Clinical

Psychology

Pergamon

Keview, Vol. 17, No. 6, pp. 6.5-665,

1997
Copyright 0 1997 Elsevkr Science l.td
Printed in the USA. All [rights reservd
0272-7358/97
$17.00 + .OO

PI1 so272-7358(97)00039-1

HYPOTHESIS
THE SEROTONIN
OF AGGRESSION REVISITED
Mitchell
The University

E. Berman
of Southern

Mississippi

Joseph 1. Tracy and Emil F: Coccaro

Medical

College of Pennsylvania

ABSTRACT.

+ Hahnemann

University

School of Medicine

Many contemporary theorists believe serotonin (5.HTT) neurotransmitterfunction-

ing plays a role in the regulation of human aggressive behavior We argue that the evidence
supporting this 5-HT hypothesis of human aggression is less compelling than commonly assumed,
due to (a) conflicting study results, and {b) signiJicant methodological limitations of existing
studies. Recent models that integrate the role of psychological and contextual variables in
5-HT-associated

aggression are reviewed. The need to incorporate psychometrically sound mea-

sures of aggression in 5-HT studies, to use experimental and longitudinal designs, and to test
hypotheses drawn from multifactorial models in future research is advocated. 0 I997 Elsevier
Scien,ce Ltd

NEUROTRANSMITTERS
among

neuronal

ters serve either

human

brain,

Careful

chemical

messengers

and peripheral

to activate or to prevent

this feature

tion flow across

behavioral

ARE

cells in the central

complex

the firing

of neurotransmitter
neural

networks

allow

communication

systems. Neurotransmit-

of downstream

functioning
associated

neurons.

helps to regulate

with emotional,

In the

informa-

cognitive,

and

experiences.
clinical

observation

of individuals

areas gave rise in the late 1800s to seminal

such as Brocas

observation

in the left cerebral

neurotransmitter
nemotransmitter
Correspondence
sippi,

that

nervous

Department

of speech

with structural
findings

localization

hemisphere

(Boring,

abnormalities

are

not

1950).

should

be addressed

of Psychology,

to Mitchell

651

brain

relationships,

E. Berman,
Hattiesburg,

to gross structural

identifiable.

relationships

P.O. Box 5025,

in specific

at the base of the third convolution

In contrast

so readily

systems in brain-behavior

lesions

on brain-behavior

Thus

in humans
University

the

defects,
role

of

had to await the

of Southern

MS 39406-5025.

Missis-

M. B. Berman, J. I. Tracy, and E. I? Coccaro

652

development
histologic

of reliable

stains,

strategies

markers

to study neurotransmitter

of biosynthetic

pathways,

functioning,

and advances

such

as

in psychopharma-

cology.
To date,

more

rotransmission.
serotonin

than
Of

(5-HT)

50 molecules

these

activity on human

lation and research.

It is believed

behavior

1992;

(Coccaro,

fore, believed

or suspected

substances,

aggression

to play a role in neu-

the

has been

potential

the source

that 5-HT serves to modulate

Spoont,

to be associated

sion, suicide,

are known

neurotransmitter

1992).

Defects

or constrain

in the serotonin

with a variety of extreme

arson, and alcoholism

(e.g., Coccaro,

influence
of much

ongoing

system are, there-

behaviors,

1992; Linnoila

of

specu-

including

aggres-

SCVirkkunen,

1992;

van Praag et al., 1990).

The earliest published
activity and human

human study directly addressing

aggression

Coyer, & Major, 1979), but the number

of this literature
support
human

led earlier

the notion

et al., 1990).
examined

(e.g., Coccaro,

however, concluding

aggression

evidence

activity plays an important

1992; Linnoila

may be premature.

& Virkkunen,
that 5HT

idea

that

Virkkunen,
ological

5-HT

1992).

regulates

Second,

aggressive

functioning

flaws and limitations

attitudes, or personality

behavior

of existing

plays an

First, surprisingly few studies have

(e.g.,

Coccaro,

studies.

Finally,

1992;

Linnoila

&

to the method-

equivocal

or does not seem to attenuate

Many studies

traits to support

previous reviewers have paid little attention

evidence either is not acknowledged

to

role in

1992; van Praag

the relation between .5-HT status and actual aggressive behaviors.

in this area have relied on measures of emotions,

the

that there is compelling

neurotransmitter

For several reasons,

integral role in human

Ballenger,

of studies in this area has grown rapidly. Surveys

reviewers to conclude

that serotonin

aggressive behavior

the relation between serotonin

is less than 20 years old (i.e., Brown, Goodwin,

or contradictory

the conclusions

drawn

by reviewers.
The primary
5-HT

purpose

and aggression

of this paper is to attempt

literature

human

studies

that include

ratings

of actual aggressive

or a documented
sures of anger
aggression
distinct

history

and biologic

variables

The second
ceptualizations
perspectives.

purpose

First,

anger

and

of aggression

(see Archer,

of 5-HT-related

(Biaggio

research

EVIDENCE

FOR SEROTONERGIC

Measurement

of 5-HT Activity

& Maiuro,

efforts

of

conceptually
Second,

anger

behavior

of this issue).
biopsychosocial

by the literature,

and explain

con-

support for these

developing

divergent

may help increase

REGULATION

on mea-

hypothesis

aggressive

contemporary

to the expression

on

behavior,

relying

1985).

between

and evaluate the empirical

conceptualizations

how and why 5-HT activity contributes

of aggressive
Studies

are considered

the relation

hypothesis is supported

of the

self- or clinician-

the serotonin

1991, for a discussion

aggression

(e.g.,

behavior).

hostility

of this paper is to examine

biopsychosocial

behavior

observations

or violent

examination

in the past. We will focus

will not be used to support

may help guide future

important,

laboratory

may underestimate

If the serotonin

a more critical

done

of aggressive

behaviors,

the construct
measures

models

measures

for two reasons.

from

has been

of aggressive

or hostility

and hostility

than

findings.

testable
More

our understanding

of

of aggressive behavior.

