Psychological disorders Flashcards
Drug mechanism
Antagonist
agonist :
Most commonly abused drugs are derived from plants
(e.g., nicotine in tobacco)
• Antagonist
– Drug that blocks a neurotransmitter
• Agonist
– Drug that mimics or increases an effect
Drug’s affinity for a receptor
Efficacy
• Drug’s affinity for a receptor
– Measure of drug’s tendency to bind to it
– Ranges from strong to weak
lect : high affinity = binds well
low affinity - doesnt bind as well
Efficacy: tendency to activate the receptor • A drug’s effectiveness and side effects vary from one
person to another
– Abundance of each type of receptor varies between
individuals
Predispositions
People differ in their predisposition to alcohol or drug
abuse
• Certain aspects of brain function and behavior are
present from the start in people with a familial
disposition to addiction
– Not all individuals develop addiction
Genetic Influences
• Twin studies confirm strong influence of genetics on
vulnerability to alcohol/drugs
• Many addiction-linked genes have been identified, each
with a small effect
– Genes affect the probability of substance use, but effects
vary depending on environment
– People with a gene for producing less acetaldehyde
dehydrogenase metabolize acetaldehyde (from alcohol)
more slowly
§ Those individuals tend to drink less and have fewer
problems with alcohol abuse (e.g., China and Japan)
Environmental Influences
• Prenatal environment contributes to risk for alcoholism
• Childhood environment is critical
– Careful parenting supervision decreases likelihood of
developing impulsive behavior that leads to abuse
• Alcoholics that develop alcohol problems before age 25
tend to have family history and a genetic predisposition and rapid onset of problems
Behavioral Predictors of Abuse
research findings
• Research findings
– Sons of alcoholics show less than average intoxication
after drinking a moderate amount of alcohol § Low level of intoxication may influence person to keep
drinking § Probability of developing alcoholism is greater than 60
percent
– Alcohol decreases stress for most people, but more so
for sons of alcoholics
pic in slide 9
Synaptic Mechanisms
• Nearly all abused drugs affect several kinds of
receptors
• The effects while the drug is in the brain differ from
effects that occur during withdrawal, and effects
responsible for cravings
• Efforts to alleviate drug abuse must consider a variety
of mechanisms
The Role of Dopamine
James Olds and Peter Milner , what did they do ?
Nucleus accumbens , what is it ?
• James Olds and Peter Milner (1954)
– Stimulating rat brains: missed target and hit septum
causing rats to respond favorably
– Discovered that rats would push a lever to produce
electrical self-stimulation of the brain
• Nucleus accumbens
– Central to reinforcing experiences of all types
– Location where addictive drugs release dopamine or
norepinephrine
Other experiences that release dopamine in the
nucleus accumbens
– Sexual excitement – Music – Taste of sugar – Imagining something pleasant – Habitual gambling and video game playing
Dopamine release essential for all addictions and all
substance abuse?
– Not so fast: dopamine contributes to reinforcement, but
no longer appears to be as central as previously believed
Cravings
• Insistent search for the activity
– Distinctive feature of addictions
• Even after long period of abstinence, cues can trigger a
craving
• Studies in rats show repeated exposure to an addictive
substance alters receptors to become more responsive
to the addictive substance
– Less responsive to other types of reinforcement
Tolerance
– Decrease in effect as an addiction develops
– Drug tolerance is learned, to a large extent
§ Can be weakened through extinction procedures
Withdrawal
– Body’s reaction to absence of the drug
– One hypothesis is that addictive behavior is an attempt to avoid withdrawal symptoms
Modified hypothesis ?
for tolerance and withdrawal .
explain the study .
