Psychiatric Disorders

June 29, 2011

Brainstorming: Psychiatric Disorders PTSD Bipolar Disorder Psychopathology Asperger’s Schizophrenia OCD Depression Paranoia ADHD Anxiety Munchausen: Brad & Vivian

DSM & Psychiatric Disorders Schizophrenia: Ime & Chloe Schizophreniform Disorder: Varun & William,

Brad & Vivian Schizoaffective Disorder: Karla & Leandra, , Ice &

Hannah Delusional Disorder : Ime & Chloe, Maria & Allie Shared Psychotic Disorder: Stephanie & Krystal,

Maria & Allie Dissociative Amnesia: Juan & Paige, Melissa &

Kyle Dissociative Identity Disorder: Stephanie &

Krystal, Varun & William, Brad & Vivian Bipolar Disorder: Karla & Leandra, Ice & Hannah Cyclothymia: Juan & Paige, Melissa & Kyle

Neurobiology of Mental Illness

http://www.npr.org/programs/atc/features/2002/aug/schizophrenia/

Schizophrenia

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The Dopamine Hypothesis Positive symptoms

Delusions Hallucinations Disorganized behavior

Dopamine hypothesis: Overactivity of

dopamine in mesolimbic pathway (VTA to nucleus accumbens and amygdala)

http://thebrain.mcgill.ca/flash/a/a_03/a_03_cl/a_03_cl_que/a_03_cl_que.html

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Dopamine Hypothesis Mesolimbic system important for reinforcement of behavior

We all have irrational thoughts, but usually brush them aside

But if mesolimbic system was active when the thought occurred, we might take it more seriously, leading to delusions

Confirming piece of evidence: schizophrenics often report euphoria at onset of positive symptoms

Disordered thinking? System so active that it does not discriminate between

thoughts, making it hard to follow a logical sequence Terrifying element of delusions?

Strong dopaminergic projection to amygdala

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Dopamine HypothesisEvidence for excessive dopamine

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Dopamine and Schizophrenia

Dopamine agonists (cocaine, amphetamine) produce symptoms of psychosis.

Dopamine antagonists reduce psychotic behavior.

Patients may have abnormalities involving dopamine autoreceptors.

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Long-term Use of Typical Neuroleptics Often Produce Serious Side Effects Chlorpromazine:

A “typical neuroleptic” A dopamine receptor blocker for D2 receptors

Clozapine: An “atypical neuroleptic” An antipsychotic drug that blocks D4 receptors in the

nucleus accumbens

Tardive dyskinesia involves tremors and involuntary movements.

Supersensitivity: increased sensitivity of neurotransmitter receptors (D2) to dopamine

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Dopamine HypothesisEvidence for increase in D3 receptors

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Problems With an Excessive Dopamine Hypothesis 25% of patients do not respond to dopamine

antagonists. Atypical antipsychotic medications (clozapine) act

primarily on neurotransmitters other than dopamine.

Drugs change dopamine activity immediately, but patient may not improve for weeks.

PCP produces symptoms similar to schizophrenia by blocking the NMDA glutamate receptor.

Roll of The Dice

http://science.education.nih.gov/supplements/nih5/mental/guide/nih_mental_masters.pdf

PET Scanning: Normal vs. Schizophrenia

PET Scanning Depression

Stress

How Does Stress Affect the Brain? Stress causes the release

of corticotropin releasing factor (CRF or CRH) from the hypothalamus.

This activates the anterior pituitary and causes the release of ACTH (adrenocorticotrophic hormone).

ACTH then activates the adrenal cortex and causes the release of glucocorticoids like cortisol.

http://www.stanford.edu/group/hopes/treatmts/lifestyleandhd/an2.html

Negative Feedback Loops The body can sense

high levels of cortisol or corticosterone in the blood.

To keep these levels from rising too high, it will take steps to help decrease the production of CRH in the brain, causing the whole cycle to slow.

Hippocampus

Joels M. (2008) Stress, the hippocampus, and epilepsy. Epilepsia 50 (4): 586-597.

