C H A P T E R
29
Alcohol and Violence in Psychopathy
and Antisocial Personality Disorder:
Neural Mechanisms
Nathan J. Kolla1,2,3,4 and Christine C. Wang5
1
Forensic Psychiatrist, Centre for Addiction and Mental Health (CAMH), Toronto, ON, Canada 2Violence Prevention
Neurobiological Research Unit, CAMH, Toronto, ON, Canada 3Department of Psychiatry and Criminology, University
of Toronto, Toronto, ON, Canada 4Waypoint Centre for Mental Health Care, ON, Canada 5Medical Student,
University of Toronto, Toronto, ON, Canada
LIST OF ABBREVIATIONS
ASPD
DSM
5-HT
CNS
5-HIAA
CSF
DA
DAT
SPECT
MAO-A
OFC
VS
fMRI
MAOA-H
MAO-L
PCL-R
IPV
SUDs
antisocial personality disorder
Diagnostic and Statistical Manual of Mental Disorders
serotonin or 5-hydroxytryptophan
central nervous system
5-hydroxyindoleacetic acid
cerebrospinal fluid
dopamine
dopamine transporter
single-photon emission computed tomography
monoamine oxidase-A
orbitofrontal cortex
ventral striatum
functional magnetic resonance imaging
high in vitro activity MAO-A genotype
low in vitro activity MAO-A genotype
Psychopathy Checklist-Revised
intimate partner violence
substance use disorders
INTRODUCTION
Research has consistently shown that alcohol affects
people in different ways. One adverse outcome of alcohol use can be violent behavior. Personality disorders
have also been linked to alcohol misuse and violence.
This chapter considers the interrelationship between
alcohol, ASPD, psychopathy, and violence. We begin
with a definition and description of terms and then
Neuroscience of Alcohol.
DOI: https://doi.org/10.1016/B978-0-12-813125-1.00029-5
provide a fulsome discussion of the neural underpinnings of violent behavior when both alcohol misuse
and ASPD or psychopathy is present.
Many terms have been used to describe the misuse
of alcohol. From a psychiatric perspective, the DSM-5
(American Psychiatric Association, 2013) defines problematic use of alcohol as the manifestation of an alcohol
use disorder that may be mild, moderate, or severe in
intensity. The previous edition of the DSM (American
Psychiatric Association, 2000) categorized harmful use
of alcohol as either alcohol abuse or alcohol dependence. Alcoholism is a colloquial expression that has
garnered criticism given its vagueness, although it also
connotes problematic alcohol use. For the purposes of
this chapter, we use the term “alcohol misuse” to
encompass all forms of harmful alcohol use.
ASPD is a condition characterized by a longstanding
pattern of disregard for, and infringement of, the
rights of others. According to the DSM-5, the adverse
behavior must have occurred by the age of 15 years
and three or more of the following must be present: (1)
inability to conform to social norms and lawful behaviors; (2) deceitfulness, persistent lying, and conning
others; (3) impulsivity; (4) aggressiveness as indicated
by repeated physical fights or assaults; (5) reckless disregard for safety; (6) irresponsibility; and (7) lack of
remorse. The individual must also be at least 18 years
old and conduct disorder needs to have been present
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© 2019 Elsevier Inc. All rights reserved.
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29. ALCOHOL AND VIOLENCE IN ANTISOCIAL PERSONALITY DISORDER
before the age of 15 years. Most individuals with
ASPD have a record of criminal offending and approximately 85% have enacted violence toward others
(Robins & Regier, 1991; Samuels et al., 2004). Other
research has identified ASPD as the psychiatric disorder with the highest rate of violence toward strangers,
intimate partners, and children (Coid et al., 2006).
There is evidence that ASPD belongs to an externalizing spectrum of behaviors that includes alcohol misuse
(Krueger et al., 2002), and the odds of ASPD individuals having any alcohol use disorder was reported as
8.0 in one investigation (Compton, Conway, Stinson,
Colliver, & Grant, 2005).