• Modified hypothesis: person with an addiction may use
the substance to cope with stress • Studies in rats have shown:
– Receiving an addictive drug during a withdrawal period is
a powerful experience § Associated relief can cause craving the drug under other
types of stressful experiences
Treatments
• Some addicts able to decrease use or quit on their own
• Alcoholics Anonymous (or similar group)
• Cognitive-behavioral therapy
– Contingency management includes rewards for
remaining drug-free
• Medication—not as common, but some options are
available
Medications to Combat Alcohol Abuse
• Antabuse (disulfiram)
– Results in sickness after drinking
– Taking a nausea-inducing drug after drinking, to
associate the two—learned aversion § Approach has not become popular
• Naloxone and naltrexone
– Block opiate receptors and decrease pleasure from
alcohol
• Drug effectiveness varies with user’s motivation to quit
Medications to Combat Opiate Abuse
• Methadone as a safer alternative – Similar to heroin and morphine § Activates same brain receptors and produces same effects – Can be taken orally, absorbs slowly, and leaves the brain slowly § “Rush” and withdrawal both reduced • Buprenorphine and LAAM – Similar to methadone
Mood Disorders
• Major depression symptoms
– Person feels sad and helpless most of the day every day
for long periods of time
– Person does not enjoy anything and cannot imagine
enjoying anything
– Fatigue, feelings of worthlessness, or contemplation of
suicide
– Trouble sleeping
– Cognitive problems: low motivation, impaired memory,
concentration problems, and impaired sense of smell
Major Depressive Disorder
• Absence of happiness is a more reliable symptom than
increased sadness
– More common in women during the reproductive era
– Affects five percent of adults with a given year
§ 10 percent lifetime prevalence
• Some people suffer long-term depression
– More common to have periodic episodes of depression
Genetics of depression
• Depression has a moderate degree of heritability
• No one gene has been identified as clearly linked to
depression
– People with early-onset depression (before age 30) more
likely to have relatives with depression as well as relatives with anxiety disorders, neuroticism, ADD, OCD, IBS, and migraine headaches
– Late onset depression (after age 45) linked to relatives
with circulatory problems
what is the hypothesis + evidence of genetics in regards to depression ?
• Hypothesis: the effect of a gene varies with the
environment • Evidence:
– Young adults with the short form of the serotonin
transporter gene who experienced stressful experiences had a major increase in probability of developing depression
– Long-form of gene less susceptible to stressful events;
one long and one short-moderate risk – Short-form may increase depressive reaction to stressful
events—especially childhood stress
Abnormalities of Hemispheric Dominance - Depression
• Brain activity associated with depression
– Decreased activity in the left prefrontal cortex
– Increased activity in the right prefrontal cortex
– Imbalance stable over the years, despite symptom
changes
• People with depression tend to gaze to the left when
asked to do a verbal task
– Most people gaze to the right
Antidepressant Drugs – Categories
• Many drugs used to treat psychiatric disorders
discovered by accident
• Categories of antidepressant drugs
– Tricyclics
– Selective serotonin reuptake inhibitors (SSRIs)
– Monoamine oxidase inhibitors (MAOIs)
– Atypical antidepressants
Tricyclics
• Tricyclics (such as imipramine; Tofranil)
– Block transporter proteins that reabsorb serotonin,
dopamine, and norepinephrine into the presynaptic neuron after release
– Also block histamine receptors, acetylcholine receptors,
and certain sodium channels
– Side-effects include drowsiness, dry mouth, difficulty
urinating, and heart irregularities
pic slide 29
SSRIs
• Selective serotonin reuptake inhibitors (SSRIs)
– Block the reuptake of the neurotransmitter serotonin
– Examples: fluoxetine (Prozac), sertraline (Zoloft),
fluvoxamine (Luvox), citalopram (Celexa), and paroxetine (Paxil)
– Work in a similar fashion to tricyclics but specific to the
neurotransmitter serotonin
SNRIs
• Serotonin norepinephrine reuptake inhibitors (SNRIs) – Examples: duloxetine (Cymbalta) and venlafaxine
(Effexor) – Block reuptake of serotonin and norepinephrine
• Unlike other antidepressants, the SNRIs improve
certain aspects of memory
MAOIs
• Monoamine oxidase inhibitors (MAOIs)
– Block the enzyme monoamine oxidase that metabolizes
catecholamines and serotonin into inactive forms – Results in more transmitters in the presynaptic terminal
available for release
• Usually only prescribed if SSRIs and tricyclics are not
