Journal 1 Summary

A Review on the Role of Inflammation in Attention-Deficit/Hyperactivity Disorder

(ADHD), June 6, 2018, Leffa, Torres & Rohde

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized

by the impairing symptoms of inattention and/or hyperactivity/impulsivity which impairs to
certain extent the quality of life of those affected in terms of social, academic, and occupational
context.

It is diagnosed by clear evidence of symptoms showing impairment of ones quality of life in the
social, academic and occupational performance which is present in two different settings and
that started prior to 12 years of age. There are currently no biomarkers to diagnose ADHD and
the methodology of clinical interview is more relied upon.

Neurobiological basis

ADHD had been confirmed to have neurobiological basis through genetic and neuroimaging
studies showing that it has 70-80% heritability in both children and adults, with approximately
40% heritability associated to common genetic variants.

A study conducted with 20,183 ADHD patients and 35,191 controls identified 12 independent loci
exceeding genome-wide significance which are related to neural development, plasticity,
neuronal wiring, dopamine levels, intellectual disability, and speech learning development, in
addition to identified environmental factors.

Another study with 1,713 ADHD patients and 1,529 controls showed volume reduction in the
nucleus accumbens, amygdala, caudate, hippocampus, and putamen in ADHD patients. This is
supplemented by studies which show reduced activities of distinct cortical regions during tests
requiring attention and impulsivity control.

Despite several studies relative to neurobiological basis of ADHD, its pathophysiology is still
poorly understood.

The Role of Inflammation

One area of growing interest relative to the neuropathological mechanism affecting ADHD is the
immune system. This is due to the increasing evidence supporting the role of inflammation in
several neuropsychiatric disorders. For ADHD these evidence comes from 3 main lines:

1. Comorbidity with inflammatory and autoimmune disorders;

2. Biochemical markers; and
3. Genetic studies.

Comorbidity with inflammatory and autoimmune disorders

It has been observed that there is a strong association between ADHD and inflammatory and
autoimmune disorders, as it has been found by experts that ADHD patients were more likely to
have asthma, allergic rhinitis, eczema, psoriasis, thyrotoxicosis, atopic dermatitis, and allergic
conjunctivitis as compared with non-ADHD subjects.

This co-occurrence suggests a range of underlying mechanisms, including altered immune

response, common genetics, and environmental links. One suggestion is that increased cytokine
release caused by the inflammatory process may affect the prefrontal cortex functioning or that
ADHD abnormalities may be caused by the exaggerated central nervous system inflammatory
response in the fetus due to maternal inflammation.

Although data support co-occurrence of ADHD and inflammatory and autoimmune disorders, the
factor having caused such comorbidity had not been identified.

Biochemical markers

While there have been studies searching for inflammatory biomarkers involving specific
antibodies, cytokines, and neurotrophic factors, no conclusive findings had been established.
Nevertheless, it has been found that a significantly higher immunoreactivity against certain anti-
bodies in ADHD patients suggesting its relation to the autoimmune system. Moreover, several
studies on premature and low-birth-weight newborns measured 25 inflammation-related
proteins in the serum and found that children who had elevated concentration of inflammation-
related proteins during the first 2 weeks of life were more likely to have attention problems at 24
months.

The tests provided mixed results, but evidence exists to suggest that increased inflammation
during early development may be a risk factor for ADHD symptoms.

Genetic studies

There has been a genetic studies that shows that polymorphisms in genes are related to
inflammatory pathways that play a role in ADHD. It is found out that 2 single-nucleotide
polymhorpisms (SNPs) in a cytokine-related gene, the ciliary neurotrophic factor receptor
(CNTFR), were associated with ADHD inattentive symptom severity. Also there has been a
genome-wide association study that found no SNPs at the significant threshold, however a
pathway analysis found an association with SNPs involved in the regulation of gene expression,
cell adhesion and inflammation.

Even though there are numbers of genetic studies that provide evidence on the role of
inflammation in ADHD, it is important to consider that there is high variation between the
methodologies performed. Also, there is no consensus about the inflammatory-related genes
predispose to ADHD.

