A note about the References tool in Word On a PCWindo.docx

A note about the References tool in Word
On a PC/Windows system (based on Office 2010)
When you need to create a citation (giving credit for work that
you are referencing), you
click on References, then on Insert Citation. The next step is to
add a new source.
When you get to the "Create Source" window, it is suggested
that you click on the
"Show All Bibliography Fields." Here is a sample Source
screen.
Once you have entered all the source information, click on
Bibliography and then Insert
Bibliography.
This is the citation:
(Joseph, 2000)
This is how the source is entered into the References list:
Joseph, J. (2000, October). Ethics in the Workplace. Retrieved
August 3, 2015, from asae-The
Center for Association Leadership:
http://www.asaecenter.org/Resources/articledetail.cfm?ItemNum
ber=13073

Other fields on the source page would be used for a journal
article or an article from a
periodical.
On a Mac/OS system (based on Office 2013)
From the MAC Help files:
To add a citation, a works cited list, or a bibliography to your
document, you first
add a list of the sources that you used.
Add a source by using the Source Manager
The Source Manager lists every source ever entered on your
computer so that
you can reuse them in any other document. This is useful, for
example, if you
write research papers that use many of the same sources. If you
open a
document that includes citations, the sources for those citations
appear under
Current list. All the sources that you have cited, either in
previous documents or
in the current document, appear under Master list.
1. Open up your Word document.
2. On the Document Elements tab , under References ,
click Manage.

3. At the bottom of the Citations tool, click , and then click
Citation Source Manager .
1 2
3
4
1 2
3
4
4. Click New.
5. On the Type of Source pop-up menu, select a source type.
6. Complete as many of the fields as you want. The required
fields are
marked with an asterisk (*). These fields provide the minimum
information
that you must have for a citation.
7.
Note You can insert citations even when you do not have all

the publishing details.
If publishing details are omitted, citations are inserted as
numbered placeholders.
Then you can edit the sources later. You must enter all the
required information for a
source before you can create a bibliography.
8. When you are finished, click OK.The source information that
you entered
appears in the Current list and Master list of the Source
Manager.
9. To add additional sources, repeat steps 3 through 6.
10. Click Close.The source information that you entered appears
in the
Citations List in the Citations tool.
Edit a source in the Citations tool
You can edit a source directly in the document or in the
Citations tool. When you
change the source, the changes apply to all instances of that
citation throughout
the document. However, if you make a manual change to a
particular citation
within the document, those changes apply only to that particular
citation. Also,
that particular citation is not updated or overridden when you
update the citations
and bibliography.
1. On the Document Elements tab, under References, click
Manage.

2. In the Citations List, select the citation that you want to edit.
3. At the bottom of the Citations tool, click , and then click Edit
Source.
4. Make the changes that you want, and then click OK. If you
see a message
that asks whether you want to save changes in both the Master
list and the
Current list, click No to change only the current document, or
click Yes to
apply changes to the source of the citation and use it in other
documents.
Remove a source from the Citations List
Before you can remove a source from the Citations List, you
must delete all
related citations.
1. In the document, delete all the citations associated with the
source that
you want to remove.
2. Tip You can use the search field to locate citations. In the
search field , enter part of the citation.
Manage.
4. At the bottom of the Citations tool, click , and then click
Citation Source

Manager.
5. In the Current list, select the source that you want to remove,
and then
click Delete. The source now appears only in the Master list.
6.
Note If the Delete button is unavailable, or if you see a check
mark next to the source in the list, there is still at least one
related citation in the document. Delete all remaining related
citations in the document, and then try deleting
the source again.
7. Click Close. The source that you removed no longer
appears in the Citations
List.
Step 2. Insert, edit, or delete a citation (optional)
Insert a citation
1. In your document, click where you want to insert the citation.
Manage.
3. In the Citations List, double-click the source that you want to
cite. The
citation appears in the document.
Add page numbers or suppress author, year, or title for a
specific citation

Use this option to make custom changes to a citation and keep
the ability to
update the citation automatically.
Note The changes that you make by using this method apply
only to this citation.
1. Click anywhere between the parentheses of the citation. A
frame appears
around the citation.
2. Click the arrow on the frame, and then click Edit this
Citation.
3. Add page numbers, or select the Author, Year, or Title check
box to keep that
information from showing in the citation.
Make manual changes to a specific citation
If you want to change a specific citation manually, you can
make the citation text
static and edit the citation in any way that you want. After you
make the text
static, the citation will no longer update automatically. If you
want to make
changes later, you must make the changes manually.
1. Click anywhere between the parentheses of the citation. A
frame appears

around the citation.
2. Click the arrow on the frame, and then click Convert Citation
to Static Text.
3. In the document, make the changes to the citation.
Delete a single citation from the document
1. In the document, find the citation that you want to delete.
2.
Tip You can use the search field to locate citations. In the
search field , enter part of the citation.
3. Select the whole citation, including the parentheses, and then
press DELETE.
Step 3. Insert or edit a works cited list or a bibliography
A works cited list is a list of all works you referred to (or
"cited") in your
document, and is typically used when you cite sources using the
MLA style. A
works cited list differs from a bibliography, which is a list of
all works that you
consulted when your researched and wrote your document.
Insert a works cited list or a bibliography
1. In your document, click where you want the works cited list
or bibliography to

appear (usually at the very end of the document, following a
page break).
Bibliography, and
then click Bibliography or Works Cited.
Change a works cited list or a bibliography style
You can change the style of all the citations contained in a
document's works
cited list or bibliography without manually editing the style of
the citations
themselves. For example, you can change the citations from the
APA style to the
MLA style.
1. On the View menu, click Draft or Print Layout.
2. On the Document Elements tab, under References, click the
Bibliography
Style pop-up menu, and then click the style that you want to
change the
bibliography's references to. All
references in your document's bibliography change to the new
style.
Update a works cited list or a bibliography
If you add new sources to the document after you inserted the
works cited list or
bibliography, you can update the works cited list or
bibliography to include the
new sources.

1. Click the works cited list or bibliography. A frame appears
around it.
2. Click the arrow on the frame, and then click Update Citations
and
Bibliography.
,Eji| m
■ % ^ | Addiction: Diseased Brain,
H E X Divided Will, or Restless Heart?
Judith A. Judith A. Toronchuk
Toronchuk ’
Addictive disorders lay a heavy burden on global medical
resources while continu-
ing to devastate personal lives at an alarming rate. Complex
interrelated risk factors,
including biological, psychological, sociological, cultural, and
spiritual factors, must be
considered as churches and communities address the individual
and societal problems.
This article will consider multiple causes of substance and
behavioral addiction and
reflect on the issue of determinism versus free zvill. I will take
the position that addicts,
as all persons, are simultaneously constrained by their embodied

nature and yet free to
respond to God's grace. The disease model and the choice model
are not in opposition:
rather, the brain changes that occur during addiction give rise to
habits and compul-
sions which, nevertheless, can be broken as new habits are
formed through both divine
grace and grace offered by supportive others. M ultiple
approaches are needed to address
a multifactorial problem.
A ddiction rates around the world continue unabated while
church, society, and individuals struggle
to respond in an efficacious manner. Since
2014, the US and Canada have had the
highest per capita consumption of opioids
(combined prescription and illicit) in the
world. The addiction and overdose bur-
den primarily afflicts young males; in the
US in 2016, opioids were responsible for
20% of deaths among those aged 24 to 35.1
The US Centers for Disease Control and
Prevention (CDC) reports that tobacco use
in the US remains the leading preventable
cause of disease, disability, and death —
contributing to one in every five deaths.2
Globally, the World Health Organization
(WHO) estimated that, in the twentieth
century, 180 million people were killed
by tobacco.3 Why do people choose to
endanger their health, livelihood, family,
and even life itself to consume addictive
substances?
Judith A. Toronchuk holds a PhD in physiological psychology
from

McGill University and a M A of Theological Studies from
Regent College.
She taught neuroscience and psychology at Trinity Western
University for
over twenty years, has published on sensory physiology and
affective neural
systems, and served on both the ASA and CSCA Executive
Councils.
Addictive behavior illustrates the age-
old ontological conundrum of whether
human behavior is essentially deter-
mined, at various levels and by multiple
factors, or freely engaged in by the indi-
vidual. The disease model, supported by
substantial neurophysiological research,
states that substance addictions4 are recur-
ring disorders of the brain, originating in
genetic components and neuroplasticity.5
Evidence is now accumulating that an
entire spectrum of behaviors —includ-
ing compulsive gambling, eating, and
viewing of pornography — have under-
lying genetic and neural similarities with
substance abuse.6 However, because not
all users develop addiction, and most
addictions remit without treatment, this
medical model has been called into doubt
by those who stress psychosocial and
environmental influence as well as spiri-
tual and moral factors.7 In this article, we
will discuss each of these factors in turn
and attempt a holistic response.
Neural Mechanisms of
Addiction