The Fight or Flight Response

sp.eths.k12.il.us/wilburnm/.../realfightor%20flight.ppt

What is the “fight or flight response?” The body’s response to immediate physical

danger; the stress response. Energy is mobilized, either to mount an aggressive response against the danger, or to run away.

It is our body’s primitive automated, inborn response that prepares the body to “fight” or “flee” from perceived attack, harm or threat to our survival.

sp.eths.k12.il.us/wilburnm/.../realfightor%20flight.ppt

What happens to us when we are under excessive stress?

Internal and external stressors both trigger a bodily reaction, called the “fight or flight” response.

Hardwired into our brains and represents a genetic wisdom designed to protect us from bodily harm

sp.eths.k12.il.us/wilburnm/.../realfightor%20flight.ppt

Sympathetic Nervous System Activated during

stress to prepare your body for “fight or flight”

Connects the spinal cord to the peripheral organs through the sympathetic ganglia

Uses acetylcholine and norepinephrine to activate the body

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/P/PNS.html

Sympathetic Activation Chemicals such as adrenaline, noreadrenaline

and cortisol are released into the blood stream.

Respiration increases, blood is forced away from digestion into our muscles and limbs, pupils dilate, awareness intensifies, sight sharpens, pain diminishes and the immune system mobilizes with increased activation.

We are focused on short-term survival

sp.eths.k12.il.us/wilburnm/.../realfightor%20flight.ppt

Can the fight or flight response become counterproductive? Many of the major stressors today trigger full

activation of the fight or flight response causing us to become aggressive and over-reactive (road rage)

Excessive stress leads to disorders of the ANS (autonomic nervous system), muscle tension, headache, upset stomach, racing heartbeat, shallow breathing, anxiety or depression.

sp.eths.k12.il.us/wilburnm/.../realfightor%20flight.ppt

How Do We Normally Calm Down?

Activation of the Parasympathetic Nervous System

“Rest and Digest” Fibers from the peripheral

organs synapse to the preganglionic fibers, which then pass through specific cranial nerves to enter the medulla and spinal cord.

Acetylcholine is important for the parasympathetic nervous system.

What is our fight or flight system designed to protect us from? When activated, the response causes a surge

of adrenaline and stress hormones to pump through the body.

This surge can result in tremendous strength or heroism

When we are in real danger, the fight or flight response is invaluable. Today, however, most of our response is due to traffic, arguments, deadlines, parents, and teachers. So, stress hormones also flow into our bodies for events that cause no real danger.

sp.eths.k12.il.us/wilburnm/.../realfightor%20flight.ppt

Psychiatric Patient Experiences

Awakenings What did you notice about the mental

hospital in Awakenings? Describe the tone and atmosphere.

How were the patients approached and treated?

How has mental illness been handled in our recent past?

Mental Illness

A brief history

Source: www.pbs.org/wgbh/amex/nash/timeline/index.html

1908 Clifford Beers publishes his autobiography, A

Mind that Found Itself, describing his dehumanizing experiences in a Connecticut mental institution

Calls for reform, founds National Committee for Mental Hygiene—an education and advocacy group

This group later becomes the National Mental Health Association

Source: www.pbs.org/wgbh/amex/nash/timeline/index.html

1930’s Drugs, electro-convulsive therapy, insulin-

induced comas, and surgery (lobotomy) used to treat people with schizophrenia

Source: www.pbs.org/wgbh/amex/nash/timeline/index.html

1940’s In 1946, President Harry Truman signs

National Mental Health Act, establishing National Institute of Mental Health (1949)

In 1949, Australian psychiatrist, J. F. J. Cade introduces use of lithium to treat psychosis. Later this becomes a very useful drug in treating bi-polar disorder.

Source: www.pbs.org/wgbh/amex/nash/timeline/index.html

1950’s

Anti-psychotic drugs introduced for treatment of psychosis. First anti-psychotic drug, chlorpromazine (Thorazine).

In 1955, there were 560,000 patients in state psychiatric hospitals. The advent of anti-psychotic drugs makes it possible for a dramatic reduction in state hospital populations.