OF AGGRESSION

IN HUMANS

Neurotransmitter
activity is typically assessed using one of the following strategies: (a)
central neurochemical
measures,
(b) hormonal
measures following pharmacochallenge of neuroregulatory
systems, or (c) peripheral measures obtained from urine or

Serotonin and Aggression

blood

(e.g., concentration

ters).

Each

strategy

of neurotransmitter

provides

an index

653

metabolites;

platelet

of neurotransmitter

binding

parame-

activity that can be corre-

lated with dimensional

measures of aggression
(e.g., self- or other-rating
scales) or
used to discriminate
groups of individuals characterized
by aggressive behavior (e.g.,
violent

criminal

Peripheral
source

offenders).

measures,

about central

though

nervous

easy to obtain,

evidence

for the 5-HT

hypothesis

complex

and equivocal,

and has been recently

& Coccaro,

in press).

Neurochemical
Concentration

are considered

system functioning

(see Coccaro

of aggression

Therefore,

peripheral

provided

the least informative

& Ravoussi,

1994).

by peripheral

reviewed elsewhere

The

measures

(Berman,

studies will not be included

is

Ravoussi,

in this review.

Measures and Aggression

of 5-HIAA (5-hydroxyindoleacetic

acid, a major metabolite

of 5-HT)

in

cerebrospinal
fluid (CSF) taken from a puncture in the lumbar sack has been used as
an index of central 5-HT activity. CSF 5-HIAA is produced by neurons in the spinal
column,
brain.

and levels of this metabolite

For this reason,

neurotransmitter
neuronal

activity. However,

activity in specific

Brown

and colleagues

association
involving

between
26 men

participants

brain

CSF

5-HIAA

confined
Lifetime

ratings

and

explosive,

obsessive

military
1982).

men diagnosed

Thus,

5-H&4

and aggression

second

behaviors

not be related

disorder

and antisocial

and psychiatric

1979).

All

behaviors

interviews.

were
Rating

An index of behavioral

with CSF 5-HIAA levels. Specifically,

personality

diagnoses.

was reported

studies

disorder

Weaker
disorder

for the

study of 12

(Brown

et al.,

between

p < .08).
to include
about

with no diagnosable

school

diag-

schizoid,

support

in a follow-up

personality

is a failure

the item content

(e.g.,

et al.,

but no other major

trend was found for the association

(e.g., assault, fighting)

to aggression

(Brown

and hysterical

behavior

in individuals

concerns

an inverse
in a study

with those with passive-aggressive,

with DSM-ZZZ borderline

Brown

to report
in humans

diagnosis,

the results of these studies tell us nothing

shortcoming

aggressive

records

immature,

personality

of the

groups.

unit

disorder

and CSF 5-HIAA levels (T = -.53,

shortcoming

behavior

forensic

associated

compared

of aggressive

of

about

a total life-history
of aggression
score (BrownCSF 5-HIAA was negatively associated with BGA

In the latter study, a nonsignificant

BGA scores
One

compulsive

hypothesis

of the

no information

researchers

aggressive

for almost 61% of the variance.

had lower CSF 5-HIAA

serotonin

the earliest

of various aggressive

(p. 135) was also inversely

men with antisocial,

noses

and

from hospital

(r = - .%), accounting

impulsivity

cortex

useful indexes

regions.

to a military

using information

one of the more

CSF 5-HIAA levels provide

were among

scores were summed

to produce
Goodwin Aggression
scale: BGA).
scores

with 5HIAA in the frontal

had at least one ZXM-ZZpersonality

psychopathology.
calculated

correlate

CSF 5-HIAA is considered

any comparison

the association
personality

of CSF

disorder.

of the BGA. This scale reflects

and antisocial
disciplinary

behaviors

problems,

both

that may or may

problems

with the

legal system). It is therefore unclear from the results of these studies whether low CSF
5-HIAA is related specifically to aggressive behavior. Brown et al. (1979) reported high
interrater
agreement
for the BGA (T = .98), but the procedures
used to derive this
statistic were not described.
Test-retest stability and internal consistency
statistics for
the scale were not reported,
standardized
administration

and almost no validity evidence was provided.

and scoring procedures
prohibits comparison

Lack of
of BGA

scores across studies.

used routinely

Despite

by different

The findings

negative

a satnple of alcoholics
measure

In conttzt

Specifically,

correlation

(r = - ..?l)

(n = .57) and healthy

Scalia-Totnba,

& Bertilsson,

partner

replicated,
Limson
between

9HIAA

on CSF 5HIAA

levels than alcoholic

(1990)

cxanlitlrd

the relation

between

behavior

disorders

tivity disorder

[ADHD],

oppositional

obsessive
(SF

compulsive

5HIAA

disorder

only in the disruptive

between

In contrast
relation

significant.

complicating
CSF 5HIAA

1990; Simeon
of self-tllntilation

(i.e.,

major

with major

mental

depression

diagnos~~s tot- both

data obtained
had higher
on either

conduct

disorder

of impulsive

scores

negative

above,

behavior,

affect,

two studies
behavior

but

and aggresof statistical

demographic

variables

disorders

personality

disorder

of aggressive
Results

than non-selfltnutilators,
ittdexes

found

indicated

Lucas, SC
with a

of self-mutilation

(n

and percentages

of

each group,

the most common

was quantified

using

that self-mutilators

but the groups

of 5HT

to find a

individuals

within

being

behavior

failed

(Gardner,

with no history

and personality

CSF-.5-HIAA levels or peripheral

age-corrected

only 3 of 32 correlations

et al. ( 1992) compared

interview.

with

of the results.

reviewed

Life history

hyperac-

children

of aggressive

behavior,

and Potter

deficit

and

was made for the number

(rr = 26) to individuals

and borderline

attention

However,

without
per se.

both in children

with expectations,

and a historv of aggressive

disorders

Hibbs,

n = 33)

with ratings

the interpretation

from a sem-structured

significant correlatiotts
were found in either

disorder,

group.

