Aggression
Aggression
Pervasive
Innate
Social behavior
Rarely results in injury (violence)
Why be aggressive?
Establish / maintain social rank
Secure resources
Protect territory
Winning is rewarding
Because your dopamine-transporter – expressing neurons in the hypothalamic
premammillary
nucleus are active
Aggression activates PMv DAT neurons
Aggressive mice have more active PMV DAT neurons
Stimulating these neurons causes the resident mouse to attack an intruder
Silencing these neurons causes an aggressive mouse to stop attacking
Activating those neurons makes Subs dominant; silencing those neurons makes Doms submissive
The mouse on the left is dominant
But silencing its neurons while activating the neurons of the submissive mouse reverses the dominance hierarchy!
And the reversal is long-lasting even after stimulation is stopped
Why study aggression?
80% chance of being the victim of a violent crime within lifetime
Dropping nationally
Increasing among very young
Want to understand what leads to violence
Difficulties in Researching aggression
Defining aggression
Spanking
Capital punishment
Yelling
Assigning bad grade
Defining aggression
Predatory aggression
Stalking / killing of another species
Social aggression
Unprovoked aggression directed at same-species individual to establish dominance
Defensive aggression
Aggression in response to threat / to protect resources
Is aggression / violence genetic?
Tends to run in families
Modeling aggression?
Sex differences in aggression
Amount
Type
Testosterone tied to aggression, but not necessarily violence
Serotonin and aggression
Receptor knockout
Depleting serotonin
Augmenting serotonin
Natural differences in people:
Arsonists, violent criminals, people who die by suicide
Low levels of serotonin in CSF
Legal implications
Sniper Charles Whitman
Killed several people from tower in Texas
Left note begging people to examine his brain for dysfunction
Had tumor pressing on amygdala
Legal implications
Legal implications
3-year follow-up of 58 violent offenders
Recidivists had lower CSF 5-HIAA
CSF 5-HIAA and blood glucose nadir predict recidivism correctly in 85%
Legal implications
Assume biological explanation
Should sentencing be harsher or more lenient?
Does that mean treatment is possible?
Conduct disorder
Childhood & adolescence
Boys > girls
2-16% of children in U.S.
Precursor to anti-social personality disorder
Symptoms of conduct disorder
Aggressive behavior e.g. cruelty to animals, sexual assault
Destructive behavior e.g. arson, vandalism
Deceitful behavior e.g. lying, theft
Violation of rules e.g. skipping school, running away
No / low remorse
Genes related to conduct disorder
Serotonin-related genes
Dopamine-related genes
Hormone-related genes
Gene X Environment in conduct disorder
Findings from twin & adoption studies
Serotonin-related genes (2 sections)
Dopamine-related genes (2 sections)
Hormone-related genes
Limitations of molecular genetic studies w candidate genes
Genetic risk score
Epigenetics
Resilience
Therapeutic implications
Findings from twin & adoption studies
6.7% with LOW genetic risk + adverse environment show signs
12.1% with HIGH genetic risk + favorable environment show signs
40% of ppl with HIGH genetic risk + adverse environment
Adoption studies: 9mo olds with high risk showed high frustration /irritability
Twins / adoption not great representation
Serotonin-related genes
SERT
Long : risk for males
Short: risk for females
Linked to aggression etc.
MAOA interacts with all sorts of stuff to determine neuroanatomy
MAOA alleles affect aggression in both sexes
Dopamine-related genes
Dopamine receptor: lower expression and less binding increase susceptibility
Dopamine Transporter: no evidence of interaction with environment
Reward… rule following
COMT: interacts with DAT, influence reward processing
Hormone-related genes
Testosterone
high
Cortisol
Low
Increased dominance, lower empathy
Androgen receptor
Glucocorticoid receptor
Sensitivity affects dominance-related aggression
Limitations of molecular genetic studies w candidate genes
Gene can’t diagnose (yet?)
Need better understanding of biological underpinnings
Need HUGE sample sizes
Unrealistic
Comorbidities
Genetic risk score
Polygenic risk
Knowing multiple genes helps decide risk
IDing all the genes is tough
Epigenetics
Methylation
Reversible
Good target
Good basic research
Suicide higher methylation
Resilience
Social factors
Prosocial environment
Parenting
High Cort is bad without stress but good in the face of stress
Self esteem
adaptable
Therapeutic implications
Parenting programs
Psychosocial interventions
Adomoxetine stimulants
ADHD; off-label
Neurofeedback
Individualized medicine based on your genotype!
SSRIs
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