Anti-psychotic drugs introduce new problem: sometimes serious side effects

Source: www.pbs.org/wgbh/amex/nash/timeline/index.html

Mid-1960’s Deinstitutionalization: number of

institutionalized mentally ill people in the US drops from 560,000 to 130,000 by 1980.

Deinstitutionalization possible because anti-psychotic drugs control symptoms, but long-term institutionalized people need ongoing mental health treatment and an array of social services that are not uniformly available.

Results: homelessness, “revolving door syndrome,” concern in the community about discharged patients

Source: www.pbs.org/wgbh/amex/nash/timeline/index.html

1963 Community Mental Health Centers

Construction Act passes, providing federal money to develop a network of community mental health centers.

Note that this occurs after deinstitutionalization was well underway.

Source: www.pbs.org/wgbh/amex/nash/timeline/index.html

1990 New generation of anti-psychotic drugs

introduced—clozapine, etc. Drugs appear to be more effective and

have fewer side effects

Source: www.pbs.org/wgbh/amex/nash/timeline/index.html

1992 Survey of American jails finds that 7% of

inmates (100,000) are seriously mentally ill

Most of these individuals receive little, if any, treatment

Source: www.pbs.org/wgbh/amex/nash/timeline/index.html

What Is a Mental Health Institution

Like?

Girl, Interrupted

http://thegirlwiththebluebow.blogspot.com/2011/03/girl-interrupted-bcb-review.html

http://readingon.library.emory.edu/issue1/articles/Miller/RO%20-%202006%20-%20Miller.pdf

http://readingon.library.emory.edu/issue1/articles/Miller/RO%20-%202006%20-%20Miller.pdf

http://readingon.library.emory.edu/issue1/articles/Miller/RO%20-%202006%20-%20Miller.pdf

http://readingon.library.emory.edu/issue1/articles/Miller/RO%20-%202006%20-%20Miller.pdf

One term of the sale was that Emory would accept the facility in its current state of disrepair. The central building, depicted in the photos above, was littered with medical equipment and signage from its active period. Outly-ing residency buildings arrayed around the central building were in worse condition: overgrown, broken.

http://readingon.library.emory.edu/issue1/articles/Miller/RO%20-%202006%20-%20Miller.pdf

http://readingon.library.emory.edu/issue1/articles/Miller/RO%20-%202006%20-%20Miller.pdf

Most rooms in the facility looked out onto the 42-acre estate. Although much of the view would be blocked by the building’s cladding, and much of the grounds immediately surrounding the building had been paved and developed, the land just beyond was still rolling manicured hills and scattered southern trees.

http://readingon.library.emory.edu/issue1/articles/Miller/RO%20-%202006%20-%20Miller.pdf

http://www.flickr.com/photos/nrbelex/2088995271/in/set-72157603376031618/

http://www.flickr.com/photos/judester/230742436/in/set-72157594262952659/

Aggressive Behavior and

Disorders

Neeraja Murali

Behavioral Responses of Interest Anger

Emotional response to a perceived grievance Can be active or passive

Hostility Often used as a synonym for anger Active or passive manifestation of anger

Impulsivity Predisposition toward rapid, unplanned rxns to stimuli

without regard to negative consequences Aggression

Behavior that is meant to cause harm or pain

DSM Classification Published by the American Psychiatric Association Codes correspond w/ ICD-9 Lists categories of mental disorders and criteria

for diagnosis 5 axes:

Axis I: Clinical Disorders Axis II: Personality Disorders and Mental Retardation Axis III: General Medical Conditions Axis IV: Psychosocial and Environmental Problems Axis V: Global Assessment of Functioning

Anger & Hostility Action of the amygdala leads to activation of sympathetic

response Progression to rage is not associated with the brain During “refractory period”, anger threshold is lowered Genetic predisposition

Specific genes increase the risk of socially harmful behavior: nature & nurture both important to manifestation of anger (Wang et. al)

NO genetic predisposition to violence! Anger and social position: correlation between anger and

perception of social influence (Tiedens et. al) Angry facial expressions associated with power and high social

position Angry characters vs sad characters & perceived social status

Impulsivity No consensus on how to measure and define

impulsivity Best understood through examining disorders

associated with impulsivity Impulse-Control Disorders

Seeking a small, short-term gain at the expensive of a large, long-term loss

IED, pathological gambling, trichotillomania, kleptomania

Seems to be associated with serotonin

ADHD

ADHD is largely neurological in nature Developmental in nature: traits such as impulse control are

lagging Prevalence is 5% worldwide Brain function is suspected to be decreased in ADHD

patients

Aggression What motivates people to cause harm? How does violent behavior help animals in

survival?

