Inflammation, aggression and
personality
Sara Bromander1,3,Rolf Anckarsäter2, Marianne Kristiansson3,
Thomas Nilsson1 ,Kaj Blennow1, Henrik Zetterberg1, Henrik
Anckarsäter1, Caroline Wass1,4
1
Institute of Neuroscience and Physiology, University of
Gothenburg, Sweden, 2Dept of Anesthesiology and Intensive Care,
Kungälv Hospital, Sweden 3Dept of Clinical Neuroscience, Division
of Forensic Psychiatry, Karolinska Institutet, Huddinge, Sweden
4Schizophrenia and Addiction Program, Centre for Addiction and
Mental Health, Toronto, ON, Canada
INFLAMMATION
The reaction of the tissues to
something that is not welcome and
possibly dangerous
INFLAMMATION
• Different markers may be measured
• Both inflammatory and anti-inflammatory
• A connection between inflammation and
behaviour has long been suspected
Inflammation and behaviour
Background:
• There is a relationship between stress, inflammation and
different forms of psychiatric pathology (Dantzer 2004,
Dean 2010)
•
The way the brain reacts to stress, especially in
relationship to personality factors, is still insufficiently
known
• One way to look at the brain is to study cerebrospinal fluid
(CSF) (Anckarsäter 2005, Söderström 2001), another to
look at different markers in blood
Inflammation and psychiatric disorders
• Classical sickness behavior after cytokine
therapy (Dantzer et al 2004)
• Increased risk of schizophrenia and autism
after prenatal maternal infections (Freedman et al
2010)
• Inflammatory dysbalance in several
psychiatric disorders
Inflammation and aggression
• Hostility is associated with increased levels
of several inflammatory markers (Marsland et al 2008)
• There seems to be a connection between
variants of the CRP gene and impulsive
personality traits (Suchankova et al 2009)
• Measures of hostility/anger are increased in
persons undergoing cytokine therapy (Kraus et al
2003)
Surgical Stress Study
General aim: to identify neurochemical and
endocrine reactions to surgical stress
Specific aims:
• To study the relationship between personality,
inflammatory and neurochemical markers
•To examine central and peripheral inflammatory
markers before, directly after and in the morning
after surgery
Surgical Stress Study
Methods and materials:
35 neurologically healthy patients
Cerebrospinal fluid, Blood & Urine samples
Before (A-samples), 3 hours after (B-samples) and
the morning after (C-samples) knee arthoplastic
surgery
Subjects were asked to fill out personality
questionnaires before arriving at the hospital
Exclusion criteria:
Psychotropic, anticoagulant, anti-parkinson or
corticosteroid treatment
Results
• Markers for dopamin and serotonin activity
as well as for a ”leaky” blood-brain barrier, as
well as for several cytokines, correlated with
markers for impulsive and aggressive
personality traits
• Inflammation seems to be independently
regulated centrally and peripherally, mirrored
in levels of different cytokines.
Conclusion
•
There seems to be a connection between the
levels of different inflammatory biomarkers and
personality, including destructive personality
traits
• The brain´s immune system seems to be
activated during surgery in a way that is
different from in the periphery
Immunological Aspects of
Aggression Study (IAGGS)
hypotheses
 Levels of inflammatory markers differ
between violent offenders and normal
controls
 Levels of inflammatory markers correlate
with violent/aggressive behavior
• Levels of inflammatory markers correlate
with aggressive personality traits
IAGGS
materials and methods
• 64 patients undergoing forensic psychiatric
evaluation and 64 healthy controls
• Blood samples at two separate occasions, 2
weeks in between
• Personality and anxiety questionnaires
IAGGS
materials and methods

Life History of Aggression scale: A 12 item scale assessing various aspects of
aggressive behavior.

State Trait Anxiety Inventory: A short questionnaire assessing statedependent level of anxiety.

Beck Depression Inventory: Assessment of depressive symptoms.

