Presentation Review – ADHD
The presentation was well done and covered the breadth of the topic. However, there were a few
minor inaccuracies and omissions that this review will explore in more depth.
ADHD Typology
Slide 13 of the PowerPoint mentions that ADHD can be organized into three main typologies
including inattentive, hyperactive/impulsive, and combined (though it does not appear that this
slide was shown in the presentation). The presentation did not put emphasis on the inattentive
and hyperactive/impulsive typologies and opted to focus more on the combined typology. This is
also evident on slides 2 and 14 where it is not stated that a diagnosis of ADHD can made based
on either inattentiveness and/or hyperactivity and impulsivity. This distinction is important
because as it will discussed below certain animal models are more valid for specific typologies
of ADHD. Moreover, certain comorbid may be more difficult to detect in certain typologies. For
example, Jensen and colleagues (1997) theorized that learning disorders in individuals with
inattentive-type ADHD is more likely to go undetected because these individuals exhibit less
disruptive behavior that would alert parents and teachers and many of the behaviors associated
with inattentive-type ADHD are similar to various learning disorders.
Neuroanatomy
In the presentation, it was correctly pointed out that there are significant reduction in brain
volume within children especially in regions connected to the dopamine pathways. However, the
presentation should have noted that this pattern of reduction is not as clear in adults as it is in
children in specific brain regions. A study using voxel-based morphometry conducted by
Seidman and colleagues (2011) found that there was a significant increase in the volume of the
dorsolateral prefrontal cortex (the presentation slides mentioned that these regions have been
shown to decrease in terms of volume, and that has been shown to be true in children) and
inferior parietal lobule. In comparison, an older MRI study by Seidman and colleagues (2006)
found that there were volume reductions in the dorsolateral prefrontal cortex consistent with
studies in children. These contradictory results indicate that there needs to be further imaging on
the brains of adults with ADHD.
Genetics
On slide 49, the study you have referenced by Ribases and colleagues (2012) mentions 9 genes
that are involved in dopamine transmission, however, only 5 genes were written on this slide.
Moreover, DRD2, which is one of the genes mentioned on this slide, has not been found to be
significantly associated with ADHD according to the studies cited by Ribases and colleagues
(2012). Moreover, the meta-analysis by Faraone and colleagues (2005) failed to find a significant
pooled association between DRD2 and ADHD. Moreover, another meta-analysis by Gizer and
colleagues (2009) found the association between DRD2 and ADHD to be inconclusive.
Moreover, in the presentation (on slide 50) the focus was DAT1, DRD4, DRD5, and DBH. All
of the genes mentioned have been associated with ADHD. However, the presentation should
have also covered 5-HTT, which is the gene that codes for the serotonin transporter; this gene is
responsible for the reuptake of the serotonin from the synaptic cleft; this gene has been found to
be overexpressed in people with ADHD (Faraone et al., 2005). HTR1B, which is the gene that
codes for the serotonin HTR1B receptor, has also been found to be significantly related to
ADHD (Faraone et al., 2005). Finally, the under-expression of SNAP-25 in mice has been shown
to result in reduced striatal dopamine and serotonin levels; there have been significant
associations found between SNAP-25 and ADHD within pooled human family studies (Faraone
et al., 2005).
Animal Models
The presentation provided a very brief overview of some of the useful animal models. However,
a more extensive review the validity and utility of the various models should be performed for
the final report. One key point that should be mentioned is that certain animal models are more
valid for certain typologies of ADHD. For example, the Naples High-Excitability Rat (NHE) has
been found to be inattentive yet not impulsive/hyperactive; thus, this rat might be a useful model
for inattentive-type ADHD (Sagvolden et al., 2005).
Moreover, there was an omission on slide 59 concerning the spontaneously hypertensive rat. On
this slide it was mentioned that this modified rat stimulates hyperactivity, however what is not
mentioned is that these rats also express impulsivity and inattentiveness (Sagvolden et al., 2005).
In addition, the SHRs meet most of the criteria for face, construct, and criterion predictive
validity; this makes them the best model to use for studying combined-type ADHD (Sagvolden
et al., 2005). For more information on the different and most valid rodent models for ADHD it is
best to view the article, “rodent models of attention-deficit/hyperactivity disorder” by Sagvolden
and colleagues (2005).
Comorbidity
In the presentation it was correctly mentioned that those with ADHD were at a higher risk of
developing substance abuse problems. An interesting study by Mannuzza and colleagues (2008)
showed that the risk of ADHD patients developing substance abuse problems was significantly
associated with the age at which methylphenidate treatment was started. More specifically, the
earlier the treatment was started the lower the chance of developing a substance abuse disorder.
Moreover, these findings are supported by animal data in rats suggesting that later preference in
rats is relatively decreased by exposure to methylphenidate in early development.
In the presentation it was correctly mentioned how children responded best to behavioral
therapies combined with stimulants; however, there was no mention of potential treatments for
adult sufferers of ADHD. Safren and colleagues (2005) found that adults responded best to a
combination of cognitive-behavioral therapy and stimulants.
References
Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A.,
Sklar, P. (2005). Molecular genetics of attention-deficit/hyperactivity disorder. Biological
psychiatry, 57(11), 1313-1323.
Gizer, I. R., Ficks, C., & Waldman, I. D. (2009). Candidate gene studies of ADHD: a metaanalytic review. Human genetics, 126(1), 51-90.
Jensen, P. S., Martin, D., & Cantwell, D. P. (1997). Comorbidity in ADHD: implications for
research, practice, and DSM-V. Journal of the American Academy of Child & Adolescent
Psychiatry, 36(8), 1065-1079.
Mannuzza, S., Klein, R. G., Truong, N. L., Moulton III, J. L., Roizen, E. R., Howell, K. H.,
Castellanos, F. X. (2008). Age of methylphenidate treatment initiation in children with
ADHD and later substance abuse: prospective follow-up into adulthood. The American
journal of psychiatry, 165(5), 604-609.
Ribasés, M., Ramos-Quiroga, J. A., Hervás, A., Sánchez-Mora, C., Bosch, R., Bielsa, A.,
Cormand, B. (2012). Candidate system analysis in ADHD: Evaluation of nine genes
involved in dopaminergic neurotransmission identifies association with DRD1. The
World Journal of Biological Psychiatry, 13(4), 281-292.
Safren, S. A., Otto, M. W., Sprich, S., Winett, C. L., Wilens, T. E., & Biederman, J. (2005).
Cognitive-behavioral therapy for ADHD in medication-treated adults with continued
symptoms. Behaviour research and therapy, 43(7), 831-842.
Sagvolden, T., Russell, V. A., Aase, H., Johansen, E. B., & Farshbaf, M. (2005). Rodent models
of attention-deficit/hyperactivity disorder. Biological psychiatry, 57(11), 1239-1247.
Seidman, L. J., Biederman, J., Liang, L., Valera, E. M., Monuteaux, M. C., Brown, A., Makris,
N. (2011). Gray matter alterations in adults with attention-deficit/hyperactivity disorder
identified by voxel based morphometry. Biological psychiatry, 69(9), 857-866.
Seidman, L. J., Valera, E. M., Makris, N., Monuteaux, M. C., Boriel, D. L., Kelkar, K.,
Biederman, J. (2006). Dorsolateral prefrontal and anterior cingulate cortex volumetric
abnormalities in adults with attention-deficit/hyperactivity disorder identified by
magnetic resonance imaging. Biological psychiatry, 60(10), 1071-1080.