Sitneo;)

a sexual

acquaintance.

CSF, studies of children

Hamburger,

disorder;

No adjustment

et al., 1992).

groups.

aggression

used to obtain

defiant

= 26). The groups wet-e similar on rele&ult

specific

a nonintimate

(ZSF 5-HIAA and aggression

to the suggesti\,e findings

between

Cowdry,
history

behavior

lower CSF

violent tnen had

was found for aggression

Rapoport,

correlated

(:SF .5-HIAA and measures

sion wet-e statistically

tests conducted,

analyses revealed
nonalcoholic

givett that (a) Each subtype group of

( n = 43). Consistettt

levels were inversely

of murder

Tuck, &Aring;sberg,

(1,) multiple t-tests were conducted

Kruesi,

with disruptive

in

of the

violent men, and men who murdered

of the procedttrc

However,

characteristics

(Lidberg,

tI~nn men who murdered

for T>pe I error; and (c) no relationship

ttonexistent.

and aggression

one study found that men convicted

1985). However, exploratory

Due to the invasive nature

associaa modest

(n = 15) using a tnodification

and psychometric

The Lidberg et al. findings arc difficult to interpret

are almost

found

in this study.

violent tnen consisted of only 5 to 10 suejects;

adjustment

but with statistical

CSF 5HIAA

subtypes of violent men. Specifically,

had lower CSF 9HIAA

of the BGA have been

et al. (1991)

volunteers

procedures,

than healthy controls

in certain

lower (SF

scoring

were not described

to these positive findings,

were tto different

5HIAA

have been

magnitude.

of the BGA. Itetn content,

aggression

various versions

groups.

of the Brown group

tions of less impressive

bttc significant

these limitations,
research

functioning.

did not differ

Moreover,

no

between indexes of 5HT functioning

and aggressive behavior
<group. Gardner
et al. (1990) exatnined
CSF metabolites
in

wome~t diagnosed with borderline

personality disorder. They found no differences
between subjects with a history of physical violence directed toward another person
(n = 9) and those without a history of violence (n = 8). The studies by Gardner et al.
and Simeon et al. do not report psychometric
data or scoring procedures
for their
aggressiott measures.
A series of(3F 5HIAA ittvestigatiotts by one research group provides some support
for the idea that low 5-HT is associated specifically with an impulsive
subtype
aggressive behavior
(e.g., I,intloila
et al., 19X3; Virkkutnen,
Nuutila, Goodwin,

of
&

65.5

Serotonin and Aggression

Linnoila,

1987; Virkkunen,

men who committed

Rawlings et al., 1994). In a frequently

or attempted

to commit

reported

to have lower CSF 5HIAA

(Linnoila

et al., 1983).

homicide,

concentrations

Men were categorized

cited study of 36 Finnish

impulsively violent men were

than

nonimpulsively

violent

men

as impulsively violent if, based on clinical

judgment,
no rationale could be determined for their act (i.e., it was not premeditated)
and the offender was not close to his victim. The authors concluded, that ...low 5-HIAA
concentration

in the CSF of violent

violence per se (p. 2610).

functioning

is principally

not conclusively
categorize
argued

(e.g.,

unknown

unplanned

intrafamilial

by Lidberg

than

Indeed,

et al. (1985))

lower CSF 5HL4A

a marker

of impulsivity than

was not reported.

is more likely to occur

in casual relationships

the results of Linnoila

in which homicide

levels. More important,

in intimate

et al. (1983)

among intimates was associated with

the study by Limroila

recruited

were compared

in the United

a history of violent behavior,

on this lack of economic
impulsive.
both

The

violent

controls.

results

men

These

destructive

et al. (1983)

in nature

In an attempt
controls

why these

results

to provide further

support

were

compared

Rawlings
homicide.

The

controls

fell between

offenders
between

having

cautiously.
group.

as impulsive

Offenders

offenders

included

both

was defined
indicated

offenders.

and nonimpulsive

being close to healthy

First,
to the

Second,

is unclear.
but not

and

link,
healthy

arsonists

as in Linnoila

that impulsive

However,

of

are at

aggression-serotonin

nonimpulsive

to
than

forms

There

and, in contrast

in the control

as

and
et al.

offenders

CSF 5-HIAA levels of

offenders,

controls

with CSF

and nonimpulsive

generally

higher

CSF

5-HIAA

levels.

offenders

and healthy

controls

on CSF 5-HIAA make these results

impulsive

somewhat difficult to interpret. The

5HIAA levels could be interpreted
well-planned

behavior
compared

impulsive

be interpreted

of the arsonists

results

the impulsive

offenders

that

nationality

behavior

had lower CSF 5-HTAA than nonimpulsive

5-HIAA levels of impulsive

also had

had lower CSF 5-HIAA

for an impulsive

et al., 1994).

et al. (1987).

the fire-setting

idea

men

gain. Based

acts may have been premeditated

to both

Impulsive

The arsonists

5-HT functioning.

were included

for these individuals

(Virkkunen,

healthy

for the
should

behavior

arson).

and Virkkunen

men

group were of a different

men who committed

(1983)

support

revenge

offenders

classified

with compromised

the fire-setting
(e.g.,

et al., 1987).

violent

and 10 healthy

had lower CSF 5-HIAA

and that violent

both men and women

That is, the motivation

impulsive

the authors

also provide

arsonists

did not set fires for economic

that arsonists

are associated

however,

the validity of labeling

economic

motive,

in the control

groups,

States (Virkkunen

indicated

results

least two reasons,

forensic

did not

is associated with

of 20 impulsively

to 20 Finnish

but apparently

and controls,

behaviors

participants

is

CSF 5-HIAA.

