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Magnesium supplementation in children with attention deficit hyperactivity disorder

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Abstract and Figures

Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with associated mineral deficiency. Aim: To assess magnesium level in ADHD children and compare it to the normal levels in children. Then, to detect the effect of magnesium supplementation as an add on therapy, on magnesium deficient patients. Methods: The study was conducted on 25 patients with ADHD and 25 controls. All subjects had magnesium estimation in serum and hair. ADHD children were further assessed by Wechsler intelligence scale for children, Conners’ parent rating scale, and Wisconsin card sorting test. Then magnesium deficient patients were assigned into 2 groups, those who received magnesium, and those who did not. The difference between the studied groups was assessed by Conners’ parents rating scale and Wisconsin card sorting test. Results: Magnesium deficiency was found in 18 (72%) of ADHD children. The magnesium supplemented group improved as regards cognitive functions as measured by the Wisconsin card sorting test and Conners’ rating scale. The patients reported minor side effects from magnesium supplementation. Conclusion: Magnesium supplementation in ADHD, proves its value and safety.
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ORIGINAL ARTICLE
Magnesium supplementation in children
with attention deficit hyperactivity disorder
Farida El Baza, Heba Ahmed AlShahawi, Sally Zahra
*
, Rana Ahmed AbdelHakim
Ain Shams University, Cairo, Egypt
Received 20 May 2015; accepted 27 May 2015
Available online 7 July 2015
KEYWORDS
ADHD;
Magnesium;
Supplementation;
Treatment
Abstract Background: Attention deficit hyperactivity disorder (ADHD) is a common neurodevel-
opmental disorder with associated mineral deficiency.
Aim: To assess magnesium level in ADHD children and compare it to the normal levels in
children. Then, to detect the effect of magnesium supplementation as an add on therapy, on
magnesium deficient patients.
Methods: The study was conducted on 25 patients with ADHD and 25 controls. All subjects had
magnesium estimation in serum and hair. ADHD children were further assessed by Wechsler
intelligence scale for children, Conners’ parent rating scale, and Wisconsin card sorting test.
Then magnesium deficient patients were assigned into 2 groups, those who received magnesium,
and those who did not. The difference between the studied groups was assessed by Conners’ parents
rating scale and Wisconsin card sorting test.
Results: Magnesium deficiency was found in 18 (72%) of ADHD children. The magnesium
supplemented group improved as regards cognitive functions as measured by the Wisconsin card
sorting test and Conners’ rating scale. The patients reported minor side effects from magnesium
supplementation.
Conclusion: Magnesium supplementation in ADHD, proves its value and safety.
Ó2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Ain Shams University. This is
an open access article underthe CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
1. Introduction
Attention-deficit/hyperactivity disorder (ADHD) is a com-
mon, early-onset and enduring neuropsychiatric disorder
characterized by developmentally inappropriate deficits in
attention, hyperactivity, increased impulsivity and emotional
deregulation, resulting in impairments in multiple domains of
personal and professional life [1].
Evidence for dietary/nutritional treatments of attention-def
icit/hyperactivity disorder (ADHD) varies widely; however
recommended daily allowance of minerals and essential fatty
acids is an ADHD-specific intervention [2].
Magnesium is the fourth most abundant mineral in the
body and is essential for good health [3]. Its biological
importance evolves from being an essential trace mineral
involved in over 300 metabolic reactions including cellular
*Corresponding author.
E-mail addresses: faridabaz@hotmail.com (F. El Baza), hebaelshahawi
@yahoo.com (H.A. AlShahawi), sallyzahra@yahoo.com (S. Zahra),
ranahak@hotmail.com (R.A. AbdelHakim).
Peer review under responsibility of Ain Shams University.
The Egyptian Journal of Medical Human Genetics (2016) 17, 63–70
HOSTED BY
Ain Shams University
The Egyptian Journal of Medical Human Genetics
www.ejmhg.eg.net
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http://dx.doi.org/10.1016/j.ejmhg.2015.05.008
1110-8630 Ó2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Ain Shams University.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
energy generation, nucleic acid production (DNA, RNA), and
protein synthesis. Magnesium (Mg
+2
) is, also, the most abun-
dant intracellular divalent cation [4].
The mineral magnesium is necessary for sufficient brain
energy and aids smooth transmission of communications
through the central nervous system, calms the central nervous
system and is an important component in the making of
serotonin [5].
Magnesium deficiency is typified by a number of reductions
in cognitive ability and processes, and in particular a reduced
attention span along with increased instances of aggression,
fatigue and lack of concentration [6]. Other common symp-
toms of magnesium deficiency include becoming easily
irritated, nervousness, fatigue and mood swings [6].
Given the nature of these symptoms and the significant
amount of overlap that they share with ADHD, this led
many experts involved in the treatment and care of ADHD
to hypothesize that children who suffer from ADHD also have
magnesium deficiency as well.
In the current study, magnesium level in children with
attention deficit hyperactivity disorder (ADHD) will be
compared to normal children, in both serum and hair. Then,
the effects of magnesium supplementation in magnesium
deficient patients will be assessed.
2. Subjects and methods
This study is a case-control prospective interventional compar-
ative study. It was conducted on 25 patients with ADHD and
25 age and sex matched controls.
2.1. Participants
Patients were considered ineligible for the study, if they
fulfilled criteria of ADHD according to DSMIV, their age
range was between 6 and 16 years and their IQ above 70.
Ineligibility for the study included presence of other medical
conditions as significant anemia, chronic illness, hearing or
vision impairment, medication side effects which may result
in hyperactivity and impaired sleep rhythm.
Twenty five healthy children recruited from the sibs of the
ADHD group were included in the study as a control group.
Both patients and healthy controls were recruited from
Children’s hospital and institute of psychiatry, Ain Shams
University, Cairo, Egypt. The work has been carried out in
accordance with the code of Ethics of the World Medical
Association (Declaration of Helsinki) for experiments involv-
ing humans.
2.2. Study design
Patients were recruited from the clinic randomly. After
explaining the purpose of the study, written consents from
parents and the acceptance of the ethics committee of Ain
Shams University were obtained. Data were collected through
the administration of the predesigned questionnaires to the
parents.
Each patient in this study was subjected to the following;
Full detailed medical history including presence of organic or
psychological diseases, perinatal and developmental history,
family history of similar cases, and the previous treatment
which was received.
Clinical Examination included; body measurements,
physical examination and neurological examination.
2.3. Investigations
Serum magnesium level was assayed by auto analyzer [7].
