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Aggression-1.pptx

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