Psychopathy is a well-researched personality disorder that shares commonalities with ASPD. In addition
to early and pervasive criminal behavior, psychopathy
features such maladaptive personality traits as egocentricity, callousness, empathic deficits, manipulativeness, and impulsivity (Miller & Lynam, 2012). Some
evidence indicates that psychopathy is a more severe
form of ASPD (Coid & Ullrich, 2010). Although alcohol
misuse is not as well-studied in psychopathy as in
ASPD, some research indicates that alcohol use disorders are more common among individuals with psychopathy than those without the disorder. One study
found that 93% of incarcerated males with psychopathy met criteria for an alcohol use disorder compared
with 65% of prisoners without psychopathy (Smith &
Newman, 1990).
What follows is a comprehensive account of investigations reporting on neurobiological findings in individual with ASPD or psychopathy who misuse alcohol
and are violent.
NEUROBIOLOGICAL MECHANISMS
Neurochemistry
Serotonin
Numerous studies investigating the neurochemical
correlates of aggression among individuals with alcohol
misuse and a history of violence have highlighted possible serotonergic dysfunction. Mounting evidence
points to a central 5-HT deficit underpinning violence
in offenders with problematic alcohol use. 5-HT is a
monoamine neurotransmitter that plays a key role in
modulating behavioral responses, such as aggression
and cooperation (Kiser, Steemers, Branchi, & Homberg,
2012). In the CNS, 5-HT arises from specialized groups
of cell bodies known as the raphe nuclei that are located
in the brainstem reticular formation (Brown &
Bowman, 2002). Postmortem autoradiography has
demonstrated that presynaptic and postsynaptic serotonin receptors in the human brain are concentrated in
the diencephalon, striatum, and cingulate cortex, where
the density of 5-HT reuptake is highest (Bäckstöm &
Marcusson, 1987; Backstrom, Bergstrom, & Marcusson,
1989). Low levels of 5-HIAA, a metabolite of 5-HT,
have also been correlated with a greater likelihood of
committing violent offenses when individuals are under
the influence of alcohol (Virkkunen, Nuutila, Goodwin,
& Linnoila, 1987). Whether comorbid alcohol misuse is
present or not, associations between deficient 5-HT
metabolism and violent behavior have been consistently
reported in the literature (Brown et al., 1982; Linnoila
et al., 1983).
Behavioral and environmental factors, in addition to
the effects of 5-HT, also contribute to vulnerability for
alcohol misuse and aggression. Cloninger’s influential
dichotomy theory proposed two patterns of alcohol
misuse, and differing neurobiological substrates of the
two types have also been proposed (Cloninger,
Bohman, & Sigvardsson, 1981). In Cloninger’s nomenclature, Type 1 alcoholics are characterized by endorsing stable social behavior, harm avoidance, and
preserved impulse control, along with a later onset of
alcohol misuse. Type 2 alcoholics, on the other hand,
exhibit antisocial personality traits, highly impulsive
behavior, and earlier problems with alcohol. Several
independent studies have corroborated the validity of
this typology (Laakso et al., 2000; Tiihonen et al., 1995).
These two phenotypes are also accompanied by differences in 5-HIAA metabolism. For example, whereas
Type 1 alcoholics typically have higher levels of
5-HIAA measured from the CSF, Type 2 alcoholics
show lower levels of CSF 5-HIAA metabolites (Higley
& Linnoila, 1997). Other investigations provide support for this finding by providing similar evidence of
reduced 5-HIAA in the CSF of men with early
onset alcohol misuse and impulsivity (Linnoila et al.,
1983; Virkkunen et al., 1987). In a study investigating
the relationship between impulsivity and 5-HT activity, the concentration of CSF 5-HIAA was compared in
impulsive arsonists, violent offenders, and a group of
10 healthy controls. Arsonists, who exemplified an
extreme form of impulse control disorder, were found
to demonstrate significantly lower CSF 5-HIAA metabolites than the other groups. The vast majority of the
arsonists also fulfilled DSM-III criteria for alcohol
abuse (American Psychiatric Association, 1980). The
authors hypothesized that alcohol abuse may have
represented an attempt to self-medicate, as alcohol
consumption could have acutely improved impulse
control by releasing 5-HT, although chronic depletion of
5-HT would ultimately exacerbate impulsivity (Linnoila
et al., 1983; Lovinger, 1999; Virkkunen et al., 1987).