For organisms to learn and successfully
repeat behaviors that result in survival of
218 Perspectives on Science and Christian Faith
Judith A. Toronchuk
the individual and the species, certain brain mecha-
nisms for motivation, emotion, and executive control
must be activated.8 Substance abuse occurs when
these normal mechanisms become overwhelmed
due to repeated, supranormal phasic activation by
particular external substances. Pleasurable behaviors
including eating, drinking, music, video games, and
social and sexual interactions are all accompanied
by release of the neurotransmitter dopamine in the
nucleus accumbens (NAc), a small subcortical area
in the ventral striatum which codes for salience of
rewards and reward cues. This area, part of the lim-
bic system, is rich in dopamine receptors, and it sends
output to forebrain areas responsible for attention,
memory, and executive control. The current view of
most researchers is that most abused substances pro-
mote, by direct or indirect means, rapid phasic bursts
of dopamine release three to five or more times
greater than that provided by nonaddictive reinforc-
ers which produce more tonic release.9 The universal
dopamine theory of addiction is the most prevalent
theory among researchers, although others propose
that addiction involves disruptions of multiple trans-
mitters and that different drugs produce different
neural adaptations as discussed below.10
Dopamine release in NAc flags an event as worth

attending to and the cues associated with it as worth
learning so that the rewarding behavior may be
repeated. After it was discovered in 1954 that rats
will press a lever thousands of times per hour to
receive electrical stimulation at this location in the
brain, it was proposed that the NAc was a "plea-
sure center," but this is now seen as too simplistic.
The ability to learn and remember the salient cues
predicting rewards depends on an extensive neural
pathway which extends from the midbrain ventral
tegmental area (VTA) where dopaminergic neurons
originate, to the NAc where dopamine is released,
then to the orbitofrontal cortex which participates
in evaluation and executive control, and finally to
other structures involved in memory and emotions.
Dopamine released by VTA axons into synapses in
NAc attaches briefly to receptors on NAc neurons
and then is rapidly taken up again into the releasing
axons by means of molecular transporter molecules.11
Cocaine blocks these transporter molecules, whereas
amphetamine and its derivatives cause the trans-
porters on the dopaminergic axons to run in reverse.
In either event, the dopamine available in the syn-
apse to stimulate the postsynaptic cell is increased.
Reward has both "wanting" and "liking" compo-
nents because, as addicts come to realize, one can
"want" something that one does not really "like";
thus the NAc should not be simplistically referred to
as the brain's "pleasure center."
Dopamine release in NAc produces "wanting" rather
than "liking" by focusing attention on the stimuli
already associated with reward.12 At the same time,
the memory of reinforcement causes decreased activ-
ity in the frontal cortical executive circuits which

normally provide inhibitory control over behavior.13
The most recent hypothesis is that dopamine release
is time-locked to unexpected or novel stimuli and
acts as a reward prediction signal.14 This mechanism
underlies learning of the behaviors necessary to
provide a mammal with food, drink, and social part-
ners, and results in the long-term structural changes
in synapses which normally underlie learning. The
mechanism functions as it should if the organism
learns, for example, where food is available and
repeats whatever behavior procured it. The problem
arises when supraphysiological bursts of dopamine
produced by addictive substances cause attention,
emotion, and motivation to focus exclusively on
drug-related cues. Psychostimulants such as cocaine,
methamphetamine, MDMA, and "bath salts" directly
affect the NAc.15 The increased bursting activity pro-
duced by these drugs is necessary and sufficient on
its own to promote reinforcement directly. Evidence
indicates that indirect processes, reviewed below,
which often involve endogenous opioid or cannabi-
noid receptors, are needed to indirectly activate the
dopamine response to the presence of opiates, etha-
nol, cannabis, and nicotine.16 Dopamine is of primary
importance in stimulant addiction and cue-triggered
craving for opioids, but perhaps the endogenous
opiates and GABA17 systems play the primary role
in producing satisfaction ("liking" as opposed to
"wanting") in opioid and cannabis addiction.18
Nonaddictive behaviors cause the slow, lengthy
release of dopamine in NAc, stimulating high affinity
D2 receptors which sustain moderate levels of moti-
vation necessary to procure and consume rewards.19
Large rapid bursts of dopamine stimulate both D2
and lower affinity D1 receptors which signal expec-

tation of reward and cause drug "highs." Activity in
the midbrain VTA itself is influenced by reciprocal
innervation from widespread limbic and lower-level
areas involved in memory, emotion, attention, and
Volume 70, Number 4, December 2018 219
A r t ic le
Addiction: Diseased Brain, Divided Will, or Restless Heart?
motivation. Most cells in the NAc also receive mul-
tiple varied inputs regarding stimulus salience from
widespread limbic areas via dopamine, glutamate,
endocannabinoids, and other inputs. Conditioning
to salient cues can be induced by dopamine bursts
large enough to activate the D1 receptors. Stimuli
associated with the drug thus become conditioned
and eventually trigger phasic release of dopamine
from VTA onto the NAc. The VTA neurons are
themselves normally under tonic inhibition due to
the transmitter GABA.20 The timing of dopamine
bursts is likely controlled by VTA local interneurons
and other GABA-releasing axons from those ventral
brain regions, subject to neuroplastic changes, which
are involved in evaluation of rewards, attention,
arousal, and memory. Among the changes in the
brain associated with repeated drug use are altered
firing patterns in VTA and its input areas due to cel-
lular-level mechanisms which normally accompany
learning.
Endogenous opioids (including endorphins) and
endogenous cannabinoids (endocannabinoids) inter-
act in complex ways with the dopamine system

in natural and drug-produced hedonic responses
along with additional transmitters, many involved in
eating and satiety.21 In addition, the release of dopa-
mine is increased by glutamate released in the VTA
by dorsal raphe cells.22 Serotonin (5-HT) from dor-
sal raphe cells also plays a lesser but more complex
role. One type of serotonin receptor23 (5-HT2C) in the
VTA seems to decrease stimulant-induced reinforce-
ment, while another (5-HT1B) indirectly increases
dopamine release by disinhibition of GABAa
receptors.24 Endogenous opioids and endogenous
cannabinoids also interact in complex ways with
the dopamine system in natural and drug-produced
hedonic responses. Other transmitters and modula-
tors involved in natural rewards, including leptin,
insulin, galanin, neuropeptide Y, substance P, and
melanocortins, also influence the system. Many of
these substances are involved in regulation of eating.
In summary, the control of dopamine release is com-
plicated and much more research will be necessary
to paint a complete picture.
Opiate drugs, including heroin, fentanyl, and oxy-
codone, stimulate opioid receptors directly. Most
opioid abusers start with prescription drugs but
soon discover less expensive alternatives on the
street.25 When prescriptions run out or are limited,
users often turn to cheaper illicit drugs such as her-
oin. However, fentanyl is even cheaper than heroin,
and users are often unaware that what they buy on
the street as heroin or oxycodone may be substan-
tially fentanyl.26 Fentanyl, in combination with street
drugs, was responsible for over 80% of the more
than 1,420 overdose deaths in British Columbia in
2017.27 Synthetic opioids mimic the effects of these

neuromodulatory endogenous opioids by binding to
|i opioid receptors, which are plentiful in both VTA
and NAc.28 One effect of p receptor stimulation is to
release the "brakes" in the VTA by disinhibiting nor-
mal inhibitory modulation GABAergic neurons in
the VTA, which in turn disinhibit dopamine release
in the NAc. Most of the reinforcing effects of opioid
drugs are due to direct stimulation of p receptors
on the NAc cells. Naturally occurring endorphins
decrease sensitivity to pain, increase relaxation, and
cause drowsiness by blocking the brainstem area
(locus coeruleus) that responds to arousing stim-
uli. Hence, opioids reduce both anxiety and pain,
and normally function to promote positive feelings
brought on by contact and social interaction. The
effect that endorphins have on cortical emotional
systems helps explain why relational loss is per-
ceived in humans as similar to pain and panic. Social
pain in humans, separation distress in animals, and
the affective component of physical pain all involve
the anterior cingulate cortex and the insula; further-
more, g opioid receptors are implicated in each of
these types of pain.29
Alcohol use disorders are among the most common
mental disorders, with 36% of adult males in the US
meeting the criteria for the disorder at some time in
their lives.30 Ethanol has widespread complex inter-
actions with GABA, serotonin (5-HT), endorphins,
endocannabinoids, glutamate, and nicotinic recep-
tors, although the major contributor to pleasurable
sensations is the mesolimbic dopamine system.
It also acts on the inhibitory GABA interneurons
which normally act as "brakes" controlling VTA
cells, thereby indirectly producing increased release
of dopamine in NAc.31 Ethanol's facilitation of the

inhibitory transmitter GABA in widespread areas of
the brain leads to muscle relaxation, decreased anxi-
ety, decreased behavioral inhibition, and eventually
loss of consciousness. Stress-related circuits, includ-
ing those of corticotropin-releasing hormone (CRH)
and neuropeptide Y, are also eventually affected,
contributing to the adverse effects of ethanol with-
Judith A. Toronchuk
drawal by producing anxiety and depression. In
adolescents, alcohol alters the development of grey
and white matter and disrupts pathways involved in
attention, verbal learning, visuospatial processing,
and memory. In rodents, this causes decreased cog-
nitive flexibility, behavioral inefficiency, increased
anxiety, impulsivity, and risk-taking, as well as
impaired neurogenesis and epigenetic alterations as
further discussed below.32
The main psychoactive ingredients in cannabis are
A-9-tetrahydrocannabinol (A-9-THC) and cannabidiol
(CBD) which mimic the effects of endocannabinoids
at their receptor sites.33 Cannabiniod receptors
are one of the most abundant receptors occurring
throughout the brain, and activation produces a
variety of effects on hunger, nausea, memory, sen-
sation, and subjective perception of time. Similar
to endocannabinoids, A-9-THC is believed to indi-
rectly decrease inhibition on dopaminergic neurons
by inhibiting GABA release in the VTA. After pro-
longed use, synaptic plasticity required for encoding

of memory can be disrupted, and therefore learning
can be impaired, especially during periods of brain
development or reorganization.34 A-9-THC also has
psychoactive effects and increases anxiety, whereas
CBD can facilitate learning and reduce anxiety,
and when taken together with A-9-THC may ame-
liorate its harmful effects, especially on memory.
Unfortunately, the levels of A-9-THC in street can-
nabis has risen threefold over the last twenty years
while that of CBD has declined to negligible levels.
Legalization has been suggested as a way to stan-
dardize and control the ratio of A-9-THC to CBD
and therefore reduce possible harms caused by
cannabis.35
Endocannabinoids affect neurodevelopment by
interacting directly with the glutamate pathways
which play a major role in two processes prevalent
during adolescence —the development of axonal
connections and the process of pruning irrelevant
synapses. Adolescent exposure to A-9-THC thus
alters the normal maturational fluctuations of the
glutamate receptors which underlie learning mecha-
nisms, leading to decreases in dopamine activity in
adulthood and to increased levels in stress-related
signaling. In regular cannabis users, the hippocam-
pus (involved in long-term memory) has decreased
volume, although CBD in addition to A-9-THC may
ameliorate this effect.36 Neuroimaging studies also
reveal decreased volume in the orbitofrontal cor-
tex, a major area for executive control.37 Because the
effects of cannabis on cognition seem dependent
on the maturational state of the brain, adolescents
appear to be the most vulnerable to neural changes.38
The present consensus is that cannabis has addictive