Linnoila

controls

relation-

the victim

et al. seem at odds with those

In a follow up study, CSF 5-HIAA levels in a subgroup

from

used to

It could also be

or when

address the issue of whether a life history of violent behavior, in general,

compromised

.5-HT

for the reliability and validity of the method

violence

violence)

to the aggressor.

reported

Evidence

as impulsive versus nonimpulsive

that impulsive,

ships

is more

associated with an impulsive subtype of aggressive behavior was

supported.

offenders

offenders

For several reasons, however, the idea that compromised

violent

behaviors

rather

Nonsignificant

differences

fact that nonimpulsive

offenders
had high CSF
to mean that 5-HT plays a substantial
role in
than impulsive

aggression.

In summary, the idea that 5-HT regulates aggressive behavior is modestly supported
by CSF 5-HIAA studies. Although CSF 5-HIAA levels were inversely related to aggressive behavior in some studies (Brown et al., 1979, 1982; Limson et al., 1981), other

M. B. Berman, J. I. Tracy, and E. I! Coccaro

656

studies provide modest

1990;

Simeon

conflicting

(Kruesi et al., 1990; Lidberg

et al.,

findings

1992)

support

regarding

for

human

the

aggression

in several ways. The most obvious explanation

5-HIAA and a life history
given that several
comings

of aggressive

studies

sizes, a tendency
extraneous
of aggression

measures

significant

to include

with questionable

Pharmacochallenge

assessment

measuring

hormonal

controlled,

to a probe

No probe,
stimulation
specific

is thought

are produced

hormones

more

example,

consistent

aggressive

personality
1989).

results

than

Fenfluramine
challenge

correlated

BGA in the personality-disordered

group

controls

or individuals

with depression.

aggression

and 5-HT

individuals

with personality

The

results of other

hypothesis

functioning

1994; OKeane

with 30 mg d-fenfluramine

functioning.
subtype system.
functioning),

of the glands

or

that manufacture

in adults

was examined
and

18 with no
receptors

that prolactin

(r = -.57,

it is possible

For

evidence

(Coccaro

of

et al.,

by both releasing
response

on a modified

p < .05),

some-

studies.

in 20 men with

procedure

with scores
Thus,

have provided

by neurochemical

postsynaptic

indicated

may be found

to fenflu-

version

of the

but not in the healthy

that a relation

only in certain

between

populations

(e.g.,

psychopathology).

(Coccaro,

et al., 1992).

output is
hormonal

results from the

disorders,

pharmacochallenge

of aggression

reduced

or receptor

functioning

is a drug that stimulates

was inversely

hormonal

to drug infusion

pharmacochallenge

Results

systems and then

Because

neurotransmitter

provided

depressive

its reuptake.

involves administer-

neurotransmitter

behavior

those

and 5-HT

25 with

and the use

1994).

of aggressive

using a fenffuramine

5-HT and blocking

ramine

& Kavoussi,

studies
behavior

disorders,

psychopathology

responses.

activation

uncontrolled

groups,

functioning

(which would reflect

short-

small sample

important

neurotransmitter

response

CSF

properties.

compromised

by the direct

include

activity in the brain,

if hormonal

between

Methodological

These

to a single neurotransmitter

(Coccaro

Pharmacochallenge
what

to reflect

to determine

of brain neurons

if the effects

prolactin)

neurotransmitter

however, is specific

It is also difficult

one or more

(e.g., cortisol,

in part, through

response

of nemotransmitter

that targets

The

is least satisfactory

comparison

psychometric

Measures and Aggression

(probe)

findings.

findings.

appropriate

Pharmacochallenge

ing a drug

This explanation

groups that differ on potentially

a failure

et al.,

of aggression.

is that there is no relation

for the contradictory

to compare

variables,

hypothesis

and CSF 5-HIAA may be explained

behavior.

have reported

may also account

et al., 1985) or no (Gardner

5-HT

studies also provide

Berman,

OKeane

Kavoussi, & Hauger,

et al. found that prolactin

(an isomer

of fenfluramine)

support

for the 5-HT

1996; Moeller
response

et al.,

to challenge

was lower in nine

nonde-

pressed, nonpsychotic
men convicted of murder compared with nine healthy controls.
This result supports the notion that 5-HT functioning
is inversely related to aggressive
behavior.

However,

the forensic

and control

groups

differed

on several

important

uncontrolled
variables (e.g., height, weight, and the stress of incarceration
in a
forensic hospital). Correlations
between prolactin response and measures of aggressive behavior within groups were not reported.
A recent study showed that prolactin
response
to d-fenfluramine
was inversely
related both to scores on a modified version of the BGA and to a laboratory task of
aggressive behavior in 14 males with personality disorder diagnoses (Coccaro et al.,
1996). In contrast to most studies in this area, interrater
agreement
and internal

657

Serotonin and Aggression

consistency

data for the aggression

that growth
5-HT,,

hormone

receptors,

of cocaine

response

was inversely

dependence

(Moeller

ratings were reported.

to buspirone,
correlated

(r = - .73),

Another

an agonist

recent

study found

that stimulates

postsynaptic

with BGA scores in 10 adults with a history

but not in 10 age- and gender-matched

controls

et al., 1994).

As with central
children

neurochemical

have been

data do not support

children.