effective
– High blood pressure results with some food
Atypical Antidepressant Drugs
• Miscellaneous group of drugs with antidepressant
effects and milder side effects • Example: bupropion (Wellbutrin)
– Inhibits the reuptake of dopamine and to some extent
norepinephrine, but not serotonin
• Ketamine
– Antagonizes NMDA type glutamate receptors
– Produces rapid antidepressant effects in people who
don’t respond to other medications
– Not suitable (produces delusions and hallucinations) but
may lead to something similar
St. John’s Wort - herbs for depression
• Herb often used as a treatment for depression
– Nutritional supplement not regulated by the FDA
– Effectiveness about the same as standard
antidepressants – Increases the production of a liver enzyme that
decreases the effectiveness of other medications
How Are Antidepressants Effective? — Neurotransmitters
• Most people with depression have normal levels of
neurotransmitters
– Decreasing serotonin in control groups does not provoke
depression
• Drugs affect neurotransmitters in synapses quickly
(minutes to hours)
– Result improving mood often requires weeks
BDNF
• People with depression have lower than average brain-
derived neurotrophic factor (BDNF): important for
synaptic plasticity • As a result, people with depression show:
– Smaller than average hippocampus
– Impaired learning
– Reduced production of hippocampal neurons
§ Prolonged use of antidepressants increases BDNF
production
New Neurons in the Hippocampus
• Proliferation of new neurons in the hippocampus is
important for antidepressant effects
– Independent of whether BDNF is responsible
• Studies show antidepressants may not be helpful at all,
especially for mild depression
Alternatives to Antidepressant Drugs
• Cognitive-Behavioral Therapy
– Shown to be equally effective for all levels of depression
– Causes increased metabolism in same brain areas as
antidepressants – More likely to reduce relapse months or years later
• Exercise has modest antidepressant benefits
– Best as a supplement to other treatments • Supplements
– Omega-3 fatty acids and B vitamins
– Research has not been conclusive
Electroconvulsive Therapy (ECT)
• Electrically induced seizure used for the treatment of
severe depression
– For patients who have not responded to antidepressant
medication – Side effects include memory impairment
§ Minimized when shock is only to right hemisphere – High risk of relapse without continued treatment
• How ECT relieves depression is unknown
– Proliferates neurons in the hippocampus
– Increases BDNF
Altered Sleep Patterns in depression
• Disruption of sleep patterns is common in depression
– Typically fall asleep but awaken early and are unable to
get back to sleep
– Enter REM sleep sooner than normal
– Sleep pattern disruption increases the likelihood of
depression later on
– Periodic sleep deprivation sometimes helpful- implies
disrupted circadian rhythms play a role
§ Additional evidence: seasonal affective disorder (SAD)
Seasonal Affective Disorder
• Form of depression that regularly occurs during a
particular season, such as winter
– Most prominent closer to the poles • Patients with SAD have phase-delayed sleep and
temperature rhythms
– Most depressed people have phase-advanced patterns
• Treatment often uses very bright lights
– Used one hour or more daily
– Benefits are unexplained, but substantial • Many people with SAD have a mutation on a gene
responsible for regulating circadian rhythms
Deep Brain Stimulation
• Physician implants battery powered device into the
brain to deliver periodic stimulation
– Targets brain areas that increase activity as a result of
antidepressant drugs
• Still in experimental stage • Encouraging results • Alternative: optogenic stimulation
– Can control individual connections
Unipolar and Bipolar Disorder
• Unipolar disorder
– Characterized by alternating states of normality and
depression
• Bipolar disorder (formerly manic-depressive disorder)
– Characterized by alternating states of depression and
mania – Mania: restless activity, excitement, laughter, self-
confidence, rambling speech, and loss of inhibition
Bipolar Disorder
I , II
• Bipolar disorder I: characterized by full blown episodes
of mania
• Bipolar disorder II: characterized by much milder manic
phases, called hypomania
• Onset is usually in teenage years or early 20s
• Brain’s use of glucose increases during periods of
mania and decreases during periods of depression
Treatments for Bipolar Disorder
• First treatment—lithium: a salt that stabilizes mood and
prevents relapse in mania or depression
• Drugs: valproate (Depakote) and carbamazepine
• Drugs work by:
– Decreasing glutamate activity