Hair magnesium level (Fresh, clean hair sample) was sub-
jected to Inductively Coupled Mass Spectroscopy (ICP-MS)
which has been cited as currently the most sensitive and com-
prehensive technique available for multi-element analysis of
trace elements to measure hair magnesium in both cases and
controls [8].
2.4. Scales
DSM (IV) to confirm the diagnosis of ADHD in cases and to
exclude concomitant psychiatric disease [9].
Conners’ parent rating scales using an Arabic version for
detection of the severity of ADHD [10]. Items are scored on
14 subscales but in our study we used only the hyperactivity,
inattention, oppositional and impulsivity scores.
Wisconsin’s card sorting test (WCST) is a neuropsycholog-
ical test of ‘‘set-shifting’’, i.e. the ability to display flexibility in
the face of changing schedules of reinforcement. It’s a measure
of executive function.We used computerized versions of the
task (Microsoft Windows-compatible version 4.0). It has the
advantage of automatically scoring the test, which was quite
complex in the manual version [11].
Wechsler intelligence scale for children (WISC) using the
Arabic version for IQ assessment [11].
We compared the ADHD group (25 patients) with the
matched control group (25 children) as regards different
variables mainly the hair and serum magnesium. The ROC
Curve (Receiver Operating Characteristics) was used for the
diagnosis of decreased magnesium level in hair among
ADHD children as there is no available reference in Egypt
for hair Magnesium in this age group. Using ROC Curve,
0
0.2
0.4
0.6
0.8
1
1.2
4
14.5
24.5
32.5
38
40.5
44
48.5
52.5
60
66
90.5
98
140
Percent
Sensitivity Specificity
Figure 1 Using ROC Curve the cut off value for deficient
magnesium level in hair was equal or less than 60.
64 F. El Baza et al.
the cut off value for deficient Magnesium level in hair was
equal or less than 60 as shown in Fig. 1. And according to this
cut off value; the magnesium deficient ADHD patients were
found to be 18 (group B) and the ADHD cases with normal
hair magnesium were 7 cases (group A).
The magnesium deficient children were randomly assigned
into 2 equal groups. The first group received magnesium sup-
plementation in a dose of 200 mg/day as an add on therapy to
the standard medical treatment. The second group received
standard medical therapy alone. After 8 weeks the 2 groups
will be compared with Conners’ parent rating scale and
Wisconsin card sorting test.
2.5. Statistical analysis
The collected data were revised, coded, tabulated and intro-
duced to a PC using Statistical package for Social Science.
Data were presented and suitable analysis was done according
to the type of data obtained for each parameter.
I. Descriptive statistics: mean, standard deviation (±SD),
minimum and maximum values (range) for numerical
data and frequency and percentage of non-numerical
data were applied.
II. Analytical statistics: included The ROC Curve (receiver
operating characteristic) which provides a useful way
to evaluate the sensitivity and specificity for quantitative
diagnostic measures that categorize cases into one of
two groups. Student t test was used to assess the statisti-
cal significance of the difference between the two study
group means. Correlation analysis (using Pearson’s
method): To assess the strength of association between
two quantitative variables. The correlation coefficient
denoted symbolically by ‘‘r’’ defines the strength and
direction of the linear relationship between two
variables. Chi square test: was used to examine the
relationship between two qualitative variables. Fisher’s
exact test: was used to examine the relationship between
two qualitative variables when the expected count was
less than 5 more than 20% of cells. Paired t-test was
used to assess the statistical significance of the difference
between two means measured twice for the same study
group.
3. Results
In the current study, there was no significant difference regard-
ing the age and gender among normal children (control) and
ADHD patients Table 1. i.e the two samples were homogenous
(Pvalue > 0.05).
There was a significant difference between cases and con-
trols as regards hair magnesium level but there was no signif-
icant difference as regards serum magnesium level Table 2.
Magnesium deficiency was more common in males than in
females, otherwise the other characteristics showed no signifi-
cant difference (Table 3).
Also, there was no statistically significant difference as
regards attention, memory loss, fear, restlessness, insomnia,
tics, cramps and dizziness between the two groups.
At the beginning of the study there was no statistically
significant difference between the two groups as regards the
different psychiatric scales Table 4.
However, when we correlated hair magnesium level to the
different psychiatric scales among children with ADHD we
found a significant correlation between hair magnesium and
total IQ and an indirect significant correlation between hair
magnesium and the hyperactivity components of Conners’
scale Table 5.
The magnesium deficient patients (18 patients) were then
randomly divided into two groups; Group B 1 (9 patients)
received magnesium supplementation, Group B 2 (9 patients)
received their standard medical treatment without magnesium
supplementation.
Comparison between the psychiatric scales at baseline and
at follow up among magnesium treated ADHD cases who
had low hair magnesium level (group B1) showed that there
was a highly significant improvement in hyperactivity and
impulsivity, and also a significant improvement in inattention,
opposition and conceptual level Table 6.
While, comparison between the psychiatric scales at base-
line and at follow up among untreated low hair Magnesium
ADHD cases showed that there was no such improvement
Table 7.
Percentage of improvement of the psychiatric scales at fol-
low up among magnesium treated (group B1) and untreated
(group B2) Fig. 2.
Percentage of change in Categories completion, Conceptual
level, Oppositional and impulsivity components of Conners’
scale although showed improvement at follow up in
Table 1 Comparison between cases and controls regarding
personal characteristics.
Type P
*
Sig
Cases
N=25
Controls
N=25
%%
Sex Male 20 80.0 19 76.0 0.107 NS
Female 5 20.0 6 24.0
Age Mean ± SD 7.74 ± 1.48 7.40 ± 1.35 0.534
**
NS
NS = non significant; Sig = significance.
*
Chi square test.
**
Student’s ttest.
Table 2 Comparison between cases and control as regards
serum and hair magnesium level.
Type PSig
Cases N= 25 Controls
N=25
Mean ±SD Mean ±SD
Serum Mg (mg/dl) 2.23 0.13 2.32 0.28 0.366 NS
Hair Mg (mg/kg) 54.48 16.65 109.20 26.34 0.0001 HS
SD = standard deviation; NS = non significant; HS = highly
significant; Sig = significance.
Magnesium in ADHD 65
magnesium treated patients of group B1 rather than untreated
patients of group B2. However these changes were not statisti-
cally significant (60%, 60%, 55.6% and respectively).
However, the percentage of change in the inattention as
well as hyperactivity components of Conners’ scale showed
a statistically significant improvement (77.7% and 88.9%
respectively).