Stoff

disruptive

an inverse

find a relation
frequency

between

prolactin

most other

reports,
(Pine

has been replicated

in individuals

diagnosed

dependence,

and

or healthy

healthy

controls,

males

between

hormonal

to fenfluramine

in
with

response

et al. (1994)

to

also failed to

and a scale assessing

However,

the

higher prolac-

as aggressive

compared

with

which is in the opposite

direction

from

in a study of 34 younger

men

studies

with personality
with a history

volunteers).
depressed

One

measures,
that would

an artifact

some

behavior.

brothers

disorders,

explanation

of convicted

of different

for an inverse

for these conflicting

statistical

to determine

depressed

findings

a restricted

associations.

if these

data distributions

of cocaine

not in children,

may exhibit

relation

has been shown

adults with a history

(but

and children

thus attenuating
help

support

This relationship

of violence

individuals,

scores on aggression
statistics

provide

and aggressive

descriptive
Moeller

behavior

and adolescent

Halperin

of boys classified

of

pharmacochallenge

and aggressive

acts in boys with ADHD.

This finding,

pharmacochallenge

adults,

5-HT

relation

investigations

in adults,

et al., 1997).

5-HT functioning

merely

no

behavior.

response

of aggressive

as nonaggressive.

delinquents
Overall,

between

were found in a subgroup

those classified

between

found

and aggressive

and intensity

tin responses

relation

to studies

in a study of prepubertal

disorders,

challenge

few pharmacochallenge

In contrast

et al. (1992),

behavior

fenfluramine

studies,

conducted.

is that
range of

Unfortunately,

conflicting

findings

are not always presented

are

(but see

et al., 1994).

Experimental Studies of 5-HT and Human Aggression

The studies discussed
tal or longitudinal
5-HT

neurotransmission

studies

and

measurement

conducted.

aggressive

about

the direction

aggressive

behavior

tonin being

of potential

the cause of aggressive

static, and is influenced

brain

It could

chemistry,

behaviors.

& Linnoila,

1991; Kraemer,

(Galvin

et al., 1991; Gerra

Ebert,

study involving

neurotransmitter
& McKinney,

has

that engaging

than compromised

in both nonhuman

Schmidt,

behavior

are uninformative

be argued

rather

Indeed,

by early social influences

Suomi,

studies

between

few experimental

no longitudinal

of nonexperimental

Experimen-

relation

status and aggressive

relationships.

alters serotonin

designs.

a causal

Unfortunately,

To date,

neurobiological

results

research

to establish

behavior.

conducted.

of both

In addition,

nonexperimental

is necessary

in this area have been

repeated
been

so far employed

methodology

in

sero-

activity is not

primates
1989)

(Higley,

and humans

et al., 1993).

For these reasons, investigators have begun to use experimental

methodology
(that
is, manipulation
of neurotransmitter
activity and random assignment
to treatment
conditions)

to examine

studies, aggressive

5-HT

behavior

example,

aggressive

behavior

of shock

or loud noise

functioning

is observed

and human

can be operationally

delivered

aggressive

behavior.

using one of several laboratory

to a fictitious

defined
participant,

In these

paradigms.

as the intensity

For

or duration

or the number

of points

with monetary

value taken

away. There

struct validity of these paradigms

is substantial

(see Giancola

evidence

supporting

& Chermack,

At this time, all published experimental

studies have used healthy
teers with no documented
psychopathology.
Manipulation
of dietary
been

used to alter .5-HT functioning

necessary

for the synthesis

tryptophan
primates

is correlated
(Young,

experimental
tryptophan
Young,
have

been

aggressive

due

1986).

Smith

to the

failure

behavior

received

posthoc

evidence

opponent

an

tryptophan
cebo

study, participants

placebo-controlled

study found

nist, produced

lower aggressive

Creson,

Although

1995).

included

in this study, it was also associated

similar

increased
ongoing

In summary,
ing central

specifically

experimental

population

studies

1995).

option.

It

aggressive

inactive

pla-

A recent

and 5-I-IT, 1s ago(Cherek,

Spiga, &

with lower aggres-

with decreased

response
decreased

5-HT,,,

behavior

None of these

problematic.

with placebo

studies have provided

behavior

is,

responding
therefore,

on

unclear

behavior,

or merely

evidence

that manipulat-

modest

in humans.

may be due to the exclusive

may, in general,

exhibit

sup-

low levels

The limited

use of healthy

of aggressive

behavior

effects

found

volunteers.

This

urlder controlled

conditions.
THEORIES

Though

who
found

in general.

5-HT can alter aggressive

in experimental
laboratory

5-HT
behavior

group tended

aggressive

PCBond,

was associated

topographically
pressed

increased

a putative

sive responding
whether

(Pihl et

participants

pharmacologically

compared

consumption

nonaggressive

adversary

than

of the results

that eltoprazine,

eltoprazine

used a laboratory

by a fictitious

(Cleare

may

retaliatory

study using a similar paradigm

interpretation

responding

Pihl,

results

to elicit

adversary

defined

(Smith,

nonsignificant

study, this group

depletion

however,

making

earliest

decreasing

with aggression

in the tryptophan-depleted

provocative

studies,

conditions,

and lower
The

nor

participant

manipulation

provocative

that tryptophan

manipulation

control

behavior,

acid is

of dietary

1981).

increasing

that their

diet. Another

was moderately

This amino

levels in humans

to a fictitious

In a follow-up

research voluntryptophan
has

or depletion

neither

aggressive

delivered

tbr a moderately

studies.

8c Gauthier,

levels of provocation

a tryptophan-augmented

modest
when

that

of a provocation

different

shocks

Young

et al. suggested

in participants.