III. PSYCHOLOGY, BEHAVIOR, AND ADDICTION
NEUROBIOLOGICAL MECHANISMS
Dopamine
Dopaminergic activity has also been implicated in
aggression and alcohol misuse. DA is a catecholamine
neurotransmitter that acts on both the CNS and sympathetic branch of the peripheral nervous system
(Yanowitch & Coccaro, 2011). Rodent studies initially
established the importance of dopaminergic signaling
in modulating aggressive behavior. For instance, in an
analysis examining the behavior of mice attacking
intruders, assayed by the resident-intruder paradigm,
increased DA turnover was detected in the nucleus
accumbens, a region of the brain associated with
impulsivity, reward, and motivation (Basar et al., 2010;
Haney, Noda, Kream, & Miczek, 1990). Mice with deletion mutations in the DAT gene have also shown
increased extracellular concentrations of DA and a
greater propensity for aggressive behavior (Giros,
Jaber, Jones, Wightman, & Caron, 1996).
Both animal and human studies have also reported
a strong association between increased dopaminergic
transmission and aggressive behavior in the context of
excessive alcohol use (Kuikka et al., 1998). For example, a SPECT study conducted in a group of impulsive
violent offenders and nonviolent offenders, both with
alcohol misuse, measured striatal DAT density using
the radionuclide [123I]β-CIT. The heterogeneity of DAT
distribution was also examined. Heterogeneity of DAT
density was calculated by measuring the relative dispersion of the regional count densities when the striatum was divided into a number of subregions. The
authors found that striatal DAT density was significantly lower in nonviolent offenders with alcohol misuse than in healthy controls. Conversely, violent
offenders with alcohol misuse displayed higher striatal
DAT density and greater heterogeneity in right striatal
regions. The authors attributed the increased DAT
heterogeneity to a higher density of synapses that
increased overall dopaminergic transmission, leaving
these individuals more vulnerable to aggression and
antisocial behavior (Kuikka et al., 1998).
The association between violent behavior and
monoamine transporter deficiency has been further
investigated in a SPECT study imaging 5-HT and DA
reuptake sites in the brain through their specific binding of [123I]β-CIT (Tiihonen et al., 1997). Key to the
study’s methodology was investigating three distinct
groups: (1) violent offenders with alcohol misuse; (2)
nonviolent controls with alcohol misuse; and (3)
healthy controls. Thus, the investigators were able to
distinguish the effects of violent behavior versus those
of alcohol misuse on 5-HT or DA. By quantifying
[123I]β-CIT binding to 5-HT and DA transporters,
279
Tiihonen et al. (1997) found lower 5-HT transporter
density in the midbrain of violent offenders with alcohol misuse compared to nonviolent controls with alcohol misuse and healthy controls. This finding suggests
that lower serotonergic functioning may not be specifically related to alcohol misuse but rather to coexisting
violent behavior or habitual impulsivity.
Monoamine Oxidase-A
Another neural substrate associated with pathological aggression and impulsivity is MAO-A. MAO-A is
an enzyme located on outer mitochondrial membranes
that metabolizes 5-HT and DA, in addition to other
neurotransmitters. It exhibits the highest levels of
activity in the striatum and hypothalamus (Youdim,
Edmondson, & Tipton, 2006). The neuromodulatory
influence of MAO-A on impulsivity was investigated
in a PET study measuring MAO-A density in violent
offenders with ASPD (Kolla et al., 2015). Fifty percent
of the sample in this study also had comorbid alcohol
dependence. The OFC and VS were chosen as primary
regions of interest, as past studies of ASPD had found
abnormalities in these areas related to impulsivity
(Dalley, Everitt, & Robbins, 2011; Meyer et al., 2008).
