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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
5
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
6
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
7
Dopamine HypothesisEvidence for excessive dopamine
8
Dopamine and Schizophrenia
Dopamine agonists (cocaine, amphetamine) produce symptoms of psychosis.
Dopamine antagonists reduce psychotic behavior.
Patients may have abnormalities involving dopamine autoreceptors.
9
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
10
Dopamine HypothesisEvidence for increase in D3 receptors
11
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
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