Conclusion

In ADHD the indication from comorbidity with inflammatory and autoimmune disorders, serum
biomarkers and genetic studies can be found. The biomarkers measured in patients with ADHD
gave unclear results but increased inflammation during the early development appears to be
related to an ADHD phenotype. Because ADHD is a highly hereditary disorder it might be
expected that polymorphisms in inflammatory-related dene are present in patients.

Although the study on role of inflammation in ADHD does not support nor contradicts what
is stated in the DSM 5, the result of this can supplement the information and may be
useful for future researches.
Journal 2 Summary
A systematic Review of Attention Deficit Hyperactivity Disorder (ADHD) and
Mathematical Ability: Current Findings and Future Implications, August 27, 2015, Tosto,
Momi, Asherson & Malki

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder with a high

global prevalence of 5.29 % characterized by severe and impairing difficulties with sustain
attention, restless over activity, and impulse control. There are three clinical presentations of
ADHD: predominantly inattentive (ADHD-I), predominantly hyperactive-impulse (ADHD-H) and
combined (ADHD-C) type clinical presentation. Although the three clinical presentations of ADHD
shows core symptoms, the disorder is highly heterogeneous and connected with a plethora of
different impairments that includes cognitive and behavioural deficits.

Mathematical ability showed positive association with socio-economic status in adulthood due to
more opportunities. Recent studies have demonstrated links between mathematical ability and
ADHD. There are several studies that is linked to attentional processes in ADHD with
mathematical abilities, as plays a key role in mathematical ability investigation focusing on the
association between the inattentive domain of ADHD and mathematics may provide further
insight into the disorder and the mechanisms of mathematical learning. The aim of the
systematic review was to give an overview of studies up to date.

Cross Sectional and longitudinal studies included assessed the difference between ADHD cases
and healthy controls and the association between ADHD and mathematical performance.
Following quality assessment, all the papers rated as either high or medium with no papers
achieving a low-quality rating score:
In high quality rating studies, 20 out of 24 was reported to be statistically significant negative
association between ADHD symptoms and mathematical performance wherein 7 of these were
negatively associated with the inattention subtype and 3 out of the 11 remaining showed a
significant association in hyperactivity-impulsivity. Of the three longitudinal studies, they did not
find a significant correlation between the ADHD-C subtype and mathematical ability for the span
of 8 years of assessment. Other two longitudinal studies was reported to have a negative
correlation between ADHD and mathematical abilty at baseline and follow up. Children with
ADHD in mathematical achievement scores decreased over time.
In medium quality rating studies, it shows that six out of ten was reported to be significantly
negative association between ADHD and mathematical performance. It was reported that there
is a significant association only with the ADHD-C subtype but not with the inattention group.

The overall studies revealed that a significant association even after controlling for IQ, age,
socioeconomic status, and other potential attenuating factors such as psychostimulant
medication. Regardless of the statistical power, most of the studies showed a lower performance
on mathematical tests in ADHD participants compared with healthy controls. To sum up all,
there is a negative association between ADHD and mathematics and this association is stronger
for the inattentive symptoms. The genetic studies showed that the covariation of ADHD and
mathematics is due to genetic factors but environmental factors still plays a role. Further
research is necessary to investigate specific factors to determine the association between ADHD
and mathematical ability.

The study shows that there is a significant genetic correlation between mathematics and
ADHD. It is greater for the inattentive component compared with the hyperactive-
impulsive component which supported the DSM 5 that claims inattentive behaviour is
associated with various underlying cognitive processes.
Journal 3 Summary
Genetics of Attention Deficit Hyperactivity Disorder, February 19, 2018, Faraone & Larsson

Attention deficit hyperactivity disorder is a childhood onset condition with impairing symptoms of
inattention, impulsivity and hyperactivity. There are lot of studies showed how genes play in the
etiology of ADHD. This includes the studies on family twin and adoption. Adoption studies says
that familial factors are more associated to genetic factors rather than the environmental factors
and adopted relatives are more likely to develop ADHD.