The study indicated that lower MAO-A total distribution volume, a measure of MAO-A density, was
present in the OFC and VS of ASPD compared with
controls, as seen in Fig. 29.1 (Kolla et al., 2015).
Behavioral, self-report and clinically rated measures
of impulsivity, such as the PCL-R, were also negatively
correlated with VS MAO-A levels, as seen in Fig. 29.2
(Kolla et al., 2015).
Differences between offenders with alcohol misuse
and those without were not examined. These findings
suggest that MAO-A may be implicated in the impulsive behavior characteristic of ASPD or ASPD with
alcohol dependence. Subsequent fMRI work in this
sample revealed that activation of corticostriatal pathways associated with impulsive behavior could also
relate to VS MAO-A levels (Kolla et al., 2016).
Certain MAO-A genetic polymorphisms have
also shown a relationship with violent behavior. The
MAO-A gene is located on the X chromosome, and a
variable nucleotide tandem repeat polymorphism can
alter its transcriptional activity, resulting in either high
(MAOA-H) or low (MAOA-L) in vitro activity. One
further study exploring the genetic background of
extreme aggression in Finnish prisoners revealed an
association between aggressive behavior and MAOA-L
(Tiihonen et al., 2015). The authors discussed how a
low DA metabolism rate could be associated with the
III. PSYCHOLOGY, BEHAVIOR, AND ADDICTION
FIGURE 29.1 Lower MAO-A total distribution volume in ASPD. Results of a multivariate analysis of variance (MANOVA) indicated
that ASPD was associated with lower MAO-A total distribution volume in the OFC and VS compared with controls (MANOVA group effect:
F2,33 5 6.8, P 5 .003). An effect of diagnosis on MAO-A total distribution volume was also present across all brain regions shown in the figure. Horizontal bars indicate mean MAO-A total distribution volume values. Source: Data are from Kolla, N. J., Matthews, B., Wilson, A. A.,
Houle, S., Michael Bagby, R., Links, P., . . . Meyer, J. H. (2015). Lower monoamine oxidase-A total distribution volume in impulsive and violent male offenders with antisocial personality disorder and high psychopathic traits: An [11C]-harmine positron emission tomography study.
Neuropsychopharmacology, 40(11), 2596 2603, with permission from the Publishers.
FIGURE 29.2 VS MAO-A total distribution volume association with measures of impulsivity in ASPD. VS MAO-A total distribution
volume is negatively associated with measures of impulsivity in ASPD. (A) VS MAO-A total distribution volume is negatively correlated with
risky performance during the latter half of the Iowa Gambling Task (Pearson’s r 5 2 0.52, P 5 .034). (B) VS MAO-A total distribution
volume is negatively correlated with self-reported impulsivity on the NEO Personality Inventory-Revised (Pearson’s r 5 2 0.50, P 5 .034).
(C) Lower VS MAO-A total distribution volume was present in ASPD subjects who were rated the most impulsive on the PCL-R (PCL-R
score 5 2) when compared to subjects rated less impulsive (PCL-R 5 1). (means (horizontal bars): 17.4 versus 21.5; t16 5 2.8, P 5 .013).
Source: Data are from Kolla, N. J., Matthews, B., Wilson, A. A., Houle, S., Michael Bagby, R., Links, P., . . . Meyer, J. H. (2015). Lower monoamine
oxidase-A total distribution volume in impulsive and violent male offenders with antisocial personality disorder and high psychopathic traits: An [11C]-harmine positron emission tomography study. Neuropsychopharmacology, 40(11), 2596 2603. doi:10.1038/npp.2015.106, with permission from the
Publishers.
