Abstract Attention deficit/hyperactivity disorder (ADHD) is characterised by different kinds of problems, such aspoor concentration, anti-social behaviour and drug abuse. The first symptoms start appearing in childhood. The majority of ADHD patients suffer from different types of disorders, such as anti-social personality, anxiety and mood disorders (Wilens& Spencer, 2010). ADHD is associated with the development of abnormal structures in the prefrontal cortex (Arnsten& Li, 2005).Moreover, there are differences instructures of brain between patients with ADHD and normal people.Neuroimaging studies have shown reduced white matter volumes and cortical thickness in patients with ADHD (Castellanos et al., 2002). In addition, another neurobiological factor, which contributes to the development of ADHD, is the levels of dopamine (Curatolo, D'Agati, &Moavero, 2010) and the levels of norepinephrine. The dysregulation of norepinephrine and dopamine levels can affect the function of prefrontal cortex.Furthermore, the size of corpus callosum (CC) is smaller in ADHD children (Luders et al., 2009).

1. 1
The Effects of Dysregulated Dopamine Levels on Cognitive Performance
in Young People withADHD and the Use of Methylphenidate Treatment
Abstract
Attention deficit/hyperactivity disorder (ADHD) is characterised by different kinds of
problems, such aspoor concentration, anti-social behaviour and drug abuse. The first
symptoms start appearing in childhood. The majority of ADHD patients suffer from
different types of disorders, such as anti-social personality, anxiety and mood
disorders (Wilens& Spencer, 2010). ADHD is associated with the development of
abnormal structures in the prefrontal cortex (Arnsten& Li, 2005).Moreover, there are
differences instructures of brain between patients with ADHD and normal
people.Neuroimaging studies have shown reduced white matter volumes and cortical
thickness in patients with ADHD (Castellanos et al., 2002). In addition, another
neurobiological factor, which contributes to the development of ADHD, is the levels
of dopamine (Curatolo, D'Agati, &Moavero, 2010) and the levels of norepinephrine.
The dysregulation of norepinephrine and dopamine levels can affect the function of
prefrontal cortex.Furthermore, the size of corpus callosum (CC) is smaller in ADHD
children (Luders et al., 2009).
Introduction
ADHD is a common childhood developmental disorder and it is very usual in young
boys.However, ADHD can be a chronic mental disorder with severe symptoms. Thus,
this mental disorder can be diagnosed into adulthood (Wilens& Spencer, 2010). The

2. 2
diagnosis of ADHD in young people and adults can be based on criteria in the
Diagnostic and Statistical Manual of Mental Disorders (DSM) (American Psychiatric
Association, 1994). The first diagnostic criteria of ADHD were included in DSM-III
in 1980 (American Psychiatric Association, 1980).Additionally, there was update of
ADHD diagnostic criteria in DSM-IV-TR. According to DSM, the diagnosis of
ADHD depends on frequency and repeatability of symptoms. Specifically, the main
features of ADHD are inattention, impulsivity and hyperactivity. So, the young people
with ADHD show attention deficits and it is difficult for them to concentrate and pay
attention to their tasks. In addition, they have not effective communication skills,
because of their impulsiveness. Also, another characteristic of ADHD is hand
flapping, because of hyperactivity. Furthermore, the diagnosis of ADHD is possible at
early age, if there are some symptoms, which may affect “social and school
functioning” (Curatolo, D'Agati, &Moavero, 2010).
ADHD is associated with mood and anxiety disorders. There is a significant increase
of depressive and anxiety symptoms, because of ADHD (Kessler et al., 2006) (Jensen,
Shervette, Xenakis,&Richters, 1993). An important research study in bipolar children
with ADHD symptoms showed that “rates of ADHD ranging from 57% to 98% in
bipolar children; and rates of bipolar disorder in 22% of ADHD children and
adolescents” (Faraone, Biederman, Wozniak, Mundy, Mennin, & O'Donnell,
1997).Moreover, ADHD patients suffer from cognitive problems and hyperactivity.
The patients with bipolar disorder (BPD) show mood and psychotic symptoms.
Therefore, patients, who show ADHD and BPD symptoms, can suffer from both of
these disorders (Wilens, Biederman, Wozniak, Gunawardene, Wong, &Monuteaux,
2003).