As regards the side effects of magnesium supplementation
in our patients (group B1) 22.2% experienced adverse effects
in the form of mild abdominal pain and diarrhea Table 8.
4. Discussion
In the current study, there is a robust finding of decreased hair
magnesium in 18 (72%) of children with ADHD, while serum
hair magnesium is normal. This could be explained on genetic
and metabolic basis. Metabolically, Mg
2+
transport may be
reduced without change in serum MG
2+
concentrations.
This supports the finding of low hair follicle Mg
+2
, while
serum Mg
2+
is normal. Furthermore, abnormalities in
TRPM6 genes, which regulates the entry of magnesium into
Table 3 Comparison between cases with normal (group A) and low hair magnesium (group B) as regards personal and medical
characteristics.
Mg in hair diagnosis PSig
Normal Mg (group A) N= 7 Decreased Mg (group B) N=18
N% N %
Sex Male 3 42.9% 17 94.4% 0.012 S
Female 4 57.1% 1 5.6%
Age Mean ± SD 7.8 ± 1.2 7.7 ± 1.6 0.917 NS
Maternal age at conception Mean ± SD 25.7 ± 3.3 25.3 ± 5.1 0.836 NS
Number of sibling Mean ± SD 1.6 ± 1.3 1.7 ± 0.7 0.700 NS
Order of birth Mean ± SD 1.9 ± 0.9 1.8 ± 0.9 0.840 NS
Consanguinity Negative 6 85.7% 14 77.8% 0.999 NS
Positive 1 14.3% 4 22.2%
Socioeconomic Unprivileged 6 85.7% 11 61.1% 0.362 NS
Privileged 1 14.3% 7 38.9%
Family history Non 4 57.1% 12 66.7% 0.434 NS
ADHD 0 0.0% 3 16.7%
Mother’s occupation Negative 5 71.4% 14 77.8% 0.739 NS
Positive 2 28.6% 4 22.2%
Perinatal asphyxia Negative 3 42.9% 15 83.3% 0.066 NS
Positive 4 57.1% 3 16.7%
Development Delayed 1 14.3% 7 38.9% 0.362 NS
Normal 6 85.7% 11 61.1%
Medical treatment Ritalin 6 85.7% 12 66.7% 0.341 NS
Atomoxetine 1 14.3% 6 33.3%
Serum Mg (mg/dl) Mean ± SD 2.2 ± 0.1 2.3 ± 0.1 0.081 NS
Table 4 Comparison between cases with normal (group A) and low hair magnesium (group B) as regards different psychiatric scales.
Mg in hair PSig
Normal Mg (group A)
N=7
Decreased Mg (group B)
N=18
Mean ±SD Mean ±SD
Wechesler scale Verbal skills Comprehension 9.6 1.5 9.9 2.8 0.676 NS
Arithmetic 7.7 2.5 8.7 3.7 0.541 NS
Similarities 11.1 2.5 10.2 3.7 0.490 NS
Digit span 5.9 2.0 7.6 2.9 0.158 NS
Performance skills Picture completion 8.9 2.5 8.7 2.7 0.908 NS
Block design 9.0 2.1 8.6 2.5 0.677 NS
Digit symbol 8.0 3.6 8.9 3.0 0.577 NS
Total IQ Verbal IQ 96.6 8.6 99.2 17.4 0.712 NS
Performance IQ 95.1 13.5 96.9 14.1 0.779 NS
Total IQ 95.9 10.5 97.7 15.6 0.775 NS
Wisconson’s card sorting test Categories completion 3.5 2.1 2.9 2.0 0.643 NS
Conceptual level 48.8 33.0 41.4 27.0 0.672 NS
Connors’ Oppositional 67.7 8.4 67.8 11.8 0.978 NS
Inattention 75.9 9.1 71.2 12.4 0.381 NS
Hyperactivity 78.6 11.3 79.4 9.0 0.859 NS
Impulsivity 82.7 11.4 78.2 9.2 0.308 NS
66 F. El Baza et al.
epithelial cells and controls Mg
2+
urinary excretion could be a
putative factor in the previous finding [12].
The results gives us the clue that the total serum magnesium
concentration is not the best method to evaluate the magne-
sium status; as changes in serum protein concentrations may
affect the total concentration without necessarily affecting
the ionized fraction or total body magnesium status, since
about 30% of serum magnesium is bound to proteins [13].
For this reason, we used both serum and hair magnesium to
assess magnesium status.
Magnesium interacts with noradrenergic and dopaminergic
system [14]. The role of noradrenergic and dopaminergic sys-
tem in the pathophysiology of ADHD has been extensively
studied. In addition, stimulants and atomoxetine act through
adrenergic and dopaminergic receptors [15]. Thus, magnesium
deficiency could be related to the pathophysiology of ADHD.
In agreement with our results came a study done by
Kozielec [16] who observed low magnesium level in ADHD
children; where Magnesium deficiency was found in 95 percent
of ADHD patients examined, most frequently in hair (77.6
percent), in red blood cells (58.6 per cent) and in blood serum
(33.6 percent) indicating that magnesium deficiency in children
with ADHD occurs more frequently than in healthy children.
Mousain-Bosc et al. [17] reported that, intraerythrocytic
magnesium were lower in children with ADHD, while serum
magnesium was normal.
Similar results were obtained also from another Egyptian
study, where serum ferritin, zinc and magnesium levels were
lower in ADHD children than controls (p= 0.001) [18].
We can speculate that magnesium deficiency in ADHD due
to behavioral manifestation related to the core pathology of
ADHD [19]. Children with ADHD may suffer from feeding
problems owing to their stubbornness and unexpected reac-
tions to the parent’s orders [20]. They lack the attention
required to sit through a meal to obtain adequate levels of
nutrient intake, as well as the appetite suppressant effects of
treatment medication [21].
In the current study, magnesium deficiency was more
prevalent in males than in females. Also, no significant differ-
ence was observed regarding serum magnesium and sociode-
mographic data. This finding was supported by previous
study, where magnesium levels were higher in girls with
ADHD [22]. This gender difference seen in our studies, could
be partly due to the hormonal difference between males and
females where estrogen secretion is responsible for the better
magnesium utilization by young female adolescents (it may
slow the metabolic rate and hence increases the magnesium
level in hair) [23].
At the beginning of the study there was no significant dif-
ference among cases with normal (group A) and cases with
low hair magnesium (group B) as regards the different psychi-
atric scales. This could be explained by the fact that ADHD is
largely a heterogeneous disorder stemming from genetics and
environmental factors [24] and, small sample size in the current
study. For that reason also not all the patients who received
the magnesium supplementation improved at follow up.