NEUROBIOLOGICAL MECHANISMS
low-activity MAO-A genotype, which might result in
higher levels of aggression during alcohol intoxication.
In a related study where 34% of the sample presented with ASPD, PCL-R scores predicted impulsive
re-convictions in MAOA-H but not MAOA-L offenders. Results also revealed that PCL-R factor 2 scores,
which assess antisocial behaviors, were a strong predictor of recidivism in both MAOA-H and MAOA-L
groups after controlling for alcohol exposure and age.
Conversely, the effect of PCL-R total score decreased
significantly when MAO-A genotype, alcohol exposure, and age were all considered (Tikkanen et al.,
2011). MAOA-H offenders were also at increased risk
to commit severe recidivistic violent crimes after exposure to healthy drinking, as demonstrated in another
study by the same authors (Tikkanen et al, 2010). The
investigation concluded that MAOA-H carriers were
more vulnerable to the negative effects of alcohol than
individuals with MAOA-L (Tikkanen et al., 2010). An
additional study considered the relationship between
MAO-A genotype and experience of childhood sexual
abuse on development of ASPD in a sample of adult
females belonging to an American Indian community
(Ducci et al., 2008). Among the 291 females examined,
168 had a lifetime alcohol use disorder. Some 39 individuals had a concurrent alcohol use disorder and
ASPD. Control participants had no history of alcohol
misuse or ASPD. Results revealed that subjects who
were homozygous for the MAOA-L allele and had a
history of childhood sexual abuse endorsed higher
rates of alcohol misuse, ASPD, and more ASPD symptoms than individuals homozygous for MAOA-H who
had been similarly abused. These results suggest that
relationships between MAO-A genotype, alcohol misuse, ASPD, and violence are also relevant to females.
Neuroelectrophysiology
Neuroelectrophysiological
techniques,
which
include electroencephalogram, event-related potentials,
and event-related oscillations, can identify potential
effects of alcohol and maladaptive personality traits
on commission of violent behavior. Informationprocessing paradigms that require participants to
identify target stimuli activate a late evoked potential
component known as P3. One electrophysiological
study compared the P3 component of event-related
potentials in Type 2 alcoholics and individuals who
misused alcohol, but did not manifest other prototypical Type 2 characteristics (Branchey, BuydensBranchey, & Lieber, 1988). Antisocial and aggressive
behavior were evaluated using the Buss Durkee
Hostility Inventory (Buss & Durkee, 1957) and data
from a questionnaire asking about disciplinary
281
problems at work or in the army, assaults on people,
incarceration for aggressive behavior, property damage, incarceration for other crimes, and commission of
crimes not resulting in incarceration. Results indicated
that P3 amplitudes were lower in patients who had
had a prior incarceration or who had been incarcerated
for crimes involving violence versus subjects without
these histories. A significant negative correlation also
emerged between Buss Durkee Hostility Inventory
scores and P3 amplitudes. The authors were unable to
localize the source driving their results, acknowledging
that the observed P3 alterations may have been due to
externalizing conditions in persons who misuse alcohol or alcohol use itself.
Structural Brain Changes
A strong body of evidence links violence and alcohol misuse with structural brain changes. There has
been a particular focus on the hippocampus. The hippocampus is a key structure of the limbic system that
plays a central role in memory formation and spatial
navigation (Nadel & Hupbach, 2008). Hippocampal
fibers converge to form the fornix, which in turn contributes to other pathways involving limbic regions.
One such region is the amygdala that plays a key role
in emotional processing (Heimer et al., 2008).
Postmortem studies have distinguished decreased hippocampal volumes among chronic alcoholics (Laakso
et al., 2000). MRI studies have also identified hippocampal alterations in the context of numerous psychiatric and neurologic conditions (Bremner et al., 1995;
Frisoni et al., 1999; Laakso et al., 2000; Lawrie &
Abukmeil, 1998; Soares & Mann, 1997).