Temperament and Character Inventory (TCI)

Swedish University Scales of Personality (SSP), personality assessment
scales
•
Cornell Coding guide for violent incidents: Instrumental versus hostile/reactive
aggression
IAGGS
materials and methods

C-Reactive Protein (CRP): a marker of general inflammation

Cytokines (IL- 1,2, 5, 6, 8, 10, 13, TNF)- immunological markers previously
found to be affected by peripheral stress

Brain Derived Neurotrophic Factor (BDNF): an important growth factor known
to be implicated in both brain plasticity and psychiatric disorders. The serum
levels of this growth factor show a high correlation with CNS levels .

S-100B: An astrocyte-derived cytokine-like protein which is present in
increased levels in serum in cases of brain damage, and also in several
psychiatric disorders.

Beta-trace protein (TP): a marker of blood brain barrier integrity that may be
assessed in serum.

Genetic markers
IAGGS
Inclusion criteria

Free from illegal drugs for at least four weeks

For the offender group: Convicted of a violent crime

Age between 18-65 years old.

For the control group: Not convicted of any violent crime

Both genders

Willingness to provide informed consent
IAGGS
Exclusion criteria

Current treatment with antipsychotic or antidepressant medication,
as these have been shown to influence levels of inflammatory
markers.

Ongoing infection or inflammatory disease.

Ongoing illicit substance abuse

In healthy controls: History of violent aggressive behavior

In healthy controls: History of psychiatric disorder
IAGGS
We hope to better be able to elucidate the
correlations between violent behaviour and
the inflammatory system, thus hopefully
contributing to future treatment methods for
forensic psychiatric patients
Contributions:
•
Swedish Board of Forensic Medicine
•
Gothenburg Medical Society
•
Bror Gadelius Memorial Fund
•
Knut and Alice Wallenberg Foundation
•
Rolf Anckarsäter, Marianne Kristiansson, Thomas Nilsson, Kaj
Blennow, Henrik Zetterberg, Henrik Anckarsäter, Caroline
Wass
Karolinska Scales of
Personality (KSP) n=19
Comprises 135 items covering 4 factors grouped into 15
subscales.
Four alternative answers on a Likert scale
Well-known and validated
Temperament and Character
Inventory (TCI) n=22
Based on 238 statements consisting of four
temperament and three character dimensions.
Well known and validated
Two alternatives:
• ”true”
• ”false”
Serum concentrations of IL-8 and IL-10 were significantly increased during and after surgery,
as compared to baseline. In addition, serum TNF decreased significantly comparing
concentration during with after surgery. CSF concentrations of IL-2, IL-8, IL-10, IL-13 and TNF
increased significantly comparing baseline concentrations to concentrations both during and
after surgery. CSF concentrations of IL-5 increased significantly after, but not during, surgery.
Interesting correlations were found between low CSF IL-10, inhibited aggression and social
anxiety, and between high levels of CSF IL-10 and verbal aggression. Levels of CSF IL-8 were
negatively correlated with Conscience. Serum levels of IFN-and IL-10 were positively
correlated with Guilt and negatively with self-directedness, and, for IFN-, Goal-orientation.
A negative correlation was also seen between serum TNF and Helpfulness.
Limitations
•Small sample
•Several possible confounders like diabetes,
hypertension and different medications
•Anaesthesia
•Continuous sampling not possible
. Results: Serum IL-8 and IL-10 increased during and after surgery. SerumTNFa decreased after surgery and CSF IL-2, IL-8, IL-10, IL-13 and TNF-a increased
during and after surgery and CSF IL-5 increased after surgery. Correlations
(p<0.01) were found between CSF IL-10, Inhibited aggression and Social anxiety
and between CSF IL-10 and Verbal aggression. CSF IL-8 correlated negatively
with Conscience. Serum IFN-g and IL-10 correlated positively with Guilt and
negatively with Self-directedness, and IFN-g with Goal-orientation, serum TNF
and Helpfulness correlated negatively.
Conclusion: The present findings demonstrate that marked increases in brain
cytokines differ from peripheral fluctuations. Furthermore, several cytokines were
correlated with baseline destructive personality traits. These relationships
indicate that peripheral stressors may induce central inflammatory changes,
different from those in the periphery. Moreover, CNS inflammatory m processes
may be related to destructive personality traits.