In this second

to set higher

1989;

reported

of shock

of these

Enhancement

in CSF 5-HIAA

& Finn,

diets affected

and duration

task that incorporated

al., 1995).

Pihl,

in participants

8c Ervin,

5-HT.

with changes

Ervin,

study in this area

as the intensity

in several

of central

the con-

in press).

not definitive,

studies

have reported

havior

in humans.

OF 5-HT

AND

some neurochemical,
inverse

How

associations

5-HT

activity

AGGRESSION

pharmacochallenge,
between

influences

5-HT

and experimental

activity and aggressive

aggressive

behavior

be-

in humans,

however, is not yet known. Multifactorial

models have been developed to explain the
role of 5-HT in aggression. All models assume that reduced 5-HT functioning
is not
specific to aggressive behavior, but that aggression is merely one behavioral correlate
of compromised
psychological

neurotransmitter

processes

The Low Serotonin

Linnoila

posited

Syndrome

and Virkkunen

low serotonin

syndrome

(1992)

functioning.
to be responsible

The

models

differ,

for the expression

however,

in the

of aggression.

(LSS) Model
propose

a disinhibition

model

of aggression

(p. 46). Th is model holds that decreased

called

5-HT functioning

and Aggression

Serolonin

is associated
specific

with a biologically

to aggressive

other

problematic

individuals

determined

behavior.

One

behaviors

are

impulsive

implication

largely

659

personality

of this model

the

result

with low 5-HT lack the appropriate

of internal

internal

style that

is not

is that aggressive
processes.

controls

and

That

is,

to resist destructive

impulses.
As discussed
impulsive

earlier,

behaviors.

ers who

do not

nonimpulsive

there

dependence
to classifj
impulse

Further

have been

to the LSS model,

psychological

impulsive

processes

individuals

reduced

5-HT

hypoglycemia
amounts
term,

conclusively

activity is associated
and depressed

of alcohol

Virkkunen,

Kallio

measures

(e.g.,

as

et al.,

et al., 1989).

Sheline,

demonstrated

of

of impulsivit)

Coccaro

Kavoussi,

Lish,

8~

Kallio et al.,

that low 5-HT is

with sleep,

use of alcohol
outbursts

glucose

individuals.

activity is associated

model

gressive behavior.
impulsive

could

factors

for its limited

emphasis

alcohol

model

the environmental

does not address

of aggressive

on contextual

and

with a general

predisposition

to engage

the factors

that may elicit

traits.

is, although

LET

about

personality

to impulsive

That

aggression

or psychological

with human

is postulated,

factors

necessary

agin
a
this

for ~hc

behavior.

The lnforma tion-Processing

(1992)

and impulsive

1989).

associated

with impulsive

predisposition

aggressive

for the observation

consumption)

does little to inform

acts in individuals

consumption
the continued

alcoholism

& Lieber,

biologically-determined
expression

early onset

long-

exacerbates

of impulsive

accounts

Noumair,

Even if 5-HT is associated

acts, this model

aggressive

than

alcohol

to

excessive

However,

this issue),

the likelihood

with both

levels.

Because

therefore,

Branchey,

and a proneness
depression,

5-HT

8c Giancola,

ill

Specifically,

activity and further

and mood.

model,

be criticized

(other

disruption

behavior.

behavior

consumption.

to alleviate

raising

5-HT

affect increases
This

Buydens-Branchey,

LSS

temporarily

(see Chermack

that low 5-HT

psychological

sleep

depresses

violence

(e.g.,

with both

metabolism,

behavior

to relieve negative

in these

by alcohol

In an attempt

to aggressive

of aggressive

regulation

mood.

consumption

related

for the development

are consumed,

can elicit aggressive

Spoont

appealing

and alcoholics

et al., 1992; Virkkunen,

5-HT is only indirectly

posited

involves mood

heavy alcohol

problems

The

It is intuitively

low

alcohol

with trait impulsivity.

According
The

it has not been

than

for the idea

with early onset

(e.g.,

Coccaro,

Simeon

5-HIAA

from studies showing

on self-report

et al., 1996;

et al., 1991;

regulates

are valid representations

5-HT activity in some

Coccaro

For these reasons,

associated

support

CSF

support

attempters,

behaviors

5-HT

gain and murder-

lower

comes

suicide

or not these

that

Further

1992, for a review).

this issue, scores

Limson

to have

and individuals

has only modest

(e.g.,

1996;

notion

by economic

behaviors

murderers,

with reduced

but not all studies

1994).

whether

complicating

associated

Csernansky,

& Virkkunen,

problems

seem

attempters

of arsonists,

However,

for the

et al., 1987).

with impulsive

(see Linnoila

control

1994).

crime

Virkkunen

suicide

the behavior

impulsive.

their

(e.g.,

activity in violent

support

who are not motivated

premeditate

criminals

that low 5-HT is associated

5-HT

is some

Arsonists

proposes

Model
an information

(i.e.,

signal)

processing

model

of 5-HT-

related aggression that puts greater emphasis on external factors than the LSS model.
She argues that 5-HT neurotransmission
fine-tunes
an organisms
behavioral
responses

to internal

signals

(i.e., changes

in various

hormonal

and neurotransmitter

systems)

and to external

tive, the primary

stabilize

signals (i.e., environmental

function

information

flow. This results in controlled

tive output when the organism

Preclinical

studies

neuroregulatory
behavior

is confronted

support

circuits.

both in behaviors

(rather

behaviors

on signals generated
The information

processing
5-HT

behavior.

the psychological

However,

aggressive

behavior

what different
cessing

implied

from

formation

responses

organism

heightened

decreased

sensitivity

to pain when

conditions

are

response

mation

options
model

not yet been

directly

An important

flight),

5-HT functioning

prosocial

behaviors

5-HT

functioning

in group

drug administration,
destabilize

settings.