potential, although the risk of dependence after first
exposure has been reported at 8.9%, compared with
higher rates of 20.9% for cocaine, 22.7% for alcohol,
and 67.5% for nicotine.39 Although statistics on long-
term use of cannabis are not clear, lower addictive
potential than alcohol or tobacco, and hence less-
compulsive use suggests lower mortality.
Nicotine, despite its high-addictive potential in
humans, differs from most other drugs in that it
produces reinforcement without euphoria and is
less strongly reinforcing in animals.40 It activates the
hypothalamic-pituitary-adrenal (HPA) axis which
governs the body's stress response and can block
pain from the stimulation of nerve cells. Nicotine
directly stimulates certain types of acetylcholine
receptors and, depending on the site of action and
subtype of receptor, alters release of dopamine,
norepinephrine, serotonin, glutamate, GABA, and
endogenous opioids.41 Stimulation of a4(32 subunits
of the nicotinic receptors on dopaminergic neurons
in NAc contributes to the rewarding effect. The
endorphin/p opioid system, glutamate, and endo-
cannabinoid systems are also implicated. Consistent
with reports that stress increases cigarette smoking,
activation of the dynorphin/x opioid system associ-
ated with stress and negative states may be involved
in nicotine dependence and withdrawal.42 The opioid
antagonist naltrexone decreases nicotine use, further
supporting the hypothesis that endogenous opioids
contribute to nicotine reinforcement.
Behavioral Addictions
The neurophysiological mechanisms for uncontrolled
gambling, internet use, gaming, pornography, and
sexual acting out have been shown to be remarkably

similar to those elicited in psychoactive substance
abuse. Obesity, overeating, and compulsive shop-
ping are now being researched along these lines.43
Many of these behavioral disorders share similarities
with substance abuse, including preexisting vulner-
abilities due to failed regulation of the mesolimbic
dopamine system by frontal regions. Dopamine
agonists can trigger in some Parkinson's patients
Article
compulsive gambling, sex, and shopping, further
suggesting that dopamine dysregulation may be
involved in these behaviors. Even the intense eupho-
ria and attentional focus of romantic relationships
share many facets of addiction because the basic cir-
cuitry for romantic love and attachment necessary
for survival of the species shares the same circuitry
co-opted by drugs.44 Is it possible that there is a
continuum which stretches from normal, necessary
behaviors of eating, romantic love, attachment, and
social behavior, through mildly disordered behav-
iors, which then finally ends in the disfunctionality
of addiction? If so, this might mean that addiction,
rather than being a disease afflicting only some, is a
risk factor carried by all.
Gambling disorder (GD) is the first nonsubstance
disorder classified by the American Psychiatric
Association in the Diagnostic and Statistical Manual of
Mental Disorders, 5th Edition: DSM-5 in the category

of "Substance-Related and Addictive Disorders."
Both D2 and p opioid receptors are implicated in GD,
and opioid antagonists such as naloxone are the most
promising drugs of treatment. As with drug abuse,
deficits exist in executive functions, decision mak-
ing, and inhibitory control because of diminished
activation of the ventromedial prefrontal cortex con-
trol mechanisms.45 Similarly, fixations, tolerance, and
withdrawal also occur. The heritability of pathologi-
cal gambling, estimated from twin studies, is similar
to alcohol and drug abuse. GD also shares genetic
vulnerability factors with antisocial behaviors, alco-
hol dependence, and major depressive disorder, as
well as having a 96% comorbidity rate with lifetime
psychiatric disorder.
Obsessive and compulsive eating share disruptions
in transmitter and hormone systems, which again
overlap normal systems for food reward and the
disordered systems associated with drug reward.46
Chocolate cravers show greater activation in many
reward areas which are also activated in drug crav-
ing. Dopamine release in the NAc varies as a function
of food palatability, and an inverse relationship has
been reported between D2 receptors and BMI.47 One
suggestion is that reduced dopamine levels occur
in the obese, promoting overeating of highly palat-
able foods as compensation for reward deficiency.
Endocannabinoid and endorphin systems normally
interact with the dopamine system to help regulate
food intake. Furthermore, chemical signals involved
in normal satiety and hunger (i.e., leptin, insulin,
ghrelin) not only influence the sensitivity of the brain
dopamine system to the rewarding effects of food,
but also modulate sensitivity to the rewarding effects

of various drugs.48 The rewarding effects of foods,
particularly those rich in fat and sugar, can trigger
neuroadaptations in brain reward, stress circuitry,
and prefrontal control systems that are similar to
those produced by addictive drugs. As stated above,
mechanisms which evolved for survival are difficult
for most people to control.
Internet gaming disorder is included in the current
diagnostic manual, DSM-5, under the heading of
"Conditions for Further Study." William Struthers
presents the case for the addictive properties of inter-
net pornography,49 but other internet activities such
as cybersex, online relations, shopping, and surfing
may also be addictive. The findings for all the inter-
net disorders are consistent with neuroimaging and
with neurobiological and psychological models of
substance disorder.50 Game-related pictures elicit
fMRI activation patterns in both NAc and in the
orbitofrontal cortex of heavy-internet-gaming users
that are similar to those found in substance abusers.
Grey matter reductions in orbitofrontal regions and
alterations in the dopamine system have also been
reported in excessive internet gaming users.
Genetic and Epigenetic Influences
Genetic variations in the dopamine system have
been correlated with substance abuse, obesity,
pathological gambling, and several other disor-
ders.51 Neuroimaging studies show that individuals
with lower density of D2 receptors find stimulant
drugs more pleasant than those with high density.
Nevertheless, not all of these low-density people
become addicted, and fully 33% of all people have
the allele associated with addiction. One puzzling
question is why some users of drugs, alcohol, and

tobacco become dependent, but others do not. Exact
incidence varies with the type of substance, but only
about 10% of individuals using illegal drugs or alco-
hol become addicted, even though 30%-70% of that
risk may be attributable to genetics.52 As discussed
in this issue by Robin Rylaarsdam, because large
numbers and combinations of genes, plus epigenetic
factors, are implicated, it is difficult to identify spe-
cific addiction-related alleles and any one allele may
increase a person's risk factor by only a very small
percentage.53
Judith A. Toronchuk
Genetic coding influences drug risk via two types
of mechanisms: (1) the psychoactive effects are
influenced by receptors; and (2) the ability to metab-
olize external substances is controlled by enzymes.
Variants of GABA receptors may be implicated in
many sorts of addictions, including alcohol. The
risk for nicotine addiction is increased by numerous
polymorphisms in the genes that encode the various
nicotinic receptor subunits. Genetic variants of the
p opioid receptor have been found which modulate
the effectiveness of the opioid antagonist naltrexone
and which are also associated with relapse of alco-
hol abuse.54 Regarding the second mechanism, a
protective factor against alcohol abuse is provided
by those variants of the genes for alcohol dehydro-
genase and acetaldehyde dehydrogenase, which
result in unpleasant side effects, as Rylaarsdam
notes. Nicotine addiction is also affected by variants

of genes for the enzyme that breaks down nicotine in
the liver.
The term "Reward Deficiency Syndrome" (RDS) was
coined in 1996 to suggest that genetic differences in
the dopamine receptor system might be involved
in addiction and impulsive disorders.55 Carriers of
the A1 allele of the D2 receptor gene have 30%-40%
fewer D2 receptors available for dopamine signal-
ing. Dysfunction in the dopamine receptor system
has been associated with several disorders, includ-
ing alcohol and substance abuse, obesity, and
pathological gambling. Neuroimaging studies show
that individuals with lower density of D2 recep-
tors find stimulant drugs more pleasant than those
with high density, perhaps due to increased sensi-
tivity caused by fewer receptor sites. Individuals
with alcohol-use disorders have reduced levels
of D2 receptors in the NAc region, but the causal
genetic relationship is not clear. Because D2 recep-
tor levels are also affected by stress (and in monkeys
by stress-associated social hierarchies), D2 levels
influencing the predisposition to drug use could be
epigenetically influenced by environmental factors.56
However, the recurring theme of reduced dopamine
activation may explain why most abusers of alcohol
have another substance use disorder: at least one-half
use tobacco; and one-third, other drugs.57 Clearly the
vulnerability to substance abuse is polygenic and
influenced by the environment; nevertheless, under-
standing of genetic variations may someday provide
useful tools for treatment strategies.
Neuroplasticity in Emotion and
Control Circuits: Dividing of the Will?
The concept of divided will introduced by Augustine

addresses Paul's dilemma in Romans 7:18. As
Augustine states it,
This partial willing and partial non-willing is thus
not so bizarre, but a sickness of the mind, which
cannot rise with its whole self on the wings of truth
because it is heavily burdened by habit. There are
two wills, then, and neither is the whole: what one
has the other lacks.58
This passage from his Confessions echoes the common
experience of addicted persons so aptly described as
burdened by habit that they often want, but do not
want, a drug or behavior. "Wanting" something
and "liking" it are not the same, but this is only one
example of dual-process thinking. The concept of
the divided mind has been popularized by Daniel
Kahneman in Thinking, Fast and Slow which char-
acterizes two brain systems: one — unconscious,
instinctive, and emotional; and the other—con-
scious, logical, and deliberative.59 Both systems are
necessary for normal adult thought, but, in certain
situations, the rapid unconscious system gives rise
to thought habits which become difficult to break.
This insight from Kahneman suggests a useful way
to think about addiction in terms of habit driven by
unconscious systems.
Repeated use of addictive substances eventually
restructures the synaptic pathways from the NAc
and VTA, causing an increase in the number of stim-
ulated dendrites, while other usual reinforcers come
to stimulate fewer dendrites.60 The incentive salience
system of the NAc can motivate for short-term, but
not long-term goals. As attention becomes more nar-
rowly focused on the drug, long-term changes occur

