study was based on family history makes the methodology accessible to social workers. The language was more accessible and less technical than previous articles.

Sprich-Buckminster, S., Biederman, J., Milberger, S., Faraone, S.V., et al, (1993). Are perinatal complications relevant to the manifestation of ADD? Issues of comorbidity and familiality. Journal of the American Academy of Child & Adolescent Psychiatry,32(5), 1032-1037.

The authors evaluated the role of pregnancy, delivery, and infancy complications (PDICs) in the etiology of attention deficit disorder (ADD). They point out many of the articles reviewed here as implicating a genetic basis for ADD, but note that the studies cannot explain the disorder solely based on genetics. For this reason they believe it is important to look at the environmental factors involved. The subjects were 6-17 year old boys and their first-degree relatives; 73 boys had ADD, 26 served as psychiatric controls, and 26 served as normal controls. Information on PDICs was obtained from the mothers in a standardized manner blind to the subjects' clinical status.

It was found that the association between ADD and PDICs was strongest for the comorbid and nonfamilial subtypes. In contrast, noncomorbid and familial ADD subgroups differed less from normal controls in the risk for PDICs. In other words, children who did not have disorders other than ADD were more similar to the normal controls and thus PDIC's were less a factor. The authors concluded that PDICs may be part of nongenetic etiologic mechanisms in ADD, especially for children who have comorbid disorders.

This article serves as a good balance for the genetic etiology literature. This article emphasizes the importance of the birthing process on later development. This is an area that social workers often do not consider to be important possibly because they feel it is the concern and domain of the medical community. Like most of the articles, this study is not applicable to girls and non-Caucasian males. The language is slightly technical and they are testing 5 hypotheses which becomes quite complicated in the explanation. This study was conducted with the same team that has done many of the genetic etiology studies reviewed in this paper, lending credibility to the results and usefulness of the study as an extension of the literature.