– Blocking the synthesis of the brain chemical arachidonic
acid, which is produced during brain inflammation
Schizophrenia
• Deteriorating ability to function in everyday life for at
least six months, paired with at least two of the
following symptoms, including at least one of the first
three:
– Hallucinations, that is, hearing voices
– Delusions: unjustifiable beliefs
– Disorganized speech
– Grossly disorganized behavior
– Weak or absent signs of emotion, speech, and
socialization
Diagnosis of schizophrenia
• Positive symptoms
– Behaviors that are present that should be absent
– Examples: hallucinations, delusions, disorganized
speech, and disorganized behavior
• Negative symptoms
– Absent behaviors that should be present (weak emotion,
speech, and socialization) – Usually stable over time and difficult to treat
• Cognitive symptoms
– Limitations of thought and reasoning common in
schizophrenia – Example: difficulty using and understanding abstract
concepts – Hypothesis: due to impairments in attention and working
memory
Differential Diagnosis - schizophrenia
• One that rules out other conditions with the same
symptoms • Conditions that resemble schizophrenia
– Substance abuse
– Brain damage
– Undetected hearing deficits
– Huntington’s disease
– Nutritional abnormalities
Demographic Data
schizophrenia
• Half of 1 percent affected worldwide • More common for men than women, but occurs in all
ethnic groups in all parts of the world • Many mysteries remain:
– Link to colon cancer & certain autoimmune diseases
– Characteristic body odor ( trans-3-methyl-2-hexenoic
acid) – Women having schizophrenic breakdowns & male versus
female children – Deficits in pursuit eye movements
Genetics
schizophrenia
• Research suggests a genetic component, but does not
depend on a single gene • Monozygotic twins have a much higher concordance
rate (agreement) than dizygotic twins
– But monozygotic twins only have a 50 percent
concordance rate
• Greater similarity between dizygotic twins than siblings suggests a prenatal/postnatal environmental effect
Adopted Children Who Develop Schizophrenia
• Adopted children studies suggest a genetic role
– Prenatal environment of the biological mother cannot be
discounted
• Environmental influence, such as family environment
shown to have a role
– See Figure 14.15
Gene and schizophrenia
• Many genes more common in individuals with
schizophrenia
– Difficult to replicate results
– Large number of more common genes produce small
effects
• DISC1 (disrupted in schizophrenia 1) gene controls rate
of generation of new neurons • Possibly caused by new gene mutations or
mic rodeletion of chromosomes
Prenatal and Neonatal Environment
intermediate and low risk factors
• Intermediate risk factors – Living in a crowded city – Toxoplasma gondii • Low risk factors – Poor maternal nutrition – Premature birth or low birth weight – Complications during delivery – Head injuries in early childhood – Extreme stress or illness of mother during pregnancy
Prenatal and Neonatal Environment
blood type
Mother/child blood type differences increase the
likelihood of schizophrenia • If the mother has a Rh-negative blood type and the
baby is Rh-positive, the child has about twice the
probability of developing schizophrenia
– Response weak in first child but stronger in later
pregnancies, and especially for boys
Prenatal and Neonatal Environment
season of birth
Season-of-birth effect
– Tendency for people born in winter to have slightly (5–
8%) greater probability of developing schizophrenia – More pronounced in latitudes far from the equator – Possible explanation: increased likelihood of viral
infection in mother (e.g., flu virus)
Prenatal and Neonatal Environment
viral infections
• Result of viral infections in the mother
– Increased cytokines in the mother that impairs brain
development of fetus – Fever that slows divisions of fetal neurons
• Conclusion
– Wide variety of genetic and environmental influences
can cause schizophrenia
Mild Brain Abnormalities schizophrenia
• Most people with schizophrenia have:
– Less gray matter and white matter
– Larger than average ventricles
– Minor abnormalities in subcortical areas
– Smaller hippocampus
§ Areas of increased metabolism, followed by atrophy – Deficits of memory and attention consistent with damage
to the prefrontal cortex
• Lateralization differences in people with schizophrenia
– Right planum temporale slightly larger
– Lower than normal activity in left hemisphere
– More likely to be left-handed
Long-Term Course
of schizophrenia
• Schizophrenia previously thought to be a progressive
disorder
– New studies show varied outcomes
– The more recent experience is that people diagnosed