in motivation, emotion, and executive control. Due to
physiological adaptation to the high levels of dopa-
mine, chronic use of a drug often leads to a decrease
in the subjective feeling of pleasure, and increasingly
greater amounts are necessary to produce the same
"high." Eventually substance abusers try to avoid the
distress, irritability, and restlessness of the decreased
dopamine release by compulsive pursuit of the sub-
stance. Thus changes in motivation are accompanied
by changes in emotional mechanisms. The memory
of substance reinforcement also decreases activity in
the frontal cortical executive circuits that normally
A rtic le
provide inhibitory control over all adult behavior
and allow adults to consciously make wise decisions.
Whenever frontal cortex is damaged or its output
decreased, the ability to voluntarily regulate behav-
ior becomes impaired. Behavioral control shifts from
the prefrontal areas involved in conscious decisions
to the dorsal striatum, which is involved in habitual
motor patterns.61
Allostatic dysregulation of the reward circuits, along
with the recruitment of stress responses, gives rise
to addiction through a shift from impulsive action
learned via the mechanisms of positive reinforce-
ment, to compulsive action learned through either
negative reinforcement or habit formation.62 The
initial bursts of dopamine during intoxication cause

positive reinforcement, which eventually leads to
learning drug cues. The normal molecular basis of
learning is based on the repeated activation of syn-
apses, leading to increased efficacy due to long-term
facilitation in synapses and dendrites. These normal
mechanisms of learning allow cues associated with
the drug or behavior to become conditioned and
behavioral habits to form.
Following chronic drug use, epigenetic changes occur
in gene expression in the NAc, causing increased
activation of the gene that codes for dynorphin.63
Unlike other endogenous opiates, dynorphin inhib-
its the VTA and further dopamine release, and it also
facilitates anxiety-like states. The VTA then activates
the amygdala (associated with fear) leading to nega-
tive emotions, activates stress systems, and decreases
sensitivity to natural rewards. Hormones, such as
cortisol, that enhance stress responses are released;
and the heightened feeling of stress facilitates craving
and relapse. Chronic use decreases subjective reward
and often leads to tolerance due to adaptation to
increased dopamine, necessitating greater amounts
of the drug to produce the usual "high." This sensi-
tization to stress is referred to as the "dark side" of
addiction because individuals become focused on
compulsively seeking more of the drug to prevent
withdrawal and irritability. "Wanting" now occurs
in the absence of "liking." Eventually longer-term
epigenetic changes occur in the brain. Dynorphin
then comes to be suppressed during abstinence,
and sensitivity returns to the reward path. This new
sensitization means that less drug is now needed to
activate the mechanisms of "wanting." These epigen-
etic changes can remain for months.64

Depressive disorders and compulsive running also
involve similar epigenetic changes. The processing
of cue salience and the ability to exert self-control
both require dopamine release and the presence of
receptors in the prefrontal cortex; however, neuro-
imaging shows reduced dopamine activity in this
area in addicts due to reduction in D2 receptors (with
the exception of cannabis users).65 Due to impaired
prefrontal control, the ability to inhibit risky behav-
iors and delay reward is reduced, and flexibility in
making further choices is impaired. This sensitiza-
tion to drug cues can also cause craving in abstinent
former users. Cues associated with the drug, such as
paraphernalia, places, and people, increase anticipa-
tory activity in the sensitized NAc and related areas
and reinstate craving. This mechanism helps explain
the increased risk of overdose death when a former
addict suddenly uses their previously accustomed
dose.
Emotional and motivational systems that evolved
to promote survival are difficult to control with
conscious effort. Marc Lewis has provided a develop-
mental-learning model of addiction which attempts
to bridge the gap between the false dichotomy of
disease and choice models.66 Habits form as activity
in the NAc restructures and over time strengthens
activity in the dorsal striatum (motor program area)
and amygdala (emotion center). Axons normally
grow from the ventral striatal area of NAc to the
dorsal striatum as habits form.67 Automatization of
habits frees up cognitive processes for other things,
allowing us to drive and talk at the same time. This
shift in activation also occurs when an addiction
forms. The repetitive strengthening of this pathway
over time can lead to habits of drug use and eventu-

ally to compulsion similar to obsessive-compulsive
disorder (OCD)—which primarily involves the dor-
sal striatum—as attention becomes modified by drug
use and focused on drug cues.68 At the same time, the
executive control pathways from the prefrontal cor-
tex become disengaged. These well-researched brain
changes lead many researchers to classify addiction
as a disease, but Lewis, a developmental neuro-
psychologist, sees it as an extreme form of processes
normally used in learning.
These normal modifications of the brain are revers-
ible, leaving open the possibility of unlearning if new
habits are formed. Furthermore, as in OCD, these
changes occur in pathways below consciousness,
Judith A. Toronchuk
causing them to seem irrational even to the addict.
Augustine wrote of his struggle, "Any sort of habit
is bondage."69 Lewis contends that brain changes
are normal rather than genetically preprogrammed
and depend on feedback from the environment. The
mutually reinforcing repetitions of certain behaviors,
especially during childhood, also play a role in the
development of anxiety and depression. And the
brain self-organizes as learning occurs and as habits
emerge.
Animals, children, addicts, and those with damaged
prefrontal connectivity find delaying rewards diffi-
cult because they have less executive control over the

dorsal striatum from the prefrontal cortex than do
normal human adults. Adolescence is a time of brain
reorganization during which the prefrontal areas
are last to develop all their connections. The NAc,
amygdala, and dorsal striatum develop earlier than
prefrontal areas; this leads to imbalances in activa-
tion during adolescent development.70 Dopaminergic
axons continue to grow from the striatum to the pre-
frontal cortex during adolescence, and target choice
appears to be malleable.71 Top-down regulation of
these striatal areas increases as the frontal cortex
develops. The result of this temporary imbalance is
that adolescents have even less top-down control
of the lower areas associated with emotion, reward,
and habit than younger children, leaving them espe-
cially vulnerable to the effects of addictive drugs.
Psychological Factors
The neurophysiological and genetic data help
explain why addiction is so difficult to treat; how-
ever, we are not fully determined mechanisms, and
so other factors must be considered. A study of over
12,000 individuals reported probability estimates of
life-time remission from dependence at 84% for nico-
tine, 91% for alcohol, 97% for cannabis, and 99% for
cocaine.72 Median time to remittance was 26 years
for nicotine, 14 for alcohol, 6 for cannabis, and 5 for
cocaine. Although we can describe many risk fac-
tors, including age, gender, ethnicity, education, and
presence of personality disorders that affect risk,
nevertheless, addiction is not usually life-long. Most
Viet Nam vets who used drugs (about 90%) stopped
after their return. The dopamine receptors influenc-
ing predisposition to drug use are likely controlled
not only by genetic factors, but also by environmen-
tal factors, including social stress.73

It has long been known that early environment
plays a role even in the development of morphine
self-administration in animals.74 Childhood trauma
and neglect have been shown to affect the course of
neurological development of the brain as the circuits
involved in reward anticipation and emotional regu-
lation are changed.75 The final configuration of the
mammalian brain is due to sculpting by experience
during development and is particularly malleable
during periods of neural development. Childhood
patterns of personality development become en-
trenched due to neuronal plasticity and can underlie
depression and anxiety disorders.76
In a review of the effects of maltreatment and
maternal deprivation on the brain, developmental
neuropsychiatrist Martin Teicher asserts, "Maltreat-
ment-related childhood adversity is the leading pre-
ventable risk factor for mental illness and substance
abuse."77 Maltreatment alters brain development and
affects the structure of prefrontal and orbitofrontal
cortical areas, amygdala, and hippocampus which
are involved in, among other things, emotional regu-
lation and anticipation of rewards — things that are
crucial for avoiding addiction. It is also associated
with reduced response to anticipated rewards in
parts of the striatum, perhaps leading to enhanced
risk for addiction.
The well-known research by John Bowlby and Mary
Ainsworth, dating from the 1950s, showed that in
order to thrive infants must not only be fed, but must
also be in an emotionally satisfying, nurturing rela-
tionship with a stable caregiver in order to develop
emotional regulation.78 Addiction could thus be seen

as an attachment disorder with attempts at self-
repair in traumatized individuals.79 Self-medication
may thus represent an adaption to uncontrollable
environmental factors that leads to loss of stabil-
ity, loss of relationships, and loss of self. The basic
circuitry for romantic love and attachment, which
is evolutionarily prepared for survival of the spe-
cies, includes and overlaps the circuitry co-opted
by drugs, particularly opiates; and dopamine is
also a major contributor to pair bonding in animals.
Augustine, too, according to his own account in
Confessions, suffered childhood abuse.
In order to fully understand the addiction crisis, indi-
vidual stress and trauma must also be located in a
wider social context. Peer use is one of the strongest
A r t ic le
Addiction: Diseased Brain, Divided W ill, or Restless Heart?
predictors for adolescent use of alcohol. According to
addiction specialist Gabor Mate, adolescents whose
primary relationships are with peers do not eas-
ily learn emotional attunement with others because
their peers are equally emotionally immature and
cannot model appropriate emotional control. A
child's lack of emotional attunement with her care-
giver is exacerbated by the lack of support given to
the mother by the extended family, tribe, or commu-
nity. Sociologist Peter Berger claims society, created
by humans, acts back on human creators who then
become the objectified products of society, often los-

ing individual identity in the process.80 This entails
a form of self-objectification that forces individuals
to construct their own identity. As the framework of
tradition and the support of known community are
diminished in modern society, individuals become
isolated from their traditional base and social roles.81
The mechanisms of social dislocation foster addic-
tion as families are uprooted, and people turn
inward because they no longer feel connected.82
Socioeconomic status in humans and animals has
been correlated with D2/D3 receptor availability
in the striatum; and, as seen above, density of these
receptors is lower in addicted humans, although the
causal relationship here is unclear.83
When given a choice between cocaine and food, or
cocaine and sweetened water or milk, most primates
and rats choose the tasty substance, even when it is
nonnutritive.84 Self-administration by animals in bare
cages pressing levers for intravenous drugs might,
in fact, be partly a function of boredom and lack
of choice. While boredom and loneliness are com-
mon in dislocated individuals, the greater problem
in modern culture is loss of meaning. Psychiatrist
Viktor Frankl asserted in 1946 that addiction along
with depression and aggression are due to a feel-
ing of emptiness and meaninglessness he called the
"existential vacuum."85 External substances provide
focus and identity for individuals who lack self-
identity and a sense of control over their otherwise
uncontrollable lives. While social conditions are not
responsible for addiction in any one individual, they
lower the playing field for all, and the vulnerable
succumb as they seek to temporarily fill the excruci-
ating void.