3. 3
In addition, one of the most severe symptoms of ADHD is substance abuse. Findings
of research indicate that there is a significant rise of alcohol and drug abuse. Also, the
risk of smoking is increased in patients with ADHD. Specifically,“ADHD adolescents
and adults become addicted to cigarette smoking at twice the rate compared to non-
ADHD individuals” (Wilens& Spencer, 2010).However, the risk for alcohol and drug
abuse is reduced in treated young girls with ADHD compared to untreated (Wilens,
Adamson, Monuteaux, Faraone, Schillinger, Westerberg, &Biederman, 2008).
Neurobiological basis of ADHD
As it has been mentioned before, the dysregulation of dopamine levels affects in
neurobiological bases of Attention-Deficit Hyperactivity Disorder (ADHD).
Nowadays, there are different kinds of treatment for ADHD, such as
psychopharmacological therapy with the use of stimulants (Curatolo, D'Agati,
&Moavero, 2010). The immediate release of methylphenidate and atomoxetine can
decrease the symptoms of ADHD. In addition, the use of functional MRI (fMRI) can
provide useful information about effects of methylphenidate on brain functions
(Schweren, Zeeuw&Durston, 2013). ADHD is a very complicated mental disorder,
which requires the use of a complex therapy plan “that includes psychosocial,
behavioural and educational advice and interventions” (Curatolo, D'Agati, &Moavero,
2010).
Moreover, the development of structural imaging studies can help for observation of
abnormal brain structures in patients with ADHD. For instance, researchers used
structural magnetic resonance imaging (MRI) (Seidman et al., 2006)and they
observed that anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex

4. 4
(DLPFC) are smaller to ADHD patients. Additionally, the dorsolateral prefrontal
cortex (DLPFC) is associated with the function of working memory that contributes to
“ability to retain information while processing new information” (Wilens& Spencer,
2010). On the other hand, the function of anterior cingulate cortex (ACC) includes
person’s ability to “focus on one task” and make his/her choice among different
options (Wilens& Spencer, 2010).Furthermore, there are so many research studies
about effects of reward on cognitive tasks (Luman, Tripp &Scheres,
2010).Specifically, these research studies examinedhow reward sensitivity is
associated with cognitive performance in patients with ADHD (Luman, Tripp
&Scheres, 2010).
Research Questions and Hypotheses
This research can be addressed by questionsabout neurobiological basis of ADHD,
such as the dysregulation of dopamine levels in young people with ADHD. Moreover,
questions about the development of brain structures in young people with ADHD. It is
hypothesised that the participants, who have received long-term methylphenidate
therapy, will present better results in cognitive performance compared to the
participants,who had not received methylphenidate before. Also, it ishypothesised that
the participants, who had not received methylphenidate before, will improve their
cognitive performance after the administration of methylphenidate.
Methods
First of all, the sample of this research will be children and adolescents between the
ages of 9 and 17. There will be two different groups. The first group will consist of 60

5. 5
children and adolescents with ADHD, who have received long-term methylphenidate
therapy. The second group will consist of 60 children and adolescents with ADHD,
who had not received methylphenidate before.
Before use of methylphenidate, it is important to measure one aspect of attention. For
this reason children and adolescents of the two groups will be given a cognitive
task.This cognitive task will examine the children's and adolescents’ ability to sustain
their attention. Therefore, participants of the two groups will try to focus on a
stimulus for 15 minutes. It is possible that there will be difference on results of
cognitive task between these groups. The first group may perform better the cognitive
task than the other group, because of the long-term use of methylphenidate.
Moreover,it will be necessary to use the functional MRI (fMRI), because the
method/analysis of fMRI can provide information about dysregulation of dopamine
levels and effects of this (dysregulation) on cognitive task.
Then, the children and adolescents of two groups will receive a dosage of
methylphenidate. After 30 minutes, they (children and adolescents) will be given the
same cognitive taskas before. As regards children and adolescents of first group, their
performancemay remain stable in cognitive task. It is possible that the performance of
the second group will be improved in cognitive task after the administration of
methylphenidate. In addition, it will be necessary to use fMRI, because fMRI will
provide information about the effects of methylphenidate on dopamine levels and
structures of brain. The method/analysisof fMRI may present a significant increase of
dopamine levels and functional connectivity between frontostriatal brain structures
and other brain regions. Wong and Stevens (2012) conducted research and they
studied this functional connectivity. Moreover, the cognitive symptoms of ADHD
participants, such as poor concentration and inattention,will be decreased.

6. 6
Anticipated Results
As it is known, methylphenidate can block the reuptake of dopamine (Schiffer et al.,
2006) and it is also possible to enhance reward sensitivity (Volkow et al., 2004).
Therefore, an anticipated result can be the significant increase of dopamine levels
andthe improvement of reward sensitivity. The increase of dopamine levels can
enhance dopamine responses to reward and the participants of second group can
improve their cognitive performance after methylphenidate administration. On the
other hand, the use of methylphenidate will not affect the participants of the first
group to the same extend as those of the second group.The first group will not present
great differences in cognitive performance after the administration of
methylphenidate.
Discussion
The benefits of this research proposal can be very useful for understanding the
effects of dopamine levels on cognitive tasks in young people with ADHD and how
methylphenidate treatment can improve reward sensitivity. Furthermore, the findings
of research will provide information for the important role of long-term use of
methylphenidate in young people with ADHD.Finally, this research will provide
further knowledge for neurobiological basis of ADHD.

7. 7
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