An MRI study that specifically examined the hippocampus in Type 1 alcoholics without ASPD and Type
2 alcoholics with ASPD found group differences in
hippocampal volume (Laakso et al., 2000). Both alcoholic groups had smaller right hippocampi compared
with controls consisting of healthy volunteers representing a wide age range, while left hippocampal
volumes showed no differences compared with controls. Among the Type 1 alcoholics, the duration of
alcohol misuse was inversely correlated with hippocampal volume, suggesting an association between
alcoholism and cumulative volume loss related to alcohol misuse. On the other hand, there was a significant
positive correlation between age and right hippocampal volume in Type 2 alcoholics. The authors proposed
that the structural changes observed in Type 2 alcoholics were due to correlates of violent behavior as
opposed to alcohol misuse. They suggested that
inborn, developmental, or other fundamental deficiencies related to primary psychopathology were more
III. PSYCHOLOGY, BEHAVIOR, AND ADDICTION
282
29. ALCOHOL AND VIOLENCE IN ANTISOCIAL PERSONALITY DISORDER
likely alternatives to explain the relationship between
age and hippocampal volume as opposed to alcohol
use.
Alterations of the amygdala have also shown a relationship with alcohol dependence, antisocial behavior,
and violence (Hill et al., 2001; Zhang et al., 2013). In an
MRI study of individuals who were dependent on
alcohol and perpetrated IPV, a correlation between
alcohol dependence and amygdala volume was discerned. Specifically, results showed that persons who
misused alcohol and had a history of IPV presented a
significant volume reduction in the right amygdala
compared with nonviolent alcoholic-dependent
patients and healthy controls (Zhang et al., 2013). Since
the amygdala has been implicated in the rewarding
effects of alcohol (Koob, 1999) and exerts influence
over social interactions (Adolphs, Tranel, & Damasio,
1998), the authors concluded that structural deficits in
the right amygdala may have been associated with
impulsivity and aggression in alcoholics with a history
of criminal violence (Zhang et al., 2013). In discussing
possible confounds, the authors noted that both the
violent alcohol-dependent group and nonviolent
alcohol-dependent group had the same lifetime consumption of alcohol, making it less likely that a neurotoxic effect of alcohol influenced amygdala volume.
They did concede, however, that amygdala size could
contribute to age of onset of drinking, as the group of
alcohol-dependent perpetrators had an earlier drinking
onset.
Another MRI study parsed alterations in brain
structure associated with persistent violent behavior
from those related to alcohol misuse and other SUDs.
Changes in gray matter volume were compared in violent offenders and lifelong substance users (Schiffer
et al., 2011). Among participants with a history of violent behavior and substance use, MRI findings
revealed increased gray matter volume in regions comprising the mesolimbic reward system, namely the
amygdala, left nucleus accumbens, and right caudate
head. Conversely, among participants with a substance
abuse history who did not exhibit violent behavior,
reduced gray matter volumes were noted in the prefrontal cortex, OFC, and premotor area. Differences in
gray matter volume between men with and without
SUDs were correlated with response inhibition scores
based on a questionnaire and results of a response
inhibition task measuring impulsivity. Participants
with SUDs obtained higher scores on measures of
response inhibition during the go/no-go task versus
those without SUDs. The authors suggested that their
results signaled a correlation between gray matter volume in the mesolimbic reward system and aggression.
They also opined that the findings of decreased gray
matter volumes in the prefrontal cortex, OFC, and
premotor area were associated with the presence of
SUDs. One study limitation is that offenders used multiple substances, in addition to alcohol. Thus, it is not
possible to attribute findings to the sole effect of
alcohol.
A final MRI study examined the relationship
between MAO-A genetic variants and amygdala and
OFC surface areas in a sample of males with ASPD,
where approximately 50% endorsed alcohol dependence, and healthy controls (Kolla, Patel, Meyer, &
Chakravarty, 2017). A group 3 genotype interaction
emerged, such that the ASPD group with MAOA-L
had reduced surface area in the right basolateral
nucleus of the amygdala and increased surface area in
the right anterior cortical amygdaloid nucleus (Kolla
et al., 2017).