Genetic linkage was the first genome wide method applied to ADHD. Although there is an
overlap with the suggestive findings it does not met genom-wide significance. It shows that DNA
variants in genes or regulatory regions increase the risk to develop ADHD. In other case, genetic
defect may lead to ADHD in the absence of other DNA variants. Up to now, there is no known
reason what variants make up the polygenic component. Even though there is evidence for
genes as the risk factors for ADHD, it does not mean that the environment factor was disprove
as a source of etiology.

The above study suggests that in terms of adoption, familial factors of ADHD are
attributable to genetic factors which further support what is the DSM 5 saying that ADHD
is elevated in the first-degree biological relatives of individuals with ADHD. The heretabilty
is substantial. But in here, it does not mean that environmental factors was excluded as
one of the source of etiology.

Journal 4 Summary
The Effect of ADHD on the Life of an Individual, Their Family and Community from Pre
School to Adult Life, January 21, 2015, Harpin

Attention deficit hyperactivity disorder is a chronic, debilitating disorder which may impact upon
many aspects of individual’s life, it includes academic difficulties, social skills problem and
strained parent-child relationship. It is important to consider the effectiveness of the treatment
for ADHD on how the disorder will affect the daily lives of a child, young people, and their family.
As the child with ADHD grows, the effects of it may change. Associated difficulties such as
delayed development oppositional behaviour and poor social skills may be present with a child
ADHD.

Preschool Years

If ADHD is possible with this stage, it is more important to support or offer parent advices
because even in this early stage, parental stress is huge and when a child with ADHD doesn’t
respond to ordinary parental requests.

Primary School Years

Child with ADHD are easily begin to be noticed as other child without starts to develop the skills
of maturity. Comorbid problems such as specific learning difficulties may start to affect the child.
There is a data from self-evaluation the showed that the children with ADHD view their most
problematic behaviour are less within their control and more prevalent than children with ADHD.
It was also said that ADHD in child was a great factor to predict depression on mothers.
ADHD in Young People

In a study by Edward et al examined teenagers with ADHD and ODD rated themselves as having
more parent-teen conflict than did community controls. Moreover, a survey to 11 to 15 years old
reported that those with hyperkenesis were twice as likely as the overall population to have “a
severe lack of friendship”. Young people with ADHD have a higher risk of having academic
failure, dropping out of school,teenage pregnancy and criminal behaviour. Person with ADHD are
easily distracted from concentrating that is why compared with age matched controls, drivers
with ADHD are at increased risk of traffic violations.

Adult Life

They are the one who have higher risk to be dismissed from employment and tried number of
jobs before being able to find one at which they can succeed. Also the risk of drug and substance
abuse is significantly increased in adults with persisting ADHD synptoms and have not been
receiving treatment. The genetic aspects of ADHD mean that adult with ADHD have a higher
tendency to have a child with ADHD.

Mannuzza’s review of the long term prognosis in ADHD conclude that childhood ADHD does not
prevent high educational and vocational achievement. Current treatment for ADHD focused on
the short term relief which means that the important times of the day is unaffected by treatment
regimes. This may negatively impact on the child and family functioning.

In the study the effect of ADHD on life of an individual, their family and community from
preschool to adult life shows that during adult life, ADHD are more likely to be dismissed
from employment that will support what’s the DSM 5 is saying that adults has a poorer
occupational attainment, attendance and higher probability of unemployment as well as
elevated interpersonal conflict. The DSM 5 also stated that one of the functional
consequences of ADHD are traffic accidents and violations, in the above study they also
declared that compared with age matched controls, drivers with ADHD are at increased
risk of traffic violations. In addition, it was said in the study that adult with ADHD has a
risk of having drug and substance abuse that supported the differential diagnosis of the
DSM 5 in substance abuse disorder.