Social and Cultural Factors
Although much of the medical model has been
largely confirmed, it does not always take social con-
text into account. The concept of addiction as disease
is reified, according to sociologist Robert Granfield,
by insisting that individuals are sovereign entities
able to make choices apart from cultural context.86 As
he wryly notes, addiction is not an equal opportunity
disease; some individuals are more vulnerable than
others. Those constrained at the bottom of the social
order have less choice to "just say no."
In a historical analysis of addictions, Bruce Alexander
argues that prevalence tends to wax and wane, with
periods of social chaos, such as the decline of the
Greek and Roman empires, characterized by addic-
tive behaviors.87 Plato argued that the main cause of
alcohol abuse in Greece was the structure of society
itself. In what Plato called "just societies," addic-
tion is rarely problematic, but in tyrannical societies
almost everyone succumbs. Alcoholism, Alexander
claims, was also a serious problem in the declining
Roman Empire as evidenced by Augustine's descrip-
tion in Confessions of his mother's early behavior.
The present period is also a time of social chaos and
inequality. The economically depressed regions of the
US South and Appalachia are among the most drug-
afflicted areas. While not dealing specifically with
addiction, J.D. Vance's H illb illy Elegy sheds light on
the problems caused by community disruption and
dislocation of families.88 A study on mortality rates in
the US shows that rates among white working-class
males without tertiary education are unexpectedly
rising, while they continue to decrease among better

educated males, white females, and nonwhite indi-
viduals.89 The authors of this study assert that the
increase is due to alcohol- and drug-related deaths
plus suicide—diseases of despair. Indeed, addiction
has become a worldwide problem as the UN esti-
mates that 5% of adults worldwide used illicit drugs
in 2014, and 29 million suffer from drug use dis-
orders. Alcohol, tobacco, and illicit drug use account
for 12% of worldwide mortality.90
Technology and consumerism tend to interact in a
complexity of ways to produce, sustain, and in turn
be supported by substance use. Opiates were adver-
tised and mass marketed in patent medicines in the
late nineteenth and early twentieth centuries, allow-
ing them to become acceptable to the public at that
time. For example, the evangelical reformer William
Wilberforce used the tincture of opium known as
laudanum daily for 45 years, ostensibly for stom-
ach pain. The fentanyl crisis is partly iatrogenic
Judith A. Toronchuk
due to physician overprescription of opioid pain
medication. Oxycontin makers indulged for profit
in fraudulent claims about the nonaddictiveness
of their products.91 Modern advertising is complex,
potentially ambiguous, and affects all of us. It is well
known that the tobacco industry continued to relent-
lessly promote cigarettes even after evidence showed
them to be addictive. A 1979 report for Reynolds
Tobacco discussed industry plans to enlist the ven-

erable sociologist Peter Berger in their campaign
against antismoking publicity.92 In 1991 Berger pro-
duced a report, paid for by Philip Morris, in which he
appealed to personal liberty to smoke, arguing that
antismoking publicity would discourage liberty to
smoke, in spite of the known health and social costs
of smoking.93 Arguing in favor of freedom of choice,
some politicians continue to speak out against big
government regulation of the tobacco industry, but
they, in contrast, reject legalization of less-addicting
cannabis. The point here is that social, economic, and
political factors beyond the control, and sometimes
even awareness, of the individual play definite roles
in the choice of addictive substance.
Harm reduction policies of providing safe injection
sites, needles, Narcan kits, and methadone have been
controversial among those who see them as exchang-
ing one opioid for another or as encouraging addicts
to continue their habits without consequence. The
continued use and development of overdose rever-
sal methods such as naloxone; use and development
of methadone and other treatment drugs; and
development of alternative medications, includ-
ing cannabinoids, to relieve pain are supported by
Francis Collins and his colleagues at the National
Institutes of Health (NIH).94 Daniel Mallinson, in this
issue, presents policy options for both governments
and the church in light of both evidence-based sci-
ence and social ethics.95 Catholic scholar Irene Pettus
points out the harms that overzealous Christian atti-
tudes have inflicted on drug abusers, as well as on
those in chronic and terminal pain who cannot access
controlled medicines.96 In her view, churches that
hold attitudes of rejecting not only drug users but
also harm reduction, have damaged individuals and

groups when they ought instead to play a prophetic
role, ministering to the marginalized and criminal-
ized. She reminds us that pain-reducing opiates are
largely unavailable to non-Western people, even for
terminal illness, partly because of policies based on
fear of addiction.
Meaning vs. Despair:
Restless Hearts
At one time addiction was seen as a moral or spiritual
problem, rather than as a physical problem. Addicts
were counselled to find moral and spiritual strength
to just abstain. Turning aside from the view of uni-
versal sinfulness, AA tends to classify the alcoholic
as the victim of a disease yet within a framework
that has moral and spiritual implications.97 Not all
agree that AA is the most effective form of treatment,
but it does work for many, partly because members
develop new habits through the support of a strong
social network which provides unconditional love
and grace no matter how many times they relapse.
Of course, support, community, love, and grace are
what we should also expect to find within the body
of Christ. Social support itself produces natural levels
of dopamine, and treatments that provide individu-
als the slow release of dopamine associated with
social support rather than supraphysiologic bursting,
do seem to show the greatest promise. In particular,
the various 12-step programs that utilize continued
social support can be combined with medical treat-
ments and cognitive therapy.98 Kent Dunnington,
in this issue, sees AA as the best recovery regimen
because it aims for a humble reconstitution of the self
in the face of the challenges of accepting one's own
guilt, shame, and failure while building a new iden-
tity.99 Addicts often lack the self-identity needed to

trust or invest in their future self. Its development,
however, is undercut by guilt, shame, and failure.
The admission of powerlessness over alcohol and the
need to cast one's self on a higher power reflect how
difficult it is for prideful creatures to ask for grace.
Dunnington avers that 12-step programs allow
addicts to see self-hood as grace received, by learn-
ing to the rest in the unconditional love of others.
Nevertheless, AA leads to a theological challenge —
one can either recognize the Creator as revealed in
Jesus Christ, or define AA's "higher power" as one
likes, thereby turning one's life over to an essentially
self-created divinity.100 Acknowledging the pres-
ent emphasis on widespread behavioral addictions,
Linda Mercadante asks if AA's insistence on total
abstinence is a new form of effortful Pelagianism.
Previously we were all sinners; now we are all dis-
eased. She points out that addiction and sin are fellow
travelers, but not to be equated. This conclusion is
echoed in this issue by Janet Warren reminding us
A rtic le
that we all do need development of our self-narra-
tive, because we all face difficulty in acceptance of
our guilt, shame, and failures.101
In Confessions Book X, Augustine describes his
sexuality, need for love, and need for adulation
in terms reminiscent of behavioral addictions. On

becoming bishop, he even refused to allow women
to enter his residence.102 He also describes his post-
conversion attempts to not enjoy the taste of food
or the music of hymns, seemingly replacing his
earlier addictions with what psychologist Bruce
Alexander considers moralistic obsession. The ten-
dency to merely replace one addiction with another
is common, and as stated above, comorbidity is
high. Although AA's cofounder Bill Wilson gave up
alcoholism, he struggled as a chain smoker until his
death from smoking-related emphysema. Alexander
opines that Augustine cured his addiction by adopt-
ing a different, more preferable and healthier, form
of addiction that provided him with both social sup-
port and ecstatic experience. A valid question here
might be if addiction to religion is possible. Religion
can become, like addiction, just another way to gain
control of one's life. Dunnington notes that addiction
to God is indeed possible if religion is grounded in a
desire to control God.103 True submission recognizes
that even our relationship with God is possible only
through grace —in thankfully accepting who we are
and accepting God's grace.
Paul's dilemma in Romans 7:15-19 illustrates the
moral problem of willing to do one thing, but doing
the opposite. Morality has to do with actions, right
and wrong, whereas spirituality has to do with the
intent of the heart and openness to God's action in
one's life (Rom. 8:1-8). Rather than a form of control-
ling life by means of religion, spirituality involves
relationship with God. True relationship occurs in
freedom rather than self-abnegation, honestly accept-
ing that we are less than what we wish we were. We
cannot control our lives or God's opinion of us, but
we must accept grace and unconditional love.

Habitual substance abuse changes circuits in the
brain and decreases frontal cortical activity because
epigenetic changes are fostered by habitual sub-
stance abuse. Habit formation provides one of many
examples of how the mind and the brain in mutual
relationship grow together and shape each other. An
addict becomes more and more trapped in a vicious
spiral because repetition of a behavior creates path-
ways in the brain like ruts in an unpaved road. On
the other hand, cortical thickness can be physically
increased through meditation, and studies have
shown that prayer also affects the brain.104 Thus
spiritual disciplines can form habits that enable us to
become progressively more of what God intends. As
new habits are formed, step by small step, old path-
ways in the brain become progressively less activated
and newer pathways are gradually strengthened.
Functional imaging has shown that rational cogni-
tive strategies that lead to reduction of craving for
both food and nicotine can produce activation in the
prefrontal-striatal pathway, as well as reduced acti-
vation in the ventral striatum.105 Imaging studies also
show that, even though addiction results in loss of
grey matter in the frontal cortex, the volume of grey
matter in the frontal pathways increases again after
months or years of abstinence.106 The brain is always
changing in response to the stimulation it receives.
New synaptic growth can allow us to renew our
minds. Spiritual disciplines can form new habits.
Over time, perhaps, relationship with God may even
reverse the neural damage done by abusive relation-
ships with a parent or spouse.
Recovery, however, can be slow because it requires

repeated instantaneous decisions to resist craving in
spite of competition between the striatal habit sys-
tem and the frontal control system. The competition
for activation will replay again and again, requiring
a long series of moment by moment choices. Drugs
such as buprenorphine or methadone can make each
decision point a little easier by satisfying the ven-
tral striatum's craving mechanism. Each decisive
moment of temptation, however, will contain a mea-
sure, sometimes very small, of free will with which
one can grasp the proffered grace. We must avoid
both Pelagian perfectionism of moral responsibil-
ity, and Manichean determinism of external factors,
while recognizing that we are surrounded at each
moment by God's prevenient grace reaching out
to enable choices as we reach out in return. Paul's
injunction in Romans 12:2 to be transformed by the
renewal of the mind is intended for all of us, not just
addicts, and it extends by the Spirit's gracious work
over our entire lifetime. A
Notes
T. Gomes, et al., "The Burden of Opioid-Related Mortality
in the United States," JAMA Network Open 1, no. 2 (2018):
el80217, doi:10.1001 /jamanetworkopen.2018.0217.
Judith A. Toronchuk
2National Institute on Drug Abuse Blog Team, "Tobacco,
Nicotine, & E-Cigarettes," accessed April 20,2017, https://
teens.drugabuse.gov/drug-facts/tobacco-nicotine-e
-cigarettes.