Hostile/affective/retaliatory aggression vs instrumental/predatory/goal-oriented aggression

Animal models can shed light on human aggressive behavior

Continuum of aggression

Categories of AggressionMoyer (1968):

1. Territorial defense 2. Predatory aggression 3. Inter-male aggression 4. Fear-induced aggression 5. Irritable aggression 6. Maternal aggression 7. Instrumental aggression

Considers stimuli, environment, and neural circuits in addition to the specific aggression

Brain (1979):

1. Self-defensive behavior. 2. Social conflict3. Predatory attack 4. Parental defense5. Reproductive termination

Focuses on the utility of the aggressive behavior to the animal and NOT on the evoking stimuli/environment

However, all these factors should be considered

Biology of Aggression Two areas known to be of

importance in aggression Amygdala: stimulation

augments aggressive behavior

Hypothalamus: causes aggressive behavior when stimulated, has serotonin and vasopressin receptors

Heritability is still being studied

2 Major Hormones of importance: Testosterone Serotonin Others known to be

important as well

Disorders Associated w/ Aggression Schizophrenia

“+” and “-” symptoms as well as cognitive symptoms

Characterized by impairment in perception or expression of reality

Increased dopaminergic activity in mesolimbic pathway

Tx w/ phenothiazines can reduce psychotic symptoms

Research also examines possibility of glutamate + reduced receptor fcn

Often comorbid w/ depressive or anxiety disorders and substance abuse

Other Disorders Associated w/ Aggression ADHD PTSD Drug abuse Depression Dementia/Alzheimer’s Antisocial disorders Mood disorders Panic disorder These are not necessarily associated w/ violence and

aggression, but can be Very frequent comorbidities

Neural Correlates of Aggression

Alisha Epps

Key Regions Hypothalamus Amygdala Periqueductal Gray

(PAG) Prefrontal Cortex Brainstem Perceptual System

Medial Nucleus

Basal Nucleus

Central Nucleus

Medial Hypothalamus

Lateral Hypothalamus

Dorsal PAG

Ventral PAG

Amygdala

Neural Pathways

Prefrontal Cortex Key role in guiding behavior using

emotional reactions When damaged, often properly state the

correct behavior given a theoretical situation, but do not act accordingly in reality

Antisocial personality, impulsive murderers show decreased PFC volume

Likely helps inhibit aggressive behavior

Orbitofrontal Cortex Receives input from:

Dorsomedial thalamus Temporal cortex Ventral Tegmental Area Olfactory Amygdala

Sends outputs to: Cingulate Cortex Hippocampal Formation Temporal Lobe Lateral Hypothalamus Amygdala Other Cortical Regions

Serotonin Low levels of 5-HIAA correlate with risk-

taking, high aggression Vervet monkeys given 5-HT agonist:

become dominant 5-HT 1B KO mice are quicker to attack

opponent 5-HT controls risk taking, which impacts

aggressive behavior—Therefore, 5-HT alone does not fully explain aggression

5-HT & Human Aggression? Decreases in 5-HIAA correlate with aggression, assault,

murder, & abuse Some case studies suggest that Prozac decreases irritability

& aggression Short allele for SERT: increase in right amygdala activity

when viewing fearful/aggressive faces

Other Neurotransmitters Acetylcholine

Agonists induce biting, aggressive behaviors Dopamine

DAT KO mice are more aggressive Norepinephrine

DBH KO mice show reduced aggression GABA

GAT KO mice show less aggression

Other Possible Factors Opioids Glucocorticoids CCK (Cholecystokinin) Vasopressin Cytokines Omega-3 Polyunsaturated

Fatty Acids Experience & Genetics