OUTLINE • Psychology of aggression • Reactive vs. instrumental

• Neurobiology of aggression • Limbic system • Neurochemistry • Reactive vs. instrumental

• Disorders and treatment of inappropriate aggression

PRE-QUESTION #1 A 70 year-old man lives by himself. He often yells at visitors, accusing them of stealing his belongings. He has occasionally hit his visitors. Which of the following are not true: a) Benzodiazepines are a first-line drug b) Cognitive/behavioral therapy for both the patient and the patient’s family can be helpful c) Beta-blockers are potentially indicated d) Anti-psychotic drugs are potentially indicated e) This is a form of reactive aggression

PRE-QUESTION #2 A cat encounters a mouse. The cat hisses, bears its teeth and swats at the mouse. This type of aggression: a) Is known as instrumental aggression b) Requires the prefrontal cortex to coordinate c) Will be retained after transections caudal to hypothalamus d) Is known as reactive aggression e) Is a typical predator response

NEUROBIOLOGY OF AGGRESSION • Eagle Scout • Marine • Engineer • Doting husband and son • Aug 1, 1966: • Stabbed his mother and wife • Killed 14 people from University Tower

• “I do not really understand myself these days. I am supposed to be an average reasonable and

intelligent young man.“

• Glioblastoma in his amygdala

Charles Whitman

AGGRESSION SECONDARY TO MEDICAL ILLNESS: • Elderly female • Progressive memory difficulty • Living by herself • Friends and family come by: • Puts soda cans in pillowcase and swings around like a weapon

• Went into nursing home: • Frequent fights and scratches neighbors

• Aggression is her major issue

INAPPROPRIATE AGGRESSION IS SEEN IN: • • • • • • • • • •

affective disorders schizophrenia traumatic brain injury brain tumors complex partial seizures encephalitis cerebrovascular disease Alzheimer's disease normal pressure hydrocephalus and others…

AGGRESSION: • Behavior is easy to define:

• An organism doing intentionally harm to another organism

• Aggression is critical to survival for most species: • Competition for limited resources: • Territory • Food • Mates

• Aggression is highly conserved. Even: • • • •

Organized aggression Strategic (instrumental) aggression Weapon use Sexual aggression

• Aggression can be replaced by hierarchies

• Aggression in modern society tends to be maladaptive

AGGRESSION: • Some forms are socially acceptable:

• Two main forms: Reactive vs. Instrumental

REACTIVE AGGRESSION: • Triggered: • Threatening/frustrating event

• Involves unplanned, enraged attacks on the object perceived to be the source of threat/frustration. • High degree of autonomic arousal • Exhibited by all mammals • Rapid and crude • Highly aversive

REACTIVE AGGRESSION • Part of the mammalian graduated response to threat: • Low levels of danger from distant threats induce freezing. • Higher levels of danger from close threats induce attempts to escape the immediate environment. • Higher levels of danger still, when the threat is very close and escape impossible, initiate reactive aggression.

• This is ‘fight or flight’ • Closely tied to fear processing

INAPPROPRIATE REACTIVE AGGRESSION: RISK FACTORS • Exposure to a threatening environment. • Physical and sexual abuse. • Being male • Testosterone • Monamine oxidase polymorphisms • Socialization

• Being young • Prefrontal cortex not fully developed til mid-20’s

• Increased risk in neurologic and psychiatric disorders. • PTSD, childhood bipolar disorder, borderline personality disorder, intermittent explosive disorder, psychopathy, and “acquired sociopathy” following damage to orbital frontal cortex.

INSTRUMENTAL AGGRESSION • Purposeful and goal directed. • Lower level of autonomic arousal • Need not be accompanied by an emotional state and can be considered “cold.” • Animal model is predatory aggression:

• Occurs during food-seeking in certain omnivorous and carnivorous species.

• Human examples:

• Political assassinations • Murder-for-hire • Planned serial killings

• Often can be rewarding

INSTRUMENTAL AGGRESSION • The capacity for instrumental aggression may lie latent in all of us • ‘Milgram Experiment’ • Yale, 1950’s • Volunteers shocked actors • 50% went to the highest voltage

• ‘Stanford Prison Experiment’

• 1971 • 24 college students: 12 ‘guards’ and 12 ‘prisoners’ • Guards resorted to inhumane treatment of prisoners (instrumental) • Prisoners: • Rage reactions (reactive) • Adopted hierarchy

• ‘Hazing’ practices

PATHOLOGICAL? • We like some aggression:

• Although reactive or instrumental aggression does not necessarily imply pathology, it may.

• Not conventionally considered sufficiently threatening or • If disproportionate in extent, severity, and persistence and occurs out of context.