’World Health Organization, WHO Report on the Global
Tobacco Epidemic: Tire MPOWER Package (Geneva: WHO,
2008).
4The National Institute on Drug Abuse (NIDA) defines
addiction as "characterized by compulsive drug seeking
and use, despite harmful consequences." The American
Psychiatric Association in Diagnostic and Statistical Manual
of Mental Disorders, 5th Edition: DSM-5 (Arlington, VA:
American Psychiatric Association, 2013) refers to "sub-
stance use disorders" rather than addiction. See NIDA,
"Drug Misuse and Addiction," in Drugs, Brains, and Behav-
ior: The Science of Addiction, July 20, 2018, accessed August
22, 2018, https://w w w .drugabuse.gov/publications
/ drugs-brains-behavior-science-addiction/ drug-abuse
-addiction.
“The medical model is supported by researchers at NIDA,
e.g., Nora D. Volkow, George F. Koob, and A. Thomas
McLellan, "Neurobiologic Advances from the Brain Dis-
ease Model of Addiction," New England Journal of Medicine
374, no. 4 (2016): 363-71; and Nora D. Volkow and George
Koob, "Brain Disease Model of Addiction: Why Is It So
Controversial?," Lancet Psychiatry 2, no. 8 (2015): 677-79.
The model is disputed by, e.g., Wayne Hall, Adrian Carter,
and Cynthia Forlini, "The Brain Disease Model of Addic-
tion: Is It Supported by the Evidence and Has It Delivered
on Its Promises?," Lancet Psychiatry 2, no. 1 (2015): 105-10.
6For example, Volkow, Koob, and McLellan, "Neurobio-
logic Advances"; Joseph Frascella et al., "Shared Brain
Vulnerabilities Open the Way for Nonsubstance Addic-
tions: Carving Addiction at a New Joint?," Annals of the
N.Y. Academy of Sciences 1187 (2010): 294-315; and William
M. Struthers, Wired for Intimacy: Hoio Pornography Hijacks

the Male Brain (Downers Grove, IL: InterVarsity Press,
2009).
7Kent Dunnington, Addiction and Virtue: Beyond the Mod-
els of Disease and Choice (Downers Grove, IL: InterVarsity
Press, 2011); Bruce K. Alexander, The Globalization of Addic-
tion: A Study in Poverty of the Spirit (Oxford, UK: Oxford
University Press, 2008); and Gabor Mate, In the Realm of
Hungry Ghosts: Close Encounters with Addictions (Berkeley,
CA: North Atlantic Books, 2010).
“Discussed in Judith Toronchuk and George F. R. Ellis,
"Affective Neuronal Selection: The Nature of the Primor-
dial Emotion Systems," Frontiers in Psychology 3 (2012):
article 589.
9Nora D. Volkow and Marisela Morales, "The Brain
on Drugs: From Reward to Addiction," Cell 162, no. 4
(August 13, 2015): 712-25, http://dx.doi.org/10.1016
/j.cell.2015.07.046.
’“David J. Nutt et al., "The Dopamine Theory of Addiction:
40 Years of Highs and Lows," Nature Reviews Neuroscience
16, no. 5 (2015): 304-12; and Aldo Badiani et al., "Addic-
tion Research and Theory: A Commentary on the Surgeon
General's Report on Alcohol, Drugs, and Health," Addic-
tion Biology 23 (January 23,2018): 3-5.
’’Neurotransmitter receptors are proteins embedded in
neural membranes to which transmitters briefly bind.
Transporters are embedded proteins which actively move
transmitters across membranes.
12Kent C. Berridge and Terry E. Robinson, "Parsing
Reward," TRENDS in Neurosciences 26, no. 9 (2003):
507-13.

’’Nora D. Volkow, Joanna S. Fowler, and Gene-Jack Wang,
"The Addicted Human Brain: Insights from Imaging
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RESEARCH ARTICLE Open Access
Prevalence and profile of adverse drug
reactions in high-risk pregnancy: a cohort
study
Kathlen Dayanne Lopes da Silva1, Flávia Evelyn Medeiros
Fernandes2, Thiago de Lima Pessoa2,
Sara Iasmin Vieira Cunha Lima3*, Antônio Gouveia Oliveira1,3
and Rand Randall Martins1,3
Abstract
Background: Commonly used drugs in pregnant women include
antihypertensives, hypoglycemic agents,
analgesics, antimicrobials, antiemetics and antispasmodics but
the use of medicines during pregnancy, especially in
high-risk pregnancy, may be associated with high risk of
adverse drug reactions (ADR). The objective of this study
was to determine the risk of an adverse drug reaction in
hospitalized high-risk pregnant women and the factors
associated with their occurrence.
Methods: The study received IRB approval and all patients gave

written informed consent. Observational cohort
study conducted from September 2015 to November 2016 in
1070 pregnant women consecutively admitted to the
high risk sector of the University Maternity Januário Cicco in
Brazil. ADR were detected through daily active search.
Risk factors for the occurrence of ADR were determined using
multivariate logistic regression.
Results: The mean age of the study population was 26.2 ± 7.2
years and gestational age was 31.2 ± 7.2 weeks. The
average number of previous pregnancies was 2.4 ± 1.8 and
46.4% reported cases of previous abortion/miscarriage.
ADR were observed in 10.7% of women. The main medicines
involved, with the incidence rate of ADR per 100
prescriptions of the drug (IR), were parenteral scopolamine (IR
14.9%), methyldopa (IR 15.9%), insulin (IR 8.46%), oral
scopolamine (IR 3.58%), captopril (IR 2.38%) and ceftriaxone
(IR 18.4%). Multivariate analysis showed that only
gestational age in weeks (odds-ratio 0.97, 95% confidence
interval 0.95–0.98) was related to the occurrence of
adverse reactions.
Conclusion: Lower gestational age is a risk factor for high-risk
pregnant women, increasing the likelihood of
adverse reactions, with parenteral medications being those that
have the highest potential risk of harm.
Keywords: Pregnancy, Adverse drug reaction, High-risk
pregnancy
Background
High-risk pregnancy is characterized by a high incidence
of complications to the mother and/or the fetus during
labor or in the postpartum which require specialized
care [1]. The frequency of high-risk pregnancy ranges
from 25.6 to 63.5% [2–8] with about 216 maternal

deaths per 100,000 births [9]. The leading causes of
death include cardiovascular disease, preeclampsia or
eclampsia, haemorrhage, venous thromboembolism, and
amniotic embolism [10]. Non-singleton pregnancies,
diabetes mellitus, arterial hypertension and pre-eclamp-
sia [2, 7, 9] are risk factors for complicated pregnancies,
especially in the third trimester, and harm to newborns
[3]. The third trimester of pregnancy is associated with
worsening of pre-existing chronic comorbidities, obstet-
ric complications, and drug administration [11]. Antihy-
pertensive and hypoglycemic agents, analgesics,
antimicrobials, antiemetics, antispasmodics, vitamins
and minerals are commonly used in pregnancy [12–14],
but their use in high-risk pregnant women may be asso-
ciated with an increased likelihood of adverse drug reac-
tions (ADR). The pharmacokinetics of many drugs are
altered during pregnancy due to changes in its
© The Author(s). 2019 Open Access This article is distributed
under the terms of the Creative Commons Attribution 4.0
International License
(http://creativecommons.org/licenses/by/4.0/), which permits
unrestricted use, distribution, and
reproduction in any medium, provided you give appropriate
credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were
made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/) applies to
the data made available in this article, unless otherwise stated.
* Correspondence: [email protected]
3Postgraduate Program in Pharmaceutical Sciences, UFRN,
Natal, RN, Brazil
Full list of author information is available at the end of the
article

Silva et al. BMC Pregnancy and Childbirth (2019) 19:199
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parameters, including impaired absorption, increased
volume of distribution, increased metabolic rate and
changes in renal excretion, and these changes may be
more marked in conditions associated with high-risk
pregancy. In addition, many drugs have not been evalu-
ated in pregnant women through clinical trials and,
therefore, the risk of their use during pregnancy not
known [11, 15].
A few studies have estimated the incidence of ADR
during pregnancy at around 10% [14, 16, 17], but in gen-
eral they were based on small samples and the identifica-
tion of ADR was not through active search. In addition,
the drugs involved and the clinical manifestations of
ADR have not been adequately described and, to the
best of our knowledge, no studies have yet attempted to
identify risk factors for the occurrence of ADR. The aim
of this study was to estimate, in hospitalized high-risk
pregnancy, the risk and type of adverse drug reactions,
the drugs more often involved, and the patient factors at
admission that may predict their occurrence.
Methods
Observational, prospective cohort study conducted in
the 38-bed pregnancy ward of a maternity school in the

city of Natal, RN, Brazil. All high risk patients admitted
to the unit between September 2015 and November
2016 were included in this study. Patients were consid-
ered high risk if in the investigator’s judgment they pre-
sented a clinical condition that if unattended could
threaten the life of the mother or the fetus/newborn.
Women in whom symptoms of ADR could not be
assessed, such as women with cognitive impairment or
in coma, were not included. Consent was obtained from
a legal representative (first-degree relative) on behalf of
participants when they presented impossibility to sign
due to difficulty of movement.
In all subjects, data was prospectively collected on
clinical variables (age, gestational age, previous pregnan-
cies, abortions and admission diagnosis) and the medica-
tions administered throughout the whole length of
hospital stay (including the postpartum period). ADRs
were defined as any harmful or undesirable and uninten-
tional response occurring with medications at doses
normally used in humans for prophylaxis, diagnosis or
treatment of a disease, or for modification of
physiological functions [18]. The identification and
characterization of the ADRs was through active search
conducted by two clinical pharmacists: every morning,
after the administration of the first daily dose of medica-
tion, each patient was questioned about potential dis-
comforts related to the use of drugs. In addition, the
clinical charts were checked daily for clinical and labora-
tory changes that could somehow be related to the pre-
scribed drugs. When an ADR was suspected, both
pharmacists applied the Naranjo’s algorithm [19] to as-
sess the causal relationship between the prescribed drugs
and the observed clinical manifestations, and the clinical
event was classified as definite, probable, possible and