However, there was a significant correlation between hair
magnesium and total IQ, and an indirect significant correlation
between hair magnesium and hyperactivity score. Previous
studies demonstrate that magnesium deficiency was associated
with deficient cognitive function and low academic achieve-
ment in adolescent girls. Moreover, familial hypomagnesemia
was related to inattention, mental retardation and speech
problems [25].
Table 5 Correlation between magnesium hair and serum levels and the psychiatric scales among children with ADHD.
Total IQ Categories completion Conceptual level Oppositional Inattention Hyperactivity Impulsivity
Hair Mg
Mg/kg
r0.749 0.028 0.105 0.173 0.311 0.663 0.086
P
*
0.0001 0.939 0.773 0.493 0.210 0.003 0.734
Sig HS NS NS NS NS S NS
Serum Mg
Mg/dl
r0.097 0.651 0.565 0.996 0.370 0.704 0.946
P
*
0.340 0.133 0.168 0.001 0.187 0.080 0.014
Sig NS NS NS NS NS NS NS
R= correlation coefficient; NS = non significant; HS = highly significant.
*
Pearson correlation test.
Table 6 Comparison between psychiatric scales at baseline
and at follow up among magnesium treated cases (group B1).
Mean N±SD PSig
Categories
completion
Before
treatment
3.40 5 2.074 0.061 NS
After
treatment
5.80 5 0.447
Conceptual level Before
treatment
49.20 5 30.376 0.038 S
After
treatment
81.00 5 10.173
Oppositional Before
treatment
64.44 9 12.022 0.024 S
After
treatment
52.78 9 10.022
Inattention Before
treatment
69.89 9 13.797 0.012 S
After
treatment
53.44 9 8.918
Hyperactivity Before
treatment
79.22 9 9.066 0.001 HS
After
treatment
55.33 9 10.380
Impulsivity Before
treatment
77.44 9 8.705 0.001 HS
After
treatment
56.44 9 10.608
SD = standard deviation; NS = non significant; HS = highly
significant; S = significant; Sig. = Significance.
*
Paired ttest.
Magnesium in ADHD 67
In phase 2 of the current study, magnesium deficient
patients were randomly assigned into two groups; those who
received magnesium supplementation and those who did not.
On follow up; in the magnesium supplemented group,
Conners’ parents rating scores sub items improved, with a
highly significant improvement in the hyperactivity
(p= 0.001) and the impulsivity domain (p= 0.001). Other
sub items improved, but the improvement was not statistically
significant. The highly significant improvement seen in hyper-
activity could be due to the fact that magnesium is needed for
relaxation at the neuromuscular junctions [26]. Similarly, fol-
low up of cognitive function using Wisconsin card sorting test,
showed significant improvement in the category completion
(p= 0.061) in the conceptual level (p= 0.038).
In the current study; despite the general improvement of
Conners’ scores in group B1 compared to group B2 after sup-
plementation, this improvement pushed the patient from one
category of the rating scale (obtained at beginning of the
study) to another only in the change in inattention
(p= 0.05), and the hyperactivity (p= 0.001) sub items of
Conners’ scale; otherwise the changes in the other components
were not statistically significant.
On the other hand, follow up of the magnesium unsupple-
mented group showed that the cognitive function and
Conners’ rating scale sub items did not improve, except for
Table 7 Comparison between the psychiatric scales at baseline and at follow up among untreated ADHD cases with magnesium who
had low hair magnesium levels (group B2).
Mean N±SD PSig
Categories completion Baseline 2.40 5 2.074 0.063 NS
Follow up 3.60 5 1.517
Conceptual level Baseline 33.60 5 23.891 0.066 NS
Follow up 43.00 5 21.966
Oppositional Baseline 71.22 9 11.300 0.018 S
Follow up 66.89 9 10.994
Inattention Baseline 72.56 9 11.588 0.237 NS
Follow up 70.56 9 11.970
Hyperactivity Baseline 79.67 9 9.500 0.201 NS
Follow up 76.44 9 8.805
Impulsivity Baseline 78.89 9 10.093 0.062 NS
Follow up 71.78 9 8.941
SD = standard deviation; NS = non significant; S = significant; Sig. = Significance.
*
Paired ttest.
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
Percent
Categories completion
Conceptual level
Oppositional
Inattention
Hyperactivity
Improvement at follow up
Treated with Mg
Untreated
0%
88.9%
11.1%
77.7%
22.2%
55.6%
20%
0%
60% 60%
Figure 2 Improvement of psychiatric scales at follow up among treated (group B1) and untreated group (group B2).
Table 8 Adverse effects among magnesium treated cases
(group B1).
Adverse effect (Group B1) N=9 %
Negative 7 77.8
Positive 2 22.2
68 F. El Baza et al.
the oppositional scale, as parents of this group were assigned
to behavioral therapy.
Our results match with those obtained by Nogovitsina [27]
where analysis was done after 30 days of magnesium supple-
mentation to ADHD patients and showed improvement in
the form of significant decrease in the total point scores on
all scales (p< 0.05; p< 0.001) There was also a significant
decrease in point scores on the ‘‘anxiety’’ and ‘‘impairment
of attention and hyperactivity’’ scales.In another study, sup-
plementation of ADHD patients with Mg-B6 regimen for at
least 2 months significantly modified the clinical symptoms of
the disease: namely, hyperactivity and aggressiveness were
reduced, school attention was improved. When the Mg-B6
treatment was stopped, clinical symptoms of the disease reap-
peared in few weeks [17]. Similar results were obtained by
other studies [27,28].
These results suggest that magnesium supplementation, or
at least proper amounts of magnesium in the diet, may prove
to be beneficial for children with ADHD. Further research is
needed to help to identify the etiology, impact, and possible
therapeutic implications of low micronutrient status in
ADHD, given the essential nature of these micronutrients in
the production of the neurotransmitters involved in ADHD.
Regarding the side effects of supplementation, we found
that 22% of the cases given the treatment suffered from mild
attacks of abdominal pain or diarrhea. This is consistent with
Jaing [29] who reported that oral magnesium supplementation
can cause mild side effects, such as diarrhea and abdominal
cramps.
Although, our study is limited by small number of cases,
but it has an advantage on other studies in that we used mag-
nesium without B6 in treatment of ADHD, the use of sibs as a
control group and the use of objective scales (Wisconsin card
sorting test) in the assessment of response to magnesium
treatment.