Indeed,

drugs

that lowered

decision-making,
behavior,

sive behavior).

social information

increased

sensitivity

hierarchies

productive
fenses

serotonergic

or elevated

behavior

common
functioning

infor-

to underhave

Males

threats

evidence

indicates

that

free-ranging

& Yuwiler,

in the colony
treated

was associated

5-HT functioning

group

1991).

of

Before

was removed

to

with 5-HT-enhancing

to positive social overtures,

(see

or
and

This effect was not found when treated with

solitary aggressive

among

is that intact,

decision-making

experiments,

male animal

partners.

Scott,

may have implications

increased

social

affiliative

(impulsive
facilitate

aggreseffective

which leads to the attainment

In addition,

cohesion,
group

behavior

with effective

may therefore

and decision-making,

may facilitate

primate

Pollack,

behavior

to reproductive

aggressive

against

unplanned

processing

high rank and access

inance

Brammer,

social dominance.
Dominance

Intact

The

this model

model

with effective

some

hierarchy.

5-HT.

and decreased

from

versus

drugs that either lowered or raised indexes

McGuire,

dominance

drugs quickly achieved

Geen,

responding,
framework

drawn

vehicle-controlled

the highest-ranking

the existing

that these

1993;

by this model.

processing

be associated

were administered

(Raleigh,

the
cues,

and reduced

to suggest

theoretical

of the information
should

this may be so. In a series of crossover,

vervet male monkeys

is reduced,

or threatening

(Berkowitz,

but hypotheses

in-

controlling

in humans.

implication

elevated,

activity

in aggressive

a promising

pro-

modulates

suppression,

aggression

of

are some-

information

structures

exists

is not addressed

aggression,
tested

of

theory

The

5-HT

evidence

will engage

provides

BHT-associated

When

the idea

to aggressive

functioning

with behavioral

antecedents
(e.g.,

model.

to provocative

Substantial

why an organism

processing

standing

aroused.

important

However,

cues.

effects

GABA).

for the exhibition

processing

and anatomical

sensitivity

to cues associated

dopamine,

responsible

neurotransmitter
systems

1992, for

modulatory

is not specific

information

with the LSS

5-HT

to environmental

experiences

sensitivity

other

that

flow in neurotransmitter

fight/flight

1990).

mechanisms

associated

holds

and exploratory
(Spoont,

with the LSS model

functioning

by Spoonts

those

perspective

(e.g.,

has in common

neurotransmitter

various

5-HT activity is associated

by punishment

systems

demands.

in stabilizing

to result from serotonins

model

that compromised

reduced

or

and affec-

environmental

to novel environments

neurotransmitter

to this perspec-

cognitive,

plays a role

suppressed

responses)

are proposed

by other

behavioral,

For example,

normally

than neophobic

a review). These

According

system is to constrain

with changing

the idea that 5-HT

information

with increases

cues).

of the 5-HT neurotransmitter

reduce

members,
1992).

and foster
the

of

of stable dom-

the occurrence

Thus,

for group

existence

of counter-

cooperative

presence

de-

of intact

stability and survival.

Scrotonin and Aggression

661

The Irritable Aggression Model

According

to this perspective,

state of hyperirritability.

reduced

However,

confronted

with a noxious

for arousal

and goal directed

serotonergic

aggressive

environmental

activity produces

behavior

event and the neuronal

behavior

(e.g.,

dopamine,

ciently activated

(e.g., Coccaro,

1989).

mood,

the threshold

at which an organism

reducing

Although

not yet directly

threatening,
occur

provocative,

increases

muricidal

OBrien,
behaviors
placed

associated

with central

primarily

provocative

diet

5-HT

when

In humans,

moderate

behavior

al., 1995).

In the absence

of provocative

behavior

may be moderated

heighten

perception

A shortcoming
compromised
However,

behavior

which

Pihl,

can

to a

aggressive

for the role of

monkeys

& Young,

exhibited

1987).

aggressive

be considered

and whether

a highly

exhibited

functioning

That

limited

Genetic

are acknowledged

SUMMARY

behavior

social behaviors

avoid the various

changes

is causally

in humans.

5-HT

activity may

or attack.
on the

on the

development

of

development

of 5-HT

(e.g.,

1992,

Spoont,

serve some adaptive

p.

5-HT system,

function

over time,

DIRECTIONS
is associated

with aggressive

However, this evidence

given the lack of experimental

related

to aggression,

behavior

seems less compelling

or is merely

evidence,
correlated

5-HT status is likely to play but a small role in such

as aggression.

First, more attention should

actual effects in the population,

is, decreased

by theorists

AND FUTURE

It is still unclear,

methodological

The

in any model.

at least in some populations.

with aggressive

(Pihl et
may not

et al., 1986).

events on the developing

exists to suggest that 5-HT functioning

assumed.