BIOLOGY OF AGGRESSION • Genetic factors – twin, adoption, and family studies estimate heritability from 44% to 72% in adults – most do not differentiate reactive from instrumental. • Major anatomical players: • • • •

Orbitofrontal cortex Amygdala Septum Hypothalamus

• Major chemical players • Serotonin • Testosterone • Dopamine

HYPOTHALAMUS AND BIOLOGY OF RAGE: • Ventromedial hypothalamic stimulation • Strong autonomic arousal • Activation of periaqueductal gray • Mimics ‘reactive aggression’ • Easy to trigger when PFC gone

HYPOTHALAMUS AND BIOLOGY OF RAGE: • Ventromedial hypothalamic stimulation • Strong autonomic arousal • Activation of periaqueductal gray • Mimics ‘reactive aggression’ • Easy to trigger when PFC gone

• Lateral hypothalamic stimulation • Coordinated motor activity • Lower autonomic arousal • Mimics ‘instrumental aggression’

REACTIVE AGGRESSION • Does not depend on cerebral cortex: • Animal work indicates that this progressive response is mediated by a “basic threat system” • Runs from medial amygdaloid areas downward, largely via the stria terminalis to the medial hypothalamus, • from there to the periaqueductal gray.

• Prefrontal cortex can inhibit this response

INSTRUMENTAL AGGRESSION • Biology here is less well understood • Need executive functioning to carry out plans • May have disrupted amygdala circuitry for emotion:

(instrumental)

(reactive)

NEUROCHEMISTRY OF AGGRESSION: • Serotonin:

• Lesions of the serotonin system (raphe nuclei)

• Lead to aggressive behavior in animals • Related to activity at 5HT1a and 5HT1b receptors

• Nonhuman primates:

• aggression is associated with low levels of 5-HIAA in CSF

• Humans:

• Polymorphisms in MAO-A gene promoter associated with aggression

• Literature supports an overall inverse relationship between serotonin levels and aggression

• Testosterone

• Strong association with sexual aggression

• Castration of sex offenders appears to diminish recidivism

• Also associated with other forms of violence • Likely plays a permissive role

• Dopamine:

• Aggression tends to be associated with dopamine release in limbic structures • Blockade of dopamine receptors tends to diminish aggressive behavior

PRIMARY DISORDERS OF AGGRESSION • Inappropriate aggression seen secondarily in many disorders • Primary disorders: • Psychopathy • Intermittent explosive disorder

PSYCHOPATHY • A personality disorder

• a.k.a. “antisocial personality disorder” or “sociopathy”

• Psychopathy is defined by:

• pervasive pattern of abnormal interpersonal relationships, emotion and behavior.

• Key component:

• Lack of empathy • But with superficial emotional responses and may be of high intelligence • Lack of fear conditioning:

• 1-2% general population • 10-20% prison population • Major risk factor for both instrumental and reactive aggression

(Arch Gen Psychiatry. 2005;62[7]:799–805)

INTERMITTENT EXPLOSIVE DISORDER • This is an impulse-control disorder

• Same category as pyromania, kleptomania, pathological gambling, trichotillomania etc…

• Characterized by episodes of impulsive aggression that is: • unpremeditated, • disproportionate reaction to any provocation, real or perceived

• Men > women, associated with bipolar disease • Cannot be due to psychopathy or brain injury • Association with orbitofrontal cortex dysfunction and low serotonin turnover

TREATMENTS FOR INAPPROPRIATE AGGRESSION: • First: Identify the type, and the trigger • Reduce the perceived threat

• Cognitive/behavioral therapy: • Reduce inappropriate responses to perceived threats

• Pharmacologic therapies: • Serotonin: SSRIs, buspirone • Benzodiazepines: May worsen aggression • Antipsychotics: May diminish perceived threats. Block dopamine. Powerful sedating agents. • Beta-blockers: James-Lange theory

EMBARRASSING HISTORY: PSYCHOSURGERY FOR AGGRESSION • Kluver-Bucy (again): • Extreme placidity

• Amygdalotomy: • Sometimes court-ordered

• Lobotomy: • “Prefrontal leukotomy” • Developed by Moniz in 1930s • Nobel Prize 1949

• Popularized by Walter Freeman • “Icepick lobotomies”

• Often made patients worse • Stopped in late 1960s

SUMMARY • Reactive aggression:

• Driven by amygdala, ventromedial hypothalamus, periaqueductal gray • Inhibited by prefrontal cortex • Associated with fear/aversion • High autonomic arousal • Common secondary form of aggression • Rx: Deal with (perceived) threats, meds to decrease limbic/autonomic arousal

• Instrumental aggression: • • • • •

Driven by reward, goal-associated circuity Shallow emotionality Low autonomic arousal Seen in psychopathy Rx: ????

PRE-QUESTION #1 A 70 year-old man lives by himself. He often yells at visitors, accusing them of stealing his belongings. He has occasionally hit his visitors. Which of the following are not true: a) Benzodiazepines are a first-line drug s b) Cognitive/behavioral therapy for both the patient and the patient’s family can be helpful c) Beta-blockers are potentially indicated d) Anti-psychotic drugs are potentially indicated e) This is a form of reactive aggression

PRE-QUESTION #2 A cat encounters a mouse. The cat hisses, bears its teeth and swats at the mouse. This type of aggression: a) Is known as instrumental aggression b) Requires the prefrontal cortex to coordinate c) Will be retained after transections caudal to hypothalamus d) Is known as reactive aggression e) Is a typical predator response