5. Conclusion
Mg supplementation for few weeks significantly reduced the
clinical symptoms of ADHD. Further studies on larger sam-
ples and over longer periods of time are needed to generalize
the study.
Conflict of interest
The authors declare no conflict of interest. There is no finan-
cial and personal relationship with other people or organiza-
tions that could inappropriately influence their work.
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70 F. El Baza et al.
... China [72][73][74][75][76][77] and India [78][79][80][81][82][83] contributed six (5.6%) studies each, and Brazil [84][85][86][87][88] five (4.8%), while Palestine [89][90][91][92], Sri Lanka [93][94][95][96] and Turkey [97][98][99][100] contributed four (3.8%) each. Seven other countries contributed two (1.9%) studies each [101][102][103][104][105][106][107][108][109][110][111][112][113][114], and twelve countries one (0.9%) each [115][116][117][118][119][120][121][122][123][124][125][126]. ...
... The most common settings were schools (n = 37; 34.6%) [10,25,26,36,37,46,47,53,54,56,66,[73][74][75]83,87,89,90,92,93,96,97,102,105,[107][108][109][110][111][112]114,116,117,121,123,126,128] and outpatient clinics (n = 35; 32.7%) [23,24,27,28,[30][31][32][33]35,39,40,42,48,49,55,58,[60][61][62][63]67,[69][70][71]77,79,80,84,86,88,95,98,99,118]. Over one-fifth of studies did not report the settings in which interventions were delivered [34,38,41,43,50,51,57,59,64,65,68,72,78,82,85,100,101,104,106,119,120,125,127]. ...
... Interventions were mostly delivered in one-to-one configuration (n = 58; 54.2%) [10,25,[28][29][30][31][33][34][35][36][37][38][39][40][41][43][44][45][46]48,[50][51][52][57][58][59][60][61][62][63][64][65][66][67][68][69]72,74,[77][78][79][80][81]84,85,87,88,94,95,98,99,104,106,113,120,123,125,127] or in groups (n = 34; 31.5%) [24,25,42,49,[53][54][55][56]70 124,126]. ...
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Background Treatments for mental health problems in childhood and adolescence have advanced in the last 15 years. Despite advances in research, most of the evidence on effective interventions comes from high-income countries, while evidence is scarce in low- and middle-income countries (LMICs), where 90% of world's children and adolescents live. The aim of this review was to identify evidence-based interventions tested in LMICs to treat or prevent child and adolescent mental health problems. Methods We conducted a systematic review of seven major electronic databases, from January 2007 to July 2019. We included randomised or non-randomised clinical trials that evaluated interventions for children or adolescents aged 6 to 18 years living in LMICs and who had, or were at risk of developing, one or more mental health problems. Results were grouped according to the studied conditions. Due to the heterogeneity of conditions, interventions and outcomes, we performed a narrative synthesis. The review was registered at PROSPERO under the number CRD42019129376. Findings Of 127,466 references found through our search strategy, 107 studies were included in narrative synthesis after the eligibility verification processes. Nineteen different conditions and nine types of interventions were addressed by studies included in the review. Over 1/3 of studied interventions were superior to comparators, with psychoeducation and psychotherapy having the highest proportion of positive results. One-third of studies were classified as presenting low risk of bias. Interpretation This review shows that different interventions have been effective in LMICs and have the potential to close the mental health care gap among children and adolescents in low-resource settings.
... However, the interaction between biological and environmental factors could explain the rising incidence of ADHD [12,13]. Many studies claimed nutritional deficiencies (e.g., zinc, magnesium, ferritin, and omega-3 fatty acid) for the development of ADHD [14][15][16][17][18][19][20]. ...
... Nutrients intakes were extracted based on the Egyptian food composition table [20]. Principal Component Analysis (PCA) with Equimax rotation was performed on energy-adjusted intakes, and four factors (i.e., nutrient patterns) of an Eigen value ≥ 1 were extracted. ...
Article
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Background Attention Deficit Hyperactive Disorder (ADHD) diagnosis has been growing among children, with great public health concern. The relationship between nutrient intake pattern and ADHD remains unclear. Aim To identify the nutrient intake patterns and its association with ADHD in children. Subjects and methods The study involved 146 children with ADHD, 141 control sibling, and 146 community controls. ADHD diagnosis was confirmed using the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) criteria following the assessment by the long-form Conner’s Scale. Dietary intakes were assessed using a semi-quantitative food frequency questionnaire. Nutrients patterns were identified using the principal component analysis (PCA). Results ADHD children have significantly higher mean total energy intake than community controls and siblings (8867.9, 4481.9 and 7308.2 KJ, respectively, p < 0.001). Four nutrient patterns extracted by the PCA explained 75.9% of the total variance. Lower tertiles of “predominantly calcium-phosphorus; pattern 1” and “predominantly-vitamins; pattern 3” were significantly associated with increasing odds of ADHD, compared to community controls (p for trend: 0.002 and 0.005, respectively), while the same associations were noted in “predominantly-vitamins” and “predominantly Zinc-Iron; pattern 2” when compared to siblings (p for trend: <0.001 and <0.001, respectively). However, Higher tertiles of macronutrients; pattern 4” were associated with increased ADHD odds, compared to either community controls or siblings (p for trend: 0.017 and <0.001, respectively). Conclusion Lower intakes of nutrients patterns of minerals and vitamins, and higher intakes of macronutrients were associated with increased likelihood of ADHD in children.
... ADHD is a neuropsychiatric disease associated with a deficit in attention, hyperactivity, emotional dysregulation, and impulsivity and thereby affecting personal and professional life. Magnesium is effective in ADHD by modulating dopaminergic and noradrenergic transmission, as both these systems are involved in the pathophysiology of ADHD [5]. Studies showed lower levels of magnesium in serum, hair, and erythrocyte of ADHD-affected children when compared with the control group [33]. ...
... Overall, studies indicated that magnesium supplementation through diet is beneficial in children with ADHD [5]. ...
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Magnesium is an essential cation present in the body that participates in the regulation of various vital body functions. Maintaining normal level of magnesium is essential for proper brain functions by regulating the activities of numerous neurotransmitters and their receptors. Various studies have been reported that magnesium level is found to be declined in both neurological and psychiatric diseases. Declined magnesium level in the brain initiates various cumbersome effects like excitotoxicity, altered blood–brain permeability, oxidative stress, and inflammation, which may further worsen the disease condition. Shreds of evidence from the experimental and clinical studies proved that exogenous administration of magnesium is useful for correcting disease-induced alterations in the brain. But one of the major limiting factors in the use of magnesium for treatment purposes is its poor blood–brain barrier permeability. Various approaches like the administration of its organic salts as pidolate and threonate forms, and the combination with polyethylene glycol or mannitol have been tried to improve its permeability to make magnesium as a suitable drug for different neurological disorders. These results have shown their experimental efficacy in diseased animal models, but studies regarding the safety and efficacy in human subjects are currently underway. We present a comprehensive review on the role of magnesium in the maintenance of normal functioning of the brain and various approaches for improving its BBB permeability.