In conclusion, there is an association between alcohol misuse and levels of serotonin and dopamine modulated by MAO-A. MRI analyses also indicate that
structural changes, such as hippocampal alterations
and decreased amygdala volumes, show a relation
with alcohol misuse and a history of violent behavior.
Highly impulsive males with ASPD also show lower
MAO-A total distribution volume in the OFC and VS.
A limitation common to virtually all studies is that it is
impossible to discern whether alcohol misuse produced the neural anomalies or whether they were
present prior to the onset of alcohol misuse and subsequently led to increased vulnerability. While results
require replication in related samples, this work supports the need to address a wide variety of neurobiological correlates to better understand the association
between antisocial personality disorder/psychopathy,
alcohol misuse, and violence. Secondary prevention of
violence must, therefore, adopt a more nuanced
approach that considers the multitude of brain abnormalities predisposing vulnerable individuals who misuse alcohol to engaging in violence.
MINI-DICTIONARY OF TERMS
Alcohol misuse From a psychiatric perspective, the Diagnostic and
Statistical Manual of Mental Disorders (DSM) Fifth Edition
defines problematic use of alcohol as manifestation of an alcohol
use disorder that may be mild, moderate, or severe in intensity.
The previous edition of the DSM categorized harmful use of
alcohol as either alcohol abuse or alcohol dependence. For the
purposes of the chapter, we use the term “alcohol misuse” to
encompass all forms of harmful alcohol use.
Antisocial personality disorder A condition characterized by a longstanding pattern of disregard for and infringement of the rights
of others.
Psychopathy A personality disorder with characteristic features
including impulsivity, manipulativeness, egocentricity, and callousness, along with a history of past and pervasive criminal
behavior.
III. PSYCHOLOGY, BEHAVIOR, AND ADDICTION
REFERENCES
Monoamine oxidase-A An enzyme located on brain outer mitochondrial membranes that metabolizes serotonin and dopamine, along
with other neurotransmitters.
Dopamine A catecholamine neurotransmitter associated with
reward and motivation mechanisms. Dopamine acts on both the
central nervous system and the sympathetic branch of the peripheral nervous system.
KEY FACTS
Monoamine Oxidase-A
• Monoamine oxidase-A is an enzyme that degrades
neurotransmitters, such as serotonin, dopamine, and
norepinephrine.
• Evidence from preclinical and clinical studies
support an association between monoamine
oxidase-A brain levels and aggression.
• Monoamine oxidase-A is a treatment target in
certain mood disorders and neurodegenerative
illnesses.
• Monoamine oxidase-A levels have been shown to be
lower in individuals with antisocial personality
disorder (Kolla et al., 2015).
• The morphology of the amygdala shows a
relationship to the monoamine oxidase-A gene in
antisocial personality disorder (Kolla et al., 2017).
SUMMARY POINTS
• Robust evidence supports an association between
neurochemical dysfunction and violence in
individuals with an alcohol misuse history.
• Type 1 alcoholics have higher levels of serotonin
and decreased dopamine levels.
• Type 2 alcoholics display lower levels of serotonin
and increased dopamine levels.
• Monoamine oxidase-A, an enzyme that modulates
serotonin and dopamine activity, may underlie
pathological aggression.
• Monoamine oxidase-A genetic polymorphisms
make individuals more vulnerable to alcohol’s
negative effects, including violence.
• Magnetic resonance imaging analyses show
decreased hippocampal volumes in Type 1 and
Type 2 alcoholics.
• Alcohol misuse and violent behavior present with
decreased amygdala volumes.
• Secondary prevention of violence must adopt a
more nuanced approach that considers the
multitude of brain abnormalities predisposing
alcohol misuse to violence.
283
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