(Smith

emphasis

influences

of environmental

incorporated

functioning

for eliciting

in humans

5-HT functioning

by humans

to, provocation

is their

or not these biological

5-HT

necessary

studies suggest that the effect of 5-HT on aggressive

functioning.

the effects

than commonly

seem

decreased

decreased

by provocation.

of all models

are not systematically

complex

support

the

(Marks,

rats habituate
decreasing

this method

to

when

neurons

a study of vervet

or provocation
stimuli,

of, or responsivity

5-HT

nemotransmitter

whether

using

for food,

levels of attack

the level of aggressive

in humans,

that

Ervin,

when 5-HT activity is experimentally

results of these animal and human

Evidence

can be reduced

thereby

(Chamberlain,

behavior

of 5-HT neurons

of 5-HT

from

stimuli.

social encounter.

aggressive

336).

for aggressive

to propose

comes

reduced

competing

to provocative

5-HT activity. Further

aggression

are suffiwith irritable

exists for the idea that

lesioning

destruction

with pre-exposure,

with compromised

in 5-HT

primates

the

It is reasonable

on a tryptophan-depletion

behaviors

affect

this effect

before

(i.e., a mouse)

associated

provocation

are necessary

in rats. However,

1977).

stimulus

stimuli

responds

some evidence

is

systems responsible

norepinephrine)

chemical

to mice

& Paxinos,

provocative

in humans,

a generalized

if the organism

low 5-HT is associated

state. For example,

behavior

is preexposed

Specifically,

or noxious

in a hyposerotonergic

animal

Male

tested

only occurs

It is therefore

shortcomings

common

important

that future

in this research

studies

area.

be paid to using sample sizes large enough to detect

especially for investigations
studying various subtypes

of aggressive individuals. Second, studies of group differences

should include appropriate comparison
groups. That is, 5-HT status must also be examined in individuals
without marked aggression while controlling
for as many relevant confounding
variables as possible. Between-group
research should also examine and report correla-

tions between 5-HT status and aggressive behavior within each group, and report descriptive statistics for both

biologic

and behavioral

measures.

whether a relation between 5-HT and aggression

testing

hypotheses

drawn from

multifactorial

This

would help

elucidate

is limited to certain populations.

rnodels

should

receive

Third,

consideration

in

future research efforts. Laboratory

paradigms exist that allow for the experimental
manipulation of environmental
variables proposed to be important in 5-HT-associated
aggressive behavior, such as perceived
Kelly, 1990; Taylor,

1967).

provocation

As discussed

experimentally

manipulated

by dietary precursors

By continued

implementation

of experimental

ronmental

or attack (Cherek,

earlier,

serotonergic

be examined

under controlled,

ing methodological
Research

laboratory

sound, standardized

conditions.

measures

Finally, the development

continue

to address

the

specific

forms

by 5-HT. Th e impulsive versus nonimpulsive

discussed earlier, provides a promising starting

of aggressive

distinction,

tations

point.

unexamined,

mediator

deserve

consideration.

human

behavior

cessing

and emotional

drugs

that

reducing
indirect

5-HT

forms

that

(e.g.,

psychotherapeutic
It is also possible
competency
impulsive

Prozac

was rlseful
objects)

Such results,

hypothesis

interventions

ies of at-risk individuals

also

of 5-HT on

in information

pro-

serotonin

of other

systems deserve
behavior,

(Prozac),

,4 recent

neu-

may be useful

in reducing

verbal

treatment
effective

environment

in aggressive
increases

to learn social

may reduce

in adults. In

the probability

information

after

in 5-HT activity.

intact 5-HT functioning

important

An interest-

behavior

and the opportunity

costly and time-consuming,

the

for the manage1985).

will produce

may provide

support

for aggressive

in childhood

Though

and

outpatients

however, do not necessarily

Weisser, & Balleweg,

in

placebo-

outbursts

in personality-disordered

have also been

attention.

it follows that

double-blind,

may also lead to enduring

skills during childhood

behavior.

biologic

is that reductions

that a stable rearing

aggressive

behavior

on the functioning

are the only useful

(see Bornstein,

interventions

this way, psychosocial

differences

as fluoxetine

interventions

behaviors

yet untested,

aggressive

the limi-

important,

that the influence

with aggressive

behavior.

approaches

Psychotherapeutic

ing, though

such

breaking

& Kavoussi, in press).

ment of aggressive

of multiple

is associated

aggressive

idea that pharmacotherapy

behavior,

by individual

is dependent

activity,

of

study found

and

Potentially

It is also likely that the link between

and the interaction

increase

5-HT
to expect

behavior

despite

systems. Thus, at the micro level, both the role of specific

5-HT functioning

aggression

(Coccaro

controlled

and aggression

some

controlled

between

it is reasonable

regulation.

and hormonal

subtypes

If reduced

variables

Indeed,

is partially

neurotransmission
receptor

and use of

of aggressive behavior are the most press-

needs in this area.

should

rotransmitter

of envi-

by some models may

controlled
but

properties.

the interaction

predicted

&

may also be

and drugs with serotonergic

methodologies,

events and 5-HT status on aggressive behavior

psychometrically

Spiga, Steinberg,

functioning

of adult

longitudinal

about

stud-

how biological,

psychological,
and contextual factors combine to affect the development
of aggressive
behavior. For example, children of parents who have a history of violent behavior may
be followed across time to determine which factors inoculate, and which facilitate, the
development

of neurotransmitter

tion of these relationships.

In summary, there is suggestive,

and behavioral

abnormalities,

but far from definitive,

evidence

and also the directhat 5-HT abnor-

malities are associated with human aggressive behavior. Future systematic research on
this potentially
important
biologic variable may provide crucial information
about
how individual differences
in human aggressive behavior develop, and how biological

Serotonin

and Aggression

66.?

and psychological factors combine to elicit or inhibit destructive, aggressive acts. More
precise identification
of the nervous system distribution of serotonin receptors
(Tecott, Maricq, & Julius, 1993) will allow more specific tests of the serotoninaggression hypothesis through imaging techniques such as PET or fMRI. For instance,
viewing aggressive scenes or other inductions of aggressive mental states should
produce reliable activation in forebrain amygdaloid areas. Serotonin-aggression
findings also need to be evaluated for their consistency with other findings about serotonins role in behavior. Serotonin abnormalities
have been noted in obsessivecompulsive disorder, eating disorders, mood disorders, among others. Articulations of
the serotonin hypothesis of aggression need to be integrated with such findings to
provide a full understanding of the role of serotonin in human behavior.

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