... It is also required for normal brain development and optimal nerve transmission via regulation of excitatory neurotransmitter glutamate and the inhibitory actions of gamma aminobutyric acid (GABA) [35]. Abnormal serum and hair magnesium levels, however, have been associated with behavioural changes such as hyperactivity, nervousness, and aggression in children [33,[73][74][75]. In the present study, higher levels of maternal objective hardship were associated with higher magnesium levels and higher CBCL Attention subscale and Externalizing Problem scores in boys. ...
Article
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Background Exposure to adverse experiences during pregnancy, such as a natural disaster, can modify development of the child with potential long-term consequences. Elemental hair analysis may provide useful indicators of cellular homeostasis and child health. The present study investigated (1) if flood-induced prenatal maternal stress is associated with altered hair elemental profiles in 4-year-old children, and (2) if hair elemental profiles are associated with behavioural outcomes in children. Methods Participants were 75 children (39 boys; 36 girls) whose mothers were exposed to varying levels of stress due to a natural disaster (2011 Queensland Flood, Australia) during pregnancy. At 4 years of age, language development, attention and internalizing and externalizing problems were assessed and scalp hair was collected. Hair was analyzed by inductively coupled plasma mass spectrometry (ICP-MS) for 28 chemical elements. Results A significant curvilinear association was found between maternal objective hardship and copper levels in boys, as low and high maternal objective hardship levels were associated with the highest hair copper levels. Mediation analysis revealed that low levels of maternal objective hardship and high levels of copper were associated with lower vocabulary scores. Higher levels of maternal objective hardship were associated with higher magnesium levels, which in turn were associated with attention problems and aggression in boys. In girls, high and low maternal objective hardship levels were associated with high calcium/potassium ratios. Conclusion Elemental hair analysis may provide a sensitive biomonitoring tool for early identification of health risks in vulnerable children.
... A meta-analysis of twelve studies found that serum and hair magnesium concentrations were significantly lower in children with ADHD than controls [25]. Treatment studies have demonstrated beneficial effects of magnesium alone or combined magnesium and vitamin B 6 supplementation on hyperactivity, aggression, oppositional behavior, and attention in children with ADHD [26][27][28][29], though most of these studies did not involve treatment randomization or control groups [26,27,29], and all had small sample sizes (n = 18-75). In another trial that did not involve a control group, symptoms of hyperactivity/ impulsivity decreased in children after combined polyunsaturated fatty acid, magnesium, and zinc supplementation [30]. ...
Article
Background Although researchers increasingly recognize the role of nutrition in mental health, little research has examined specific micronutrient intake in relation to antisocial behavior and callous–unemotional (CU) traits in children. Vitamin B6 and magnesium are involved in neurochemical processes implicated in modulating antisocial behavior and CU traits. The current study examined dietary intakes of magnesium and vitamin B6 in relation to antisocial behavior and CU traits. Method : We enrolled 11–12 year old children (n = 446, mean age = 11.9 years) participating in the Healthy Brains and Behavior Study. Magnesium and vitamin B6 dietary intake were assessed with three 24-hour dietary recall interviews in children. CU traits and antisocial behavior were assessed by caregiver-reported questionnaires. We controlled for age, sex, race, total energy intake, body mass index, social adversity, ADHD or learning disability diagnosis, and internalizing behavior in all regression analyses. Results Children with lower magnesium intake had higher levels of CU traits, controlling for covariates (β = −0.18, B = −0.0066, SE = 0.0027, p < 0.05). Vitamin B6 intake was not significantly associated with CU traits (β = 0.061, B = 0.19, SE = 0.20, p > 0.05). Neither magnesium (β = 0.014, B = 0.0020, SE = 0.0093, p > 0.05) nor vitamin B6 (β = 0.025, B = 0.33, SE = 0.70, p > 0.05) were significantly associated with antisocial behavior. Conclusions Findings suggest that low dietary intake of magnesium may play a role in the etiology of CU traits but not general antisocial behavior. More studies are needed to determine if magnesium supplementation or diets higher in magnesium could improve CU traits in children.
... Glikogen Sintase Kinase-3 isoform β (GSK-3β) merupakan kinase serin yang berpengaruh sebagai inhibitor pada berbagai penyakit salah satunya yakni Alzheimer [24]. Selain itu, peranan magnesium juga dilaporkan dapat memperbaiki kemampuan kognitif pasien yang mengalami gangguan neurodevelopmental seperti pada kejadian anak-anak hiperaktif [25]. ...
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Konsumsi lemak yang berlebih berdampak pada ketidakseimbangan sistem saraf utamanya pada otak. Pisang berlin unripe atau unripe banana flour (UBF) mengandung magnesium dan flavonoid. Tujuan penelitian yakni untuk mengetahui pengaruh tepung pisang berlin unripe terhadap fungsi kognitif tikus yang diinduksi HFD. Tikus wistar sebanyak 18 ekor dikelompokkan menjadi kelompok tikus normal (K-), kelompok tikus yang diinduksi HFD (K+), dan tikus yang diinduksi HFD+UBF. HFD diinduksi selama 9 minggu dan intervensi UBF diberikan selama empat minggu. Parameter yang diuji yakni kandungan pakan HFD+UBF fungsi kognitif tikus setelah diinduksi HFD (Pretest) dan setelah intervensi UBF (Postest). Pengukuran fungsi kognitif dengan menggunakan labirin. Hasil penelitian menunjukkan bahwa tikus yang diinduksi HFD setelah diberi UBF (posttest) mengalami peningkatan fungsi kognitif dibandingkan sebelum diberi perlakuan UBF (pretest) (P<0,05). Simpulan diperoleh bahwa tepung pisang berlin unripe mampu memperbaiki fungsi kognitif tikus yang diinduksi HFD. Kata kunci: HFD, Kognitif, UBF
... It is well accepted that magnesium might be useful as a therapeutic agent in the treatment of ADHD because it has been reported that the serum magnesium level in ADHD children was lower than the controls [389,390]. Moreover, magnesium supplementation (alone or in combination with vitamins or other metals) significantly improved ADHD symptoms [391,392]. Magnesium supplementation along with standard treatment ameliorated inattention, hyperactivity, impulsivity, opposition, and conceptual level in children with ADHD. A very recent paper assessed that magnesium and vitamin D supplementation in children with ADHD disorder was effective on conduct problems, social problems, and anxiety/shy scores compared with placebo intake [381,388]. ...