Journal 5 Summary
Tracking Distraction the Relationship Between Mind-Wandering, Meta-Awareness, and
ADHD Symptomatology, August 1, 2014, Franklin, Mrazek, Anderson, Johnston, Smallwood,
Kingston & Schooler

Attention deficit hyperactivity disorder is widely recognized as a serious mental health concern
that is characterized by inattention, hyperactivity and impulsivity. In the currents study, they
examined the relationship between mind-wandering, meta-awareness and ADHD
symptomatology in college students. The study found that a composite of ADHD score was
positively correlated with both frequency of minw-wandering and lack of the awareness of mind
wandering. Even though prior work has been suggested a link between ADHD symptomatology
and mind-wandering, it is not been clearly demonstrated befor a naturalistic settings.

A more detailed analysis of the PDA data revealed that participants with higher DAHD scores are
more likely to have a mind-wandering episodes that are detrimental and interfere with their daily
lfe. It reveals that for the first time particular mind deficit related to DAHD symptomatology in a
community sample. The present study showed new evidence on the association between meta
awareness, mind wandering and symptomatology participants that are high on ADHD scales are
more likely to be unaware that they are mind wandering. Also the present study provides new
insights into the relationship of the three. The study findings suggested that some of the
negative consequences mind wandering offset by strategies that pushes meta wareness. Lastly,
the relationship between ADHD mind wandering episodes reveals that there may be some
beneficial aspects of the mind wandering experience for those with ADHD symptomatology.

Mind-wandering and meta-awareness was not indicated in the DSM5, but the result was a
great start to show new studies that may be correlated with the disorder. It also might
provide promising directins for future researchers and studies that can be potentially help
those with a tendency of having ADHD to manage their symptoms.

Journal 6 Summary
A Pilot Trial of Mindfulness Meditation Training for ADHD in Adulthood: Impact on Core
Symptoms, Executive Fucntioning, and Emotion Dysregulation, December 4, 2013,
Mitchell, Mclyntre, English, Dennis, Beckham & Kollins

ADHD is a developmental disorder that persists into adulthood for the majority of cases and
occurs in approximately 4% of adult population.Mindfulness intervention training gather
empirical interest as an intervention for ADHD in adulthood. Although there is no yet study of
mindfulness as a standalone treatment. The study assessed the feasibility of treatment
acceptability and preliminary efficacy of a group based mindfulness. Meditation training for
adults with ADHD on core symptoms, functional impairment associated with core symptoms, EF
and emotions dysregulation. The study creates a sample composed solely of adults diagnosed
with ADHD. The analysis includes the Mindfulness awareness program is a feasible and
acceptable treatment and the preliminary efficacy of mindfulness meditation training for adult
ADHD. Treatment outcome variables were expanded beyond core ADHD symptoms and
considered the effects of mindfulness in EF and emotion dysregulation.

The study above does not support nor contradict what is stated in the DSM 5, however the
result of this study may be useful and may add to the growing literature suggesting that
mindfulness meditation for ADHD in adulthood can be helpful.

Journal 7 Summary
Fathers with Childhood ADHD, Parenting and their Young Children;s Behaviour:
Offspring of the Pittsburgh ADHD Longitudinal Study (PALS), June 5, 2018, Jospeh,
Kennedy, Gnagy, Perlman, Pelham, Molina

ADHS is the most common childhood behaviour disorder with an estimated worldwide prevalence
of 5%. The study show an initial yet important effort to characterized offspring of fathers with
research quality diagnosis in childhood parenting factors that may impact their children’s
functioning. There are more ADHD symptoms to the children of fathers with ADHD that is why it
I more easy to identify or detect ADHD in child as early as 3 years. The advantage of early
detection of the symptoms is before the academic success, child with ADHD symptoms can be
treated early.
According to the recent study, parent-training can be effective to mothers but there is no yet
proven study to fathers that is why this topic focused on it. It was also proven that there is lower
chances of supportive responses from fathers with childhood ADHD toward this negative
emotions of their child. Therefore, the parent-training can benefit fathers with childhood ADHD
also it will help them as their children develops.

Although the result of the study does not support nor contradict what is already stated in
the DSM 5, the study will still benefit and supplement the information needed for
developing better assessment and treatment because if you could detect ADHD earlier,
treatment can be administer early.