with schizophrenia vary in their outcome § Poverty, social support, drug abuse, and other factors can
influence outcome
Early Development and Later Psychopathology
• Most cases of schizophrenia are not diagnosed until
age 20 or later
– Problems often observed in childhood
§ Impulse control, attention, and memory
• Dorsolateral prefrontal cortex one of the slowest brain
areas to mature
– Area shows consistent signs of deficit in schizophrenia
patients
Treatments for Schizophrenia
• Chlorpromazine (Thorazine)
– Drug used to treat schizophrenia
– Relieves the positive symptoms of most patients • Antipsychotic/neuroleptic drugs
– Category of drugs tend to relieve schizophrenia and
similar conditions
Antipsychotic Drugs
• Two chemical families of antipsychotic drugs used to
treat schizophrenia
– Phenothiazines: includes chlorpromazine
– Butyrophenones: includes halperidol (Haldol) • Both drugs block dopamine synapses
Antipsychotic Drugs and Dopamine (1 of 2)
• Dopamine hypothesis of schizophrenia
– Schizophrenia results from excess activity at dopamine
synapses in certain areas of the brain
• Substance-induced psychotic disorder
– Hallucinations and delusions resulting from repeated
large doses of amphetamines, methamphetamines, or cocaine § Each prolongs activity at dopamine synapses
• Research indicates increased activity specifically at the
D
receptor – Schizophrenics had twice as many D2 receptors
occupied as normal
2
Mesolimbocortical System
• The mesolimbocortical system
– Set of neurons that project from the midbrain tegmentum
to the limbic system and prefrontal cortex – Site where drugs that block dopamine synapses produce
their benefits
• Drugs also block dopamine in the mesostriatal system
– Result is tardive dyskinesia, characterized by tremors
and involuntary movements
Second-Generation Antipsychotics
• Atypical antipsychotics
– Seldom produce movement problems
– Examples: clozapine, amisulpride, risperidone,
olanzapine, aripiprazole – Have less effect on dopamine D2 receptors than
haloperidol – More strongly antagonize serotonin type 5-HT2 receptors
Atypical antipsychotics side effects
• Atypical antipsychotics side effects
– Weight gain
– Immune system impairment • Do not increase quality of life more than the older drugs • In summary: schizophrenia cannot be explained by a
single gene or single neurotransmitter
The Role of Glutamate
• The glutamate hypothesis
– Problem relates partially to deficient activity at glutamate
synapses, especially in the prefrontal cortex – In many brain areas, dopamine inhibits glutamate
release
– Alternately, glutamate stimulates neurons that inhibit
dopamine release
– Increased dopamine thus produces the same effects as
decreased glutamate
PCP
• Further support for the glutamate hypothesis comes
from the effects of phencyclidine (PCP; “angel dust”),
a drug that inhibits the NMDA glutamate receptors
• At larger doses, it produces both positive and negative
symptoms of schizophrenia. PCP is an interesting
model for understanding schizophrenia:
– PCP (and ketamine) produce little psychotic response in
preadolescents. The symptoms of schizophrenia usually emerge after puberty as do the psychotic effects of PCP.
– PCP produces a relapse for someone who has
recovered from schizophrenia.
Autism Spectrum Disorders (ASD)
• Includes autism and what was called Asperger’s
syndrome in the past • Includes people with varying degrees of difficulty
– Ranges from relatively mild to severe • Once rarely diagnosed
– More commonly diagnosed today • Much more common in boys than in girls
Autism Spectrum Disorder Characteristics
• Deficits in social and emotional exchange
• Deficits in nonverbal communication
– Examples: gestures, facial expressions
• Repetitive movements
• Resistant to change in routine
• Unusually weak or strong responses to stimuli
Autism Spectrum Disorders - Causes
• Infants with autism make a normal amount of eye
contact at two months
– Eye contact declines over time • Genetics and other causes
– Many genes linked to autism, but no one gene is found in
a high percentage of people with autism – Many cases may result from mutations and
microdeletions in one or more genes
• Some mothers of children with autism have antibodies
that attack certain brain proteins
– Studies in monkeys have confirmed this is a contributing
factor
• Prenatal nutrition
– Adequate amounts of folic acid during pregnancy halves
the risk of having an autistic child
Treatments for ASD
• No medical treatment for central problems of decreased
social behavior and communication • Risperidone sometimes reduces stereotyped behaviors
– Has serious side effects • Behavioral treatments focus on attention and
reinforcing favorable behaviors