Article
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Magnesium plays an important role in many physiological functions. Habitually low intakes of magnesium and in general the deficiency of this micronutrient induce changes in biochemical pathways that can increase the risk of illness and, in particular, chronic degenerative diseases. The assessment of magnesium status is consequently of great importance, however, its evaluation is difficult. The measurement of serum magnesium concentration is the most commonly used and readily available method for assessing magnesium status, even if serum levels have no reliable correlation with total body magnesium levels or concentrations in specific tissues. Therefore, this review offers an overview of recent insights into magnesium from multiple perspectives. Starting from a biochemical point of view, it aims at highlighting the risk due to insufficient uptake (frequently due to the low content of magnesium in the modern western diet), at suggesting strategies to reach the recommended dietary reference values, and at focusing on the importance of detecting physiological or pathological levels of magnesium in various body districts, in order to counteract the social impact of diseases linked to magnesium deficiency.
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Attention Deficit Hyperactivity Disorder is a neurodevelopmental disorder which is characterised by a distinct clinical pattern of inattention, hyperactivity as well as impulsivity, which in turn interferes with the day-to-day activities of the affected individual. Although conventional allopathic medications have been found to provide symptomatic relief, they are accompanied with a plethora of side effects which overshadow and outweigh the potential therapeutic benefits. Hence, various alternative approaches in the management of Attention Deficit Hyperactivity Disorder (ADHD) are actively being investigated. Over the past few decades, numerous studies have been initiated and have delved into potential alternative strategies in the treatment and management of ADHD. The primary focus of this article is to discuss the etiology, pathophysiology coupled with a financial background as well as alternative strategies in the treatment and management of ADHD. Review of literature on the clinical trials on alternative treatment approaches for ADHD showed that, plants and dietary supplements have beneficial effects in ADHD management. But in-depth studies still needs to be conducted because the trials reported till now have smaller sample size and needs to be be scaled up to get a broader understanding and knowledge of the potential impact of alternative forms of natural treatment on the patient population with ADHD. Also it is very important for the manufacturer of the alternative formulations to develop effective protocols and processes for the safe, effective, and robust manufacturing of such natural remedies, which fall in line with the expectation of the FDA to gain regulatory clearance for its manufacturing and sale, which can lead to better therapeutic outcomes in patients.
Chapter
Different factors such as environmental pollution, nutrition, mental and physical exercises, and genetic factors affect the development and performance of the attention control system. These factors and their positive and negative effects are explained briefly in this chapter.
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Attention deficit hyperactivity disorder is a behavioral syndrome of childhood characterized by inattention, hyperactivity and impulsivity. There were many etiological theories showed dysfunction of some brain areas that are implicated in inhibition of responses and functions of the brain. Minerals like zinc, ferritin, magnesium and copper may play a role in the pathogenesis and therefore the treatment of this disorder. This study aimed to measure levels of zinc, ferritin, magnesium and copper in children with attention deficit hyperactivity disorder and comparing them to normal. This study included 58 children aged 5-15 years with attention deficit hyperactivity disorder attending Minia University Hospital from June 2008 to January 2010. They were classified into three sub-groups: sub-group I included 32 children with in-attentive type, sub-group II included 10 children with hyperactive type and sub-group III included 16 children with combined type according to the DSM-IV criteria of American Psychiatric Association, 2000. The control group included 25 apparently normal healthy children. Zinc, ferritin and magnesium levels were significantly lower in children with attention deficit hyperactivity disorder than controls (p value 0.04, 0.03 and 0.02 respectively), while copper levels were not significantly different (p value 0.9). Children with inattentive type had significant lower levels of zinc and ferritin than controls (p value 0.001 and 0.01 respectively) with no significant difference between them as regards magnesium and copper levels (p value 0.4 and 0.6 respectively). Children with hyperactive type had significant lower levels of zinc, ferritin and magnesium than controls (p value 0.01, 0.02 and 0.02 respectively) with no significant difference between them as regards copper levels (p value 0.9). Children with combined type had significant lower levels of zinc and magnesium than controls (p value 0.001 and 0.004 respectively) with no significant difference between them as regards ferritin and copper levels (p value 0.7 and 0.6 respectively). Children with attention deficit hyperactivity disorder had lower levels of zinc, ferritin and magnesium than healthy children but had normal copper levels.
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Familial hypomagnesaemia (FH) is a rare genetic condition. Neuromuscular and cardiovascular manifestations are well described, whereas cognitive and psychosocial development of children with FH is generally overlooked. Nine patients with FH were evaluated with psychiatric examination and psychometric tests for cognitive and psychosocial outcome. Nine children (median age 10.1 yrs, range 3-16.3 yrs, 5 boys and 4 girls) with FH participated. Psychiatric symptoms were hyperactivity, irritability, sleep and speech problems and finger sucking. Common psychiatric diagnoses were Attention Deficit Hyperactivity Disorder, borderline intelligence, mild mental retardation and speech disorders. Parent-rated Child Behavior Checklist and Child Health Questionnaire mean scores were between 0.32-0.79, and 0.4-2.12, respectively; indicating the worsened psychosocial well-being besides considerable psychiatric diagnoses. Cognitive and psychosocial outcome in FH may influence morbidity, quality of life and social performance. Neuropsychiatric evaluation should be a routine part of management of children with FH.
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Children with feeding problems often have multiple co-occurring medical and developmental conditions; however, it is unknown whether patterns of comorbidity exist and whether they relate to important feeding-related health outcomes. The main objective of this study was to examine (1) the relationship between the number of medical and developmental comorbidities and important feeding-related health outcomes; (2) how various comorbidities interact and form empirically derived patterns; and (3) how empirically derived patterns of comorbidity relate to weight status, nutritional variety, and child and parent mealtime behavior problems. The medical records of 286 children (mean age = 35.56 months) seen at an outpatient feeding disorders clinic were reviewed. Child weight status, nutritional variety, and child and parent mealtime behavior problems were assessed using standardized measures. The lifetime occurrence of medical and developmental conditions was reliably coded. Empirically derived patterns of comorbidity were generated via latent class analyses. Latent class analyses generated 3 comorbidity patterns: "Behavioral" (58% of cases), "Developmentally Delayed" (37%), and "Autism Spectrum Disorder" (ASD, 5%). The Autism Spectrum Disorder group was found to have less nutritional variety compared to the Behavioral and Developmentally Delayed groups. No differences were found between groups in terms of percent ideal body weight, or severity of child or parent mealtime behavior problems. Multiple co-occurring conditions of children with feeding problems were empirically reduced to 3 patterns of comorbidities. Comorbidity patterns were largely unrelated to weight status and child or parent mealtime behavior problems. This suggests that medical and developmental conditions confer general, rather than specific, risk for feeding problems in children.