doubtful ADR. Only probable and definite ADR were
considered in this study.
A sample size of 1070 would afford an estimate of the
proportion of women experiencing and ADR with an
error of ±1.8%, with 95% confidence, assuming a preva-
lence of ADR near 10%. The characteristics of the
patients are presented descriptively as mean ± standard
deviation, or absolute and relative frequencies as appro-
priate. Drugs involved in ADRs are described as inci-
dence rate of ADRs for every 100 prescriptions of the
drug. The identification of risk factors for the occurrence
of ADRs was performed through univariate and multi-
variate logistic regression. Only the variables presenting
a p-value < 0.20 in univariate analysis were included in
the multiple regression model, and for the final model
only variables with a p-value < 0.05 were retained. Statis-
tical analysis was performed using Stata 12.0 (Stata
Corporation, College Station, TX, USA).
Results
A total of 1070 women with high-risk pregnancy were
included in this study, The mean age of the study popu-
lation was 26.2 ± 7.3 (range: 16–53) years, the mean ges-
tational age was 31.2 ± 7.2 (range 26–40) weeks, and the
average length of stay was 4.4 ± 5.4 (range 1–73) days.
The average number of previous pregnancies was 2.4 ±
1.8 and 46.4% women reported previous abortions or
miscarriages. The most common admission diagnoses
were hypertension (50.2%), preterm labor (27.2%) and
gestational diabetes (19.1%). The most often prescribed
drugs were nifedipine (38.6%), captopril (31.2%),
simethicone (30.2%), scopolamine (28.7%), ferrous sulfate
(22.8%) and methyldopa (20.9%) (Table 1). In the postpar-
tum period about 29% (n = 310) of the pregnant women
returned to the high-risk ward and were monitored.

The proportion of high-risk pregnant women presenting
one or more ADRs was 10.7% (114 women, 95% confi-
dence interval (CI): 8.9–12.7%). The description of the
observed ADRs is presented in Table 2. The more common
ADR were somnolence, blurred vision, nausea,
hypoglycemia, dizziness, tachycardia, diarrhea and cough.
Uncommon adverse drug reactions, occurring in less than
0.5%, included vomiting, constipation, flushing, drowsiness,
phlebitis, dyschromia and abdominal pain. Laboratory
changes were rare and included increased urea/creatinine
(0.09%) and increased aminotransferases (0.09%).
Table 3 presents the drugs implicated in ADRs and the
estimated incidence of ADR for each 100 prescriptions
of the drug. Parenteral scopolamine, methyldopa, insulin
NPH, oral scopolamine, captopril and ceftriaxone were
Page 2 of 6
the drugs most often implicated, while ceftriaxone,
parenteral scopolamine, methyldopa, insulin NPH, and
parenteral tramadol are the drugs with higher risk of
ADR. All ADR were classified as probable by the Nar-
anjo algorithm.
Univariate analysis of the association of patient vari-
ables at admission with ARD in high-risk pregnancy
(Table 4) showed that maternal age (OR 0.98, 95% CI:
0.95–1.01) and gestational age (OR 0.97, 95% CI: 0.94–
0.98) were associated with the occurrence of ADR. How-
ever, after multivariate analysis only gestational age
(adjusted odds ratio: 0.97, 95% CI: 0.94–0.98, p = 0.03)

was related to the occurrence of ADR.
Discussion
Many studies in the literature discuss ADR in hospital-
ized patients, however only a few have investigated their
occurrence in pregnant women. Our study involved the
active search for ADRs in over one thousand high-risk
pregnant women observed throughout their stay in a
specialized unit over a period of 15 months in a refer-
ence maternity school and the main findings of this
study were that about 1 out of 9 high-risk pregnancies
admitted to a hospital will develop one or more ADRs,
that parenteral scopolamine and oral methyldopa are the
medications most frequently involved in ADRs, that par-
enteral drugs such as scopolamine, ceftriaxone and insu-
lin have the greatest risk of ADR. Regardless of the
administered drugs, lower gestational age and lower
gestational age are likely important predictors of ADR.
Published studies on ADR in pregnancy have shown
very different prevalences among them, with estimates
ranging between 0.3 and 20.0% [14, 16]. The only Brazil-
ian work on the topic [17] reported that 8.8% women
from a sample of 294 high-risk hospitalized pregnant
women suffered an ADR. Hernández-Hernández et al.
[16], in a Mexican cohort of 207 pregnant women,
observed ADR in 12.1%. In contrast, a French study
Table 1 Characteristics of the study population (N = 1070)
Variables Values
Age, years (m, sd) 26.2 7.3
Gestational age, weeks (m, sd) 31.2 7.2

Number of pregnancies (m, sd) 2.4 1.8
Previous abortion/miscarriage (n, %) 496 46.4
Admission diagnosis (n, %)
Arterial hypertension 536 50.2
Preterm labor 290 27.2
Gestational diabetes 204 19.1
Pyelonephritis 105 9.8
Others 521 57.7
Length of hospitalization, days (m, sd) 4.4 5.4
Number of drugs (m, sd) 4.9 2.5
Drugs (n, %)
Nifedipine (oral) 413 38.6
Captopril (oral) 334 31.2
Simethicone (oral) 323 30.2
Scopolamine (oral) 307 28.7
Ferrous sulphate (oral) 244 22.8
Methyldopa (oral) 224 20.9
m mean, sd standard deviation

Table 2 Adverse drug reactions observed in a cohort of 1070
high-risk pregnancies
Adverse Drug reaction number of patients %
Somnolence 24 2.24
Blurred vision 16 1.50
Nausea 11 1.03
Hypoglycemia 11 1.03
Dizziness 10 0.93
Tachycardia 8 0.75
Diarrhea 8 0.75
Cough 7 0.65
Vomiting 5 0.47
Constipation 5 0.47
Facial flushing 2 0.19
Drowsiness 2 0.19
Increased urea and creatinine 1 0.09
Phlebitis 1 0.09
Increased aminotranferases 1 0.09
Dyschromia 1 0.09

Abdominal pain 1 0.09
Table 3 Frequency distribution of drugs involved in ADRs and
incidence of ADRs per 100 prescriptions of each drug
Drug Number of ADR Incidence rate of ADR
/ 100 prescriptions
Scopolamine (parenteral) 27 14.9
Methyldopa (oral) 18 8.04
Insulin NPH (parenteral) 11 8.46
Scopolamine (oral) 11 3.58
Captopril (oral) 8 2.38
Ceftriaxone (parenteral) 7 18.4
Ferrous sulphate (oral) 5 2.05
Tramadol (parenteral) 3 6.00
Others 24 2.04
Page 3 of 6
found ADR in only 0.3% of pregnancies, but data on
ADR were obtained by self-reporting [20]. A European
study evaluating the frequency of medication-related
problems in hospitalized pregnant women reported ADR

in 9.9% of them [14]. Several other papers were based on
rather small samples, on retrospective data collection, or
ADR were identified only through self-reporting.
Although the occurrence rate is rather high, ADR in
high-risk pregnant women tend to be of low severity.
Clinical manifestations such as somnolence, facial flush-
ing and blurred vision are self-limited and usually did
not imply changes in pharmacotherapy. Of the adverse
reactions detected, only hypoglycemia related to insulin
use presents a greater risk to the patient and the need
for immediate intervention.
Parenteral scopolamine and oral use of methyldopa
were identified as more involved in ADR, a finding simi-
lar to that described in another study [19]. The use of
scopolamine was more common in postpartum. This
drug, because of its anticholinergic action in several
organs, has the potential for a wide range of adverse
reactions due to an extension of its pharmacodynamic
profile resulting in excessive anticholinergic activity [21].
On the other hand, its antimuscarinic action may be po-
tentiated by the association with other drugs with anti-
cholinergic properties, such as antiemetics [22]. In this
study, the observed effects correspond to those de-
scribed in the literature: dizziness, tachycardia, blurred
vision, constipation and somnolence. Methyldopa is the
drug of choice for gestational hypertension due to the
absence of teratogenicity and fetal toxicity. Medications
like methyldopa that act on the central nervous system
can cause sedation, drowsiness, depression and have a
significant effect on psychomotor performance [23].
However, only sedation related to the use of methyldopa
was detected in this study. Some anti-hypertensive medi-
cines administered to patients in this study, such as
captopril, were prescribed only in the postpartum.

The drugs for parenteral use (ceftriaxone, scopolamine
and insulin) presented a greater risk for the development
of ADR. A large study that analyzed risk factors for ad-
verse events in hospitalized patients characterized the
parenteral route as more implicated the occurrence of
ADR [24]. Critical patients also have this characteristic,
and intravenous administration is responsible for a 3%
increase in the risk of ADR for each drug used [25].
The multivariate model identified only low gestational
age as a factor related to the occurrence of ADR in high
risk pregnancy. This can be explained because during
pregnancy several organ systems are affected by substan-
tial anatomical and physiological changes. Many of these
significantly affect the pharmacokinetic (absorption, dis-
tribution, metabolism, and elimination) and pharmaco-
dynamic properties of different therapeutic agents [26].
In our results, drugs more involved with ADR have
hydrophilic properties (scopolamine, methyldopa, insulin
and captopril). The rise of total body water, blood vol-
ume, and capillary hydrostatic pressure significantly in-
creases the volume of distribution of hydrophilic
substrates; however, these changes stabilize and decrease
in the last weeks of pregnancy [27]. Theoretically, lower
gestational age would require higher doses of hydro-
philic drugs due to hemodilution, thus implying a higher
risk of ADR. In contrast, in pregnancy the renal plasma
flow increases by 25 to 50% and glomerular filtration
rate by 50% and there is an increase in the activity of the
organic cation and anion transporters [28]. Therefore, it
is unclear whether the ADR were a consequence of
pharmacokinetic changes in pregnancy [27].
The study presents as main limitation the collection of

data in a single institution. Despite this, some methodo-
logical characteristics validate the results, such as the
large sample size, the prospective cohort design, and
ADR detection through daily active search.
The characterization of the prevalence, medications
involved and clinical manifestations of ADR allows the
multiprofessional team to better manage the occurrence
of these reactions. Information on drug toxicity is essen-
tial for the development of strategies that minimize the
risk of harm and improve safety in the pharmacotherapy
Table 4 Univariate and multivariate analysis of patient variables
associated with ADR in high-risk pregnant women
Characteristics Univariate Analysis Multivariate Analysis
odds ratio 95% CI p value adjusted odds ratio 95% CI p value
Age (years) 0.98 0.95 1.01 0.17 0.99 0.96 1.02 0.38
Gestational age (weeks) 0.97 0.94 0.99 0.03 0.97 0.94 0.98 0.03
Number of pregnancies 0.95 0.84 1.08 0.44 – – – –
Previous abortion 0.97 0.67 1.43 0.88 – – – –
Admission diagnosis
Gestational diabetes 1.21 0.76 1.95 0.42 – – – –
Arterial hypertension 0.95 0.65 1.41 0.81 – – – –
Pyelonephritis 1.45 0.81 2.60 0.21 – – – –

of 6
of hospitalized pregnant women. Despite the predomin-
ance of ADR of mild severity, new research evaluating
potential clinical outcomes associated with the occur-
rence of ADR in high-risk pregnancy is needed.
Conclusion
Our study found that ADR in high-risk pregnancy are
usually of mild severity but occur in about one tenth of
patients, and that lower gestational age increases the risk
of their occurrence in this population. Parenteral scopol-
amine and oral methyldopa are the drugs more often
involved in ADRs. However, parenteral drugs such as
scopolamine, ceftriaxone and insulin have a greater risk
for the development of ADR.
Additional File
Additional File 1: ADR study database in pregnant women. The
database that supports our findings in this study is presented as
an
additional file. (XLSX 386 kb)
Abbreviations
ADR: Adverse Drug Reaction; WHO: World Health
Organization
Acknowledgements
We wish like to thank the Teaching and Research Department of
Maternidade Escola Januário Cicco and the Clinical Pharmacy
staff that
assisted with data collection.

Funding
This research did not receive any specific grant from funding
agencies in the
public, commercial, or not-for-profit sectors.
Availability of data and materials
The dataset used for analysis in this study is submitted as
Additional file 1.
Authors’ contributions
RRM and AGO designed the study. KDLS, FEMF and TLP were
responsible for
the active search and monitoring pregnant women. KDLS and
SIVCL did the
collecting data. RRM and AGO did the statistical analysis of the
database.
FEMF and TLP interpreted the data. SIVCL and KDLS wrote
the manuscript.
All authors read and approved the final manuscript.
Ethics approval and consent to participate
This study was approved by the Research Ethics Committee of
Onofre Lopes
University Hospital with number 508.201 and all study patients,
or their legal
representatives (first-degree relatives) when they presented
impossibility to
sign due to difficulty of movement, signed an Informed Consent
Form. All
consent procedures used were previously approved by the
Institution’s
Research Ethics Committee.
Consent for publication
Not applicable.

Competing interests
The authors declare that they have no competing interests.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional
claims in
published maps and institutional affiliations.
Author details
1Pharmacy Department, Federal University of Rio Grande do
Norte (UFRN),
Centro de Ciências da Saúde, Av. General Gustavo Cordeiro de
Farias,
Petrópolis, Natal, RN 59012-570, Brazil. 2University Maternity
Januário Cicco.
Multiprofessional Residency in Health, UFRN, Natal, RN,
Brazil. 3Postgraduate
Program in Pharmaceutical Sciences, UFRN, Natal, RN, Brazil.
Received: 20 April 2018 Accepted: 29 April 2019
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Research Paper Using Word
This assignment has two goals: 1) have students, via research,
increase their understanding of impacts of information
technology on current world issues, and 2) learn to correctly use
the tools and techniques within Word to format a research
paper, including use of available References and citation tools.
These skills will be valuable throughout a student’s
academic career.
The paper will require a title page, NO abstract, three to five
full pages of content with incorporation of a minimum of 3
external resources from credible sources and a Works
Cited/References page. Wikipedia and similar general
information
sites, blogs or discussion groups are not considered creditable
sources for a research project. No more than 10% of the
paper may be in the form of a direct citation from an external
source. Choose your topic from the list of topics that follow
these organization steps.
Paper organization
Open Word and save a blank document with the following
name:
“Student’s LastNameFirstInitial Research Paper”
The paper should be organized in the following way:
1. Title page:
a. Center in the middle of the page (horizontally and vertically)
the title (subject) of the paper and below that
your name

2. Body of the paper:
a. Use 12-point Arial font
b. Set the margins at 1”
c. Length – 3-5 full pages, not counting the title page or the
References page.
d. Include a minimum of 3 APA-formatted citations and related
References page. Every reference must be cited
at least once, and every citation have an entry in the References
list. If you are not familiar with APA format,
it is recommended that you use the References feature in Word
for your citations and Reference List or refer
to the "Citing and Writing" option under the
Resources/Library/Get Help area in the LEO classroom. It is
important to review the final format for APA-style correctness
even if generated by Word.
e. Include at least two (2) informational footnotes. Footnotes
are not used to list a reference! Footnotes contain
information about the topic to which the footnote has been
attached.
f. Place the references on a separate page following the body of
the paper. Note: Use a hard return (CTRL
Enter) after the end of your paper body and the start of the
References page.
3. Organization of the content of the paper:
Include the following sections in the paper (include, in bold,
the headings identified here):
a. Introduction - Identify the issue or idea. Explain why was the
topic selected and what you are trying to
achieve (what is your end goal). The introduction should not be
more than half a page; details will be

discussed in the follow-on areas.
b. Areas of interest, activity or issue – Define the issue or idea
in greater detail. Define the specific problem
or problems or new idea. Identify other underlining or related
issues as well as dependencies. Explain what
impacts will result if not addressed.
c. Research Findings – Summarize your research findings and
what they contribute to the study of the issue
or idea. You must identify (cite) the sources of the research or
class material related to your topic that you
include in the findings.
d. Proposed solution(s), idea(s), courses of action(s). List
solutions, ideas or courses of action with an
analysis of its effectiveness (how will your suggestions affect
or change the current situation). If more than
one idea is suggested, provide an analysis that covers all
proposed suggestions.
e. Conclusion – Summarize the conclusions of your paper.
A list of topics from which students can choose is provided
here:
Topics for Research Paper
The focus of the paper should be on one of the following:
1. How has information technology led to the struggle between
online and brick-and-mortar stores? What do the
next 5-10 years look like?

2. How has information technology opened up the potential for
5G networks? Are there any downsides to
the implementation of this technology?
3. How has information technology impacted the use of robots
in your local stores?
4. How has information technology supported the development
of monopolies – Amazon, Microsoft, telecom
companies? Will these monopolies survive?
of facial recognition software and the current issues
related to its use?
6. How has information technology led to the use of biometrics
and the potential for rise of an International “Big
Brother”?
7. How has information technology led to the development of
the Internet of Things and the concern about the
impact of privacy laws (or lack thereof) on the IOT?
of Facebook and other social media sites? Should
social media sites be regulated?
9. Who/what is Huawei and what are the issues the U.S. and
other countries are having with Huawei?
10. How has information technology changed the political
process within the past 5 years?

Writing Quality for the Research Paper
• All Grammar, Verb Tenses, Pronouns, Spelling, Punctuation,
and Writing Competency should be without error.
• Be particularly careful about mis-matching a noun and
pronoun. For example, if you say "A person does this…" then
do
not use "their" or "they" when referring to that person. "Person"
is singular; "their" or "they" is plural.
• Remember: there is not their, your is not you're, its is not it's,
too is not to or two, site is not cite, and who should be
used after an individual, not that. For example, "the person
WHO made the speech" not "the person THAT made the
speech."
• in the previous sentence. It is more business-like to say "In a
professional paper one should not use contractions,"
rather than saying, "In a professional paper you don't use
contractions."
• In a professional paper one does not use contractions (doesn't,
don't, etc.) and one
does not use the personal I, you or your. Use the impersonal as
in the previous
sentence. It is more business-like to say "In a professional paper
one should not use
contractions," rather than saying, "In a professional paper you
don't use contractions."
• Remember: spell-check, then proofread. Better yet, have a
friend or colleague read it before submitting it. Read it out
loud to yourself. Read it as if you are submitting it to your boss.

Grading Criteria
Paper Mechanics
Format- title pg,
font, margins, paper
length
0.5 Title page included: Arial 12-point font used; margins set at
1”;
body of the paper is 3-5 pages, double spaced (not counting title
page and References page).
APA work -
citations and
references
0.5 A minimum of 3 correctly formatted citations matched to
references; both citations and references in APA format.
Footnotes 0.5 A minimum of 2 footnotes that contain additional
information
but are NOT references.
Mechanics-
grammar, spelling,

etc.
1.5 Grammar, spellings, and punctuation correct throughout the
paper.
Content
Introduction 2 This is a summary of the topic. Simply identify
the issue
without going into great detail, explain why was the topic
selected and what the you are trying to achieve (what is your
end goal). The introduction should not be more than half a
page; details will be discussed in the follow-on areas.
Issue 2.0 Define the issue or idea. Define the specific problem
or
problems or new idea. Identify other underlying or related
issues as well as dependencies. Explain what impacts will
result if not addressed.
Findings 2.0 Identify research or class material related to your
topic.
Summarize your findings and what they contribute to the
study of the issue or idea. Sources must be identified in
citations and the related References list.

Solution
s/actions 3.0 List solution, idea or courses of action with an
analysis of its
effectiveness (how will your suggestions affect or change the
current situation). If more than one idea is suggested,
provide an analysis that covers all proposed suggestions.
Conclusion 2 Summarize the conclusions of your paper. In a
paragraph
briefly identify the issue, the findings, your proposed
solution/actions. However, do not simply repeat the words in
the previous sections.
You can find instructions on how to use the References tool in
Word on a PC or on a Mac in a file included in the
Assignment link.

A note about the References tool in Word On a PCWindo.docx

A note about the References tool in Word On a PCWindo.docx

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