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Polyunsaturated fatty acids are essential nutrients for humans. They are structural and functional components of cell membranes and pre-stages of the hormonally and immunologically active eicosanoids. Recent discoveries have shown that the long-chained omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also play an important role in the central nervous system. They are essential for normal brain functioning including attention and other neuropsychological skills. In our large observational study we monitored 810 children from 5 to 12 years of age referred for medical help and recommended for consuming polyunsaturated fatty acids (PUFA) in combination with zinc and magnesium by a physician over a period of at least 3 months. The food supplement ESPRICO® (further on referred to as the food supplement) is developed on the basis of current nutritional science and containing a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc. Study objective was to evaluate the nutritional effects of the PUFA-zinc-magnesium combination on symptoms of attention deficit, impulsivity, and hyperactivity as well as on emotional problems and sleep related parameters. Assessment was performed by internationally standardised evaluation scales, i.e. SNAP-IV and SDQ. Tolerance (adverse events) and acceptance (compliance) of the dietary therapy were documented. After 12 weeks of consumption of a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc most subjects showed a considerable reduction in symptoms of attention deficit and hyperactivity/impulsivity assessed by SNAP-IV. Further, the assessment by SDQ revealed fewer emotional problems at the end of the study period compared to baseline and also sleeping disorders. Mainly problems to fall asleep, decreased during the 12 week nutritional therapy. Regarding safety, no serious adverse events occurred. A total of 16 adverse events with a possible causal relationship to the study medication were reported by 14 children (1.7%) and only 5.2% of the children discontinued the study due to acceptance problems. Continuation of consumption of the food supplement was recommended by the paediatricians for 61.1% of the children. Our results suggest a beneficial effect of a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc consumption on attentional, behavioural, and emotional problems of children and adolescents. Thus, considering the behavioural benefit in combination with the low risk due to a good safety profile, the dietary supplementation with PUFA in combination with zinc and magnesium can be recommended.
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Attention-deficit/hyperactivity disorder (ADHD) is a common, early-onset and enduring neuropsychiatric disorder characterized by developmentally inappropriate deficits in attention, hyperactivity, increased impulsivity and emotional dysregulation, resulting in impairments in multiple domains of personal and professional life. ADHD has long been considered a disorder of childhood that resolves gradually with maturation during adolescence; however, this view was contested by systematic follow-up studies documenting the persistence of ADHD across the lifespan. In this article, we present converging evidence from clinical and genetic studies arguing for a remarkable perseverance of ADHD-related symptomatology, taking into account the disorder's variable and changing phenotype moderated by a high rate of comorbidity throughout the lifecycle. We also cover findings highlighting alterations in structural and functional neuroanatomy based on neuropsychological, psychophysiological and brain imaging approaches, and discuss options for deficit-focused pharmacological and psychotherapeutic interventions at different stages of life. In addition, we develop a fusion model of disease risk underlying the pathway to ADHD etiology. Finally, we argue for large-scale, systematic studies to explore factors predicting the long-term outcome of the disease and the possibilities to exploit those predictors with more personalized treatment strategies to enhance remittance and/or coping.
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Evidence for dietary/nutritional treatments of attention-deficit/hyperactivity disorder (ADHD) varies widely, from double-blind, placebo-controlled trials to anecdotal. In guiding patients, clinicians can apply the SECS versus RUDE rule: treatments that are Safe, Easy, Cheap, and Sensible (SECS) require less evidence than those that are Risky, Unrealistic, Difficult, or Expensive (RUDE). Two nutritional treatments appear worth general consideration: Recommended Daily Allowance/Reference Daily Intake multivitamin/mineral supplements as a pediatric health intervention not specific to ADHD and essential fatty acids, especially a mix of eicosapentaenoic acid, docosahexaenoic acid, and γ-linolenic acid as an ADHD-specific intervention. Controlled studies support the elimination of artificial food dyes to reduce ADHD symptoms, but this treatment may be more applicable to the general pediatric population than to children with diagnosed ADHD. Mineral supplementation is indicated for those with documented deficiencies but is not supported for others with ADHD. Carnitine may have a role for inattention, but the evidence is limited. Dimethylaminoethanol probably has a small effect. Herbs, although "natural," are actually crude drugs, which along with homeopathic treatments have little evidence of efficacy. Consequences of delayed proven treatments need consideration in the risk-benefit assessment of dietary/nutritional treatments.
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This study examined the effects of the attention-deficit/hyperactivity disorder treatments, methylphenidate (MPH) and atomoxetine (ATM), on prefrontal cortex (PFC) function in monkeys and explored the receptor mechanisms underlying enhancement of PFC function at the behavioral and cellular levels. Monkeys performed a working memory task after administration of a wide range of MPH or ATM doses. The optimal doses were challenged with the α(2)-adrenoceptor antagonist, idazoxan, or the D(1) dopamine receptor antagonist, SCH23390 (SCH). In a parallel physiology study, neurons were recorded from the dorsolateral PFC of a monkey performing a working memory task. ATM, SCH, or the α(2) antagonist, yohimbine, were applied to the neurons by iontophoresis. MPH and ATM generally produced inverted-U dose-response curves, with improvement occurring at moderate doses, but not at higher doses. The beneficial effects of these drugs were blocked by idazoxan or SCH. At the cellular level, ATM produced an inverted-U dose-response effect on memory-related firing, enhancing firing for preferred directions (increasing "signals") and decreasing firing for the nonpreferred directions (decreasing "noise"). The increase in persistent firing for the preferred direction was blocked by yohimbine, whereas the suppression of firing for the nonpreferred directions was blocked by SCH. Optimal doses of MPH or ATM improved PFC cognitive function in monkeys. These enhancing effects appeared to involve indirect stimulation of α(2) adrenoceptors and D(1) dopamine receptors in the PFC. These receptor actions likely contribute to their therapeutic effects in the treatment of attention-deficit/hyperactivity disorder.